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1. Corrigendum to 'Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)' Nutrition, Metabolism and Cardiovascular diseases volume 32 issue 1 (2022) 1-16

Author: Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: N/A
Published: 2023

2. Corrigendum to 'Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)' [Dig Liver Dis 54 (2022) 170-182]

Author: Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: N/A
Published: 2023

3. The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma

Author: Lai, Quirino, De Matthaeis, Nicoletta, Finotti, Michele, Galati, Giovanni, Marrone, Giuseppe, Melandro, Fabio, Morisco, Filomena, Nicolini, Daniele, Pravisani, Riccardo, Giannini, Edoardo G, Aglitti, A, Aliberti, C, Baccarani, U, Bhoori, S, Borzio, M, Brancaccio, G, Burra, P, Cabibbo, G, Casadei Gardini, A, Carrai, P, Cillo, U, Conti, F, Cucchetti, A, D'Ambrosio, R, Dell'Unto, C, Di Costanzi, Gg, Di Sandro, S, Foschi, Fg, Fucilli, F, Gambato, M, Gasbarrini, Antonio, Giuliante, Felice, Ghinolfi, D, Grieco, Antonio, Gruttaduria, S, Guarino, M, Kostandini, A, Iavarone, M, Lenci, I, Levi Sandri, Gb, Losito, F, Lupo, Lg, Manzia, Tm, Mazzocato, S, Mescoli, C, Miele, Luca, Muley, M, Persico, M, Plaz Torres, Mc, Pompili, Maurizio, Ponziani, Francesca Romana, Rapaccini, Gian Ludovico, Rendina, M, Renzulli, M, Rossi, Marco, Rreka, E, Russo, Fp, Sacco, R, Sangiovanni, A, Sessa, A, Simonetti, N, Sposito, C, Tortora, R, Trevisani, F, Viganò, L, Viganò, M, Villa, E, Vincenzi, V, Violi, P, Vitale, A, Gasbarrini, A (ORCID:0000-0002-7278-4823), Giuliante, F (ORCID:0000-0001-9517-8220), Grieco, A (ORCID:0000-0002-0544-8993), Miele, L (ORCID:0000-0003-3464-0068), Pompili, M (ORCID:0000-0001-6699-7980), Ponziani, FR (ORCID:0000-0002-5924-6238), Rapaccini, GL (ORCID:0000-0002-6467-857X), Rossi, M (ORCID:0000-0002-4539-5670), Lai, Quirino, De Matthaeis, Nicoletta, Finotti, Michele, Galati, Giovanni, Marrone, Giuseppe, Melandro, Fabio, Morisco, Filomena, Nicolini, Daniele, Pravisani, Riccardo, Giannini, Edoardo G, Aglitti, A, Aliberti, C, Baccarani, U, Bhoori, S, Borzio, M, Brancaccio, G, Burra, P, Cabibbo, G, Casadei Gardini, A, Carrai, P, Cillo, U, Conti, F, Cucchetti, A, D'Ambrosio, R, Dell'Unto, C, Di Costanzi, Gg, Di Sandro, S, Foschi, Fg, Fucilli, F, Gambato, M, Gasbarrini, Antonio, Giuliante, Felice, Ghinolfi, D, Grieco, Antonio, Gruttaduria, S, Guarino, M, Kostandini, A, Iavarone, M, Lenci, I, Levi Sandri, Gb, Losito, F, Lupo, Lg, Manzia, Tm, Mazzocato, S, Mescoli, C, Miele, Luca, Muley, M, Persico, M, Plaz Torres, Mc, Pompili, Maurizio, Ponziani, Francesca Romana, Rapaccini, Gian Ludovico, Rendina, M, Renzulli, M, Rossi, Marco, Rreka, E, Russo, Fp, Sacco, R, Sangiovanni, A, Sessa, A, Simonetti, N, Sposito, C, Tortora, R, Trevisani, F, Viganò, L, Viganò, M, Villa, E, Vincenzi, V, Violi, P, Vitale, A, Gasbarrini, A (ORCID:0000-0002-7278-4823), Giuliante, F (ORCID:0000-0001-9517-8220), Grieco, A (ORCID:0000-0002-0544-8993), Miele, L (ORCID:0000-0003-3464-0068), Pompili, M (ORCID:0000-0001-6699-7980), Ponziani, FR (ORCID:0000-0002-5924-6238), Rapaccini, GL (ORCID:0000-0002-6467-857X), and Rossi, M (ORCID:0000-0002-4539-5670)
Abstract: Aim To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. Methods A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. Results A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p < 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006). Conclusions Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.
Published: 2023

4. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: An individual patient data meta-analysis

Author: Mozes, F. E., Lee, J. A., Selvaraj, E. A., Jayaswal, A. N. A., Trauner, M., Boursier, J., Fournier, C., Staufer, K., Stauber, R. E., Bugianesi, E., Younes, R., Gaia, S., Lupsor-Platon, M., Petta, S., Shima, T., Okanoue, T., Mahadeva, S., Chan, W. -K., Eddowes, P. J., Newsome, P. N., Wong, V. W. -S., de Ledinghen, V., Fan, J., Shen, F., Cobbold, J. F., Sumida, Y., Okajima, A., Schattenberg, J. M., Labenz, C., Kim, W., Lee, M. S., Wiegand, J., Karlas, T., Yilmaz, Y., Aithal, G. P., Palaniyappan, N., Cassinotto, C., Aggarwal, S., Garg, H., Ooi, G. J., Nakajima, A., Yoneda, M., Ziol, M., Barget, N., Geier, A., Tuthill, T., Brosnan, M. J., Anstee, Q. M., Neubauer, S., Harrison, S. A., Bossuyt, P. M., Pavlides, M., Anstee, Q., Daly, A., Johnson, K., Govaere, O., Cockell, S., Tiniakos, D., Bedossa, P., Oakley, F., Cordell, H., Day, C., Wonders, K., Bossuyt, P., Zafarmand, H., Vali, Y., Lee, J., Ratziu, V., Clement, K., Pais, R., Schuppan, D., Schattenberg, J., Vidal-Puig, T., Vacca, M., Rodrigues-Cuenca, S., Allison, M., Kamzolas, I., Petsalaki, E., Oresic, M., Hyotylainen, T., Mcglinchey, A., Mato, J. M., Millet, O., Dufour, J. -F., Berzigotti, A., Harrison, S., Cobbold, J., Mozes, F., Akhtar, S., Banerjee, R., Kelly, M., Shumbayawonda, E., Dennis, A., Erpicum, C., Graham, M., Romero-Gomez, M., Gomez-Gonzalez, E., Ampuero, J., Castell, J., Gallego-Duran, R., Fernandez, I., Montero-Vallejo, R., Karsdal, M., Erhardtsen, E., Rasmussen, D., Leeming, D. J., Fisker, M. J., Sinisi, A., Musa, K., Betsou, F., Sandt, E., Tonini, M., Rosso, C., Armandi, A., Marra, F., Gastaldelli, A., Svegliati, G., Francque, S., Vonghia, L., Ekstedt, M., Kechagias, S., Yki-Jarvinen, H., Porthan, K., van Mil, S., Papatheodoridis, G., Cortez-Pinto, H., Valenti, L., Miele, Luca, Trautwein, C., Aithal, G., Hockings, P., Newsome, P., Wenn, D., Rodrigues, C. M. P., Chaumat, P., Hanf, R., Trylesinski, A., Ortiz, P., Duffin, K., Brosnan, J., Mcleod, E., Ertle, J., Ostroff, R., Alexander, L., Kjaer, M. S., Mikkelsen, L. F., Balp, M. -M., Brass, C., Jennings, L., Martic, M., Loeffler, J., Hanauer, G., Shankar, S., Pepin, K., Ehman, R., Myers, J., Ho, G., Torstenson, R., Myers, R., Doward, L., Miele L. (ORCID:0000-0003-3464-0068), Mozes, F. E., Lee, J. A., Selvaraj, E. A., Jayaswal, A. N. A., Trauner, M., Boursier, J., Fournier, C., Staufer, K., Stauber, R. E., Bugianesi, E., Younes, R., Gaia, S., Lupsor-Platon, M., Petta, S., Shima, T., Okanoue, T., Mahadeva, S., Chan, W. -K., Eddowes, P. J., Newsome, P. N., Wong, V. W. -S., de Ledinghen, V., Fan, J., Shen, F., Cobbold, J. F., Sumida, Y., Okajima, A., Schattenberg, J. M., Labenz, C., Kim, W., Lee, M. S., Wiegand, J., Karlas, T., Yilmaz, Y., Aithal, G. P., Palaniyappan, N., Cassinotto, C., Aggarwal, S., Garg, H., Ooi, G. J., Nakajima, A., Yoneda, M., Ziol, M., Barget, N., Geier, A., Tuthill, T., Brosnan, M. J., Anstee, Q. M., Neubauer, S., Harrison, S. A., Bossuyt, P. M., Pavlides, M., Anstee, Q., Daly, A., Johnson, K., Govaere, O., Cockell, S., Tiniakos, D., Bedossa, P., Oakley, F., Cordell, H., Day, C., Wonders, K., Bossuyt, P., Zafarmand, H., Vali, Y., Lee, J., Ratziu, V., Clement, K., Pais, R., Schuppan, D., Schattenberg, J., Vidal-Puig, T., Vacca, M., Rodrigues-Cuenca, S., Allison, M., Kamzolas, I., Petsalaki, E., Oresic, M., Hyotylainen, T., Mcglinchey, A., Mato, J. M., Millet, O., Dufour, J. -F., Berzigotti, A., Harrison, S., Cobbold, J., Mozes, F., Akhtar, S., Banerjee, R., Kelly, M., Shumbayawonda, E., Dennis, A., Erpicum, C., Graham, M., Romero-Gomez, M., Gomez-Gonzalez, E., Ampuero, J., Castell, J., Gallego-Duran, R., Fernandez, I., Montero-Vallejo, R., Karsdal, M., Erhardtsen, E., Rasmussen, D., Leeming, D. J., Fisker, M. J., Sinisi, A., Musa, K., Betsou, F., Sandt, E., Tonini, M., Rosso, C., Armandi, A., Marra, F., Gastaldelli, A., Svegliati, G., Francque, S., Vonghia, L., Ekstedt, M., Kechagias, S., Yki-Jarvinen, H., Porthan, K., van Mil, S., Papatheodoridis, G., Cortez-Pinto, H., Valenti, L., Miele, Luca, Trautwein, C., Aithal, G., Hockings, P., Newsome, P., Wenn, D., Rodrigues, C. M. P., Chaumat, P., Hanf, R., Trylesinski, A., Ortiz, P., Duffin, K., Brosnan, J., Mcleod, E., Ertle, J., Ostroff, R., Alexander, L., Kjaer, M. S., Mikkelsen, L. F., Balp, M. -M., Brass, C., Jennings, L., Martic, M., Loeffler, J., Hanauer, G., Shankar, S., Pepin, K., Ehman, R., Myers, J., Ho, G., Torstenson, R., Myers, R., Doward, L., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Objective Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. Design Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. Results Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. Conclusion Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.
Published: 2022

5. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)

Author: Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Federici M., Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), and Federici M.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
Published: 2022

6. Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: Time for reappraisal of BMI-driven approach?

Author: Younes, R., Govaere, O., Petta, S., Miele, Luca, Tiniakos, D., Burt, A., David, E., Vecchio, Fabio Maria, Maggioni, M., Cabibi, D., Mcleod, D., Pareja, M. J., Fracanzani, A. L., Aller, R., Rosso, C., Ampuero, J., Gallego-Duran, R., Armandi, A., Caviglia, G. P., Zaki, M. Y. W., Liguori, Antonio, Francione, P., Pennisi, G., Grieco, Antonio, Birolo, G., Fariselli, P., Eslam, M., Valenti, L., George, J., Romero-Gomez, M., Anstee, Q. M., Bugianesi, E., Miele L. (ORCID:0000-0003-3464-0068), Vecchio F. M. (ORCID:0000-0002-9197-2264), Liguori A., Grieco A. (ORCID:0000-0002-0544-8993), Younes, R., Govaere, O., Petta, S., Miele, Luca, Tiniakos, D., Burt, A., David, E., Vecchio, Fabio Maria, Maggioni, M., Cabibi, D., Mcleod, D., Pareja, M. J., Fracanzani, A. L., Aller, R., Rosso, C., Ampuero, J., Gallego-Duran, R., Armandi, A., Caviglia, G. P., Zaki, M. Y. W., Liguori, Antonio, Francione, P., Pennisi, G., Grieco, Antonio, Birolo, G., Fariselli, P., Eslam, M., Valenti, L., George, J., Romero-Gomez, M., Anstee, Q. M., Bugianesi, E., Miele L. (ORCID:0000-0003-3464-0068), Vecchio F. M. (ORCID:0000-0002-9197-2264), Liguori A., and Grieco A. (ORCID:0000-0002-0544-8993)
Abstract: Objective The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD. Design The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) 10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069). Conclusions Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds. Lay summary NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD.
Published: 2022

7. Editorial: The broader aspects of non-alcoholic fatty liver disease in children

Author: Mandato, C., Miele, Luca, Socha, P., Vajro, P., Miele L. (ORCID:0000-0003-3464-0068), Mandato, C., Miele, Luca, Socha, P., Vajro, P., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: N/A
Published: 2022

8. TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models

Author: Longo, M., Meroni, M., Paolini, E., Erconi, V., Carli, F., Fortunato, F., Ronchi, D., Piciotti, R., Sabatini, S., Macchi, C., Alisi, A., Miele, Luca, Soardo, G., Comi, G. P., Valenti, L., Ruscica, M., Fracanzani, A. L., Gastaldelli, A., Dongiovanni, P., Miele L. (ORCID:0000-0003-3464-0068), Longo, M., Meroni, M., Paolini, E., Erconi, V., Carli, F., Fortunato, F., Ronchi, D., Piciotti, R., Sabatini, S., Macchi, C., Alisi, A., Miele, Luca, Soardo, G., Comi, G. P., Valenti, L., Ruscica, M., Fracanzani, A. L., Gastaldelli, A., Dongiovanni, P., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Background & Aims: The I148M Patatin-like Phospholipase Domain-containing 3 (PNPLA3), the rs641738 in the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) locus, and the E167K Transmembrane 6 Superfamily Member 2 (TM6SF2) polymorphisms represent the main predisposing factors to nonalcoholic fatty liver disease (NAFLD) development and progression. We previously generated a full knockout of MBOAT7 in HepG2 cells (MBOAT7-/-), homozygous for I148M PNPLA3. Therefore, we aimed to investigate the synergic impact of the 3 at-risk variants on liver injury and hepatocellular carcinoma (HCC) in a large cohort of NAFLD patients, and create in vitro models of genetic NAFLD by silencing TM6SF2 in both HepG2 and MBOAT7-/- cells. Methods: NAFLD patients (n = 1380), of whom 121 had HCC, were stratified with a semiquantitative score ranging from 0 to 3 according to the number of PNPLA3, TM6SF2, and MBOAT7 at-risk variants. TM6SF2 was silenced in HepG2 (TM6SF2-/-) and MBOAT7-/- (MBOAT7-/-TM6SF2-/-) through Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Results: In NAFLD patients, the additive weight of these mutations was associated with liver disease severity and an increased risk of developing HCC. In HepG2 cells, TM6SF2 silencing altered lipid composition and induced the accumulation of microvesicular lipid droplets (LDs), whereas the MBOAT7-/-TM6SF2-/- cells showed a mixed microvesicular/macrovesicular pattern of LDs. TM6SF2 deletion strongly affected endoplasmic reticulum and mitochondria ultrastructures, thus increasing endoplasmic reticulum/oxidative stress. The mitochondrial number was increased in both TM6SF2-/- and MBOAT7-/-TM6SF2-/- models, suggesting an unbalancing in mitochondrial dynamics, and the silencing of both MBOAT7 and TM6SF2 impaired mitochondrial activity with a shift toward anaerobic glycolysis. MBOAT7-/-TM6SF2-/- cells also showed the highest proliferat
Published: 2022

9. Non-alcoholic fatty liver disease and the risk of fibrosis in Italian primary care services: GPS-NAFLD Study

Author: Miele, Luca, Grattagliano, I., Lapi, F., Dajko, M., De Magistris, A., Liguori, Antonio, De Matthaeis, Nicoletta, Rossi, A., Gasbarrini, Antonio, Cricelli, Claudio, Grieco, Antonio, Miele L. (ORCID:0000-0003-3464-0068), Liguori A., De Matthaeis N., Gasbarrini A. (ORCID:0000-0002-7278-4823), Cricelli C., Grieco A. (ORCID:0000-0002-0544-8993), Miele, Luca, Grattagliano, I., Lapi, F., Dajko, M., De Magistris, A., Liguori, Antonio, De Matthaeis, Nicoletta, Rossi, A., Gasbarrini, Antonio, Cricelli, Claudio, Grieco, Antonio, Miele L. (ORCID:0000-0003-3464-0068), Liguori A., De Matthaeis N., Gasbarrini A. (ORCID:0000-0002-7278-4823), Cricelli C., and Grieco A. (ORCID:0000-0002-0544-8993)
Abstract: Background and aims: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally. This study aimed to determine the prevalence of NAFLD and the probability of liver fibrosis in Italian primary care services. Methods: We carried out a population-based and nested case–control study including all individuals aged 18 years and above registered at Italian primary care services. Data were collected from the general practitioners' network from 2010 to 2017. NAFLD cases were identified via the ICD-9-CM and Hepatic Steatosis Index score > 36 and were matched each up to 10 controls. Other causes of liver diseases were excluded. The risk of fibrosis was assessed using the FIB-4 and NAFLD fibrosis scores (NFS). Results: NAFLD was present in 9% of the primary care population with high regional variability. Among NAFLD subjects: 25% had diabetes, 10% had chronic kidney disease, 11% had cardiovascular disease and 28% were obese. Furthermore, 30% had at least two comorbidities and 13% had cirrhosis. Once cirrhosis was excluded, the risk of any degree of fibrosis was 13.8% with NFS and 20.5% with FIB-4 in subjects <65 years. Conclusions: Even if there is an identification gap in primary care, recorded cases with NAFLD have a high frequency of associated comorbidities. Despite regional variability, a close relation between cirrhosis and NAFLD exists (OR: 3.48, 95% CI: 3.23–3.76). Therefore, the use of non-invasive tests should be promoted in primary care as a useful tool for the early identification of fibrosis risk, independently of evidence of steatosis.
Published: 2022

10. Availability of a Web and Smartphone Application to Stratify the Risk of of Early Allograft Failure Requiring Liver Retransplantation

Author: Avolio, Alfonso Wolfango, Contegiacomo, Andrea, Agnes, Salvatore, Marrone, Giuseppe, Moschetta, Giovanni, Miele, Luca, Melcher, Ml, Avolio, AW (ORCID:0000-0003-2491-7625), Contegiacomo, A (ORCID:0000-0003-1489-6314), Agnes, S (ORCID:0000-0002-3341-4221), Marrone, G, Moschetta, G, Miele, L (ORCID:0000-0003-3464-0068), Avolio, Alfonso Wolfango, Contegiacomo, Andrea, Agnes, Salvatore, Marrone, Giuseppe, Moschetta, Giovanni, Miele, Luca, Melcher, Ml, Avolio, AW (ORCID:0000-0003-2491-7625), Contegiacomo, A (ORCID:0000-0003-1489-6314), Agnes, S (ORCID:0000-0002-3341-4221), Marrone, G, Moschetta, G, and Miele, L (ORCID:0000-0003-3464-0068)
Abstract: [Image: see text]
Published: 2022

11. Project for interventional Oncology LArge-database in liveR Hepatocellular carcinoma - Preliminary CT-based radiomic analysis (POLAR Liver 1.1)

Author: Iezzi, Roberto, Casà, C, Posa, Alessandro, Cornacchione, Patrizia, Carchesio, F, Boldrini, Luca, Tanzilli, A, Cerrito, Lucia, Fionda, B, Longo, V, Miele, Luca, Lancellotta, V, Cellini, Francesco, Tran, H E, Ponziani, Francesca Romana, Giuliante, Felice, Rapaccini, Gian Ludovico, Grieco, Antonio, Pompili, Maurizio, Gasbarrini, Antonio, Valentini, Vincenzo, Gambacorta, Maria Antonietta, Tagliaferri, Luca, Manfredi, Riccardo, Iezzi, R (ORCID:0000-0002-2791-481X), Posa, A, Cornacchione, P, Boldrini, L, Cerrito, L, Miele, L (ORCID:0000-0003-3464-0068), Cellini, F (ORCID:0000-0002-2145-2300), Ponziani, F R (ORCID:0000-0002-5924-6238), Giuliante, F (ORCID:0000-0001-9517-8220), Rapaccini, G L (ORCID:0000-0002-6467-857X), Grieco, A (ORCID:0000-0002-0544-8993), Pompili, M (ORCID:0000-0001-6699-7980), Gasbarrini, A (ORCID:0000-0002-7278-4823), Valentini, V (ORCID:0000-0003-4637-6487), Gambacorta, M A (ORCID:0000-0001-5455-8737), Tagliaferri, L (ORCID:0000-0003-2308-0982), Manfredi, R (ORCID:0000-0002-4972-9500), Iezzi, Roberto, Casà, C, Posa, Alessandro, Cornacchione, Patrizia, Carchesio, F, Boldrini, Luca, Tanzilli, A, Cerrito, Lucia, Fionda, B, Longo, V, Miele, Luca, Lancellotta, V, Cellini, Francesco, Tran, H E, Ponziani, Francesca Romana, Giuliante, Felice, Rapaccini, Gian Ludovico, Grieco, Antonio, Pompili, Maurizio, Gasbarrini, Antonio, Valentini, Vincenzo, Gambacorta, Maria Antonietta, Tagliaferri, Luca, Manfredi, Riccardo, Iezzi, R (ORCID:0000-0002-2791-481X), Posa, A, Cornacchione, P, Boldrini, L, Cerrito, L, Miele, L (ORCID:0000-0003-3464-0068), Cellini, F (ORCID:0000-0002-2145-2300), Ponziani, F R (ORCID:0000-0002-5924-6238), Giuliante, F (ORCID:0000-0001-9517-8220), Rapaccini, G L (ORCID:0000-0002-6467-857X), Grieco, A (ORCID:0000-0002-0544-8993), Pompili, M (ORCID:0000-0001-6699-7980), Gasbarrini, A (ORCID:0000-0002-7278-4823), Valentini, V (ORCID:0000-0003-4637-6487), Gambacorta, M A (ORCID:0000-0001-5455-8737), Tagliaferri, L (ORCID:0000-0003-2308-0982), and Manfredi, R (ORCID:0000-0002-4972-9500)
Abstract: N/A
Published: 2022

12. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)

Author: Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Federici M., Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), and Federici M.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
Published: 2022

13. Copy number variation and expression of exportin-4 associates with severity of fibrosis in metabolic associated fatty liver disease

Author: Metwally, M., Bayoumi, A., Khan, A., Adams, L. A., Aller, R., Garcia-Monzon, C., Arias-Loste, M. T., Bugianesi, E., Miele, Luca, Anna, A., Latchoumanin, O., Han, S., Alenizi, S., Sharkawy, R. E., Elattar, A., Gallego-Duran, R., Fischer, J., Berg, T., Liddle, C., Romero-Gomez, M., George, J., Eslam, M., Miele L. (ORCID:0000-0003-3464-0068), Metwally, M., Bayoumi, A., Khan, A., Adams, L. A., Aller, R., Garcia-Monzon, C., Arias-Loste, M. T., Bugianesi, E., Miele, Luca, Anna, A., Latchoumanin, O., Han, S., Alenizi, S., Sharkawy, R. E., Elattar, A., Gallego-Duran, R., Fischer, J., Berg, T., Liddle, C., Romero-Gomez, M., George, J., Eslam, M., and Miele L. (ORCID:0000-0003-3464-0068)
Published: 2021

14. A comparative study of serum angiogenic biomarkers in cirrhosis and hepatocellular carcinoma

Author: Pocino, Krizia, Napodano, C., Marino, Mariapaola, Di Santo, R., Miele, Luca, De Matthaeis, Nicoletta, Gulli, F., Saporito, R., Rapaccini, Gian Ludovico, Ciasca, Gabriele, Basile, Umberto, Pocino K. (ORCID:0000-0003-2456-5308), Marino M. (ORCID:0000-0001-9155-6378), Miele L. (ORCID:0000-0003-3464-0068), De Matthaeis N., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Ciasca G. (ORCID:0000-0002-3694-8229), Basile U., Pocino, Krizia, Napodano, C., Marino, Mariapaola, Di Santo, R., Miele, Luca, De Matthaeis, Nicoletta, Gulli, F., Saporito, R., Rapaccini, Gian Ludovico, Ciasca, Gabriele, Basile, Umberto, Pocino K. (ORCID:0000-0003-2456-5308), Marino M. (ORCID:0000-0001-9155-6378), Miele L. (ORCID:0000-0003-3464-0068), De Matthaeis N., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Ciasca G. (ORCID:0000-0002-3694-8229), and Basile U.
Published: 2021

15. The KLB rs17618244 gene variant is associated with fibrosing MAFLD by promoting hepatic stellate cell activation

Author: Panera, N., Meroni, M., Longo, M., Crudele, A., Valenti, L., Bellacchio, E., Miele, Luca, D'Oria, V., Paolini, E., Maggioni, M., Fracanzani, A. L., Alisi, A., Dongiovanni, P., Miele L. (ORCID:0000-0003-3464-0068), Panera, N., Meroni, M., Longo, M., Crudele, A., Valenti, L., Bellacchio, E., Miele, Luca, D'Oria, V., Paolini, E., Maggioni, M., Fracanzani, A. L., Alisi, A., Dongiovanni, P., and Miele L. (ORCID:0000-0003-3464-0068)
Published: 2021

16. Upper limits of downstaging for hepatocellular carcinoma in liver transplantation

Author: Biolato, M., Galasso, T., Marrone, G., Miele, Luca, Grieco, A., Miele L. (ORCID:0000-0003-3464-0068), Biolato, M., Galasso, T., Marrone, G., Miele, Luca, Grieco, A., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
Published: 2021

17. The rs599839 a>g variant disentangles cardiovascular risk and hepatocellular carcinoma in nafld patients

Author: Meroni, M., Longo, M., Paolini, E., Alisi, A., Miele, L., De Caro, E. R., Pisano, G., Maggioni, M., Soardo, G., Valenti, L. V., Fracanzani, A. L., Dongiovanni, P., Miele L. (ORCID:0000-0003-3464-0068), Meroni, M., Longo, M., Paolini, E., Alisi, A., Miele, L., De Caro, E. R., Pisano, G., Maggioni, M., Soardo, G., Valenti, L. V., Fracanzani, A. L., Dongiovanni, P., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Background and Aims: Dyslipidemia and cardiovascular diseases (CVD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2‐PSRC1‐SORT1 gene cluster, has been associated CVD, but its impact on metabolic traits and on the severity liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 had HCC (NAFLD‐HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC), and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n = 125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima‐media thickness, carotid plaques and hypertension (p <0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The minor G allele was associated with higher risk of HCC, independently of fibrosis severity (odds ratio (OR): 5.62; 95% c.i. 1.77–17.84, p = 0.003), poor prognosis and advanced tumor stage (p <0.05) in the overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p < 0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p < 0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p < 0.0001). In TCGA, PSRC1 over‐expression promoted more aggressive HCC development (p < 0.05). Conclusions: In sum, the rs599839 A>G variant is associated with protection against dyslipidemia and CVD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively.
Published: 2021

18. The histone variant macroh2a1 impacts circadian gene expression and cell phenotype in an in vitro model of hepatocellular carcinoma

Author: Carbone, A., De Santis, E., Cela, O., Giambra, V., Miele, Luca, Marrone, G., Grieco, Antonio, Buschbeck, M., Capitanio, N., Mazza, T., Mazzoccoli, G., Miele L. (ORCID:0000-0003-3464-0068), Grieco A. (ORCID:0000-0002-0544-8993), Carbone, A., De Santis, E., Cela, O., Giambra, V., Miele, Luca, Marrone, G., Grieco, Antonio, Buschbeck, M., Capitanio, N., Mazza, T., Mazzoccoli, G., Miele L. (ORCID:0000-0003-3464-0068), and Grieco A. (ORCID:0000-0002-0544-8993)
Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death worldwide. A foremost risk factor for HCC is obesity/metabolic syndrome‐related non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH), which is prompted by remarkable changes in transcription patterns of genes enriching metabolic, immune/inflammatory, and circadian pathways. Epigenetic mechanisms play a role in NAFLD‐associated HCC, and macroH2A1, a variant of histone H2A, is involved in the pathogenesis modulating the expression of oncogenes and/or tumor suppressor genes and interacting with SIRT1, which crucially impacts the circadian clock circuitry. Hence, we aimed to appraise if and how macroH2A1 regulated the expression patterns of circadian genes in the setting of NAFLD‐associated HCC. We took advantage of an in vitro model of liver cancer represented by HepG2 (human hepatocarcinoma) cells stably knocked down for macroH2A1 and conducted whole transcriptome profiling and deep phenotyping analysis. We found up‐regulation of PER1 along with several deregulated circadian genes, enriching several important pathways and functions related to cancer onset and progression, such as epithelial‐to‐mesenchymal transition, cell cycle deregulation, and DNA damage. PER1 silencing partially mitigated the malignant phenotype induced by the loss of macroH2A1 in HCC cells. In conclusion, our findings suggest a modulatory role for the core circadian protein PER1 in liver carcinogenesis in the context of a lack of the macroH2A1 epigenetic and transcriptional landscape.
Published: 2021

19. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Author: Asselta, R., Paraboschi, E. M., Gerussi, A., Cordell, H. J., Mells, G. F., Sandford, R. N., Jones, D. E., Nakamura, M., Ueno, K., Hitomi, Y., Kawashima, M., Nishida, N., Tokunaga, K., Nagasaki, M., Tanaka, A., Tang, R., Li, Z., Shi, Y., Liu, X., Xiong, M., Hirschfield, G., Siminovitch, K. A., Walker, E., Xie, G., Mason, A., Myers, R., Peltekian, K., Ghent, C., Atkinson, E., Juran, B., Lazaridis, K., Lu, Y., Gu, X., Jing, K., Amos, C., Affronti, A., Brunetto, M., Coco, B., Spinzi, G., Elia, G., Ferrari, C., Lleo, A., Muratori, L., Muratori, P., Portincasa, P., Colli, A., Bruno, S., Colloredo, G., Azzaroli, F., Andreone, P., Bragazzi, M., Alvaro, D., Cardinale, V., Cazzagon, N., Rigamonti, C., Floreani, A., Rosina, F., Ciaccio, A., Cristoferi, L., D'Amato, D., Malinverno, F., Mancuso, C., Massironi, S., Milani, C., O'Donnell, S. E., Ronca, V., Barisani, D., Lampertico, P., Donato, Federica, Fagiuoli, Stefano, Almasio, P. L., Giannini, E., Cursaro, C., Colombo, M., Valenti, L., Miele, Luca, Andriulli, A., Niro, G. A., Grattagliano, I., Morini, L., Casella, G., Vinci, Maria Rosaria, Battezzati, P. M., Crosignani, A., Zuin, M., Mattalia, A., Calvaruso, V., Colombo, S., Benedetti, A., Marzioni, M., Galli, A., Marra, F., Tarocchi, M., Picciotto, A., Morisco, F., Fabris, L., Croce, L. S., Tiribelli, C., Toniutto, P., Strazzabosco, M., Ch'Ng, C. L., Rahman, M., Yapp, T., Sturgess, R., Healey, C., Czajkowski, M., Gunasekera, A., Gyawali, P., Premchand, P., Kapur, K., Marley, R., Foster, G., Watson, A., Dias, A., Subhani, J., Harvey, R., Mccorry, R., Ramanaden, D., Gasem, J., Evans, R., Mathialahan, T., Shorrock, C., Lipscomb, G., Southern, P., Tibble, J., Gorard, D., Palegwala, A., Jones, S., Dawwas, M., Alexander, G., Dolwani, S., Prince, M., Foxton, M., Elphick, D., Mitchison, H., Gooding, I., Karmo, M., Saksena, S., Mendall, M., Patel, M., Ede, R., Austin, A., Sayer, J., Hankey, L., Hovell, C., Fisher, N., Carter, M., Koss, K., Piotrowicz, A., Grimley, C., Neal, D., Lim, G., Levi, S., Ala, A., Broad, A., Saeed, A., Wood, G., Brown, J., Wilkinson, M., Gordon, H., Ramage, J., Ridpath, J., Ngatchu, T., Grover, B., Shaukat, S., Shidrawi, R., Abouda, G., Ali, F., Rees, I., Salam, I., Narain, M., Brown, A., Taylor-Robinson, S., Williams, S., Grellier, L., Banim, P., Das, D., Chilton, A., Heneghan, M., Curtis, H., Gess, M., Drake, I., Aldersley, M., Davies, M., Jones, R., Mcnair, A., Srirajaskanthan, R., Pitcher, M., Sen, S., Bird, G., Barnardo, A., Kitchen, P., Yoong, K., Chirag, O., Sivaramakrishnan, N., Macfaul, G., Jones, D., Shah, A., Evans, C., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Fraser, A., Mills, P., Shallcross, C., Campbell, S., Bathgate, A., Shepherd, A., Dillon, J., Rushbrook, S., Przemioslo, R., Macdonald, C., Metcalf, J., Shmueli, U., Davis, A., Naqvi, A., Lee, T., Ryder, S. D., Collier, J., Klass, H., Ninkovic, M., Cramp, M., Sharer, N., Aspinall, R., Goggin, P., Ghosh, D., Douds, A., Hoeroldt, B., Booth, J., Williams, E., Hussaini, H., Stableforth, W., Ayres, R., Thorburn, D., Marshall, E., Burroughs, A., Mann, S., Lombard, M., Richardson, P., Patanwala, I., Maltby, J., Brookes, M., Mathew, R., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Panter, S., Shearman, J., Bray, G., Butcher, G., Forton, D., Mclindon, J., Cowan, M., Whatley, G., Mandal, A., Gupta, H., Sanghi, P., Jain, S., Pereira, S., Prasad, G., Watts, G., Wright, M., Neuberger, J., Gordon, F., Unitt, E., Grant, A., Delahooke, T., Higham, A., Brind, A., Cox, M., Ramakrishnan, S., King, A., Collins, C., Whalley, S., Li, A., Fraser, J., Bell, A., Wong, V. S., Singhal, A., Gee, I., Ang, Y., Ransford, R., Gotto, J., Millson, C., Bowles, J., Thomas, C., Harrison, M., Galaska, R., Kendall, J., Whiteman, J., Lawlor, C., Gray, C., Elliott, K., Mulvaney-Jones, C., Hobson, L., Van Duyvenvoorde, G., Loftus, A., Seward, K., Penn, R., Maiden, J., Damant, R., Hails, J., Cloudsdale, R., Silvestre, V., Glenn, S., Dungca, E., Wheatley, N., Doyle, H., Kent, M., Hamilton, C., Braim, D., Wooldridge, H., Abrahams, R., Paton, A., Lancaster, N., Gibbins, A., Hogben, K., Desousa, P., Muscariu, F., Musselwhite, J., Mckay, A., Tan, L., Foale, C., Brighton, J., Flahive, K., Nambela, E., Townshend, P., Ford, C., Holder, S., Palmer, C., Featherstone, J., Nasseri, M., Sadeghian, J., Williams, B., Rolls, S. -A., Hynes, A., Duggan, C., Crossey, M., Stansfield, G., Macnicol, C., Wilkins, J., Wilhelmsen, E., Raymode, P., Lee, H. -J., Durant, E., Bishop, R., Ncube, N., Tripoli, S., Casey, R., Cowley, C., Miller, R., Houghton, K., Ducker, S., Wright, F., Bird, B., Baxter, G., Keggans, J., Hughes, M., Grieve, E., Young, K., Williams, D., Ocker, K., Hines, F., Martin, K., Innes, C., Valliani, T., Fairlamb, H., Thornthwaite, S., Eastick, A., Tanqueray, E., Morrison, J., Holbrook, B., Browning, J., Walker, K., Congreave, S., Verheyden, J., Slininger, S., Stafford, L., O'Donnell, D., Ainsworth, M., Lord, S., Kent, L., March, L., Dickson, C., Simpson, D., Longhurst, B., Hayes, M., Shpuza, E., White, N., Besley, S., Pearson, S., Wright, A., Jones, L., Gunter, E., Dewhurst, H., Fouracres, A., Farrington, L., Graves, L., Marriott, S., Leoni, M., Tyrer, D., Dali-kemmery, L., Lambourne, V., Green, M., Sirdefield, D., Amor, K., Colley, J., Shinder, B., Jones, J., Mills, M., Carnahan, M., Taylor, N., Boulton, K., Tregonning, J., Brown, C., Clifford, G., Archer, E., Hamilton, M., Curtis, J., Shewan, T., Walsh, S., Warner, K., Netherton, K., Mupudzi, M., Gunson, B., Gitahi, J., Gocher, D., Batham, S., Pateman, H., Desmennu, S., Conder, J., Clement, D., Gallagher, S., Orpe, J., Chan, P., Currie, L., O'Donohoe, L., Oblak, M., Morgan, L., Quinn, M., Amey, I., Baird, Y., Cotterill, D., Cumlat, L., Winter, L., Greer, S., Spurdle, K., Allison, J., Dyer, S., Sweeting, H., Kordula, J., Aiba, Y., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Kawai, Y., Kohn, S. -S., Gervais, O., Migita, K., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Higuchi, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Takikawa, H., Ohira, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Carbone, M., Cardamone, G., Duga, S., Gershwin, M. E., Seldin, M. F., Invernizzi, P., Donato F., Fagiuoli S., Miele L. (ORCID:0000-0003-3464-0068), Vinci M., Asselta, R., Paraboschi, E. M., Gerussi, A., Cordell, H. J., Mells, G. F., Sandford, R. N., Jones, D. E., Nakamura, M., Ueno, K., Hitomi, Y., Kawashima, M., Nishida, N., Tokunaga, K., Nagasaki, M., Tanaka, A., Tang, R., Li, Z., Shi, Y., Liu, X., Xiong, M., Hirschfield, G., Siminovitch, K. A., Walker, E., Xie, G., Mason, A., Myers, R., Peltekian, K., Ghent, C., Atkinson, E., Juran, B., Lazaridis, K., Lu, Y., Gu, X., Jing, K., Amos, C., Affronti, A., Brunetto, M., Coco, B., Spinzi, G., Elia, G., Ferrari, C., Lleo, A., Muratori, L., Muratori, P., Portincasa, P., Colli, A., Bruno, S., Colloredo, G., Azzaroli, F., Andreone, P., Bragazzi, M., Alvaro, D., Cardinale, V., Cazzagon, N., Rigamonti, C., Floreani, A., Rosina, F., Ciaccio, A., Cristoferi, L., D'Amato, D., Malinverno, F., Mancuso, C., Massironi, S., Milani, C., O'Donnell, S. E., Ronca, V., Barisani, D., Lampertico, P., Donato, Federica, Fagiuoli, Stefano, Almasio, P. L., Giannini, E., Cursaro, C., Colombo, M., Valenti, L., Miele, Luca, Andriulli, A., Niro, G. A., Grattagliano, I., Morini, L., Casella, G., Vinci, Maria Rosaria, Battezzati, P. M., Crosignani, A., Zuin, M., Mattalia, A., Calvaruso, V., Colombo, S., Benedetti, A., Marzioni, M., Galli, A., Marra, F., Tarocchi, M., Picciotto, A., Morisco, F., Fabris, L., Croce, L. S., Tiribelli, C., Toniutto, P., Strazzabosco, M., Ch'Ng, C. L., Rahman, M., Yapp, T., Sturgess, R., Healey, C., Czajkowski, M., Gunasekera, A., Gyawali, P., Premchand, P., Kapur, K., Marley, R., Foster, G., Watson, A., Dias, A., Subhani, J., Harvey, R., Mccorry, R., Ramanaden, D., Gasem, J., Evans, R., Mathialahan, T., Shorrock, C., Lipscomb, G., Southern, P., Tibble, J., Gorard, D., Palegwala, A., Jones, S., Dawwas, M., Alexander, G., Dolwani, S., Prince, M., Foxton, M., Elphick, D., Mitchison, H., Gooding, I., Karmo, M., Saksena, S., Mendall, M., Patel, M., Ede, R., Austin, A., Sayer, J., Hankey, L., Hovell, C., Fisher, N., Carter, M., Koss, K., Piotrowicz, A., Grimley, C., Neal, D., Lim, G., Levi, S., Ala, A., Broad, A., Saeed, A., Wood, G., Brown, J., Wilkinson, M., Gordon, H., Ramage, J., Ridpath, J., Ngatchu, T., Grover, B., Shaukat, S., Shidrawi, R., Abouda, G., Ali, F., Rees, I., Salam, I., Narain, M., Brown, A., Taylor-Robinson, S., Williams, S., Grellier, L., Banim, P., Das, D., Chilton, A., Heneghan, M., Curtis, H., Gess, M., Drake, I., Aldersley, M., Davies, M., Jones, R., Mcnair, A., Srirajaskanthan, R., Pitcher, M., Sen, S., Bird, G., Barnardo, A., Kitchen, P., Yoong, K., Chirag, O., Sivaramakrishnan, N., Macfaul, G., Jones, D., Shah, A., Evans, C., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Fraser, A., Mills, P., Shallcross, C., Campbell, S., Bathgate, A., Shepherd, A., Dillon, J., Rushbrook, S., Przemioslo, R., Macdonald, C., Metcalf, J., Shmueli, U., Davis, A., Naqvi, A., Lee, T., Ryder, S. D., Collier, J., Klass, H., Ninkovic, M., Cramp, M., Sharer, N., Aspinall, R., Goggin, P., Ghosh, D., Douds, A., Hoeroldt, B., Booth, J., Williams, E., Hussaini, H., Stableforth, W., Ayres, R., Thorburn, D., Marshall, E., Burroughs, A., Mann, S., Lombard, M., Richardson, P., Patanwala, I., Maltby, J., Brookes, M., Mathew, R., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Panter, S., Shearman, J., Bray, G., Butcher, G., Forton, D., Mclindon, J., Cowan, M., Whatley, G., Mandal, A., Gupta, H., Sanghi, P., Jain, S., Pereira, S., Prasad, G., Watts, G., Wright, M., Neuberger, J., Gordon, F., Unitt, E., Grant, A., Delahooke, T., Higham, A., Brind, A., Cox, M., Ramakrishnan, S., King, A., Collins, C., Whalley, S., Li, A., Fraser, J., Bell, A., Wong, V. S., Singhal, A., Gee, I., Ang, Y., Ransford, R., Gotto, J., Millson, C., Bowles, J., Thomas, C., Harrison, M., Galaska, R., Kendall, J., Whiteman, J., Lawlor, C., Gray, C., Elliott, K., Mulvaney-Jones, C., Hobson, L., Van Duyvenvoorde, G., Loftus, A., Seward, K., Penn, R., Maiden, J., Damant, R., Hails, J., Cloudsdale, R., Silvestre, V., Glenn, S., Dungca, E., Wheatley, N., Doyle, H., Kent, M., Hamilton, C., Braim, D., Wooldridge, H., Abrahams, R., Paton, A., Lancaster, N., Gibbins, A., Hogben, K., Desousa, P., Muscariu, F., Musselwhite, J., Mckay, A., Tan, L., Foale, C., Brighton, J., Flahive, K., Nambela, E., Townshend, P., Ford, C., Holder, S., Palmer, C., Featherstone, J., Nasseri, M., Sadeghian, J., Williams, B., Rolls, S. -A., Hynes, A., Duggan, C., Crossey, M., Stansfield, G., Macnicol, C., Wilkins, J., Wilhelmsen, E., Raymode, P., Lee, H. -J., Durant, E., Bishop, R., Ncube, N., Tripoli, S., Casey, R., Cowley, C., Miller, R., Houghton, K., Ducker, S., Wright, F., Bird, B., Baxter, G., Keggans, J., Hughes, M., Grieve, E., Young, K., Williams, D., Ocker, K., Hines, F., Martin, K., Innes, C., Valliani, T., Fairlamb, H., Thornthwaite, S., Eastick, A., Tanqueray, E., Morrison, J., Holbrook, B., Browning, J., Walker, K., Congreave, S., Verheyden, J., Slininger, S., Stafford, L., O'Donnell, D., Ainsworth, M., Lord, S., Kent, L., March, L., Dickson, C., Simpson, D., Longhurst, B., Hayes, M., Shpuza, E., White, N., Besley, S., Pearson, S., Wright, A., Jones, L., Gunter, E., Dewhurst, H., Fouracres, A., Farrington, L., Graves, L., Marriott, S., Leoni, M., Tyrer, D., Dali-kemmery, L., Lambourne, V., Green, M., Sirdefield, D., Amor, K., Colley, J., Shinder, B., Jones, J., Mills, M., Carnahan, M., Taylor, N., Boulton, K., Tregonning, J., Brown, C., Clifford, G., Archer, E., Hamilton, M., Curtis, J., Shewan, T., Walsh, S., Warner, K., Netherton, K., Mupudzi, M., Gunson, B., Gitahi, J., Gocher, D., Batham, S., Pateman, H., Desmennu, S., Conder, J., Clement, D., Gallagher, S., Orpe, J., Chan, P., Currie, L., O'Donohoe, L., Oblak, M., Morgan, L., Quinn, M., Amey, I., Baird, Y., Cotterill, D., Cumlat, L., Winter, L., Greer, S., Spurdle, K., Allison, J., Dyer, S., Sweeting, H., Kordula, J., Aiba, Y., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Kawai, Y., Kohn, S. -S., Gervais, O., Migita, K., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Higuchi, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Takikawa, H., Ohira, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Carbone, M., Cardamone, G., Duga, S., Gershwin, M. E., Seldin, M. F., Invernizzi, P., Donato F., Fagiuoli S., Miele L. (ORCID:0000-0003-3464-0068), and Vinci M.
Abstract: Background & Aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10–4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10–6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028–1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09–1.26; P = 9.93 × 10–8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10–9; OR, 1.33; 95% CI, 1.21–1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.
Published: 2021

20. Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus

Author: Bayoumi, A., Elsayed, A., Han, S., Petta, S., Adams, L. A., Aller, R., Khan, A., Garcia-Monzon, C., Arias-Loste, M. T., Miele, Luca, Latchoumanin, O., Alenizi, S., Gallego-Duran, R., Fischer, J., Berg, T., Craxi, A., Metwally, M., Qiao, L., Liddle, C., Yki-Jarvinen, H., Bugianesi, E., Romero-Gomez, M., George, J., Eslam, M., Miele L. (ORCID:0000-0003-3464-0068), Bayoumi, A., Elsayed, A., Han, S., Petta, S., Adams, L. A., Aller, R., Khan, A., Garcia-Monzon, C., Arias-Loste, M. T., Miele, Luca, Latchoumanin, O., Alenizi, S., Gallego-Duran, R., Fischer, J., Berg, T., Craxi, A., Metwally, M., Qiao, L., Liddle, C., Yki-Jarvinen, H., Bugianesi, E., Romero-Gomez, M., George, J., Eslam, M., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases.
Published: 2021

21. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)

Author: Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Federici M., Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), and Federici M.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the past years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato, the Società Italiana di Diabetologia and the Società Italiana dell’Obesità reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l’Eccellenza delle cure and Istituto Superiore di Sanità. Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence Level of evidence of recommendations for each PICO question were reported according to available evidence.
Published: 2021

22. The pathophysiology of gut-liver connection

Author: Maroni, L., Fianchi, F., Miele, Luca, Svegliati Baroni, G., Miele L. (ORCID:0000-0003-3464-0068), Maroni, L., Fianchi, F., Miele, Luca, Svegliati Baroni, G., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: The physiological functions of the liver and the intestine are intimately connected by tightly regulated mechanisms. The liver secretes bile acids in the intestine, which are fundamental in lipid digestion but also regulate the composition of the gut microbiota. In turn, the intestine regulates the synthesis of bile acids by a feedback loop based on the FXR/FGF-19 axis, and secretes in the blood stream a number of incretins that participate in glucose and lipid metabolism, at least in part by modulating hepatic functions. Moreover, alteration of the gut permeability induced by a variety of factors (including dysbiosis) deeply influences the quantity and quality of metabolites and bacterial products that reach the liver via the portal blood and modulate hepatic molecular pathways. The dysregulation of the gut-liver axis plays therefore a crucial role in the pathogenesis of many metabolic diseases, and is actively studied in the context of nonalcoholic fatty liver disease (NAFLD). Strategies aiming at restoring intestinal permeability, modulating dysbiosis, or influencing molecular pathways involved in the regulation of the gut-liver axis have actively been investigated as potential new therapies for NAFLD. In the present chapter, the physiopathological bases of the "leaky gut hypothesis" and their relevance to the development of NAFLD will be presented in details. Moreover, current knowledge on incretins and bile acid pathway modulation in NAFLD will be discussed. © 2021 Copyright
Published: 2021

23. Gemelli decision tree Algorithm to Predict the need for home monitoring or hospitalization of confirmed and unconfirmed COVID-19 patients (GAP-Covid19): preliminary results from a retrospective cohort study

Author: Vetrugno, Giuseppe, Laurenti, Patrizia, Franceschi, Francesco, Foti, Francesco, D'Ambrosio, Floriana, Cicconi, M, La Milia, Daniele Ignazio, Di Pumpo, Marcello, Carini, E, Pascucci, Domenico, Boccia, Stefania, Pastorino, Roberta, Damiani, Gianfranco, De-Giorgio, F, Oliva, Antonio, Nicolotti, Nicola, Cambieri, Andrea, Ghisellini, R, Murri, Rita, Sabatelli, G, Musolino, M, Gasbarrini, Antonio, Montini, Luca, Miele, Luca, Gemelli-Against-Covid, Group, Vetrugno, G (ORCID:0000-0003-0181-2855), Laurenti, P (ORCID:0000-0002-8532-0593), Franceschi, F (ORCID:0000-0001-6266-445X), Foti, F, D'Ambrosio, F, LA Milia, D I, Di Pumpo, M, Pascucci, D (ORCID:0000-0002-5804-2284), Boccia, S (ORCID:0000-0002-1864-749X), Pastorino, R (ORCID:0000-0001-5013-0733), Damiani, G (ORCID:0000-0003-3028-6188), Oliva, A (ORCID:0000-0001-7120-616X), Nicolotti, N, Cambieri, A, Murri, R (ORCID:0000-0003-4263-7854), Gasbarrini, A (ORCID:0000-0002-7278-4823), Montini, L (ORCID:0000-0003-4602-5134), Miele, L (ORCID:0000-0003-3464-0068), Vetrugno, Giuseppe, Laurenti, Patrizia, Franceschi, Francesco, Foti, Francesco, D'Ambrosio, Floriana, Cicconi, M, La Milia, Daniele Ignazio, Di Pumpo, Marcello, Carini, E, Pascucci, Domenico, Boccia, Stefania, Pastorino, Roberta, Damiani, Gianfranco, De-Giorgio, F, Oliva, Antonio, Nicolotti, Nicola, Cambieri, Andrea, Ghisellini, R, Murri, Rita, Sabatelli, G, Musolino, M, Gasbarrini, Antonio, Montini, Luca, Miele, Luca, Gemelli-Against-Covid, Group, Vetrugno, G (ORCID:0000-0003-0181-2855), Laurenti, P (ORCID:0000-0002-8532-0593), Franceschi, F (ORCID:0000-0001-6266-445X), Foti, F, D'Ambrosio, F, LA Milia, D I, Di Pumpo, M, Pascucci, D (ORCID:0000-0002-5804-2284), Boccia, S (ORCID:0000-0002-1864-749X), Pastorino, R (ORCID:0000-0001-5013-0733), Damiani, G (ORCID:0000-0003-3028-6188), Oliva, A (ORCID:0000-0001-7120-616X), Nicolotti, N, Cambieri, A, Murri, R (ORCID:0000-0003-4263-7854), Gasbarrini, A (ORCID:0000-0002-7278-4823), Montini, L (ORCID:0000-0003-4602-5134), and Miele, L (ORCID:0000-0003-3464-0068)
Abstract: OBJECTIVE: To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring.PATIENTS AND METHODS: We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity.RESULTS: Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G(2) value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G(2) and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated.CONCLUSIONS: We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.
Published: 2021

24. Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores

Author: Bianco, C., Jamialahmadi, O., Pelusi, S., Baselli, G., Dongiovanni, P., Zanoni, I., Santoro, L., Maier, S., Liguori, Antonio, Meroni, M., Borroni, V., D'Ambrosio, R., Spagnuolo, Rocco, Alisi, A., Federico, A., Bugianesi, E., Petta, S., Miele, Luca, Vespasiani-Gentilucci, U., Anstee, Q. M., Stickel, F., Hampe, J., Fischer, J., Berg, T., Fracanzani, A. L., Soardo, G., Reeves, H., Prati, D., Romeo, S., Valenti, L., Liguori A., Spagnuolo R., Miele L. (ORCID:0000-0003-3464-0068), Bianco, C., Jamialahmadi, O., Pelusi, S., Baselli, G., Dongiovanni, P., Zanoni, I., Santoro, L., Maier, S., Liguori, Antonio, Meroni, M., Borroni, V., D'Ambrosio, R., Spagnuolo, Rocco, Alisi, A., Federico, A., Bugianesi, E., Petta, S., Miele, Luca, Vespasiani-Gentilucci, U., Anstee, Q. M., Stickel, F., Hampe, J., Fischer, J., Berg, T., Fracanzani, A. L., Soardo, G., Reeves, H., Prati, D., Romeo, S., Valenti, L., Liguori A., Spagnuolo R., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Background & Aims: Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. Methods: We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5). Results: In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p = 0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p <10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p <0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p <10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ~90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p <10-5) and without cirrhosis (p <0.05). Conclusions: Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy of HCC detection and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings. Lay summary: By analyzing variations in genes that contribute to fatty liver disease, we developed
Published: 2021

25. TACROLIMUS BLOOD-BILE RATIO FOR THE EARLY DETECTION OF THE REJECTION GRAFT INJURY AFTER LIVER TRANSPLANTATION

Author: Pascale, Mm, Bianco, G, Ferri, L, Giovinazzo, F, Liguori, A, Marrone, G, Miele, L, Grieco, A, Agnes, S, Miele, L (ORCID:0000-0003-3464-0068), Agnes, S (ORCID:0000-0002-3341-4221), Pascale, Mm, Bianco, G, Ferri, L, Giovinazzo, F, Liguori, A, Marrone, G, Miele, L, Grieco, A, Agnes, S, Miele, L (ORCID:0000-0003-3464-0068), and Agnes, S (ORCID:0000-0002-3341-4221)
Abstract: N/A
Published: 2021

26. COVID-19 and hepatic involvement: The liver as a main actor of the pandemic novel

Author: Napodano, Cecilia, Pocino, Krizia, Stefanile, A, Marino, Mariapaola, Miele, Luca, Gulli, F, Basile, V, Pandolfi, Franco, Gasbarrini, Antonio, Rapaccini, Gian Ludovico, Basile, Umberto, Napodano, C (ORCID:0000-0002-8720-6284), Pocino, K (ORCID:0000-0003-2456-5308), Marino, M (ORCID:0000-0001-9155-6378), Miele, L (ORCID:0000-0003-3464-0068), Pandolfi, F (ORCID:0000-0001-8799-8173), Gasbarrini, A (ORCID:0000-0002-7278-4823), Rapaccini, GL (ORCID:0000-0002-6467-857X), Basile, U, Napodano, Cecilia, Pocino, Krizia, Stefanile, A, Marino, Mariapaola, Miele, Luca, Gulli, F, Basile, V, Pandolfi, Franco, Gasbarrini, Antonio, Rapaccini, Gian Ludovico, Basile, Umberto, Napodano, C (ORCID:0000-0002-8720-6284), Pocino, K (ORCID:0000-0003-2456-5308), Marino, M (ORCID:0000-0001-9155-6378), Miele, L (ORCID:0000-0003-3464-0068), Pandolfi, F (ORCID:0000-0001-8799-8173), Gasbarrini, A (ORCID:0000-0002-7278-4823), Rapaccini, GL (ORCID:0000-0002-6467-857X), and Basile, U
Abstract: In the natural history of SARS-CoV-2 infection, liver injury is frequent but quite mild and it is defined as any liver damage occurring during disease progression and treatment of infection in patients with or without pre-existing liver diseases. The underlying mechanisms for hepatic injury in patients with COVID-19 are still unclear but the liver damage in SARS-CoV-2 infection seems to be directly caused by virus-induced cytopathic effects. In this review, we will summarize all data of updated literature, regarding the relationship between SARS-CoV-2 infection, acute response and liver involvement. An overview will be given on liver injury, liver transplant and the possible consequences of COVID-19 in patients with pre-existing liver diseases.
Published: 2021

27. Nonalcoholic fatty liver disease (Nafld) as model of gut–liver axis interaction: From pathophysiology to potential target of treatment for personalized therapy

Author: Fianchi, Francesca, Liguori, Antonio, Gasbarrini, Antonio, Grieco, Antonio, Miele, Luca, Fianchi F., Liguori A., Gasbarrini A. (ORCID:0000-0002-7278-4823), Grieco A. (ORCID:0000-0002-0544-8993), Miele L. (ORCID:0000-0003-3464-0068), Fianchi, Francesca, Liguori, Antonio, Gasbarrini, Antonio, Grieco, Antonio, Miele, Luca, Fianchi F., Liguori A., Gasbarrini A. (ORCID:0000-0002-7278-4823), Grieco A. (ORCID:0000-0002-0544-8993), and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, affecting both adults and children and will result, in the near future, as the leading cause of end-stage liver disease. Indeed, its prevalence is rapidly increasing, and NAFLD is becoming a major public health concern. For this reason, great efforts are needed to identify its pathogenetic factors and new therapeutic approaches. In the past decade, enormous advances understanding the gut–liver axis—the complex network of cross-talking between the gut, microbiome and liver through the portal circulation—have elucidated its role as one of the main actors in the pathogenesis of NAFLD. Indeed, evidence shows that gut microbiota is involved in the development and progression of liver steatosis, inflammation and fibrosis seen in the context of NAFLD, as well as in the process of hepatocarcinogenesis. As a result, gut microbiota is currently emerging as a non-invasive biomarker for the diagnosis of disease and for the assessment of its severity. Additionally, to its enormous diagnostic potential, gut microbiota is currently studied as a therapeutic target in NAFLD: several different approaches targeting the gut homeostasis such as antibiotics, prebiotics, probiotics, symbiotics, adsorbents, bariatric surgery and fecal microbiota transplantation are emerging as promising therapeutic options.
Published: 2021

28. COVID-19, adaptative immune response and metabolic-associated liver disease

Author: Miele, Luca, Napodano, Cecilia, Cesario, Alfredo, De Magistris, A., Pocino, Krizia, Basile, Umberto, Rapaccini, Gian Ludovico, Gasbarrini, Antonio, Grieco, A., Miele L. (ORCID:0000-0003-3464-0068), Napodano C. (ORCID:0000-0002-8720-6284), Cesario A. (ORCID:0000-0003-4687-0709), Pocino K. (ORCID:0000-0003-2456-5308), Basile U., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Miele, Luca, Napodano, Cecilia, Cesario, Alfredo, De Magistris, A., Pocino, Krizia, Basile, Umberto, Rapaccini, Gian Ludovico, Gasbarrini, Antonio, Grieco, A., Miele L. (ORCID:0000-0003-3464-0068), Napodano C. (ORCID:0000-0002-8720-6284), Cesario A. (ORCID:0000-0003-4687-0709), Pocino K. (ORCID:0000-0003-2456-5308), Basile U., Rapaccini G. L. (ORCID:0000-0002-6467-857X), and Gasbarrini A. (ORCID:0000-0002-7278-4823)
Abstract: Metabolic diseases are associated with a higher risk of a severer coronavirus disease 2019 (COVID-19) course, since fatty liver is commonly associated with metabolic disorders, fatty liver itself is considered as a major contributor to low-grade inflammation in obesity and diabetes. Recently a comprehensive term, metabolic (dysfunction) associated fatty liver disease (MAFLD), has been proposed. The hepatic inflammatory status observed in MAFLD patients is amplified in presence of severe acute respiratory syndrome coronavirus 2 infection. Intestinal dysbiosis is a powerful activator of inflammatory mediator production of liver macrophages. The intestinal microbiome plays a key role in MAFLD progression, which results in non-alcoholic steatohepatitis and liver fibrosis. Therefore, patients with metabolic disorders and COVID-19 can have a worse outcome of COVID-19. This literature review attempts to disentangle the mechanistic link of MAFLD from COVID-19 complexity and to improve knowledge on its pathophysiology.
Published: 2021

29. The role of elastography in non-Alcoholic fatty liver disease

Author: Liguori, Antonio, Ainora, Maria Elena, Riccardi, Laura, Dematthaeis, N., Pizzolante, Fabrizio, Gasbarrini, Antonio, Zocco, Maria Assunta, Grieco, Antonio, Rapaccini, Gian Ludovico, Miele, Luca, Liguori A., Ainora M. E., Riccardi L., Pizzolante F., Gasbarrini A. (ORCID:0000-0002-7278-4823), Zocco M. A. (ORCID:0000-0002-0814-9542), Grieco A. (ORCID:0000-0002-0544-8993), Rapaccini G. (ORCID:0000-0002-6467-857X), Miele L. (ORCID:0000-0003-3464-0068), Liguori, Antonio, Ainora, Maria Elena, Riccardi, Laura, Dematthaeis, N., Pizzolante, Fabrizio, Gasbarrini, Antonio, Zocco, Maria Assunta, Grieco, Antonio, Rapaccini, Gian Ludovico, Miele, Luca, Liguori A., Ainora M. E., Riccardi L., Pizzolante F., Gasbarrini A. (ORCID:0000-0002-7278-4823), Zocco M. A. (ORCID:0000-0002-0814-9542), Grieco A. (ORCID:0000-0002-0544-8993), Rapaccini G. (ORCID:0000-0002-6467-857X), and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Non-Alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its prevalence is even higher in patients with risk factors such as type 2 diabetes and obesity. Liver biopsy is the gold standard for diagnosis of non-Alcoholic steatohepatitis (NASH), particularly for the assessment of fibrosis stage that is a key prognostic factor. Noninvasive methods for assessment of liver fibrosis are a huge need in contemporary hepatology in order to stratify patient s risk of advanced and progressive liver disease. In this perspective different imaging techniques have been developed in last decades and showed high performance in liver fibrosis evaluation. Strengths and weaknesses of all imaging methods are summarized in this review. (Cite this article as: Liguori A, Ainora ME, Riccardi L, De Matthaeis N, Pizzolante F, Gasbarrini A, et al. The role of elastography in non-Alcoholic fatty liver disease. Minerva Gastroenterol.
Published: 2021

30. A machine-learning parsimonious multivariable predictive model of mortality risk in patients with Covid-19

Author: Murri, Rita, Lenkowicz, Jacopo, Masciocchi, Carlotta, Iacomini, C., Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, G., Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Armuzzi, Alessandro, Barba, Marta, Baroni, Silvia, Bellesi, Silvia, Bentivoglio, Anna Rita, Biasucci, Luigi Marzio, Biscetti, Federico, Candelli, Marcello, Capalbo, Gennaro, Cattani Franchi, Paola, Chiusolo, Patrizia, Cingolani, Antonella, Corbo, Giuseppe Maria, Covino, Marcello, Cozzolino, A. M., D'Alfonso, Maria Elena, De Angelis, Giulia, De Pascale, Gennaro, Frisullo, Giovanni, Gabrielli, M., Gambassi, Giovanni, Garcovich, M., Gremese, Elisa, Grieco, Domenico Luca, Iaconelli, A., Iorio, Raffaele, Landi, Francesco, Larici, Anna Rita, Liuzzo, Giovanna, Maviglia, Riccardo, Miele, Luca, Montalto, Massimo, Natale, Luigi, Nicolotti, Nicola, Ojetti, Veronica, Pompili, Maurizio, Posteraro, Brunella, Rapaccini, Gian Ludovico, Rinaldi, R., Rossi, Elena, Santoliquido, Angelo, Sica, Simona, Tamburrini, Enrica, Teofili, Luciana, Testa, Antonia Carla, Tosoni, A., Trani, Carlo, Varone, Francesco, Verme, L. Z. D., Murri R. (ORCID:0000-0003-4263-7854), Lenkowicz J., Masciocchi C., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), Valentini V. (ORCID:0000-0003-4637-6487), Armuzzi A. (ORCID:0000-0003-1572-0118), Barba M. (ORCID:0000-0001-6084-7666), Baroni S. (ORCID:0000-0002-3410-2617), Bellesi S., Bentivoglio A. (ORCID:0000-0002-9663-095X), Biasucci L. M. (ORCID:0000-0002-6921-6497), Biscetti F. (ORCID:0000-0001-7449-657X), Candelli M. (ORCID:0000-0001-8443-7880), Capalbo G., Cattani P. (ORCID:0000-0003-4678-4763), Chiusolo P. (ORCID:0000-0002-1355-1587), Cingolani A. (ORCID:0000-0002-3793-2755), Corbo G. (ORCID:0000-0002-8104-4659), Covino M. (ORCID:0000-0002-6709-2531), D'Alfonso M., De Angelis G. (ORCID:0000-0002-7087-7399), De Pascale G. (ORCID:0000-0002-8255-0676), Frisullo G., Gambassi G. (ORCID:0000-0002-7030-9359), Gremese E. (ORCID:0000-0002-2248-1058), Grieco D. L. (ORCID:0000-0002-4557-6308), Iorio R. (ORCID:0000-0002-6270-0956), Landi F. (ORCID:0000-0002-3472-1389), Larici A. (ORCID:0000-0002-1882-6244), Liuzzo G. (ORCID:0000-0002-5714-0907), Maviglia R., Miele L. (ORCID:0000-0003-3464-0068), Montalto M. (ORCID:0000-0001-8819-3684), Natale L. (ORCID:0000-0002-7949-5119), Nicolotti N., Ojetti V. (ORCID:0000-0002-8953-0707), Pompili M. (ORCID:0000-0001-6699-7980), Posteraro B. (ORCID:0000-0002-1663-7546), Rapaccini G. (ORCID:0000-0002-6467-857X), Rossi E. (ORCID:0000-0002-7572-9379), Santoliquido A. (ORCID:0000-0003-1539-4017), Sica S. (ORCID:0000-0003-2426-3465), Tamburrini E. (ORCID:0000-0003-4930-426X), Teofili L. (ORCID:0000-0002-7214-1561), Testa A. (ORCID:0000-0003-2217-8726), Trani C. (ORCID:0000-0001-9777-013X), Varone F., Murri, Rita, Lenkowicz, Jacopo, Masciocchi, Carlotta, Iacomini, C., Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, G., Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Armuzzi, Alessandro, Barba, Marta, Baroni, Silvia, Bellesi, Silvia, Bentivoglio, Anna Rita, Biasucci, Luigi Marzio, Biscetti, Federico, Candelli, Marcello, Capalbo, Gennaro, Cattani Franchi, Paola, Chiusolo, Patrizia, Cingolani, Antonella, Corbo, Giuseppe Maria, Covino, Marcello, Cozzolino, A. M., D'Alfonso, Maria Elena, De Angelis, Giulia, De Pascale, Gennaro, Frisullo, Giovanni, Gabrielli, M., Gambassi, Giovanni, Garcovich, M., Gremese, Elisa, Grieco, Domenico Luca, Iaconelli, A., Iorio, Raffaele, Landi, Francesco, Larici, Anna Rita, Liuzzo, Giovanna, Maviglia, Riccardo, Miele, Luca, Montalto, Massimo, Natale, Luigi, Nicolotti, Nicola, Ojetti, Veronica, Pompili, Maurizio, Posteraro, Brunella, Rapaccini, Gian Ludovico, Rinaldi, R., Rossi, Elena, Santoliquido, Angelo, Sica, Simona, Tamburrini, Enrica, Teofili, Luciana, Testa, Antonia Carla, Tosoni, A., Trani, Carlo, Varone, Francesco, Verme, L. Z. D., Murri R. (ORCID:0000-0003-4263-7854), Lenkowicz J., Masciocchi C., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), Valentini V. (ORCID:0000-0003-4637-6487), Armuzzi A. (ORCID:0000-0003-1572-0118), Barba M. (ORCID:0000-0001-6084-7666), Baroni S. (ORCID:0000-0002-3410-2617), Bellesi S., Bentivoglio A. (ORCID:0000-0002-9663-095X), Biasucci L. M. (ORCID:0000-0002-6921-6497), Biscetti F. (ORCID:0000-0001-7449-657X), Candelli M. (ORCID:0000-0001-8443-7880), Capalbo G., Cattani P. (ORCID:0000-0003-4678-4763), Chiusolo P. (ORCID:0000-0002-1355-1587), Cingolani A. (ORCID:0000-0002-3793-2755), Corbo G. (ORCID:0000-0002-8104-4659), Covino M. (ORCID:0000-0002-6709-2531), D'Alfonso M., De Angelis G. (ORCID:0000-0002-7087-7399), De Pascale G. (ORCID:0000-0002-8255-0676), Frisullo G., Gambassi G. (ORCID:0000-0002-7030-9359), Gremese E. (ORCID:0000-0002-2248-1058), Grieco D. L. (ORCID:0000-0002-4557-6308), Iorio R. (ORCID:0000-0002-6270-0956), Landi F. (ORCID:0000-0002-3472-1389), Larici A. (ORCID:0000-0002-1882-6244), Liuzzo G. (ORCID:0000-0002-5714-0907), Maviglia R., Miele L. (ORCID:0000-0003-3464-0068), Montalto M. (ORCID:0000-0001-8819-3684), Natale L. (ORCID:0000-0002-7949-5119), Nicolotti N., Ojetti V. (ORCID:0000-0002-8953-0707), Pompili M. (ORCID:0000-0001-6699-7980), Posteraro B. (ORCID:0000-0002-1663-7546), Rapaccini G. (ORCID:0000-0002-6467-857X), Rossi E. (ORCID:0000-0002-7572-9379), Santoliquido A. (ORCID:0000-0003-1539-4017), Sica S. (ORCID:0000-0003-2426-3465), Tamburrini E. (ORCID:0000-0003-4930-426X), Teofili L. (ORCID:0000-0002-7214-1561), Testa A. (ORCID:0000-0003-2217-8726), Trani C. (ORCID:0000-0001-9777-013X), and Varone F.
Abstract: The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk sc
Published: 2021

31. Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution and proinflammatory phenotype of platelets

Author: Miele, Luca, Alberelli, M. A., Martini, Maurizio, Liguori, Antonio, Marrone, Giuseppe, Cocomazzi, Alessandra, Vecchio, Fabio Maria, Landolfi, Raffaele, Gasbarrini, Antonio, Grieco, Antonio, De Candia, Erica, Miele L. (ORCID:0000-0003-3464-0068), Martini M. (ORCID:0000-0002-6260-6310), Liguori A., Marrone G., Cocomazzi A., Vecchio F. M. (ORCID:0000-0002-9197-2264), Landolfi R. (ORCID:0000-0002-7913-8576), Gasbarrini A. (ORCID:0000-0002-7278-4823), Grieco A. (ORCID:0000-0002-0544-8993), De Candia E. (ORCID:0000-0003-0942-2819), Miele, Luca, Alberelli, M. A., Martini, Maurizio, Liguori, Antonio, Marrone, Giuseppe, Cocomazzi, Alessandra, Vecchio, Fabio Maria, Landolfi, Raffaele, Gasbarrini, Antonio, Grieco, Antonio, De Candia, Erica, Miele L. (ORCID:0000-0003-3464-0068), Martini M. (ORCID:0000-0002-6260-6310), Liguori A., Marrone G., Cocomazzi A., Vecchio F. M. (ORCID:0000-0002-9197-2264), Landolfi R. (ORCID:0000-0002-7913-8576), Gasbarrini A. (ORCID:0000-0002-7278-4823), Grieco A. (ORCID:0000-0002-0544-8993), and De Candia E. (ORCID:0000-0003-0942-2819)
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation.
Published: 2021

32. Clinical characteristics of metabolic associated fatty liver disease (MAFLD) in subjects with myotonic dystrophy type 1 (DM1)

Author: Miele, Luca, Perna, Alessia, Dajko, M., Zocco, Maria Assunta, De Magistris, A., Nicoletti, Tommaso Filippo, Biolato, Marco, Marrone, Giuseppe, Liguori, Antonio, Maccora, Daria, Valenza, Venanzio, Rossi, Salvatore, Riso, V., Di Natale, Daniele, Gasbarrini, Antonio, Grieco, A., Silvestri, Gabriella, Miele L. (ORCID:0000-0003-3464-0068), Perna A., Zocco M. A. (ORCID:0000-0002-0814-9542), Nicoletti T. F., Biolato M., Marrone G., Liguori A., Maccora D., Valenza V. (ORCID:0000-0002-0023-6625), Rossi S., Di Natale D., Gasbarrini A. (ORCID:0000-0002-7278-4823), Silvestri G. (ORCID:0000-0002-1950-1468), Miele, Luca, Perna, Alessia, Dajko, M., Zocco, Maria Assunta, De Magistris, A., Nicoletti, Tommaso Filippo, Biolato, Marco, Marrone, Giuseppe, Liguori, Antonio, Maccora, Daria, Valenza, Venanzio, Rossi, Salvatore, Riso, V., Di Natale, Daniele, Gasbarrini, Antonio, Grieco, A., Silvestri, Gabriella, Miele L. (ORCID:0000-0003-3464-0068), Perna A., Zocco M. A. (ORCID:0000-0002-0814-9542), Nicoletti T. F., Biolato M., Marrone G., Liguori A., Maccora D., Valenza V. (ORCID:0000-0002-0023-6625), Rossi S., Di Natale D., Gasbarrini A. (ORCID:0000-0002-7278-4823), and Silvestri G. (ORCID:0000-0002-1950-1468)
Abstract: Background: Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. Methods: We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD Results: 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55).
Published: 2021

33. Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution and proinflammatory phenotype of platelets

Author: Miele, Luca, Alberelli, M. A., Martini, Maurizio, Liguori, Antonio, Marrone, G., Cocomazzi, Alessandra, Vecchio, Fabio Maria, Landolfi, Raffaele, Gasbarrini, Antonio, Grieco, A., De Candia, Erica, Miele L. (ORCID:0000-0003-3464-0068), Martini M. (ORCID:0000-0002-6260-6310), Liguori A., Cocomazzi A., Vecchio F. M. (ORCID:0000-0002-9197-2264), Landolfi R. (ORCID:0000-0002-7913-8576), Gasbarrini A. (ORCID:0000-0002-7278-4823), De Candia E. (ORCID:0000-0003-0942-2819), Miele, Luca, Alberelli, M. A., Martini, Maurizio, Liguori, Antonio, Marrone, G., Cocomazzi, Alessandra, Vecchio, Fabio Maria, Landolfi, Raffaele, Gasbarrini, Antonio, Grieco, A., De Candia, Erica, Miele L. (ORCID:0000-0003-3464-0068), Martini M. (ORCID:0000-0002-6260-6310), Liguori A., Cocomazzi A., Vecchio F. M. (ORCID:0000-0002-9197-2264), Landolfi R. (ORCID:0000-0002-7913-8576), Gasbarrini A. (ORCID:0000-0002-7278-4823), and De Candia E. (ORCID:0000-0003-0942-2819)
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation.
Published: 2021

34. The diagnostic performance of PIVKA-II in metabolic and viral hepatocellular carcinoma: A pilot study

Author: Basile, Umberto, Miele, Luca, Napodano, Cecilia, Ciasca, Gabriele, Gulli, F., Pocino, Krizia, De Matthaeis, Nicoletta, Liguori, Antonio, DE MAGISTRIS, A., Marrone, Giuseppe, Biolato, Marco, Marino, Mariapaola, Di Giacinto, Flavio, Gasbarrini, Antonio, Grieco, Antonio, Rapaccini, Gian Ludovico, BASILE U., MIELE L. (ORCID:0000-0003-3464-0068), NAPODANO C. (ORCID:0000-0002-8720-6284), CIASCA G. (ORCID:0000-0002-3694-8229), POCINO K. (ORCID:0000-0003-2456-5308), DE MATTHAEIS N., LIGUORI A., MARRONE G., BIOLATO M., MARINO M. (ORCID:0000-0001-9155-6378), DI GIACINTO F. (ORCID:0000-0002-6726-7768), GASBARRINI A. (ORCID:0000-0002-7278-4823), GRIECO A. (ORCID:0000-0002-0544-8993), RAPACCINI G. L. (ORCID:0000-0002-6467-857X), Basile, Umberto, Miele, Luca, Napodano, Cecilia, Ciasca, Gabriele, Gulli, F., Pocino, Krizia, De Matthaeis, Nicoletta, Liguori, Antonio, DE MAGISTRIS, A., Marrone, Giuseppe, Biolato, Marco, Marino, Mariapaola, Di Giacinto, Flavio, Gasbarrini, Antonio, Grieco, Antonio, Rapaccini, Gian Ludovico, BASILE U., MIELE L. (ORCID:0000-0003-3464-0068), NAPODANO C. (ORCID:0000-0002-8720-6284), CIASCA G. (ORCID:0000-0002-3694-8229), POCINO K. (ORCID:0000-0003-2456-5308), DE MATTHAEIS N., LIGUORI A., MARRONE G., BIOLATO M., MARINO M. (ORCID:0000-0001-9155-6378), DI GIACINTO F. (ORCID:0000-0002-6726-7768), GASBARRINI A. (ORCID:0000-0002-7278-4823), GRIECO A. (ORCID:0000-0002-0544-8993), and RAPACCINI G. L. (ORCID:0000-0002-6467-857X)
Published: 2020

35. High Prevalence and Gender-Related Differences of Gastrointestinal Manifestations in a Cohort of DM1 Patients: A Perspective, Cross-Sectional Study

Author: Perna, A., Maccora, Daria, Rossi, S., Nicoletti, Tommaso Filippo, Zocco, Maria Assunta, Riso, V., Modoni, Anna, Petrucci, A., Valenza, Venanzio, Grieco, Antonio, Miele, Luca, Silvestri, Gabriella, Maccora D., Nicoletti T. F., Zocco M. A. (ORCID:0000-0002-0814-9542), Modoni A., Valenza V. (ORCID:0000-0002-0023-6625), Grieco A. (ORCID:0000-0002-0544-8993), Miele L. (ORCID:0000-0003-3464-0068), Silvestri G. (ORCID:0000-0002-1950-1468), Perna, A., Maccora, Daria, Rossi, S., Nicoletti, Tommaso Filippo, Zocco, Maria Assunta, Riso, V., Modoni, Anna, Petrucci, A., Valenza, Venanzio, Grieco, Antonio, Miele, Luca, Silvestri, Gabriella, Maccora D., Nicoletti T. F., Zocco M. A. (ORCID:0000-0002-0814-9542), Modoni A., Valenza V. (ORCID:0000-0002-0023-6625), Grieco A. (ORCID:0000-0002-0544-8993), Miele L. (ORCID:0000-0003-3464-0068), and Silvestri G. (ORCID:0000-0002-1950-1468)
Published: 2020

36. Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia

Author: Basile, Umberto, Marino, Mariapaola, Gragnani, L., Napodano, Cecilia, Gulli, F., Pocino, Krizia, Lorini, S., Santini, Stefano Angelo, Basile, V., Miele, Luca, Zignego, A. L., Rapaccini, Gian Ludovico, Basile U., Marino M. (ORCID:0000-0001-9155-6378), Napodano C. (ORCID:0000-0002-8720-6284), Pocino K. (ORCID:0000-0003-2456-5308), Santini S. A. (ORCID:0000-0003-1956-5899), Miele L. (ORCID:0000-0003-3464-0068), Rapaccini G. L. (ORCID:0000-0002-6467-857X), Basile, Umberto, Marino, Mariapaola, Gragnani, L., Napodano, Cecilia, Gulli, F., Pocino, Krizia, Lorini, S., Santini, Stefano Angelo, Basile, V., Miele, Luca, Zignego, A. L., Rapaccini, Gian Ludovico, Basile U., Marino M. (ORCID:0000-0001-9155-6378), Napodano C. (ORCID:0000-0002-8720-6284), Pocino K. (ORCID:0000-0003-2456-5308), Santini S. A. (ORCID:0000-0003-1956-5899), Miele L. (ORCID:0000-0003-3464-0068), and Rapaccini G. L. (ORCID:0000-0002-6467-857X)
Published: 2020

37. PREVALENCE OF ADVANCED LIVER FIBROSIS AMONG PRIMARY CARE PATIENTS WITH NAFLD. RESULTS FROM GENERAL PRACTITIONER DATABASE NAFLD (GPS-NAFLD) STUDY

Author: Miele, L, Lapi, F, Grattagliano, I, Liguori, A, Dajko, M, Marrone, G, Biolato, M, Napodano, C, De Magistris, A, Rapaccini, G, Rossi, A, Gasbarrini, A, Cricelli, C, Grieco, A, Miele, L (ORCID:0000-0003-3464-0068), Napodano, C (ORCID:0000-0002-8720-6284), Rapaccini, G (ORCID:0000-0002-6467-857X), Gasbarrini, A (ORCID:0000-0002-7278-4823), Miele, L, Lapi, F, Grattagliano, I, Liguori, A, Dajko, M, Marrone, G, Biolato, M, Napodano, C, De Magistris, A, Rapaccini, G, Rossi, A, Gasbarrini, A, Cricelli, C, Grieco, A, Miele, L (ORCID:0000-0003-3464-0068), Napodano, C (ORCID:0000-0002-8720-6284), Rapaccini, G (ORCID:0000-0002-6467-857X), and Gasbarrini, A (ORCID:0000-0002-7278-4823)
Abstract: N/A
Published: 2020

38. A polygenic risk score for progressive non-alcoholic fatty liver disease risk stratification

Author: Bianco, C, Pelusi, S, Baselli, Ga, Zanoni, I, Taliento, A, Dongiovanni, P, Rametta, R, Borroni, V, Federico, A, Gentilucci, Uv, D'Ambrosio, R, Bugianesi, E, Petta, S, Miele, L, Reeves, Hl, Fracanzani, Al, Soardo, G, Prati, D, Valenti, L, Miele, L (ORCID:0000-0003-3464-0068), Bianco, C, Pelusi, S, Baselli, Ga, Zanoni, I, Taliento, A, Dongiovanni, P, Rametta, R, Borroni, V, Federico, A, Gentilucci, Uv, D'Ambrosio, R, Bugianesi, E, Petta, S, Miele, L, Reeves, Hl, Fracanzani, Al, Soardo, G, Prati, D, Valenti, L, and Miele, L (ORCID:0000-0003-3464-0068)
Abstract: N/A
Published: 2020

39. The European NAFLD Registry: A real-world longitudinal cohort study of nonalcoholic fatty liver disease

Author: Hardy, T., Wonders, K., Younes, R., Aithal, G. P., Aller, R., Allison, M., Bedossa, P., Betsou, F., Boursier, J., Brosnan, M. J., Burt, A., Cobbold, J., Cortez-Pinto, H., Day, C. P., Dufour, J. -F., Ekstedt, M., Francque, S., Harrison, S., Miele, Luca, Nasr, P., Papatheodoridis, G., Petta, S., Tiniakos, D., Torstenson, R., Valenti, L., Holleboom, A. G., Yki-Jarvinen, H., Geier, A., Romero-Gomez, M., Ratziu, V., Bugianesi, E., Schattenberg, J. M., Anstee, Q. M., Miele L. (ORCID:0000-0003-3464-0068), Hardy, T., Wonders, K., Younes, R., Aithal, G. P., Aller, R., Allison, M., Bedossa, P., Betsou, F., Boursier, J., Brosnan, M. J., Burt, A., Cobbold, J., Cortez-Pinto, H., Day, C. P., Dufour, J. -F., Ekstedt, M., Francque, S., Harrison, S., Miele, Luca, Nasr, P., Papatheodoridis, G., Petta, S., Tiniakos, D., Torstenson, R., Valenti, L., Holleboom, A. G., Yki-Jarvinen, H., Geier, A., Romero-Gomez, M., Ratziu, V., Bugianesi, E., Schattenberg, J. M., Anstee, Q. M., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS ‘Liver Investigation: Testing Marker Utility in Steatohepatitis’ consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
Published: 2020

40. Presence of Serum Antinuclear Antibodies Does Not Impact Long-Term Outcomes in Nonalcoholic Fatty Liver Disease

Author: Younes, R., Govaere, O., Petta, S., Miele, Luca, Tiniakos, D., Burt, A., David, E., Vecchio, Fabio Maria, Maggioni, M., Cabibi, D., Fracanzani, A. L., Rosso, C., Blanco, M. J. G., Armandi, A., Caviglia, G. P., Zaki, M. Y. W., Liguori, Antonio, Francione, P., Pennisi, G., Grieco, Antonio, Valenti, L., Anstee, Q. M., Bugianesi, E., Miele L. (ORCID:0000-0003-3464-0068), Vecchio F. M. (ORCID:0000-0002-9197-2264), Liguori A., Grieco A. (ORCID:0000-0002-0544-8993), Younes, R., Govaere, O., Petta, S., Miele, Luca, Tiniakos, D., Burt, A., David, E., Vecchio, Fabio Maria, Maggioni, M., Cabibi, D., Fracanzani, A. L., Rosso, C., Blanco, M. J. G., Armandi, A., Caviglia, G. P., Zaki, M. Y. W., Liguori, Antonio, Francione, P., Pennisi, G., Grieco, Antonio, Valenti, L., Anstee, Q. M., Bugianesi, E., Miele L. (ORCID:0000-0003-3464-0068), Vecchio F. M. (ORCID:0000-0002-9197-2264), Liguori A., and Grieco A. (ORCID:0000-0002-0544-8993)
Abstract: INTRODUCTION: We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD). METHODS: ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months. RESULTS: Although ANA-positive cases had a higher prevalence of nonalcoholic steatohepatitis at baseline, the occurrence of liver-related events, hepatocellula carcinoma, cardiovascular events, extrahepatic malignancy, and overall survival were similar to ANA-negative. DISCUSSION: Once AIH has been ruled out, the long-term outcomes and survival are unaffected by the presence of ANA in patients with NAFLD.
Published: 2020

41. Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease

Author: Bayoumi, Jalil, I., Metwally, M., Adams, L. A., Aller, R., Garcia-Monzon, C., Arias-Loste, M. T., Miele, Luca, Petta, S., Craxi, A., Gallego-Duran, R., Fischer, J., Berg, T., Qiao, L., Liddle, C., Bugianesi, E., Romero-Gomez, M., George, J., Eslam, M., Miele L. (ORCID:0000-0003-3464-0068), Bayoumi, Jalil, I., Metwally, M., Adams, L. A., Aller, R., Garcia-Monzon, C., Arias-Loste, M. T., Miele, Luca, Petta, S., Craxi, A., Gallego-Duran, R., Fischer, J., Berg, T., Qiao, L., Liddle, C., Bugianesi, E., Romero-Gomez, M., George, J., Eslam, M., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17047200 variant was not associated with fibrosis or any other histological features, or with hepatic TLL1 expression. In conclusion, the TLL1 rs17047200 variant is not a risk variant for fibrosis in Caucasian patients with MAFLD. However, TLL1 could be involved in the pathogenesis of liver fibrosis.
Published: 2020

42. Neurotensin up-regulation is associated with advanced fibrosis and hepatocellular carcinoma in patients with MAFLD

Author: Dongiovanni, P., Meroni, M., Petta, S., Longo, M., Alisi, A., Soardo, G., Valenti, L., Miele, Luca, Grimaudo, S., Pennisi, G., Antonio, G., Consonni, D., Fargion, S., Fracanzani, A. L., Miele L. (ORCID:0000-0003-3464-0068), Dongiovanni, P., Meroni, M., Petta, S., Longo, M., Alisi, A., Soardo, G., Valenti, L., Miele, Luca, Grimaudo, S., Pennisi, G., Antonio, G., Consonni, D., Fargion, S., Fracanzani, A. L., and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: Background & aims: Neurotensin (NTS), a 13-aminoacid peptide localized in central nervous system and gastrointestinal tract, is involved in lipid metabolism and promotes various cancers onset mainly by binding to neurotensin receptor 1 (NTSR1). Increased plasma levels of pro-NTS, the stable NTS precursor, have been associated with type 2 diabetes (T2D), cardiovascular diseases and metabolic associated fatty liver disease (MAFLD). We aimed to evaluate 1) the impact of NTS rs1800832 and NTSR1 rs6090453 genetic variants on liver damage in 1166 MAFLD European individuals, 2) the relation between NTS variant and circulating pro-NTS and 3) the hepatic NTS expression by RNAseq transcriptomic analysis in 125 bariatric patients. Results: The NTS rs1800832 G allele was associated with hepatic fibrosis (OR 1.27, 95% confidence interval (CI). 1.02–1.58; p = 0.03), even more in carriers of both NTS and NTSR1 G risk alleles (OR 1.17, 95% CI. 1.03–1.34; p = 0.01), with cirrhosis (OR 1.58, 95% CI. 1.07–2.34; p = 0.02) and HCC (OR 1.98, 95% CI. 1.24–3.2; p = 0.004). Pro-NTS circulating levels were correlated with T2D (p = 0.005), BMI, (p = 0.04), age (p = 0.0016), lobular inflammation (p = 0.0025), fibrosis>2 (p < 0.0001), cirrhosis (p = 0.0009) and HCC (p < 0.0001) and more so after stratification for the NTS G allele. Transcriptomic data showed that hepatic NTS expression correlated with that of fibrogenic genes (p < 0.05). Conclusions: NTS rs1800832 variant is associated with advanced fibrosis and HCC in MAFLD patients likely affecting NTS protein activity. The rs6090453 NTSR1 gene variant synergizes with NTS rs1800832 mutation to promote liver damage. Prospective studies are necessary to confirm NTS role in liver disease progression.
Published: 2020

43. Multimodal sequential treatment for occluded TIPS: Case report and review of literature

Author: De Matthaeis, Nicoletta, Di Stasi, Carmine, Pizzolante, Fabrizio, Manfredi, Riccardo, Rapaccini, Gian Ludovico, Miele, Luca, De Matthaeis N., Di Stasi C. (ORCID:0000-0002-6822-3599), Pizzolante F., Manfredi R. (ORCID:0000-0002-4972-9500), Rapaccini G. L. (ORCID:0000-0002-6467-857X), Miele L. (ORCID:0000-0003-3464-0068), De Matthaeis, Nicoletta, Di Stasi, Carmine, Pizzolante, Fabrizio, Manfredi, Riccardo, Rapaccini, Gian Ludovico, Miele, Luca, De Matthaeis N., Di Stasi C. (ORCID:0000-0002-6822-3599), Pizzolante F., Manfredi R. (ORCID:0000-0002-4972-9500), Rapaccini G. L. (ORCID:0000-0002-6467-857X), and Miele L. (ORCID:0000-0003-3464-0068)
Abstract: N/A
Published: 2020

44. beta-Klotho gene variation is associated with liver damage in children with NAFLD

Author: Dongiovanni, P, Crudele, A, Panera, Nadia, Romito, I, Meroni, M, De Stefanis, C, Palma, A, Comparcola, D, Fracanzani, Al, Miele, Luca, Valenti, L, Nobili, Valerio, Alisi, A, Panera, N, Miele, L (ORCID:0000-0003-3464-0068), Nobili, V, Dongiovanni, P, Crudele, A, Panera, Nadia, Romito, I, Meroni, M, De Stefanis, C, Palma, A, Comparcola, D, Fracanzani, Al, Miele, Luca, Valenti, L, Nobili, Valerio, Alisi, A, Panera, N, Miele, L (ORCID:0000-0003-3464-0068), and Nobili, V
Abstract: Background & Aim: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in adults and children. Along with obesity, diabetes and insulin resistance, genetic factors strongly impact on NAFLD development and progression. Dysregulated bile acid metabolism and the fibroblast growth factor 19 (FGF19) pathway play a pivotal role in NAFLD pathogenesis. However, the mechanism through which the FGF19 receptor system is associated with liver damage in NAFLD remains to be defined.Methods: We evaluated the impact of the rs17618244 G>A beta-Klotho (KLB) variant on liver damage in 249 pediatric patients with biopsy-proven NAFLD and the association of this variant with the expression of hepatic and soluble KLB. In vitro models were established to investigate the role of the KLB mutant.Results: The KLB rs17618244 variant was associated with an increased risk of ballooning and lobular inflammation. KLB plasma levels were lower in carriers of the rs17618244 minor A allele and were associated with lobular inflammation, ballooning and fibrosis. In HepG2 and Huh7 hepatoma cell lines, exposure to free fatty acids caused a severe reduction of intracellular and secreted KLB. Finally, KLB downregulation obtained by the expression of a KLB mutant in HepG2 and Huh7 cells induced intracellular lipid accumulation and upregulation of p62, ACOX1, ACSL1, IL-1 beta and TNF-alpha gene expression.Conclusion: In conclusion, we showed an association between the rsl 7618244 KLB variant, which leads to reduced KLB expression, and the severity of NAFLD in pediatric patients. We can speculate that the KLB protein may exert a protective role against lipotoxicity and inflammation in hepatocytes.Lay summary: Genetic and environmental factors strongly impact on the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). The FGF19/FGFR4/KLB pathway plays a pivotal role in the pathogenesis of NAFLD. The aim of the study was to investigate the impact of
Published: 2020

45. SARS-CoV2 RNA detection in a pancreatic pseudocyst sample

Author: Schepis, Tommaso, Larghi, Alberto Leonardo, Papa, A, Miele, Luca, Panzuto, F, De Biase, L, Annibale, B, Cattani, P, Rapaccini, Gian Ludovico, Schepis, T, Larghi, A, Miele, L (ORCID:0000-0003-3464-0068), Rapaccini, GL (ORCID:0000-0002-6467-857X), Schepis, Tommaso, Larghi, Alberto Leonardo, Papa, A, Miele, Luca, Panzuto, F, De Biase, L, Annibale, B, Cattani, P, Rapaccini, Gian Ludovico, Schepis, T, Larghi, A, Miele, L (ORCID:0000-0003-3464-0068), and Rapaccini, GL (ORCID:0000-0002-6467-857X)
Abstract: The involvement of gastrointestinal system in SARS-CoV2 related disease, COVID-19, is increasingly recognized. COVID-19 associated pancreatic injury has been suggested, but its correlation with pancreatic disease is still unclear. In this case report, we describe the detection of SARS-CoV2 RNA in a pancreatic pseudocyst fluid sample collected from a patient with SARS-CoV2 associated pneumonia and a pancreatic pseudocyst developed as a complication of an acute edematous pancreatitis. The detection of SARS-CoV2 within the pancreatic collection arise the question of whether this virus has a tropism for pancreatic tissue and whether it plays a role in pancreatic diseases occurrence. (C) 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Published: 2020

46. Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD)

Author: Buzova, D., Maugeri, A., Liguori, Antonio, Napodano, Cecilia, Lo Re, O., Oben, J., Alisi, A., Gasbarrini, Antonio, Grieco, Antonio, Cerveny, J., Miele, Luca, Vinciguerra, Maria, Liguori A., Napodano C. (ORCID:0000-0002-8720-6284), Gasbarrini A. (ORCID:0000-0002-7278-4823), Grieco A. (ORCID:0000-0002-0544-8993), Miele L. (ORCID:0000-0003-3464-0068), Vinciguerra M., Buzova, D., Maugeri, A., Liguori, Antonio, Napodano, Cecilia, Lo Re, O., Oben, J., Alisi, A., Gasbarrini, Antonio, Grieco, Antonio, Cerveny, J., Miele, Luca, Vinciguerra, Maria, Liguori A., Napodano C. (ORCID:0000-0002-8720-6284), Gasbarrini A. (ORCID:0000-0002-7278-4823), Grieco A. (ORCID:0000-0002-0544-8993), Miele L. (ORCID:0000-0003-3464-0068), and Vinciguerra M.
Abstract: Background: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. Results: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. Conclusions: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.
Published: 2020

47. Gastrointestinal symptoms and digestive comorbidities in an Italian cohort of patients with COVID-19

Author: Papa, A., Covino, M., Pizzolante, F., Miele, L., Lopetuso, L. R., Bove, V., Iorio, R., Simeoni, B., Vetrone, L. M., Tricoli, L., Mignini, I., Schepis, T., D'Alessandro, A., Coppola, G., Nicoletti, T., Visconti, E., Rapaccini, G., Papa A. (ORCID:0000-0002-4186-7298), Covino M. (ORCID:0000-0002-6709-2531), Pizzolante F., Miele L. (ORCID:0000-0003-3464-0068), Lopetuso L. R., Bove V., Iorio R. (ORCID:0000-0002-6270-0956), Simeoni B., Vetrone L. M., Mignini I., Schepis T., D'Alessandro A., Coppola G., Nicoletti T., Visconti E., Rapaccini G. (ORCID:0000-0002-6467-857X), Papa, A., Covino, M., Pizzolante, F., Miele, L., Lopetuso, L. R., Bove, V., Iorio, R., Simeoni, B., Vetrone, L. M., Tricoli, L., Mignini, I., Schepis, T., D'Alessandro, A., Coppola, G., Nicoletti, T., Visconti, E., Rapaccini, G., Papa A. (ORCID:0000-0002-4186-7298), Covino M. (ORCID:0000-0002-6709-2531), Pizzolante F., Miele L. (ORCID:0000-0003-3464-0068), Lopetuso L. R., Bove V., Iorio R. (ORCID:0000-0002-6270-0956), Simeoni B., Vetrone L. M., Mignini I., Schepis T., D'Alessandro A., Coppola G., Nicoletti T., Visconti E., and Rapaccini G. (ORCID:0000-0002-6467-857X)
Abstract: OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes. PATIENTS AND METHODS: Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint. RESULTS: A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint). CONCLUSIONS: Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faeca
Published: 2020

48. Mediterranean diet and the prevention of non-alcoholic fatty liver disease: Results from a case-control study

Author: Giraldi, Luca, Miele, Luca, Aleksovska, K., Manca, F., Leoncini, Emanuele, Biolato, Marco, Arzani, D., Pirro, Maria Antonia, Marrone, Giuseppe, Cefalo, Chiara Maria Assunta, Racco, S., Liguori, Antonio, Rapaccini, Gian Ludovico, Miggiano, G. A., Gasbarrini, Antonio, Boccia, Stefania, Grieco, Antonio, Giraldi L., Miele L. (ORCID:0000-0003-3464-0068), Leoncini E., Biolato M., Pirro M. A., Marrone G., Cefalo C., Liguori A., Rapaccini G. (ORCID:0000-0002-6467-857X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Boccia S. (ORCID:0000-0002-1864-749X), Grieco A. (ORCID:0000-0002-0544-8993), Giraldi, Luca, Miele, Luca, Aleksovska, K., Manca, F., Leoncini, Emanuele, Biolato, Marco, Arzani, D., Pirro, Maria Antonia, Marrone, Giuseppe, Cefalo, Chiara Maria Assunta, Racco, S., Liguori, Antonio, Rapaccini, Gian Ludovico, Miggiano, G. A., Gasbarrini, Antonio, Boccia, Stefania, Grieco, Antonio, Giraldi L., Miele L. (ORCID:0000-0003-3464-0068), Leoncini E., Biolato M., Pirro M. A., Marrone G., Cefalo C., Liguori A., Rapaccini G. (ORCID:0000-0002-6467-857X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Boccia S. (ORCID:0000-0002-1864-749X), and Grieco A. (ORCID:0000-0002-0544-8993)
Abstract: OBJECTIVE: Few studies report that Mediterranean dietary (MD) pattern has a beneficial role in the progression of non-alcoholic fatty liver disease (NAFLD). Evidence on its potential effect on the onset of disease are, however, scanty. With our study, we evaluated whether MD affects the risk of NAFLD with a large case-control study performed in Italy. PATIENTS AND METHODS: Three hundred and seventy-one cases of NAFLD and 444 controls were questioned on the demographic data and their dietary habits before diagnosis. Additionally, information about lifestyles and other related diseases, such as hypertension and diabetes mellitus were collected. The MD adherence was assessed using a pre-defined Mediterranean Diet Score (MDS). Odds ratios (OR) and 95% confidence intervals (CI) were obtained using a multiple logistic regression model. RESULTS: A high adherence to the MD is significantly associated with decreased risk of NAFLD (OR: 0.83 95% CI: 0.71-0.98). When the different MD components were examined separately, higher legumes consumption (OR: 0.62 95% CI: 0.38-0.99) and high fish consumption (OR 0.38 95% CI: 0.17-0.85) were reported to be protective against NAFLD. CONCLUSIONS: Our study shows that a high adherence to the MD decreases the risk of NAFLD.
Published: 2020

49. COVID-19 and hepatic involvement: The liver as a main actor of the pandemic novel

Author: Napodano, Cecilia, Pocino, Krizia, Stefanile, Annunziata, Marino, Mariapaola, Miele, Luca, Gulli, F., Basile, V., Pandolfi, Franco, Gasbarrini, Antonio, Rapaccini, Gian Ludovico, Basile, Umberto, Napodano C. (ORCID:0000-0002-8720-6284), Pocino K. (ORCID:0000-0003-2456-5308), Stefanile A., Marino M. (ORCID:0000-0001-9155-6378), Miele L. (ORCID:0000-0003-3464-0068), Pandolfi F. (ORCID:0000-0001-8799-8173), Gasbarrini A. (ORCID:0000-0002-7278-4823), Rapaccini G. L. (ORCID:0000-0002-6467-857X), Basile U., Napodano, Cecilia, Pocino, Krizia, Stefanile, Annunziata, Marino, Mariapaola, Miele, Luca, Gulli, F., Basile, V., Pandolfi, Franco, Gasbarrini, Antonio, Rapaccini, Gian Ludovico, Basile, Umberto, Napodano C. (ORCID:0000-0002-8720-6284), Pocino K. (ORCID:0000-0003-2456-5308), Stefanile A., Marino M. (ORCID:0000-0001-9155-6378), Miele L. (ORCID:0000-0003-3464-0068), Pandolfi F. (ORCID:0000-0001-8799-8173), Gasbarrini A. (ORCID:0000-0002-7278-4823), Rapaccini G. L. (ORCID:0000-0002-6467-857X), and Basile U.
Abstract: In the natural history of SARS-CoV-2 infection, liver injury is frequent but quite mild and it is defined as any liver damage occurring during disease progression and treatment of infection in patients with or without pre-existing liver diseases. The underlying mechanisms for hepatic injury in patients with COVID-19 are still unclear but the liver damage in SARS-CoV-2 infection seems to be directly caused by virus-induced cytopathic effects. In this review, we will summarize all data of updated literature, regarding the relationship between SARS-CoV-2 infection, acute response and liver involvement. An overview will be given on liver injury, liver transplant and the possible consequences of COVID-19 in patients with pre-existing liver diseases.
Published: 2020

50. Assessment of neurological manifestations in hospitalized patients with COVID-19

Author: Luigetti, Marco, Iorio, Raffaele, Bentivoglio, Anna Rita, Tricoli, Luca, Riso, Vittorio, Marotta, Jessica, Piano, Carla, Primiano, Guido Alessandro, Zileri Del Verme, L., Lo Monaco, Maria Rita, Calabresi, Paolo, Abbate, V., Acampora, N., Addolorato, G., Agostini, F., Ainora, M. E., Akacha, K., Amato, E., Andreani, F., Andriollo, G., Annetta, Maria Giuseppina, Annicchiarico, B. E., Antonelli, Massimo, Antonucci, G., Anzellotti, G. M., Armuzzi, A., Baldi, F., Barattucci, I., Barillaro, C., Barone, F., Bellantone, R. D. A., Bellieni, A., Bello, G., Benicchi, A., Benvenuto, F., Berardini, L., Berloco, F., Bernabei, R., Bianchi, A., Biasucci, D. G., Biasucci, L. M., Bibbo, S., Bini, A., Bisanti, A., Biscetti, F., Bocci, M. G., Bonadia, N., Bongiovanni, F., Borghetti, A., Bosco, G., Bosello, Silvia Laura, Bove, V., Bramato, G., Brandi, V., Bruni, T., Bruno, C., Bruno, D., Bungaro, M. C., Buonomo, A., Burzo, L., Calabrese, A., Calvello, M. R., Cambieri, A., Cambise, C., Camma, G., Candelli, M., Canistro, G., Cantanale, A., Capalbo, G., Capaldi, L., Capone, E., Capristo, E., Carbone, L., Cardone, S., Carelli, S., Carfi, A., Carnicelli, A., Caruso, C., Casciaro, F. A., Catalano, L., Cauda, R., Cecchini, A. L., Cerrito, L., Cesarano, M., Chiarito, A., Cianci, Rossella, Cicchinelli, S., Ciccullo, A., Cicetti, M., Ciciarello, F., Cingolani, A., Cipriani, M. C., Consalvo, M. L., Coppola, G., Corbo, G. M., Corsello, A., Costante, F., Costanzi, M., Covino, M., Crupi, D., Cutuli, S. L., D'Addio, S., D'Alessandro, A., D'Alfonso, M. E., D'Angelo, E., D'Aversa, F., Damiano, F., De Berardinis, G. M., De Cunzo, T., De Gaetano, D. K., De Luca, G., De Matteis, G., De Pascale, G., De Santis, P., De Siena, M., De Vito, F., Del Gatto, V., Del Giacomo, P., Del Zompo, F., Dell'Anna, A. M., Della, P. D., Di Gialleonardo, L., Di Giambenedetto, S., Di Luca, R., Di Maurizio, L., Di Muro, M., Dusina, A., Eleuteri, D., Esperide, A., Fachechi, D., Faliero, D., Falsiroli, C., Fantoni, M., Fedele, A., Feliciani, D., Ferrante, C., Ferrone, G., Festa, R., Fiore, M. C., Flex, A., Forte, E., Franceschi, Francesco, Francesconi, A., Franza, L., Funaro, B., Fuorlo, M., Fusco, D., Gabrielli, M., Gaetani, E., Galletta, C., Gallo, A., Gambassi, G., Garcovich, M., Gasbarrini, A., Gasparrini, I., Gelli, S., Giampietro, A., Gigante, L., Giuliano, G., Giupponi, B., Gremese, E., Grieco, Domenico Luca, Guerrera, M., Guglielmi, V., Guidone, C., Gulli, A., Iaconelli, A., Iafrati, A., Ianiro, Gianluca, Iaquinta, A., Impagnatiello, M., Inchingolo, R., Intini, E., Iorio, R., Izzi, I. M., Jovanovic, T., Kadhim, C., La Macchia, R., La Milia, D. I., Landi, F., Landi, G., Landi, R., Landolfi, R., Leo, M., Leone, P. M., Levantesi, L., Liguori, A., Liperoti, R., Lizzio, M. M., Lo Monaco Maria, R., Locantore, P., Lombardi, F., Lombardi, G., Lopetuso, L., Loria, V., Losito, A. R., Lucia, M. B. P., Macagno, F., Macerola, N., Maggi, G., Maiuro, G., Mancarella, F., Mangiola, F., Manno, A., Marchesini, D., Maresca, G. M., Marrone, G., Martis, I., Martone, A. M., Marzetti, Emanuele, Mattana, C., Matteo, M. V., Maviglia, R., Mazzarella, A., Memoli, C., Miele, Luca, Migneco, A., Mignini, I., Milani, A., Milardi, D., Montalto, M., Montemurro, G., Monti, F., Montini, Luca, Morena, T. C., Morra, V., Morretta, C., Moschese, D., Murace, C. A., Murdolo, M., Murri, Rita, Napoli, M., Nardella, E., Natalello, G., Natalini, D., Navarra, S. M., Nesci, A., Nicoletti, A., Nicoletti, R., Nicoletti, T. F., Nicolo, R., Nicolotti, N., Nista, E. C., Nuzzo, E., Oggiano, M., Ojetti, V., Pagano, F. C., Paiano, G., Pais, C., Pallavicini, F., Palombo, A., Paolillo, F., Papa, Alfredo, Papanice, D., Papparella, L. G., Paratore, M., Parrinello, G., Pasciuto, G., Pasculli, P., Pecorini, G., Perniola, S., Pero, E., Petricca, L., Petrucci, M., Picarelli, C., Piccioni, A., Piccolo, A., Piervincenzi, E., Pignataro, G., Pignataro, R., Pintaudi, G., Pisapia, L., Pizzoferrato, M., Pizzolante, F., Pola, R., Policola, C., Pompili, M., Pontecorvi, F., Pontecorvi, V., Ponziani, F., Popolla, V., Porceddu, E., Porfidia, A., Porro, L. M., Potenza, A., Pozzana, F., Privitera, G., Pugliese, D., Pulcini, G., Racco, S., Raffaelli, F., Ramunno, V., Rapaccini, G. L., Richeldi, Luca, Rinninella, Emanuele, Rocchi, S., Romano, B., Romano, S., Rosa, F., Rossi, L., Rossi, R., Rossini, E., Rota, E., Rovedi, F., Rubino, C., Rumi, G., Russo, A., Sabia, L., Salerno, A., Salini, S., Salvatore, L., Samori, D., Sandroni, Claudio, Sanguinetti, M., Santarelli, L., Santini, P., Santolamazza, D., Santoliquido, A., Santopaolo, F., Santoro, M. C., Sardeo, F., Sarnari, C., Saviano, A., Saviano, L., Scaldaferri, Franco, Scarascia, R., Schepis, T., Schiavello, F., Scoppettuolo, G., Sedda, D., Sessa, F., Sestito, L., Settanni, C., Siciliano, M., Siciliano, V., Sicuranza, R., Simeoni, B., Simonetti, J., Smargiassi, A., Soave, P. M., Sonnino, C., Staiti, D., Stella, C., Stella, L., Stival, E., Taddei, E., Talerico, R., Tamburello, E., Tamburrini, E., Tanzarella, E. S., Tarascio, E., Tarli, C., Tersali, A., Tilli, P., Timpano, J., Torelli, E., Torrini, F., Tosato, M., Tosoni, A., Tricoli, L., Tritto, M., Tumbarello, M., Tummolo, A. M., Vallecoccia, M. S., Valletta, F., Varone, F., Vassalli, F., Ventura, G., Verardi, L., Vetrone, L., Vetrugno, G., Visconti, E., Visconti, F., Viviani, A., Zaccaria, R., Zaccone, C., Zelano, L., Zileri Dal Verme, L., Zuccala, G., Luigetti M. (ORCID:0000-0001-7539-505X), Iorio R. (ORCID:0000-0002-6270-0956), Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Tricoli L., Riso V., Marotta J., Piano C., Primiano G., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Calabresi P. (ORCID:0000-0003-0326-5509), Annetta M. G. (ORCID:0000-0001-7574-1311), Antonelli M. (ORCID:0000-0003-3007-1670), Bosello S. (ORCID:0000-0002-4837-447X), Cianci R. (ORCID:0000-0001-5378-8442), Franceschi F. (ORCID:0000-0001-6266-445X), Grieco D. L. (ORCID:0000-0002-4557-6308), Ianiro G. (ORCID:0000-0002-8318-0515), Marzetti E. (ORCID:0000-0001-9567-6983), Miele L. (ORCID:0000-0003-3464-0068), Montini L. (ORCID:0000-0003-4602-5134), Murri R. (ORCID:0000-0003-4263-7854), Papa A. (ORCID:0000-0002-4186-7298), Richeldi L. (ORCID:0000-0001-8594-1448), Rinninella E. (ORCID:0000-0002-9165-2367), Sandroni C. (ORCID:0000-0002-8878-2611), Scaldaferri F. (ORCID:0000-0001-8334-7541), Luigetti, Marco, Iorio, Raffaele, Bentivoglio, Anna Rita, Tricoli, Luca, Riso, Vittorio, Marotta, Jessica, Piano, Carla, Primiano, Guido Alessandro, Zileri Del Verme, L., Lo Monaco, Maria Rita, Calabresi, Paolo, Abbate, V., Acampora, N., Addolorato, G., Agostini, F., Ainora, M. E., Akacha, K., Amato, E., Andreani, F., Andriollo, G., Annetta, Maria Giuseppina, Annicchiarico, B. E., Antonelli, Massimo, Antonucci, G., Anzellotti, G. M., Armuzzi, A., Baldi, F., Barattucci, I., Barillaro, C., Barone, F., Bellantone, R. D. A., Bellieni, A., Bello, G., Benicchi, A., Benvenuto, F., Berardini, L., Berloco, F., Bernabei, R., Bianchi, A., Biasucci, D. G., Biasucci, L. M., Bibbo, S., Bini, A., Bisanti, A., Biscetti, F., Bocci, M. G., Bonadia, N., Bongiovanni, F., Borghetti, A., Bosco, G., Bosello, Silvia Laura, Bove, V., Bramato, G., Brandi, V., Bruni, T., Bruno, C., Bruno, D., Bungaro, M. C., Buonomo, A., Burzo, L., Calabrese, A., Calvello, M. R., Cambieri, A., Cambise, C., Camma, G., Candelli, M., Canistro, G., Cantanale, A., Capalbo, G., Capaldi, L., Capone, E., Capristo, E., Carbone, L., Cardone, S., Carelli, S., Carfi, A., Carnicelli, A., Caruso, C., Casciaro, F. A., Catalano, L., Cauda, R., Cecchini, A. L., Cerrito, L., Cesarano, M., Chiarito, A., Cianci, Rossella, Cicchinelli, S., Ciccullo, A., Cicetti, M., Ciciarello, F., Cingolani, A., Cipriani, M. C., Consalvo, M. L., Coppola, G., Corbo, G. M., Corsello, A., Costante, F., Costanzi, M., Covino, M., Crupi, D., Cutuli, S. L., D'Addio, S., D'Alessandro, A., D'Alfonso, M. E., D'Angelo, E., D'Aversa, F., Damiano, F., De Berardinis, G. M., De Cunzo, T., De Gaetano, D. K., De Luca, G., De Matteis, G., De Pascale, G., De Santis, P., De Siena, M., De Vito, F., Del Gatto, V., Del Giacomo, P., Del Zompo, F., Dell'Anna, A. M., Della, P. D., Di Gialleonardo, L., Di Giambenedetto, S., Di Luca, R., Di Maurizio, L., Di Muro, M., Dusina, A., Eleuteri, D., Esperide, A., Fachechi, D., Faliero, D., Falsiroli, C., Fantoni, M., Fedele, A., Feliciani, D., Ferrante, C., Ferrone, G., Festa, R., Fiore, M. C., Flex, A., Forte, E., Franceschi, Francesco, Francesconi, A., Franza, L., Funaro, B., Fuorlo, M., Fusco, D., Gabrielli, M., Gaetani, E., Galletta, C., Gallo, A., Gambassi, G., Garcovich, M., Gasbarrini, A., Gasparrini, I., Gelli, S., Giampietro, A., Gigante, L., Giuliano, G., Giupponi, B., Gremese, E., Grieco, Domenico Luca, Guerrera, M., Guglielmi, V., Guidone, C., Gulli, A., Iaconelli, A., Iafrati, A., Ianiro, Gianluca, Iaquinta, A., Impagnatiello, M., Inchingolo, R., Intini, E., Iorio, R., Izzi, I. M., Jovanovic, T., Kadhim, C., La Macchia, R., La Milia, D. I., Landi, F., Landi, G., Landi, R., Landolfi, R., Leo, M., Leone, P. M., Levantesi, L., Liguori, A., Liperoti, R., Lizzio, M. M., Lo Monaco Maria, R., Locantore, P., Lombardi, F., Lombardi, G., Lopetuso, L., Loria, V., Losito, A. R., Lucia, M. B. P., Macagno, F., Macerola, N., Maggi, G., Maiuro, G., Mancarella, F., Mangiola, F., Manno, A., Marchesini, D., Maresca, G. M., Marrone, G., Martis, I., Martone, A. M., Marzetti, Emanuele, Mattana, C., Matteo, M. V., Maviglia, R., Mazzarella, A., Memoli, C., Miele, Luca, Migneco, A., Mignini, I., Milani, A., Milardi, D., Montalto, M., Montemurro, G., Monti, F., Montini, Luca, Morena, T. C., Morra, V., Morretta, C., Moschese, D., Murace, C. A., Murdolo, M., Murri, Rita, Napoli, M., Nardella, E., Natalello, G., Natalini, D., Navarra, S. M., Nesci, A., Nicoletti, A., Nicoletti, R., Nicoletti, T. F., Nicolo, R., Nicolotti, N., Nista, E. C., Nuzzo, E., Oggiano, M., Ojetti, V., Pagano, F. C., Paiano, G., Pais, C., Pallavicini, F., Palombo, A., Paolillo, F., Papa, Alfredo, Papanice, D., Papparella, L. G., Paratore, M., Parrinello, G., Pasciuto, G., Pasculli, P., Pecorini, G., Perniola, S., Pero, E., Petricca, L., Petrucci, M., Picarelli, C., Piccioni, A., Piccolo, A., Piervincenzi, E., Pignataro, G., Pignataro, R., Pintaudi, G., Pisapia, L., Pizzoferrato, M., Pizzolante, F., Pola, R., Policola, C., Pompili, M., Pontecorvi, F., Pontecorvi, V., Ponziani, F., Popolla, V., Porceddu, E., Porfidia, A., Porro, L. M., Potenza, A., Pozzana, F., Privitera, G., Pugliese, D., Pulcini, G., Racco, S., Raffaelli, F., Ramunno, V., Rapaccini, G. L., Richeldi, Luca, Rinninella, Emanuele, Rocchi, S., Romano, B., Romano, S., Rosa, F., Rossi, L., Rossi, R., Rossini, E., Rota, E., Rovedi, F., Rubino, C., Rumi, G., Russo, A., Sabia, L., Salerno, A., Salini, S., Salvatore, L., Samori, D., Sandroni, Claudio, Sanguinetti, M., Santarelli, L., Santini, P., Santolamazza, D., Santoliquido, A., Santopaolo, F., Santoro, M. C., Sardeo, F., Sarnari, C., Saviano, A., Saviano, L., Scaldaferri, Franco, Scarascia, R., Schepis, T., Schiavello, F., Scoppettuolo, G., Sedda, D., Sessa, F., Sestito, L., Settanni, C., Siciliano, M., Siciliano, V., Sicuranza, R., Simeoni, B., Simonetti, J., Smargiassi, A., Soave, P. M., Sonnino, C., Staiti, D., Stella, C., Stella, L., Stival, E., Taddei, E., Talerico, R., Tamburello, E., Tamburrini, E., Tanzarella, E. S., Tarascio, E., Tarli, C., Tersali, A., Tilli, P., Timpano, J., Torelli, E., Torrini, F., Tosato, M., Tosoni, A., Tricoli, L., Tritto, M., Tumbarello, M., Tummolo, A. M., Vallecoccia, M. S., Valletta, F., Varone, F., Vassalli, F., Ventura, G., Verardi, L., Vetrone, L., Vetrugno, G., Visconti, E., Visconti, F., Viviani, A., Zaccaria, R., Zaccone, C., Zelano, L., Zileri Dal Verme, L., Zuccala, G., Luigetti M. (ORCID:0000-0001-7539-505X), Iorio R. (ORCID:0000-0002-6270-0956), Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Tricoli L., Riso V., Marotta J., Piano C., Primiano G., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Calabresi P. (ORCID:0000-0003-0326-5509), Annetta M. G. (ORCID:0000-0001-7574-1311), Antonelli M. (ORCID:0000-0003-3007-1670), Bosello S. (ORCID:0000-0002-4837-447X), Cianci R. (ORCID:0000-0001-5378-8442), Franceschi F. (ORCID:0000-0001-6266-445X), Grieco D. L. (ORCID:0000-0002-4557-6308), Ianiro G. (ORCID:0000-0002-8318-0515), Marzetti E. (ORCID:0000-0001-9567-6983), Miele L. (ORCID:0000-0003-3464-0068), Montini L. (ORCID:0000-0003-4602-5134), Murri R. (ORCID:0000-0003-4263-7854), Papa A. (ORCID:0000-0002-4186-7298), Richeldi L. (ORCID:0000-0001-8594-1448), Rinninella E. (ORCID:0000-0002-9165-2367), Sandroni C. (ORCID:0000-0002-8878-2611), and Scaldaferri F. (ORCID:0000-0001-8334-7541)
Abstract: Background and purpose: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. Methods: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. Results: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. Conclusions: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.
Published: 2020

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