Search

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.MethodsWe analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.ResultsMAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002–2003, to 77.3% and 28.9% in 2018–2019, respectively, pConclusionsThe prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

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.

The prevalence of acute diverticulitis (AD) has progressively increased in recent decades, with correspondingly greater morbidity and mortality. The aim of the study is to develop a predictive score to identify patients with the highest risk of complicated AD. The clinical records of 1089 patients referred to the emergency department (ED) over a five-year period were reviewed. In multivariate analysis, male sex (p &lt, 0.001), constipation (p = 0.002), hemoglobin &lt, 11.9 g/dL (p &lt, 0.001), C reactive protein &gt, 80 mg/L (p &lt, 0.001), severe obesity (p = 0.049), and no proton pump inhibitor treatment (p = 0.003) were independently associated with complicated AD. The predictive assessment of complicated (PACO)-diverticulitis (D) score, including these six variables, was applied to the retrospective cohort and then validated prospectively in a cohort including 282 patients. It categorized patients into three risk classes for complicated AD. The PACO-D score showed fair discrimination for complicated AD with an area under the receiver operating characteristic curve of 0.674 and 0.648, in the retrospective and prospective cohorts, respectively. The PACO-D score could be a practical clinical tool to identify patients at highest risk for complicated AD referred to the ED so that appropriate diagnostic and therapeutic resources could be appropriately allocated. Further external validation is needed to confirm these results.

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and represent a common finding in highly prevalent metabolic disorders (i.e. type 2 diabetes, metabolic syndrome, obesity). Non-alcoholic steatohepatitis (NASH) requires liver biopsy for grading and staging the liver damage by the assessment of steatosis, inflammation and fibrosis. In parallel with the development of numerous 'liquid' biomarkers and algorithms that combine anthropometric and laboratory parameters, innovative hepatic imaging techniques have increasingly been developed to attempt to overcome the need for biopsy, both in diagnosis and staging of NAFLD, and in possible use in the follow-up of the disease. In this review, we focused on the different imaging techniques trying to highlight the strengths and disadvantages of different approaches, particularly for ultrasound techniques, in stratifying liver injury and fibrosis in patients with NAFLD / NASH.

Enterocutaneous fistulas (ECFs) is a manifestation of penetrating Crohn's disease (CD) that is challenging to treat and has considerable morbidity and mortality rates.This review aims to explore the practical and updated principles for the optimal treatment of ECFs in CD patients.Optimal ECF management requires a multidisciplinary approach. Treatment first includes fluid resuscitation and electrolyte rebalancing with control of sepsis by means of antibiotics and, when indicated, drainage of infected collections. Subsequent therapeutic steps include nutritional support, control of the fistula output and treatment of peristomal skin. Anti-TNF-α therapy seems to have limited utility only after sepsis is resolved and intestinal stenosis excluded. However, ECFs heal in only approximately one-third of cases without surgical intervention. Thus, correct surgical timing combined with adequate nutritional support, sepsis resolution and skin care is considered the appropriate preoperative setting.

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE). Alongside the traditional acquired and genetic risk factors for VTE, patients with IBD have pathogenic and clinical peculiarities that are responsible for the increased number of thromboembolic events occurring during their life. A relevant role in modifying this risk in a pro or antithrombotic manner is played by pharmacological therapies and surgery. The availability of several biological agents and small-molecule drugs with different mechanisms of action allows us to also tailor the treatment based on the individual prothrombotic risk to reduce the occurrence of VTE. Available review articles did not provide sufficient and updated knowledge on this topic. Therefore, we assessed the role of each single treatment, including surgery, in modifying the risk of VTE in patients with IBD to provide physicians with recommendations to minimize VTE occurrence. We found that the use of steroids, particularly if prolonged, increased VTE risk, whereas the use of infliximab seemed to reduce such risk. The data relating to the hypothesized prothrombotic risk of tofacitinib were insufficient to draw definitive conclusions. Moreover, surgery has an increased prothrombotic risk. Therefore, implementing measures to prevent VTE, not only with pharmacological prophylaxis but also by reducing patient- and surgery-specific risk factors, is necessary. Our findings confirm the importance of the knowledge of the effect of each single drug or surgery on the overall VTE risk in patients with IBD, even if further data, particularly regarding newer drugs, are needed.

Background and aim Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods and results We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 controls. PTPN2 genotype distribution did not significantly differ between patients and controls. In the entire population, patients with PTPN2 rs2542151 T→G (dominant model) have a higher prevalence of diabetes; 345 patients (60.9%) underwent liver biopsy: 198 (57.4%) had steatohepatitis and 75 (21.7%) had advanced fibrosis. At multiple logistic regression analysis PTPN2 rs2542151 T→G was associated with T2DM (OR 2.14, 95% CI 1.04–4.40, P = 0.03). Patients who underwent liver biopsy, rs2542151 T→G of PTPN2 was independently associated with severe steatosis (OR 2.00, 95% CI 1.17–3.43, p = 0.01) and severe fibrosis (OR 2.23, 95% CI 1.06–4.72, P = 0.03). Conclusion Our study shows that NAFLD patients with rs2542151 T→G of PTPN2 have a higher severity of fatty liver disease and a higher prevalence of T2DM. These results suggest that individual genetic susceptibility to intestinal permeability could play a role in liver disease progression.

Background: The role of clinically significant portal hypertension on the prognosis of cirrhotic patients undergoing hepatic resection for hepatocellular carcinoma (HCC) is debated. Aims: In this study, our aim was to assess the role of clinically significant portal hypertension after hepatic resection for HCC in patients with cirrhosis. Methods: We assessed the prognostic role of the presence of clinically significant portal hypertension (oesophageal/gastric varices/portal hypertensive gastropathy or a platelet count 100 vs 86 months, P = 0.742). Conclusions: Presence of clinically significant portal hypertension has no influence on survival of patients with well-compensated cirrhosis undergoing hepatic resection for HCC. © 2013 John Wiley & Sons A/S.

Although the etiology of liver disease affects the features of hepatocellular carcinoma (HCC) diagnosed during surveillance, it is not known whether it influences patients' survival. We analyzed the impact of etiology on the characteristics and outcome of HCC detected during surveillance.In this cohort study, 742 patients with HCC detected during semiannual or annual surveillance were selected from the ITA.LI.CA database, including 1,834 consecutive patients observed in three primary and seven tertiary care settings for HCC. Patients were grouped according to etiology: hepatitis B virus (HBV, 87), hepatitis C virus (HCV, 461), alcohol (59), and multietiology (135).In all etiologic groups, most HCCs were unifocal (51-68%) and most of them wereor=3 cm (60-69%). Unifocal HCCs were less common in the multietiology group (P=0.050) and slightly more frequent in the HCV group (P=0.087). Besides etiology, only age was associated with gross pathology (P=0.023). About two-thirds of HCCs in all groups were discovered at Cancer of the Liver Italyn Program (CLIP) stage 0 or 1. The 1-, 3-, and 5-yr survival rates were comparable among groups (HBV 81%, 47%, and 22%; HCV 86%, 49%, and 24%; alcohol 76%, 41%, and 25%; multietiology 75%, 37%, and 24%; P=0.446). The surveillance interval did not influence survival, which was independently predicted by serum alpha-fetoprotein, Child-Pugh class, gross pathology, cancer size, vascular invasion, and treatment.In patients with HCC diagnosed during surveillance: (a) single nodules are less common in multietiology cases and (b) prognosis is independent of etiology, being dictated by liver function, oncologic features, and treatment.

The clinical and instrumental findings revealed a case of autoimmune polyendocrine syndrome (APS) type 3B+C in a 41-year-old Caucasian woman with unexplained refractory iron-deficiency anaemia secondary to autoimmune atrophic gastritis and a long-term history of two different autoimmune diseases-Hashimoto's disease and vitiligo. Indeed the occurrence in the same patient of three or more autoimmune diseases defines APS. The first classification of APS was suggested by Neufeld and Blizzard in 1980 and it included four main types of APS on the basis of clinical features. The only case of APS type 3B+C was described by Amerio et al in 2006.

To determine whether proliferative patterns in flat rectal mucosal samples can predict the recurrence of adenomatous colorectal polyps, after polypectomy, biopsy specimens from normal looking rectal mucosa were obtained at endoscopy from 55 patients diagnosed for the first time as having adenomatous colorectal polyps. Epithelial cell proliferation was assessed in biopsy specimens through 3H-thymidine autoradiography. After polypectomy, patients were followed for 24 months and underwent complete colonoscopy every 6 months to detect and remove any metachronous lesions. In 40 patients second biopsy specimens were taken during one of the follow up colonoscopies to evaluate the stability of proliferative indices over time. The ratio of labelled (S phase) to total cells (labelling index) for the entire crypt, as well as ratios for each of the five equal compartments into which the crypt had been divided longitudinally, was calculated for each patient. Mean labelling indices for upper crypt compartments 3 and 4 + 5 in the 22 patients in whom polyps recurred were significantly higher (respectively p < 0.05 and p < 0.01) than those of the 33 without recurrence suggesting that an upward shift of the crypt's replicative compartment is associated with polyp recurrence. Labelling indices remained essentially unchanged in those patients who underwent biopsy twice. Reproducible kinetic parameters such as these might be useful in planning follow up of patients with adenomatous polyps after polypectomy.

Background A consensus on the most reliable staging system for hepatocellular carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic Liver Cancer (BCLC) system, adopted by the American Association for the Study of Liver Diseases (AASLD). We investigated how many patients are diagnosed in "very early" and "early" stage, follow the AASLD guidelines for treatment and whether their survival depends on treatment. Methods Data were collected in 530 "very early" and "early" HCC patients recruited by a multicentric Italian collaborative group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival and the log rank to test the statistical significance of difference between groups. Cox's multivariate stepwise regression analysis was used to pinpoint independent prognostic factors and the adjusted relative risks (hazard ratios) were calculated as well. A statistical analysis based on the chi-square test was used to identify significant differences in clinical or pathological features between patients. A P-value < 0.05 was considered statistically significant. Results "Very early" HCC were 3%; Cox multivariate analysis did not identify variables independently associated with survival. The patients following AASLD recommendations (20%) did not show longer survival. In "early" HCC patients (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients treated according to the AASLD criteria survived longer (p = 0,004). The Cox analysis however identified only age, gender, number of lesions and Child class as independent predictors of survival. Conclusion patients with very early" HCC were very few in this analysis. In most instances they were not treated with the treatment suggested as the most appropriate by the AASLD guidelines and the type of treatment had no impact on survival, even though the number of patients was relatively low and part of the patients were diagnosed before the introduction of the guidelines: this analysis, therefore, might not be considered as conclusive and should be validated. The "early" stage group involved more patients, rarely treated according to the guidelines, both overall and also in those diagnosed after their publication; the survival was in part predicted by the type of treatment, with better results in those treated according to AASLD indications.

Background/aim We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. Methods Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy + granulocyte-colony stimulating factor (5 μg/kg/day for 6 days) and standard therapy + granulocyte-colony stimulating factor (15 μg/kg/day s.c. for 6 days). Data on CD34 + cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. Results CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. Conclusions Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation.

Franco Trevisani ], Stefania De Notafiis ], Mafia Chiara Cantafinil, Giardudovico Rapaccini 2, Fabio Fafinati 3, Luisa Benvegnu 4, Marco Zoli 1 , Paolo Del Poggio 5, Mafia Anna Di Nolfo 6, Mauro Bernardi 1.1Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna; 2Unit of Internal Medicine 11, Catholic University of Rome; 3Unit of Gastroenterology, University of Padua; 4Department of Experimental and Clinical Medicine, University of Padua; 5 Unit of Medicine, Treviglio-Caravaggio Hospital, Treviglio; 6Unit of Medicine, Bolognini Hospital, Seriate, Italy