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Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). Results: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin–bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82–0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0–0.8%, 1.5–4.8%, and 8.1–19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7–100% and a negative predictive value of 99.3–100%. The cut-off value of 60 resulted in a specificity of 56.6–95.8% and a positive predictive value of 6.6–15.7%. Conclusions: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. Lay summary: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin–bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity. © 2020 European Association for the Study of the Liver

Background & Aims: The effects of long-term antiviral therapy on survival have not been adequately assessed in chronic hepatitis B (CHB). In this 10-centre, ongoing cohort study, we evaluated the probability of survival and factors affecting survival in Caucasian CHB patients who received long-term entecavir/tenofovir therapy. Methods: We included 1,951 adult Caucasians with CHB, with or without compensated cirrhosis and without hepatocellular carcinoma (HCC) at baseline, who received entecavir/tenofovir for ≥12 months (median, six years). Kaplan–Meier estimates of cumulative survival over time were obtained. Standardized mortality ratios (SMRs) were calculated by comparing death rates with those in the Human Mortality Database. Results: The one-, five-, and eight-year cumulative probabilities were 99.7, 95.9, and 94.1% for overall survival, 99.9, 98.3, and 97.4% for liver-related survival, and 99.9, 97.8, and 95.8% for transplantation-free liver-related survival, respectively. Overall mortality was independently associated with older age and HCC development, liver-related mortality was associated with HCC development only, and transplantation-free liver-related mortality was independently associated with HCC development and lower platelet levels at baseline. Baseline cirrhosis was not independently associated with any type of mortality. Compared with the general population, in all CHB patients mortality was not significantly different (SMR 0.82), whereas it was lower in patients without HCC regardless of baseline cirrhosis (SMR 0.58) and was higher in patients who developed HCC (SMR 3.09). Conclusion: Caucasian patients with CHB and compensated liver disease who receive long-term entecavir/tenofovir therapy have excellent overall and liver-related eight-year survival, which is similar to that of the general population. HCC is the main factor affecting their overall mortality, and is the only factor affecting their liver-related mortality. Lay summary: Caucasian patients with chronic hepatitis B with or without compensated cirrhosis who receive long-term entecavir or tenofovir therapy have excellent overall eight-year survival, which is similar to that of the general population. Hepatocellular carcinoma is the main factor affecting their overall mortality, and is the only factor affecting liver-related mortality in this setting. © 2018 European Association for the Study of the Liver

Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC). Sera from 146 patients with chronic hepatitis B or C, 140 with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and 114 healthy individuals served as disease and healthy controls. Available serum samples during remission from 50 AIH and 39 PBC patients were also investigated by paired analyzes. DNase1-activity was significantly lower in AIH, PBC and PSC compared to viral hepatitis (p < 0.02, p < 0.001, p = 0.03), NAFLD/NASH (p < 0.001) and healthy (p < 0.001). No significant difference was found in between each specific ALD. In AIH, DNAse1-activity was positively correlated with aspartate aminotransferase (AST) (p < 0.02), bilirubin (p < 0.01) and increased IgG (>1400 mg/dl; p < 0.05); in PBC, with AST (p < 0.01), alanine aminotransferase (ALT) (p < 0.03) and anti-mitochondrial antibodies (AMA) (p = 0.008). In PSC, DNase1-activity was inversely associated with alkaline phosphatase (ALP) (p < 0.05). In AIH, complete responders were characterized by increased baseline DNase1-activity compared to partial responders, relapsers and non-responders (p < 0.02), whereas it was significantly increased after achievement of remission (p < 0.001). Serum DNase1-activity is significantly decreased in ALD patients, indicating its potential implication in their pathogenesis. Furthermore, DNase1-activity could be used as a new surrogate biomarker for predicting response to AIH treatment. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Background & Aims Risk scores for hepatocellular carcinoma (HCC) developed in Asians offer poor-moderate predictability in Caucasian patients with chronic hepatitis B (CHB). This nine center cohort study aimed to develop and validate an accurate HCC risk score in Caucasian CHB patients treated with the current oral antivirals, entecavir/tenofovir. Methods We included 1815 adult Caucasians with CHB and no HCC at baseline who received entecavir/tenofovir for ≥12 months. Using data from eight centers (derivation dataset, n = 1325), a HCC risk score was developed based on multivariable Cox models and points system for simplification. Harrell's c-index was used as discrimination, bootstrap for internal validation and the data from the 9th and largest center (validation dataset, n = 490) for external validation. Results The 5-year cumulative HCC incidence rates were 5.7% and 8.4% in the derivation and validation dataset, respectively. In the derivation dataset, age, gender, platelets and cirrhosis were independently associated with HCC. The PAGE-B score was developed based on age, gender and platelets (c-index = 0.82, 0.81 after bootstrap validation). The addition of cirrhosis did not substantially improve the discrimination (c-index = 0.84). The predictability of PAGE-B score was similar (c-index = 0.82) in the validation dataset. Patients with PAGE-B ≤9, 10-17, ≥18 had 5-year cumulative HCC incidence rates of 0%, 3%, 17% in the derivation and 0%, 4%, 16% in the validation dataset. Conclusion PAGE-B, which is based only on baseline patients' age, gender and platelets, represents a simple and reliable score for prediction of the 5-year HCC risk in Caucasian CHB patients under entecavir/tenofovir. © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A large collection of Staphylococcus aureus including a. 745 clinically significant isolates that were consecutively recovered from human infections during 2012-2013, b. 19 methicil-lin-susceptible (MSSA), randomly selected between 2006-2011 from our Staphylococcal Collection, c. 16 human colonizing isolates, and d. 10 strains from colonized animals was investigated for the presence and the molecular characteristics of CC398. The study was conducted in Thessaly, a rural region in Greece. The differentiation of livestock-associated clade from the human clade was based on canSNPs combined with the presence of the 3 bacteriophage and the tetM, scn, sak, and chp genes. Among the 745 isolates, two MRSA (0.8% of total MRSA) and thirteen MSSA (2.65% of total MSSA) were found to belong to CC398, while, between MSSA of our Staphylococcal Collection, one CC398, isolated in 2010, was detected. One human individual, without prior contact with animals, was found to be colonized by a MSSA CC398. No CC398 was identified among the 10 S. aureus isolated from animals. Based on the molecular markers, the 17 CC398 strains were equally placed in the livestock-associated and in the human clades. This is the first report for the dissemination of S. aureus CC398 among humans in Greece. © 2015 Sarrou et al.