Hepatitis C virus (HCV) possesses a second open reading frame (ORF) within the core gene encoding an additional protein, known as the alternative reading frame protein (ARFP), F or core+1. The biological significance of the core+1/ARF protein remains elusive. However, several independent studies have shown the presence of core+1/ARFP antibodies in chronically HCV-infected patients. Furthermore, a higher prevalence of core+1/ARFP antibodies was detected in patients with HCV-associated hepatocellular carcinoma (HCC). Here, we investigated the incidence of core+1/ARFPantibodies in chronically HCV-infected patients at different stages of cirrhosis in comparison to chronically HCV-infected patients at earlier stages of disease. Using ELISA, we assessed the prevalence of anti-core+1 antibodies in 30 patients with advanced cirrhosis [model for end-stage liver disease (MELD) ≥15] in comparison with 50 patients with mild cirrhosis (MELD <15) and 164 chronic HCV patients without cirrhosis. 28.7 % of HCV patients with cirrhosis were positive for anti-core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV patients. Moreover, there was significantly higher positivity for anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %) compared to those with early cirrhosis (24 %) (P<0.05). These findings, together with the high prevalence of anti-core+1 antibodies in HCV patients with HCC, suggest that core+1 protein may have a role in virus-associated pathogenesis, and provide evidence to suggest that the levels of anti-core+1 antibodies may serve as a marker for disease progression.

Introduction:According to the Baveno VI workshop, patients with compensated advanced liver disease, platelet count (PLT) >150,000/μL and liver stiffness measurement (LSM) <20 kPa can avoid screening endoscopy for high-risk varices (HRVs). The purpose of this study was to validate these criteria in a multicenter Greek cohort and consider other approaches that may further decrease the number of endoscopies.Methods:We prospectively enrolled patients with advanced liver disease (defined as LSM >12 kPa) and evaluated them according to the Baveno VI criteria. Exclusion criteria were splanchnic vein thrombosis, use of β-blockers, and esophageal varices. Screening endoscopy was conducted within 6 months of liver stiffness and laboratory measurements.Results:One-hundred seven consecutive patients were enrolled in the study to undergo LSM and screening endoscopy. Of these, 13 met the Baveno VI criteria (12.1%); none of the latter had HRVs. Additional parameters were examined, among which the quotient PLT/log10LSM exhibited the largest area under the curve; concerning the latter, values ≤122,000 μL-1 x kPa-1 predicted high-risk varices with 100% sensitivity and negative predictive value (NPV), preventing 20.6% of patients from unneeded screening endoscopy (P=0.003). Moreover, values ≤92,000 μL-1 x kPa-1 exhibited 86% sensitivity and 94% NPV, preventing 44.9% of patients from unneeded screening endoscopy (P=0.001), while maintaining a tolerable percentage of overlooked patients with HRVs (6.3%).Conclusions:The Baveno VI criteria were successfully validated in our study. The quotient PLT/log10LSM can be used to further decrease the number of screening endoscopies in patients with advanced liver disease.

-Context -Accumulating data propose that active injecting drug users might not differ from the general population in terms of sustained virological response when adherent to therapy for chronic hepatitis C. However, current guidelines contain restrictive recommendations for therapy in this group of patients. Objective -Therefore, we evaluated a cohort of chronic hepatitis C patients regarding the potent influence of active drug using on initial informed consent, compliance and sustained virological response to treatment. Method -For that purpose, 162 consecutive patients (of which 62 active injecting drug users), who had been evaluated during the last 6 years in our center for chronic hepatitis C and proposed to receive treatment with pegylated interferon alpha and ribavirin, were enrolled. Initial informed consent, compliance, and sustained virological response as well as data regarding age, gender, body mass index, genotype, viral load, coinfection with HBV/HDV/HIV, administered interferon alpha (2a or 2b), liver function tests, liver histology, urban residence, ethnicity, and concomitant use of alcohol were collected and analyzed in respect with injecting drug using. Results -Injecting drug using was positively correlated with male gender (P<0.001), young age (P<0.001), native origin (P = 0.043), and concomitant use of alcohol (P<0.001). Comparable initial informed consent (P = 0.836), compliance (P = 0.879), and sustained virological response (P = 0.132) were observed between injecting drug users and non-injecting drug users. The results were confirmed using a multiple regression model. Conclusion -Our data further support that active injecting drug users do not constitute a distinct chronic hepatitis C patient group in terms of initial informed consent, compliance, or sustained virological response. Therefore, injecting drug using should not be a major determinant influencing the decision for treatment of chronic hepatitis C in eligible patients.

Summary Background Tenofovir alafenamide (TAF) has exhibited a favourable safety profile on estimated glomerular filtration (eGFR) and bone mineral density (BMD), but has not been extensively studied in patients with renal impairment and/or BMD disorders. Aims To assess predictors of eGFR changes and other safety and efficacy outcomes during 24‐month TAF therapy in patients with chronic hepatitis B with renal and/or BMD disorders/risks. Methods Adult patients who started TAF at 13 clinics throughout Greece were prospectively included. Main exclusion criteria were hepatitis D, active malignancy and bisphosphonates recent use. MDRD formula was used for eGFR estimation. Results TAF was initiated in 176 patients (91% switched from another agent). At 12 and 24 months, HBV DNA was undetectable in 97% and 100%, and ALT was normal in 96% and 95% of patients. Median ALT decreased from baseline to month 12/24 (p < 0.001). Mean eGFR decreased from previous treatment initiation to baseline (p < 0.001), increased at 12 months and remained stable at 24 months (p ≤ 0.001). An increase in eGFR of >3 ml/min at 12 month was observed in 50% of patients and was associated mainly with baseline eGFR 30–60 ml/min. In patients with baseline phosphate <2.5 mg/dl, mean serum phosphate increased at month‐12/24 (p < 0.001). Median BMD did not change significantly from baseline to 12 months but improved at 24 months (p = 0.001). Conclusions In mostly switched patients with renal and/or BMD disorders/risks, eGFR improved after 12‐24 months of TAF treatment, especially in patients with baseline eGFR 30–60 ml/min. TAF may also improve low serum phosphate, BMD and ALT, whereas it maintains or induces virological suppression.

BackgroundIt has been suggested that hepatitis C virus (HCV) core+1 protein plays a crucial role in the viral life cycle, potentially affecting liver cirrhosis and the development of hepatocellular carcinoma.MethodsTo investigate its relationship with the outcome of HCV standard combination therapy with peginterferon-α plus ribavirin, we screened 139 consecutive HCV patients (119 with chronic HCV infection and 20 who spontaneously cleared HCV) for the presence of anti-core+1 antibodies (Abs). In addition, liver fibrosis was determined by FibroScan in all but one patients.ResultsTwenty-nine patients were cirrhotic (stiffness >12.5 kPa, F4 METAVIR), all of them with mild liver cirrhosis (Child-Pugh score A). Eighty-six of 139 patients were treatment-experienced with standard combination therapy. Fifty of them had achieved a sustained virological response, while 36 were non-responders. The prevalence of anti-core+1 Abs in patients with chronic HCV infection was 22.69% (27/119 patients): 18% (9/50 patients) in responders and 36.11% (13/36 patients) in non-responders (P=0.050). Five (17.24%) of the 29 cirrhotic patients and 22 (24.72%) of the 89 non-cirrhotic patients were positive for anti-core+1 Abs (P=0.405). Furthermore, the presence of anti-core+1 Abs correlated with the poor response interleukin (IL) 28B genotype TT (P=0.040). No correlation between spontaneous clearance and anti-core+1 Abs was observed (P=0.088).ConclusionThe presence of anti-core+1 Abs might be correlated with the poor response IL28B TT genotype and may negatively affect the outcome of standard combination treatments in HCV patients, suggesting that core+1 may play a biological role in the course of HCV infection.