Clinical significance of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role in the progression to cirrhosis remains unclear.Although OBI has been well documented in human immunodeficiency virus(HIV) -positive patients,especially among those coinfected with hepatitis C virus,further studies are needed to determine its current clinical impact in HIV setting.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.

Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health outcome.In this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral treatment.AIM To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey zone.METHODS Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV mutants.RESULTS High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E genotype.Since HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS deletions.The HCC related variants were the major strains and persisted over time(up to 48 mo).Patients with preS deletions had a significant higher prevalence of F2 fibrosis stage than the negatives(57%vs 10%,P=0.0078).CONCLUSION HBV genetic analysis of selected populations,like sub-Saharans infected with HBV-E/A genotypes,will allow identification of subpopulations with risk of HCC development due to accumulation of high-risk HBV variants,thus commanding their increased clinical surveillance.

Management of betablocked patients after sustained virological response in hepatitis C cirrhosis

BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after directacting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/μL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk. CONCLUSION Portal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.