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Background and Aim: Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) methylation of tumor suppressor genes are emerging potential biomarkers in HCC. We aimed to evaluate the cfDNA methylation status of RASSF1 and CDKN2AIP genes in patients with liver cirrhosis (LC) with or without HCC caused by HBV. Materials and Methods: A total of 47 patients with HBV cirrhosis were included in the study. Patients were divided into two groups: HCC and LC (HCC+LC, n=22) and HBV cirrhosis only (LC, n=25). cfDNA was isolated from the plasma samples of the patients. Methylation analysis was performed for RASSF1 and CDKN2AIP genes. Results: Mean methylation percentage of CDKN2AIP gene was 0.001±0.004% in the HCC+LC group and 0.008±0.004 % in the LC only group. The mean methylation percentage of RASSF1 gene was 5.1±16.1% in the HCC+LC group and 9.7±25.9% in the LC only group. The methylation rate of CDKN2AIP was significantly lower in the HCC+LC group (p=0.027). A positive correlation was found with the absence of cfDNA methylation of CDKN2AIP gene in the presence of HCC (R=0.667, p=0.018). Conclusion: cfDNA methylation of CDKN2AIP and RASSF1 genes may provide important diagnostic information regarding the development of HCC in the setting of HBV cirrhosis. [ABSTRACT FROM AUTHOR]

Introduction: There are limited data about the safety of tenofovir disoproxil fumarate (TDF) in chronic renal failure (CRF). In this study, we aimed to evaluate the safety and efficacy of TDF in renal transplant recipients and hemodialysis patients with chronic hepatitis B (CHB) during long-term follow-up. Material and methods: CHB patients undergoing hemodialysis (group 1), renal transplant recipients (group 2) and patients with normal renal function were included in the study. All patients were treated with TDF for at least 6 months. The groups were compared with regards to safety and efficacy. HBV-DNA levels were studied using a Cobas-TaqMan 96 system. Results: A total of 217 patients with CHB (group 1: 8 patients, group 2: 9 patients, group 3: 200 patients) were enrolled in this study. The frequency of clinical adverse effects was significantly higher in groups 1 and 2 compared with group 3 (37.5% vs. 11.1% vs. 0.5%, respectively, p < 0.001). However, no patients discontinued the drug due to the adverse effects. Serum creatinine levels were similar at baseline and at the end of follow-up in groups 1 and 2 (6.5 ±1.8 mg/dl and 6.9 ±1.5 mg/dl; 1.3 ±0.2 and 1.4 ±0.4 mg/dl, respectively, p < 0.05). HBV-DNA negativity rates were comparable at the 12th month and at the end of follow-up (50-83% for group 1, 60-67% for group 2 and 70-75% for group 3, respectively, p > 0.05). Conclusions: Clinical adverse effects of TDF were more common in patients with CRF in comparison with patients without CRF. However, the occurrence of adverse effects did not necessitate discontinuation of the drug. TDF was safe and effective for this group of patients. [ABSTRACT FROM AUTHOR]

Background & Aims To evaluate the efficacy of tenofovir in chronic hepatitis B ( CHB) patients with adefovir resistance ( ADF-R) and suboptimal response to adefovir ( ADF-S). Methods Nucleos(t)ide analogue ( NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response ( CVR) ( HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR. Results A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg+) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity ( HR = 0.56, 95% CI 0.36-0.86, P = 0.008), high baseline HBVDNA level ( HR = 0.64, 95% CI 0.55-0.74, P < 0.001) and ADF-R ( HR = 0.47, 95% CI 0.28-0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments. Conclusion CVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV. [ABSTRACT FROM AUTHOR]

Background: Levels of prohepcidin, a homeostatic regulator of iron absorption, are altered in chronic hepatitis C and liver cirrhosis. However, data on the potential alterations of prohepcidin in patients with HBV-related liver disease are scarce. We investigated whether serum prohepcidin is related to iron overload and perenchymal dysfuction in HBV-related liver disease.Methods: Three groups of subjects were studied: 66 patients with chronic hepatitis B, 32 patients with HBV-related cirrhosis, and 42 healthy controls without evidence of liver disease. Serum levels of prohepcidin were determined by enzyme-linked immunosorbent assay.Results: Serum prohepcidin levels were significantly lower in patients with HBV-related cirrhosis (175.85 ± 71.5 ng/ml) than in patients with chronic hepatitis B (209.02 ± 62.7 ng/ml P < 0.05) and controls (222.4 ± 128.4 ng/ml, P < 0.05). After adjustment for potential confounders, prohepcidin was found to be an independent predictor of ferritin levels in multiple linear regression analysis (β = -1.10, t = -3.11, P < 0.01).Conclusion: These results demonstrate that prohepcidin levels are reduced in patients with HBV-related cirrhosis and are an independent correlate of serum ferritin. [ABSTRACT FROM AUTHOR]

Summary Objectives Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (≥2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. Methods HBeAg-negative CHB patients with PNALT (≤40 IU/l) and high serum HBV DNA (≥2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage ≥2 and/or HAI ≥6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. Results A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123 680 ± 494 500 IU/ml; the HBV DNA load was 2000–20 000 IU/ml in 68 patients (56.6%) and ≥20 000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI ≥6). Forty-three patients (35.9%) had a fibrosis stage ≥2. Forty-eight patients (40%) had a fibrosis stage ≥2 and/or HAI ≥6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage ≥2 and/or HAI ≥6 included age and HBV DNA viral load. Patients with HBV DNA 2000–20 000 IU/ml were more likely to require treatment compared to those with a viral load ≥20 000 IU/ml. The optimal age cut-off to predict fibrosis stage ≥2 and/or HAI ≥6 was 46 years. Conclusions Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years. [ABSTRACT FROM AUTHOR]