Hepatitis B core antigen expression in hepatocytes reflects viral response to entecavir in chronic hepatitis B patients.

BACKGROUND/AIMS: Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B. METHODS: We enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy. RESULTS: Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy. CONCLUSIONS: Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.

Effects of metabolic syndrome on fibrosis in chronic viral hepatitis.

BACKGROUND/AIMS: Metabolic syndrome, comprising diabetes, hypertension, central obesity, and dyslipidemia, is increasingly prevalent worldwide. We aimed to study the relationship between metabolic syndrome and the risk of liver fibrosis in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC). METHODS: In total, 954 patients (CHB, 850; CHC, 104 patients) with liver biopsy were included in the retrospective analysis. Extensive clinical and histological data were available. Metabolic syndrome was defined using the International Diabetes Federation definition of metabolic syndrome, 2006 criteria. Histological lesions were evaluated according to the histology activity index system. RESULTS: Metabolic syndrome was present in 6% of patients and significantly more prevalent in patients with CHC than in patients with CHB (5% vs 13%, p<0.001). Patients with metabolic syndrome were older among patients with CHB and patients with CHC, and, as expected, were mainly overweight or obese. Fibrosis was significantly more severe in patients with metabolic syndrome than in those without, regardless of whether they had CHB and CHC (CHB, 3.3±2.1 vs 2.4±1.3, p=0.025; CHC, 2.6±1.5 vs 1.3±0.7, p=0.006). Liver fibrosis (stages 3 to 4) was independently associated with increased age, higher transaminase level and metabolic syndrome (odds ratio, 2.421; p=0.017). CONCLUSIONS: Metabolic syndrome is associated independently with severe fibrosis in patients with chronic viral hepatitis B and C.

Promoter polymorphisms of pri-miR-34b/c are associated with hepatocellular carcinoma.

BACKGROUND: Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). This study aimed to assess whether polymorphisms in the single-nucleotide polymorphism miR-34b/c T>C (rs4938723) and TP53 Arg72Pro (rs1042522) increase the risk of HCC and influence outcome in patients with HCC. PATIENTS AND METHODS: We enrolled 157 HCC patients and 201 cancer-free control subjects from the Korean population. MicroRNA polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: We found that the miR-34b/c TC+CC frequency was significantly higher in HCC patients than in controls (adjusted odds ratio [AOR]: 1.580; 95% confidence interval [CI]: 1.029-2.426). The miR-34b/c CC-TP53 Arg/Arg combination significantly increased the risk of HCC (AOR: 13.644; 95% CI: 1.451-128.301). The SNPs miR-34b/c T>C and TP53 Arg72Pro(G>C) had no influence on survival of HCC patients. CONCLUSIONS: Our findings suggest that loss of the T allele in miR-34b/c T>C, and the miR-34b/c CC-TP53 Arg/Arg combination increases the risk of HCC in the Korean population.

Prevalence of occult hepatitis B virus infection in hemodialysis patients.

BACKGROUND/AIMS: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. METHODS: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. RESULTS: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. CONCLUSIONS: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.

Associations of Expressions of HBcAg and HBsAg with the Histologic Activity of Liver Disease and Viral Replication.

BACKGROUND/AIMS: Subcellular localization of hepatitis B virus (HBV) core antigen (HBcAg) and HBV surface antigen (HBsAg) is known to be related to the activity of liver disease and the level of HBV replication. The aim of this study was to determine the correlation between histologic activity, viral replication, and the intracellular distributions of HBcAg and HBsAg. METHODS: We enrolled 670 patients with chronic hepatitis B who underwent liver biopsy at Bundang CHA hospital between 1997 to 2007. The data from medical records were reviewed retrospectively. RESULTS: The stage of fibrosis was higher (3.31+/-1.34 vs. 2.43+/-1.39, mean+/-SD, p<0.01) and the grade of necroinflammatory activity was higher (9.39+/-3.11 vs. 6.13+/-3.40, p<0.001) for the cytoplasmic expression of HBcAg (cHBcAg) than for the nuclear expression of HBcAg (nHBcAg). The serum HBV DNA level was 677.30+/-983.14 pg/mL in cHBcAg, 1274.46+/-1417.28 pg/mL in nHBcAg, 1121.01+/-1121.0 pg/mL in c-nHBcAg, and 229.47+/-678.92 pg/mL in negative (p<0.001). HBeAg was seropositive in 74.7% of patients with cHBcAg, 90.6% in those with nHBcAg, 90.3% in those with n-cHBcAg, and 55.6% in those with negative (p<0.001). The histologic stage and grade of hepatitis were not significantly correlated with the subcellular localization of intrahepatic HBsAg (p>0.05). CONCLUSIONS: These observations suggest that the histologic activity of hepatitis is higher and viral replication is lower in cHBcAg positive patients than in those with nHBcAg.