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Background: It has been suggested hepatic steatosis contributes to seroclearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B virus (HBV) infection. Although HBsAg seroclearance generally confers favorable outcome, hepatic steatosis may account for progressive liver fibrosis and cirrhosis. Further studies are needed to compare clinical and virological characteristics post HBsAg seroclearance between subjects with hepatic steatosis and those without. Methods: One-hundred and fifty-five HBsAg carriers with HBsAg seroclearance were enrolled. Subjects with moderate-severe hepatic steatosis as diagnosed by ultrasonography were designated as having hepatic steatosis. Results: There were 69 subjects with hepatic steatosis and 86 without. Subjects with hepatic steatosis had significantly higher body mass index (BMI; 27.8 ± 3.5 vs. 23.0 ± 3.1, P < 0.001), were more likely to be male (78.3 vs. 63.9 %, P = 0.05), and were significantly younger at HBsAg seroclearance (48.7 ± 8.9 years vs. 53.4 ± 8.9 years, P = 0.001), than those without. The frequency of anti-HBsAg seroconversion (56.5 vs. 59.3 %, P = 0.72) and HBV viremia (20.3 vs. 15.1 %, P = 0.40) was not significantly different between subjects with and without hepatic steatosis, but the incidence of abnormal AST and ALT was significantly higher in the former (23.2 vs. 0 %, P < 0.0001; and 30.4 vs. 0 %, P < 0.0001, respectively), and progression to liver cirrhosis tended to be more likely in the former than in the latter (10.1 vs. 3.5 %, P = 0.09). Conclusions: In HBsAg carriers with increased body mass index, hepatic steatosis can accelerate HBsAg seroclearance by approximately 5 years. However, the beneficial effects of HBsAg seroclearance should be balanced against the harmful effects of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Background/Aims: The role of viral factors in the pathogenesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is still inconclusive. Whether virological features such as viral load or mutants might change with the progression of HCC remains unknown. A case-control study including patients with early HCC and HBsAg carriers who are presumed to be at the minimal potential of HCC as controls might better identify factors significantly associated with HCC development. Methods: Virological features were compared between 59 patients with early HCC (a solitary tumor of size ≤3 cm) and 101 patients with non-early HCC. A case-control study was performed by comparing 59 patients with early HCC and 1:2 age-matched inactive carriers with persistent normal alanine aminotransferase (ALT) levels. Results: HBV DNA levels, HBV genotypes, and the frequency of precore A1896 and basal core promoter T1762/A1764 mutations showed no significant difference between patients with early HCC and those with non-early HCC. In the case-control study, patients with early HCC had significantly higher HBV DNA levels, and higher frequencies of genotype C HBV and basal core promoter T1762/A1764 mutation, but a similar frequency of precore A1896 mutation. Multiple logistic regression analysis identified HBV DNA levels ≥2,000 IU/mL and basal core promoter T1762/A1764 mutation as being independent factors for HCC development. Additionally, there was a synergistic effect between high viral load and basal core promoter T1762/A1764 mutation on HCC development. Conclusions: Virological features did not change significantly with the progression of HCC. HBV DNA levels ≥2,000 IU/mL and basal core promoter T1762/A1764 mutation were two independent viral factors for HCC. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Mortality and hepatitis B surface antigen (HBsAg) seroclearance are the two extremes of prognostic destination of chronic hepatitis B virus (HBV) infection. Their relative roles in the decline of HBsAg prevalence with increasing age are unknown.METHODS:HBsAg-seropositive subjects with near normal alanine aminotransferase (ALT) were followed up every 3 to 12 months for >1 year. Serum HBsAg was assayed at entry and re-assayed at 3- to 5-year intervals. The morbidity and mortality data were obtained from hospital records, cancer registration, and the national mortality database. The mortality and HBsAg-seroclearance rates were examined by survival analysis.RESULTS:At entry, 1,386 subjects (20.9%) were hepatitis B e antigen (HBeAg) seropositive and 5,235 were HBeAg seronegative. The mean follow-up period was 13.6±5.4 years (median 13.2; range 1–29.1). HBsAg seroclearance occurred more frequently (555 cases, 8.4%) than mortality (97 cases, 1.5%; P<0.001; overall HBsAg seroclearance/mortality ratio: 5.6), of which only 40% were liver-related cases. Cox regression analysis revealed that male sex, HBeAg negativity, older age, low maximal ALT level, and hepatic steatosis were factors associated with HBsAg seroclearance. The estimated annual HBsAg seroclearance rate was around 1.05–1.61% after the age of 50 years, whereas the estimated mortality rate was quite low before the age of 60 and increased from 0.41% per year at ages 60–64 to 1.19% per year at ages 70–74 years.CONCLUSIONS:The HBsAg seroclearance over mortality rate was 5.6 in this cohort. This suggests that HBsAg seroclearance is the main reason for decreasing HBsAg prevalence with increasing age in the population. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocyte expression of HBV surface, core, and x antigens (HBsAg, HBcAg and HBxAg), semi-quantitated by immunopathology, were correlated with clinical and virological data in 80 patients with chronic hepatitis B.Results: Seventy patients were HBsAg positive in cytoplasm, 61 were HBcAg positive, including 45 in both nucleus and cytoplasm and 16 in cytoplasm only, and 47 were HBxAg positive in cytoplasm. The detection rates for HBcAg increased while those for HBsAg and HBxAg decreased with HBV DNA levels. Positive HBcAg staining usually suggested the presence of HBV DNA levels >10(6) copies/ml. HBcAg, HBsAg, and HBxAg expressions showed no significant differences between patients with genotype B and C. Serum HBeAg and HBV DNA levels correlated positively with nuclear or cytoplasmic HBcAg expression but inversely with HBsAg expression. By multiple regression analysis, HBV DNA levels correlated significantly only with nuclear HBcAg expression. ALT levels and inflammatory grades correlated with cytoplasmic HBcAg expression. There was an inverse quantitative relationship between HBcAg and HBsAg expression. Furthermore, HBxAg expression correlated significantly with HBsAg expression as well as male gender.Conclusions: With diminishing HBV DNA levels following HBeAg seroconversion, HBcAg expression decreased but HBsAg expression increased with a concomitant increase in HBxAg expression. Whether the finding that a significantly higher expression of HBxAg observed in males than females may account for the gender difference in long-term sequelae of chronic HBV infection needs further investigation. [ABSTRACT FROM AUTHOR]

Background/aims: Chronic hepatitis B and hepatitis C are common causes of liver fibrosis and cirrhosis. We performed a comparative study on the expression of alpha-smooth muscle actin (alpha-SMA) in hepatic stellate cells (HSCs), a marker of HSC activation, in patients with chronic hepatitis B and hepatitis C.Patients and Methods: Using immunohistochemistry and a semi-quantitative scoring method, the expression of alpha-SMA in HSCs was studied in patients with chronic hepatitis B (n = 50) and hepatitis C (n = 50). The HSC activation index was correlated with age, sex, AST, ALT, viral genotype, viral titers, degrees of hepatic steatosis, necroinflammatory grades and fibrotic stages.Results: The HSC activation index correlated significantly (P < 0.05) with necroinflmmatory grades and fibrotic stages in chronic hepatitis B or hepatitis C. Besides, the HSC activation index also correlated significantly (P < 0.05) with hepatic steatosis and marginally significantly (P = 0.08) with serum viral titers in chronic hepatitis C. There was no significant difference in biochemical and histological activities between patients with hepatitis B and hepatitis C, but the latter had a significantly higher HSC activation index than the former. Multiple regression analysis in all 100 patients showed that the HSC activation index correlated significantly (P < 0.05) with necroinflammatory grades, fibrotic stages and hepatitis C (versus hepatitis B).Conclusion: In chronic viral hepatitis, the HSC activation index correlated significantly and independently with necroinflammation and fibrosis. Additionally, the HSC activation index was significantly higher in patients with chronic hepatitis C. These data may be compatible with the postulation that hepatitis C virus can directly activate HSCs. [ABSTRACT FROM AUTHOR]

The issue of spontaneous relapse of hepatitis in anti-HBe positive asymptomatic HBsAg carriers was rarely reported before and deserves further exploration. A total of 1241 anti-HBe positive asymptomatic adult HBsAg carriers were prospectively followed up. Of these, 661 (53%) were males, and the mean (±SD) age was 35.6 ± 9.1 years. Relapse of hepatitis was defined as elevation of ALT more than twice the upper limit of normal accompanied by detectable serum HBV DNA by hybridization assays. During a mean follow up of 12.3 years, hepatitis relapsed in 211 patients with an annual rate of 1.46%. The cumulative probabilities of hepatitis relapse were 10.2%, 17.4%, 19.3%, 20.2%, and 20.2%, respectively, after 5, 10, 15, 20, and 25 years of follow up. Multivariate analyses showed that the probability of hepatitis relapse correlated significantly with male sex ( P < 0.0001) and age at entry ( P = 0.007). The cumulative probability of hepatitis relapse after 20 years was 26.9% for males and only 12.5% for females, and was 13.1% for those of age <30 years at entry but increased to 29.4% for those of age 40–49 years at entry. Hepatitis relapsed in about 20% of asymptomatic HBsAg carries during 25 years of follow up. Relapse of hepatitis occurred more frequently during earlier years of follow up. Males were more likely to have relapse of hepatitis than females. In addition, relapse of hepatitis was significantly less frequent in patients who were younger than 30 years at study entry, possibly implicating more favorable outcome of earlier HBeAg seroconversion. [ABSTRACT FROM AUTHOR]

To elucidate the long-term natural course following the onset of cirrhosis in patients with chronic hepatitis B. Ninety-three patients with chronic hepatitis B who had developed cirrhosis during regular follow-up were included in this long-term follow-up study. At the time of cirrhosis detection, 30% of the patients were seropositive for hepatitis B e antigen (HBeAg) and 73% had a HBV-DNA level >104 copies/ml. Follow-up studies included liver biochemistry, viral markers, α-fetoprotein and ultrasonography every 3–6 months. During a mean follow-up period of 102 ± 60 (12–246; median 97) months, 32 patients (34.4%) experienced 55 episodes of hepatitis flare (7.0%/year), 15 (53.6%) of 28 HBeAg-positive patients seroconverted to anti-HBe (6.3%/yr) and 12 (12.9%) lost HBsAg (1.5%/year). Overall disease progression was observed in 25 (26.9%, 3.2%/year) patients: 12 (12.9%, 1.5%/year) hepatic decompensation, 21 (22.6%, 2.7%/year) hepatocellular carcinoma and 11 (11.8%, 1.4%/year) died. Multivariate analysis showed that age at onset of cirrhosis ( P = 0.015) and persistent HBeAg seropositivity ( P = 0.019) were the independent factors for overall disease progression. These results suggest that patients with older age at onset of cirrhosis and persistent HBeAg seropositivity following the onset of cirrhosis were independent factors for the disease progression in the first 10-year after the development of cirrhosis in patients with chronic hepatitis B. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether there was a particular hepatitis B virus (HBV) X protein (HBx) mutant associated with Taiwanese patients with hepatocellular carcinoma (HCC). Initially, the entire coding region of HBx gene from the serum samples of 14 Taiwanese patients were sequenced. A novel mutant, HBx-A31, was preferentially found in patients with HCC. Sera from 67 patients with HCC and 100 patients with chronic hepatitis B were thus subjected for codon 31 analysis using a dual amplification created restriction site method. HBx-A31 was detected more frequently in patients with HCC (52% versus 12%; P<0.001) and in patients with liver cirrhosis (44% versus 6%; P<0.001). Site directed mutagenesis experiment revealed that HBx-A31 was less effective in transactivating HBV enhancer I-X promoter complex, less efficient in supporting HBV replication, and less potent in enhancing TNF-α induced increment of CPP32/caspase 3 activities in HepG2 cells. In conclusion, a prevalent HBx mutant was identified in Taiwanese patients with hepatocellular carcinoma. Development of this mutant might represent a strategy of the virus to escape immune surveillance and thus contribute to the process of multiple-step hepatocarcinogenesis. Oncogene (2000) 19, 5213–5220. [ABSTRACT FROM AUTHOR]

Taiwan is an endemic area for hepatitis B virus (HBV) infection, which is responsible for up to 80% of chronic liver diseases there. In contrast to an HBV carrier rate of 15-20% in the general population, only 1% of its population are seropositive for anti-HCV. To evaluate the role of HCV infection in chronic liver diseases in Taiwan, serum anti-HCV was studied using an enzyme immunoassay in 123 'healthy' administration staff of the hospital, 724 hepatitis B surface antigen (HBsAg)-positive and 157 HBsAg-negative patients with chronic liver disease. The prevalence of anti-HCV was 0.8% in the hospital staff, 24.3% in HBsAg-positive and 80.9% in HBsAg-negative patients with chronic liver diseases. Anti-HCV was positive in 10 (9.6%) of 104 HBsAg-positive and 31 (77.5%) of 40 HBsAg-negative patients with inactive chronic hapatitis; 94 (27.2%) of 346 HBsAg-positive and 53 (85.5%) of 62 HBsAgnegative patients with active chronic hepatitis; 49 (26.1%) of 181 HBsAg-positive and 33 (86.8%) of 38 HBsAg-negative patients with cirrhosis; 23 (26.7%) pf 86 HBsAg-positive and 10 (58.8%) of 17 HBsAg-negative patients with hepatocellular carcinoma. In HCV infected HBsAg-positive patients, the optical density was usually lower, and anti-HCV became negative in 27% on follow-up. HCV infection tends to occur more frequently in older, HBeAg-negative and anti-HD-positive patients with chronic HBV infection. It is concluded that HCV not only is the major agent for non-B chronic liver diseases but also plays a significant role in HBsAg-positive chronic liver diseases in Taiwan. [ABSTRACT FROM AUTHOR]