Hung-Da Tung

Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis

Background. We aimed to evaluate the validity of ultrasonography (US) in the diagnosis of cirrhosis in patients with chronic hepatitis B virus (HBV) or C virus (HCV) infection. Methods: A total of 210 patients, 67 with chronic HBV and 143 with HCV infection, were evaluated for the cirrhotic status of liver by both needle biopsy and US. According to the pathological findings, a fibrosis score 4 on the histology activity index was the gold standard for the diagnosis of cirrhosis. A US scoring system consisting of liver surface, parenchyma, vascular structure, and splenic size was used to describe the severity of hepatic parenchymal damage. Results: Cirrhosis was found in 27 (40%) of the 67 HBV patients and in 51 (36%) of the 143 HCV patients pathologically. The mean fibrosis scores were 0.95, 1.24, 2.35, 2.95, 3.8 and 3.7 in patients with US scores of 4, 5, 6, 7, 8, and 9 or more, respectively. The US scores were significantly correlated with the hepatic fibrosis scores (P < 0.05). Based on the receiver operating characteristic (ROC) curve, a US score of 7 was the best cutoff point for the prediction of HBV-related cirrhosis, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 77.8%, 92.5%, 87.5%, 86.0%, and 86.6%, respectively. In HCV-related cirrhosis, a US score of 6 provided results of 82.4%, 70.7%, 60.9%, 87.8%, and 74.8%, respectively. The specificity, positive predictive value, and accuracy were significantly higher in patients with HBV than in those with HCV infection (P = 0.012, P = 0.032, and P = 0.079, respectively). Conclusions: Cirrhosis can be predicted well by US, especially in patients with HBV infection.

Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma.

The objective of this study was to examine the usefulness of platelet counts in the diagnosis of cirrhosis and for identifying high‐risk individuals in a community‐based hepatocellular carcinoma (HCC) screening program.

Long‐term effect of interferon alpha‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis

Summary.  We assessed the efficacy of interferon (IFN) alpha‐2b plus ribavirin therapy in patients with hepatitis C virus (HCV)‐related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty‐two HCV‐cirrhotic patients receiving IFN alpha‐2b (3 or 5 MU thrice weekly) and oral ribavirin (1000–1200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan–Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log‐rank test and by multivariate Coxs regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow‐up period of 37 (12–63) months, HCC developed in 11 patients with non‐SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan–Meier method also showed that old age (≥60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Coxs regression analysis, non‐SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha‐2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV‐related cirrhosis.

Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan

Background: Hepatitis B virus (HBV) infection is a major health problem. HBV genotypes may be associated with progression of liver disease. The distribution and clinical implications of HBV genotypes in southern Taiwan are evaluated. Methods: We used a polymerase chain reaction-restriction fragment length polymorphism genotyping method to determine HBV genotypes. Results: The genotype distribution for 265 patients with chronic HBV infection was as follows: A, 3 (1%); B, 158 (60%); C, 90 (34%); D, 7 (2.5%); E, 0; F, 0; and unclassified, 7 (2.5%). Compared with genotype B patients, genotype C patients had a higher hepatitis B e antigen positive rate and higher fibrosis score. There was no significant difference in the mean age between genotype B and genotype C patients with hepatocellular carcinoma (HCC). However, when patients were stratified by age, the prevalence of genotype C was significantly higher in young HCC patients (around 50 years of age) than in age-matched asymptomatic carriers (40% versus 10%, P ≺ 0.001). Using multivariate analysis, the significant risk factors for advanced liver disease (cirrhosis or HCC) for patients with chronic HBV infection were old age, male gender and genotype C. Conclusions: These results suggest that genotype C is associated with more severe liver diseases than the B variant.

Combination therapy with interferon‐α and ribavirin in patients with dual hepatitis B and hepatitis C virus infection

Background:  Patients with dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection have responded poorly to interferon (IFN) monotherapy. The purpose of the present paper was to assess the effect of combined IFN‐α and ribavirin therapy in patients infected with both hepatitis B and C.

Durability of lamivudine-induced HBeAg seroconversion for chronic hepatitis B patients with acute exacerbation

BACKGROUND/AIMS Lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B was reported to be durable by several studies but controversy still exists. The aim of this study was to evaluate the durability of the responses of lamivudine treatment. METHODS Among 53 chronic hepatitis B patients who had acute exacerbation and had finished lamivudine therapy after at least 6 months of treatment, 31 patients achieved full HBeAg seroconversion twice at least 1 month apart, and subsequently stopped lamivudine therapy. Post-treatment monitoring was continued for up to 87 weeks. Alanine transaminase (ALT), HBeAg and hepatitis B virus (HBV) DNA were used as indicators for relapse. RESULTS The cumulative relapse rates at 48 and 72 weeks post-treatment were 45.4% and 56.3%, respectively. During follow up, normal ALT levels precluded relapse while ALT levels over two times the upper limit of normal indicated relapse, which correlated well with HBeAg or HBV DNA reappearance. Patients older than 25 years were more likely to experience post-treatment relapse. CONCLUSIONS Lamivudine-induced full HBeAg seroconversion was not durable in the Taiwanese population. ALT levels were useful for relapse detection. Age was the only independent predictive factor for relapse.

Correlation of quantitative assay of hepatitis B surface antigen and HBV DNA levels in asymptomatic hepatitis B virus carriers.

Objective This study was to elucidate the correlation between quantity of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels in asymptomatic carriers. Methods Based on the presence of the hepatitis B e antigen (HBeAg) and HBV DNA levels, 67 asymptomatic carriers were divided into four groups. HBV DNA was determined by hybridization (sensitivity 141 500 copies/ml) and polymerase chain reaction (PCR, sensitivity < 103 copies/ml). Cases of groups I (n = 18), II (n = 17) and III (n = 16) were negative for HBeAg and had HBV DNA levels of < 103 (PCR undetectable), 103 to 105 (PCR detectable) and > 105 copies/ml (hybridization detectable), respectively. Cases of group IV (n = 16) were positive for HBeAg and high HBV DNA levels (> 2 × 107 copies/ml). HBsAg was determined quantitatively by the ARCHITECT HBsAg assay. Results Our data showed HBsAg levels were correlated with HBV DNA (r = 0.709; P < 0.001) on a log scale. The mean log HBsAg (IU/ml) of groups I, II, III and IV were 2.68 ± 0.8, 2.93 ± 1.03, 3.22 ± 0.45, 4.83 ± 0.19, respectively. That of group IV was significantly higher than the mean log HBsAg of any other group (P < 0.001). The best cut-off for HBsAg in differentiating group IV from other groups was 15 000 IU/ml with both sensitivity and specificity of 100%. That of group I was significantly lower than those of group III (P = 0.035) and IV (P < 0.001). The best cut-off in differentiating group I from the other groups was 1600 IU/ml with a sensitivity of 69.4% and a specificity of 66.7%. Conclusion Quantitative measurement of HBsAg titres may be an easy and economical reference for HBV replication in HBV carriers.

Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis

Abstract Background and Aims:  Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long‐term reversibility of thyroid dysfunction.

Antiviral therapy after non-surgical tumor ablation in patients with hepatocellular carcinoma associated with hepatitis C virus.

Background:  Antiviral therapy for chronic hepatitis C virus (HCV) infection has led to a reduction in the incidence of hepatocellular carcinoma (HCC). The purpose of the present paper was to assess whether antiviral therapy might suppress tumor recurrence and influence overall survival in patients with HCV‐related HCC who had complete ablation of nodules by non‐surgical treatments.

Neither Diabetes Mellitus nor Overweight Is a Risk Factor for Hepatocellular Carcinoma in a Dual HBV and HCV Endemic Area: Community Cross-Sectional and Case–Control Studies

OBJECTIVES:Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are well-known risk factors for hepatocellular carcinoma, and diabetes mellitus (DM) and overweight have also been reported as risk factors for hepatocellular carcinoma (HCC). We tried to elucidate the roles of DM and overweight in HCC development in a dual HBV and HCV endemic area of southern Taiwan.METHODS:In 2004, a community-based comprehensive screening program was conducted in Tainan County. Hepatitis B surface antigen (HBsAg), anti-HCV, α-fetoprotein, complete blood counts, triglyceride, cholesterol, and glucose levels were examined. DM was defined as fasting blood sugar >126 mg per 100 ml, and overweight was defined as a body mass index >24 kg m−2. Subjects with thrombocytopenia (platelet count <150 × 109 l−1) and elevated α-fetoprotein (>20 ng ml−1) underwent ultrasonographic screening for HCC. A total of 56,307 adults (>40 years old) participated, and 72 new HCC cases were detected and confirmed.RESULTS:In comparisons of all 72 HCC cases with the other 144 individual age-, sex-, residency-, HBsAg-, and anti-HCV-matched controls, only thrombocytopenia and high alanine transaminase (ALT) levels were shown to be independent risk factors. Neither DM nor overweight was shown to be significant in any of the analyses.CONCLUSIONS:On the basis of the community-based cross-sectional and case–controlled studies, neither DM nor overweight was a risk factor for HCC in a dual HBV and HCV endemic area. However, male gender, age (≧65 years), HBsAg, anti-HCV, thrombocytopenia, and high ALT levels were independent risk factors for HCC.