Chao- Hung

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.u2002 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 5u2003MU thrice weekly) and oral ribavirin (1000–1200u2003mg/day) for 24 or 48u2003weeks 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 (Pu2003<u20030.001) and low viral load (Pu2003=u20030.018) 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 (Pu2003=u20030.0178), whereas there was no difference between those with transient biochemical response and nonresponse (Pu2003=u20030.5970). The Kaplan–Meier method also showed that old age (≥60u2003years) (Pu2003=u20030.0034) and genotype 1b (Pu2003=u20030.0104) were associated with HCC occurrence. Using Coxs regression analysis, non‐SVR (odds ratiou2003=u20033.521, Pu2003=u20030.036), male (odds ratiou2003=u20036.269, Pu2003=u20030.011) and old age (odds ratiou2003=u20033.076, Pu2003=u20030.049) 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:u2002 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.

Mutations in the NS5A and E2-PePHD region of hepatitis C virus type 1b and correlation with the response to combination therapy with interferon and ribavirin.

summary. Nonstructural 5A (NS5A) and the second envelope (E2) proteins of hepatitis C virus (HCV) have the potential to block interferon (IFN)‐induced RNA‐dependent protein kinase (PKR) and may therefore interfere with the response to IFN therapy, but controversy still exists regarding the relevance of this. This study aimed to assess whether mutations in these regions correlated with the response to combination therapy, IFN and ribavirin. Pretreatment parameters were analysed in 57 HCV‐1b patients who had received IFN‐α2b (3 or 5 MU three times weekly) and ribavirin (800–1200u2003mg per day) for 24u2003weeks. The amino acid sequences of the NS5A and PKR‐eIF2α phosphorylation homology domain (E2‐PePHD) were deduced from the corresponding coding sequence, which were determinated by direct sequencing of the HCV genome amplified by the polymerase chain reaction. Twenty (36%) patients achieved a sustained virological response (SVR). The mean number of amino acid substitutions in the NS5A–PKR binding domain (2209–2274), interferon sensitivity‐determining region (ISDR) (2209–2248), and E2‐PePHD sequence (659–670) in patients with and without SVR were 4.53u2003±u20033.31 vs 2.83u2003±u20031.78 (Pu2003=u20030.094), 2.45u2003±u20032.74 vs 1.03u2003±u20031.32 (Pu2003=u20030.042) and 0.25u2003±u20030.70 vs 0.03u2003±u20030.17 (Pu2003=u20030.109), respectively. Patients with a mutant‐type (≥u20034) NS5A–ISDR had a higher rate of SVR (six of nine, 67%) than those with wild‐type (five of 22, 23%) (Pu2003=u20030.038). Stepwise multiple logistic regression analysis of the factors (age, gender, viral load, cirrhosis rate, IFN dosage and amino acid substitutions) revealed that the mutation in NS5A–ISDR (≥u20034 vs <u20034) was the only independent variable of treatment outcome. Our study showed that NS5A–ISDR mutations were correlated with the SVR to combination therapy in chronic HCV‐1b patients in Taiwan.

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

Background:u2002 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.

Mutations in the interferon sensitivity-determining region (nonstructural 5A amino acid 2209-2248) in patients with hepatitis C-1b infection and correlating response to combined therapy of pegylated interferon and ribavirin

Backgroundu2002 Most reports suggest that mutations in the interferon sensitivity‐determining region (ISDR) correlate with response to conventional interferon‐based therapies in hepatitis C virus‐1b (HCV‐1b) patients. However, the correlation between ISDR region mutations and response to pegylated interferon plus ribavirin therapy in HCV‐1b patients remains unclear.

Clinical-guide risk prediction of hepatocellular carcinoma development in chronic hepatitis C patients after interferon-based therapy

Background:Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies.Methods:From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed.Results:Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13–2.65 for aged 60–69 and aHR=2.20, 95% CI=1.43–3.37 for aged ⩾70), Male gender (aHR=1.74, 95% CI=1.26–2.41), platelet count <150 × 109/l (HR=1.91, 95% CI=1.27–2.86), α-fetoprotein ⩾20u2009ngu2009ml−1 (HR=2.23, 95% CI=1.58–3.14), high fibrotic stage (HR=3.32, 95% CI=2.10–5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10–2.14), and non SVR (HR=2.40, 95% CI=1.70–3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively.Conclusion:The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.

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 >126u2009mg per 100u2009ml, and overweight was defined as a body mass index >24u2009kgu2009m−2. Subjects with thrombocytopenia (platelet count <150 × 109u2009l−1) and elevated α-fetoprotein (>20u2009ngu2009ml−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.