A Comparative Cross-sectional Study of the Development of Hepatocellular Carcinoma in Patients with Liver Cirrhosis Caused by Hepatitis B Virus, Alcohol, or Combination of Hepatitis B Virus and Alcohol / 대한소화기학회지

BACKGROUND/AIMS: Alcohol may be a cocarcinogen in patients with chronic viral hepatitis. We investigated the effect of alcohol on the development of hepatocellular carcinoma (HCC) in liver cirrhosis (LC) caused by hepatitis B virus (HBV). METHODS: All patients with LC or HCC associated with HBV or alcohol, admitted between March 2001 and June 2005, were included. Patients were divided into three groups according to the etiology of LC: Alcohol (AL), HBV, or HBV+alcohol (HBV+AL). Age and laboratory data at the enrollment of study were analyzed. The logistic regression coefficiency for the prevalence of HCC was calculated by using variables such as age, gender, serologic markers, and etiology of LC. RESULTS: In LC patients (n=342), the proportions of AL, HBV, and HBV+AL groups were 44%, 39%, and 17%, respectively. The proportions of HCC in AL, HBV and HBV+AL groups were 17%, 55%, and 76%, respectively. Age at the diagnosis of HCC was younger in HBV+AL than in AL group (p=0.036). In logistic regression analysis for the risk factor of HCC, odds ratio of age was 1.056 (p<0.001). Odds ratios of HBV and HBV+AL group comparing AL were 8.449 (p<0.001) and 17.609 (p<0.001), respectively. Therefore, old age and chronic alcohol intake in patients with HBsAg were the risk factors of HCC. CONCLUSIONS: Chronic alcohol intake may be an additive factor for the development of HCC in patient with LC caused by HBV. However, a prospective cohort study is needed to confirm these findings.

Clinical and Virologic Characteristics of Lamivudine Resistance in HBV-associated Chronic Liver Disease / 대한간학회지

BACKGROUND/AIMS: Lamivudine therapy in chronic hepatitis B has been shown to be effective in inhibiting HBV replication. However, lamivudine resistance has been developed with prolonged use. We studied to determine the prevalence, predictive factors, and clinical outcomes of lamivudine resistance. Mutations in YMDD motif of HBV polymerase, which have been associated with lamivudine resistance, were also assessed. METHODS: 170 patients with HBV-associated chronic liver disease who have received lamivudine for at least one year, were studied. The clinical, biochemical, and virologic characteristics were analyzed and compared according to presence (resistance group) or absence (non-resistance group) of DNA breakthrough. Their clinical outcomes were regularly followed. Stored sera before treatment and after DNA breakthrough were examined for detection of HBV polymerase mutation by direct sequencing and/or RFLP. RESULTS: Cumulative rates of lamivudine resistance after one and two years of treatment were 11% and 34%, respectively. In the resistance group, as compared to the non-resistance group, age, the presence of HBeAg before treatment, and disappearance of HBeAg during treatment, were significantly different. The predictive factors associated with lamivudine resistance were not found. ALT and HBV-DNA level after lamivudine resistance was variable, but jaundice or hepatic failure was absent. Mutation in YMDD motif was detected in 73% and other variable mutations were detected before treatment and after DNA breakthrough. CONCLUSIONS: Lamivudine resistance increases the longer the duration of treatment and clinical outcomes are variable. The mutation in YMDD motif was found in about 2/3 of cases. Other causes for lamivudine resistance may be considered.