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HBV GENOTYPE C IS ASSOCIATED WITH MORE FREQUENT FLARES IN ALT, PROGRESSION TO CIRRHOSIS AND HEPATOCELLULAR CARCINOMA COMPARED TO GENOTYPE B IN PATIENTS WITH CHRONIC HEPATITIS B

SK Fung, FS Wong, DK Wong, AS Lok
BACKGROUND AND AIM: The most common hepatitis B virus (HBV) genotypes among Asians are B and C. Genotype C has been reported in studies in Asian countries to be associated with more aggressive liver disease and hepatocellular carcinoma (HCC). The aim of this study was to compare the rate of ALT flares, incidence of cirrhosis and HCC among a cohort of Canadian patients with HBV genotype B and C.

PATIENTS AND METHODS: Untreated adult patients with chronic hepatitis B attending the University Health Network Liver Clinic (Toronto, ON) were prospectively enrolled in an observational study. Liver biochemistry, complete blood count and prothrombin time were measured every 3 months; HBV serology and HBV DNA levels every 6 months. HBV genotype was determined using a line probe assay. Patients were monitored for ALT flares, development of cirrhosis and HCC. A flare in ALT was defined as a rise in ALT > 3xULN [ULN, 40 IU/L] in patients with normal ALT at baseline. Cirrhosis was determined using abdominal ultrasound or liver biopsy; HCC was diagnosed using radiologic criteria with or without liver biopsy. Statistical analysis was performed using SPSS 13.0.
RESULTS: 135 predominantly Asian (95%) adult patients (65% M: 35% F) with a mean age of 41±13 years were followed for 18±13 months. At baseline, 60 (44%) patients were found to have HBV genotype B, while 75 (56%) had genotype C. There was no significant difference in age or baseline ALT levels between the groups, but HBeAg was more prevalent (59% vs. 37%, p=0.01) and HBV DNA level was higher (7.3 vs. 6.6 log copies/ml, p=0.03) among genotype C patients. During follow-up, the probability of developing a flare in ALT at months 12, 24 and 36 was 30%, 42% and 50% for genotype C patients compared to 14%, 23% and 32% for genotype B (p=0.01). Multivariate analysis identified male gender (OR=2.7), presence of HBeAg (OR=2.7) and genotype C (OR=2.1) as predictors of ALT flares. Progression to cirrhosis was more prevalent among genotype C patients (20% vs. 8%, p=0.02). Additionally, 8 cases of HCC were diagnosed and all occurred among genotype C patients (11% vs. 0%, p=0.02).
DISCUSSION: Compared to HBV genotype B, genotype C is associated with a higher risk of ALT flares, development of cirrhosis and HCC. Patients infected with genotype C may require closer follow-up and vigilant screening for the development of HCC. Larger studies are required to confirm our findings.

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