THE GENOTYPE SHIFT AND ITS CLINICAL IMPACT OF ACUTE HEPATITIS A IN KOREA: NATIONWIDE MULTICENTER STUDY

초록

Background/Aims: Recently, explosive increasing incidence and the more serious clinical features of acute hepatitis A(AHA)has been reported in Korea. Almost all reported genotype was IA until the end of 1900s in Korea(Byun et al. 2001;16:519-524). Therefore, we investigated whether there is a genotype shift and the change of genotype influence the clinical features in Korean AHA. Methods: Nationwide 24 major medical centers participated in this study. From June 2007 to May 2009, we enrolled 1333 AHA patients, prospectively. Among them, we performed nested RT-PCR using 546 patients’ serum samples. We performed phylogenetic analysis and then compared the clinical features according to genotype. Results: Hepatitis A virus(HAV) RNA was positive in 359/ 546 (66%). Among 351 patients with identified genotype, IIIA were 178(51%) and IA were 173(49%). The sequences of genotype IA were identical to previously reported Korean genotype IA and new genotype IIIA showed close relationship and 100% homology with NOR24/Norway sequence(AJ299467). Interestingly, higher genotype IIIA(63%) AHA was identified in Seoul of capital city than other provinces(31%)(p=0.003). To find the time of genotype shift, we retrospectively analysed the genotype using stored serum samples of AHA from 2000 to 2006. All 41 samples with positive HAV RNA showed genotype IA. It suggested that genotype shift occurred abruptly around mid 2000s. There was no difference in age and sex between patients with two genotype. In baseline laboratory test, patients with genotype IIIA showed significantly higher AST(3827 ±3780 vs. 2682 ±2854 IU/L, p=0.002) and ALT(3407 ±2436 vs. 2891 ±1940 IU/L, p=0.031) and showed significantly lower platelet count(159 ±74 vs. 178 ±85 103mm3, p=0.038) than patients with genotype IA. In peak or lowest laboratory data,patients with genotype IIIA showed significantly higher AST(4351 ±4151 vs. 3136 ±2953 IU/L, p=0.002) andALT(3889 ±2510 vs. 3401 ±2510 IU/L, p=0.047) andshowed significantly lower platelet count(149 ±72 vs. 167 ±78 103mm3, p=0.036) than patients with genotype IA. How-ever, in clinical outcomes, there is no differences in hospital stay(8.9 vs. 9.3 days), the incidence of cholestatic hepatitis(1.8% vs. 0%), acute kidney injury(4.7% vs. 4.6%) and acute liver failure(1.2% vs. 1.2%) and mortality(0.6% vs. 0.6%) between patients with IA and IIIA. Conclusions: In Korean AHA, genotype shift was identified and genotype IIIA HAV was being autochthonous. Although there was significant difference in biochemical response of AHA between genotype IA and IIIA, any difference in clinical outcomes such as complicated cases or mortality was not identified.