Comparative analysis of disease severity between genotypes IA and IIIA of hepatitis A virus

Abstract

Although hepatitis A is a major health problem worldwide, it has not yet been clarified whether or not viral factors affect the clinical characteristics. This study aimed to investigate if a genotype of hepatitis A virus (HAV) affects disease severity among adolescent and adult populations. Clinical data and specimens were collected from patients ≥16-years-of-age with acute hepatitis A at two university hospitals in Korea during the two study periods: 1998 and 1999 (n = 45), and 2009 (n = 66). Nucleotide sequencing of the complete VP1 region of the HAV isolates was performed for phylogenetic analysis and genotyping. Clinical parameters related to disease severity were compared by HAV genotype to determine its clinical relevance. Of the 87 patients, 47 were male and the mean age was 29.8 ± 8.1 years. The genotype IIIA (93.0%, 53/57) was predominant in the year 2009, whereas IA (93.3%, 28/30) was the major genotype in 1998 and 1999. When comparing disease severity between the two HAV genotypes, the patients with genotype IIIA were older and had higher alanine aminotransferase (ALT) levels, prolonged prothrombin times and lower serum albumin levels. In a multivariate logistic regression model, higher ALT levels ≥ 1,000 IU/L (odds ratio [OR] 11.7, 95% confidence interval [CI] 2.5-54.0) and longer hospitalization (OR 22.49, 95%CI 4.6-132.5) were associated independently with genotype IIIA. In conclusion, this study indicates that HAV genotype might be one of the viral factors responsible for the disease severity of hepatitis A.

Possible widespread presence of hepatitis A virus subgenotype IIIA in Japan: Recent trend of hepatitis A causing acute liver failure

“…In the present study, the mean age of subgenotype IA and IIIA patients was 49 ± 9.6 and 49.5 ± 27.5 years, respectively. A recent study from Korea reported that HAV genotype influences the severity of liver disease and that a higher ALT level (>1000 IU/L) and longer hospitalization were significantly associated with subgenotype IIIA 7 . All HAV‐associated acute liver failure patients in the study of Fujiwara et al 4 .…”

“…It was reported that almost all acute hepatitis A cases (93.6%) were caused by subgenotype IA and only 2.1% by subgenotype IIIA, 4 and that all acute liver failures were caused by subgenotype IA. Thus, the possibility of a changing pattern in circulating HAV genotypes such as that reported in Korea 7 might need to be entertained in Japan as well.…”

“…Until early 2000, almost all isolates tested had been identified as subgenotype IA 8 . A more recent study showed that subgenotype IIIA has been predominant since 2008 7 . In addition, a rise in the frequency of hepatitis A outbreaks has recently been observed in South Korea, our immediate neighbor, although the number of hepatitis A cases in Japan has been progressively decreasing during the last several years 9 .…”

“…[4][5][6] Recent studies on HAV genotypes from South Korea have shown a distinct pattern change in circulating HAV genotypes over the past 10 years. 7 Until early 2000, almost all isolates tested had been identified as subgenotype IA. 8 A more recent study showed that subgenotype IIIA has been predominant since 2008.…”

Full-Length Genomic Sequence of Subgenotype IIIA Hepatitis A Virus Isolate in Republic of Korea

“…Previouse studies on HAV genotypes in Republic of Korea have shown a distinct changing pattern in circulating HAV genotypes over the past 10 years [24]. Until 2004, subgenotype IA was the most prevalent in the Republic of Korea [25].…”