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We read with great interest the article by Zhang et al (Gut 2008;57:1713–20). Hepatitis B virus (HBV) infection is a global health problem and at least eight HBV genotypes (A–H) have been identified. Genotypes A and D are prevalent in Western countries, whereas genotypes B and C are common in Asian countries. The clinical significance of HBV genotype in terms of disease progression and response to antiviral treatments has been increasingly recognised; however, the association of HBV genotypes with the development of chronic infection in acute hepatitis B patients remains to be elucidated. In this timely community-based study from China, the authors indicated that HBV genotype C is more likely to cause chronic infection than genotype B. These findings indeed improve our understanding of the role of HBV genotype in the progression to chronic infection. Nevertheless, some of their data are discrepant with those previous reports and thus deserve further discussion.
First, few studies have addressed the distribution and clinical significance of HBV genotypes in patients with acute hepatitis B. Our recent data showed that all Taiwanese patients with acute HBV infection had either genotype B (63%) or C (37%) infection.1 The distribution of HBV genotypes in patients with acute hepatitis B was comparable with that in hepatitis B surface antigen (HBsAg)-positive blood donors and patients with chronic hepatitis B.2 Reports from Japan also revealed a similar distribution of HBV genotypes between patients with acute and chronic hepatitis B.3 4 All these observations suggest that the distribution of HBV genotypes in acute hepatitis B merely reflects the predominance of certain genotypes in a given geographic area. In this study, of particular note is that the proportion of HBV genotype B was found to be significantly higher in patients with acute hepatitis B than in asymptomatic carriers by using a case–control study design. Since only 68 of 294 (23%) patients with acute hepatitis B could be genotyped, the possibility of selection bias cannot be excluded. This possible bias may confound their subsequent analyses and major conclusion that HBV genotype C is more prone to causing chronic infection than is genotype B. Further large prospective studies on a reasonable number of patients with acute hepatitis B with different HBV genotypes are required to clarify this interesting and important issue.
Second, the authors claimed that asymptomatic carriers with HBV genotype B infection had a significantly higher serum viral load as well as hepatitis B e antigen (HBeAg) positivity than those with genotype C infection. It is known that the positivity of HBeAg in HBV carriers is age dependent. Our recent 14-year prospective study on 4841 Taiwanese HBV carriers demonstrated that HBV viral load and the rate of HBeAg positivity were higher in patients with genotype C than age-matched patients with genotype B.5 In addition, our follow-up study also showed that patients with genotype C had a lower annual incidence of spontaneous HBeAg seroconversion than patients with genotype B (7.9% vs 15.5%, respectively).6 These lines of evidence indicate that patients with HBV genotype C usually have an infrequent, delayed HBeAg seroconversion and therefore a longer duration of high HBV replication than patients with genotype B. Accordingly, the results of the current study contradict existing evidence, and the authors may re-analyse their data by stratifying the age of patients.
In summary, despite recent advances in the molecular characterisation of HBV strains helping us to understand the association of HBV genotypes with clinical outcomes of HBV infection, identification of viral factors predictive of chronicity in adult-acquired acute infection remains a compelling task in the global control of HBV infection.
Competing interests: None.
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