We read with great interest the nested case–control study by Gounder et al.[1] The study included 238 case patients and 435 control patients with sex, genotype and age-matched at cohort entry, and concluded that hepatitis B surface antigen (HBsAg) seroclearance was not associated with reduced risk of hepatocellular carcinoma (HCC) development. This is contradictory to observations of previous studies that HCC could occur at a lower rate after HBsAg seroclearance.[2-4] A most recent systematic review with meta-analysis has shown that HBsAg seroclearance is significantly associated with a reduced risk for HCC compared with persistently positive HBsAg (relative risk = 0.34, 95% CI: 0.20–0.56, P < 0.001).[5]
The following points require clarification/further discussion. First, as HCC development can be reduced by anti-viral treatment,[6, 7] anti-viral therapy in two of the case patients before HBsAg seroclearance and 32 control patients may have biased the results. What would be the results if these patients were excluded? Second, age ≥50 years at the time of HBsAg seroclearance is a risk factor for HCC development.[3, 8] The age at the time of HBsAg seroclearance was not reported in this study, but three of the four case patients who developed HCC were of advanced age and the remaining one was cirrhotic. Given the age at cohort entry of 28.8 years and a follow-up period of 28.9 years from cohort entry in case-patients, the median age at HBsAg seroclearance can be calculated to be 57.7 years, which is much higher than the age (45–51 years) reported in previous studies.[2-4] Third, HBV DNA was detected in 48% of case patients after HBsAg seroclearance for ≥9 years. This is extremely high as compared with 1–14.3% ever reported in the literatures,[3, 9] including that in their own previous study (17.7%).[10] Perhaps old age at HBsAg seroclearance and high proportion of viremia after HBsAg seroclearance might increase the HCC development in the study by Gounder's et al.[1] More information is needed for a valid discussion.
Acknowledgements
Declaration of personal interests: YC Chen have no financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work. YF Liaw has involved in clinical trials or served as a global advisory board member of Roche.
Declaration of funding interests: None.
References
1
Gounder PP, Bulkow LR, Snowball M, et al. Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther 2016; 43: 1197–207. 作者: StephenW 时间: 2016-6-15 17:49