Association of dynamic changes in serum levels of HBV DNA and risk of hepatocellular carcinoma

Abstract

Background and aimsWe aimed to examine the risk of HCC associated with the long-term change patterns in HBV DNA levels.MethodsWe conducted a longitudinal study of 6,301 participants with chronic HBV infection (CHB) from October 2012 to June 2019 and measured serum levels of HBV DNA at enrollment and during follow-up. The dynamic change patterns of HBV DNA were identified by group-based trajectory models. The associations between change patterns of HBV DNA and HCC were estimated using Cox regression models.ResultsDuring 35,112 person-years of follow-up, 182 participants developed HCC (518.34 per 105 person-years). Five trajectory groups of repeated measurement of HBV DNA were identified. The risk of HCC was significantly higher for the “high, fast-declined” group whose HBV DNA spontaneously decreased from > 2000 IU/mL at baseline compared with those with persistent undetected HBV DNA (reference group; 963.96 per 105 person-years, HR = 2.62, 95% CI, 1.82 to 3.77, P < 0.001). In addition, the “rebound” group whose HBV DNA level increased from undetectable level to > 20,000 IU/mL from baseline to the end of follow-up also showed an obviously higher cumulative HCC incidence rate (1193.29 per 105 person-years, HR = 4.17, 95% CI, 1.87 to 9.31, P < 0.001). The positive association remained stable after taking the potential effect of time-dependent antiviral treatment into account.ConclusionsSignificant variability in serum levels of HBV DNA presented during long-term follow-up. Regular monitoring of serum levels of HBV DNA and antiviral treatment are required for the clinical management of CHB patients, as well as those with undetected HBV DNA.