Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men

Abstract

Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotype and DNA levels (i.e. viral load) were tested using polymerase chain reaction-based assays on plasma samples from 112 cases and 1031 non-cases. Prediagnostic plasma levels of HBV DNA were measured in multiple samples collected from each man (total 7706 samples), taken over periods of up to 16 years before diagnosis. Baseline viral load influenced HBV genotype-specific HCC risks and predicted the persistence of high viral load (>/=4.39 log copies/ml) that can cause HCC. Moderate to high tracking of viral load was observed within 9 years. Hepatitis B e antigen (P < 0.0001), genotype C HBV infection (P = 0.0369) and longitudinal alanine aminotransferase (ALT) elevation (defined as ALT abnormality in >/=50% of the visits) (P = 0.0005) were positively related to longer duration of persistence for high viral load. After multivariate adjustment, HBV genotype C [odds ratio (OR) = 5.97, 95% confidence interval (CI) = 3.44-10.34], high viral load detected at >/=50% of the visits (compared with sustained low viral load: OR = 5.04, 95% CI = 2.31-11.00) and longitudinal ALT elevation (compared with sustained normal ALT levels: OR = 2.84, 95% CI = 1.46-5.51) accounted for 43.5, 57.2 and 24.9% of HCCs, respectively. The results suggest that maintenance of viral load <4.39 log copies/ml was associated with sustained normalization of ALT levels and decreased risk of HCC.

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

“…This is largely influenced by the HBV genotype and host immune status. Previous studies have demonstrated that the presence of HBeAg and persistently high serum HBV DNA levels are risk factors for the occurrence of cirrhosis and HCC [12][13][14] . Moreover, chronic infection with HBV genotype C is more likely to cause liver cirrhosis than genotype B [15] .…”

Relationship between hepatitis B virus infection and chronic kidney disease in Asian populations: a meta-analysis

“…Firstly, HBV is hepatotropic viruses, and it has been documented that HBV infection have clinically and histologically more severe liver disease and higher risk of HCC and cirrhosis. 25,26 The possible explanation why HBV infection did not correlate with CKD, proteinuria, or low eGFR may be related to the competing risk of death. Secondly, the immune response to HBV is present only in patients with active hepatitis B, and this response plays a role in both hepatitis B and HBV associated nephropathy.…”

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

“…A retrospective study conducted among Taiwan population demonstrated that if the HBV load is greater than 105 copies/ml, the odd ratio for HCC risk would reach 2.5 (95%CI=1.1-5.7), furthermore, the author also observed a lower odd ratio of 2.3 between HCC risk and HBV load among noncirrhotic hepatocellular carcinoma patients . A case-cohort study in Taiwan revealed that high viral load can cause HCC and low viral load (<4.39 log copies/ml) was associated with sustained normalization of ALT levels and decreased risk of this disease (Wu et al, 2008). Similarly, a research performed in Hong Kong (Chan et al, 2008) also reported positive association between high HBV load and HCC risk with a hazard ratio of 1.62 among Hong Kong population.…”