Serum hepatitis B virus (HBV) DNA levels can fluctuate markedly during the course of chronic HBV infection. Both case-control and cohort studies have shown a significant, dose-response association between serum HBV DNA levels measured at the time of initial evaluation and the subsequent risk of cirrhosis. A similar direct relationship has been shown for the risk of hepatocellular carcinoma (HCC) in cross-sectional, case-control, and cohort studies. Interventional studies have shown a strong correlation between the indices of disease activity seen on liver biopsy and levels of serum HBV DNA. These studies have also shown that reduction in HBV DNA levels correlate strongly with improvements in liver histology. For patients with HCC, prognosis (including risk of death, metastasis, and recurrence following surgery) is worse with higher serum HBV DNA levels. The preponderance of the evidence in the published literature demonstrates that serum HBV DNA level is an important and independent risk factor for disease progression in chronic hepatitis B. The relative importance of serial HBV DNA measurements, the loss of hepatitis B e and surface antigens, as well as the emergence of HBV mutants in the progression of chronic hepatitis B, especially in young patients, is an important need for future research. (Hepatology 2009;49:S72–S84.)

Hepatitis B virus (HBV) infection causes infant fulminant hepatitis (IFH), and chronic HBV infection may progress to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Taiwan launched a nationwide HBV immunization program for newborns in July 1984,¹ which has successfully lowered the prevalence of chronic HBV carriers, incidence of HCC, and mortality of IFH in vaccinated birth cohorts.^2-4 The mortality of CLD before and after HBV immunization has never been examined. We assessed the 30-year outcomes of the immunization program.

The relation between aflatoxin B₁ (AFB₁) and cirrhosis in chronic carriers of hepatitis B virus (HBV) remains inconclusive. This case‐control study nested in a large community‐based cohort aimed to assess the effect of AFB₁ exposure on cirrhosis and HCC in chronic HBV carriers. Serum AFB₁‐albumin adduct levels at study entry were measured in 232 cirrhosis cases, 262 HCC cases and 577 controls. Multivariate‐adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. Among all chronic HBV carriers, the time intervals between study entry and diagnosis of HCC, cirrhosis, cirrhotic HCC, and non‐cirrhotic HCC were all significantly (p < 0.0001) shorter in participants with high serum levels of AFB₁‐albumin adducts than those with low/undetectable levels. There were significant dose‐response relations with serum AFB₁‐albumin adduct level at study entry for cirrhosis (p‐trend = 0.0001) and cirrhotic HCC (p‐trend < 0.0001) newly diagnosed within 9 years after entry as well as non‐cirrhotic HCC (p‐trend = 0.021) newly diagnosed within 4 years after entry. The aORs (95% CIs) for high versus undetectable serum AFB₁‐albumin adduct levels were 2.45 (1.51–3.98) for cirrhosis (p = 0.0003), 5.47 (2.20–13.63) for cirrhotic HCC (p = 0.0003), and 5.39 (1.11–26.18) for non‐cirrhotic (p = 0.0368) HCC, respectively. There remained a significant dose‐response relation between serum AFB₁‐albumin adduct level and HCC risk (p‐trend = 0.0291) in cirrhosis patients, showing an aOR (95% CI) of 3.04 (1.11–8.30) for high versus undetectable serum levels (p = 0.0299). It is concluded that AFB₁ exposure may increase the risk of cirrhosis and HCC in a dose‐response manner among chronic HBV carriers.