Natural history of chronic hepatitis B: phases in a complex relationship.

Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a complex interplay of virological, environmental and host factors. The dynamic relationship between the virus and host evolves over the duration of the infection and different phases of the disease have been observed and described. These have been conceptualized in terms of the state of balance between the host immune system and the hepatitis B virus and have been given the labels immune tolerant, immune clearance, immune control and immune escape although other nomenclature is also used. Host factors, such as age at infection, determine progression to chronicity. Virological factors including hepatitis B viral load, mutations and genotype also have an impact on the adverse outcomes of the infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the natural history of CHB has evolved significantly over the past few decades and characterizing the phase of disease of CHB remains an integral part of managing this virus in the clinic.

Longitudinal observation of viral load changes in untreated HBeAg negative chronic hepatitis B.

INTRODUCTION: An HBV DNA level of 2000 IU/ml has been used to differentiate HBeAg negative chronic hepatitis B from the inactive carrier state. We sought to examine the nature and frequency of fluctuations in viral load and ALT around this threshold. METHODS: A retrospective review of St Vincent's Hospital database was performed to identify patients who had been observed, untreated, with HBV DNA and ALT levels over a period of at least 18 months. RESULTS: 27 HBeAg negative patients with HBV DNA < 2000 IU/ ml at baseline (Group 1) and 20 HBeAg negative patients with HBV DNA > or = 2000 IU/ml (Group 2) were identified. Of group 1 patients, only 8/27 had persistently normal ALT and HBV DNA persistently <2000 IU/ml over a median followup of 24 months. 11/27 (41%) Group 1 patients showed fluctuations above 2000 IU/ml over a median of 24 months followup, most of which were transient and in the range <20,000 IU/ml. They were accompanied by persistently normal ALT in 5/11 (45%). 8 of 20 (40%) Group 2 patients had a drop of HBV DNA to <2000 IU/ml over followup. These had a significantly lower baseline HBV DNA (8610 v/s 208763, p = 0.03) than those that remained persistently >2000 IU/ml. CONCLUSIONS: Minor fluctuations in HBV DNA up to 20,000 IU/ ml, accompanied by persistently normal ALT occur frequently in HBeAg negative chronic hepatitis B.

Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B.

BACKGROUND/AIMS: To evaluate the association between demographical features, serum ALT and HBV DNA and the prevalence of significant fibrosis and inflammation on liver biopsy in patients with chronic hepatitis B. METHODS: In this cross-sectional study of patients on St Vincent's Hospital HBV database, patients were classified into three groups on the basis of HBeAg status and HBV DNA level and the prevalence of significant (F2/3/4) fibrosis and (A2/3) inflammation in each group was established. Patients were also divided into HBeAg-positive and -negative groups and examined for the prevalence of significant fibrosis/inflammation in the strata of HBV DNA and ALT. Predictors of significant fibrosis and inflammation in HBeAg-positive and -negative patients were examined by logistic regression. RESULTS: Three hundred and ninety four patients (HBeAg positive=198; HBeAg negative=196) with liver biopsy were identified. Fifty-eight percent of HBeAg-negative patients with HBV DNA >25,000 IU/ml had F2/3/4 fibrosis. HBV DNA and F2/3/4 were positively correlated in HBeAg-negative patients [odds ratio (OR) 1.42, P=0.001] but inversely correlated in HBeAg-positive patients (OR 0.71, P=0.03). HBV DNA was an independent predictor of significant fibrosis in HBeAg negative (P=0.03) but not HBeAg-positive patients. In HBeAg-positive patients, age was the only predictor of significant fibrosis (P=0.001) and ALT the only predictor of significant inflammation (P=0.003). In the whole cohort there was a close positive association between inflammation and fibrosis. CONCLUSION: Increasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis only in patients with HBeAg-negative CHB.