Hepatitis B Disease Progression Dependent on HBV Genotype

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Hepatitis B Disease Progression Dependent on HBV Genotype

By Brian Boyle, MD

The course of chronic hepatitis B virus (HBV) infection varies widely from patient-to-patient. Some patients with HBV experience little or no progression of their liver disease and may spontaneously undergo seroconversion from being HBV e antigen (HBeAg) positive to negative, and, in some cases, this may be accompanied by the loss of HBV DNA.

In other cases, however, HBV is associated with significant liver damage, which, in come cases, ultimately leads to cirrhosis or hepatocellular carcinoma (HCC) and death.

Unlike hepatitis C virus (HCV), the liver damage caused by HBV is largely due to the host immune response and not a direct cytopathic effect. As a result, host and viral factors may significantly influence the likelihood and rate of HBV disease progression.

Genetic variability of HBV may be one of these factors and HBV has been classified into at least 7 genotypes, named A to G, with the prevalence of each genotype varying by geographical region. It has been proposed that HBV genotype may correlate with the clinical progression of HBV disease, and in some studies genotype C has been shown to be more frequent in severe liver disease.

In order to evaluate the association of HBV genotype and HBV disease progression, investigators from Japan, a country with high rates of HBV infection, examined the influence of HBV genotypes on the progression of liver disease in patients with HBV.

In the study, the medical records of 585 patients with chronic HBV infection, including 258 with biopsy-proven chronic liver disease (CLD) and 74 with HCC, were examined. The investigators found that the mean ages of both patients with advanced fibrosis/cirrhosis and with HCC were significantly older in genotype B than in genotype C patients (P = .018, P = .024, respectively).

Both the HBeAg negativity rate at biopsy and the cumulative HBe seroconversion rate in patients with CLD were significantly higher in genotype B patients than genotype C patients (P < .01, P = .022, respectively). A multivariate analysis showed that genotype B, presence of precore mutation, higher ALT levels, and severe histologic activity were independent factors for HBe seroconversion.

Among all the biopsy-proven CLD patients, the ratio of patients with advanced fibrosis in genotype B was significantly lower than that in genotype C (4/30 (13%) vs. 74/224 (33%), respectively; P = .034). The distribution of each genotype between CLD and HCC was very similar (B and C: 11.2% and 87.0% vs. 10.8% and 89.2%, respectively).

The authors conclude from these data that "based on the clinical data of 258 patients with biopsy-proven CLD, the proportion of patients with advanced fibrosis (F3 or F4) in genotype B was significantly lower than that in genotype C, suggesting that genotype C was associated more with advanced fibrotic liver disease.

"The median age of patients with advanced fibrosis (F3 or F4) with genotype B was significantly higher than patients with the same condition with genotype C. Because in most Japanese patients with chronic hepatitis B, HBV infections occur vertically from their mothers at birth, the duration of infection is almost the same as the age of the patients. Therefore, these data suggest that genotype B HBV chronic infection required a longer duration for progression of liver fibrosis than genotype C infection."

01/03/03

Reference
H Sumi and others. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003; 37:19-26.


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