Patients with HBV Genotype B Infection Have More

OCD

[B]Patients with HBV Genotype B Infection Have More Severe Exacerbations of Disease and Higher Risk of Hepatic Decompensation and Mortality Compared with Patients with HBV Genotype C Infection[/B]

There is growing evidence that hepatitis B virus (HBV) genotypes may play some role in causing different disease profiles in chronic hepatitis B (CHB). Among Asians, who constitute ?gt;75% of the worldwide population of individuals with CHB, genotypes B and C are the 2 most common HBV genotypes. ?/sup>

Though genotype B can be subdivided into genotype Bj, representing genotype B found among infected individuals from Japan, and genotype Ba, representing genotype B found among individuals from the rest of Asia, most infected non-Japanese Asians have genotype Ba only. In this article, references to genotype B refer to genotype Ba unless otherwise noted.

A study from Taiwan shows that young patients with hepatocellular carcinoma are more likely to be infected with HBV genotype B than genotype C, whereas patients with more-advanced liver disease are more likely to be infected with genotype C than genotype B.

Other studies demonstrate that, compared with patients with genotype C infection, patients with genotype B infection have more serious liver disease . Recent studies show that patients with genotype B achieve hepatitis B e antigen (HBeAg) seroconversion a decade earlier than do patients with genotype C. Regarding responsiveness to treatment, there is some evidence that patients with genotype B respond better to IFN-alfa when compared with patients with genotype C.

However, the effect of HBV genotypes on HBV disease exacerbations has not been studied. We aimed to investigate, in a cross-sectional study, the relationship of HBV genotypes to the probability and severity of HBV disease exacerbations among Chinese patients with CHB.

During the period 2000  2001, 73 patients (group I) who were admitted to Queen Mary Hospital, The University of Hong Kong, Hong Kong, with severe exacerbations of hepatitis B disease and symptoms of hepatitis were recruited for our study. All 73 patients had tested positive for hepatitis B surface antigen for >6 months.

"Severe exacerbation" of disease was defined as an increase of alanine aminotransferase (ALT) levels to >10 times the upper limit of normal (ULN). Patients with evidence of other hepatotrophic virus infection, checked by testing with antibodies to hepatitis A, C, D, and E, were excluded. Patients with a history and clinical features of drug-induced hepatitis, alcoholic hepatitis, and steatohepatitis were also excluded.

There were no differences in the median age, sex ratio, proportion of HBeAg to antibody to HBeAg positivity, proportion of patients with ultrasonographic evidence of cirrhosis, and median HBV DNA level between the 4 groups of patients. Group I patients (i.e., with severe exacerbations) had a significantly higher median ALT level, lower median albumin level, and higher median bilirubin level compared with the other 3 groups (all P < .001).

There were no significant differences in the prevalence of genotype B and genotype C between the 4 groups (all P = NS). In total, there were 102 patients with single genotype B infection and 183 patients with single genotype C infection.

Infection with genotype B was associated with a higher prevalence of precore mutations (84 [82.4%] of 102 patients), compared with infection with genotype C (54 [29.5%] of 183). In contrast, infection with genotype C was associated with a higher prevalence of core promoter mutations (165 [90.2%] of 183 patients), compared with infection with genotype B (35 [34.3%] of 102; P < .001).

All patients with exacerbations of disease (groups I, II, and III) were categorized according to whether they were infected with HBV genotypes B or C. Patients infected with genotype B had a higher median ALT level, higher median bilirubin level, and lower median albumin level during periods of exacerbation, compared with patients infected with genotype C. This means that patients infected with genotype B had more severe exacerbations compared with those had by patients infected with genotype C.

Because nearly all patients we studied with HBV infection in the Chinese population became infected during the perinatal period or within the first 1-2 years of life, it is unlikely that there is any difference in the duration of infection for patients infected with genotypes B and C.

The higher rates of hepatic decompensation and mortality among patients infected with genotype B compared with patients infected with genotype C suggests that HBV genotype B may be more immunogenic and hence cause more severe immune-system-mediated damage. Studies have shown that patients infected with genotype B have earlier HBeAg seroconversion, compared with patients with genotype C.

Infection with genotype B was associated with precore mutations and infection with genotype C was associated with core promoter mutations.

The present study suggests that patients with HBV genotype B infection had more severe exacerbations of disease and a higher risk of hepatic decompensation and mortality due to severe exacerbations, compared with patients with HBV genotype C infections.

Previous longitudinal studies of acute exacerbations in patients with chronic HBV infection have demonstrated convincingly that acute exacerbations are usually not associated with infection with viral genotypes other than the original genotype. Further longitudinal studies should be designed to follow up a large population of patients with CHB and define the impact of the difference in exacerbations of disease among patients infected with genotypes B and C on the progression of the disease and the development of complications.

08/29/03

Reference
M-F Yuen and others. Role of Hepatitis B Virus Genotypes in Chronic Hepatitis B Exacerbation. Clinical Infectious Diseases 37: 593-597. August 15, 2003.