By Liz Highleyman

It is well known viral genotype plays an important role in treatment response in people with hepatitis C. The influence of hepatitis B virus (HBV) genotypes, however, has been less extensively studied.

Two presentations at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) last month in San Francisco looked at HBV genotype in relation to HBV DNA levels in HBV monoinfected individuals and liver disease progression in HIV-HBV coinfected patients.

HBV Viral Load

H. Krarup and colleagues looked at relationships between HBV genotype, HBV DNA levels, patient gender, and country of origin. The study included samples from 802 consecutive HBV DNA positive patients in Denmark. A majority (n = 427) were men, and the median ages were 37 for men and 30 for women. 195 samples could not be genotyped, mostly due insufficient material or too low viral load.

Results

• Of the 607 genotyped samples, the following distribution was found:

• 11.2% genotype A;
• 14.3% genotype B;
• 19.4% genotype C;
• 50.3% genotype D;
• 2.3% genotype E;
• 0.5% genotype F;
• 1.5% genotype G;
• 0.8% more than 1 genotype.

• A significant difference was observed in HBV DNA levels between patients with genotype A compared with B and C (P < 0.008), and between genotype D compared with B and C (P < 0.007).

• No difference in viral load was observed between patients with genotypes A and D or those with B and C.

• HBV DNA levels were as follows:

• Genotype A: 1.2 x 10(5) IU/mL
• Genotype B: 1.4 x 10(7) IU/mL;
• Genotype C: 1.4 x 10(7) IU/mL;
• Genotype D: 1.0 x 10(5) IU/mL.

• No differences in viral load were observed according to patient gender, either overall or within different genotype subgroups.

• A significant difference in gender distribution was observed in the 4 predominant genotype groups, with more women having genotypes B or C, while more men had A or D (P < 0.001).

• Women were significantly younger than men in the genotype B (30 vs 41 years) and genotype D (30 vs 35 years) groups, but there was no significant age difference in the genotype A (32 years vs 35 years) or genotype C (29 vs 31 years) groups.

• More than 65% of patients with genotype A came from Africa, 73% with genotype B and 95% with genotype C came from Southeast Asia, and 75% with genotype D came from the Middle East, Afghanistan, or India.

"We found the median of serum HBV DNA levels 100 times higher in genotypes B and C compared to genotypes A and D," the investigators concluded. "More women than men had genotypes B or C, as opposed to genotypes A or D. The distribution of genotypes was as expected from ethnic origin of the patients."

Liver Fibrosis

D.Y. Dao and colleagues looked at the relationship between HBV genotype and liver fibrosis in HIV-HBV coinfected patients, given that previous studies have indicated such an association in HBV monoinfected individuals.

The researchers examined a cohort of 141 HIV positive/HBV surface antigen (HBsAg) positive patients at a large inner city HIV clinic. Just under half were African American and 37% were Caucasian.

The median follow-up period was 37 months. HBV genotyping was done by direct sequencing. Baseline demographics and liver function tests results were obtained through chart reviews. Non-invasive serum biomarkers (APRI and Fib-4) were used to assess fibrosis stage at the last clinical follow-up visit. Scores were classified as either absent or minimal fibrosis (stage 1) or moderate or advanced fibrosis (stage 2 or higher).

Results

• 100 patients (75%) had HBV genotype A, while 41 (25%) had non-A genotypes:

• Genotype G: 17 patients (13%);
• Genotype D: 8 patients (6%);
• Mixed genotype A/G: 4 patients (3%);
• Genotype F: 2 patients (1.5%);
• Genotype H: 2 patients (1.5%).
• Unable to determine genotype: 7 patients.

• African Americans were more likely than Caucasians to have genotype A (83% vs 67%, respectively; P = 0.06).

• 7 of 17 patients with non-A genotypes had advanced fibrosis, compared to 6 of 64 with genotype A (41% vs 9%; P = 0.0015).

• Fib-4 showed that 8 of 24 patients with non-A genotypes had advanced fibrosis, compared to 9 of 68 genotype A patients (33% vs 13%; P = 0.03).

• Median alanine aminotransferase (ALT) levels were higher in patients with non-A genotypes compared to genotype A (65 vs 30 IU; P < 0.0001).

• 18 of 20 patients with non-A genotypes were hepatitis B "e" antigen (HBeAg) positive, compared to 44 of 62 genotype A patients (90% vs 71%; P = 0.08).

"This cross-sectional analysis reveals that HBV genotype appears to play a role in the natural history of the HIV-HBV coinfected patients," the investigators concluded.

"Genotype A is the most prevalent, but there is a high prevalence of genotype G in HIV-HBV coinfected population," they continued. "Non-A genotypes are associated with more liver fibrosis on follow-up evaluation."

Finally, they noted, "HBV genotypes may be an important tool to predict those who may be at greatest risk for liver disease progression in the HIV-HBV coinfected population."

12/2/08

References

H Krarup, P Madsen, A Bentzen-Petersen, and others. Higher Levels of HBV-DNA in Genotypes B and C Compared to Genotypes A and D. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 870.

DY Dao, H Yuan, R Joshi, and others. Non-A Hepatitis B Genotypes are Associated with More Liver Fibrosis in HIV/HBV Patients. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 869.