SUMMARY: Hepatitis B virus (HBV) genotype G, found in 17% of a Texas cohort of HIV/HBV coinfected patients, was associated with more aggressive liver fibrosis progression, according to a poster presented at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last week in San Francisco. Investigators also found that African-Americans tended to have milder fibrosis, while Hispanics were at greater risk of advanced liver disease.

By Liz Highleyman

Over years or decades, chronic hepatitis B can lead to advanced liver disease, and some evidence indicates that this may happen more rapidly in HIV/HBV coinfected people. But the effect of HBV genotypes on disease progression in this population is not fully understood.

Doan Dao from the University of Texas Southwestern Medical Center and colleagues examined the prevalence and impact of genotype on liver fibrosis in coinfected patients.

Genotype G is a defective form of HBV that replicates poorly in most settings, the investigators noted as background. Prior research indicated that this genotype is present in less that 1% of HBV monoinfected people, is hepatitis B "e" antigen (HBeAg) negative, and typically results in low HBV DNA viral load.

Experiments in immunocompromised animals suggest that HBV genotype G frequently mixes with other genotypes to enhance its replication capacity, they continued. The resulting mixed form causes cellular steatosis (fat accumulation) and has direct cytopathic (cell-killing) effects on liver cells, thereby promoting liver fibrosis.

The investigators determined HBV genotype(s) in stored serum samples from 133 HIV positive individuals with hepatitis B surface antigen (HBsAg) who received care at a Dallas teaching hospital.

Most participants (84%) were men, the median age was 42 years, about half were black, 38% were white, and 11% were Hispanic. About one-quarter were positive for hepatitis C virus (HCV) as well as HIV and HBV. Most (again, 84%) had absent or mild fibrosis at baseline. The median CD4 cell count was quite low, at 190 cells/mm3.

The researcher quantified HBV DNA levels and measured HBeAg and anti-HBe antibody titers. They used the Fib-4 non-invasive biomarker index (which includes ALT, AST, and platelet levels) to assess fibrosis stage. The median follow-up time was 35 months (range 0 to 110 months).

Results

	The HBV genotype distribution among the study participants was as follows:
	Genotype A: 74%; Genotype G: 17%; Genotypes D: 5%; Genotype F: 1.5%; Genotype H: 1.5%.
	Genotype G appeared in mixtures with other HBV genotypes, confirmed by the presence of high HBeAg levels (87%), HBeAg positive, undetectable HBe antibodies (86%), and high HBV DNA levels (median 8.0 log10 copies/mL).
	Genotype G was associated with a significantly greater frequency of advanced fibrosis (39%) compared with genotype A (1%).
	African-American patients had a significantly higher prevalence of mild fibrosis compared with white or Hispanics patients.
	In a multivariate analysis, having HBV genotype G was associated with increased fibrosis (odds ratio [OR] 4.3, or more than 4-fold higher risk), while being African-American was associated with milder fibrosis (OR 0.17).

"HBV genotype G was prevalent in the HIV-infected population but likely had gained replicative fitness and HBeAg production by mixing with other genotypes, most likely genotype A," the researchers concluded. "HBV genotype G in the mixed form with other HBV genotypes would explain the high HBV DNA and HBeAg levels observed.

"Despite significantly shorter time of follow-up, patients with HBV genotype
G appear [to] have more advanced fibrosis [among] HIV/HBV coinfected patients," they continued. "The reason for this more aggressive disease is unclear."

Finally, they recommended, "In HIV/HBV coinfection, HBV genotyping may be an important tool to assess if the patient is at increased risk for liver disease progression."

University of Texas Southwestern Medical Center, Dallas, TX.

2/26/10

Reference
D Dao, J Balko, N Attar, and others. Genotype G Hepatitis B Virus (HBV) and Advanced Liver Fibrosis in HIV/HBV Co-infected Patients. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 626).