Hepatitis B genotype B associated with poorer liver-related outcomes in Taiwanese patients co-infected with HIV and hepatitis B

Michael Carter
Published:
13 December 2011

Liver-related outcomes are poorer in HIV-positive patients who are co-infected with hepatitis B virus genotype B compared to co-infected patients with hepatitis B genotype C, Taiwanese investigators report in the online edition of Clinical Infectious Diseases.

The prospective, observational study involved individuals who commenced antiretroviral therapy containing 3TC (lamivudine, Epivir, also in the combination pill Combivir), a drug which has activity against both viruses. The patients were recruited between 1997 and 2008, and followed until 2010.

“Patients with [hepatitis B virus] genotype B co-infection were at higher risk of developing hepatitis flares, liver disease-related deaths, HBeAg seroconversion, and lamivudine resistance mutations than those with genotype C coinfection,” write the authors. Genotype did not affect HIV-related outcomes.

HIV and hepatitis B share transmission modes. Therefore, large numbers of patients are co-infected with these viruses. There are eight hepatitis B genotypes (A – H). The distribution of genotypes varies according to geographical region, and genotypes B and C predominate in Asia.

Little is known about the differential impact of these two genotypes on liver-related outcomes in patients co-infected with HIV and hepatitis B.

Therefore, investigators in Taiwan recruited 145 co-infected patients starting antiretroviral therapy to a study analysing the clinical, immunological and virological outcomes of patients according to hepatitis B genotype.

The hepatitis B-related outcomes included the risk of hepatitis flares, liver disease-related death, hepatitis B e antigen (HBeAg) seroconversion, and the development of strains of hepatitis B with resistance to 3TC. Changes in CD4 cell count and HIV viral load were also compared according to genotype.

A total of 96 patients were co-infected with genotype B and 49 with genotype C were recruited. There were no significant baseline differences between the patients.

However, they had severe immune suppression at the time they started HIV treatment, and their median CD4 cell count was just 117 cells/mm3. Median baseline HIV viral load was approximately 125,000 copies/ml. Median hepatitis B viral load at the start of the study was 63,000 copies/ml.

Patients were treated with 3TC-containing antiretroviral therapy for a median of 2.8 years. During this time, none of the patients received any other antiretroviral drugs with activity against hepatitis B.

Compared to patients with genotype C, those with genotype B co-infection were significantly more likely to experience hepatitis flares (44% vs. 27%, p = 0.04), die of liver-related causes (9% vs. 0%, p = 0.03), have HBeAg seroconversion (62% vs. 25%, p = 0.03), and developed strains of hepatitis B with resistant to 3TC (31% vs. 12%, p < 0.001).

Analysis that controlled for potentially confounding factors confirmed the relationship between genotype B co-infection and a number of liver-related outcomes.

Compared to individuals with genotype C, those with genotype B had a higher risk of hepatitis flares (AHR = 4.13; 95% CI, 2.87-5.39; p = 0.01) and were also more likely to develop 3TC-resistant hepatitis B (AHR = 8.67; 95% CI, 6.37-10.98, p = 0.001).

However, there was no significant difference in mortality risk between the genotypes. Nor did HIV-related outcomes differ between the two groups of patients, who had similar falls in viral load and increases in CD4 cell count.

“Hepatitis B genotype B is the most predominant genotype in hepatitis B virus and HIV-co-infected Taiwanese patients,” conclude the investigators. “Patients with genotype B co-infection are more likely to experience acute exacerbations of hepatitis, HBeAg seroconversion, lamivudine resistance, and liver disease-related death than those with genotype C coinfection when they receive [HIV therapy] containing lamivudine as the only active agent against hepatitis B virus.”

Reference

Sheng W-H et al. Differential clinical and virologic impact of hepatitis B virus genotypes B and C on HIV-coinfected patients receiving lamivudine-containing highly active antiretroviral therapy. Clin Infect Dis, online edition. DOI: 10/1093/cid/cir851, 2011 (click here for the free abstract).