A French study has found that the degree of liver damage in patients infected with both hepatitis B and HIV is affected by the strain or 'genotype' of hepatitis B virus. This leads the investigators to call for testing of hepatitis B genotypes in patients co-infected with HIV. The study’s findings are published in the 14th February edition of AIDS.
There are seven known genotypes of the hepatitis B virus, which are given the letters A to G. Previous studies have shown that genotype can affect the speed of liver disease progression in HIV-negative patients. However, its effects in patients who also have HIV have not been analysed before.
To gain more information on the role of hepatitis B virus genotypes in liver disease, investigators from seven French HIV clinics examined the risk factors for liver damage or 'fibrosis' in 104 HIV-positive patients, as part of a larger prospective study.
The investigators compared the patients’ risk factors for liver damage to the degree of fibrosis detected in liver biopsies. Risk factors included hepatitis B genotype, duration of HIV and hepatitis B infection and treatments for both viruses, as well as infection with hepatitis C or D, alcohol intake and body mass index.
Seventy (67%) of the patients had ‘extensive’ fibrosis, with a score of two or greater on the METAVIR scale, which runs from zero to four.
After adjusting the data for the known risk factors for fibrosis, the researchers found that the odds of a patient having a METAVIR score of two or more were 12.6 times greater when they were infected with genotype G than the more common genotype A (p < 0.009).
“Hepatitis B virus genotype G is a determinant of liver fibrosis in HIV / hepatitis B virus-co-infected patients,” they conclude. “Hepatitis B virus genotyping should be considered as part of the management of patients with multiple risk factors for rapid profession of liver fibrosis.”
Although usually rare, genotype G was found in 13% of the patients included in this study. “Genotype G is thought to occur mainly in Western countries and to be transmitted by men having sex with men,” the investigators explain. “The relatively high frequency of this genotype in our study population may, therefore, reflect the predominance of male homosexuals and supports previous data.”
Other factors that were independently linked to fibrosis were exposure to efavirenz (Sustiva; odds ratio: 3.6, p < 0.03) and length of HIV infection (odds ratio: 3.9, p < 0.01). However, there was no significant association between fibrosis and the use of anti-hepatitis B drugs, resistance to lamivudine (3TC, Zeffix / Epivir) or mutations in the hepatitis B virus.
The study was limited by only including patients who had had liver biopsies as part of their medical care. Compared to co-infected patients who had not had liver biopsies taken, the patients included in the study had markers of more severe hepatitis B disease, including higher levels of hepatitis B virus in the blood, antibodies against hepatitis B and higher levels of the liver enzyme alanine aminotransferase (ALT). They were also more likely to have received interferon therapy.
The investigators also stop short of directly linking efavirenz use to liver damage. “The observed association between efavirenz exposure and the degree of liver fibrosis may not be a causal one,” they write. “Other non-nucleoside reverse transcriptase inhibitors, such as nevirapine, have been linked to a higher risk of hepatotoxicity in HIV-infected patients with hepatitis C virus or hepatitis B virus co-infection.
“Prospective studies are needed to draw firm conclusions on the impact of nevirapine and efavirenz on liver fibrosis,” they add.
Lacombe K et al. Major role of hepatitis B genotypes in liver fibrosis during coinfection with HIV. AIDS 20: 419-427, 2006.