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Gene Patterns Predict Fibrosis in HIV/HCV Coinfected People

Certain haplogroups, or gene pattern clusters, were associated with reduced risk of liver fibrosis among European patients with HIV and hepatitis C coinfection.

By Liz Highleyman

Due to overlapping transmission routes, many HIV positive people are coinfected with hepatitis C virus (HCV). Studies have shown that HIV/HCV coinfected patients tend to experience more rapid liver disease progression and do not respond as well to interferon-based therapy. But progression is highly variable, and researchers continue to learn more about factors that influence the course of disease.

As described in the June 13, 2011, advance online edition of AIDS, Monica García-Álvarez and colleagues investigated whether mitochondrial DNA (mtDNA) variations, or polymorphisms, influence liver fibrosis progression in HIV/HCV coinfected patients.

The researchers examined associations between European haplogroups and liver disease outcomes. Haplotypes are sets of DNA sequences at different chromosome locations that are associated with each other or are transmitted together. Haplogroups are sets of haplotypes that share a common ancestor. Haplogroup research often focuses on mtDNA, which is inherited solely from the mother.

The present cross-sectional study included 231 participants in Spain who underwent genotyping, or analysis of their genetic pattern. (This study looked at human genotypes, not viral genotypes, which are used to assess drug resistance or, in the case of HCV, likelihood of treatment response.)

A recent study of the European population found that the most common haplogroups were H (41%) and U (21%); the distribution of mtDNA haplogroups in the present analysis was generally similar to that seen in other studies of Europeans and HIV positive Caucasians, except for a lower frequency of haplogroups Uk and X among HIV/HCV coinfected patients compared with healthy controls, which the authors suggested could be due to chance.

Liver fibrosis was estimated based on the Metavir scale and fibrosis progression rate was calculated by dividing the fibrosis stage (F0 to F4) by the estimated duration of HCV infection.


The major haplogroup HV was significantly associated with reduced risk of disease progression:
Advanced liver fibrosis: odds ratios (OR) 0.35, or about one-third as likely;
Cirrhosis: OR 0.16, or 84% risk reduction;
High fibrosis progression rate: OR 0.43.
Within the major haplogroup HV, sub-haplogroup H was also significantly associated with less progression:
Advanced fibrosis: OR 0.40;
Cirrhosis: OR 0.14;
High fibrosis progression rate: OR 0.47, or about half the risk.
In contrast, however, the closely related major haplogroup U was significantly associated with increased risk of cirrhosis (OR 5.25, or more than 5 times higher).

"The mtDNA haplogroups HV and H were associated with slower fibrosis progression, and the haplogroup U was associated with faster fibrosis progression in HIV/HCV coinfected patients," the study authors concluded. "These data suggest that mtDNA haplogroup may play a significant role in liver fibrogenesis during HCV infection."

The researchers suggested that differences in cellular energy production and metabolism between the haplogroups -- such as variations in production of ATP and reactive oxygen species -- might help explain the association with fibrosis, but the link is not straightforward.

Investigator affiliations: Laboratory of Molecular Epidemiology of Infectious Diseases and Laboratory of Mitochondrial Diseases, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid. Spain; Infectious Diseases-HIV Unit, Internal Medicine Department, and Pathology Department, Hospital General Universitario "Gregorio Marañón," Madrid, Spain.


M García-Álvarez, M Guzmán-Fulgencio, J Berenguer, et al. European mitochondrial DNA haplogroups and liver fibrosis in human immunodeficiency virus and hepatitis C virus coinfected patients. AIDS (abstract). June 13, 2011 (Epub ahead of print).




















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