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.
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
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.
major haplogroup HV was significantly associated with reduced
risk of disease progression:
liver fibrosis: odds ratios (OR) 0.35, or about one-third
OR 0.16, or 84% risk reduction;
fibrosis progression rate: OR 0.43.
the major haplogroup HV, sub-haplogroup H was also significantly
associated with less progression:
fibrosis: OR 0.40;
fibrosis progression rate: OR 0.47, or about half
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).
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,
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).