E D I T O R I A L C O M M E N TA R Y HIV/AIDS
Liver Fibrosis and Antiretroviral Therapy
Department of Infectious Diseases, Pitie-Salpetriere Hospital, Paris, France
(See the article by Verma et al. on pages 46–54)
It is estimated that 30% of HIV-infected a lack of linear progression of ﬁbrosis and rhosis development, compared with the
patients are coinfected with hepatitis C vi- uncertainty regarding the date that HCV HCV-monoinfected population. Verma et
rus (HCV). Since the introduction of infection was acquired . In addition, al.  explained the absence of a similar
combined HAART regimens, liver disease because antiretroviral drugs are prescribed beneﬁt among patients in group 4 because
has emerged as an important cause of in combinations, it is difﬁcult to deter- of the delay between the diagnosis of HIV
death among people living with HIV in- mine which drug is responsible for hepatic infection and the initiation of combined
fection, especially among HIV-HCV– harm . The few available studies have HAART. In this study, use of nevirapine
coinfected patients . Complications of provided conﬂicting results [5–9]. was not associated with life-threatening or
HCV-related liver disease are the leading In this issue of the journal, Verma et al. long-term adverse consequences. The au-
cause of hospitalization and death among  have addressed the impact of type and thors concluded that it is not just the pres-
people living with HIV infection . In- duration of antiretroviral therapy on liver ence or duration of HAART, but also the
deed, as was previously reported in Clin- ﬁbrosis in HIV-HCV–coinfected patients. short delay between diagnosis of HIV
ical Infectious Diseases, the progression of HIV-HCV–coinfected patients were ret- infection and the initiation of HAART
liver ﬁbrosis is accelerated in HIV-HCV– rospectively recruited by reviewing charts that positively inﬂuences liver ﬁbrosis in
coinfected patients, compared with HCV- for the period 1994–2004. To be eligible, HIV-HCV–coinfected patients. This ob-
monoinfected patients . Therefore, patients had to have a positive HCV PCR servation would provide support for early
management of chronic HCV infection is result, to have undergone a liver biopsy, initiation of HAART in HIV-infected pa-
a major public health issue in the HIV- and to have complete clinical data avail- tients who are coinfected with HCV.
infected population. able. Fibrosis was evaluated with the Ishak However, one must not forget that HIV
modiﬁed histological activity index, a val- cannot be eradicated with current available
The impact of antiretroviral dugs on the
idated score that dissociates necroinﬂam- antiretroviral drugs and that prolonged use
progression of HCV-related liver ﬁbrosis
matory score and ﬁbrosis stage. Patients of these drugs is associated with toxicity.
is far from clear, and studies aimed to as-
were classiﬁed according to type of anti- Although HAART-induced immune res-
sess this issue are difﬁcult to conduct. The
retroviral therapy, as follows: patients in toration may attenuate the increased risk
prospect of sequential liver biopsies is not
group 2 had received no treatment or only of cirrhosis associated with HIV-HCV coin-
easily accepted by patients, and the ﬁbrosis
nucleoside reverse-transcriptase inhibitors fection, it may also cause liver damage .
progression rate is often used to assess the
(NRTIs), those in group 3 had received a In addition, HIV-HCV–coinfected patients
speed of ﬁbrosis development, but this pa-
diagnosis after 1996 and thus received are more prone to develop hepatotoxicity
rameter is not always relevant, because of
combined HAART, and those in group 4 caused by HAART than are HIV-mono-
had initially received mono- or dual-drug infected subjects . Some drugs, such as
Received 14 October 2005; accepted 14 October 2005;
electronically published 2 December 2005.
therapy, which was then switched to com- stavudine  and nevirapine , have
Reprints or correspondence: Dr. Jade Ghosn, Dept. of bined HAART after 1996; group 1 in- been associated with a harmful impact on
Infectious Diseases, Pitie-Salpetriere Hospital, 47-83,
Boulevard de l’Hopital, 75013 Paris, France (jade.ghosn
cluded HCV-monoinfected patients. The the liver, which may subsequently enhance
@psl.ap-hop-paris.fr). main ﬁnding was that patients in group 3 the progression of liver ﬁbrosis. Data on
Clinical Infectious Diseases 2006; 42:271–2 had similar necroinﬂammatory scores, ﬁ- the effect of protease inhibitors are scant
2005 by the Infectious Diseases Society of America. All
brosis stages, rates of ﬁbrosis progression, and contradictory. Therefore, because the
1058-4838/2006/4202-0018$15.00 and prevalences of and mean times to cir- major goal for persons treating HIV-HCV–
Liver Fibrosis and Antiretroviral Therapy • 55
coinfected patients is to slow or interrupt ties) of HAART and ribavirin. Patients 7. Tural C, Fuster D, Tor J, et al. Time on an-
tiretroviral therapy is a protective factor for
liver ﬁbrosis, the best way to achieve this who are not willing to receive pegylated liver ﬁbrosis in HIV and hepatitis C virus
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8. Sterling RK, Wilson MS, Sanyal AJ, et al. Im-
published, large, randomized studies have pact of highly active antiretroviral therapy on
shown that this combination was potent, the spectrum of liver disease in HCV-HIV
yielding sustained virological response in Potential conﬂicts of interest. J.G.: no conﬂicts. coinfection. Clin Gastroenterol Hepatol 2004;
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HCV genotype 1 and genotype 2/3, re- Effect of antiretroviral drugs on liver ﬁbrosis
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56 • Ghosn