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Liver Fibrosis and Antiretroviral Therapy

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					                                                                            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
Jade Ghosn
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 [4]. In addition,        al. [10] 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 [4]. The few available studies have        HAART. In this study, use of nevirapine
coinfected patients [1]. 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                      [10] have addressed the impact of type and      thors concluded that it is not just the pres-
people living with HIV infection [2]. 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 [3]. 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 [11].
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 [12]. 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 [13] and nevirapine [9], 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
rights reserved.
                                                              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
goal is to treat HCV infection with pegy-      IFN and ribavirin or who have contrain-                    (HCV) co-infected patients. J Viral Hepat
lated IFN and ribavirin. Indeed, recently      dications may benefit from early HAART.                     2003; 10:118–25.
                                                                                                       8. Sterling RK, Wilson MS, Sanyal AJ, et al. Im-
published, large, randomized studies have                                                                 pact of highly active antiretroviral therapy on
                                               Acknowledgments
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;
                                                                                                          2:432–9.
29% and 62% of patients coinfected with                                                                9. Macias J, Castellano V, Merchante N, et al.
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