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.
References
HCV genotype 1 and genotype 2/3, re- Effect of antiretroviral drugs on liver ﬁbrosis
spectively [14]. Nonetheless, few HIV- 1. Rosenthal E, Poiree M, Pradier C, et al. Mor- in HIV-infected patients with chronic hepatitis
tality due to hepatitis C-related liver disease C: harmful impact of nevirapine. AIDS
HCV–coinfected patients are treated, es- in HIV-infected patients in France (Mortavic 2004; 18:767–74.
pecially because of the overlapping and 2001 study). AIDS 2003; 17:1803–9. 10. Verma S, Wang C-H, Govindarajan S, Kanel
additive toxicities of HAART and anti- 2. Bica I, McGovern B, Dhar R, et al. Increasing G, Squires K, Bonacini M. Do type and du-
mortality due to end-stage liver disease in pa- ration of antiretroviral therapy attenuate liver
HCV drugs. tients with human immunodeﬁciency virus ﬁbrosis in HIV–hepatitis C virus–coinfected
Current guidelines for the treatment of infection. Clin Infect Dis 2001; 32:492–7. patients? Clin Infect Dis 2006; 42:46–54 (in
people living with HIV infection recom- 3. Martinez-Sierra C, Arizcorreta A, Diaz F, et al. this issue).
Progression of chronic hepatitis C to liver ﬁ- 11. Sulkowski MS, Thomas DL, Chaisson RE,
mend that HAART not be initiated until brosis and cirrhosis in patients coinfected with Moore RD. Hepatotoxicity associated with an-
the CD4 cell count is !350 cells/mm3. hepatitis C virus and human immunodeﬁ- tiretroviral therapy in adults infected with hu-
HIV-HCV–coinfected patients with a CD4 ciency virus. Clin Infect Dis 2003; 36:491–8. man immunodeﬁciency virus and the role of
4. Pineda JA, Macias J. Progression of liver ﬁ- hepatitis C or B virus infection. JAMA 2000;
cell count of 1350 cells/mm3 should ﬁrst brosis in patients coinfected with hepatitis C 283:74–80.
be assigned to receive anti-HCV treat- virus and human immunodeﬁciency virus un- 12. Bonacini M. Liver injury during highly active
ment, because tolerance of this treatment dergoing antiretroviral therapy. J Antimicrob antiretroviral therapy: the effect of hepatitis C
Chemother 2005; 55:417–9. coinfection. Clin Infect Dis 2004; 38(Suppl 2):
would be optimal in the absence of 5. Vento S, Garofano T, Renzini C, Casali F, Fer- S104–8.
HAART. For HIV-HCV–coinfected pa- raro T, Concia E. Enhancement of hepatitis C 13. Sulkowski MS, Mehta SH, Torbenson M, et
tients who require HAART, the availability virus replication and liver damage in HIV- al. Hepatic steatosis and antiretroviral drug use
coinfected patients on antiretroviral combi- among adults coinfected with HIV and hep-
of new ﬁxed NRTI combinations, such as nation therapy. AIDS 1998; 12:116–7. atitis C virus. AIDS 2005; 19:585–92.
abacavir and lamivudine or tenofovir and 6. Benhamou Y, Di Martino V, Bochet M, et al. 14. Torriani FJ, Rodriguez-Torres M, Rockstroh
emtricitabine, may prove to be helpful for Factors affecting liver ﬁbrosis in human im- JK, et al. Peginterferon alfa-2a plus ribavirin
munodeﬁciency virus-and hepatitis C virus- for chronic hepatitis C virus infection in HIV-
reducing the additive toxicities (especially coinfected patients: impact of protease inhib- infected patients. N Engl J Med 2004; 351:
mitochondrial and hematological toxici- itor therapy. Hepatology 2001; 34:283–7. 438–50.

56 • Ghosn