Influence of interferon-based therapy on liver fibrosis progression in HIV/HCV coinfected patients: A retrospective repeated liver biopsy analysis
ABSTRACT Hepatitis C virus (HCV) coinfection is one of the leading causes of mortality in human immunodeficiency virus-infected patients. The current standard of care leads to cure only in a part of these patients. The course of the disease is determined by the rapidity of liver fibrosis progression (LFP). The influence of interferon on LFP in coinfected patients has yet not been evaluated by comparative liver biopsies.
We extracted data of patients who had serial liver biopsies from a hospital database. Histopathological findings were compared to factors possibly linked to fibrosis progression. Furthermore, we studied the impact of response to interferon treatment on fibrosis progression.
Hundred and twenty-six patients were included, 68 had received anti-HCV treatment, and 58 had not. The median time between the first and the last biopsy was 4 years. Worsened fibrosis was observed in 35 of 58 (60%) untreated patients, and 22 of 50 (44%) patients in the nonresponder/relapser group, and in 5 out of 18 (28%) in the SVR group. Liver fibrosis evolution was significantly better in patients achieving a SVR than in untreated and NR/R patients (p<0.02, odds-ratio [95% CI] for improvement vs. stability vs. worsening=3.16 [1.24-8.07]). This result persisted after adjustment for known predictors of liver fibrosis progression, HBsAg, CD4, and alcohol consumption: adjusted odds ratio=2.89 [1.09-7.68], p=0.03.
HCV treatment can stop fibrosis progression and induce its regression. Nonresponders to treatment may even have a fast fibrosis progression. It remains to be clarified if the same factors that induce nonresponse to treatment may also induce faster fibrosis progression.
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ABSTRACT: INTRODUCTION: Since the advent of combined antiretroviral therapy (cART), liver-related mortality has become the leading cause of non-AIDS-related deaths in human immunodeficiency virus (HIV) infected patients in Western countries. OBJECTIVE: To investigate the incidence, mortality and risk factors of end-stage liver disease (ESLD) in HIV and hepatitis C virus (HCV) coinfected former plasma donors (FPDs) and blood recipients (BRs). METHOD: A retrospective study was conducted. RESULTS: Of 321 HIV-HCV coinfected patients, 42 (13.1%) developed ESLD and 40 (12.5%) died. Factors that were independently associated with ESLD included older age at baseline (Odds ratios [OR]: 2.444, P=0.035), alanine aminotransferase (ALT) greater or equal to 2 (the upper limit of normal [ULN]) at the end of follow-up (OR: 16.460, P=0.000), hepatitis B virus (HBV) (OR: 2.525, P=0.043), CDC stage C (OR: 5.806, P=0.001), duration of cART greater than 5 years (OR: 3.256, P=0.010), and CD4 count greater or equal to 200 cells/mm(3) at the end of follow-up (OR: 0.383, P=0.016). The probability of developing ESLD in HIV-HCV coinfected BRs was significantly higher than in FPDs (P=0.008). Mortality was also significantly higher in HIV-HCV coinfected patients with ESLD than in those without ESLD (P=0.000). CONCLUSION: In the cART era, ESLD was common among HIV-HCV coinfected Han Chinese patients and was responsible for reducing patient survival time.Gastroentérologie Clinique et Biologique 04/2012; 36(6). DOI:10.1016/j.clinre.2012.02.007 · 1.64 Impact Factor
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ABSTRACT: With the licensing of the first hepatitis C (HCV) protease inhibitors (PI), telaprevir (TVR) and boceprevir (BOC), cure rates for chronic HCV infection will substantially improve. Human immunodeficiency virus- chronic hepatitis C (HIV-HCV) co-infected patients are in urgent need for these new drugs, because they are facing both severe liver disease and lower response rates than HCV monoinfected patients. The currently available efficacy data are however, limited to two phase II trials. Fortunately, TVR and BOC appear to be able to improve cure rates in co-infected patients. A major challenge for clinicians will be the management of drug-drug interactions of antiretroviral drugs and new PI. As HCV PI are also metabolized by the cytochrome P450 3A4 system interactions are probable as well with non-nucleoside reverse transcriptase inhibitors as with HIV PI. To our knowledge, TVR can only be safely used with one protease inhibitor, boosted atazanavir, and also with efavirenz (EFV), although this combination requires TVR dose adjustments. Boceprevir should not be combined with HIV PI and should not be combined with EFV. The approval of TVR and BOC will create new chances of cure also for HIV-HCV co-infected patients. However, the decision who to treat or not has to be taken carefully on the basis of fibrosis stage and previous treatment outcomes. In addition, HIV therapy needs to be optimized according to the available drug-drug interaction data.Liver international: official journal of the International Association for the Study of the Liver 04/2012; 32(8):1194-9. DOI:10.1111/j.1478-3231.2012.02796.x · 4.85 Impact Factor
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ABSTRACT: Abstract To evaluate the course of liver fibrosis, 328 HIV-hepatitis C virus (HCV)-coinfected patients (210 HCV treated and 118 HCV untreated) were followed-up for 38-42 months. Liver fibrosis was assessed by biopsy or elastometry at baseline and by elastometry afterward, in addition to other noninvasive indexes. A combined liver stiffness stage (LSS) was established and evaluated over time. Eighty patients had sustained virological response (SVR) and 130 had treatment failure (TF) after a standard course of peginterferon-ribavirin therapy. LSS decreased significantly in all fibrosis indexes during HCV therapy in treated patients, but the improvement persisted only in those with SVR. At the end of study, median elastometry values suffered variations of -29%, -5.0%, and +15.4% in SVR, TF, and untreated patients, respectively. Likewise, LSS worsened in 2.5%, 33.1%, and 39% of these groups, respectively: [OR (95% CI) 19.3 (4.4-119), p<0.001] for TF vs. SVR; [24.9 (5.6-154), p<0.001] for no therapy vs. SVR; and [1.29 (0.74-2.3), p=0.40] for no therapy vs. TF. LSS improved in 53.8%, 19.2%, and 5.9% of these groups, respectively: [4.88 (2.51-9.53), p<0.001] for SVR vs. TF; 18.4 (7.17-49.4), p<0.001 for SVR vs. no therapy; and 3.78 (1.47-10.1), p=0.003 for TF vs. no therapy. Independent predictive factors of LSS improvement or worsening were as follows: alcohol abuse [OR (95% CI) 0.48 (0.20-0.99), p=0.047] and [2.45 (1.19-5.03), p=0.016], respectively; SVR [27.7 (6.41-168), p<0.001] and [0.15 (0.07-0.31), p<0.001], respectively; and lower baseline CD4 counts [1.92 (1.08-3.45), p=0.026] and [0.31 (0.15-0.63), p=0.001], respectively. SVR was usually associated with regression of noninvasive liver fibrosis markers, whereas TF and HCV-untreated patients experienced poorer outcomes.AIDS research and human retroviruses 06/2012; 29(2). DOI:10.1089/AID.2012.0108 · 2.33 Impact Factor