Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults.
ABSTRACT To define the incidence of fibrosis progression among hepatitis C virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters the risk of progression, and to determine the utility of liver biopsy to predict future disease.
This prospective cohort evaluated 184 HIV/HCV-co-infected individuals who had at least two liver biopsies (median interval 2.9 years).
Biopsies were scored according to the Ishak modified histological activity index scoring system by a single pathologist blind to biopsy sequence. Significant fibrosis progression was defined as an increase of at least two Ishak fibrosis units between the first and second liver biopsy. Logistic regression analysis was used to assess determinants of fibrosis progression.
A total of 174 non-cirrhotic patients were eligible; the majority were African-American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis was identified in 136 patients (77%). Significant fibrosis progression occurred in 41 patients (24%). Measures of HIV disease and its treatment before and after initial biopsy were not significantly different in progressors and non-progressors. Fibrosis progression was not associated with HCV treatment, which was received by 37 patients (21%) but only three sustained HCV-RNA suppression. In adjusted analysis, only an elevated serum aspartate aminotransferase level between biopsies was associated with progression (odd ratio 3.4, 95% confidence interval 1.4-7.9).
Over a 3-year interval, significant fibrosis progression can occur in co-infected individuals even if minimal disease was detected on initial biopsy. In this context, factors other than treatment for HIV or HCV modify the risk of fibrosis progression.
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ABSTRACT: Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy. To evaluate the risk factors of liver fibrosis progression (LFP) and to investigate the role of antiretroviral therapy (ARV) in HIV/HCV patients who underwent paired liver biopsy. We retrospectively studied 58 patients followed at two Infectious Diseases Departments in Northern Italy during the period 1988-2005. All specimens were double-blinded and centrally examined by two pathologists. LFP was defined when an increase of at least one stage occurred in the second biopsy, according to the Ishak-Knodell classification. In a univariate analysis, serum levels of alanine aminotransferase (ALT) > 150 IU/L at the first biopsy (P = 0.02), and a > 20% decrease in CD4+ cell count between the two biopsies (P = 0.007), were significantly associated with LFP. In multivariate analysis, a > 20% decrease in CD4+ cell count remained independently associated to LFP (Odds Ratio, 3.99; 95% confidence interval, 1.25-12.76; P < 0.02). Analysis of life survival curves confirmed the correlation between CD4+ cell count and LFP. Our findings highlight that in HIV/HCV coinfected patients, an effective antiretroviral therapy that assures a good immune-virological profile contributes to reducing the risk of LFP.Hepatitis Monthly 07/2011; 11(7):525-31. · 2.19 Impact Factor
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ABSTRACT: Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum) block hepatitis C virus (HCV) infection and inhibit T cell proliferation in vitro. An intravenous formulation of silibinin (SIL), a major component of silymarin, displays anti-HCV effects in humans and also inhibits T-cell proliferation in vitro. We show that SIL inhibited replication of HIV-1 in TZM-bl cells, PBMCs, and CEM cells in vitro. SIL suppression of HIV-1 coincided with dose-dependent reductions in actively proliferating CD19+, CD4+, and CD8+ cells, resulting in fewer CD4+ T cells expressing the HIV-1 co-receptors CXCR4 and CCR5. SIL inhibition of T-cell growth was not due to cytotoxicity measured by cell cycle arrest, apoptosis, or necrosis. SIL also blocked induction of the activation markers CD38, HLA-DR, Ki67, and CCR5 on CD4+ T cells. The data suggest that SIL attenuated cellular functions involved in T-cell activation, proliferation, and HIV-1 infection. Silymarin-derived compounds provide cytoprotection by suppressing virus infection, immune activation, and inflammation, and as such may be relevant for both HIV mono-infected and HIV/HCV co-infected subjects.PLoS ONE 01/2012; 7(7):e41832. · 4.09 Impact Factor
Article: Histologic outcomes in hepatitis C-infected patients with varying degrees of virologic response to interferon-based treatments.[show abstract] [hide abstract]
ABSTRACT: Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR.Hepatology 10/2010; 52(4):1193-200. · 11.66 Impact Factor