ObjectiveNoninvasive tests that can be used in place of liver biopsy to diagnose fibrosis have major limitations. They either leave a significant proportion of patients without a definitive diagnosis or produce inaccurate results. Moreover, the performance of these tests is lower in HIV/hepatitis C virus (HCV) coinfection. Against this background, we examined the utility of serum matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1 (TIMP-1) measurements in combination with routine clinical data to predict fibrosis in HIV/HCV-coinfected patients. MethodsPatients with a liver biopsy who had not received anti-HCV therapy were included in the study. A model including variables independently associated with fibrosis was constructed. Diagnostic accuracy was determined by measuring the area under the receiver operating characteristic curve (AUROC). Positive (PPV) and negative (NPV) predictive values were calculated. ResultsNinety patients were included in the study. Aspartate aminotransferase (AST), platelet count and MMP-2 were predictors of significant fibrosis (F ! 2) and cirrhosis (F4). A score constructed using these variables yielded an AUROC of 0.76 for F ! 2 and 0.88 for F4. Score cut-offs detected (value ! 3.5) and excluded (value 1.5) F ! 2 with a PPV of 87% and an NPV of 88%. Thirty-one patients (34%) were correctly diagnosed using these cut-offs, with four (13%) incorrect classifications. Cirrhosis was excluded with a certainty of 98% and diagnosed with a probability of 83%. Two (17%) of 12 patients were misclassified as having cirrhosis. The AST to platelet count index and MMP-2 levels were sequentially applied to detect F ! 2. Forty-one patients (46%) were identified with this approach, with six (15%) misclassifications. ConclusionMMP-2 levels can be used in combination with AST and platelet count to aid the diagnosis of liver fibrosis in HIV/HCV-coinfected patients.Keywords: aspartate aminotransferase to platelet count index, hepatitis C virus, liver fibrosis, matrix metalloproteinase 2, noninvasive diagnosis of fibrosis IntroductionThe extent of liver fibrosis has prognostic and management implications in chronic hepatitis C. The diagnosis of fibrosis has traditionally relied on liver biopsy. However, this procedure is invasive, limited because of variability issues [1,2] and difficult to apply sequentially. Because of these issues, noninvasive tests that can be used in place of liver biopsy are needed. Among such tests, those employing simple blood indexes, based on routinely available data, and transient elastometry (TE) have been validated in patients with chronic hepatitis C virus (HCV) and HIV coinfection [3][4][5][6].Simple indexes are easy to implement and cost-effective. However, the diagnostic yield of these indexes is lower in HIV/HCV-coinfected patients [3,4]. In particular, the DOI: 10.1111/j.1468-1293.2010.00836.x HIV Medicine (2011 r 2010 British HIV Association 14 diagnosis of cirrhosis cannot be established confidently [3]. TE seems a promising technique for ...
A considerable number of patients undergoing methadone maintenance treatment (MMT) are not considered for treatment against hepatitis C virus (HCV) infection due to a possible lower adherence and efficacy in this population. We aimed to compare the response rates to HCV treatment in patients with or without MMT. HCV-infected patients who initiated pegylated interferon plus ribavirin were included in this prospective cohort study. The relation between sustained virologic response (SVR) and MMT was analyzed. A total of 214 patients were included in the study [81 (37.9%) with and 133 (62.1%) without MMT]. No differences in HCV and interleukin 28B (rs12979860) genotype distribution were observed between the two groups. Of these patients, 103 (48.1%) achieved SVR. Among the patients who received MMT, 39 (48.1%) reached SVR compared to 64 (48.1%) subjects without MMT (p = 0.99). The frequency of voluntary drop-out and treatment discontinuations due to adverse events was comparable between the patients with and without MMT [10 (12.3%) versus 14 (10.5%), p = 0.68, and 4 (4.9%) versus 9 (6.8%), p = 0.59, respectively]. The efficacy of HCV therapy in MMT patients is similar to that found in subjects not taking methadone. MMT patients should be equally considered for treatment with pegylated interferon plus ribavirin in HCV-infected patients.
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