Comparison of the prognostic value of liver biopsy and FIB-4 index in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. METHODS: We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis. RESULTS: The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4. CONCLUSIONS: FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.

Clinical effects of viral relapse after interferon plus ribavirin in patients co-infected with human immunodeficiency virus and hepatitis C virus.

BACKGROUND & AIMS: Sustained viral response (SVR) after therapy with interferon-ribavirin (IF-RB) reduces liver-related (LR) complications and mortality in HIV/HCV-co-infected patients. Here, we assess the impact of end-of-treatment response with subsequent relapse (REL) on LR events (LR death, liver decompensation, hepatocellular carcinoma, or liver transplantation), and liver stiffness (LS) by transient elastography. METHODS: We analyzed the GESIDA 3603 Cohort (HIV/HCV-co-infected patients treated with IF-RB in 19 centers in Spain). Response to IF-RB was categorized as SVR, REL, and no response (NR). The study started when IF-RB was stopped and ended at death or the last follow-up visit. Multivariate regression analyses were adjusted for age, sex, HIV category of transmission, CDC clinical category, nadir CD4+ cell count, HCV genotype, HCV-RNA viral load, and liver fibrosis. RESULTS: Of 1599 patients included, response was categorized as NR in 765, REL in 250 and SVR in 584. Median follow-up was more than 4 years in each group. Taking the group of patients with NR as reference, we found that the adjusted hazard ratios (95% confidence interval) of liver-related events (liver-related death, liver decompensation, hepatocellular carcinoma, liver transplantation) for patients with REL and for patients with SVR were 0.17 (0.05; 0.50) and 0.03 (0; 0.20), respectively. We also found that SVR was followed by less liver stiffness than both REL and NR. However, REL was associated with less liver stiffness than NR. CONCLUSIONS: Best outcomes were achieved with an SVR. However, REL was associated with less LR mortality, decompensation, and liver stiffness than NR.

Effect of accompanying antiretroviral drugs on virological response to pegylated interferon and ribavirin in patients co-infected with HIV and hepatitis C virus.

OBJECTIVES: The effects of antiretroviral drugs on the response to pegylated interferon plus ribavirin remain uncertain. We evaluated whether antiretroviral drugs affected the response to pegylated interferon plus ribavirin in patients co-infected with HIV and hepatitis C virus (HCV). METHODS: We conducted a retrospective analysis of two cohorts of HIV/HCV-co-infected patients treated with pegylated interferon plus ribavirin between 2001 and 2007 in Spain. The outcome measure was sustained virological response (SVR). Logistic regression models were used to test possible associations between non-response and pre-treatment characteristics, including accompanying antiretroviral drugs. RESULTS: The study sample comprised 1701 patients: 63% were infected with HCV genotype (G) 1 or 4 and 88% were taking highly active antiretroviral therapy (HAART). Factors independently associated with increased odds of SVR were G2 or 3, HVC RNA <500,000 IU/mL and CDC clinical category A or B. When we adjusted for these prognostic factors and dose of ribavirin/kg, the adjusted odds ratio (AOR) of SVR for patients without HAART was 1.31 [95% confidence interval (CI) 0.91-1.88; P = 0.144]. Taking the backbone of tenofovir and lamivudine/emtricitabine as a reference, we found that, with the exception of regimens including zidovudine, the effect of other nucleoside reverse transcriptase inhibitor backbones had little effect on SVR. The AOR of SVR for zidovudine and lamivudine was 0.65 (95% CI 0.46-0.93, P = 0.017). We carried out several sensitivity analyses, the results of which were consistent with the findings of the primary analysis. CONCLUSIONS: Our results suggest that, with the exception of regimens including zidovudine, accompanying antiretroviral drugs have little effect on the virological response to pegylated interferon plus ribavirin in HIV/HCV-co-infected patients.

Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus.

UNLABELLED: Human immunodeficiency virus (HIV) infection modifies the natural history of chronic hepatitis C, thus promoting more rapid progression to cirrhosis and end-stage liver disease. The objective of our study was to determine whether hepatitis C virus (HCV) clearance is associated with improved clinical outcomes in patients positive for HIV and HCV. It was an ambispective cohort study carried out in 11 HIV units in Spain and involved 711 consecutive patients positive for HIV/HCV who started interferon plus ribavirin therapy between 2000 and 2005. We measured sustained virologic response (SVR), i.e., undetectable HCV RNA at 24 weeks after the end of treatment, and clinical outcomes, defined as death (liver-related or non-liver-related), liver decompensation, hepatocellular carcinoma, and liver transplantation. Of 711 patients who were positive for HIV/HCV, 31% had SVR. During a mean follow-up of 20.8 months (interquartile range: 12.2-38.7), the incidence rates per 100 person-years of overall mortality, liver-related mortality, and liver decompensation were 0.46, 0.23, and 0.23 among patients with SVR and 3.12, 1.65, and 4.33 among those without SVR (P = 0.003, 0.028, and <0.001 by the log-rank test), respectively. Cox regression analysis adjusted for fibrosis, HCV genotype, HCV RNA viral load, Centers for Disease Control and Prevention clinical category, and nadir CD4+ cell count showed that the adjusted hazard ratio of liver-related events was 8.92 (95% confidence interval, 1.20; 66.11, P = 0.032) for nonresponders in comparison with responders and 4.96 (95% confidence interval, 2.27; 10.85, P < 0.001) for patients with fibrosis grade of F3-F4 versus those with F0-F2.Because this was not a prospective study, selection and survival biases may influence estimates of effect. CONCLUSION: Our results suggest that the achievement of an SVR after interferon-ribavirin therapy in patients coinfected with HIV/HCV reduces liver-related complications and mortality.

Anticuerpos frente al citoplasma de los neutrófilos: más allá de las vasculitis / Anti-neutrophil cytoplasmic antibodies: beyond vasculitis

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