María Mancebo

Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C

OBJECTIVESnTo assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C.nnnMETHODSnEighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months.nnnRESULTSnSeventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner.nnnCONCLUSIONnThe incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID.

Risk of Liver Decompensation Among HIV/Hepatitis C Virus–Coinfected Individuals With Advanced Fibrosis: Implications for the Timing of Therapy

BACKGROUNDnMost human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-infected patients who are currently receiving boceprevir or telaprevir-based therapy against HCV show cirrhosis. However, the risk of liver decompensation (DC) among HIV/HCV-coinfected patients with stage 3 fibrosis in the short term could be high enough to not allow delays. We aimed at assessing the risk of DC among HIV/HCV-coinfected individuals with advanced fibrosis (F3-F4).nnnMETHODSnEight hundred ninety-two HIV/HCV-coinfected patients, naive or without sustained virologic response to HCV therapy, were included in this cohort. Fibrosis was staged by biopsy in 317 patients and by liver stiffness measurement (LSM) in 575 individuals. Precirrhosis was defined as an LSM of 9.5-14.6 kilopascals (kPa), and cirrhosis as an LSM of ≥14.6 kPa.nnnRESULTSnFor patients with biopsy, the probability of remaining free of DC for F3 vs F4 was 99% (95% confidence interval [CI], 95%-100%) vs 96% (95% CI, 91%-98%) at 1 year, and 98% (95% CI, 94%-100%) vs 87% (95% CI, 81%-92%) at 3 years. The only factor independently associated with DC was fibrosis stage (F4 vs F3, subhazard ratio [SHR], 2.1; 95% CI, 1.07-4.1; P = .032). For patients with LSM, the probability of remaining free of DC for precirrhosis vs cirrhosis was 99% (95% CI, 96%-100%) vs 93% (95% CI, 89%-96%) at 1 year, and 97% (95% CI, 94%-99%) vs 83% (95% CI, 77%-87%) at 3 years. Factors independently associated with DC were platelet count (<100 × 10(3) vs ≥100 × 10(3): SHR, 1.86; 95% CI, 1.01-3.42; P = .046) and LSM (cirrhosis vs precirrhosis: SHR, 5.67; 95% CI, 2.27-14.1; P < .0001).nnnCONCLUSIONSnAs in patients with cirrhosis, immediate therapy against HCV is warranted for patients with precirrhosis and HIV coinfection, as they are at risk of DC soon after the diagnosis of advanced fibrosis.

Reassessment of Genotype 1 Hepatitis C Virus Subtype Misclassification by LiPA 2.0: Implications for Direct-Acting Antiviral Treatment

ABSTRACT The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.

HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study

Objective: HIV/HCV-coinfected patients and hepatitis C virus (HCV) monoinfected subjects are thought to respond equally to direct-acting antiviral (DAA)-based therapy despite the lack of data derived from clinical trials. This study is aimed to evaluate the impact of HIV coinfection on the response to DAA-based treatment against HCV infection in the clinical practice. Patients and Methods: In a prospective multicohort study, patients who initiated DAA-based therapy at the Infectious Disease Units of 33 hospitals throughout Spain were included. The primary efficacy outcome variables were the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12). Results: A total of 908 individuals had reached the SVR12 evaluation time-point, 426 (46.9%) were HIV/HCV-coinfected, and 472 (52%) received interferon (IFN)-free therapy. In an intention-to-treat analysis, SVR12 rates in subjects with and without HIV-coinfection were 55.3% (94/170 patients) versus 67.3% (179/266 subjects; p = 0.012) for IFN-based treatment and 86.3% (221/256 subjects) versus 94.9% (205/216 patients, p = 0.002) for IFN-free regimens. Relapse after end-of-treatment response to IFN-free therapy was observed in 3/208 (1.4%) HCV-monoinfected subjects and 10/231 (4.4%) HIV/HCV-coinfected individuals (p = 0.075). In a multivariate analysis adjusted for age, sex, transmission route, body-mass index, HCV genotype, and cirrhosis, the absence of HIV-coinfection (adjusted odds ratio: 3.367; 95% confidence interval: 1.15-9.854; p = 0.027) was independently associated with SVR12 to IFN-free therapy. Conclusions: HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.

Low risk of liver decompensation among human immunodeficiency virus/hepatitis C virus–coinfected patients with mild fibrosis in the short term

Liver fibrosis is used to make decisions about the timing of therapy against hepatitis C virus (HCV) in routine clinical practice, which should be based on the short‐term likelihood of liver decompensations. Thus, we aimed at evaluating the risk of decompensations and death among human immunodeficiency virus (HIV)/HCV–coinfected individuals according to their baseline fibrosis classified by either liver biopsy or liver stiffness measurement (LSM). Patients coinfected with HIV/HCV, naive or without sustained virological response to HCV therapy, were included in this cohort. Fibrosis was classified by biopsy in 683 patients and by LSM in 1046 individuals. Reference categories were fibrosis stage 0 and LSM <6 kPa. For patients with biopsy, the adjusted subhazard ratio for decompensations and 95% confidence interval (95% CI) by fibrosis stage were as follows: stage 1, 2.3 (0.27‐20.3), Pu2009=u20090.443; stage 2, 2.8 (0.33‐24), Pu2009=u20090.345; stage 3, 4.91 (0.60‐41), Pu2009=u20090.137; stage 4, 9.89 (1.25‐79.5), Pu2009=u20090.030. For patients with LSM, the adjusted subhazard ratio and 95% CI by LSM category were as follows: 6‐9.4 kPa, 1.89 (0.18‐20.3), Pu2009=u20090.599; 9.5‐14.5 kPa, 6.59 (0.73‐59.2), Pu2009=u20090.092; ≥14.6 kPa, 59.5 (8.3‐427), Pu2009<u20090.0001. Regarding the risk of death, the adjusted hazard ratio and 95% CI for death by fibrosis stage were as follows: stage 1, 1.3 (0.4‐4.11), Pu2009=u20090.677; stage 2, 2.68 (0.86‐8.36), Pu2009=u20090.090; stage 3, 2.58 (0.82‐8.15), Pu2009=u20090.106; stage 4, 4.35 (1.43‐13.3), Pu2009=u20090.010. For patients with LSM, the adjusted hazard ratio and 95% CI for death by LSM were as follows: 6‐9.4 kPa, 1.7 (0.63‐4.79), Pu2009=u20090.288; 9.5‐14.5 kPa, 3.38 (1.2‐9.5), Pu2009=u20090.021; ≥14.6 kPa, 12.7 (4.9‐33.6), Pu2009<u20090.0001. Conclusion: Patients coinfected with HIV/HCV without advanced fibrosis are at very low risk of decompensations in the short term; deferral of HCV therapy for a few years and monitoring fibrosis progression is a safe option until cheaper, more effective, and more convenient HCV treatment becomes widely available. (Hepatology 2015;61:1503–1511)

The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients.

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12–3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23–6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01–11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.

Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus–Infected Patients With Nonalcoholic Fatty Liver Disease

BackgroundnAntiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues.nnnMethodsnHIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP.nnnResultsnOverall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029).nnnConclusionsnAfter 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL.nnnClinical Trials RegistrationnNCT01900015.

Bacterial translocation and clinical progression of HCV-related cirrhosis in HIV-infected patients

The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV‐coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV‐coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well‐conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver‐related death (LRD) and death of any cause. After a median (Q1‐Q3) follow‐up of 51 (27‐72) months, 67 patients (24%; 95% CI: 19‐29) developed their first LD or died during follow‐up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83‐196, 197‐355, >355 [copies/μL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1‐0.6, 0.6‐1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV‐coinfected patients with compensated cirrhosis.

Changes in the response to treatment against chronic hepatitis C between 1999 and 2015: data from a prospective cohort.

Background The drug options and strategies for treatment against hepatitis C virus (HCV) infection have changed considerably in the last few years. The aim of this study was to compare the changes in the proportion of nonresponders and patients who achieved a sustained virologic response (SVR) from 1999 to 2015 in one single cohort. Patients and methods A total of 522 patients treated against chronic hepatitis C were included prospectively. The time periods were 1999–2002 [interferon (IFN)/ribavirin (RBV)], 2002–2009 (pegylated-IFN/RBV), 2010–2011 (use of IL28B genotype), 2012–2014 (pegylated-IFN/RBV/direct-acting antivirals) and 2015 (IFN-free direct-acting antiviral-based therapy). Results The numbers of nonresponders in the study periods in chronological order were as follows: 14 (40%), 76 (21.3%), 7 (8%), 10 (13%), and 0; P=1.1×10–7 and r2=0.837. The corresponding numbers of patients who achieved SVR were 9 (25.7%), 14 (40.9%), 44 (50.6%), 51 (66.2%), and 64 (90.1%), P=3.3×10–15 and r2=0.997. Characteristics that may impair SVR, such as advanced fibrosis, genotype 1 infection, HIV coinfection, or treatment experience, did not decrease in the last time periods. Conclusion The proportion of nonresponders was significantly reduced using the IL28B genotype as a predictive tool and direct-acting antivirals further improved treatment outcome. Concomitantly, the rates of SVR showed a linear increase.

Paritaprevir/ritonavir/ombitasvir plus dasabuvir in HIV/HCV-coinfected patients with genotype 1 in real-life practice

Background Data on the efficacy, safety, and concomitant use with other drugs of the combination ritonavir-boosted paritaprevir/ombitasvir plus dasabuvir (PrOD) in HIV/HCV-coinfected patients in real life are limited. The objectives of this study were to analyze these topics in HIV/HCV-coinfected subjects bearing HCV genotype 1 (GT1). Methods One hundred and eighty-two HIV/HCV-coinfected patients with GT1 (87 1a, 71 1b, 23 other) treated with PrOD, plus ribavirin (RBV) in 119 cases, in routine clinical practice were analyzed. The main variable of efficacy was sustained virological response (SVR) 12 weeks after completing therapy in an intention-to-treat (ITT) analysis and that of safety treatment discontinuation because of adverse effects. Factors associated with SVR were analyzed with a modified ITT (mITT) strategy. Results One hundred and seventy-two (94%) patients attained SVR, 3 (2%) experienced a relapse and two (1%) discontinued therapy due to adverse events. The rates of SVR in subjects with GT 1a and 1b by mITT were, respectively, 97% and 98%. Sixty-five (98%) out of 66 patients with cirrhosis and 107 (98%) out of 110 (p = 1) non-cirrhotics achieved SVR. Fifty-five (95%) patients on concomitant darunavir therapy developed SVR vs. 117 (99%) (p = 0.105) of those without DRV. RBV dose was reduced in 13 (11%) patients and permanently discontinued in 2 (2%), with no impact on SVR. Conclusions PrOD is highly effective and well tolerated in HIV/HCV-coinfected patients with GT1 in routine clinical practice. RBV is often required. However, RBV dose reduction or discontinuation is uncommonly needed and do not impair the SVR rate.