Burden of significant liver damage in people living with HIV after microelimination of the hepatitis C virus.

BACKGROUND: Once HIV/HCV-coinfection microelimination has been virtually achieved in some countries, there is no information about the burden of liver disease among people living with HIV (PLWH). The aim of this study was to define the current prevalence and causes of significant liver damage (SLD) in PLWH. METHODS: Cross-sectional study including 619 PLWH. SLD was defined as liver stiffness (LS) ≥ 7.2 kPa measured by transient elastography. Nonviral liver damage (NVLD) was considered if there was no evidence injury due to chronic hepatitis C virus (HCV) infection, active hepatitis B (HBV) or E virus infections. RESULTS: One hundred and twelve of 619 (18.2%) PLWH showed SLD, including 34/112 (5.5%) with LS ≥14 kPa. 72/112 (64.3%) had cured HCV infection, 4/112 (3.6%) active HBV infection, and 2/112 HBV/prior HCV coinfection. Thus, 40 (35.7%) showed NVLD. Metabolic associated steatohepatitis (MASH) was present in 29/40 (72.5%) of patients with NVLD, alcoholic liver damage in 2/40 (2.5%) and mixed steatohepatitis in 5/40 (12.5%). CONCLUSIONS: After HIV/HCV microelimination the burden of liver damage is high among PLWH. Persistent injury after HCV is a very frequent cause of SLD. However, NVLD, mainly due to MASH, is also a common condition in this population.

Liver stiffness change with HCV cure in HIV-infected patients on non-nucleoside analogues.

BACKGROUND: Liver stiffness (LS) at sustained viral response (SVR) is strongly associated with a lower incidence of subsequent hepatic events. HIV NNRTIs may have a beneficial impact on fibrogenesis. OBJECTIVES: Our aim was to analyse the influence of NNRTI-based therapy on the change in LS from starting direct-acting antiviral (DAA) therapy to achieving SVR in HIV/HCV-coinfected patients. METHODS: Three hundred and thirteen HIV/HCV-coinfected patients who fulfilled the following criteria were included: (i) had achieved SVR with an IFN-free, DAA-including regimen; (ii) LS ≥9.5 kPa before therapy; (iii) LS measurement available at SVR; (iv) seronegative for HBsAg; and (v) ART containing 2 NRTIs plus either 1 NNRTI or 1 integrase inhibitor (INI) or 1-2 NRTIs plus 1 PI. LS changes were assessed. RESULTS: Seventy-four patients received NNRTI-based combinations [53 (71.6%) rilpivirine and 16 (21.6%) efavirenz] and 239 patients received other regimens. At baseline, the median (IQR) LS was 16.7 kPa (11.8-25.6) in the NNRTI group and 17.3 kPa (11.9-27.4) in the non-NNRTI group (P = 0.278). The median (IQR) percentage of LS decrease from baseline to SVR was 35.2% (18.2%-52.3%) for NNRTI-based therapy and 29.5% (10%-45.9%) for PI- or INI-based therapy (P = 0.018). In multivariate analysis, adjusted for sex, age, HCV genotype, NRTI backbone and propensity score for HIV therapy, NNRTI-based regimen use was associated with a higher LS decrease [ß = 11.088 (95% CI = 1.67-20.51); P = 0.021]. CONCLUSIONS: Treatment with NNRTI plus 2 NRTI combinations is associated with a higher LS decline than other ART combinations in HIV/HCV-coinfected patients receiving DAA-based therapy.

Incidence of recently acquired hepatitis C virus infection among HIV-infected patients in southern Spain.

OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.

Similar prevalence of hepatic steatosis among patients with chronic hepatitis C with and without HIV coinfection.

Hepatic steatosis (HS) is frequently observed in HIV-infected patients. It is not known whether HIV infection is an independent risk factor for HS development. We aimed to analyze whether HIV coinfection was associated with a higher frequency of HS in patients with chronic hepatitis C. This was a retrospective cross-sectional study. 574 subjects with chronic hepatitis C virus (HCV) infection were included, 246 (43%) of them coinfected with HIV. All of them underwent transient elastography with controlled attenuation parameter (CAP) measurement. HS was defined as CAP ≥ 248 dB/m. 147 individuals (45%) showed HS in the HCV-monoinfected group and 100 (40.7%) in the HIV/HCV-coinfected group (p = 0.318). HS was associated with body mass index (BMI) [<25 Kg/m2 vs. ≥25 Kg/m2, 67 (23.5%) vs. 171 (62.9%); p = 0.001], with plasma HDL-cholesterol [<50 mg/dL vs. ≥50 mg/dL, 122 (48.6%) vs. 95 (37.5%), p = 0.012], with plasma triglycerides [<150 mg/dL vs. ≥150 mg/dL, 168 (40.2%) vs. 65 (52.4%); p = 0.016] and with plasma total cholesterol [<200 mg/dL vs. ≥200 mg/dL, 181 (41%) vs. 53 (52.5%); p = 0.035]. In the multivariate analysis, HS was associated with BMI [adjusted OR (AOR) = 1.264 (1.194-1.339); p = 0.001], age [AOR = 1.029 (1.001-1.058); p = 0.047] and HCV genotype 3 infection [AOR = 1.901 (1.081-2.594); p = 0.026]. HIV coinfection was not associated with HS [AOR = 1.166 (0.719-1.892); p = 0.534]. In conclusion, HIV coinfection is not related with an increased frequency of HS in HCV-infected patients.

Screening for Hepatocellular Carcinoma in HIV-Infected Patients: Current Evidence and Controversies.

PURPOSE OF REVIEW: This review aims to summarize evidence regarding hepatocellular carcinoma (HCC) screening in the specific context of HIV infection and discuss areas of uncertainty. RECENT FINDINGS: It has not been definitely established if HCC incidence in HIV/HCV-coinfected patients with cirrhosis is above the 1.5%/year threshold that makes screening cost-effective. Outside cirrhosis or HBV infection, available data do not support surveillance. The performance of currently recommended ultrasound (US) screening strategy is poor in HIV-infected patients, as rates of early-stage HCC detection are low. Magnetic resonance imaging-based surveillance strategies or liquid biopsy are innovative approaches that should be specifically tested in this setting. HIV-infected patients with cirrhosis are at risk of HCC. US surveillance identifies patients with early-stage HCC who will benefit of curative therapies, although the quality of the evidence supporting screening remains limited. The HIV population should be a priority group to assess and validate new surveillance strategies.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

How well are we performing the initial assessment of HIV-positive patients? Results from a multicentre cohort in Spain.

OBJECTIVES: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004-2017. METHODS: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. RESULTS: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. CONCLUSIONS: The initial assessment of HIV-infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations.

Impact of interferon-free regimens on the glomerular filtration rate during treatment of chronic hepatitis C in a real-life cohort.

Little data are available on renal toxicity exerted by direct-acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct-acting antivirals against hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD-EPI formula. A total of 1131 patients were included; 658 (58%) were HIV/HCV-coinfected patients. Among the 901 patients treated for 12 weeks, median (interquartile range) eGFR was 100 (87-107) at baseline vs 97 (85-105) mL/min per 1.73 m2 at week 12 of follow-up (FU12) post-treatment (P < .001). For HIV-coinfected subjects who received tenofovir plus a ritonavir-boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104 (86-109) vs 104 (91-110) mL/min per 1.73 m2 (P = .913). Among subjects receiving ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented with eGFR <30 mL/min per 1.73 m2 . In conclusion, eGFR slightly declines during therapy with all-oral DAAs and this effect persists up to 12 weeks after stopping treatment in subjects with normal to moderately impaired renal function, regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to have an impact on eGFR.

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.

Impact of Ethylene Glycol Toxicity on Donor Organ Viability: A Case Report.

Using kidneys from deceased donors whose demise was secondary to ethylene glycol (EG) toxicity requires considerable thought and planning. The exact impact that kidneys from these donors could have is unclear. The shortage of viable organs and growing wait list mortality should lead us to consider these allografts as potential life-saving transplants. Because it is crucial for the transplant community to use every available allograft, we need to develop processes that optimize each possible scenario. This article is a discussion of the viability of kidneys from a donor with EG-induced brain death and a proposed algorithm for encouraging the use of renal allografts after EG toxicity.

Rural habitat as risk factor for hepatitis E virus seroconversion in HIV-infected patients: A prospective longitudinal study.

Our objective was to determine the incidence and clinical manifestations of acute hepatitis E virus (HEV) in HIV-infected patients. A prospective longitudinal study including HIV-infected HEV-seronegative patients was conducted; HEV seroconversion (to IgG and/or IgM) was the main outcome variable. All patients were tested for HEV antibodies every 3-6 months. For patients who developed HEV seroconversion, a data collection protocol was followed to identify associated clinical manifestations and analytical alterations. A total of 627 patients (89.9%) were followed during a median of 11.96 months (IQR: 8.52-14.52 months) and formed the study population. Forty-one patients developed detectable anti-HEV antibodies (7.2 cases per 100 patients/year). Our study found a high incidence of HEV in HIV-infected patients in southern Spain strongly associated with a rural habitat.

Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection.

OBJECTIVE: The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens. PATIENTS AND METHODS: From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12 evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-not-detected (TND), below the lower limit of quantification (LLOQTD) and ≥LLOQ. RESULTS: A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir±ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12 in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTD and ≥LLOQ, SVR12 was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association) 0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004. CONCLUSIONS: TW4-response indicates the probability of achieving SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting.

Fat mass and obesity-associated gene variations are related to fatty liver disease in HIV-infected patients.

OBJECTIVES: Fatty liver disease (FLD) is frequently observed in HIV-infected patients. Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity-associated (FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms (SNPs) within the FTO, previously related to obesity or T2DM, with FLD in HIV-infected patients. METHODS: FLD was defined as a value of the controlled attenuation parameter (CAP) ≥ 238 dB/m, obtained by transient elastography. Four SNPs within FTO intron 1 (rs11642841, rs8050136, rs9939609 and rs9940128) were genotyped in 421 individuals using a custom Golden Gate protocol. The results were replicated in a validation sample consisting of a further 206 HIV-infected patients. Multivariate logistic regression analyses were conducted in the entire population. RESULTS: Three SNPs (rs8050136, rs9939609 and rs9940128) were associated with FLD, with rs9940128 showing the strongest association. This polymorphism also showed an association with FLD in the validation sample. In total, rs9940128 was genotyped in 627 HIV-infected patients, including 267 (42.6%) FLD-diagnosed individuals. The frequency of FLD among rs9940128 AA carriers was 55.7% (63 of 113 individuals) and that in patients without this genotype was 39.7% (204 of 514 individuals) [P = 0.009; adjusted odds ratio 1.88; 95% confidence interval (CI) 1.17-3.01]. CONCLUSIONS: Variations within FTO may be predictors of FLD in HIV-infected patients independently of metabolic factors.

KIR2DS2 as predictor of thrombocytopenia secondary to pegylated interferon-alpha therapy.

Our aim was to evaluate the killer cell immunoglobulin-like receptors (KIRs) as a marker for the development of thrombocytopenia secondary to Peg-interferon (IFN) therapy in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. Patients were naive to HCV treatment, receiving a first course of Peg-IFN/Ribavirin combination therapy. Total platelet count (cells ml-1) was determined at each visit, determining platelet decline from baseline to weeks 1, 2, 4, 8 and 12 after starting therapy. The end point of the study was development of thrombocytopenia, defined as a platelet count of <1 50 000 cells ml-1. Fifty-eight HIV/HCV co-infected patients were included in the study, of whom 20 (34.4%) developed thrombocytopenia. The absence of KIR2DS2 was associated with higher and faster rate of thrombocytopenia (54.2% vs 22.5%; P=0.012; 6.6 vs 10.3 weeks; P=0.008). The absence of KIR2DS2 was associated with a greater decline in platelet count and development of thrombocytopenia during Peg-IFN treatment in HIV/HCV co-infected patients.

High frequency of potential interactions between direct-acting antivirals and concomitant therapy in HIV/hepatitis C virus-coinfected patients in clinical practice.

OBJECTIVES: The aim of the study was to analyse the frequency and degree of potential drug-drug interactions (DDIs) between direct-acting antivirals (DAAs) and concomitant medication used by HIV/hepatitis C virus (HCV)-coinfected patients, including antiretroviral therapy (ART) and other drugs. METHODS: All patients with HIV infection and viraemic HCV genotype 1, 3 or 4 coinfection attending a tertiary care centre in Spain (November 2014 to November 2015) were included in the study. DDIs were classified as major, i.e. drugs should not be co-administered, or minor, i.e. close monitoring, dosage alteration or change in timing may be required if drugs are co-administered, following the http://www.hep-druginteractions.org database recommendations. RESULTS: A total of 244 patients were included in the study, of whom 224 (92%) were previous injecting drug users. Major DDIs were found for: paritaprevir-r/ombitasvir plus dasabuvir (3D), in 60 (44%) of 138 individuals with genotype 1; paritaprevir-r/ombitasvir (2D), in 22 (37%) of 60 individuals with genotype 4; sofosbuvir/ledipasvir (SOF/LDV), in four (2%) of 198 patients with genotype 1 or 4; simeprevir (SMV) plus SOF, in 160 (81%) of 198 patients with genotype 1 or 4; daclatasvir (DCV) plus SOF, in seven (3%) of 244 patients with genotype 1, 3 or 4 (P < 0.001). Minor DDIs were found for: 3D, in 123 (89%) individuals with genotype 1; 2D, in 52 (87%) individuals with genotype 4; SOF/LDV, in 154 (78%) patients with genotype 1 or 4; SMV plus SOF, in 129 (65%) patients with genotype 1 or 4; DCV plus SOF, in 149 (61%) patients with genotype 1, 3 or 4 (P < 0.001). CONCLUSIONS: Drug-drug interactions between DAAs and ART or other commonly prescribed medications are frequently found among HIV/HCV-coinfected patients. Potential major and minor DDIs are more frequent with 3D, 2D and SMV plus SOF regimens.

HLA-B18 as a risk factor of short-term progression to severe liver fibrosis in HIV/HCV co-infected patients with absent or minimal fibrosis: implications for timing of therapy.

Our aim was to analyze the influence of HLA-B haplotypes on liver fibrosis progression in HIV/hepatitis C virus (HCV) co-infected patients. Retrospective longitudinal study including HIV/HCV, non-cirrhotic and HCV treatment-naïve patients. The main outcome variable was liver fibrosis progression of at least one stage. One hundred and four patients constituted the study population (F0-F1: 62 (59.6%); F2: 22 (21.2%); F3: 20 (19.2%)). During a median follow-up of 54.5 months (IQR: 26.2-77), 45 patients (43.3%) showed an increase in the stage of liver fibrosis (time to event: 29 (IQR: 14-49.5) months). HLA-B18pos patients more frequently had a higher and faster fibrosis progression rate (73.3%; 24 (IQR: 8-29) months) than HLA-B18neg patients (38.2%; 34.5 (IQR: 14.7-51.2) months). This association was also observed in the development of F3-F4 fibrosis among F0-F2 patients (HLA-B18pos: 69.2%; 18 (6.5-37) months vs HLA-B18neg: 28.2%; 37 (IQR: 19-52) months). These results could impact the timing of HCV therapy in F0-F2 patients.

Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients.

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV-HCV co-infected patients: final results of the Spanish BOC HIV-HCV Study.

INTRODUCTION: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. METHODS: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. RESULTS: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). CONCLUSIONS: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Changes in liver steatosis evaluated by transient elastography with the controlled attenuation parameter in HIV-infected patients.

OBJECTIVES: There are scant data on the progression of hepatic steatosis (HS) in HIV infection. We therefore evaluated changes in HS over time in HIV-infected patients using the controlled attenuation parameter (CAP). METHODS: A prospective cohort of 326 HIV-infected patients was included in this study. All patients underwent a CAP measurement. Changes in steatosis were evaluated by calculating the median (Q1-Q3) difference between baseline and 12-month CAP values. RESULTS: The median (Q1-Q3) CAP was 221 (196-252) dB/m at baseline and 224 (198-257) dB/m at the 12-month visit (P = 0.617). Significant steatosis, that is, CAP ≥ 238 dB/m, was observed in 76 individuals (37%) at baseline and in 80 (39%) at the 12-month visit (P = 0.683). The following variables were associated with ΔCAP: plasma HIV RNA [< 50 vs. ≥ 50 HIV-1 RNA copies/mL: median (Q1-Q3) ΔCAP, 4 (-21, 27) vs. -21 (-49, 4) dB/m, respectively; P = 0.024]; body mass index (BMI) [no increase vs. increase: -13 (-40, 4) vs. 14 (-6, 32) dB/m, respectively; P < 0.001]; triglycerides [no increase vs. increase: -1 (-30, 22) vs. 15 (-3, 40) dB/m, respectively; P = 0.001]; fasting plasma glucose [not impaired vs. impaired: -4 (-31, 16) vs. 30 (15, 49) dB/m, respectively; P < 0.001]; and raltegravir [no vs. yes: 5 (-20, 29) vs. -11 (-37.5, 15) dB/m, respectively; P = 0.018]. The only factor independently associated with ΔCAP was BMI [B (standard error): 9.03 (1.9); P < 0.001]. CONCLUSIONS: Increases in CAP values over a period of 12 months in HIV-infected patients were strongly associated with elevations in BMI. Other metabolic factors and antiretroviral drugs were not predictors of CAP changes independent of BMI.