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Progress in eradication of HCV in HIV positive patients with significant liver fibrosis in Vienna.

ABSTRACT: We aimed to investigate the efficacy of interferon and ribavirin-free sofosbuvir/ledipasvir (SOF/LDV) and ritonavir boosted paritaprevir/ombitasvir with or without dasabuvir (2D/3D) regimens in a real-life cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected patients. The study focused on efficacy, need for changes in antiretroviral therapy (ART) due to drug-drug interaction (DDI), and treatment-associated changes in liver stiffness.In this study 36 patients (n = 21 SOF/LDV and n = 15 2D/3D) were retrospectively analyzed. Depending on the genotype the following treatment regimens were used: HCV genotype (GT)-1: either SOF/LDV or 3D, no patient with HCV-GT2 was included, HCV-GT3: SOF/LDV, HCV-GT4: 2D.Approximately one third (35.3%) of patients were treatment-experienced and 13.9% had cirrhosis. Antiretroviral therapy had to be changed in 38.1% of SOF/LDV and 60% of 2D/3D patients prior to anti-HCV treatment due to expected DDIs. We observed sustained virologic response (SVR) rates of 100% in patients treated with SOF/LDV (19/19) and 2D/3D (14/14). One 2D/3D patient was lost to follow-up, while two SOF/LDV patients died during therapy from non-treatment-related causes. They were excluded from the analysis. Between baseline and follow-up liver stiffness decreased from 11.4 to 8.3 kPa (p = 0.008) and from 8.1 to 5.7 kPa (p = 0.001) in SOF/LDV and 2D/3D patients, respectively.We confirmed the excellent HCV eradication rates >95% in a real-life cohort of HIV/HCV coinfected patients treated with SOF/LDV and 2D/3D. We observed no HCV relapse or breakthrough. More patients treated with 2D/3D required a change in ART than patients treated with SOF/LDV. Additionally, HCV eradication led to a rapid decline in liver stiffness.

SUBMITTER: Steiner S

PROVIDER: S-EPMC5552846 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Project description:Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these conditions. However, HCV can be eradicated in most patients with the new direct-acting antivirals (DAAs) therapy. We have analyzed the effect of HCV on systemic inflammation, endothelial activation and coagulopathy in PLWH and its evolution after HCV eradication with DAAs. Twenty-five HIV/HCV coinfected (HIV/HCV group), 25 HIV monoinfected (HIV group) and 20 healthy controls (HC) were included in the study. All patients were on ART and HIV suppressed. Levels of fourteen markers of systemic inflammation, endothelial activation and coagulopathy (IL-1ß, IL-6, IL-12p70, IL-8, TNFα, D-dimer, Eotaxin, IL-18, IP-10, monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), TNFα receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)) were measured on plasma at baseline and after DAAs-mediated HCV eradication. Non-parametric tests were used to establish inter/intra-group differences. At baseline, the HIV/HCV group showed increased levels of IL-18 (p = 0.028), IP-10 (p < 0.0001), VCAM-1 (p < 0.0001) and ICAM-1 (p = 0.045), compared to the HC and HIV groups, with the highest levels for IL18 and IP10 observed in HIV/HCV patients with increased liver stiffness (≥7.1 KPa). Eradication of HCV with DAAs-based therapy restored some but not all the evaluated parameters. VCAM-1 remained significantly increased compared to HC (p = 0.001), regardless of the level of basal liver stiffness in the HIV/HCV group, and IP-10 remained significantly increased only in the HIV/HCV group, with increased level of basal liver stiffness compared to the HC and to the HIV groups (p = 0.006 and p = 0.049, respectively). These data indicate that DAAs therapy in HIV/HCV co-infected patients and HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in cases with increased liver stiffness.

Project description:Background & aimsFibrosis progression might be accelerated in patients who are coinfected with human immunodeficiency virus (HIV) and HCV (HIV/HCV). However, no studies have directly compared fibrosis progression by paired liver biopsy between patients infected with HIV and HCV versus those infected with only HCV.MethodsLiver biopsy samples were collected from patients with HIV/HCV (n = 306) and those with HCV; biopsies from 59 without a sustained virologic response (SVR) or cirrhosis were matched with those from patients with only HCV (controls) for initial fibrosis stage, demographics, and HCV treatment. For HIV/HCV patients, categorical variables at baseline and the area under the curve of continuous variables per unit time were analyzed for associations with fibrosis progression.ResultsLiver biopsies from HIV/HCV patients had more piecemeal necrosis than controls (P = .001) and increased lobular inflammation (P = .002); HIV/HCV patients also had shorter intervals between liver biopsies (4.7 vs 5.9 years, P < .0001). Between the first and second biopsies, fibrosis remained unchanged or progressed 1 or 2 units in 55%, 18%, and 18% of HIV/HCV patients, respectively, compared with 45%, 30%, and 9% of controls. The fibrosis progression rate was similar between HIV/HCV and control patients (0.12 ± 0.40 vs 0.091 ± 0.29 units/y; P = .72). In paired biopsies from 66 patients, including those with SVR, there were no associations between fibrosis progression and demographics; numbers of CD4+ T cells; levels of aspartate aminotransferase or alanine aminotransferase; use of highly active antiretroviral therapy; response to HCV therapy (no treatment, SVR, or non-response); baseline levels of FIB-4; or histologic features including inflammation, fibrosis, or steatosis.ConclusionsOn the basis of analysis of liver biopsy samples, fibrosis progression was similar between HIV/HCV-infected and HCV-infected patients; no clinical or laboratory parameters predicted disease progression.

Project description:IntroductionThe aim of our study was to investigate the potential relationship between liver fibrosis (LF) and cognitive performance in HIV+ patients.Materials and methodsWe performed a cross-sectional cohort study by consecutively enrolling HIV+ patients during routine outpatient visits at two clinical centres in Italy. Subjects with decompensated liver disease were excluded. All subjects underwent a comprehensive neuropsychological battery exploring memory, attention, psychomotor speed and language; cognitive impairment was defined as at least two abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was explored by calculating FIB4 index; in a subgroup of patients, LF was also assessed by transient elastography. Factors associated with cognitive impairment were investigated by logistic regression models.ResultsA total of 413 patients [77% males, median age 46 (IQR 39-52), 17% with past AIDS-defining events, 19% past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA <50 copies/mL, 18% co-infected with HCV] were enrolled. Seventeen patients (4%) had FIB4 >3.25 and 14/129 (3%) had liver stiffness >14KPa. Forty-seven patients (11%) were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 >1.45 showed a higher risk of cognitive impairment in comparison with those with lower values (OR 2.19, 95% CI 1.02-4.72; p=0.044) after adjusting for education (OR 0.79, 95% CI 0.71-0.88; p<0.001), past IDU (OR 1.69, 95% CI 0.67-4.23; p=0.264), diabetes (OR 2.35, 95% CI 0.62-8.86; p=0.207), HIV RNA <50 copies/mL (OR 0.47, 95% CI 0.19-1.14; p=0.095) and HCV co-infection (OR 0.88, 95% CI 0.33-2.39; p=0.807). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with fibroscan score >14KPa in comparison with fibroscan score <7KPa (OR 285.07; 95% CI 2.42-33574.06; p=0.020) after adjusting for education (OR 0.54, 95% CI 0.31-0.92; p=0.024), age (for 10 years increase) (OR 2.03, 95% CI 0.55-7.53; p=0.288), past IDU (OR 4.43, 95% CI 0.35-7.57; p=0.526), HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00-0.18; p=0.003), HIV history (for 1 year increase) (OR 0.96, 95% CI 0.83-1.12; p=0.641), CD4 cells count at nadir (OR 1.10, 95% CI 0.56-2.16; p=0.779), and HCV co-infection (OR 0.06; 95% CI 0.00-1.93; p=0.113).ConclusionsIn HIV-infected patients higher LF, estimated through non-invasive methods, is associated to a higher risk of cognitive impairment.

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Progress in eradication of HCV in HIV positive patients with significant liver fibrosis in Vienna.

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