Nonalcoholic fatty liver disease (NAFLD), insulin resistance and liver fibrosis are prevalent in individuals co-infected with HIV type 1 (HIV-1)/hepatitis C virus (HCV), even after HCV eradication. ...Our aim was to evaluate single nucleotide polymorphisms (SNPs) associated with advanced liver fibrosis in HIV-1/HCV co-infected patients.
In a cohort of 102 participants, we genotyped 16 SNPs in 10 genes previously associated with NAFLD and the innate immune response and correlated the genotypes with liver fibrosis and fat accumulation.
Multinomial logistic regression analysis identified three metabolic parameters that were significantly associated with advanced liver fibrosis (stage F3-F4): albumin odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001, percentage of visceral fat area (PVFA) (OR 1.06, 95% CI 1.01-1.12, P = 0.03) and BMI (OR 1.47, 95% CI 1.22-1.77, P < 0.0001). After adjustment for sex, albumin, PVFA and BMI, we found that three SNPs were significantly associated with advanced fibrosis, one each in PNPLA3/rs738409 (P = 0.016), ADAR-1/rs1127313 (P = 0.029) and IFIH1/rs1990760 (P = 0.033).
Our results indicate that genotyping for these SNPs can be a useful predictive tool for liver fibrosis progression and liver fat accumulation in patients co-infected with HIV-1/HCV.
We assessed non‐liver‐related non–acquired immunodeficiency syndrome (AIDS)‐related (NLR‐NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)–coinfected ...patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR‐NAR events considering death as the competing risk. The NLR‐NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR‐NAR cancer, bone events, and non‐AIDS‐related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T‐cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti‐HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5‐year follow‐up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval CI, 0.35‐0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17‐1.09; P = 0.075). Conclusion: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver‐related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344–356).
ObjectiveTo assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)–1 disease progression, virologic response (plasma HIV-1 ...RNA load of <500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART) ResultsHCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio IRR, 0.97 95% confidence interval {CI}, 0.81–1.16). However, there was a large increase in the incidence of liver disease–related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 95% CI, 6.42–21.34). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard RH, 1.13 95% CI, 0.84–1.51) and immunologic response, whether measured as a ⩾50% increase (RH, 0.94 95% CI, 0.77–1.16) or a ⩾50 cells/μL increase (RH, 0.92 95% CI, 0.77–1.11) in CD4 cell count after HAART initiation ConclusionsHCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus
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. (HEPATOLOGY 2009.)
Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV ...and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4+ T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2–long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation.
To assess the prevalence and factors associated with significant hepatic steatosis (SHS, steatosis involving ≥10% hepatocytes) in HIV-infected patients.
A prospective, cross-sectional study.
Five ...hundred and five HIV-infected patients were included in this study. All patients underwent a transient elastography examination with the controlled attenuation parameter (CAP). SHS was defined using the previously identified CAP cut-off of 238 dB/m. We analysed the associations between SHS and demographics, metabolic data, coinfections and drug therapy.
SHS was detected in 201 (40%) patients. Individuals with and without plasma HIV RNA of 50 copies/ml or less presented SHS in 168 (42%) and 33 (31%) cases, respectively (P = 0.030). Patients with SHS compared with those without SHS presented higher median (IQR) BMI BMI, 25.6 (22.5-28) vs. 22.3 (20.3-24.2) kg/m; P < 10, DBP 79 (72-85) vs. 74 (68-81) mmHg; P = 0.0001, fasting plasma glucose 95 (87-106) vs. 91 (84-97) mg/dl; P = 0.002 and triglycerides 128 (92-189) vs. 109 (80-167) mg/dl; P = 0.002, and lower HDL cholesterol 44 (37-54) vs. 48 (40-59), mg/dl; P = 0.004. In multivariate analysis, the only factor associated with SHS was BMI per unit increase, adjusted odds ratio (95% confidence interval) 1.34 (1.22-1-47); P < 10.
SHS measured by CAP is highly prevalent among HIV-infected patients. High BMI is the main predictor of SHS in this setting.
Background
The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV‐positive persons, and are available in print, online, and as a free App for ...download for iPhone and Android.
Guideline highlights
The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV‐positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre‐exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug−drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti‐hepatitis C virus (HCV) treatment with direct‐acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon‐containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes.
Conclusions
The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.
Our primary objective was to assess the independent association between liver fibrosis (LF) and abdominal fat accumulation (AFA) and fatty liver disease (FLD). We also aimed to determine the ...diagnostic accuracy of AFA and FLD for the prediction of cirrhosis measured using unenhanced low-dose computed tomography (CT). This is a cross-sectional study in stable human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with active HCV replication. CT was used to quantify fat content in segments III and VI of the liver and AFA. Transient elastometry was used to stage LF. Multivariate logistic regression, receiver operating characteristic curve analysis, and linear mixed model analysis were applied. One hundred fifteen HIV/HCV-coinfected patients were included. Cirrhosis was detected in 20.8% (24 patients). There was a high correlation between anthropometric characteristics and radiological variables. The factors independently associated with cirrhosis were albumin concentration odds ratio (OR), 0.69; 95% confidence interval (CI), 0.58-0.83;
< .0001 and visceral fat accumulation (OR, 1.02; 95% CI, 1.01-1.04;
= .0003). Multinomial analysis showed that visceral fat area (VFA) was the factor independently associated with stage F2 (OR, 1.02; 95% CI, 1.0-1.03;
< .005) and albumin concentration with stage F3 (OR, 0.75; 95% CI, 0.64-0.89;
< .001). VFA was the only radiological variable with an area under the curve >0.7 for the prediction of cirrhosis. There was no inter- or intraobserver variability in the measurement of AFA; however, high interobserver variability was recorded in the measurement of FLD. The association of VFA with cirrhosis, the high reproducibility of CT for the measurement of VFA, and the ability of VFA to predict cirrhosis make CT a suitable technique for identifying HIV/HCV-coinfected patients for closer surveillance.
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