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Genetic polymorphisms associated with fatty liver disease and fibrosis in HIV positive patients receiving combined antiretroviral therapy (cART).

ABSTRACT: Hepatic steatosis can occur with any antiretroviral therapy (cART). Although single nucleotide polymorphisms (SNPs) have been identified to predispose to alcoholic and non-alcoholic fatty liver disease, their role for treatment-associated steatosis in HIV-positive patients remains unclear. We determined the frequency of PNPLA3 (rs738409), CSPG3/NCAN (rs2228603), GCKR (rs780094), PPP1R3B (rs4240624), TM6SF (rs8542926), LYPLAL1 (rs12137855) and MBOAT7 (rs626283) by RT-PCR in 117 HIV-positive patients on cART and stratified participants based on their "controlled attenuation parameter" (CAP) into probable (CAP: 215-300 dB/m) and definite (CAP >300 dB/m) hepatic steatosis. We analyzed CAP values and routine metabolic parameters according to the allele frequencies. Sixty-five (55.6%) and 13 (11.1%) patients were allocated to probable and definite steatosis. CAP values (p = 0.012) and serum triglycerides (p = 0.043) were increased in carriers of the GCKR (rs780094) A allele. Cox logistic regression identified triglycerides (p = 0.006), bilirubin (p = 0.021) and BMI (p = 0.068), but not the genetic parameters as risk factors for the occurrence of hepatic steatosis. Taken together, according to the limited sample size, this exploratory study generates the hypothesis that genetic polymorphisms seem to exert minor effects on the risk for fatty liver disease in HIV-positive patients on cART. Nevertheless, SNPs may modify metabolic complications once metabolic abnormalities have developed. Hence, subsequent analysis of a larger cohort is needed.

SUBMITTER: Dold L

PROVIDER: S-EPMC5464588 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Genetic polymorphisms associated with fatty liver disease and fibrosis in HIV positive patients receiving combined antiretroviral therapy (cART).

Dold Leona L Luda Carolin C Schwarze-Zander Carolynne C Boesecke Christoph C Hansel Cordula C Nischalke Hans-Dieter HD Lutz Philipp P Mohr Raphael R Wasmuth Jan-Christian JC Strassburg Christian P CP Trebicka Jonel J Rockstroh Jürgen Kurt JK Spengler Ulrich U

PloS one 20170608 6

Hepatic steatosis can occur with any antiretroviral therapy (cART). Although single nucleotide polymorphisms (SNPs) have been identified to predispose to alcoholic and non-alcoholic fatty liver disease, their role for treatment-associated steatosis in HIV-positive patients remains unclear. We determined the frequency of PNPLA3 (rs738409), CSPG3/NCAN (rs2228603), GCKR (rs780094), PPP1R3B (rs4240624), TM6SF (rs8542926), LYPLAL1 (rs12137855) and MBOAT7 (rs626283) by RT-PCR in 117 HIV-positive patie ...[more]

PMID: 28594920

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Project description:Background and aimsAlthough combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.Methods116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.ResultsFifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.ConclusionThe formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.

Project description:To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ?7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (?2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.

Project description:The aim of our study was to evaluate the seasonal variations and whether short-term exposure to environmental risk factors, such as climate and air pollution, is associated with PTB-related hospital admissions in human immunodeficiency virus (HIV)-infected patients in Spain during the era of combined antiretroviral therapy (cART). A retrospective study was carried out using data from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. The primary outcome variable was hospital admissions with PTB diagnosis. The environmental risk factors evaluated were season, temperature, humidity, NO2, SO2, O3, PM10, and CO. Overall, HIV-infected patients had a lower frequency of PTB-related hospital admissions in summer (22.8%) and autumn (22.4%), but higher values in winter (26.6%) and spring (28.2%). Using a Bayesian temporal model, PTB-related hospital admissions were less frequent in summer-autumn and more abundant in winter-spring during the first years of follow-up. During the later years of follow-up, the seasonal trends continued resulting in the lowest values in autumn and the highest in spring. When considering short-term exposure to environmental risk factors, lower temperatures at 1 week (odds ratio (OR) = 1.03; p = 0.008), 1.5 weeks (OR = 1.03; p<0.001), 2 weeks (OR = 1.04; p<0.001), and 3 weeks (OR = 1.03; p<0.001) prior to PTB admission. In addition, higher concentration of NO2 at the time of admission were significantly associated with higher likelihoods of PTB-related hospital admission in HIV-infected patients when 1.5 weeks (OR = 1.1; p = 0.044) and 2 weeks (OR = 1.21; p<0.001) were used as controls. Finally, higher concentration of SO2 at 1.5 weeks prior to PTB admission was significantly associated with a higher likelihood of PTB-related hospital admissions (OR = 0.92; p = 0.029). In conclusion, our data suggest an apparent seasonal variation in hospital admissions of HIV-infected patients with a PTB diagnosis (summer/autumn vs. winter/spring), as well as a link to short-term exposure to environmental risk factors, such as temperature and ambient NO2 and SO2.

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.

Project description:BackgroundSwaziland has the highest adult HIV prevalence and second highest rate of TB/HIV coinfection globally. Recently, the Ministry of Health and partners have increased integration and co-location of TB/HIV services, but the timing of antiretroviral therapy (ART) relative to TB treatment-a marker of program quality and predictor of outcomes-is unknown.MethodsWe conducted a retrospective analysis of programmatic data from 11 purposefully-sampled facilities to evaluate timely ART provision for HIV-positive TB patients enrolled on TB treatment between July-November 2014. Timely ART was defined as within two weeks of TB treatment initiation for patients with CD4<50/μL or missing, and within eight weeks otherwise. Descriptive statistics were estimated and logistic regression used to assess factors independently associated with timely ART.ResultsOf 466 HIV-positive TB patients, 51.5% were male, median age was 35 (interquartile range [IQR]: 29-42), and median CD4 was 137/μL (IQR: 58-268). 189 (40.6%) were on ART prior to, and five (1.8%) did not receive ART within six months of TB treatment initiation. Median time to ART after TB treatment initiation was 15 days (IQR: 14-28). Almost 90% started ART within eight weeks, and 45.5% of those with CD4<50/μL started within two weeks. Using thresholds for "timely ART" according to baseline CD4 count, 73.3% of patients overall received timely ART after TB treatment initiation. Patients with CD4 50-200/μL or ≥200/μL had significantly higher odds of timely ART than patients with CD4<50/μL, with adjusted odds ratios of 11.5 (95% confidence interval [CI]: 5.0-26.6) and 9.6 (95% CI: 4.6-19.9), respectively. TB cure or treatment completion was achieved by 71.1% of patients at six months, but this was not associated with timely ART.ConclusionsThis study demonstrates the relative success of integrated and co-located TB/HIV services in Swaziland, and shows that timely ART uptake for HIV-positive TB patients can be achieved in resource-limited, but integrated settings. Gaps remain in getting patients with CD4<50/μL to receive ART within the recommended two weeks post TB treatment initiation.

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Genetic polymorphisms associated with fatty liver disease and fibrosis in HIV positive patients receiving combined antiretroviral therapy (cART).

Publications

Genetic polymorphisms associated with fatty liver disease and fibrosis in HIV positive patients receiving combined antiretroviral therapy (cART).

Similar Datasets

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