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

Leona Dold,Hans-Dieter Nischalke,Jonel Trebicka,Jan-Christian Wasmuth,Jürgen Kurt Rockstroh,Ulrich Spengler,Cordula Hansel,Raphael Mohr,Christian P Strassburg,Christoph Boesecke,Carolin Luda,Philipp Lutz,Carolynne Schwarze-Zander,Pavel Strnad

doi:10.1371/journal.pone.0178685

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.

Highlights

We report an exploratory study of 117 human immunodeficiency virus (HIV)-positive patients to check if genetic variants predisposing to alcoholic steatosis and non-alcoholic steatohepatitis (NASH) modify liver disease on antiretroviral therapy
In 2013, we decided to expand our pilot study on hepatic steatosis and prospectively recruited HIV-infected patients of Caucasian descent, who had been on can occur with any antiretroviral therapy (cART) for at least one year before study entry, at the outpatient clinic at the Bonn University Department of Internal Medicine
In two patients (1.7%) risk factors for HIV transmission could not be identified with certainty

Summary

Introduction

Our early pilot trial in 57 HIV-infected patients did not support any association between genetic risk factors and hepatic steatosis [16]. It remains unclear if genetic variants modify the risk for drug-related fatty liver disease or just reflect genetic factors of obesity and metabolic abnormalities in ASH and NASH. To clarify this issue we expanded our pilot study using transient elastography and the controlled attenuation parameter (CAP) as surrogate markers of hepatic fibrosis and steatosis [17].

Patients and methods

Statistical methods

Results

Discussion