Z Gastroenterol 2016; 54 - KV182
DOI: 10.1055/s-0036-1586958

Genetic polymorphisms in fatty liver disease in HIV positive patients receiving combined antiretroviral therapy (cART)

L Dold 1, C Luda 1, C Schwarze-Zander 1, C Bösecke 1, C Berger 2, HD Nischalke 1, RU Mohr 1, JC Wasmuth 1, CP Strassburg 1, JK Rockstroh 1, U Spengler 1
  • 1Universitätsklinikum Bonn, Medizinische Klinik I, Bonn, Deutschland
  • 2RWTH Aachen, Medizinische Klinik III, Aachen, Deutschland

Background and aims: Hepatic steatosis possibly occurs with any type of antiretroviral therapy (cART). Genome wide association studies have identified 7 single nucleotide polymorphisms (SNPs) predisposing to fatty liver disease in obesity. In this study, we analyzed if the risk of developing fatty liver under cART is associated to single nucleotide polymorphisms in HIV positive patients.

Methods: 142 HIV positive patients under cART (median 96 months of treatment duration) were recruited into the study. Using a non-invasive method “controlled attenuation parameter” (CAP) integrated in Fibroscan, we assessed liver fat and fibrosis in all participants. We further determined SNPs PNPLA3 (rs738409), CSPG3/NCAN (rs2228603), GCKR (rs780094), PPP1R3B (rs4240624), TM6SF (rs8542926), LYPLAL1 (rs12137855) and MBOAT7 (rs626283) by LightCycler real time PCR. Frequencies of genotypes tested for consistency with the Hardy-Weinberg equilibrium using an exact test. Allele and genotype frequencies were compared between patient groups and controls by T-test.

Results: We enrolled 142 HIV-infected patients (median age 47 years, 22 female/120 male) into the study. 82 HIV patients (58%) had possible fatty liver disease with a CAP value between 225 – 300 dB/m and 14 patients (9.8%) had definite hepatic steatosis (CAP > 300 dB/m). HIV positive patients with definite hepatic steatosis had significantly higher BMI (p = 0.040), ALT (p = 0.021), yGT (p = 0.004), bilirubin (p = 0.011) and triglyceride levels (p = 0.001), than the other HIV positive patients. Statistical analysis revealed significantly increased CAP values (p = 0.040) and levels of triglycerides (p = 0.007) in carriers of the GCKR (rs780094) A allele.

Conclusion: Carriers with the GCKR (rs780094) mutation have significantly higher CAP values and triglyceride levels. GCKR (rs780094) might play a role in the development of treatment associated fatty liver and influences metabolic traits in HIV positive patients receiving cART.