Single Nucleotide Polymorphisms Associated With Alimentary Fatty Liver Disease Are Not Genetic Risk Factors For Treatment-associated Hepatic Steatosis in HIV Patients On HAART - Single Nucleotide Polymorphisms Associated With Alimentary Fatty Liver Disease Are Not Genetic Risk Factors For Treatment-associated Hepatic Steatosis in HIV Patients On HAART - Open Access Pub

DOI 10.14302/issn.2324-7339.jcrhap-12-140 Hepatic steatosis may occur with any type of HAART. Recently genome wide association studies have identified 5 single nucleotide polymorphisms (SNPs) predisposing to fatty liver disease in nutritional abnormalities. Using a non-invasive method termed “controlled attenuation parameter” we assessed liver fat in HAART-treated HIV-patients and correlated hepatic steatosis to genotype distribution of the 5 SNPs. Unlike alimentary fatty liver our data do not support a role of these SNPs for fatty liver disease on HAART. Highly active antiretroviral therapy has dramatically reduced death rates from opportunistic diseases but is frequently complicated by dyslipidaemia and fatty liver disease (1). Although certain reverse transcriptase inhibitory nucleotides such as the “D” drugs didanosine and stavudine carry a particularly high risk of hepatic steatosis, fatty liver disease has been observed with any type of antiretroviral therapy. Recently two genome wide association studies have revealed that single nucleotide polymorphisms in or near the five genes PNPLA3 (rs738409), CSPG3/NCAN (rs2228603), GCKR (rs780094), PPP1R3B (rs4240624) and LYPLAL1 (rs12137855) are associated with fatty liver disease as well as distinct patterns of serum lipids and glycaemic traits (2-4). Indeed, carriers of the genetic risk variants have been observed significantly more frequently among patients with severe steatohepatitis, liver cirrhosis and liver cancer associated with alcoholic consumption and non-alcoholic liver disease (5-9). Using a novel non-invasive method termed “controlled attenuation parameter, CAP”, we performed a pilot trial to check if any of the 5 genetic variants was also differentially distributed among HIV-infected patients who had developed hepatic steatosis on highly active antiretroviral therapy (HAART). We recruited 57 HIV-infected patients (median age: 48 years, range 30 – 72 years; 8 females) into this pilot study. Patients were on HAART for a median of 81 months (range 6 – 275 months) and had a median of 468 CD4+ cells/μl (range 128-1474 cells/μl). At the time of the study 31 and 26 patients were taking a NNRTI- and PI-based antiretroviral therapy, and 33 and 29 patients had prior exposure to PIs and D-drugs, respectively. 152 healthy volunteers (median age 39 years, range 21-67 years; 59 females) served as reference for the distribution of alleles in the background population. Informed consent was obtained from all patients prior to sample acquisition, and the study was approved by the local ethics committee of the