Z Gastroenterol 2015; 53 - P65
DOI: 10.1055/s-0035-1551753

The presence of a PNPLA3 (rs738409) single nucleotide polymorphism (SNP) is not associated with increased risk for fibrosis, portal hypertension, and hepatic steatosis in HIV/HCV-coinfected patients

B Scheiner 1, 2, M Mandorfer 1, 2, P Schwabl 1, 2, B Payer 1, 2, M Aichelburg 2, 3, K Grabmeier-Pfistershammer 2, 3, A Stättermayer 1, P Ferenci 1, M Trauner 1, M Peck-Radosavljevic 1, 2, T Reiberger 1, 2
  • 1Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Vienna, Austria
  • 2Vienna HIV & Liver Study Group, Vienna, Austria
  • 3Medical University of Vienna, Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Vienna, Austria

Background and aims: HIV/HCV-coinfected patients often show hepatic steatosis, faster fibrosis progression, and a higher risk of developing end-stage liver disease. While several risk factors for faster fibrosis progression have been established, the role of a genetic variation of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) remains unclear. Thus, we examined the impact of the PNPLA3 single nucleotide polymorphism (SNP rs738409) on liver steatosis and fibrosis in a cohort of HIV/HCV-coinfected patients.

Methods: 177 HIV/HCV-coinfected patients with available data on PNPLA3 (SNP rs738409) and IL28B (SNP rs12979860) were enrolled. Liver fibrosis and steatosis was staged either by liver biopsy or by transient elastography (FibroScan® using the Controlled Attenuation Parameter (CAPTM) module). Parameters associated with advanced liver fibrosis (≥F3) and portal hypertension (hepatic venous pressure gradient, HVPG) were examined. Fibrosis progression rate (FPR in METAVIR F stages/year) was calculated using the estimated year of HCV infection.

Results: Patients tested positive for a PNPLA3 minor (G/C, n = 66) or major (G/G n = 9) risk allele (42.4%) showed comparable fibrosis stages (median F2 vs. F2; p = 0.106) and a similar amount of hepatic steatosis (CAP: 200.3 ± 44.7 vs. 217.7 ± 56.2; p = 0.484). Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.418) nor with IL28B-genotype (p = 0.637) but was independently associated with HCV-GT3 (p = 0.002), lower CD4+ nadir (p = 0.050), higher BMI (p = 0.027) and longer duration of infection (p = 0.017). Fibrosis progression rate (0.21 ± 0.27 vs. 0.46 ± 0.74 units/year; p = 0.313) and HVPG-values (3.7 ± 2.5 vs. 4.6 ± 3.1 mmHg; p = 0.172) were comparable in patients with and without PNPLA3 risk alleles.

Conclusions: The presence of a PNPLA3 risk allele had no influence on liver fibrosis progression, portal hypertension, or hepatic steatosis in HIV/HCV-coinfected patients. The small number of patients with a major PNPLA3 risk allele may represent a potential limitation.