title: The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection.
abstract: BACKGROUND
  Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear.
  
  
  METHODS
  In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)-and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes.
  
  
  RESULTS
  75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984) and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes.
  
  
  CONCLUSIONS
  The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Scheiner
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mandorfer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schwabl
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Berit Anna
authors.initials: BA
authors.lastname: Payer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Theresa
authors.initials: T
authors.lastname: Bucsics
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Simona
authors.initials: S
authors.lastname: Bota
authors.affiliation: Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.|Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Maximilian C
authors.initials: MC
authors.lastname: Aichelburg
authors.affiliation: Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.|Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grabmeier-Pfistershammer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Albert
authors.initials: A
authors.lastname: Stättermayer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.|Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D001706:Biopsy; D015331:Cohort Studies; D060085:Coinfection / Q000150:complications / Q000821:virology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D054459:Elasticity Imaging Techniques; D005234:Fatty Liver / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics*; D006801:Humans; D006975:Hypertension, Portal / Q000503:physiopathology*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011312:Pressure; D015995:Prevalence; D012306:Risk; D016896:Treatment Outcome; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent