title: Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C.
abstract: This study analysed the impact of PNPLA3 variants on liver histology of 168 HIV/hepatitis C virus (HCV)-coinfected patients who were naïve for HCV treatment. A athologist unaware of the patients' condition graded liver fibrosis and necroinflammation (Ishak) and steatosis (Kleiner). Patients were tested for PNPLA3 variants and genotyped for the PNPLA3 rs738409 C to G variant underlying the I148M substitution. All were hepatitis B surface antigen negative and stated no alcohol abuse. The mean age was 40.6 (37.6-44.1) years, 72.6% were males, 42% had HCV genotype 3, 38.9% HCV genotype 1 and 79.2% were receiving highly active antiretroviral therapy. The 79 patients with the PNPLA3 p.148I/M or M/M variants more frequently showed severe steatosis (score 3-4) than the 89 with PNPLA3 p.148I/I (43% vs. 24.7%, p 0.001), whereas no difference was observed in the degree of necroinflammation or fibrosis. Compared with 112 patients with lower scores, 56 with severe steatosis showed higher body mass index (p 0.03), higher rate of HCV genotype 3 (55.6% vs. 35.2%, p 0.01), PNPLA3 p.148I/M or M/M (60.7% vs. 39.3%, p 0.01) and lower CD4(+) cells/mm(3) (514.00 (390.5-673.0) vs. 500.00 (399.0-627.0); p 0.002). At multivariate analysis, body mass index (p 0.01), HCV genotype 3 (p 0.006), CD4(+) cell count (p 0.005) and PNPLA3 p.148I/M or M/M variants (p 0.01) were found to be independent predictors of severe liver steatosis. The PNPLA3 p.148 I/M or M/M variants and CD4(+) cell count were the only independent predictors of severe steatosis in patients with HCV non-3 genotypes. This is the first study to show that among HIV/HCV-coinfected patients the PNPLA3 p.148I/M or M/M variant have substantially less impact on steatosis for those with HCV genotype 3 than non-genotype 3.
authors.affiliation: Department of Experimental Medicine and Surgery 'F. Magrassi e A. Lanzara', Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Sagnelli
authors.affiliation: Department of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Merli
authors.affiliation: Department of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Uberti-Foppa
authors.affiliation: Department of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: H
authors.initials: H
authors.lastname: Hasson
authors.affiliation: Department of Pediatrics, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: Department of Pediatrics, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Grandone
authors.affiliation: Department of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Salpietro
authors.affiliation: Department Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Minichini
authors.affiliation: Department of Pediatrics, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: E M
authors.initials: EM
authors.lastname: Del Giudice
authors.affiliation: Department of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Department Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy. Electronic address: evangelistasagnelli@libero.it.
authors.forename: E
authors.initials: E
authors.lastname: Sagnelli
authors.affiliation: Department Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Coppola
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D006651:Histocytochemistry; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009336:Necrosis / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: HIV/HCV coinfection; PNPLA3; liver biopsy; liver histology; liver steatosis