title: Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B.
abstract: Steatosis is a common histopathological feature of chronic hepatitis B (CHB) and has been associated with severity of liver disease. Recently, the rs738409 I148M patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism has been demonstrated to influence steatosis susceptibility and fibrosis progression in patients with different liver diseases, but no data are yet available for CHB. The aim of this study was to evaluate whether PNPLA3 I148M influences steatosis susceptibility in a large series of patients with CHB. We enrolled 235 treatment-naïve CHB patients consecutively examined by percutaneous liver biopsy. In ≥2-cm-long liver tissue cores, steatosis and fibrosis were staged by Kleiner and METAVIR scores, respectively. The I148M polymorphism was determined by Taqman assays. Steatosis was present in 146 (62%) patients, of whom 24 (10%) had severe (>33% of hepatocytes) steatosis. Steatosis was independently associated with age (odds ratio [OR]: 2.67; confidence interval [CI]: 1.50-4.92; for age ≥50 years), body mass index (BMI; OR, 2.84; CI, 1.30-6.76; for BMI ≥27.5 kg/m(2) ), diabetes or impaired fasting glucose (OR, 4.45; CI, 1.10-30.0), and PNPLA3 148M allele (OR, 1.62; CI, 1.00-7.00; for each 148M allele). Independent predictors of severe steatosis were BMI (OR, 3.60; CI, 1.39-9.22; for BMI ≥27.5 kg/m(2) ) and PNPLA3 148M allele (OR, 6.03; CI, 1.23-5.0; for each 148M allele). PNPLA3 148M alleles were associated with a progressive increase in severe steatosis in patients with acquired cofactors, such severe overweight and a history of alcohol intake (P = 0.005).
  
  
  CONCLUSIONS
  In CHB patients, the PNPLA3 I148M polymorphism influences susceptibility to steatosis and, in particular, when associated with severe overweight and alcohol intake, severe steatosis.
authors.affiliation: Hepatology Unit, Ospedale San Giuseppe, Università degli Studi di Milano, Milano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Viganò
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.forename: Floriana
authors.initials: F
authors.lastname: Facchetti
authors.forename: Benedetta Maria
authors.initials: BM
authors.lastname: Motta
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: Solange
authors.initials: S
authors.lastname: Romagnoli
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.forename: Benedetta
authors.initials: B
authors.lastname: Donati
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D007558:Italy; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; 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