400 NUCLEOSIDE ANALOGUES ALONE OR COMBINED WITH VACCINATION PREVENT WHV INFECTION AND INDUCE PROTECTIVE IMMUNITY: NEW STRATEGY FOR HBV POST-EXPOSURE PROPHYLAXIS

Background and Aims: Steatosis is a common histopathological feature of chronic hepatitis B (CHB), and has been associated with the severity of liver disease.Recently, the rs738409 I148M PNPLA3 polymorphism has been demonstrated to influence steatosis susceptibility and fibrosis progression in patients with obesity, alcohol abuse, and chronic hepatitis C, but no data are yet available for CHB.Aim: To evaluate whether PNPLA3 I148M influences steatosis susceptibility in a large series of patients with biopsy proven CHB.Methods: 235 treatment-naïve CHB patients consecutively examined by percutaneous liver biopsy were enrolled.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.Results: Steatosis was present in 146 (62%) patients, of whom 22 (10%) had severe steatosis, i.e. involving >33% of hepatocytes.Steatosis was independently associated with age (OR 2.67, 1.50-4.92for age≥50 years), BMI (kg/m 2 ; OR 2.84, 1.30-6.76for BMI ≥27.5), diabetes or impaired fasting glucose (OR 4.45, 1.10-30.0),and PNPLA3 148M allele (OR 1.62, 1.00-7.0for each 148M allele).Independent predictors of severe steatosis were BMI (OR 3.60, 1.39-9.22for BMI ≥27.5 kg/m 2 ), and PNPLA3 148M allele (OR 6.03, 1.23-5.0for each 148M allele).PNPLA3 148M alleles were associated with a progressive increase in severe steatosis in patients with, but not in those without, acquired cofactors such severe overweight and a positive history of alcohol intake (p = 0.005).Conclusions: In CHB patients, the PNPLA3 I148M polymorphism influences the susceptibility to steatosis, and, in particular when associated with severe overweight and positive alcohol intake, to severe steatosis.