Susceptibility to chronic liver disease

摘要: The onset and the progression of chronic liver disease involve environmental genetic factors. Hepatic stellate cells (HSCs) are important players in these processes main storage site for retinol. We studied role obesity, alcohol patatin-like phospholipase domain-containing 3 (PNPLA3) I148M variant on susceptibility to disease. Moreover, we tried understand molecular mechanism underlying association between PNPLA3 In paper I analysed long-term effect weight loss due bariatric surgery damage a large prospective controlled cohort, Swedish Obese Subjects study. changes serum transaminases follow-up baseline values control groups. Serum at 2and 10-year were lower than group. transaminase reduction was proportional degree loss. addition, prevalence severe group during follow-up. II examined age at-risk intake incidence alcoholic cirrhosis. Both variables independent risk factors However, conferred by 148M higher subjects who started drinking earlier those later. III, tested hypothesis that is involved retinol release from HSCs. found regulated availability HSCs it has an esterase activity retinyl palmitate, which impaired mutant protein. conclusion, our data show modifying may affect natural history interplay defines individual Specifically, obesity-related reduced sustained after this prevent Age exposure affects variant. suggest mediated be one step