Raymond, Pascale

Abstract Background and Aim The association between palatin‐like phospholipase domain‐containing 3 ( PNPLA3 ) I148M ( rs738409 ) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M ( rs738409 ) polymorphism on overall and cardiovascular mortality based on the presence of nonalcoholic fatty liver disease (NAFLD). Methods The third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and National Health and Nutrition Examination Survey III‐linked mortality data through 31 December 2015 were utilized in this study. Results Of 4814 participants, 50.7% were homozygous for the C‐allele and 12.6% were homozygous for the G‐allele. During a follow up of 20 years, there were a total of 1255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M ( rs738409 ) GG genotype (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.02–1.77) or G‐allele (HR 1.22, 95% CI 1.09–1.36) in the general population. NAFLD with homozygous PNPLA3 I148M ( rs738409 ) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (HR 1.45, 95% CI 1.01–2.08). The PNPLA3 I148M ( rs738409 ) G‐allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD. Conclusions The homozygous PNPLA3 I148M ( rs738409 ) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors.

Background and aim Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis. Participants and methods Cross-sectional data from 11 325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index. Results NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01–2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03–1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18–2.72). Conclusion Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.