Scribani, Melissa

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.

AbstractBackground & AimsNonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. Smoking and diabetes mellitus (DM) have been shown to increase mortality; however, whether NAFLD adds to the detrimental effect of smoking in DM and non‐DM patients is unknown. We evaluated the possible interactive effect of NAFLD and smoking on mortality risk in a US population‐based sample.MethodsCross‐sectional data from 11 205 participants in the third National Health and Nutrition Examination Survey were analysed. NAFLD was defined as ultrasonographic hepatic steatosis without evidence of other liver diseases. Proportional hazards regression modelling was used to test for the multiplicative interaction of NAFLD and smoking on overall mortality, controlling for DM.Results36.5% of the participants had NAFLD of whom 21.1% were current smokers, while among non‐NAFLD subjects, 26.2% reported current smoking. Smoking was associated with a hazard ratio (HR) of 2.23 (95% confidence interval (CI): 1.87‐2.65) among non‐NAFLD subjects, and 2.31 (95% CI: 1.33‐2.92, P < 0.01) among NAFLD patients. In contrast, the HR for NAFLD was 1.01 (95% CI: 0.78‐1.31, P = 0.96) among smokers and 0.98 (95% CI: 0.87‐1.10, P = 0.73) among non‐smokers. There was no evidence of interaction between NAFLD and smoking (HR = 1.01, 95% CI: 0.74‐1.38, P = 0.94) in the combined model.ConclusionWe found that smoking increased mortality by two‐fold among the US population. Although the magnitude of the increase in mortality did not differ from that in non‐NAFLD subjects, smoking represents a modifiable determinant of long‐term outcomes in NAFLD patients.

Background/Aims Studies have shown that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of chronic kidney disease (CKD). However, it is unknown whether severe liver fibrosis is associated with a higher prevalence of CKD among NAFLD. We examined the diagnostic performance of noninvasive fibrosis markers in identifying prevalent CKD among NAFLD. Methods This study represents an analysis of the National Health and Nutrition Examination Survey conducted in the USA between 1988 and 1994. NAFLD was defined by ultrasonographic evidence of hepatic steatosis without other liver diseases. CKD was defined by estimated glomerular filtration rate less than 60 ml/min/1.73 m2. The presence and severity of hepatic fibrosis were determined by the NAFLD fibrosis score (NFS), FIB-4 score, APRI score, and BARD score. Multiple logistic regression was performed to generate odds ratios (ORs) and receiver operating characteristic curves were used to assess the predictive values of each marker. Results A total of 4142 individuals with NAFLD were included; 200 (4.8%) had CKD. The area under the receiver operating characteristic curves was 0.77, 0.75, 0.62, and 0.51 for the multivariable equation with FIB-4, NFS, BARD, and APRI score, respectively. Compared with patients with a low probability of developing advanced liver fibrosis, individuals with a high probability of developing fibrosis showed significantly increased odds of CKD as estimated by NFS (adjusted OR: 4.92, 95% confidence interval: 2.96–8.15) and FIB-4 (adjusted OR: 2.27, 95% confidence interval: 1.05–4.52). Conclusion Advanced liver fibrosis, defined by NFS and FIB-4 scores, is associated independently with CKD among individuals with NAFLD. FIB-4 is the best predictor of an increased risk of prevalent CKD.