Molecular Screening via Sanger Sequencing of the Genetic Variants in Non-Alcoholic Fatty Liver Disease Subjects in the Saudi Population: A Hospital-Based Study.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, along with steatosis and non-alcoholic steatohepatitis (NASH), and is associated with cirrhosis and hepatocellular carcinoma. Candidate gene and genome-wide association studies have validated the relationships between NAFLD, NASH, PNPLA3, TM6SF2, and HFE. The present study utilized five polymorphisms in three genes: PNPLA3 (I148M and K434E) TM6SF2 (E167K), and HFE (H63D and C282Y), based on undocumented case−control studies in the Saudi Arabian population. A total of 95 patients with NAFLD and 78 non-NAFLD subjects were recruited. Genomic DNA was isolated, and polymerase chain reaction and Sanger sequencing were performed using specific primers for the I148M, K434E, E167K, H63D, and C282Y. NAFLD subjects were older when compared to controls and showed the significant association (p = 0.0001). Non-significant association was found between gender (p = 0.26). However, both weight and BMI were found to be associated. Hardy−Weinberg equilibrium analysis confirmed that H63D, I148M, and K434E polymorphisms were associated. Genotype analysis showed only K434E variant was associated with NAFLD and non-NAFLD (OR-2.16; 95% CI: 1.08−4.31; p = 0.02). However, other polymorphisms performed with NAFLD and NASH were not associated (p > 0.05), and similar analysis was found when ANOVA was performed (p > 0.05). In conclusion, we confirmed that K434E polymorphism showed a positive association in the Saudi population.

Endothelial dysfunction in nonalcoholic steatohepatitis with low cardiac disease risk.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. We prospectively evaluated endothelial function by assessing flow-mediated dilatation (FMD) of the brachial artery in patients with biopsy-proven NAFLD. This prospective study included 139 patients (50 healthy controls, 47 patients with steatosis and 42 patients with steatohepatitis), all of whom were nondiabetic. Patients with long-standing or uncontrolled hypertension, smokers, and morbidly obese patients were excluded. The medians (ranges) for vascular FMD in the steatohepatitis, steatosis, and control groups were 6% (0-37.5%), 10.8% (0-40%) and 13.6% (0-50%), respectively. The control group had a higher average FMD than the NAFLD group (15.13% vs 10.46%), and statistical significance was reached when the control and steatohepatitis groups were compared (13.6% vs 6%, p = 0.027). Average alanine aminotransferase was significantly higher in the steatohepatitis group than in the steatosis and control groups (54 (U/L) vs 31 (U/L), p = 0.008). Cholesterol levels were similar between all groups. In the multivariate analysis, FMD (OR = 0.85, p = 0.035) and high triglycerides (OR = 76.4, p = 0.009) were significant predictors of steatohepatitis. In the absence of major cardiac risk factors, we demonstrated better endothelial function in healthy controls, evidenced by a higher FMD of the brachial artery than that of patients with steatohepatitis.

Prevalence of biopsy-proven nonalcoholic fatty liver among patients with gallstone disease.

BACKGROUND/AIM: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are associated with metabolic syndrome. Despite the benign nature of NAFLD, 10% of patients may develop advanced fibrosis and cirrhosis. We aimed to identify the prevalence and factors associated with NAFLD among GD patients in the Saudi population. PATIENTS AND METHODS: This is a single-center, observational cohort study that included patients seen in general surgery clinics at our institution from 2011 to 2017. All liver biopsies were taken at the same time as the cholecystectomy. Demographical and clinical data were prospectively collected from the study population. RESULTS: Of the 301 GD patients in the study, 15% had a normal body mass index (BMI), 29% were overweight, and 56% were obese. There were 143 (47.8%) patients with NAFLD, of which 125 (41.8%) showed steatosis and 18 (6%) had nonalcoholic steatohepatitis. There was a significant positive correlation between NAFLD and age (r = 0.243; P < 0.0001), and BMI (r = 0.242; P < 0.0001). Obese patients with BMI 30-40 kg/m[2] were 2.403 (P = 0.039) more likely to have NAFLD compared with normal BMI patients, and this value increased to 6.145 (P = 0.002) in patients with BMI >40 kg/m[2]. Additionally, patients with T2DM were 2.839 times (P = 0.015) more likely to have NAFLD compared with those who did not. CONCLUSIONS: The prevalence of NAFLD among GD patients is high. High BMI and diabetes are independent factors associated with NAFLD in GD patients. The results suggest that there may be a need for routine liver biopsy in selected patients during cholecystectomy.