Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population.

Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

High prevalence of functional dyspepsia in nonalcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: Gastrointestinal (GI) symptoms are frequent complaints from individuals with nonalcoholic fatty liver disease (NAFLD). Dyspepsia is a universal clinical symptom and is among the most common GI complaints observed in the general population, but its prevalence in the population with NAFLD has not been previously investigated. OBJECTIVE: To compare the prevalence of functional dyspepsia (FD) between patients with NAFLD and controls without liver disease. DESIGN AND SETTING: Cross-sectional study at the Outpatient Liver Clinic, University Hospital, Belo Horizonte, Brazil. METHODS: We included 96 NAFLD patients and 105 controls without liver disease. All participants were assessed for GI symptoms in accordance with the Rome III criteria. Evaluation methods included a questionnaire for FD (validated in Brazil), laboratory tests and upper GI endoscopy. RESULTS: Mean age and sex were similar between the groups. The NAFLD group presented higher frequency of proton-pump inhibitor usage (31.3% vs 4.8%; P < 0.001) and prevalence of FD (25.0% versus 12.4%; P = 0.021). The symptom frequencies were as follows: postprandial distress, 22.9% versus 11.4% (P = 0.030); postprandial fullness, 18.8% versus 10.5% (P = 0.095); early satiation, 8.3% versus 5.7% (P = 0.466); and epigastric pain or burning, 18.8% versus 5.7% (P = 0.004), in NAFLD patients and controls, respectively. Multivariate analysis demonstrated that female sex (odds ratio, OR 6.97; 95% confidence interval, CI: 1.51-32.12; P = 0.013) and NAFLD diagnosis (OR 2.45; 95% CI: 1.14-5.27; P = 0.021) were independently associated with FD occurrence. CONCLUSION: FD occurs more frequently in individuals with NAFLD than in controls without hepatic disease.

PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide, with significant morbidity associated with nonalcoholic steatohepatitis (NASH). Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD progression. AIM: To investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients. METHODS: This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil. The case patients (n = 148) were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease. According to the clinical protocol, patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis (n = 65). Steatohepatitis was confirmed in 54 patients. Individuals who did not have biopsy indication or NASH on histology were considered to have simple steatosis (n = 94). The control group (n = 137) was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical tests. All individuals underwent PNPLA3 and TM6SF2 genotype analysis. RESULTS: PNPLA3 CC, CG and GG genotype frequencies were 37%, 44% and 19%, respectively, in NAFLD patients and were 58%, 31% and 10% in controls (P < 0.001). In a model adjusted for gender, age, body mass index and type 2 diabetes mellitus, the G allele increased the chance of NAFLD (OR = 1.69, 95%CI: 1.21-2.36, P = 0.002) and NASH (OR = 3.50, 95%CI: 1.84-6.64, P < 0.001). The chance of NASH was even higher with GG homozygosis (OR = 5.53, 95%CI: 2.04-14.92, P = 0.001). No association was found between G allele and the features of metabolic syndrome. In histological assessment, PNPLA3 genotype was not associated with steatosis grade, although GG homozygosis increased the chance of significant NASH activity (OR = 17.11, 95%CI: 1.87-156.25, P = 0.01) and fibrosis (OR = 7.42, 95%CI: 1.55-34.47, P = 0.01) in the same adjusted model. TM6SF2 CC, CT and TT genotype frequencies were 83%, 15% and 0.7%, respectively, in NAFLD patients and were 84%, 16% and 0.7% in controls (P = 0.78). The T allele presence was not associated with NAFLD or NASH, and was not associated with histological features. CONCLUSION: PNPLA3 may be involved in susceptibility and progression of NAFLD and NASH in the Brazilian population. More advanced histological liver disease was associated with the G allele. The TM6SF2 genetic variants were not associated with NAFLD susceptibility and progressive histological forms in the population studied, but further studies are required to confirm these findings.

High prevalence of functional dyspepsia in nonalcoholic fatty liver disease: a cross-sectional study

Abstract BACKGROUND: Gastrointestinal (GI) symptoms are frequent complaints from individuals with nonalcoholic fatty liver disease (NAFLD). Dyspepsia is a universal clinical symptom and is among the most common GI complaints observed in the general population, but its prevalence in the population with NAFLD has not been previously investigated. OBJECTIVE: To compare the prevalence of functional dyspepsia (FD) between patients with NAFLD and controls without liver disease. DESIGN AND SETTING: Cross-sectional study at the Outpatient Liver Clinic, University Hospital, Belo Horizonte, Brazil. METHODS: We included 96 NAFLD patients and 105 controls without liver disease. All participants were assessed for GI symptoms in accordance with the Rome III criteria. Evaluation methods included a questionnaire for FD (validated in Brazil), laboratory tests and upper GI endoscopy. RESULTS: Mean age and sex were similar between the groups. The NAFLD group presented higher frequency of proton-pump inhibitor usage (31.3% vs 4.8%; P < 0.001) and prevalence of FD (25.0% versus 12.4%; P = 0.021). The symptom frequencies were as follows: postprandial distress, 22.9% versus 11.4% (P = 0.030); postprandial fullness, 18.8% versus 10.5% (P = 0.095); early satiation, 8.3% versus 5.7% (P = 0.466); and epigastric pain or burning, 18.8% versus 5.7% (P = 0.004), in NAFLD patients and controls, respectively. Multivariate analysis demonstrated that female sex (odds ratio, OR 6.97; 95% confidence interval, CI: 1.51-32.12; P = 0.013) and NAFLD diagnosis (OR 2.45; 95% CI: 1.14-5.27; P = 0.021) were independently associated with FD occurrence. CONCLUSION: FD occurs more frequently in individuals with NAFLD than in controls without hepatic disease.

Current management of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic inflammation and fibrosis. Lifestyle modification involving diet and enhanced physical activity associated with the treatment of underlying metabolic are the main stain in the current management of NAFLD. Insulin-sensitizing agents and antioxidants, especially thiazolidinediones and vitamin E, seem to be the most promising pharmacologic treatment for non-alcoholic steatohepatitis, but further long-term multicenter studies to assess safety are recommended.

Current management of non-alcoholic fatty liver disease / Atualidades no tratamento da doença hepática gordurosa não alcoólica

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic inflammation and fibrosis. Lifestyle modification involving diet and enhanced physical activity associated with the treatment of underlying metabolic are the main stain in the current management of NAFLD. Insulin-sensitizing agents and antioxidants, especially thiazolidinediones and vitamin E, seem to be the most promising pharmacologic treatment for non-alcoholic steatohepatitis, but further long-term multicenter studies to assess safety are recommended.

RESUMO A doença hepática gordurosa não alcoólica (DHGNA) é caracterizada pela deposição significativa de lipídios nos hepatócitos de pacientes que não apresentam história de ingestão alcoólica significativa. É a doença do fígado mais prevalente em populações ocidentais e existe forte associação da DHGNA com a resistência à insulina (RI) e com a síndrome metabólica. O tratamento objetiva reduzir a RI, o estresse oxidativo, a obesidade, a dislipidemia bem como a inflamação e a fibrose hepáticas. O tratamento atual baseia-se principalmente em modificações do estilo de vida, que incluem dieta e prática regular de exercícios físicos, associadas ao tratamento de todos os componentes da síndrome metabólica. Quanto ao tratamento medicamentoso da esteato-hepatite não alcoólica, os agentes insulino-sensibilizantes e os antioxidantes parecem os mais promissores, especialmente as tiazolidinodionas e a vitamina E, mas faltam estudos multicêntricos avaliando sua segurança a longo prazo.