BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.

Despite a growing number of investigative studies on pancreatic fat deposition, there remains no clear indication regarding the clinical relevance of fat infiltration in the pancreas, also called fatty pancreas (FP). An individual’s body weight is correlated with their pancreatic weight. Moreover, lipid infiltration causes disorders that compromise not only morphology but also metabolic functions. Fat infiltration leads to insulin resistance, type II diabetes mellitus, and pancreatic cancer; however, knowledge about pancreatic fat content and aspects related to the clinical profile remains unclear in the literature. The present review describes the current knowledge of FP, including its pathophysiology and clinical implications, as well as lifestyle changes in FP.

The nonalcoholic fatty liver disease (NAFLD) affects approximately 20%-30% of general population and is even more prevalent among obese individuals. The risk factors mainly associated with NAFLD are diseases related to the metabolic syndrome, genetics and environment. In this review, we provide a literature compilation evaluating the evidence behind dietary components, including calories intake, fat, protein, fibers and carbohydrate, especially fructose which could be a trigger to development and progression of the NAFLD. In fact, it has been demonstrated that diet is an important factor for the development of NAFLD and its association is complex and extends beyond total energy intake.

This multi-center retrospective study evaluated the long-term effects of pioglitazone therapy on liver stiffness, hepatic steatosis, and other non-invasive biomarkers in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). A total of 65 patients from three Brazilian public hospitals treated with pioglitazone at doses of 30‒45 mg/day up to 10-years were retrospectively analyzed. Hepatic parameters, including Vibration-Controlled Transient Elastography (VCTE), Controlled Attenuation Parameter (CAP), and FibroScan-AST score, were evaluated before and after treatment. Patients were stratified into two groups based on treatment duration: 1‒3 years and 4‒10 years. Significant reductions in Alanine Aminotransferase (ALT) and Gamma-Glutamyl Transferase (GGT) levels were observed in both treatment groups, indicating improvement in liver enzyme profiles. A significant decrease in CAP levels was observed only in the 4‒10 year group (p = 0.002), suggesting a reduction in liver steatosis. Improvement in FAST™ scores was observed in both groups (1‒3 years, p = 0.042; 4‒10 years, p = 0.012). In logistic regression analysis, dyslipidemia was associated with a non-significant trend toward higher odds of liver stiffness reduction (adjusted OR = 1.92, 95 % CI 0.58‒6.45, p = 0.284). These findings highlight both the metabolic and hepatic benefits of long-term pioglitazone therapy. They reinforce its potential as a cost-effective and accessible treatment option for MASLD, particularly in resource-limited settings where newer therapeutic alternatives are unavailable.

Previous large-scale genetic studies identified single-nucleotide polymorphisms (SNPs) of the membrane bound O-acyltransferase domain containing 7 (MBOAT7) and patatin-like phospholipase domain containing 3 (PNPLA3) genes as risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD). However, this has not yet been investigated in Brazilian patients. In this study, we evaluated the association between the PNPLA3 variant rs738409 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis in MASLD etiology. In parallel, we also aimed to evaluate a protective SNP of the mitochondrial amidoxime-reducing component 1 (MTARC1) gene. We also evaluated TM6SF2 rs58542926, GCKR rs1260326 and rs780094, and HSD17B13 rs72613567 and they were not associated with liver fibrosis. The study was conducted at the Department of Gastroenterology and Nutrology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), and included 113 patients with liver fibrosis (F0–F1), 99 patients with significant liver fibrosis (F2–F4), and 90 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, the PNPLA3 GG genotype was more frequent in F2–F4 (23%) and F0–F1 (22%) patients than in controls (9%; p = 0.02). The MBOAT7 TT genotype was significantly associated with fibrosis, with a prevalence of 23% in F2–F4 patients versus 10% in F0–F1 and 11% in controls (p = 0.01). This association was confirmed by regression analysis (OR = 5.01 95% CI: 1.86–13.49; p = 1.41 × 10⁻³). The protective MTARC1 AA genotypes were more frequent in controls (52%) when compared to patients with fibrosis (5% p = 2.76 × 10⁻²⁰).

The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role ...