INTRODUCTION:The PNPLA3 rs738409 C>G polymorphism has been associated with fibrosis and steatosis in Chronic Hepatitis C (CHC) patients. However, its impact on Hepatocellular Carcinoma (HCC) development in this population remains unclear. This study aimed to evaluate the impact of the PNPLA3 polymorphism on the risk of HCC development in CHC patients in Brazil. METHODS:This retrospective case-control study included 235 CHC patients with advanced fibrosis, 119 with HCC, and 116 without HCC. The PNPLA3 polymorphism was analyzed using both the dominant and recessive models. Multivariate logistic regression was performed to assess factors independently associated with HCC development. RESULTS:The HCC group exhibited a higher proportion of male patients (p < 0.0001), alcohol abuse (p < 0.001), tobacco consumption (p < 0.0001), and ALBI grade 2‒3 (p < 0.001). The PNPLA3 genotype frequencies were CC 45.4%, CG 46.2% and GG 8.4% in the HCC group, and CC 51.7%, CG 40.5% and GG 7.8% in the non-HCC group. No significant differences in genotype frequencies were observed for the dominant model (p = 0.33) or the recessive model (p = 0.92). Gender (p = 0.001), tobacco consumption (p < 0.001), and ALBI score (p = 0.012) were identified as independent factors associated with HCC development. However, the PNPLA3 G allele was not an independent factor associated with HCC risk in either the univariate analysis (OR = 1.15, 95% CI 0.63‒2.08, p = 0.65) or the multivariate analysis (OR = 0.99, 95% CI 0.49‒2.00, p = 0.98). CONCLUSION:The PNPLA3 rs738409 polymorphism was not associated with HCC development in CHC patients with advanced fibrosis in the Brazilian population. Further studies are required to confirm this finding.

Introduction and Objectives Recent data regarding the prevalence of significant and advanced MASLD-related fibrosis in Brazil is unknown. We aimed to evaluate the prevalence of significant (SF, F≥2) and advanced (AF, F≥F3) fibrosis according to its different geographic regions, and the accuracy of FIB-4 and liver elastography by VCTE (Fibroscan, Echosens, Fr) for the diagnosis of SF and AF respectively. Patients and Methods This was a sectional study in ten Brazilian University Centers (Southeast, n=6; Northeast, n=1; South, n=3). Demographic, clinic, laboratory, liver stiffness measurement by VCTE (Fibroscan®, Echosens, Fr), and liver biopsy (LB) results were registered. The AUROCs for FIB-4 and VCTE regarding SF and AF were plotted with LB as a reference. Results 2905 patients were included (53% women, 64% white, 51 ± 14 yrs, 44% T2DM) According to LB (n=2122), most form the South (72%; p<0.001), 75% were F0-F1, 12% F2, 9% F3 and 4% F4. Most data from VCTE are from Southeast (n = 1084, 85%). LSM< 8 kPa, between 8 and 12 kPa and ≥ 12 kPa was observed in 44%, 25% and 31% of patients. Most patients from the Southeast region presented a LSM ≥ 12 kPa (p = 0.01). FIB-4 score was <1.3 in 81% of patients. For F3, the AUROC for FIB-4 and LSM were 0.75 (95% CI: 0.70-0.80; p<0.01) and 0.72 (95% CI: 0.68-0.77; p<0.01) respectively and for F2, 0.67 (95% CI: 0.62-0.72; p<0.01) for FIB-4 and 0.64 (95% CI: 0.60-0.69; p<0.01) for VCTE. Conclusions Most MASLD patients with AF are from the Southeast. VCTE is primarily available in the Sotheast, affecting the stepwise fibrosis stratification of MASLD in other regions and justifying the higher proportion of LB in the South. The accuracy of FIB-4 and liver elastography by Fibroscan® is good for diagnosing AF, but not for SF.

Introduction and Objectives: Lean MASLD affects 10–15% of patients, presenting metabolic alterations despite normal BMI.Characterize the MASLD phenotype according to BMI. Materials and Methods: 68 patients with MASLD were divided into groups: lean (n=18); overweight (n=28); obese (n=22). Were evaluated: anthropometric measurements, comorbidities, liver fibrosis by transient elastography, body composition by DEXA, and muscle strength by handgrip dynamometry. The Kruskal-Wallis test was used for statistical analysis. Results: Female sex was predominant. There were no significant differences in mean age or the prevalence of comorbidities (T2DM/IR/dyslipidemia) among groups (p>0.05), except for arterial hypertension, more prevalent in the obese (p≤0.05). Aminotransferase levels were similar: ALT (p=0.440) and AST (p=0.427). Mild hepatic fibrosis (F0/F1) predominated in all groups (p=0.418); however, there was a trend toward higher liver stiffness suggesting advanced fibrosis in the lean (22.2%, 7.14%, 13.64%; p=0.340). Visceral adipose tissue area >100 cm2 was observed in 38.9% of lean, compared to 100% in the other groups (p≤0.05). Low muscle mass was more prevalent in the lean (55.6%, 14.3%, 4.5%; p≤0.05), and sarcopenia, defined as the coexistence of low lean mass and reduced muscle strength, was also more prevalent in lean (27.8%, 7.14% in overweight, 4.5% in obese; p≤0.05). Conclusions: Lean MASLD presents a higher prevalence of sarcopenia and a distinct body composition profile, despite similar comorbidities and age compared to other groups. These findings highlight the role of lean mass in the pathophysiology of lean MASLD and underscore the limitations of BMI as a sole evaluative parameter.

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).

BACKGROUND AND AIMS: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). METHODS: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. RESULTS: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). CONCLUSIONS: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.

Introduction and Objectives: MASLD ranges from isolated steatosis (STE) to steatohepatitis (MASH), cirrhosis (CIR) and hepatocellular carcinoma (HCC). Non-invasive markers have limited ability to identify different stages. Extracellular vesicles (EVs) could be a useful tool. This study aims to evaluate EVs lipid signature in disease progression. Patients and Methods: EVs were isolated from patients with STE (n=25), MASH without fibrosis (MASH; n=25), CIR (n=25) and HCC (n=18), and compared to controls (CON; n=25). Lipidomics was performed by mass spectrometric analysis of sphingolipids, oxysterols and bile acids. Results: Figure 1 shows a heatmap of lipid profiles. C24DHC was lower in MASLD vs CON, suggesting early alterations in membrane lipid homeostasis. C18-SM, C20-SM, C22-SM and Cer24-0 decreased in CIR and HCC vs others, indicating progressive disruption of sphingolipid metabolism with progression. C17-SM and C261-SM were significantly reduced in HCC vs CON, reflecting extensive lipid remodeling in late-stage. 7KC levels were significantly increased in HCC vs others, consistent with enhanced oxidative stress specifically associated with hepatocarcinogenesis. Bile acids TCA and CA were higher in HCC vs others, pointing to dysregulation of bile acid pathways in late-stage disease. All differences, p<0.05. Conclusions: Lipid composition of EVs may reflect key molecular changes during MASLD progression. The reduction of sphingolipids and accumulation of oxysterols and bile acids in advanced stages suggest disrupted lipid metabolism, oxidative stress, and hepatocellular dysfunction. These findings support the potential of EV lipidomics as a non-invasive tool for disease staging and mechanistic insight.

OBJECTIVE:To determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in men with spinal cord injury (SCI) and to identify the independent factors associated with steatosis. SUBJECTS AND METHODS:This is a cross-sectional study. Inclusion criteria were males over 18 years of age with chronic traumatic SCI enrolled in a rehabilitation programme. A multivariable logistic regression model was constructed using a stepwise variable selection procedure. RESULTS:After exclusion criteria, 160 participants were included. The prevalence of MASLD was 19%. Men with hepatic steatosis were older, had a higher prevalence of hypogonadism, obesity and diabetes mellitus. Additionally, they exhibited significantly higher levels of ALT, AST and GGT. The mean time since the SCI was 7.8 years in those with steatosis and 4.3 years in those without. Multiple logistic regression analysis revealed age (p < 0.001 OR: 1.07), time since SCI (p = 0.025, OR: 1.11) and total testosterone ≤ 300 ng/dL (p = 0.036, OR: 3.35) as significant independent variables associated with steatosis. CONCLUSION:Our findings suggest a prevalence of MASLD in men with SCI similar to that of the general population. Independent factors associated with steatosis were age, time since injury and total testosterone. Notably, individuals with testosterone levels ≤ 300 ng/dL were 3.35 times more likely to have steatosis compared to those with higher testosterone levels.

Extracellular vesicles (EVs) and microRNAs, involved in intercellular communication, have emerged as potential biomarkers in liver diseases. This study aimed to evaluate EV characteristics and microRNA transport across the full spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD). 168 patients with MASLD and 50 controls were recruited. Biochemical and clinical variables were evaluated. EVs were isolated from serum and characterized by nanoparticle tracking analysis, flow cytometry, and Western blotting. Using MiRWalk 3.0 and the TarPmiR algorithm, candidate EV-associated microRNAs related to MASLD were identified. The expression of miR-4758, miR-188, miR-1226, and miR-122, was evaluated in EVs and serum. EV size and concentration varied significantly across disease stages (p<0.001 and p<0.05, respectively), with early MASLD dominated by exosome, and later stages showing a shift toward microvesicles. In MASLD patients, interestingly, miR-122 was lower in EVs compared to serum (p<0.05). In steatosis, it was higher in serum than EVs (p<0.05), without significant differences in later stages. miR-122 in EVs increased in association with GGT and cholesterol, and decreased with elevated creatinine. Serum miR-122 was also elevated in patients with high cholesterol. In MASLD miR-4758 was higher in EVs than in serum (p<0.05), expressed in steatosis and cirrhosis (p<0.05), suggesting it is a good disease marker, and detected exclusively in serum in HCC (p<0.05). miR-4758-EVs increased with high glucose. MiR-188 and miR-1226 were exclusively expressed in serum (p<0.05), and miR-1226 was elevated in patients with high cholesterol. EV size was reduced in individuals with high triglycerides and albumin, suggesting interaction between EVs, biochemical parameters and disease stage. These findings suggest that microRNA expression and transport in EVs and serum vary across MASLD stages and associate with key biochemical parameters, supporting the clinical value of jointly assessing both compartments as potential biomarkers to distinguish early disease from advanced stages such as HCC. See also the graphical abstract(Fig. 1).

Introduction and Objectives Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, with fibrosis progression being a key determinant of clinical outcomes. Genetic polymorphisms, such as MTARC1 (rs2642438), have been implicated in modifying fibrosis risk. This study aimed to evaluate the protective role of the MTARC1 AA genotype in protecting against significant fibrosisin Brazilian patients with MASLD. Patients and Methods A total of 212 biopsy-proven MASLD patients were included, classified into, Group 1 (F0-F1, n=110): No significant fibrosis. Group 2 (F2-F4, n=102): Significant fibrosis. Additionally, 90 healthy individuals served as controls. Genotyping for MTARC1 (rs2642438) was performed using real-time PCR. Logistic regression models were used to assess the association between MTARC1 genotypes and significant fibrosis, adjusting for metabolic and clinical factors. Results The protective AA genotype was significantly more frequent in the control group (52%) than in MASLD patients (5%, p = 2.76×10⁻20).Patients carrying the AA genotype had an 81% lower risk of developing significant fibrosis (OR = 0.19; 95% CI: 0.08 - 0.45; p < 0.001).No significant associations were observed for the GG and GA genotypes regarding fibrosis progression. Conclusions The MTARC1 rs2642438 AA genotype confers strong protection against fibrosis in MASLD patients, suggesting a potential role in risk stratification and personalized management. Future studies with larger cohorts are needed to confirm these findings and elucidate the molecular pathways involved.

Introduction and Objectives The PNPLA3 rs738409 C>G polymorphism has been associated with hepatocellular carcinoma (HCC) and liver cirrhosis regardless of the etiology, although the association was stronger with non-viral etiologies. However, the influence of PNPLA3 polymorphism on Hepatitis C Virus (HCV) and whether this polymorphism could be a risk factor for HCV-related HCC is not well defined. We aimed to evaluate the influence of the PNPLA3 rs738409 C>G polymorphism on the risk of HCC occurrence in HCV patients in Brazil. Materials and Methods This study included 90 patients with HCV-related cirrhosis and HCC who underwent liver transplantation or resection at a tertiary center in Brazil and 111 patients non-HCC with HCV-related cirrhosis, as the control group. The rs738409 polymorphism was detected in the DNA extracted from patients' blood samples using the TaqMan assay. All clinical data were collected using the Research Electronic Data Capture (REDCap) tool. The statistical analyses were performed using Jamovi software version 2.3.23. Results In the HCV+HCC group there was a higher proportion of male gender (79.1% vs. 45.9%, p<0.001), history of alcoholism (80.5% vs. 22.5%, p<0.001) and smoking (68.9% vs. 25.2%, p<0.001), however there was no statistical difference in age (p=0.519) and BMI (p=0.403) between both groups. The genotype frequencies of the rs738409 polymorphism in the HCV+HCC group was CC 41,2% CC and CG/GG 58,8% vs. controls CC 49,5% and CG/GG 50,5%. The presence of the G allele was not an independent factor associated with the risk of HCC occurrence (r=0,199, p=0.53). Conclusions Even in an admixed population such as the Brazilian, there was no association between the PNPLA3 rs738409 C>G polymorphism and the risk of developing HCV-related HCC, as previously shown in published studies in caucasian and oriental population.

Conflict of interest: No Introduction and Objectives: Hepatitis C virus (HCV) still is the leading cause of hepatocellular carcinoma (HCC) in Brazil, even after the new treatments with DAAs. HCC surveillance is recommended based on liver fibrosis, whereby patients with advanced fibrosis are suitable for screening. Therefore, there is a need for tools to improve risk stratification in this population. Our aim was to assess whether the ALBI score performed at first evaluation of patients with HCV-related cirrhosis could stratify the risk of developing HCC. Patients / Materials and Methods: This study included 108 patients with HCV-related cirrhosis evaluated in the outpatient units in Hospital de Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Clinical data from the first evaluation and ALBI score with first the laboratory tests were used for the statistical analysis. The last follow-up was at the last HCC screening image in patients who did not develop HCC and at HCC diagnosis in those who did. The statistical analyses were performed using Jamovi software version 2.3.23. Results and Discussion: During follow-up, with a mean duration of 5.28 ± 4.72 years, 32 patients developed HCC. Patients who developed HCC had significantly lower albumin values (p=0.039) and a higher proportion of ALBI grade 2 (p=0.036) at the first outpatient assessment. Evaluating HCC risk over time by Kaplan-Meier, patients with ALBI grade 2 had a significantly higher risk of developing HCC than patients with ALBI grade 1 (p=0.019) when assessed at 1 year (17% vs. 8.2%), 2 years (29.3% vs. 15.4%), 5 years (40.9% vs. 21.4%) and 10 years (47.4% vs. 23.9%). Patients with ALBI grade 2 had a two-fold higher risk of developing HCC during follow-up (OR 2.27, 95%CI 1.12-4.59, p=0.023). Conclusions: Assessment of baseline ALBI score can improve HCC risk stratification in patients with HCV-related cirrhosis.

ABSTRACT Background: This study aimed to assess the frequency and intensity of anxious and depressive symptoms in patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This is a descriptive and cross-sectional study, resulting from 106 patients from the Hepatology outpatient clinic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil without a history of alcohol abuse, verified by the alcohol use disorders identification test (AUDIT). These were assessed using the sociodemographic data sheet, Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Scale (HAM-D). Results: A total of 69.8% were women and 30.2% were men, with a mean age of 61 years. The majority (71.7%) discovered MASLD through routine exams, presenting as comorbidities: Type 2 diabetes mellitus (59.4%), Dyslipidemia (49.1%), Arterial hypertension (68.9%), Obesity (61.3%) and Metabolic syndrome [MetS (63.2%)]. The HADS scale indicates 34% probability of anxiety and 33% depressive symptoms. The Hamilton’s scales of intensity indicates 63.9% severe anxiety and 54.3% severe depression. There is also a relationship between anxiety, depression and the female gender, as well as between depression and MetS. Conclusion: The findings point to the presence of anxiety and depression in more than one third of MASLD patients, most with severe symptoms. The group is concentrated in the elderly, with many comorbidities, including MetS. There was a positive correlation between anxiety, depression and being female; also, being significant between MetS and depression.

Conflict of interest No Introduction and Objectives Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, has shown efficacy in improving indirect markers of liver steatosis, inflammation, and fibrosis. It also addresses systemic and adipose tissue insulin resistance in patients with type 2 diabetes and metabolic dysfunction-associated fatty liver disease (MASLD). This study aims to evaluate whether sustained consumption of pioglitazone over 12-24 months can improve liver stiffness in individuals diagnosed with biopsy- proven metabolic dysfunction-associated steatohepatitis (MASH). Patients / Materials and Methods Retrospective data from 56 MASLD patients who received pioglitazone treatment for 12-24 months (15-30 mg daily) were gathered from three public hospitals in Brazil. Vibration-controlled transient elastography [VCTE (FibroscanTM)] was performed before and after pioglitazone treatment as a non-invasive method to monitor disease progression. Additionally, a thorough analysis of both laboratory and clinical data was conducted. Results and Discussion Most participants were female (63%, n = 35) and obese (BMI 31.1 ± 5.2) with a mean age of 58.4 ± 11.4 years. Initially, participants mostly had hypertension (71%, n = 40) and type II diabetes (61%, n = 34). During the second evaluation, the number of subjects with dyslipidemia and statin use increased. Initially, the liver stiffness measurement (LSM) median was 8.1 kPa (Min: 2.8; Max: 35.3) and 7.2 kPa (Min: 3.5; Max: 32.9) at the second evaluation. Prolonged pioglitazone treatment demonstrated LSM attenuation in 63% of cases (n = 35), resulting in an absolute reduction ranging from 0.1 to 14.4 kPa and a relative reduction ranging from 1.25% to 40.8%. Further analysis comparing the group with improved versus the group with worsened liver stiffness showed a decrease in the CAP parameter, FAST score, and levels of ALT, AST, GGT, TG, and ferritin. Conclusions The administration of pioglitazone for 12 to 24 months effectively reduced hepatic inflammation and enhanced VCTE parameters in 63% of cases.

Conflict of interest No Introduction and Objectives Recent studies have indicated that certain polymorphisms may be associated with the progression of metabolic dysfunction-associated steatotic liver disease (MASLD).To construct a predictive fibrosis score and evaluate the association of the risk genetic polymorphisms rs738409 PNPLA3, rs58542926 TM6SF2, rs641738 MBOAT7, rs1260326 and rs780094 GCKR, rs72613567 HSD17B13 and rs2642438 MARC1 in MASLD. Patients / Materials and Methods This cross-sectional and retrospective study analyzed 212 biopsy-proven MASLD patient samples from the Hospital das Clínicas, Faculty of Medicine, University of São Paulo. Samples were divided into two groups: Group 1: absent and mild fibrosis (F0-1, n=113) and Group 2: significant and advanced fibrosis (F2-4, n=99). Demographic, laboratory, and histological data were compared, along with their association and frequency with the polymorphisms. Genotyping was performed by real-time PCR allele discrimination, and statistical analysis was conducted using Jasp® and Jamovi® software. The significance level adopted was 5%. Results and Discussion Most patients were female (146; 68.9%) with an average age of 56 years and were obese (BMI of 30.7). Group 1 had a higher frequency of dyslipidemia and NAS score 0-4 (71%), higher total cholesterol levels, and lower levels of AST, ALT, GGT, and alpha-fetoprotein compared to Group 2 (p < 0.05). The regression model (ROC Curve) used the TT genotype of the MBOAT7 gene associated with age, ALT, AST, GGT, TG, HDL, LDL, and total cholesterol to predict fibrosis (AUC: 0.77; Sen: 0.61; Spe: 0.79; Acc: 0.71; R²: 0.14) (Fig. 1A). Another model with AFP (n = 76) showed (AUC: 0.80; Sen: 0.67; Spe: 0.83; Acc: 0.76; R²: 0.24) (Fig. 1B). The polymorphisms of the PNPLA3, TM6SF2, GCKR, HSD17B13, and MARC1 genes did not demonstrate risk or protection in this cohort. Conclusions This study underscores the rs641738 MBOAT7 polymorphism as a potential predictor of fibrosis in MASLD, highlighting its value in clinical assessment and management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the fastest growing cause of hepatocellular carcinoma (HCC). Several risk factors have been identified, including older age, male gender, Hispanic ethnicity, metabolic syndrome components, certain medications, tobacco and alcohol use. Genetic polymorphisms, such as PNPLA3 , TM6SF2 , and MBOAT7 variants, have been associated with increased risk of MASLD-related HCC. More recently, genetic risk scores (GRS) based on single-nucleotide polymorphisms (SNPs) have shown potential in predicting HCC risk. So far, there are a few studies that analyzed the impact of GRS in MASLD-related HCC, but they seem very promising in stratifying patients according to the risk of developing HCC. Although current GRS models have limitations, in the future, with a better understanding of these SNPs, and the discovery of other variants, they could integrate more comprehensive risk prediction models, including various data, such as etiology, fibrosis grade, serum markers, comorbidities and genetics, which will improve HCC risk prediction in MASLD.

Introduction and Objectives: Fibrosis stage is the most important prognostic factor in non-alcoholic fatty liver disease (NAFLD). Although liver biopsy is the gold standard for staging fibrosis, it is a difficult tool to use on follow-up evaluations. Non-invasive tests (NITs) were developed to first stratify patients at risk for advanced fibrosis but were not validated for follow-up. This study aimed to evaluate liver fibrosis progression, NITs variations over time and their correlation with clinical outcomes (hepatic decompensation, hepatic and extra-hepatic neoplasm; cardiovascular events and mortality). Materials and Methods: Retrospective cohort of 138 patients with biopsy proven non-alcoholic steatohepatitis (NASH). Patients underwent clinical, physical, and laboratory examinations and NIT assessments (FIB-4 and transient elastography - TE). Fibrosis progression was estimated using TE. NIT variations over time were compared with the development of clinical outcomes. Results: 138 patients were analyzed. The median age was 65 years and the median body mass index was 32Kg/m² at diagnosis. Seventy-seven patients (55%) had diabetes and 82 (59%) had hypertension at diagnosis. Fifty-six patients (40%) had advanced fibrosis (≥F3) and 18 (13%) of them had cirrhosis at biopsy. The median time of follow-up was 10 years. One hundred nineteen patients performed TE at the end of the follow-up. Fifty-nine patients progressed to cirrhosis (49,6%). Initial NAFLD activity score (NAS) was statistically associated with fibrosis progression. Twenty-four patients (17%) developed a clinical outcome. The fibrosis stage at diagnosis was associated with cirrhosis decompensation but not associated with cardiovascular events. Fibrosis progression assessed with elastography (>11,5kPa) was associated with portal hypertension development. FIB-4 elevation during follow-up (>2,7) was associated with cirrhosis decompensation. Conclusions: High-risk NAFLD patients have a high prevalence of fibrosis progression and clinical outcomes. NITs such as FIB-4 and TE might be useful tools for the evaluation of disease progression and risk of hepatic decompensation. More prospective studies are needed to better define NITs cut-offs for risk of clinical outcomes.

•In this review, we described different murine models of carcinogenesis: classic models, new transgenic and combined models, that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic physiopathological, and environmental abnormalities. •Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches. •Cholangiocarcinoma has been highlighted, with an increase in prevalence. This review has an important role in understanding the pathophysiology and the development of new drugs. Background - This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective - A review through MEDLINE and EMBASE was performed to assess articles until August 2022.Methods - Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results - In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion - Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

Introduction and Objectives: Metabolic dysfunction is influenced by several factors in patients with traumatic spinal cord injury (SCI), such as physical inactivity, modification in body mass distribution, reduction of androgenic hormones, modification in intestinal microbiota, and neuro-autonomic dysfunction itself. This study aimed to determine the prevalence of MAFLD and the independent factors associated with liver steatosis in patients with traumatic SCI. Materials and Methods: Patients with SCI hospitalized for rehabilitation were randomly assigned to participate. Blood samples were collected, and an abdominal ultrasound was performed. Exclusion criteria were non-traumatic spinal cord injury, less than one year since the injury and less than 18 years old. Patients answered a questionnaire about alcohol drinking and tobacco smoking, as well as a physical activity score. Student´s t-test or Mann Whitney test was used to compare groups (fatty liver and non-fatty liver). The chi-square test or Fisher's exact test was used to test the homogeneity between the proportions. Variables with p< 0.10 in the simple regression analysis were selected and the multiple logistic regression model was done. The significance level used for the tests was 5%. Results: Two hundred and twenty-five individuals were included initially, but 30 patients were excluded according to exclusion criteria. The mean age was 37 years and 82,6% were men. The prevalence of MAFLD was 17,4% in this population. Multiple logistic regression model showed that age (OR: 1,06 CI 1,03 – 1,09), body mass index (BMI) (OR: 1,21 CI 1,1 – 1,34), AST (OR: 1,07 CI 1,02 – 1,12), and HDL (OR: 0,942 CI 0,90 -0,98) were independent predictors of fatty liver in this population. Conclusions: The prevalence of MAFLD in traumatic spinal cord injured patients was not higher than in the general population. Age, BMI, AST and HDL were predictors of fatty liver. This population will have better long-term survival once we better understand metabolic dysfunction.