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Background: Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease, and gut microbiota dysbiosis is associated with both of them., Aim: To assess the relationship between gut dysbiosis and cardiovascular risk (CVR) in an experimental model of steatohepatitis., Methods: Adult male Sprague-Dawley rats were randomized to a control group ( n = 10) fed a standard diet and an intervention group ( n = 10) fed a high-fat choline-deficient diet for 16 wk. Biochemical, molecular, hepatic, and cardiac histopathology. Gut microbiota variables were evaluated., Results: The intervention group had a significantly higher atherogenic coefficient, Castelli's risk index (CRI)-I and CRI-II, interleukin-1β, tissue inhibitor of metalloproteinase-1 (all P < 0.001), monocyte chemoattractant protein-1 ( P = 0.005), and plasminogen activator inhibitor-1 ( P = 0.037) than the control group. Gene expression of miR-33a increased ( P = 0.001) and miR-126 ( P < 0.001) decreased in the intervention group. Steatohepatitis with fibrosis was seen in the intervention group, and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance ( P = 0.007), reduction in the mean area of cardiomyocytes ( P = 0.037), and an increase of atrophic cardiomyocytes ( P = 0.007). There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and CVR. The intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota (both P < 0.001) than controls. Nine microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and CVR., Conclusion: The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background/purpose: Cardiovascular disease (CVD) is the leading cause of death among individuals with non-alcoholic fatty liver disease (NAFLD). Recently, NAFLD was renamed metabolic-associated fatty liver disease (MAFLD). This study aimed to compare cardiovascular risk (CVR) and CVD between patients with NAFLD and MAFLD., Methods: Retrospective cross-sectional study of biopsy-proven liver steatosis performed between 2013 and 2018 at a university hospital. Cases were divided into NAFLD or MAFLD and demographic, clinical, and laboratory data were collected to assess CVR (through the atherosclerotic cardiovascular disease risk estimator and atherogenic indices) and CVD., Results: Out of 1233 liver biopsies, 171 (13.9%) presented steatosis. Of these, 109 patients met diagnostic criteria for NAFLD (63.7%) and 154 (90.1%), for MAFLD. In the NAFLD group, 78% of the cases had steatohepatitis, 24.8% had cirrhosis, and 3.7%, hepatocellular carcinoma (HCC). In the MAFLD group, 72.7% of the cases had liver inflammatory activity, 28.6% had cirrhosis, and 13.6% had HCC. In patients with MAFLD and NAFLD, CVR was intermediate/high (36.4 and 25.7%, p = 0.209) and CVD occurred in 20.1 and 12.8% (p = 0.137) of the cases, respectively, with no influence of liver injury severity. We observed a significant increase in high 10-year CVR (p = 0.020) and CVD (p = 0.007) in patients with MAFLD and concomitant viral infection (HCV and/or HBV) compared to cases with MAFLD only., Conclusion: Patients with both NAFLD and MAFLD had intermediate/high CVR, with a high rate of CVD. Patients with MAFLD and concomitant viral infection showed significantly increased CVR and CVD compared to those without viral infection.

Purpose: Obesity is a major risk factor for nonalcoholic fatty liver disease (NAFLD), affecting 25% of the worldwide population. Weight loss through bariatric surgery can improve much of the liver steatosis, inflammation, and fibrosis. However, it is not known whether there is reversal of the elastic fiber deposition process, triggered by hepatic damage and related to worse prognosis., Materials and Methods: Individuals submitted to bariatric surgery at our institution, from March 2016 to June 2017, with intraoperative liver biopsy confirming NAFLD were approached. Those who consented were submitted to a second liver biopsy 1 year later and were included. Specimens were sliced and stained with hematoxylin-eosin and Sirius red for histological assessment according to Brunt's criteria and with orcein for digital analysis morphometrics using ImageJ®. Quantification of elastic fibers was accomplished by corrected integrated density., Results: Thirty-seven patients were included. Body mass index, metabolic markers, NAFLD activity score, and fibrosis improved 1 year after the procedure. The elastic fiber density showed a significant decrease: 239.3 × 10 3 absorbance micrometer 2 (141.08-645.32) to 74.62 × 10 3 absorbance micrometer 2 (57.42-145.17), p = 0.007., Conclusion: Liver elastic fiber density decreases with the reversal of NAFLD through weight loss.

In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.

Objective: Alcoholic liver disease (ALD) is among the leading causes of death from liver disease. Among the factors involved in its pathogenesis are inflammation and increased intestinal permeability. The aim of this study was to assess the effect of Lactobacillus rhamnosus GG (LGG) on hepatic lipid accumulation, activation of inflammasomes, and gut permeability markers in experimental model of ALD with zebrafish. Methods: An experiment was conducted to assess the effective LGG dose capable of promoting intestinal colonization. Animals were divided into three groups ( n  = 64/group): ethanol group (E), ethanol + probiotic group (EP), and control group (C). Groups E and EP were exposed to 0.5% ethanol concentration for 28 days. At the end of this period, animals were euthanized, and livers were collected for Oil Red staining and assessment of the inflammasome system. Intestines were collected for evaluation of gut permeability markers. Results: The dose of 1.55 × 10 6 UFC LGG/fish/d promoted intestinal colonization. Group EP presented lower hepatic lipid accumulation, lower il-1β expression, and higher cldn15a expression when compared to group E. Conclusions: Supplementation with LGG was protective for hepatic steatosis in ALD model. In addition, LGG influenced the modulation of the inflammatory response and markers of gut permeability, improving the gut barrier structure.

Background & Aims: Gaucher disease (GD) is a multisystemic disease. Liver involvement in GD is not well characterised and ranges from hepatomegaly to cirrhosis and hepatocellular carcinoma. We aim to describe, and assess the effect of treatment, on the hepatic phenotype of a cohort of patients with GD types I and II., Methods: Retrospective study based on the review of the medical files of the Gaucher Reference Centre of the Hospital de Clínicas de Porto Alegre, Brazil. Data from all GD types I and III patients seen at the centre since 2003 were analysed. Variables were compared as pre- ("baseline") and post-treatment ("follow-up")., Results: Forty-two patients (types I: 39, III: 3; female: 22; median age: 35 y; enzyme replacement therapy: 37; substrate reduction therapy: 2; non-treated: 3; median time on treatment-MTT: 124 months) were included. Liver enzyme abnormalities, hepatomegaly, and steatosis at baseline were seen in 19/28 (68%), 28/42 (67%), and 3/38 patients (8%), respectively; at follow-up, 21/38 (55%), 15/38 (39%) and 15/38 (39%). MRI iron quantification showed overload in 7/8 patients (treated: 7; MTT: 55 months), being severe in 2/7 (treated: 2/2; MTT: 44.5 months). Eight patients had liver biopsy (treated: 6; MTT: 58 months), with fibrosis in 3 (treated: 1; time on treatment: 108 months) and steatohepatitis in 2 (treated: 2; time on treatment: 69 and 185 months). One patient developed hepatocellular carcinoma., Conclusions: GD is a heterogeneous disease that causes different patterns of liver damage even during treatment. Although treatment improves the hepatocellular damage, it is associated with an increased rate of steatosis. This study highlights the importance of a follow-up of liver integrity in these patients., (© 2020 The Authors.)

Background: Despite being the world's most widely used system for staging and therapeutic guidance in hepatocellular carcinoma (HCC) treatment, the Barcelona clinic liver cancer (BCLC) system has limitations, especially regarding intermediate-grade (BCLC-B) tumors. The recently proposed Hong Kong liver cancer (HKLC) staging system appears useful but requires validation in Western populations., Aim: To evaluate the agreement between BCLC and HKLC staging on the management of HCC in a Western population, estimating the overall patient survival., Methods: This was a retrospective study of HCC patients treated at a university hospital in southern Brazil between 2011 and 2016. Demographic, clinical, and laboratory data were collected. HCC staging was carried out according to the HKLC and BCLC systems to assess treatment agreement. Overall survival was estimated based on the treatment proposed in each system., Results: A total of 519 HCC patients were assessed. Of these, 178 (34.3%) were HKLC-I; 95 (18.3%) HKLC-IIA; 47 (9.1%) HKLC-IIB; 29 (5.6%) HKLC-IIIA; 30 (5.8%) HKLC-IIIB; 75 (14.4%) HKLC-IV; and 65 (12.5%) HKLC-V. According to the BCLC, 25 (4.9%) were BCLC-0; 246 (47.4%) BCLC-A; 107 (20.6%) BCLC-B; 76 (14.6%) BCLC-C; and 65 (12.5%) BCLC-D. The general agreement between the two systems was 80.0% - BCLC-0 and HKLC-I (100%); BCLC-A and HKLC-I/HKLC-II (96.7%); BCLC-B and HKLC-III (46.7%); BCLC-C and HKLC-IV (98.7%); BCLC-D and HKLC-V (41.5%). When sub-classifying BCLC-A, HKLC-IIB, HKLC-IIIA and HKLC-IIIB stages according to the up-to-7 in/out criterion, 13.4, 66.0, 100 and 36.7%, respectively, of the cases were classified as up-to-7 out., Conclusion: In a Western population, the general agreement between the two systems was 80.0%, although in BCLC-B cases the agreement was low, suggesting that some individuals could be candidates for the curative treatment recommended by the HKLC. The authors suggest that the BCLC system should be routinely employed, although for BCLC-B cases it should be associated with the HKLC system., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Occidental diet and metabolic profile seems to increase hepatic fibrosis (HF) in patients with chronic hepatitis C virus (HCV) infection, but there is scarce information about the diet components and their role in this setting., Objectives: This study aims to evaluate the dietary intake, metabolic profile, presence of metabolic syndrome (MetS) and cardiovascular risk in patients with chronic HCV infection according to the presence of fibrosis., Methods: Cross-sectional study which 58 patients with HCV infection without active antiviral therapy and non-cirrhotic were assessed. All patients were subjected to clinical, laboratorial and dietary evaluation, and classified according to the METAVIR score. Patients were divided as the presence of hepatic fibrosis., Results: In this sample, fifty-five percent of patients were females, the average age was 51.6 ± 9.7 years, and 79.3% were carriers of HCV genotype 1. Patients with HF presented higher energy, and fat intake as well as higher glycemic load of meals in comparison to those without HF. Patients with HF presented higher systolic and diastolic arterial pressure and higher levels of insulin., Conclusions: In conclusion, patients with HF had higher total daily energy and total fat intakes, and worse metabolic profile, characterized by a higher insulin resistance and blood pressure.

Context: There are consistent clues of worse results with grafts from older donors, especially in hepatitis C. University of Wisconsin (UW) solution is adopted for liver preservation, but other solutions are being studied, as fructose-1,6-bisphosphate (FBP)., Objective: To determinate the impact of aging of the donor on the cold ischemia injury in rat livers and compare UW and FBP., Methods: Twenty male Wistar rats were studied - 10, aging 20 weeks: 5 to preservation with UW (C-UW) and 5, FBP (C-FBP); and other 10, aging 50 weeks: 5 to UW (E-UW) and 5 to FBP (E-FBP). Rats were anesthesized, submitted to hepatectomy, and graft was kept under 2-4ºC for 8 hours. Liquid samples were taken at 2, 4, 6, and 8 hours, to determine AST and LDH. At the end, in the liver tissue thiobarbituric acid reactive substances and catalase were determined., Results: Average liver weight was similar between controls and the others (12.5 g ± 1.8 and 13.4 g ± 2.0). AST and LDH levels were higher in C-UW group (P<0.05). In the older group, there was a difference between UW and FBP preserved livers related to LDH, but not to AST. Thiobarbituric acid reactive substances were superior in control group than in the older one (P = 0.001). Catalase activity was similar between these groups (P = 0.11), but it was superior in UW preserved animals (P = 0.02)., Conclusion: Livers from older rats were similar to the controls regarding cold ischemia injury in FBP group. Surprisingly, with UW solution there was less cold ischemia injury in the elderly group. When comparing both solutions, FBP provided significantly more protection than UW in the controls. There was a trend to FBP to being better than UW in the elderly group. Further studies with liver from older donors and ischemia and reperfusion are needed.

Objective: This study compared three methods of assessing malnutrition in cirrhotics and correlated nutritional status with clinical outcome., Methods: This cross-sectional study evaluated nutritional status by subjective global assessment (SGA), prognostic nutritional index (PNI), and handgrip strength (HG) in outpatients with cirrhosis (n = 50) and two control groups with hypertension (n = 46) and functional gastrointestinal disorders (n = 49). Patients with cirrhosis were followed for 1 y to verify the incidence of major complications, the need for transplantation, and death., Results: Among patients with cirrhosis, 88% were Child-Pugh A and only 12% were Child-Pugh B. Among these, prevalences of malnutrition were 28% by SGA, 18.7% by PNI, and 63% by HG (P < 0.05). HG, but not SGA or PNI, predicted a poorer clinical outcome in patients with cirrhosis because major complications such as uncontrolled ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome developed in 65.5% of malnourished patients versus 11.8% of well-nourished ones (P < 0.05). No significant differences by any method were seen between the two groups regarding liver transplantation or death., Conclusions: There was a high prevalence of malnutrition in cirrhotic outpatients, especially when assessed by HG, which was superior to SGA and PNI in this study. HG was the only technique that predicted a significant incidence of major complications in 1 y in undernourished cirrhotic patients.

Background: Malnutrition is frequent in cirrhotic patients, and its assessment is difficult. Functional assessment through a dynamometer is a simple method and could minimize these drawbacks. Harris-Benedict prediction formulae estimates the resting energy expenditure but has not been validated for this population. One alternative is the use of indirect calorimetry., Aim: To assess nutritional status in cirrhotic patients and estimates the resting energy expenditure through indirect calorimetry and compares it to Harris-Benedict., Patients and Methods: Thirty four adult hepatitis C cirrhotic outpatients were studied, classified by Child-Pugh and model of end-stage liver disease score. The resting energy expenditure was predicted through Harris-Benedict and measured by indirect calorimetry. Nutritional assessment was done through anthropometry, subjective global assessment, hand-grip strength and a 3-day recall., Results: Fifteen (44.2%) were Child-Pug A, 12 (35.3%) B and 7 (20.6%) C, and 33 (97.1%) had model of end-stage liver disease scores less than 20. The resting energy expenditure predicted was higher than the measured (Harris-Benedict 1404.5 +/- 150.3 kcal; indirect calorimetry 1059.9 +/- 309.6 kcal). The prevalence of malnutrition varied between methods (body mass index, muscle arm circumference, subjective global assessment, triceps skinfold thickness and hand-grip strength: 0; 5.9; 17.6; 35.3 and 79.4%, accordingly). Calories and proteins intake were 80% and 85% of recommended amounts and there was inadequate intake of calcium, magnesium, iron and zinc., Conclusion: Malnutrition was frequent and hand-grip strength seemed to be the most sensitive method for its diagnosis. Calories and protein intakes were inadequate. Considering that the predicted resting energy expenditure was higher than the measured one and the need to offer higher caloric intake, the use of the predicting equation may replace indirect calorimetry.

Background: Orthotopic liver transplantation is the treatment of choice for end-stage liver disease. Malnutrition is common in this population. Early enteral nutrition is not routine in the transplant groups., Aim: To report our experience with the use of early enteral nutrition in patients undergoing orthotopic liver transplantation and also evaluate its safety., Patients/methods: We studied 41 adults submitted to orthotopic liver transplantation. Pre- orthotopic liver transplantation nutritional assessment was accomplished by the subjective global assessment and grip strength. Enteral nutrition was begun in 12 hours. Oral feeding was initiate gradually as soon as possible., Results: We studied 35 individuals, with an average of age of 45.5 years (8.93). The prevalence of malnutrition in orthotopic liver transplantation was of 77.1% determined by subjective global assessment, and 100% by grip strength. Early enteral nutrition was begun in all of the individuals in up to 12 hours, mode 10.9 hours, and maintained exclusively by medium period of 2.6 days (2.2). Oral feeding was obtained in the medium period of 9.5 days (9.7). Early enteral nutrition provided total caloric intake in 97% of the cases. Intolerance to the enteral feeding occurred in five individuals (14.2%), and in four of them it was resumed successfully after 12 hours. The prevalence of respiratory infection was of 28.6%. In only two patients (5.7%) there was aspirative bronchopneumonia., Conclusions: Early enteral nutrition is an effective method in the provision of calories and safe in application to patients undergoing orthotopic liver transplantation.