Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review.

.: Preventive effect of metformin in hepatocellular carcinoma (HCC) is not entirely clear. We aimed to evaluate the use of metformin as a protective factor of HCC in diabetic patients. .: We carried out an electronic search on PUBMED/MEDLINE, Web of Science and LILACS databases, with no limit of date, from April 2017 to January 2019. Eligible studies included cohort and case-control studies. We adressed data about the use of metformin on the risk of HCC development. Two independent reviewers extracted the data. We evaluated the quality of studies by using the Newcastle-Ottawa scale and carried out a meta-analysis using random-effects models. .: The electronic searches identified 747 studies. After reading abstracts and titles, we excluded 327 duplicated papers and 383 irrelevant references. Eight studies were selected; four case-control and four cohort studies. All studies have observed that the therapy with metformin was associated with a lower risk of HCC, compared with non-metformin therapy. Five articles reported that patients treated with insulin, or insulin secretagogues, presented increased risk of HCC compared to those treated with metformin. One study found that not only statin but also aspirin reduced the risk of HCC, if combined with metformin. A meta-analysis, using the case-control studies, found a combined Odds Ratio of 0.468; 95% CI 0.275-0.799 for the association between HCC and the use of metformin. .: The use of metformin was associated with a reduced risk of HCC, and it may be a relevant factor for preventing HCC in diabetic patients.

Recreational Anabolic-Androgenic Steroid Use Associated With Liver Injuries Among Brazilian Young Men.

BACKGROUND: The recreational use of anabolic-androgenic steroids (AAS) has reached alarming levels among healthy people. However, several complications have been related to consumption of these drugs, including liver disorders. OBJECTIVE: To evaluate the prevalence of liver injuries in young Brazilian recreational AAS users. METHODS: Between February/2007 and May/2012 asymptomatic bodybuilders who were ≥18 years old and reported AAS use for ≥6 months were enrolled. All had clinical evaluations, abdominal ultrasound (AUS), and blood tests. RESULTS: 182 individuals were included in the study. The median age (interquartile range) was 26.0 years (22.0-30.0) and all were male. Elevated liver enzyme levels were observed in 38.5% (n = 70) of AAS users, and creatine phosphokinase was normal in 27.1% (n = 19) of them. Hepatic steatosis was observed by AUS in 12.1% of the sample. One individual had focal nodular hyperplasia and another had hepatocellular adenoma. One case each of hepatitis B and C virus infection was found. A diagnosis of toxic liver injury was suggested in 23 (12.6%) AAS users without a history of alcohol or other medications/drugs consumption, or evidence of other liver diseases. CONCLUSIONS/IMPORTANCE: Young Brazilian recreational AAS users presented a wide spectrum of liver injuries that included hepatotoxicity, fatty liver, and liver neoplasm. They also presented risk factors for liver diseases such as alcohol consumption and hepatitis B and C virus infection. The results suggest that the risk of AAS use for the liver may be greater than the esthetic benefits, and demonstrate the importance of screening AAS users for liver injuries.

The influence of concomitant use of alcohol, tobacco, cocaine, and anabolic steroids on lipid profiles of Brazilian recreational bodybuilders.

Anabolic-androgenic steroids (AAS) are used to enhance physical performance and/or appearance. The aim of this study was to evaluate the influence of the concomitant use of alcohol, tobacco, cocaine, and AAS on blood lipid profiles of 145 asymptomatic male bodybuilders from the Northeast region of Brazil. Interviews, clinical exams, and serological evaluations were performed on all participants between 2007 and 2009. All subjects' self-reported use of testosterone or its derivatives, 118 individuals reported alcohol intake, 27-reported cigarette smoking, and 33 confirmed cocaine use. Four subjects were users of all drugs at the same time. Higher levels of total cholesterol and LDL-cholesterol were observed among concomitant users of alcohol, tobacco, cocaine, and AAS. The study's limitations are noted.

Hepatobiliary disease after bone marrow transplant: A cross-sectional study of 377 patients.

BACKGROUND: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis. AIMS: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre. METHODS: This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria. RESULTS: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001). CONCLUSIONS: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death.

From Nonalcoholic Steatohepatits to Steatotic Liver Disease: A Long Way.

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Hepatobiliary disease after bone marrow transplant.

INTRODUCTION: Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others. AREA COVERED: Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. EXPERT OPINION: Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.

Non-alcoholic fatty liver disease and periodontal disease: A systematic review and meta-analysis of cross-sectional studies.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, comprising hepatic steatosis, and non-alcoholic steatohepatitis. Periodontal disease (PD) may be a risk factor for the evolution of liver cirrhosis. This study aimed to evaluate the association between NAFLD and PD.We searched in Pubmed, Scopus, Cochrane, and Lilacs databases with descriptors (Non-alcoholic Fatty Liver Disease OR (non-alcoholic AND Fatty Liver AND disease) OR Nonalcoholic Steatohepatitis) AND (Periodontal Disease OR Gingivitis OR Periodontitis) from January 2021 to September 2021. We selected, by the abstract, cross-sectional, cohort (prospective and retrospective), and case-control studies that address periodontal disease in patients with Non-alcoholic Fatty Liver Disease, and aged ≥ 18 years. The search was without the restriction of language and publication time.The search resulted in 954 articles. After applying the selection criteria, five cross-sectional studies remained. A metanalysis combined the study estimates of periodontal disease in NAFLD, by using the random effects. The Odds Ratio (1.91; 95% CI 1.21-3.02; P = 0.006) indicates that the chance of presenting Periodontal disease is 91% higher in individuals with NAFLD when compared with individuals without NAFLD. There are few studies with appropriate methodology to produce sound evidence about the causal relationship between the use of NAFLD and PD, however, studies support the association. So, dental staff must be aware of this association for better management of periodontal disease in patients with NAFLD.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso).

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Diet and intestinal bacterial overgrowth: Is there evidence?

The intestinal microbiota and its role in health and disease processes have been the subject of several studies. It is known that changes in the intestinal microbiota occur due to several factors, such as the use of medication, age, lifestyle and diseases, which can modify intestinal homeostasis and lead to excessive growth of bacteria in the small intestine, triggering a clinical condition called small bowel bacterial overgrowth (SIBO). Individuals with SIBO may present gastrointestinal symptoms ranging from nausea, diarrhea and/or constipation, and flatulence to distension and abdominal pain, resulting from poor absorption of nutrients or changes in intestinal permeability. The gold-standard treatment is based on the use of antibiotics to eradicate bacterial overgrowth. Some studies have evaluated diets in the treatment of SIBO; however, the studies are of low methodological quality, making extrapolation of the results to clinical practice unfeasible. Thus, there is still not enough scientific evidence to support a specific type of diet for the treatment of SIBO.

PROBIOTIC, PREBIOTIC OR SYMBIOTIC SUPPLEMENTATION IMPACTS ON INTESTINAL MICROBIOTA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW.

BACKGROUND: Supplementation with probiotics, prebiotics and symbiotics has shown positive effects on clinical markers and risk factors for non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: To evaluate the effect of supplementation with probiotic, prebiotic or symbiotic on intestinal microbiota in NAFLD patients. METHODS: Two investigators conducted independently search for articles in the Medline databases, via PubMed, Web of Science, Embase, Scopus, Lilacs, Central Cochrane Library, Clinical Trials.gov and on the Ovid platform for the gray literature search. RESULTS: A total of 3,423 papers were identified by searching the electronic databases; 1,560 of them were duplicate and they were excluded; 1,825 articles were excluded after reading the title and abstract. A total of 39 articles were select to reading, however only four articles met the eligibility criteria to include in this systematic review. Three of the included studies that used prebiotic or symbiotic supplementation showed that after the intervention there were changes in the intestinal microbiota pattern. Only in one study such changes were not observed. A high risk of bias was observed in most assessments. CONCLUSION: Although there is a possible change in the gut microbiota of individuals with NAFLD after supplementation with symbiotics or prebiotics, a clinical indication as part of NAFLD treatment is not yet possible.

Prevalence of sarcopenia using different methods in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sarcopenia is a clinical condition associated with several liver diseases and it includes non-alcoholic fatty liver disease (NAFLD) in its broad spectrum as steatosis, steatohepatitis and fibrosis. However, the criteria to define sarcopenia are diverse, and even those established in consensus have been discussed regarding their performance in making an accurate diagnosis. AIM: To evaluate the prevalence of sarcopenia, using different methods, in patients with NAFLD, and its association with clinical-anthropometric parameters. METHODS: This was an observational study of outpatients with NAFLD. Sarcopenia was defined by the European Working Group Consensus on Sarcopenia in Older People of 2010 (EWGSOP1) and 2018 (EWGSOP2). The skeletal muscle index was used to estimate muscle mass, handgrip strength was assessed using the dynamometer and physical performance by walking a distance of four meters at usual walking speed. The non-invasive fibrosis scores, fibrosis-4 (FIB-4) index and Aspartate aminotransferase to platelet ratio index (APRI), were used to assess the absence and presence of fibrosis. RESULTS: Fifty-seven individuals with NAFLD were evaluated, the mean age (SD) was 52.7 (11.3) years and 75.4% were female. Fibrosis assessed by FIB-4 and APRI was observed in 3.7% and 16.6% of patients with NAFLD, respectively. The diagnosis of sarcopenia was identified only by EWGSOP1 in 3.5% of NAFLD patients, and the prevalence of probable/pre-sarcopenia was higher using the EWGSOP2 consensus at 26.3%, when compared to 1.8% with EWGSOP1. Sarcopenia defined by EWGSOP1, was associated with grade I steatosis, but without overweight (P < 0.05). An association between sarcopenia and fibrosis was not observed (P > 0.05). EWGSOP2 showed a greater number of patients with probable sarcopenia, and who were overweight (12 (80.0%)), with a higher degree of steatosis [11 (73.3%) and presence of fibrosis (1 (6.7%), FIB-4 and 3 (20.0%), APRI] compared to EWGSOP1 [1 (100%), 0 (0.0%), 0 (0.0%), FIB-4 and 0 (0.0%), APRI, respectively]. CONCLUSION: The present study showed that sarcopenia in NAFLD was not predominant in patients without fibrosis, by both diagnostic methods. In addition, the prevalence of probable sarcopenia also depends on the method applied.

Anthropometric clinical indicators of visceral adiposity as predictors of nonalcoholic fatty liver disease.

OBJECTIVE: This study aims to evaluate the role of anthropometric clinical indicators of visceral adiposity as predictors of NAFLD, identifying the cutoff points based on gender. METHODS: This was a cross-sectional study conducted in patients with or without NAFLD. Waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), Conicity Index (C Index), and lipid accumulation product (LAP) were evaluated. RESULTS: A total of 107 individuals were evaluated, of which 46.7% were diagnosed with NAFLD. Individuals with NAFLD presented higher values of WC, BMI, C Index, LAP, and WHtR when compared with those without NAFLD (p<0.05). For the total sample, the indicators WC, BMI, WHtR, LAP, and C Index had an area under the receiver operator characteristic curve (AUC) above 0.87, with no difference in the prediction of NAFLD in both sexes. WHtR (AUC=0.934) was the indicator of visceral adiposity with the best discriminatory power for NAFLD, followed by LAP (0.919), WC (0.912), C Index (0.907), and BMI (0.877). CONCLUSIONS: The anthropometric clinical indicators of visceral adiposity showed high performance, especially the WHtR indicator, as NAFLD predictors.

Muscle mass and cellular membrane integrity assessment in patients with nonalcoholic fatty liver disease.

OBJECTIVE: To evaluate the association between muscle mass depletion and compromising of the cell membrane integrity and clinical-anthropometric characteristics in patients with nonalcoholic fatty liver disease. METHODS: This observational study evaluated waist circumference, body mass index, and waist-to-height ratio in patients with nonalcoholic fatty liver disease. Skeletal mass index corrected by weight and impairment of cell membrane integrity were assessed using bioelectrical impedance analysis. RESULTS: In 56 patients, muscle mass depletion was observed in 62.5% and cell membrane impairment in 28.6%. The metabolic syndrome and elevated aspartate aminotransferase were the only clinical factors associated with mass depletion (p<0.05). The linear regression analysis showed association between skeletal mass index and waist-to-height ratio and waist circumference, after adjustments (p<0.05). The phase angle value was not different between those with and without mass depletion, and also it did not have correlation with skeletal mass index and clinical parameters (p>0.05). CONCLUSIONS: The prevalence of mass depletion and cell membrane impairment was higher in patients with nonalcoholic fatty liver disease. The muscle mass depletion was associated with central obesity, aspartate aminotransferase elevated, and metabolic syndrome; however, the phase angle is not associated with clinical and anthropometric data.

Fatty liver disease in severe obese patients: diagnostic value of abdominal ultrasound.

AIM: To evaluate the sensitivity and specificity of abdominal ultrasound (US) for the diagnosis of hepatic steatosis in severe obese subjects and its relation to histological grade of steatosis. METHODS: A consecutive series of obese patients, who underwent bariatric surgery from October 2004 to May 2005, was selected. Ultrasonography was performed in all patients as part of routine preoperative time and an intraoperative wedge biopsy was obtained at the beginning of the bariatric surgery. The US and histological findings of steatosis were compared, considering histology as the gold standard. RESULTS: The study included 105 patients. The mean age was 37.2+/-10.6 years and 75.2% were female. The histological prevalence of steatosis was 89.5%. The sensitivity and specificity of US in the diagnosis of hepatic steatosis were, respectively, 64.9% (95% CI: 54.9-74.3) and 90.9% (95% CI: 57.1-99.5). The positive predictive value and negative predictive value were, respectively, 98.4% (95% CI: 90.2-99.9) and 23.3% (95% CI: 12.3-39.0). The presence of steatosis on US was associated to advanced grades of steatosis on histology (P=0.016). CONCLUSION: Preoperative abdominal US in our series has not shown to be an accurate method for the diagnosis of hepatic steatosis in severe obese patients. Until another non-invasive method demonstrates better sensitivity and specificity values, histological evaluation may be recommended to these patients undergoing bariatric surgery.

Preoperative upper gastrointestinal endoscopy in obese patients undergoing bariatric surgery: is it necessary?

BACKGROUND: Obesity has been shown to be an important risk factor for several gastrointestinal diseases. However, the indication for preoperative upper gastrointestinal endoscopy (UGE) for all patients before bariatric surgery is controversial. The aim of the present study was to evaluate the spectrum of gastrointestinal diseases detected during preoperative UGE in patients undergoing bariatric surgery and the relevance of this procedure. METHODS: A series of severely obese patients, who had undergone UGE before Roux-en-Y gastric bypass from October 2004 to May 2005 were consecutively enrolled in this study. The demographic and clinical data and endoscopic diagnoses were evaluated. Gastric biopsies were performed in elective patients according to the endoscopic findings. RESULTS: The study included 162 patients, 69.8% of whom were women. The mean age was 36.7 +/- 10.8 years. Abnormal findings were observed in 77.2% of patients. Esophagitis was present in 38.9%, gastritis in 51.2% (erosive gastritis in 49.3% and nonerosive gastritis in 50.7%), gastric ulcers in 1.9%, hiatal hernia, in 8.6%, gastric polyp in .6%, and duodenitis in 6.8% of patients. No patient had esophageal or gastric varices. Helicobacter pylori infection was investigated in 96 patients and was detected in 37.5%. Gastric biopsies were performed in 36 patients, with chronic inflammation found in 72.2%, inflammatory activity in 30.6%, and intestinal metaplasia in 11.1%. Glandular atrophy was not found in any patient. CONCLUSION: The results of our study have shown that the spectrum of gastrointestinal diseases observed in severely obese patients who underwent bariatric surgery is broad. Although this issue remains highly controversial, these findings suggest that systematic preoperative UGE and H. pylori testing should be performed in all patients scheduled to undergo bariatric surgery.

Anthropometric indicators of visceral adiposity as predictors of non-alcoholic fatty liver disease: A review.

The objective was to critically analyze studies that evaluated the predictive capacity of indicators of visceral adiposity in non-alcoholic fatty liver disease (NAFLD). The bibliographic research was carried out using the electronic database PubMed, LILACS and SciELO, references of selected articles. Although we found few studies, they have already used several indicators of visceral adiposity as waist circumference, waist-to-hip ratio, waist-to-height ratio, Lipid accumulation product, Body Shape Index, Body Roundness Index and most them were good predictors of NAFLD. Thus, the anthropometric indicators may contribute for the diagnosis of NAFLD in a simple, low-cost and non-invasive way, allowing early therapeutic measures to prevent the evolution to non-alcoholic steatohepatitis.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Hyperferritinemia in patients with nonalcoholic fatty liver disease.

OBJECTIVE:: In liver diseases, hyperferritinemia (HYF) is related to injured cells in acquired and genetic conditions with or without iron overload. It is frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it is necessary to define the mean of HYF to establish the better approach for them. The present study evaluated the significance of elevated ferritin in patients with NAFLD and steatohepatitis (NASH). METHOD:: The review was performed using search instruments of indexed scientific material, including MEDLINE (by PubMed), Web of Science, IBECS and LILACS, to identify articles published in Portuguese, English and Spanish, from 2005 to May, 2016. Studies eligible included place and year of publication, diagnose criteria to NAFLD, specifications of serum ferritin measurements and/or liver histopathologic study. Exclusion criteria included studies with patients with alcohol consumption ≥ 20 g/day and other liver diseases. RESULTS:: A total of 11 from 30 articles were selected. It included 3,564 patients and they were cross-sectional, retrospective, case series and case-control. The result's analyses showed in 10 of these studies a relationship between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis and insulin resistance. CONCLUSION:: Hyperferritinemia in patients with NAFLD/NASH is associated more frequently with hepatocellular injury than hemochromatosis. These data suggest the relevance to evaluate carefully HYF in patients with NAFLD/NASH to establish appropriate clinical approach.