Epidemiology and risk factors for histopathologic characteristics of non-alcoholic fatty liver disease in South America.

BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region. AIM: To explore the associations between clinical characteristics and histopathological features of NAFLD METHODS: This was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex. RESULTS: The median age was 53 years (IQR: 41-62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2 . Sixty-seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively). CONCLUSIONS: In the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence.

Probiotic Supplementation, Hepatic Fibrosis, and the Microbiota Profile in Patients with Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: Promising results in improvement of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) have been identified following probiotic (PRO) treatment. OBJECTIVES: To evaluate PRO supplementation on hepatic fibrosis, inflammatory and metabolic markers, and gut microbiota in NASH patients. METHODS: In a double-blind, placebo-controlled clinical trial, 48 patients with NASH with a median age of 58 y and median BMI of 32.7 kg/m2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 109 colony forming units and Bifidobacterium lactis 1 × 109 colony forming units) or a placebo daily for 6 mo. Serum aminotransferases, total cholesterol and fractions, C-reactive protein, ferritin, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and leptin were assessed. To evaluate liver fibrosis, Fibromax was used. In addition, 16S rRNA gene-based analysis was performed to evaluate gut microbiota composition. All assessments were performed at baseline and after 6 mo. For the assessment of outcomes after treatment, mixed generalized linear models were used to evaluate the main effects of the group-moment interaction. For multiple comparisons, Bonferroni correction was applied (α = 0.05/4 = 0.0125). Results for the outcomes are presented as mean and SE. RESULTS: The AST to Platelet Ratio Index (APRI) score was the primary outcome that decreased over time in the PRO group. Aspartate aminotransferase presented a statistically significant result in the group-moment interaction analyses, but no statistical significance was found after the Bonferroni correction. Liver fibrosis, steatosis, and inflammatory activity presented no statistically significant differences between the groups. No major shifts in gut microbiota composition were identified between groups after PRO treatment. CONCLUSIONS: Patients with NASH who received PRO supplementation for 6 mo presented improvement in the APRI score after treatment. These results draw attention to clinical practice and suggest that supplementation with PROs alone is not sufficient to improve enzymatic liver markers, inflammatory parameters, and gut microbiota in patients with NASH. This trial was registered at clinicaltrials.gov as NCT02764047.

Serum Ferritin and NAFLD in Patients Undergoing Bariatric Surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a challenge in public health, as the prevalence of obesity and overweight has been increasing. It has been observed that serum ferritin (SF) levels are commonly elevated in NAFLD patients. PURPOSE: To assess the relationship between SF levels and NAFLD, exploring the role of SF as a non-invasive marker of NAFLD. METHODS: Clinical, anthropometric, laboratory, and histological data of patients with obesity who underwent bariatric surgery in a reference center in Brazil were retrospectively evaluated. Data were collected in the preoperative period up to the first year postoperatively. RESULTS: A total of 431 patients were analyzed. The prevalence of hyperferritinemia was 18% in the preoperative period and 14% 1 year after the surgery. After multiple regression analysis, elevated SF was not an independent predictor of steatosis, non-alcoholic steatohepatitis (NASH), or liver fibrosis. CONCLUSIONS: Increased SF levels are common in patients with NAFLD; however, SF was not considered an independent predictor of steatosis, NASH, or fibrosis.

Transjugular intrahepatic portosystemic shunt with transhepatic portal vein puncture guided by ultrasound: a technical alternative.

OBJECTIVE: Evaluation of an alternative technique to perform transjugular intrahepatic portosystemic shunt (TIPS), using abdominal ultrasound to guide portal puncture. METHODS: Retrospective analysis of TIPS performed from January 2014 to December 2018 in an interventional radiology service. TIPS were performed according to the classic technique, except at the moment of portal branch puncture, when abdominal ultrasound was used to guide it, visualized its path within the parenchyma in real-time. Qualitative and quantitative variables were analyzed considering a 95% confidence interval and application of the Student's t-test with a significance level of P < 0.05. RESULTS: Forty-one TIPS were performed. The technical success rate of ultrasound guidance in portal puncture was 100.0%. After its performance, a reduction in the portosystemic pressure gradient was observed, with an initial gradient average of 18.8 mmHg (12-25 ± 3.6 mmHg) and a final gradient of 9.2 mmHg (5-14 ± 2.4 mmHg). The mean values for the TIPS execution time, fluoroscopy time and the radiation dose, verified through the dose area product, were 65.2 ± 46.7 min, 25 ± 14.1 min and 85.6 ± 70 Gy cm2, respectively. There were no complications related to the inadvertent puncture of nontarget structures or deaths due to complications resulting from TIPS. CONCLUSION: The results demonstrate that the portal transhepatic puncture guided by the abdominal ultrasound is an effective and safe procedure and results in time of execution, time of fluoroscopy and radiation dose below the current reference values of the conventional procedure.

Fibromax and inflamatory markers cannot replace liver biopsy in the evaluation of non-alcoholic fatty liver disease.

BACKGROUND: To evaluate the performance of a non-invasive test (Fibromax™, Ferring Pharmaceutical, Saint-Prex, Switzerland) and inflamatory markers (IL-1ß, IL-6, IL-8, TNF-α, MCP-1) in the diagnosis and staging of patients with non-alcoholic fatty liver disease. METHODS: Patients older than 18 years with steatosis were prospectively evaluated at a tertiary hospital in southern Brazil. Liver biopsy, Fibromax™ test and inflamatory markers (IL-1ß, IL-6, IL-8, TNF-α, MCP-1) were performed. Measures of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used, considering liver biopsy as the gold standard. RESULTS: Seventy-three Fibromax™ tests were analyzed. SteatoTest presented a sensitivity of 95.5% and PPV of 97.0% for the diagnosis of steatosis. NashTest obtained a sensitivity of 83.3%, specificity of 37.5%, PPV of 90.9% and NPV of 23.1% for the diagnosis of non-alcoholic steatohepatitis (NASH). FibroTest presented a sensitivity of 38.9%, specificity of 92.7%, PPV of 63.6% and NPV of 82.3% to evaluate advanced fibrosis. In the evaluation of patients with grade 2 and 3 steatosis, ROC analyses showed an area under the curve (AUROC) for SteatoTest of 0.68 (P=0.015). NashTest AUROC was 0.59 (P=0.417) for the evaluation of NASH. FibroTest AUROC was 0.79 (P<0.001) for advanced fibrosis. Kappa coefficient values for SteatoTest, NashTest and FibroTest were not statistically significant. Thirty-seven patients performed also analysis of the inflamatory markers, showing that patients with inflammatory activity grade 2-3 on liver biopsy had significantly higher levels of IL6 (P=0.016) and lower TNF-α (P=0.034), but there was no other difference when analysed fibrosis or steatosis. CONCLUSIONS: The Fibromax™ test and the inflamatory markers (IL-1ß, IL-6, IL-8, TNF-α, MCP-1) did not present a satisfactory performance to be considered a good alternative to replace liver biopsy in the evaluation of non-alcoholic fatty liver disease.

Albumin in the management of hepatic encephalopathy: A systematic review and meta-analysis.

Introduction and objectives It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with albumin might be associated with improvement in survival, control of ascites, reduction in the incidence bacterial infections, renal dysfunction, hepatic encephalopathy (HE) and hyponatremia, as well as reduction in length of hospitalization in patients with cirrhosis and ascites. The objective of the present study is to evaluate the role of albumin in the management of HE. Materiales and methods:: This is a systematic review of randomized controlled trials that evaluated the use of albumin in adult patients with cirrhosis and HE. The search for eligible studies was performed in MEDLINE, EMBASE, and Cochrane CENTRAL databases until June 2020. The outcomes of interest were the complete reversal of HE and mortality. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. Results: This systematic review was registered at the PROSPERO platform (CRD42020194181). The search strategy retrieved 1,118 articles. After reviewing titles and abstracts, 24 studies were considered potentially eligible, but 22 were excluded after full-text analysis. Finally, 2 studies were included. In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR = 0.60; 95% confidence interval - CI = 0.38-0.95, p = 0.03) and mortality (RR = 0.54; 95% CI = 0.33-0.90, p = 0.02). Conclusion: Albumin administration improves HE and reduces mortality in patients with cirrhosis and HE.

VITAMIN B12 AND HOMOCYSTEINE LEVELS IN PATIENTS WITH NAFLD: A SYSTEMATIC REVIEW AND METANALYSIS.

BACKGROUND: The vitamin B12 absorption can be affected in patients with nonalcoholic fatty liver disease (NAFLD), and low serum vitamin B12 levels has been related to the high homocysteine (HCY) levels and to the degree of NAFLD. OBJECTIVE: To carry out a systematic review and metanalysis of serum vitamin B12 and HCY levels in patients with NAFLD. METHODS: Original studies including serum vitamin B12 and HCY levels in humans with NAFLD were included. The searches were performed in four databases. RESULTS: 159 studies were identified, and after excluding the duplicates and non-eligible titles, eight original articles were included. Six out of eight showed higher B12 levels in NAFLD patients (404.9±136.2 pg/mL in relation to controls 353.91±117.3 pg/mL). Seven of the eight studies also showed higher HCY levels in NAFLD patients (14.2±3.44 umol/L in relation to controls 11.05±3.6 umol/L). The results for serum vitamin B12 and HCY levels were submitted to metanalysis, showing no difference in the vitamin B12 levels between patients with NAFLD and controls. However, the levels of Hcy were higher in NAFLD patients than in controls. CONCLUSION: There was no relashionship between the vitamin B12 levels and NAFLD. The levels of HCY were significantly higher in patients with NAFLD, suggesting this could be a potential marker for liver damage.

Vitamina B12 e homocisteína em pacientes com DHGNA: revisão sistemática e metanálise / Vitamin b12 and homocysteine levels in patients with nafld: a systematic review and metanalysis

ABSTRACT BACKGROUND: The vitamin B12 absorption can be affected in patients with nonalcoholic fatty liver disease (NAFLD), and low serum vitamin B12 levels has been related to the high homocysteine (HCY) levels and to the degree of NAFLD. OBJECTIVE: To carry out a systematic review and metanalysis of serum vitamin B12 and HCY levels in patients with NAFLD. METHODS: Original studies including serum vitamin B12 and HCY levels in humans with NAFLD were included. The searches were performed in four databases. RESULTS: 159 studies were identified, and after excluding the duplicates and non-eligible titles, eight original articles were included. Six out of eight showed higher B12 levels in NAFLD patients (404.9±136.2 pg/mL in relation to controls 353.91±117.3 pg/mL). Seven of the eight studies also showed higher HCY levels in NAFLD patients (14.2±3.44 umol/L in relation to controls 11.05±3.6 umol/L). The results for serum vitamin B12 and HCY levels were submitted to metanalysis, showing no difference in the vitamin B12 levels between patients with NAFLD and controls. However, the levels of Hcy were higher in NAFLD patients than in controls. CONCLUSION: There was no relashionship between the vitamin B12 levels and NAFLD. The levels of HCY were significantly higher in patients with NAFLD, suggesting this could be a potential marker for liver damage.

RESUMO CONTEXTO: A absorção de vitamina B12 pode ser afetada em pacientes com doença hepática gordurosa não alcoólica (DHGNA), e baixos níveis séricos de vitamina B12 têm sido relacionados a níveis elevados de homocisteína (HCI) ao grau de DHGNA. OBJETIVO: Realizar revisão sistemática e metanálise dos níveis séricos de vitamina B12 e de HCI em pacientes com DHGNA. MÉTODOS: Estudos originais que incluíssem avaliação dos níveis séricos de vitamina B12 e de HCI em humanos com DHGNA foram incluídos. As buscas foram realizadas em quatro bases de dados. RESULTADOS: Foram identificados 159 estudos e, após exclusão das duplicatas e dos não elegíveis, oito artigos originais foram incluídos. Seis dos oito artigos apresentaram níveis mais elevados de vitamina B12 nos pacientes com DHGNA (404,9±136,2 pg/mL) em relação aos controles (353,91±117,3 pg/mL). Sete dos oito estudos determinaram os níveis de HCI, estando aumentados em pacientes com DHGNA (14,2±3,44 umol/L) em relação aos controles (11,05±3,6 umol/L). Os resultados dos níveis séricos de vitamina B12 e HCI foram submetidos à metanálise, mostrando que não há diferença nos níveis de vitamina B12 entre os pacientes com DHGNA e os controles. No entanto, os níveis de HCI foram maiores nos pacientes com DHGNA do que nos controles. CONCLUSÃO: Não houve relação entre DHGNA e nível sérico de vitamina B12. Os níveis de HCI foram significativamente maiores em pacientes com DHGNA, sugerindo que esse poderia ser um potencial marcador de lesão hepática.

The prognostic impact of different stages of acute kidney injury in patients with decompensated cirrhosis: a prospective cohort study.

AIM: To assess the impact of the different stages of acute kidney injury (AKI) on the prognosis of patients hospitalized with decompensated cirrhosis. METHODS: This was a prospective cohort study of consecutive patients admitted in two tertiary hospitals in southern Brazil. Participants were considered eligible if they were admitted for acute decompensation of cirrhosis. The main exposure factor was the onset of AKI. AKI stages were defined according the European recommendations. The outcomes evaluated were survival time and death rates at 28 and 90 days from hospital admission. A χ2 test was used to compare mortality between groups. Kaplan-Meier survival analyses were undertaken assessing time to event as days from AKI diagnosis to death or liver transplant. RESULTS: Two hundred and five patients were included in the study, and 121 met the criteria for AKI. Patients with AKI 1b, AKI 2 and AKI 3 had higher 90-day mortality than patients without AKI (P = 0.008, P < 0.001 and P < 0.001, respectively). However, there was no difference in 90-day mortality when patients with AKI 1a were compared with those without AKI (P = 0.742). The mean survival of patients without AKI was higher than that of patients with AKI 1b (591.4 and 305.4 days, respectively, P = 0.015), while there was no significant difference between the mean survival of patients without AKI and that of patients with AKI 1a (591.4 and 373.6 days, respectively, P = 0.198). CONCLUSION: Only AKI ≥1b seems to substantially impact mortality of patients hospitalized for acute decompensation of cirrhosis.

Treatment of hepatitis B virus infection in chronic infection with HBeAg-positive adult patients (immunotolerant patients): a systematic review.

Recently, a controversial approach suggesting the early treatment of chronic infection with hepatitis B "e" antigen-positive patients with hepatitis B virus (HBV) infection, has been proposed. The objective of this study is to systematically review medical literature regarding treatment of HBV infection in adult chronic infection with HBeAg-positive patients. A systematic review was performed according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Original studies that evaluated the effect of antivirals in adult chronic infection with HBeAg-positive patients were included. The outcomes of interest were viral load suppression, the loss/seroconversion of HBeAg, the loss/seroconversion of hepatitis B surface antigen, and the development of cirrhosis or hepatocellular carcinoma. The search for eligible studies was performed in Excerpta Medica dataBASE, PubMed and Cochrane databases until January 2020, without language or date restriction. The risk of bias was evaluated using the Newcastle-Ottawa Scale for observational studies and the Revised Cochrane Risk-of-Bias Tool for randomized controlled trials. Two hundred ninety-six articles were retrieved. After analyzing titles and abstracts, 287 articles were excluded and nine were considered potentially eligible. From these, five were excluded after full-text analysis. Finally, four articles were included. Only two were randomized controlled trials. All studies were carried out in Asian patients. Results were variable with regard to viral load, negativation/seroconversion of HBeAg and HBsAg. One study demonstrated that treated patients developed cirrhosis or hepatocellular carcinoma less frequently than untreated individuals. Overall, the studies were of poor quality. In conclusion, the present systematic review demonstrated that, at present, there is not enough evidence to recommend treating this population of patients.

Avaliação de pacientes com hepatite autoimune atendidos em ambulatório de referência do sul do Brasil / Evaluation of patients with autoimmune hepatitis in a specialized outpatient clinic in southern brazil

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by necroinflammation and autoimmune etiology. Studies evaluating the characteristics of patients with AIH are scarce in Brazil. OBJECTIVE: Our objective was to evaluate the profile of patients with AIH in a specialized center in Southern Brazil and to verify factors related to treatment response. METHODS: this was a retrospective cohort study, which analyzed demographic, epidemiological, clinical, laboratory, and histologic data. Patients with AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (IAIHG) were included. In liver biopsies, the degree of fibrosis, histological activity, presence of hepatocyte rosettes, plasma cell infiltrates, and confluent necrosis were evaluated. In the statistical analysis, the significance level was 5%. RESULTS: Forty adults patients diagnosed with AIH were included. The evaluated population predominantly consisted of women (75.0%) and the average age at diagnosis was 44.2 years. The association with extrahepatic autoimmune diseases occurred in 20.0% of cases. Clinically, 35.0% of patients presented with acute onset hepatitis, 37.5% with cirrhosis, and 27.5% with other forms of presentation. The most common clinical manifestation was jaundice (47.5%). Thirty-five patients were treated, and of these, 97.1% used prednisone combined with azathioprine. The average treatment time was 2.7 years. Response to treatment was complete or partial in 30 (85.7%) and absent in 5 (14.3%) patients. There was no statistically significant difference when evaluating response to treatment in relation to forms of presentation, histological findings, and the presence of autoantibodies. Regarding fibrosis, regression was observed in 18.75% of the cases. CONCLUSION: Most patients with AIH were young at presentation and of female sex. The association with extrahepatic autoimmune diseases and cirrhosis at presentation was seen in a considerable proportion of patients. Treatment was effective, but there were no clinical, histological or serological parameters capable of predicting treatment response.

RESUMO CONTEXTO: A hepatite autoimune (HAI) é uma doença hepática crônica, de caráter necroinflamatório e etiologia autoimune. Os estudos que avaliam as características de pacientes com HAI são escassos no Brasil. OBJETIVO: Nosso objetivo foi avaliar o perfil dos pacientes com HAI atendidos em um centro de referência do sul do Brasil e verificar fatores relacionados à resposta ao tratamento. MÉTODOS: Este foi um estudo de coorte retrospectivo, que analisou dados demográficos, epidemiológicos e clínicos. Nas biópsias hepáticas, foram avaliados o grau de fibrose, a atividade histológica, a presença de rosetas, de infiltrado plasmocitário e de necrose confluente. Na análise estatística, o nível de significância foi de 5%. RESULTADOS: Foram incluídos 40 pacientes adultos com diagnóstico de HAI. Houve predomínio do sexo feminino (75,0%), e a média de idade no diagnóstico foi de 44,2 anos. A associação com doenças autoimunes extra-hepáticas ocorreu em 20,0% dos casos. Clinicamente, 35,0% dos pacientes se apresentaram sob forma de hepatite aguda, 37,5% com cirrose e 27,5% com outras formas de apresentação. A manifestação clínica mais comum na apresentação foi a icterícia (47,5%). Trinta e cinco pacientes foram tratados, sendo que destes, 97,1% utilizaram prednisona associada com azatioprina. A média do tempo de tratamento foi 2,7 anos. A resposta ao tratamento foi completa ou parcial em 30 (85,7%) e ausente em 5 (14,3%) pacientes. Não houve diferença estatisticamente significativa quando avaliada a resposta ao tratamento em relação à forma de apresentação, aos achados histológicos e à presença de autoanticorpos. Em relação à fibrose, foi observada regressão em 18,75% dos casos. CONCLUSÃO: A maioria dos pacientes era jovem no momento do diagnóstico e do sexo feminino. A associação com doenças autoimunes extra-hepáticas e com cirrose na apresentação foi vista em uma parcela considerável dos casos. O tratamento foi eficaz, mas não houve parâmetros clínicos, histológicos ou sorológicos capazes de prever a resposta ao tratamento.

EVALUATION OF PATIENTS WITH AUTOIMMUNE HEPATITIS IN A SPECIALIZED OUTPATIENT CLINIC IN SOUTHERN BRAZIL.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by necroinflammation and autoimmune etiology. Studies evaluating the characteristics of patients with AIH are scarce in Brazil. OBJECTIVE: Our objective was to evaluate the profile of patients with AIH in a specialized center in Southern Brazil and to verify factors related to treatment response. METHODS: this was a retrospective cohort study, which analyzed demographic, epidemiological, clinical, laboratory, and histologic data. Patients with AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (IAIHG) were included. In liver biopsies, the degree of fibrosis, histological activity, presence of hepatocyte rosettes, plasma cell infiltrates, and confluent necrosis were evaluated. In the statistical analysis, the significance level was 5%. RESULTS: Forty adults patients diagnosed with AIH were included. The evaluated population predominantly consisted of women (75.0%) and the average age at diagnosis was 44.2 years. The association with extrahepatic autoimmune diseases occurred in 20.0% of cases. Clinically, 35.0% of patients presented with acute onset hepatitis, 37.5% with cirrhosis, and 27.5% with other forms of presentation. The most common clinical manifestation was jaundice (47.5%). Thirty-five patients were treated, and of these, 97.1% used prednisone combined with azathioprine. The average treatment time was 2.7 years. Response to treatment was complete or partial in 30 (85.7%) and absent in 5 (14.3%) patients. There was no statistically significant difference when evaluating response to treatment in relation to forms of presentation, histological findings, and the presence of autoantibodies. Regarding fibrosis, regression was observed in 18.75% of the cases. CONCLUSION: Most patients with AIH were young at presentation and of female sex. The association with extrahepatic autoimmune diseases and cirrhosis at presentation was seen in a considerable proportion of patients. Treatment was effective, but there were no clinical, histological or serological parameters capable of predicting treatment response.

Role of zinc supplementation in the management of chronic liver diseases: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Zinc deficiency has been associated with poor prognosis in chronic liver disease. This systematic review and meta-analysis aimed to evaluate the role of zinc supplementation in the management of chronic liver diseases. MATERIALS AND METHODS: We searched MEDLINE, LILACS, EMBASE, and Cochrane CENTRAL databases from inception to August 2018. We included randomized controlled trials evaluating adult patients with chronic liver disease of any etiology receiving zinc supplementation. Studies with other designs or evaluating chronic conditions other than liver disease were excluded. Two reviewers independently screened and extracted data from eligible studies. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized studies. RESULTS: Of 1315 studies screened, 13 were included. Six assessed chronic hepatitis C treatment, with a relative risk of 0.83 indicating no protective effect of zinc supplementation on the improvement of sustained virological response. Three evaluated response to hepatic encephalopathy treatment, with a relative risk of 0.66 indicating a favorable effect of zinc supplementation on clinical improvement of this condition. Of four studies evaluating the management of cirrhosis, two analyzed the effect of zinc supplementation on serum albumin levels, with no statistical difference between zinc and placebo groups. CONCLUSIONS: Clinical trials assessing zinc supplementation in liver diseases do not show benefits in terms of clinical improvement or disease halting. There are possible benefits of zinc supplementation on hepatic encephalopathy, however, this is based on limited evidence. This research question is still open for evaluation in larger, well-designed, clinical trials.

Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors. PATIENTS AND METHODS: This was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%. RESULTS: 441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p=0.007) and level of hemoglobin (p=0.023). CONCLUSION: Thrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels.

Acute-on-chronic liver failure: A comparison of three different diagnostic criteria.

INTRODUCTION AND AIM: Different criteria are applied for the diagnosis of acute-on-chronic liver failure (ACLF). Our aim was to compare the performance of different ACLF diagnostic criteria for predicting mortality. MATERIALS AND METHODS: This was a prospective cohort study of adult cirrhotic patients admitted to a tertiary hospital for acute decompensation (AD) of cirrhosis. The evaluated outcome was mortality at 28 and 90 days, according to the different ACLF diagnostic criteria: Chronic Liver Failure Consortium (CLIF-C), Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Prognostic performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 146 patients were included. 43 (29.5%) with ACLF according to CLIF-C definition, 14 (9.6%) with ACLF by AARC definition, and 6 (4.1%) by NACSELD definition. According to Kaplan-Meier survival analyses median survival of patients with ACLF by CLIF-C definition was 27.0 days, median survival of patients with ACLF by AARC definition was 27.0 days, and median survival of patients with ACLF by NACSELD definition was 4.0 days. The areas under the ROC curves for performance evaluation in predicting mortality at 28 days for CLIF-C, AARC and NACSELD criteria were, respectively, 0.710, 0.560 and 0.561 (p=0.002). Regarding 90-day mortality, the areas under the ROC curves were 0.760, 0.554 and 0.555 respectively (p<0.001). CONCLUSION: ACLF definition proposed by CLIF-C had better performance in predicting mortality at 28 and 90 days when compared to criteria proposed by AARC and NACSELD.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Effectiveness of chronic hepatitis C treatment with direct-acting antivirals in the Public Health System in Brazil

ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.

Effectiveness of chronic hepatitis C treatment with direct-acting antivirals in the Public Health System in Brazil.

INTRODUCTION: Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. METHODS: A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. RESULTS: A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p = 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p = 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p = 0.047). CONCLUSION: The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.

Sarcopenia and non-alcoholic fatty liver disease: Is there a relationship? A systematic review.

AIM: To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) in adult patients with sarcopenia. METHODS: Randomized clinical trials, cross-sectional or cohort studies including adult patients (over 18 years) with sarcopenia were selected. The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients. In the screening process, 44 full-text articles were included in the review and 41 studies were excluded. RESULTS: Three cross-sectional studies were included. The authors attempted to perform a systematic review, but due to the differences between the studies, a qualitative synthesis was provided. The diagnosis of NAFLD was made by non-invasive methods (image methods or any surrogate markers) in all three evaluated studies. All the studies suggested that there was an independent association between sarcopenia and NAFLD. CONCLUSION: Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.