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SUMMARY OBJECTIVE: This study aimed to evaluate the correlation between Nonalcoholic fatty liver disease and cardiac abnormalities. METHODS: Patients with Nonalcoholic fatty liver disease who attended an outpatient clinic in Southern Brazil were prospectively evaluated. Patients should be older than 18 years and have steatosis. RESULTS: A total of 174 patients were evaluated. The mean age was 63±12 years, 65% were women, 71% white, 82.2% hypertensive, 52.3% diabetic, 56.3% obese, and 30% dyslipidemic. There was no association between Nonalcoholic fatty liver disease and cardiac abnormalities, even after adjusting for age, sex, and metabolic syndrome. CONCLUSIONS: The present study did not show a direct correlation between Nonalcoholic fatty liver disease and cardiac abnormalities, regardless of metabolic syndrome.

SUMMARY OBJECTIVE: The aim of the present study was to evaluate the outcomes of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. METHODS: A retrospective longitudinal observational study was carried out evaluating 38 cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. The outcomes were evaluated in an outpatient follow-up period of 3 months. The assumed significance level was 5%. RESULTS: The indications for transjugular intrahepatic portosystemic shunt were refractory ascites in 21 (55.3%), variceal hemorrhage in 13 (34.2%), and hydrothorax in 4 (10.5%) patients. There was development of hepatic encephalopathy in 10 (35.7%) patients after transjugular intrahepatic portosystemic shunt. From the 21 patients with refractory ascites, resolution was observed in 1 (3.1%) patient, and in 16 (50.0%) patients, there was ascites control. Regarding transjugular intrahepatic portosystemic shunt after variceal bleeding, 10 (76.9%) patients remained without new bleeding or hospitalizations in the follow-up period. The global survival in the follow-up period in patients with and without hepatic encephalopathy was 60 vs. 82%, respectively (p=0.032). CONCLUSION: Transjugular intrahepatic portosystemic shunt can be considered in decompensated cirrhotic patients; however, the development of hepatic encephalopathy which can shorten survival should be focused.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide, and its prevalence increases continuously. As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis, it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise. Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver, and they help explain why liver cancer develops even in patients without cirrhosis. Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population. Currently, it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo (with or without alpha-fetoprotein), but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease. Moreover, the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases. Furthermore, it is not clear which subgroups of patients without cirrhosis should undergo surveillance. Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals. By improving surveillance, tumors could be detected in earlier stages, amenable to curative treatments.

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Os autores após contextualizarem a importância das doenças hepáticas crônicas avançadas, uma vez que ocupam o oitavo lugar no ranking de mortalidade no Brasil, ao abordarem a classificação da cirrose, ressaltam a importância da hipertensão porta clinicamente significativa (HPCS). Sendo ela o fator preponderante não só do surgimento das varizes gastroesofágicas, mas também das demais complicações da cirrose trazem reflexões em relação a uma nova postura a ser tomada. Assim, o objetivo do tratamento não seria a profilaxia do sangramento das varizes mas a profilaxia/tratamento da HPCS. Ao fazerem esta assertiva, demonstram a importância do tratamento da doença hepática de base bem como da hipertensão porta com os ß-bloqueadores não específicos. Tendo em vista, estas medidas não terem a efetividade ideal, fazem reflexões em relação ao papel das estatinas no tratamento das doenças hepáticas. Ao salientarem seu papel antioxidante; anti-inflamatório; antitrombótico; antifibrótico e na melhora da disfunção endotelial, apresentam evidências de sua utilização como arma terapêutica no tratamento dos pacientes com cirrose e HPCS. No entanto, ao ressaltarem o papel das estatinas no armamentário terapêutico, julgam ainda necessária a existência de mais estudos prospectivos randomizados para que seja tomada uma conduta mais definitiva.

Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.

BACKGROUND AND AIM Ascites is a common complication of cirrhosis, and it is associated with increased mortality. The aim of this study was to evaluate the efficacy of long-term albumin administration in decreasing mortality and other complications of patients with cirrhosis and ascites. METHODS A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials evaluating long-term albumin administration in patients with cirrhosis and ascites were considered eligible, as long as at least one of the following outcomes was evaluated: mortality, recurrence of ascites/need for paracentesis, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Meta-analysis was performed using the random-effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42019130078). RESULTS The literature search yielded 1517 references. Five randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis, involving 716 individuals. Patients receiving long-term albumin had significantly lower risk of recurrence of ascites/need for paracentesis when compared with controls (risk ratio = 0.56, 95% confidence interval = 0.48-0.67, P

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.

Infections are a frequent complication and a major cause of death among patients with cirrhosis. The important impact of infections in general and especially spontaneous bacterial peritonitis on the course of disease and prognosis of patients with cirrhosis has been recognized for many years. Nevertheless, such importance has recently increased due to the comprehension of infection as one of the most prominent risk factors for patients to develop acute-on-chronic liver failure. Furthermore, the issue of infections in cirrhosis is a focus of increasing attention because of the spreading of multidrug resistant bacteria, which is an emerging concern among physicians assisting patients with cirrhosis. In the present paper, we will review the current epidemiology of infections in patients with cirrhosis and particularly that of infections caused by resistant bacteria, demonstrating the relevance of the subject. Besides, we will discuss the current recommendations on diagnosis and treatment of different kinds of infections, including spontaneous bacterial peritonitis, and we will highlight the importance of knowing local microbiological profiles and choosing empirical antibiotic therapy wisely. Finally, we will debate the existing evidences regarding the role of volume expansion with albumin in patients with cirrhosis and extraperitoneal infections, and that of antibiotic prophylaxis of spontaneous bacterial peritonitis.

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.

BACKGROUND: Sarcopenia is a common complication in patients with cirrhosis and may lead to increased morbidity and mortality. OBJECTIVE: To investigate the prevalence of sarcopenia and its association with disease severity scores, among patients with cirrhosis. DESIGN AND SETTING: Observational and retrospective cohort study carried out in a tertiary-care hospital in southern Brazil. METHODS: This study was conducted among patients with chronic liver disease who were followed up at the gastroenterology and hepatology outpatient clinic of a tertiary-care hospital in southern Brazil and who underwent computed tomography scans of the abdomen through any indication. RESULTS: We included 83 patients in the study. In the population evaluated, there was a predominance of males (57.80%) and the mean age was 56 years. Hepatitis B or C virus was present in the genesis of the disease in 34.9% of the cases, followed by an etiology of alcohol abuse (30.1%). Sarcopenia was diagnosed in 41 (49.4%) of the patients when the cutoff point for cirrhotic patients was used. There was no significant correlation between the Child-Pugh and MELD severity scores and the occurrence of sarcopenia. CONCLUSION: Sarcopenia presents high prevalence among patients with chronic liver disease, without any association with predictors of severity.

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.

Backgrounds: Down-staging (DS) is used to convert hepatocellular carcinoma (HCC) patients outside the criteria for liver transplantation (LT) into patients within the criteria. However, LT after DS remains controversial in the literature. Aims: Compare the post-LT survival and recurrence risk of HCC patients transplanted after DS with patients transplanted within the Brazilian selection criteria. Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,119 liver transplant recipients with HCC in Brazil. HCC treatment prior to LT and whether or not the patient was enrolled after down-staging was analyzed. Survival curves were presented using the Kaplan-Meier and compared using the log-rank test. Univariate and multiple cox regression analysis was fitted. Results: 1,119 patients were included. 81% were males and mean age in the time of LT was 58 ± 8.2 years. In the majority of patients (91%) HCC was the reason for inclusion in transplant list and 8% of patients were listed after successful DS. At HCC diagnosis, 85% of patients were within Milan Criteria. TACE was the most frequent treatment performed. The overall survival (OS) of the entire series was 63% in 5 years, with an average follow-up time of 28 months and post-LT HCC recurrence was 8%. Relapse-free survival and OS, respectively, over 5 years, were 78% and 83% in DS patients and 75% and 89% in patients transplanted within criteria, with no statistical difference in the two analyzes. Evaluation of prognostic factors using simple and multiple Cox Regression did not show that DS was a risk factor for a worse survival or post-LT tumor recurrence. Conclusions: In our study, patients underwent DS show good post-transplant evolution, similar to those transplanted within criteria, suggesting that response to treatment is a good selection parameter for tumors with favorable tumor biology.

SUMMARY OBJECTIVE: Nonalcoholic fatty liver disease is the most prevalent cause of chronic liver disease worldwide. Nonalcoholic steatohepatitis is associated with increased mortality rates due to the liver and cardiovascular diseases. The gold standard for discriminating nonalcoholic fatty liver disease activity and staging is the anatomopathological examination, which is an invasive method. In this regard, noninvasive methods, such as scintigraphy, have been under investigation. This study investigated the role of scintigraphy in the diagnosis of nonalcoholic steatohepatitis in obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery. METHODS: Patients undergoing bariatric surgery and liver biopsy were prospectively included. 99mTc-phytate scintigraphy was performed to assess liver/spleen, spleen/heart, and liver/heart uptake ratios, while 99mTc-isonitrile scintigraphy assessed liver/heart ratio. To evaluate the presence of nonalcoholic steatohepatitis, the results of 99mTc-phytate scintigraphy and 99mTc-isonitrile scintigraphy were compared with the anatomopathological examination. RESULTS: Sixty-one patients with nonalcoholic fatty liver disease were allocated into two groups, namely, nonalcoholic steatohepatitis (n=49) and non-nonalcoholic steatohepatitis (n=12). The results of scintigraphic images obtained after the infusion of radiopharmaceutical 99mTc-phytate in liver/spleen, spleen/heart, liver/heart ratios and 99mTc-isonitrile liver/heart ratio presented no difference between groups with and without nonalcoholic steatohepatitis with an accuracy of 47.5, 37.7, 50.8, and 52.5%, respectively. CONCLUSION: Scintigraphy was not proven to be a useful method to differentiate patients with and without nonalcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its prevalence is increasing alongside obesity. In United States, NAFLD is already the second leading cause of liver transplantation. The spectrum of the disease ranges from simple steatosis, which has a benign course, to steatohepatitis, which may progress to cirrhosis and its complications. The rising of noninvasive methods for diagnosing and staging non-alcoholic steatohepatitis (NASH) and fibrosis decreases the need of liver biopsy, as well as the costs and the occurrence of complications related to it. OBJECTIVE: To analyze the performance of the triglyceride-glucose index to evaluate steatosis, NASH and liver fibrosis in obese patients with NAFLD. METHODS: This is a retrospective cross-sectional study. Every medical record of patients who were candidates for bariatric surgery at a leading hospital in Southern Brazil were analyzed. The triglyceride-glucose index (TyG Index), a method composed only of two simple laboratory tests (serum triglycerides and fasting glucose levels), was performed prior to surgery. The TyG Index performance regarding the anatomopathological findings was evaluated, and the AUROC curve was calculated to evaluate the best cut-off point for diagnosing steatosis, non-alcoholic steatohepatitis and liver fibrosis grade. Also, the NAFLD fibrosis Score (NFS) was evaluated. RESULTS: A total of 423 patients were evaluated. The TyG Index with a cut-off point of 8.76 excluded significant simple steatosis (grade 2-3) in obese patients, with 67.6% sensitivity, 65.1% specificity, 46.3% positive predictive value (PPV), 81.8% negative predictive value (NPV), 65.8% accuracy and 0.66 AUROC (P=0.005). In the evaluation of NASH, the TyG Index with a cut-off point of 8.82 excluded significant NASH (grade 2-3) with 57.3% sensitivity, 58.6% specificity, 33.7% PPV, 78.8% NPV, 58.2% accuracy and 0.58 AUROC (P=0.022). When evaluating liver fibrosis, the TyG Index with a cut-off point of 8.91 showed a sensitivity of 61.8%, a specificity of 62.5%, a PPV of 13.8 and a NPV of 94.4% for exclusion of advanced fibrosis (F3-4), with a 62.4% accuracy and 0.69 AUROC (P

Background and aim Bacterial infections are among the main causes of death in patients with cirrhosis. While there are unquestionable benefits of using albumin in patients with spontaneous bacterial peritonitis, the benefits of albumin are controversial for those with extraperitoneal infections. The aim was to compare the use of albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections. Methods A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials comparing albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections were considered eligible, as long as at least one of the following outcomes was evaluated: mortality and renal dysfunction. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42018107191). Results The literature search yielded 812 references. Three randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis. There was no evidence of significant difference between the groups regarding mortality in 30 days (risk ratio [RR] = 1.62, 95% confidence interval [CI]: 0.92-2.84, P = 0.09, I2 = 0%) or in 90 days (RR = 1.27, 95% CI: 0.89-1.83, P = 0.19, I2 = 0%). Regarding renal dysfunction, there was also no evidence of significant difference between the groups (RR = 0.55, 95% CI: 0.25-1.19, P = 0.13, I2 = 0%). Conclusion There is no evidence of significant benefits of using albumin for cirrhotic patients with extraperitoneal infections regarding mortality or renal dysfunction.

Variceal bleeding is a dramatic complication of cirrhosis. Primary prophylaxis against variceal bleeding is indicated for patients with high-risk varices. In order for these patients to be identified, endoscopic screening for esophageal varices has been traditionally recommended at the time of the diagnosis of cirrhosis. Considering that many patients do not have esophageal varices in the early stages of cirrhosis and, therefore, are submitted to endoscopy unnecessarily, non-invasive methods for variceal screening have been studied. Among these non-invasive methods, the most extensively studied probably are platelet count/spleen diameter ratio, liver stiffness, spleen stiffness and an association between liver stiffness and platelet count, referred to as the Baveno VI criteria. The Baveno VI criteria has recently been recommended by different medical associations for variceal screening. This is a critical review on the non-invasive methods for variceal screening, in which the performances of the different methods are presented and the limitations of the existing evidence is discussed. Despite reasonable performances of some of these methods, especially platelet count/spleen diameter ratio and the association between liver stiffness and platelet count, we understand that the available evidence still has relevant limitations and that physicians should decide on screening cirrhotic patients for esophageal varices with endoscopy or non-invasive methods on a case-by-case basis.

Background Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. Patients and methods We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. Results OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. Conclusion In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

Hepatorenal syndrome has the worst prognosis among causes of acute kidney injury in cirrhotic patients. Its definitive treatment is liver transplantation. Nevertheless, considering its high short-term mortality rate and the shortage of liver grafts, a pharmacological treatment is of utmost importance, serving as a bridge to liver transplant. The clinical management of hepatorenal syndrome is currently based on the use of a vasoconstrictor in association with albumin. Terlipressin, noradrenaline and the combination of midodrine and octreotide could be used to treat hepatorenal syndrome. Among these options, terlipressin seems to gather the strongest body of evidence regarding efficacy and should be considered the first line of treatment whenever available and in the absence of contraindications. Treatment with a vasoconstrictor and albumin should be promptly initiated after the diagnosis of hepatorenal syndrome in order for patients to have higher chances of recovery.

Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called ''Brazilian Milan Criteria'' (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. Materials and Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. Results: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p

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.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and one of the main causes of cancer-related deaths worldwide. Most HCCs develop in an inflammatory microenvironment, and mounting evidence emphasizes the importance of immune aspects in hepatocarcinogenesis. In normal physiology, both innate and adaptive immune responses are responsible for eliminating malignantly transformed cells, thus preventing the development of liver cancer. However, in the setting of impaired natural killer cells and exhaustion of T cells, HCC can develop. The immunogenic features of HCC have relevant clinical implications. There is a large number of immune markers currently being studied for the early detection of liver cancer, which would be critical in order to improve surveillance programs. Moreover, novel immunotherapies have recently been proven to be effective, and the combination of atezolizumab and bevacizumab is currently the most effective treatment for advanced HCC. It is expected that in the near future different subgroups of patients will benefit from specific immunotherapy. The better we understand the immune aspects of HCC, the greater the benefit to patients through surveillance aiming for early detection of liver cancer, which allows for curative treatments, and, in cases of advanced disease, through the selection of the best possible therapy for each individual

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cirrhosis. OBJECTIVE: To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. METHODS: We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value

To evaluate the performance of a non-invasive test (Fibromax™, Ferring Pharmaceutical, Saint-Prex, Switzerland) and inflamatory markers (IL-1β, IL-6, IL-8, TNF-α, MCP-1) in the diagnosis and staging of patients with non-alcoholic fatty liver disease.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-1β, 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.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 (P0.001) 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.The Fibromax™ test and the inflamatory markers (IL-1β, 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.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH. RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

Introduction and aim. This manuscript seeks to analyze the impact of lifestyle changes on body mass index (BMI), aminotransferases and steatosis in children and adolescents with nonalcoholic fatty liver disease (NAFLD). Material and methods. A review of PubMed, BIREME, Scopus, EMBASE, Medline and Web of Science databases 2015 was performed seeking studies addressing the impact of lifestyle interventions on children and/or adolescents with NAFLD. Inclusion were manuscripts written in Portuguese, English and Spanish, as well as age less than 18 years. Two reviewers performed the data extraction independently and differences were resolved by consensus. Outcome measures were BMI, serum aminotransferase levels and the presence of hepatic steatosis. Results. The literature search identified 71,012 articles. After excluding 46,397 duplicates and other clearly irrelevant studies, 89 publications were reviewed in detail. Another 55 studies were excluded at this stage. Subsequently, 18 were excluded due to lack of data and three new articles were found in the review of the references of previously identified manuscripts. Therefore, 19 studies that had evaluated 923 subjects (477 boys and 446 girls) aged 6-18 years were included in the review. In most studies, the intervention included aerobic exercise and diet. In nine studies, BMI improved significantly following the intervention. The vast majority of studies reported a benefit from the intervention on aminotransferase levels. Lifestyle changes also had a significant impact on steatosis, reducing the risk by 61%. Conclusion. In conclusion lifestyle changes lead to significant improvements in BMI, aminotransferase levels and hepatic steatosis in children and adolescents with NAFLD.

Introduction and aim. Excessive alcohol consumption is a public health concern worldwide and has been associated with high mortality rates. This study aimed to determine the prevalence of alcohol consumption and its influence on the prognosis of hospitalized cirrhotic patients in a tertiary care hospital. Material and methods. We reviewed the medical records of all patients with hepatic cirrhosis admitted between January 2009 and December 2014, in a referral center for liver disease in southern Brazil. Data on clinical outcomes, associated conditions, infections, and mortality were collected and compared between alcoholic and nonalcoholic patients. Results. The sample consisted of 388 patients; 259 (66.7%) were men. One hundred fifty-two (39.2%) were classified as heavy use of alcohol. Most alcoholic patients were men (n = 144; 94.7%). Mean age was 55.6 ± 8.9 years. Hepatic decompensations and infections were more prevalent in alcoholic patient. Spontaneous bacterial peritonitis and respiratory tract infection accounted for most of the infections. Excessive alcohol consumption was associated with mortality (P = 0.009) in multivariate analysis. Conclusion. On the present study, the prevalence of heavy use of alcohol was high and associated with a poorer prognosis in hospitalized cirrhotic patients, increasing the risk of infection and death.

AIM To assess the incidence of hepatocellular carcinoma (HCC) in chronic liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfected with human immunodeficiency virus (HIV). METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review. RESULTS Of 804 patients were included (399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger (36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected (P < 0.001). HCC was diagnosed in 36 patients (10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years (95%CI: 0.12-0.46 vs 0.47-1.05) (long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC. CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.

Background: Hepatocellular carcinoma (HCC) is one of the main indications for liver transplantation (LT). Bridge therapy (BT) is recommended when waiting time on transplant list is longer than six months to avoid tumor progression and dropout. Response to locoregional treatment has been considered as a good prognostic parameter in post-LT, however, its role still needs to be defined. Aims: To evaluate the role of BT for HCC on survival and post-LT tumor recurrence. Methods: Brazilian multicenter retrospective cohort study in HCC patients submitted to LT with clinical and radiological data analysis. Data related to HCC pre-LT treatment, type of treatment and the final response according to mRECIST criteria in the last pre-LT image exam were analyzed. Survival curves were presented using the Kaplan-Meier and compared using the log-rank test. Results: 1,119 patients were included. 81% were males and mean age at LT was 58 ± 8.2 years. At HCC diagnosis, 85% were within Milan criteria (MC) by imaging studies and 67%, underwent BT prior to LT. TACE/TAE were performed in 80%, PEI 9%, RFA 3%, surgery 1% and combined therapy 7%. According to mRECIST, 37% showed complete response (CR), 38% partial response (PR), 12% stable disease (SD) and 13% progressive disease (PD) after BT. The overall survival (OS) was 63% in 5 years, with a mean follow-up of 28 months. The post-LT tumor recurrence was 8%. There was no difference in the risk of post-LT tumor recurrence or survival among patients who underwent BT or not or between the various types of treatment performed. However, patients who have CR to BT had a higher recurrence-free survival compared to patients with PR, SD or PD (p = 0.019). Conclusions: This study demonstrated the role of BT in LT, since patients with complete response, had a lower risk of post-transplant tumor recurrence.

In summary, we praise the authors for their important contribution to the field of hepatocarcinogenesis, especially in association to hepatitis B infection. However, we believe the next efforts should be focused on understanding whether these findings apply to other populations at risk before providing patient-care recommendations that could exacerbate costs with unclear clinical benefit. In this regard, we hope studies such as our ESCALON Project or the Texas HCC Consortium Cohort Study would help to further understand HCC development in OBI and lead to the development of better screening methods for HCC.

Since the publication of the Brazilian Association of Hepatology recommendations for the prevention and treatment of variceal bleeding in 2010, new evidence-based data were reported in the literature. This has changed our current management for portal hypertension. This review updates the previous recommendations. It takes the new prognostic staging of cirrhosis into account allowing tailored treatment for advanced fibrosis, compensated or decompensated cirrhosis. An organizing panel of five experts reviewed all recommendations according to available data, which were subsequently scrutinized by all members of the Brazilian Association of Hepatology using a web-based approach. The accepted recommendations are presented in this manuscript.

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.

AIM To determine the incidence of hepatocellular carcinoma (HCC) and the impact of HCC surveillance on early diagnosis and survival of cirrhotic outpatients. METHODS In this retrospective cohort study, cirrhotic outpatients undergoing HCC surveillance between March 2005 and March 2014 were analyzed. Exclusion criteria were HIV coinfection; previous organ transplantation; diagnosis of HCC at first consultation; missing data in the medical chart; and less than 1 year of follow-up. Surveillance was carried out every six months using ultrasound and serum alpha-fetoprotein determination. Ten-year cumulative incidence and survival were estimated through Kaplan-Meier analysis. RESULTS Four hundred and fifty-three patients were enrolled, of which 57.6% were male. Mean age was 55 years. Hepatitis C virus and heavy use of alcohol were the main etiologic agents of cirrhosis. HCC was diagnosed in 75 patients (16.6%), with an estimated cumulative incidence of 2.6% in the 1st year, 15.4% in the 5th year, and 28.8% in the 10th year. Median survival was estimated at 17.6 mo in HCC patients compared to 234 mo in non-HCC patients (P < 0.001). Early-stage HCC was more often detected in patients who underwent surveillance every 6 mo or less (P = 0.05). However, survival was not different between patients with early stage vs non-early stage tumors [HR = 0.54 (0.15-1.89), P = 0.33]. CONCLUSION HCC is a frequent complication in patients with cirrhosis and adherence to surveillance programs favors early diagnosis.

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 autoimune 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.