Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

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.

Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study.

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 < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. CONCLUSIONS: In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used.

Spontaneous bacterial peritonitis and extraperitoneal infections in patients with cirrhosis.

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.

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.

Vasoconstrictors in hepatorenal syndrome - A critical review.

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.

Screening for esophageal varices in cirrhotic patients - Non-invasive methods.

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.

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.

Evaluation of response to hepatitis B virus vaccine in adults with human immunodeficiency virus.

INTRODUCTION AND AIM: Viral hepatitis is a serious public health problem. The risk of progression to chronic hepatitis in hepatitis B virus (HBV) infection occurs in 5-10% of adults and is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Individuals infected with human immunodeficiency virus (HIV) may have coinfection with HBV. The existence of unvaccinated groups represents a significant risk not only individually but also at the community level. The aim of this study was to evaluate HBV vaccine response in adults with HIV infection. MATERIALS AND METHODS: A retrospective, descriptive study of the cross-sectional type was carried out in an outpatient HIV referral center in southern Brazil. All medical records of adult HIV patients seen during January 2006 to December 2015 were selected. In statistical analysis, a significance level of 5% was used. RESULTS: Of the 201 patients evaluated with a complete vaccination scheme, 55.72% were males, with a mean age of 43.86±12.68 years. Vaccine response occurred in 80.10% (161/201) of the patients, and it did not correlate with age, CD4+ cell count or viral load. CONCLUSION: HBV vaccine response in a HIV population was satisfactory, highlighting the importance of vaccination for prevention, cost reduction and better prognosis in preventing HBV/HIV coinfection.

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.

Alcohol Consumption Influences Clinical Outcome in Patients Admitted to a Referral Center for Liver Disease.

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 cirrosis 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.

Non-Alcoholic Fatty Liver Disease in Children and Adolescents: Lifestyle Change - a Systematic Review and Meta-Analysis.

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). MATERIALS 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%. CONCLUSIONS: Lifestyle changes lead to significant improvements in BMI, aminotransferase levels and hepatic steatosis in children and adolescents with NAFLD.

The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib.

BACKGROUND AND AIMS: The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. MATERIAL AND METHODS: This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database. RESULTS: Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. CONCLUSION: This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.

Efficacy of entecavir and tenofovir in chronic hepatitis B under treatment in the public health system in southern Brazil.

There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.

Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients.

The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease.