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.

Prevalence, variability, and outcomes in portal hypertensive colopathy: a study in patients with cirrhosis and paired controls.

BACKGROUND: Management of portal hypertensive colopathy (PHC) has been challenged by controversial results in its prevalence and clinical relevance. OBJECTIVE: To describe the PHC prevalence and to evaluate the variability in diagnosis, the relation to severity of liver disease, and the incidence of severe outcomes. DESIGN: Cross-sectional study. SETTING: Endoscopic unit of a tertiary-care academic center in Rio de Janeiro, Brazil. PATIENTS: Patients with cirrhosis with portal hypertension and controls paired for age and sex. INTERVENTIONS: All patients were submitted to standard and image-enhanced colonoscopies, which were recorded in a coded video file and analyzed twice by a blinded endoscopist. MAIN OUTCOME MEASUREMENTS: The prevalence of PHC. RESULTS: A total of 51 patients with cirrhosis (55% male, mean age 59 years) and 51 healthy controls (43% male, mean age 61 years) were included. The top ranking colonoscopic findings were angiodysplasia-like lesions, nonspecific vascular pattern, red spots, and colorectal varices, all significantly more frequent in patients with cirrhosis compared with controls. PHC prevalence was 71% in patients with cirrhosis. For PHC, interobserver and intraobserver agreement (k values [standard error]) were 0.68 (0.09) and 0.63 (0.10), respectively. Intraobserver agreement for colonoscopic findings was satisfactory. PHC was not related to more severe liver disease or liver stiffness. Only 5 patients developed severe outcomes during follow-up. LIMITATIONS: The exclusion of patients with cirrhosis without esophageal varices and the absence of an interobserver agreement analysis by double-blinded endoscopists. CONCLUSION: PHC was highly prevalent in patients with cirrhosis, and its diagnostic agreement was satisfactory. PHC is not associated with relevant severe outcomes in a 12-month follow-up.

Interobserver variability in transient elastography analysis of patients with chronic hepatitis C.

BACKGROUND & AIMS: Transient elastography based on liver stiffness measurement is a non-invasive method to assess hepatic fibrosis. However, interobserver variability has led to controversy over its use in fibrosis evaluation. To evaluate the interobserver variation in transient elastography in chronic hepatitis C. METHODS: We performed a cross-sectional study, analysing findings from two experienced operators who each assessed 195 patients by transient elastography on the same day. Liver stiffness measurement used to define fibrosis stages, based on METAVIR score, was: <7.1 as F0F1, 7.1-9.4 as F2, 9.5-12.4, as F3 and >12.4 kPa as F4. We also assessed interobserver variation in identification of potential oesophageal varices screening based on transient elastography. RESULTS: The interobserver intraclass correlation coefficient was 0.940 (95% CI 0.863-0.967) and measurements made by operators correlated [Spearman's ρ = 0.924; P < 0.001]. However, the median liver stiffness measurement assessed by first operators was higher (11.5 vs 9.8 kPa; P < 0.001). The discordance between operators was 35% for at least one stage of fibrosis and 5% for two or more stages. Interobserver reliability values were κ = 0.61 for fibrosis stages F ≥ 2 and κ = 0.80 for cirrhosis. Among the 74 patients determined to have cirrhosis by at least one operator, there was considerable discordance in identification of those with indication for oesophageal varices screening (κ values from 0.13 to 0.61) according to several cut-offs. CONCLUSION: Although a high correlation of liver stiffness measurement between operators, interobserver variability in transient elastography was not negligible. This method should not be used as the only screening tool for oesophageal varices in chronic hepatitis C.

Enhanced liver fibrosis panel as a predictor of liver fibrosis in chronic hepatitis C patients.

BACKGROUND: Evaluation of fibrosis is crucial in the assessment of chronic hepatitis C (CHC). The enhanced liver fibrosis (ELF) is a serological panel including hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and amino-terminal propeptide of type III procollagen (PIIINP) that has shown good results in predicting liver fibrosis in distinct scenarios of chronic liver diseases. AIMS: We aimed to assess the performance of ELF on the detection of fibrosis and cirrhosis in a CHC patient cohort and to compare the results of ELF and transient elastography (TE-Fibroscan) using liver biopsy as reference. PATIENTS AND METHODS: One hundred twenty patients were prospectively evaluated by TE and ELF using an ADVIA Centaur automated system. The ELF score was calculated using the manufacturer's algorithm. Biopsies were classified according to the METAVIR score. Receiver operator characteristic curve analyses were performed to evaluate the accuracy of ELF and TE. RESULTS: The area under the receiver operator characteristic curve (AUROC) of ELF for the diagnosis of significant fibrosis was 0.81 [95% confidence interval (CI), 0.73-0.87], for advanced fibrosis was 0.82 (95% CI, 0.74-0.88), and for cirrhosis was 0.78 (95% CI, 0.70-0.85). Using the proposed cutoffs, ELF overestimated fibrosis in 66% (81/120) of cases and underestimated in 3% (3/120). We found no statistically significant difference when comparing the AUROC of ELF and TE for diagnosing fibrosis or cirrhosis. CONCLUSIONS: ELF panel is a good noninvasive fibrosis marker and showed similar results to TE in CHC patients. However, new cutoff points need to be established to improve its performance on patients with CHC.

Visceral adipose tissue, epicardial fat, and hepatic steatosis in polycystic ovary syndrome: a study of ectopic fat stores and metabolic dysfunction.

PURPOSE: In polycystic ovary syndrome (PCOS), ectopic fat accumulation remains debatable. Therefore, intra-abdominal, hepatic, and epicardial fat were compared between PCOS women and body mass index (BMI)-matched controls and their associations with metabolic and hormonal parameters were explored. Furthermore, the performance of echocardiographic epicardial adipose tissue thickness (EATT) and hepatic steatosis measurement using transient elastography-based controlled attenuation parameter (TE-CAP) in screening abdominal visceral adipose tissue (VAT) was originally evaluated. METHODS: Women aged 18-39 years with BMI < 35 kg/m² were recruited. PCOS was defined by the Rotterdam criteria. All participants underwent clinical and laboratory exams, dual-energy X-ray absorptiometry (DXA), TE-CAP, and echocardiography. A receiver operating characteristic curve was applied to evaluate the accuracy and optimal cutoff values of TE-CAP and EATT in predicting DXA-measured VAT. RESULTS: The study included 35 women with PCOS and 37 controls. PCOS women exhibited higher levels of androgens, insulin resistance (IR) parameters, LDL-cholesterol, triglycerides, VAT, and EATT. VAT correlated with IR and triglycerides, whereas EATT correlated with HDL-cholesterol. In PCOS women aged 18-29, the cutoff values of CAP and EATT for VAT were 198.0 and 3.07, respectively, with CAP showing higher area under the curves (AUC). In PCOS women aged 30-39, the cutoff values were 209.5 and 3.36, respectively, with EATT showing higher AUC. CONCLUSION: VAT correlates with more metabolic parameters in PCOS than TE-CAP or EATT. TE-CAP is useful for VAT screening in PCOS patients aged 18-39 years, whereas EATT is effective and outperforms CAP in those aged 30-39 years.

LEFT ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction.

BACKGROUND & AIMS: The current study aimed at assessing the potential role of cardiac abnormalities in the pathogenesis of circulatory and renal dysfunction in cirrhosis. METHODS: One hundred and fifty-two patients (34 without ascites, 95 with ascites without renal failure and 21 with hepatorenal syndrome) were evaluated using Doppler echocardiography. In 102 patients, diastolic function was assessed by measuring parameters related to ventricular filling velocity, mitral annulus velocity and left atrial dimensions. Cardiopulmonary pressures were also measured by cardiac catheterization in 54 patients. In 50 additional patients, left ventricular myocardial strain was performed to estimate myocardial contractility and systolic function. RESULTS: Grade 1 and 2 diastolic dysfunction was present in 41% and 16% of the patients, respectively. There was no patient with severe grade 3 diastolic dysfunction. Grade 2 diastolic dysfunction was associated with higher cardiopulmonary pressures but values were within the normal limits in all cases. Diastolic dysfunction directly correlated with liver failure but not with the degree of impairment in circulatory and renal function. The proportion of patients without or with grade 1 or 2 diastolic dysfunction was similar in patients with compensated cirrhosis, with ascites without renal failure or with hepatorenal syndrome despite marked differences in the degree of circulatory dysfunction, as indicated by plasma renin activity and noradrenaline concentration. The heart rate and systolic function were normal in all cases. There were no differences between patients without ascites, with ascites without renal failure or with HRS, despite marked differences in the activity of the renin-angiotensin system and sympathetic nervous system. These features indicate an impaired response of cardiac chronotropic and inotropic function to changes in systemic hemodynamics. CONCLUSIONS: These data indicates that: (1) diastolic dysfunction is frequent in cirrhosis but in most cases it is of mild degree and does not increase the cardiopulmonary pressure to abnormal levels. This feature, which may be due to the central hypovolemia of cirrhosis, probably accounts for the lack of symptoms associated with this condition. (2) Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. (3) In cirrhosis, there is a lack of response of the left ventricular systolic and chronotropic function to peripheral arterial vasodilation and activation of the sympathetic nervous system and this feature is an important contributory factor to the progression of circulatory dysfunction and the pathogenesis of ascites and HRS.

ALBUMIN VERSUS STANDARD MEDICAL TREATMENT IN BRAZILIAN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS.

•To assess the economic impact of implementing long-term albumin infusions in patients with cirrhosis and ascites in Brazil •Incremental cost per cirrhotic patient treated with long-term albumin was estimated based on the rates of complications and healthcare resource utilization from the ANSWER trial and local costs from the public and private healthcare system perspective in Brazil. •Implementation of long-term albumin could save up to 118,759 BRL and 189,675 BRL per patient treated in the public and private healthcare system setting, respectively. •Should results from the ANSWER trial translate into real-world effectiveness, addition of albumin to standard medical treatment could lead to improved clinical outcomes and reduced costs. Background - Cirrhosis is one of the final stages of chronic liver disease. Common causes of cirrhosis include alcoholism and viral hepatitis infections. Cirrhosis can progress from an asymptomatic, compensated phase to decompensation and the appearance of overt symptoms. There is no specific treatment for decompensated cirrhosis. The ANSWER trial positioned long-term albumin infusions as a potential treatment for patients with cirrhosis and uncomplicated ascites. Objective - This study assesses the economic impact of albumin infusions following the ANSWER trial regimen in Brazilian patients with decompensated cirrhosis from the public and private healthcare systems perspectives. Methods - The incremental cost per patient per year was calculated for standard medical treatment (SMT) plus long-term albumin infusions versus SMT alone. Costs of diuretics and albumin were obtained from Banco de Preços em Saúde and the Drug Market Regulation Chamber. Costs for complication and procedures were gathered from the published literature. Costs were transformed to 2021 Brazilian reals (BRL). Incidences of clinical complications and treatments were gathered from the ANSWER trial. Univariate sensitivity analysis was performed by increasing and decreasing all inputs by 20%. Results - The cost per patient per year was 118,759 BRL and 189,675 BRL lower for patients treated with SMT and albumin (compared to SMT only) for the public and private healthcare systems, respectively. The additional cost of albumin was offset by reduced complications and treatments (149,526 BRL and 249,572 BRL, respectively). The univariate sensitivity analysis showed cost savings for both healthcare systems in all the scenarios assessed. Conclusion - This economic analysis suggests that, if the ANSWER trial clinical outcomes translate into real-world effectiveness, addition of albumin infusions to SMT in patients with decompensated cirrhosis may lead to cost savings for the public and private healthcare systems in Brazil.

Impact of multidrug resistance on the management of bacterial infections in cirrhosis.

Patients with cirrhosis have an increased risk of infection and differently from other complications, that over the years are improving in their outcomes, infections in cirrhotic patients are still a major cause of hospitalization and death (up to 50% in-hospital mortality). Infections by multidrug-resistant organisms (MDRO) have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact. About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years. MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution. An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects, such as the type of infection (spontaneous bacterial peritonitis, pneumonia, urinary tract infection and spontaneous bacteremia), bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition (community acquired, healthcare associated or nosocomial). Furthermore, regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology. Antibiotic treatment is the most effective measure to treat infections caused by MDRO. Therefore, optimizing antibiotic prescribing is critical to effectively treat these infections. Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality. On the other hand, the supply of new agents to treat these infections is very limited. Thus, specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.

Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study.

BACKGROUND & AIMS: Treatment with albumin in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) prevents renal failure and improves survival. Whether albumin has similar beneficial effects in patients with infections other than SBP is unknown. METHODS: One hundred and ten patients with cirrhosis hospitalized for infections other than SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kgbw at diagnosis and 1 g/kgbw at day 3) (albumin group; n=56) or antibiotics alone (control group; n=54). The primary end point was survival at 3 months. Secondary end points were effects on renal and circulatory function. RESULTS: The renal function, as evaluated by differences in changes in serum creatinine and estimated glomerular filtration rate between the two groups, improved in patients treated with albumin. The circulatory function improved significantly in patients treated with albumin, but not in those from the control group. There was a trend for a lower frequency of type 1 hepatorenal syndrome in the albumin group compared to the control group (1 vs. 4 patients, respectively; p=n.s.). Probability of survival at 3 months was not significantly different among the two groups. However, when adjusted for factors with independent prognostic value, treatment with albumin was an independent predictive factor of survival. CONCLUSIONS: As compared with standard antibiotic therapy alone, treatment with albumin together with antibiotics has beneficial effects on the renal and circulatory function and shows a potential survival benefit. Further studies with large sample sizes should be performed to confirm these findings.

Risk factors associated with nonalcoholic fatty liver disease evaluated by elastography in patients with type 2 diabetes.

Objective: There is controversy about the indication for nonalcoholic fatty liver disease (NAFLD) screening in patients with type 2 diabetes mellitus (T2D). The present study aims to contribute to NAFLD surveillance in patients with T2D, assessing the association of clinical and biological variables with hepatic stiffness and steatosis. Subjects and methods: A cross-sectional design was used, with data collection from electronic medical records, including adults with T2D who underwent transient elastography (TE) between June 2018 and December 2019. Liver stiffness and steatosis were evaluated using TE and controlled attenuation parameter (CAP), respectively, with cutoff points > 8 kpa for increased stiffness and > 275 dBm for steatosis. The relationship between clinical variables and elastography results were evaluated by bivariate correlation and multivariate analysis, using SPSS 27. Seventy-nine patients (n = 79) met the inclusion and exclusion criteria. Results: Advanced fibrosis and hepatic steatosis were detected in 17,7% and in 21,5% of the patients, respectively. There was a direct and significant correlation between CAP and BMI, waist circumference, HbA1c, triglycerides levels, and insulin doses and an inverse correlation with HDL. The waist circumference, low levels of HDL cholesterol and the insulin dose maintained a significant association with CAP values in multivariate analysis. Elastography values showed an inverse correlation with HDL and a direct correlation with BMI and insulin dose. The association was only maintained for the insulin dose in multivariate analysis. Conclusion: Our results suggest that clinical factors such as insulin dose, waist circumference, and HDL cholesterol levels could identify T2D patients more likely to present NAFLD.

Albumin administration in patients with cirrhosis: Current role and novel perspectives.

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.

Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome.

UNLABELLED: Terlipressin plus albumin is an effective treatment for type 1 hepatorenal syndrome (HRS), but approximately only half of the patients respond to this therapy. The aim of this study was to assess predictive factors of response to treatment with terlipressin and albumin in patients with type 1 HRS. Thirty-nine patients with cirrhosis and type 1 HRS were treated prospectively with terlipressin and albumin. Demographic, clinical, and laboratory variables obtained before the initiation of treatment as well as changes in arterial pressure during treatment were analyzed for their predictive value. Response to therapy (reduction in serum creatinine <1.5 mg/dL at the end of treatment) was observed in 18 patients (46%) and was associated with an improvement in circulatory function. Independent predictive factors of response to therapy were baseline serum bilirubin and an increase in mean arterial pressure of >or=5 mm Hg at day 3 of treatment. The cutoff level of serum bilirubin that best predicted response to treatment was 10 mg/dL (area under the receiver operating characteristic curve, 0.77; P < 0.0001; sensitivity, 89%; specificity, 61%). Response rates in patients with serum bilirubin <10 mg/dL or >or=10 mg/dL were 67% and 13%, respectively (P = 0.001). Corresponding values in patients with an increase in mean arterial pressure >or=5 mm Hg or <5 mm Hg at day 3 were 73% and 36%, respectively (P = 0.037). CONCLUSION: Serum bilirubin and an early increase in arterial pressure predict response to treatment with terlipressin and albumin in type 1 HRS. Alternative treatment strategies to terlipressin and albumin should be investigated for patients with type 1 HRS and low likelihood of response to vasoconstrictor therapy.

Prevalence of non-alcoholic fatty liver disease and its associated factors in individuals with type 1 diabetes: a cross-sectional study in a tertiary care center in Brazil.

BACKGROUND: Data on non-alcoholic fatty liver disease (NAFLD) in individuals with type 1 diabetes (T1D) is controversial and so far, there are no published data on the Brazilian population. We investigated the prevalence of steatosis and hepatic fibrosis in a population with T1D from a tertiary care center in Brazil and its associated factors. METHODS: Ninety-five participants with T1D, aged 39 ± 13 years, with disease duration of 21 ± 9 years, being 55 (57.9%) females, from a university hospital in Rio de Janeiro, were screened for NAFLD with hepatic ultrasound (US) and transient elastography (TE). RESULTS: Prevalence of steatosis was, respectively, 12.6% and 16.8% when US and TE were used for diagnosis of NAFLD. Fibrosis was present in 8.4% of participants. A total of 31.6% of participants had at least one of the hepatic exams altered, which was associated with higher body mass index, waist circumference, hip circumference and waist-to-hip ratio,, presence of metabolic syndrome and higher triglycerides levels, even within the normal range. After multivariate analysis, presence of steatosis was only associated with metabolic syndrome and its component, triglycerides. CONCLUSION: In our study, prevalence of NAFLD in ultrasound approximates the one found with TE. Fibrosis was not frequent. Screening should be reserved for participants with T1D and metabolic syndrome, as this was the main factor associated with NAFLD. Triglycerides levels were the only component of metabolic syndrome associated with steatosis. Further studies are necessary to determine the best screening strategy for NAFLD in individuals with T1D. Also, predisposing factors for development in fibrosis in T1D should be further explored in prospective studies.

Primary prophylaxis of variceal bleeding in patients with cirrhosis: A comparison of different strategies.

Patients with cirrhosis and esophageal varices bleed at a yearly rate of 5%-15%, and, when variceal hemorrhage develops, mortality reaches 20%. Patients are deemed at high risk of bleeding when they present with medium or large-sized varices, when they have red signs on varices of any size and when they are classified as Child-Pugh C and have varices of any size. In order to avoid variceal bleeding and death, individuals with cirrhosis at high risk of bleeding must undergo primary prophylaxis, for which currently recommended strategies are the use of traditional non-selective beta-blockers (NSBBs) (i.e., propranolol or nadolol), carvedilol (a NSBB with additional alpha-adrenergic blocking effect) or endoscopic variceal ligation (EVL). The superiority of one of these alternatives over the others is controversial. While EVL might be superior to pharmacological therapy regarding the prevention of the first bleeding episode, either traditional NSBBs or carvedilol seem to play a more prominent role in mortality reduction, probably due to their capacity of preventing other complications of cirrhosis through the decrease in portal hypertension. A sequential strategy, in which patients unresponsive to pharmacological therapy would be submitted to endoscopic treatment, or the combination of pharmacological and endoscopic strategies might be beneficial and deserve further investigation.

Absence of increased liver-related inflammatory markers in type 1 diabetes with metabolic syndrome: a nested case-control study from Brazil.

To examine the relationship between metabolic syndrome and serum levels of interleukin (IL)-6 and IL-17, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP), inflammatory biomarkers involved in nonalcoholic fatty liver disease (NAFLD) pathophysiology, in patients with type 1 diabetes. METHODS: This was a cross-sectional, nested case-control study with 232 patients with type 1 diabetes (116 cases with metabolic syndrome and 116 controls without metabolic syndrome) who were matched for age and gender. A multivariable logistic regression with metabolic syndrome as the dependent variable was performed with inflammatory biomarkers and other parameters involved in NAFLD as independent variables. RESULTS: Chronic kidney disease (CKD), retinopathy, body mass index (BMI), diabetes duration, alanine aminotransferase (ALT), fatty liver index (FLI), and CPR levels were associated with metabolic syndrome in univariate analysis. However, after adjustments in multivariable analysis, none of the liver-related inflammatory biomarkers persisted associated with metabolic syndrome. CKD, BMI, and ALT were associated with metabolic syndrome and retinopathy showed a tendency for association (p = 0.06). CONCLUSION: Although CRP, a nonspecific marker of inflammation, was associated with metabolic syndrome in univariate analysis, this fact did not persist after adjustments. No other inflammatory biomarkers showed an association with metabolic syndrome in type 1 diabetes. The group with metabolic syndrome had a higher frequency of diabetes' complications and markedly increased FLI. FLI probably is more useful in detecting NAFLD than inflammatory biomarkers, but further prospective studies in individuals with type 1 diabetes, with abdominal ultrasound and FLI, are necessary to better support this hypothesis.

Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study.

BACKGROUND & AIMS: Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. METHODS: Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. RESULTS: Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. CONCLUSIONS: As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.

RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE).

Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.

Análise de custos de pacientes cirróticos descompensados recebendo albumina a longo prazo versus tratamento médico padrão nos sistemas de saúde público e privado do Brasil / Albumin versus standard medical treatment in brazilian public and private healthcare systems

ABSTRACT Background: Cirrhosis is one of the final stages of chronic liver disease. Common causes of cirrhosis include alcoholism and viral hepatitis infections. Cirrhosis can progress from an asymptomatic, compensated phase to decompensation and the appearance of overt symptoms. There is no specific treatment for decompensated cirrhosis. The ANSWER trial positioned long-term albumin infusions as a potential treatment for patients with cirrhosis and uncomplicated ascites. Objective: This study assesses the economic impact of albumin infusions following the ANSWER trial regimen in Brazilian patients with decompensated cirrhosis from the public and private healthcare systems perspectives. Methods: The incremental cost per patient per year was calculated for standard medical treatment (SMT) plus long-term albumin infusions versus SMT alone. Costs of diuretics and albumin were obtained from Banco de Preços em Saúde and the Drug Market Regulation Chamber. Costs for complication and procedures were gathered from the published literature. Costs were transformed to 2021 Brazilian reals (BRL). Incidences of clinical complications and treatments were gathered from the ANSWER trial. Univariate sensitivity analysis was performed by increasing and decreasing all inputs by 20%. Results: The cost per patient per year was 118,759 BRL and 189,675 BRL lower for patients treated with SMT and albumin (compared to SMT only) for the public and private healthcare systems, respectively. The additional cost of albumin was offset by reduced complications and treatments (149,526 BRL and 249,572 BRL, respectively). The univariate sensitivity analysis showed cost savings for both healthcare systems in all the scenarios assessed. Conclusion: This economic analysis suggests that, if the ANSWER trial clinical outcomes translate into real-world effectiveness, addition of albumin infusions to SMT in patients with decompensated cirrhosis may lead to cost savings for the public and private healthcare systems in Brazil.

RESUMO Contexto: A cirrose representa o estágio final da doença hepática crônica. Causas comuns de cirrose incluem alcoolismo e infecções por hepatite viral. A cirrose pode progredir de uma fase compensada assintomática para descompensação e aparecimento de sintomas evidentes. Não há tratamento específico para cirrose descompensada. O estudo ANSWER demonstrou que a administração de albumina a longo prazo pode representar um potencial tratamento para pacientes com cirrose e ascite não complicada. Objetivo: Nosso estudo avalia o impacto econômico da administração de albumina a longo prazo seguindo o protocolo do estudo ANSWER em pacientes brasileiros com cirrose descompensada, sob a perspectiva dos sistemas de saúde público e privado. Métodos: O custo incremental por paciente por ano foi calculado para o tratamento médico padrão (SMT) associado a administração de albumina a longo prazo comparado a SMT apenas. Os custos de diuréticos e albumina foram obtidos no Banco de Preços em Saúde e na Câmara de Regulação do Mercado de Medicamentos. Os custos de complicações e procedimentos foram coletados da literatura publicada. Os custos foram transformados em Reais de 2021 (BRL). As incidências de complicações clínicas e tratamentos foram coletadas do estudo ANSWER. Uma análise de sensibilidade univariada foi realizada aumentando e diminuindo todas as variáveis em 20%. Resultados: O custo por paciente por ano foi de R$ 118.759 e R$ 189.675 menor para pacientes tratados com SMT e albumina (comparado apenas com SMT) para os sistemas de saúde público e privado, respectivamente. O custo adicional da albumina foi compensado pela redução de complicações e tratamentos (149.526 BRL e 249.572 BRL, respectivamente). A análise de sensibilidade univariada mostrou redução de custos para ambos os sistemas de saúde em todos os cenários avaliados. Conclusão: Esta análise econômica sugere que, se os resultados clínicos do estudo ANSWER se confirmarem no mundo real, a administração de albumina associada ao SMT em pacientes com cirrose descompensada pode levar a redução de custos para os sistemas de saúde público e privado no Brasil.

RECOMMENDATIONS OF THE BRAZILIAN SOCIETY OF HEPATOLOGY FOR THE MANAGEMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS.

Acute kidney injury is a common complication of cirrhosis, occurring in up to 20% of patients hospitalized with cirrhosis. This field is rapidly changing, with significant advances in classification, biomarkers and therapy over the last few years. On the behalf of the Brazilian Society of Hepatology, a panel of experts in Hepatology and Nephrology reviewed published evidence to integrate findings and develop the recommendations presented in this manuscript.

Latent Class Analysis of Noninvasive Methods and Liver Biopsy in Chronic Hepatitis C: An Approach without a Gold Standard.

AIMS: To evaluate the applicability of the Latent Class Analysis (LCA) and accuracy of transient elastography (TE), aspartate-to-platelet-ratio-index (APRI), enhanced liver fibrosis (ELF), and liver biopsy (LB) for liver fibrosis assessment in a model without a gold standard. METHODS: Significant fibrosis was defined as TE ≥ 7.1 kPa, APRI ≥ 1.5, ELF ≥ 9.37, or LB METAVIR F ≥ 2. Cirrhosis was defined as TE ≥ 12.5 kPa, APRI ≥ 2.0, ELF ≥ 10.31, or LB as METAVIR F = 4. RESULTS: 117 patients with chronic hepatitis C were included. In the LCA, for significant fibrosis the sensitivities and specificities (95% CI) were 0.92 (0.86-0.98) and 0.79 (0.72-0.86) for TE; 0.47 (0.40-0.54) and 0.99 (0.95-1.00) for APRI; 0.81 (0.74-0.88) and 0.78 (0.71-0.85) for ELF; and 0.86 (0.68-1.00) and 0.91 (0.79-1.00) for LB. For cirrhosis, the sensitivities and specificities were 0.92 (0.76-1.00) and 0.94 (0.91-0.97) for TE; 0.57 (0.37-0.77) and 0.97 (0.93-1.00) for APRI; 0.94 (0.84-1.00) and 0.88 (0.82-0.94) for ELF; and 0.30 (0.12-0.48) and 1.00 for LB. CONCLUSION: LCA was useful to evaluate accuracy of methods for liver fibrosis staging. Sensitivities and specificities of noninvasive methods were increased in LCA compared to the use of LB as the gold standard.