Performance of eight predictive models for hepatocellular carcinoma recurrence after liver transplantation: A comparative study.

INTRODUCTION AND OBJECTIVES: Liver transplantation is the optimal treatment for patients with early hepatocellular carcinoma and cirrhosis. However, hepatocellular carcinoma recurs in approximately 15 % of individuals. This study aimed to assess the efficacy of predictive models for hepatocellular carcinoma recurrence after liver transplantation. PATIENTS AND METHODS: This retrospective study included 381 patients with HCC and evaluated the performance of the following models: R3-AFP score, alpha-fetoprotein (AFP) model, University of California, Los Angeles (UCLA) nomogram, Pre-Model of Recurrence after Liver Transplantation (MORAL), Post-MORAL, and Combo MORAL models, Risk Estimation of Tumor Recurrence (RETREAT) model and Platelet to Lymphocyte Ratio (PLR) model. RESULTS: The R3-AFP score, UCLA nomogram, AFP model, RETREAT, Combo MORAL, and Post-MORAL models exhibited comparable AUROCs, ranging from 0.785 to 0.733. The AUROCs for the R3-AFP model and AFP model were superior to those of the Pre-MORAL and PLR models. The UCLA nomogram, RETREAT score, Combo MORAL model, and Post-MORAL model performed similarly to the first two models, but were only superior to the PLR model. CONCLUSIONS: The R3-AFP model, UCLA nomogram, AFP model, RETREAT, Combo MORAL, and Post-MORAL models demonstrated a moderate predictive capacity for hepatocellular carcinoma recurrence following transplantation. No significant differences were observed among these models in their ability to predict recurrence.

Role of the phase angle in the prognosis of the cirrhotic patient: 15 years of follow-up.

BACKGROUND: In 2019, cirrhosis accounted for 2.4% of global deaths. The projection for 2030 is an increase in this index. In recent years, hospitalization costs have escalated by 36% for compensated cirrhosis and 24% for decompensated cirrhosis. Therefore, it is necessary to identify a tool capable of predicting the mortality of these patients according to their clinical condition and consequently extending their survival time. Different studies have shown that the phase angle (PA) can be a feasible method in clinical practice, with the potential to guide assertive patient management in the therapeutic of chronic liver disease. AIM: To evaluate the prognostic role of PA in cirrhotic patients over a 15-year follow-up period. METHODS: Retrospective cohort study with 129 cirrhotic patients of both sexes over 18 years old. Diagnosis of cirrhosis by liver biopsy. The first year of data collection was 2007, and data regarding outcomes was collected in 2023. Data were gathered from medical records, such as esophageal varices (EV), EV bleeding, ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, laboratory findings and PA. The cut-off value for the PA was 5.4°, a value described in 2012 by Fernandes et al for 129 patients evaluated in this study and the cut-off points for the Brazilian population presented in percentiles (P), as described by Mattiello et al. The mortality was assessed using the PA percentile through Kaplan-Meier curves and multivariate binary logistic regression models. RESULTS: Patients were divided into two groups according to the PA 5.4th (PA > 5.4°, n = 40; PA ≤ 5.4°, n = 89) PA percentile (< P50, n = 56; ≥ P50 n = 73). The percentile classification was more accurate in identifying long-term deaths than the 5.4º PA. Patients with < P50 had a higher number of relevant complications such as ascites, SBP, liver encephalopathy and HCC. PA is strongly correlated with serum albumin (P < 0.001), International Normalized Ratio (P = 0.01), total bilirubin (P = 0.02) and direct bilirubin (P = 0.003). PA is correlated with survival time (P < 0.001) and length of stay (P = 0.02). Logistic regression analysis shows that an increase of 1° in PA enlarges the cirrhotic patient's chance of survival by 17.7%. CONCLUSION: PA is a good predictor of morbidity and mortality for cirrhotic patients. The PA by percentile showed greater sensitivity in predicting mortality compared to the cut-off point of 5.4º.

Correction: Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant.

[This corrects the article on p. 688 in vol. 13, PMID: 36160465.].

Nursing Team Workload and the Apache Index of Gravity of Patients Post Liver Transplantation: A Cohort Study.

BACKGROUND: Liver transplantation is a complex treatment that demands a high workload from the nursing team. This study evaluated the nursing workload and its relationship with the severity of patients after liver transplantation. MATERIAL AND METHODS: A retrospective cohort study, with a review of 286 medical records of liver transplant patients from January 2014 to June 2018 in a hospital in southern Brazil was performed. Demographic and clinical characteristics were analyzed, as well as the outcome and the scores Model for End-Stage Liver Disease (MELD), Nursing Activity Score (NAS), and Acute Physiology and Chronic Health Evaluation IV (APACHE IV). RESULTS: Men represented 68.9% of the sample, the mean age was 57.6 years (±10), and the MELD and APACHE IV scores respectively showed means of 24.3 (±5.6) and 58.9 (±23.7). The length of stay in the intensive care unit was 5 days (range, 3-7) and mortality was 9.1%. There was a gradual reduction in the mean NAS in 24 hours (94.9 ± 18.5), 48 hours (87.2 ± 17.0), 72 hours (83.3 ± 19.6) and at discharge (82.3 ± 18.0). Associations of NAS with MELD (P ˂ .05), APACHE IV (P ˂ .001), length of stay in the intensive care unit (P ˂ .001), and death outcome (P ˂ .001) were observed. The greatest workload was in checking vital signs, water balance, and administrative tasks (P ˂ .001). CONCLUSIONS: The nursing workload in the postoperative period of liver transplantation exceeds what is recommended and is related to the severity of the patients.

Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant.

BACKGROUND: Cholangiocarcinoma (CC) is a rare tumor that arises from the epithelium of the bile ducts. It is classified according to anatomic location as intrahepatic, perihilar, and distal. Intrahepatic CC (ICC) is rare in patients with cirrhosis due to causes other than primary sclerosing cholangitis. Mixed hepatocellular carcinoma-CC (HCC-CC) is a rare neoplasm that shows histologic findings of both HCC and ICC within the same tumor mass. Due to the difficulties in arriving at the correct diagnosis, patients eventually undergo liver transplantation (LT) with a presumptive diagnosis of HCC on imaging when, in fact, they have ICC or HCC-CC. AIM: To evaluate the outcomes of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma on pathological examination after liver transplant. METHODS: Propensity score matching was used to analyze tumor recurrence (TR), overall mortality (OM), and recurrence-free survival (RFS) in LT recipients with pathologically confirmed ICC or HCC-CC matched 1:8 to those with HCC. Progression-free survival and overall mortality rates were computed with the Kaplan-Meier method using Cox regression for comparison. RESULTS: Of 475 HCC LT recipients, 1.7% had the diagnosis of ICC and 1.5% of HCC-CC on pathological examination of the explant. LT recipients with ICC had higher TR (46% vs 11%; P = 0.006), higher OM (63% vs 23%; P = 0.002), and lower RFS (38% vs 89%; P = 0.002) than those with HCC when matched for pretransplant tumor characteristics, as well as higher TR (46% vs 23%; P = 0.083), higher OM (63% vs 35%; P = 0.026), and lower RFS (38% vs 59%; P = 0.037) when matched for posttransplant tumor characteristics. Two pairings were performed to compare the outcomes of LT recipients with HCC-CC vs HCC. There was no significant difference between the outcomes in either pairing. CONCLUSION: Patients with ICC had worse outcomes than patients undergoing LT for HCC. The outcomes of patients with HCC-CC did not differ significantly from those of patients with HCC.

EXERCISE IN THE PHYSICAL REHABILITATION OF CIRROTICS: A RANDOMIZED PILOT STUDY.

BACKGROUND: Physical exercise delays the sarcopenic process and can reverse the loss of muscle strength, improve quality of life and prognosis in cirrhotic patients. OBJECTIVE: The aim was to verify the effects of face-to-face versus home aerobic exercise on the variables fatigue, respiratory and peripheral muscle strength, functional capacity and quality of life in patients with compensated cirrhosis. METHODS: Patients were selected by convenience, stratified and randomized into supervised face-to-face exercise (n=13) and home exercise without daily supervision (n=12). Patients were submitted to a program of aerobic physical exercises, with progressive duration of 30 to 50 minutes, twice a week for twelve weeks. Before starting the program and every four weeks, all patients in both groups were assessed for fatigue (fatigue severity scale), respiratory (Pimáx and Pemáx) and peripheral (concentric quadriceps peak torque) muscle strength, functional capacity (6-minute walking distance) and quality of life (Short Form-36 Health Survey questionnaire). RESULTS: The face-to-face group showed reduced fatigue (P<0.001), increased inspiratory (P<0.001), expiratory (P<0.001) and peripheral (P<0.001) muscle strength of the 6MWD (P<0.001) and improved quality of life. The home group showed no significant improvement in these variables. CONCLUSION: A face-to-face program of moderate aerobic exercise in patients with compensated cirrhosis reduces fatigue, improves functional capacity and quality of life and increases respiratory and peripheral muscle strength. Home physical exercises do not cause the same adaptive effects in this population.

Exercício na reabilitação física de cirróticos: um estudo piloto randomizado / Exercise in the physical rehabilitation of cirrotics: a randomized pilot study

ABSTRACT Background: Physical exercise delays the sarcopenic process and can reverse the loss of muscle strength, improve quality of life and prognosis in cirrhotic patients. Objective: The aim was to verify the effects of face-to-face versus home aerobic exercise on the variables fatigue, respiratory and peripheral muscle strength, functional capacity and quality of life in patients with compensated cirrhosis. Methods: Patients were selected by convenience, stratified and randomized into supervised face-to-face exercise (n=13) and home exercise without daily supervision (n=12). Patients were submitted to a program of aerobic physical exercises, with progressive duration of 30 to 50 minutes, twice a week for twelve weeks. Before starting the program and every four weeks, all patients in both groups were assessed for fatigue (fatigue severity scale), respiratory (Pimáx and Pemáx) and peripheral (concentric quadriceps peak torque) muscle strength, functional capacity (6-minute walking distance) and quality of life (Short Form-36 Health Survey questionnaire). Results: The face-to-face group showed reduced fatigue (P<0.001), increased inspiratory (P<0.001), expiratory (P<0.001) and peripheral (P<0.001) muscle strength of the 6MWD (P<0.001) and improved quality of life. The home group showed no significant improvement in these variables. Conclusion: A face-to-face program of moderate aerobic exercise in patients with compensated cirrhosis reduces fatigue, improves functional capacity and quality of life and increases respiratory and peripheral muscle strength. Home physical exercises do not cause the same adaptive effects in this population.

RESUMO Contexto: O exercício físico retarda o processo sarcopênico e pode reverter a perda de força muscular, melhorar a qualidade de vida e prognóstico em cirróticos. Objetivo: O objetivo foi verificar os efeitos do exercício aeróbico presencial versus domiciliar sobre variáveis fadiga, força muscular respiratória e periférica, capacidade funcional e qualidade de vida em pacientes com cirrose compensada. Métodos: Os pacientes foram selecionados por conveniência, estratificados e randomizados em exercício presencial supervisionado (n=13) e exercício domiciliar sem supervisão diária (n=12). Os pacientes foram submetidos a um programa de exercícios físicos aeróbicos, com duração progressiva de 30 minutos a 1 hora, duas vezes por semana durante 12 semanas. Antes de iniciar o programa e a cada 4 semanas, todos os pacientes de ambos os grupos foram avaliados quanto à fadiga (escala de gravidade da fadiga), força muscular respiratória (Pimáx e Pemáx) e periférica (pico de torque do quadríceps concêntrico), capacidade funcional (distância caminhada de 6 minutos) e qualidade de vida (questionário Short Form-36 Health Survey). Resultados: O grupo presencial apresentou redução da fadiga (P<0,001), aumento da força muscular inspiratória (P<0,001), expiratória (P<0,001), e periférica (P<0,001), da DTC6 (P<0,001) e melhora da qualidade de vida. O grupo domiciliar não apresentou melhora significativa nessas variáveis. Conclusão: Um programa presencial de exercícios aeróbicos moderados em pacientes com cirrose compensada reduz a fadiga, melhora a capacidade funcional e qualidade de vida, aumenta força muscular respiratória e periférica. Os exercícios físicos domiciliares não provocam os mesmos efeitos adaptativos nesta população.

Assessment of resting energy expenditure in patients with cirrhosis.

BACKGROUND: Malnutrition affects 20% to 50% of patients with cirrhosis. It may be associated with serious complications and has a direct impact on prognosis. Resting energy expenditure (REE) is an important parameter to guide the optimization of therapy and recovery of nutritional status in patients with cirrhosis. However, the REE of patients with cirrhosis is still unclear, casting doubt upon the optimal nutritional management approach. AIM: To identify the best method that predicts the REE of cirrhotic patients, using indirect calorimetry (IC) as the gold standard. METHODS: An observational study was performed on 90 patients with cirrhosis. REE was assessed by IC, bioelectrical impedance analysis (BIA), and predictive formulas, which were compared using Bland-Altman plots and the Student's t-test. RESULTS: REE values measured by IC (1607.72 ± 257.4 kcal) differed significantly from those determined by all other methods (BIA: 1790.48 ± 352.1 kcal; Harris & Benedict equation: 2373.54 ± 254.9 kcal; IOM equation: 1648.95 ± 185.6 kcal; Cunningham equation: 1764.29 ± 246.2 kcal), except the Food and Agriculture Organization of the United Nations, World Health Organization, and United Nations University (FAO/WHO/UNU) (1616.07 ± 214.6 kcal) and McArdle (1611.30 ± 241.8 kcal) equations. We found no significant association when comparing IC and 24-h dietary recall among different Child-Pugh classes of cirrhosis. CONCLUSION: The IOM and FAO/WHO/UNU equations have the best agreement with the CI. These results indicate a possibility of different tools for the clinical practice on cirrhotic patients.

Melatonin Attenuates Inflammation, Oxidative Stress, and DNA Damage in Mice with Nonalcoholic Steatohepatitis Induced by a Methionine- and Choline-Deficient Diet.

Nonalcoholic steatohepatitis (NASH) is a disease with a high incidence worldwide, but its diagnosis and treatment are poorly managed. In this study, NASH pathophysiology and DNA damage biomarkers were investigated in mice with NASH treated and untreated with melatonin (MLT). C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for 4 weeks to develop NASH. Melatonin was administered at 20 mg/kg during the last 2 weeks. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and hepatic tissue was dissected for histological analysis, evaluation of lipoperoxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as nuclear factor-erythroid 2 (Nrf2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), and transforming growth factor beta (TGF-ß) expression by immunohistochemistry. DNA damage was evaluated using Comet assay, while a micronucleus test in bone marrow was performed to assess the genomic instability associated with the disease. Melatonin decreased AST and ALT, liver inflammatory processes, balloonization, and fibrosis in mice with NASH, decreasing TNF-α, iNOS, and TGF-ß, as well as oxidative stress, shown by reducing lipoperoxidation and intensifying Nrf2 expression. The SOD and GPx activities were increased, while CAT was decreased by treatment with MLT. Although the micronucleus frequency was not increased in mice with NASH, a protective effect on DNA was observed with MLT treatment in blood and liver tissues using Comet assay. As conclusions, MLT slows down the progression of NASH, reducing hepatic oxidative stress and inflammatory processes, inhibiting DNA damage via anti-inflammatory and antioxidant actions.

Melatonin restores zinc levels, activates the Keap1/Nrf2 pathway, and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity.

BACKGROUND: Melatonin (MLT) is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations, due to its action against free radicals. AIM: To evaluate the effect of MLT on carbon tetrachloride (CCl4) induced liver injury in rats in terms of oxidative stress, reticular stress, and cell damage. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups: Control rats, rats treated with MLT alone, rats treated with CCl4 alone, and rats treated with CCl4 plus MLT. CCl4 was administered as follows: Ten doses every 5 d, ten every 4 d, and seven every 3 d. MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment (16th wk). RESULTS: MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl4 treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity, with a lower reduction in serum zinc levels, guaranteeing a reduction in liver damage; additionally, it increased the expression of nuclear factor (erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein 1. MLT also decreased the expression of the proteins associated with endoplasmic reticulum stress, i.e., glucose-regulated protein 78 and activating transcription factor 6, as well as of heat shock factor 1 and heat shock protein 70. CONCLUSION: MLT has a hepatoprotective effect in an experimental model of CCl4-induced liver injury, since it reduces oxidative stress, restores zinc levels, and modulates endoplasmic reticulum stress.

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats.

BACKGROUND: Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential. AIM: To evaluate MLT's effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis. METHODS: Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis. RESULTS: BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower (P < 0.001) n the groups that received MLT. DNA damage was also lower (P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1ß, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT (P < 0.001). CONCLUSION: When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

Sarcopenia, oxidative stress and inflammatory process in muscle of cirrhotic rats - Action of melatonin and physical exercise.

Sarcopenia is one of the most common features of cirrhosis, contributing to morbidity and mortality in this population. We aimed to evaluate the effect of melatonin (MLT) and exercise (EX) on the quadriceps muscle in rats with biliary cirrhosis induced by bile duct ligation (BDL). We used 48 males (mean weight = 300 g), divided into eight groups. A 20 mg/Kg MLT dose was administered via i.p. (1 x daily), and the EX, the animals were set to swim in couples for 10 min each day. Upon completion, blood, liver, and quadriceps samples were taken for analysis. In the liver enzymes analysis and comet assay results, a reduction was observed in the groups treated with MLT with/or EX comparing to the BDL group. In the evaluation of substances that react to thiobarbituric acid (TBARS), nitric oxide levels (NO), and tumor necrosis factor-alpha levels (TNF-α), there was a significant increase in the BDL group and a reduction in the treated groups. In the activity of the superoxide dismutase enzyme (SOD) and interleukin-10 levels (IL-10) concentrations, there was a significant increase in the treated groups of the BDL group. Histological analysis revealed muscle hypotrophy in the BDL group in comparison with the control group (CO) and increased muscle mass in the treated groups. There was an increase in weight gain and phase angle in the groups treated with MLT with/or EX comparing to the BDL group. We suggest that treatments may contribute to the reduction of muscle changes in cirrhotic patients.

Resting energy expenditure in cirrhotic patients with and without hepatocellular carcinoma.

BACKGROUND: The diagnosis of malnutrition in patients with independent hepatocellular carcinoma (HCC) varies from 20% to 50%, is related to important complications and has a direct impact on the prognosis. Determination of the resting energy expenditure (REE) has become an important parameter in this population, as it allows therapeutic adjustments to recover their nutritional status. The REE in cirrhosis, with and without HCC, is not clearly defined, and requires the identification and definition of the best nutritional approach. AIM: To evaluate the REE of patients with cirrhosis, with and without HCC. METHODS: This is a prospective observational study evaluating the REE of 118 patients, 33 with cirrhosis and hepatocellular carcinoma and a control group of 85 patients with cirrhosis without HCC, using indirect calorimetry (IC), bioimpedance, and predictive formulas. RESULTS: The REE determined by IC in cirrhotic patients with HCC was 1643 ± 364 and in those without HCC was 1526 ± 277 (P = 0.064). The REE value as assessed by bioimpedance was 1529 ± 501 for those with HCC and 1660 ± 385 for those without HCC (P = 0.136). When comparing the values of REE determined by IC and predictive formulas in cirrhotics with HCC, it was observed that only the formulas of the Food and Agriculture Organization (FAO)/World Health Organization (WHO) (1985) and Cunningham (1980) presented values similar to those determined by IC. When comparing the REE values determined by IC and predictive formulas in cirrhotics without HCC, it was observed that the formulas of Schofield (1985), FAO/WHO (1985), WHO (2000), Institute of Medicine (IOM) (2005) and Katch and McArdie (1996) presented values similar to those determined by IC. CONCLUSION: The FAO/WHO formula (1985) could be used for cirrhotic patients with or without HCC; as it is the one with the values closest to those obtained by IC in these cirrhotic patients.

Phase angle and non-alcoholic fatty liver disease before and after bariatric surgery.

BACKGROUND: Obesity is a global health problem that is continuing to increase in the young population. In Brazil, the frequency of obesity in 2018 was 19.8%. Several comorbidities are directly associated with obesity, such as non-alcoholic fatty liver disease (NAFLD), which is considered the most common liver disorder in Western countries and affects up to 46% of adults. Bariatric surgery is effective in treating obesity and can improve NAFLD; however, the effect of bariatric surgery on body composition, phase angle (PA), and improving NAFLD needs to be further studied. AIM: To analyze the PA in the postoperative period of bariatric surgery and to correlate it with changes in body composition and liver disease. METHODS: This study is a retrospective cohort study of the analysis of the medical records of patients undergoing bariatric surgery in a reference center of a teaching hospital in Porto Alegre over a 2-year period. Patients older than 18 years whose record contained all information relevant to the study were included. The data analyzed were body composition and PA through electrical bioimpedance and NAFLD through liver biopsy in the pre- and postoperative period. The level of significance adopted for the statistical analyses was 5%. RESULTS: We evaluated 379 patients with preoperative data. Regarding PA, 169 patients were analyzed, and 33 patients had liver biopsy pre- and postoperatively with NAFLD information. In total, 79.4% were female, with a mean age of 39.1 ± 10.6 years. The average body mass index (BMI) was 45.9 ± 7.5 kg/m². The PA showed a mean of 5.8 ± 0.62° in the preoperative period and a significant reduction in the postoperative period. A postoperative reduction in body composition data (skeletal muscle mass, fat percentage, fat mass, body cell mass, BMI and visceral fat area) was shown as well. Regarding liver disease, all patients presented a reduction in the degrees and stages of liver disease in the postoperative period, and some had no degree of liver disease at all. CONCLUSION: PA decreased after bariatric surgery, with a direct correlation with weight loss and changes in body composition. The decrease in PA was not correlated with the improvement in NAFLD.

CAPACITY OF EXERCISE AND SURVIVAL IN PATIENTS WITH CIRRHOSIS WITH AND WITHOUT HEPATOPULMONARY SYNDROME AFTER LIVER TRANSPLANTATION.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a complication associated with cirrhosis that may contribute to worsening exercise capacity and reduced survival after liver transplantation (LT). OBJECTIVE: To evaluate exercise capacity, complications and survival after LT in patients with cirrhosis and HPS and to compare these results with the results of patients with cirrhosis without HPS. METHODS: A prospective cohort study, consisting initially of 178 patients, of whom 90 underwent LT (42 with HPS and 48 without HPS). A previous evaluation consisted of the six-minute walk test (6MWT), an exercise test and manovacuometry. Those who underwent LT were evaluated for the mechanical ventilation time (MV), noninvasive ventilation (NIV) use, and survival two years after the procedure. In the statistical analysis, we used the Kolmogorov-Smirnov test, Student's t-test, the linear association square test, and the Kaplan-Meier survival curve. The data were analyzed with the SPSS 16.00 program and considered significant at P<0.05. RESULTS: The HPS group demonstrated a lower peak of oxygen consumption (VO2peak) (14.2±2.3 vs 17.6±2.6) P<0.001 and a shorter distance walked on the 6MWT (340.8±50.9 vs 416.5±91.4) P<0.001 before LT compared with the non-HPS group. The transplanted patients with HPS remained longer hours in MV (19.5±4.3 vs 12.5±3.3) P=0.02, required more NIV (12 vs 2) P=0.01, and had lower survival two years after the procedure (P=0.01) compared with the transplanted patients without HPS. CONCLUSION: Patients with HPS had worse exercise capacity before LT, more complications and shorter survival after this procedure than patients without HPS.

Capacidade de exercício e sobrevida de pacientes cirróticos com e sem síndrome hepatopulmonar após o transplante hepático / Capacity of exercise and survival in patients with cirrhosis with and without hepatopulmonary syndrome after liver transplantation

ABSTRACT BACKGROUND: Hepatopulmonary syndrome (HPS) is a complication associated with cirrhosis that may contribute to worsening exercise capacity and reduced survival after liver transplantation (LT). OBJECTIVE: To evaluate exercise capacity, complications and survival after LT in patients with cirrhosis and HPS and to compare these results with the results of patients with cirrhosis without HPS. METHODS: A prospective cohort study, consisting initially of 178 patients, of whom 90 underwent LT (42 with HPS and 48 without HPS). A previous evaluation consisted of the six-minute walk test (6MWT), an exercise test and manovacuometry. Those who underwent LT were evaluated for the mechanical ventilation time (MV), noninvasive ventilation (NIV) use, and survival two years after the procedure. In the statistical analysis, we used the Kolmogorov-Smirnov test, Student's t-test, the linear association square test, and the Kaplan-Meier survival curve. The data were analyzed with the SPSS 16.00 program and considered significant at P<0.05. RESULTS: The HPS group demonstrated a lower peak of oxygen consumption (VO2peak) (14.2±2.3 vs 17.6±2.6) P<0.001 and a shorter distance walked on the 6MWT (340.8±50.9 vs 416.5±91.4) P<0.001 before LT compared with the non-HPS group. The transplanted patients with HPS remained longer hours in MV (19.5±4.3 vs 12.5±3.3) P=0.02, required more NIV (12 vs 2) P=0.01, and had lower survival two years after the procedure (P=0.01) compared with the transplanted patients without HPS. CONCLUSION: Patients with HPS had worse exercise capacity before LT, more complications and shorter survival after this procedure than patients without HPS.

RESUMO CONTEXTO: A síndrome hepatopulmonar (SHP) é uma complicação associada à cirrose que pode contribuir para piora da capacidade de exercício e menor sobrevida após o transplante hepático (TxH). OBJETIVO: Avaliar a capacidade de exercício, as complicações e a sobrevida após TxH em cirróticos com SHP e comparar com os resultados de cirróticos sem esse diagnóstico. MÉTODOS: Estudo de coorte prospectivo, composto inicialmente por 178 pacientes, dos quais 90 foram submetidos ao TxH (42 com SHP e 48 sem SHP). Foi realizada uma avaliação prévia composta pelo teste de caminhada dos seis minutos (TC6M), teste ergométrico e manovacuometria. Os submetidos ao TxH tiveram avaliados o tempo de ventilação mecânica (VM), uso de ventilação não invasiva (VNI), e a sobrevida dois anos após o procedimento. Na análise estatística utilizamos os testes de Kolmogorov-Smirnov, o teste t de Student, o teste do quadrado de associação linear, a curva de sobrevida de Kaplan Meier. Os dados foram analisados no programa SPSS 16.00 sendo considerado significativo P<0,05. RESULTADOS: O grupo SHP apresentou menor pico de consumo de oxigênio (VO2pico) (14,2±2,3 vs 17,6±2,6) P<0,001, e menor distância percorrida no TC6M (340,8±50,9 vs 416,5±91,4) P<0,001 antes do TxH. Os pacientes com SHP transplantados permaneceram mais horas em VM (19,5±4,3 vs 12,5±3,3) P=0,02, necessitaram mais de VNI (12 vs 2) P=0,01, e tiveram menor sobrevida dois anos após o procedimento (P=0,01). CONCLUSÃO: Pacientes com SHP apresentaram pior capacidade de exercício antes do TxH, mais complicações e menor sobrevida após a realização desse procedimento.

HEPATOCELLULAR CARCINOMA PATIENTS ARE ADVANTAGED IN THE CURRENT BRAZILIAN LIVER TRANSPLANT ALLOCATION SYSTEM. A COMPETING RISK ANALYSIS.

BACKGROUND: In Brazil, the Model for End-Stage Liver Disease (MELD) score is used to prioritize patients for deceased donor liver transplantation (DDLT). Patients with hepatocellular carcinoma (HCC) receive standardized MELD exception points to account for their cancer risk of mortality, which is not reflected by their MELD score. OBJECTIVE: To compare DDLT rates between patients with and without HCC in Rio Grande do Sul, the Southernmost state of Brazil. METHODS: - We retrospectively studied 825 patients on the liver-transplant waiting list from January 1, 2007, to December 31, 2016, in a transplant center located in Porto Alegre, the capital of Rio Grande do Sul, to compare DDLT rates between those with and without HCC. The time-varying hazard of waiting list/DDLT was estimated, reporting the subhazard ratio (SHR) of waiting list/DDLT/dropout with 95% confidence intervals (CI). The final competing risk model was adjusted for age, MELD score, exception points, and ABO group. RESULTS: Patients with HCC underwent a transplant almost three times faster than patients with a calculated MELD score (SHR 2.64; 95% CI 2.10-3.31; P<0.001). The DDLT rate per 100 person-months was 11.86 for HCC patients vs 3.38 for non-HCC patients. The median time on the waiting list was 5.6 months for patients with HCC and 25 months for patients without HCC. CONCLUSION: Our results demonstrated that, in our center, patients on the waiting list with HCC have a clear advantage over candidates listed with a calculated MELD score.

Pacientes com carcinoma hepatocelular são favorecidos no atual sistema brasileiro de alocação de fígados para transplante. Análise de riscos competitivos / Hepatocellular carcinoma patients are advantaged in the current brazilian liver transplant allocation system. a competing risk analysis

ABSTRACT BACKGROUND: In Brazil, the Model for End-Stage Liver Disease (MELD) score is used to prioritize patients for deceased donor liver transplantation (DDLT). Patients with hepatocellular carcinoma (HCC) receive standardized MELD exception points to account for their cancer risk of mortality, which is not reflected by their MELD score. OBJECTIVE: To compare DDLT rates between patients with and without HCC in Rio Grande do Sul, the Southernmost state of Brazil. METHODS - We retrospectively studied 825 patients on the liver-transplant waiting list from January 1, 2007, to December 31, 2016, in a transplant center located in Porto Alegre, the capital of Rio Grande do Sul, to compare DDLT rates between those with and without HCC. The time-varying hazard of waiting list/DDLT was estimated, reporting the subhazard ratio (SHR) of waiting list/DDLT/dropout with 95% confidence intervals (CI). The final competing risk model was adjusted for age, MELD score, exception points, and ABO group. RESULTS: Patients with HCC underwent a transplant almost three times faster than patients with a calculated MELD score (SHR 2.64; 95% CI 2.10-3.31; P<0.001). The DDLT rate per 100 person-months was 11.86 for HCC patients vs 3.38 for non-HCC patients. The median time on the waiting list was 5.6 months for patients with HCC and 25 months for patients without HCC. CONCLUSION: Our results demonstrated that, in our center, patients on the waiting list with HCC have a clear advantage over candidates listed with a calculated MELD score.

RESUMO CONTEXTO: No Brasil, o escore MELD (Model for End-Stage Liver Disease) é utilizado para priorizar os pacientes para transplante hepático de doador falecido (THDF). Pacientes com carcinoma hepatocelular (CHC) recebem pontos de exceção padronizados pelo MELD para contrapesar o risco de mortalidade do seu câncer, que não é refletido pelo seu escore MELD. OBJETIVO: Comparar as taxas de THDF entre pacientes com e sem CHC no Rio Grande do Sul, o Estado mais ao sul do Brasil. MÉTODOS: Foram estudados retrospectivamente 825 pacientes em lista de espera de transplante de fígado entre 1 de janeiro de 2007 e 31 de dezembro de 2016 em um centro de transplantes localizado em Porto Alegre, capital do Rio Grande do Sul, para comparação das taxas de THDF entre aqueles com e sem CHC. Foi estimado o risco variável no tempo de lista de espera/THDF, com relato da taxa de sub-risco (SHR) de lista de espera/THDF/desistência com intervalos de confiança (IC) de 95%. O modelo final de risco competitivo foi ajustado para idade, escore MELD, pontos de exceção e grupo ABO. RESULTADOS: Os candidatos com CHC foram submetidos a um transplante quase três vezes mais rápido do que os pacientes com um escore MELD calculado (SHR 2,64; IC 95% 2,10-3,31; P<0,001). A taxa de THDF por 100 pessoas-mês foi de 11,86 para os pacientes com CHC vs 3,38 para os pacientes sem CHC. O tempo mediano de permanência em lista de espera foi de 5,6 meses para os pacientes com CHC e 25 meses para os pacientes sem CHC. CONCLUSÃO: Nossos resultados demonstraram que, em nosso centro, pacientes em lista de espera com CHC têm evidente vantagem sobre candidatos listados com um escore MELD calculado.

Bioelectrical impedance vector analysis evaluates cellularity and hydration in cirrhotic patients.

BACKGROUND: Malnutrition in cirrhotic patients is correlated with mortality and a better response to liver transplantation. However, recovery of the nutritional status in these patients is a challenge due to the difficulty in establishing a reliable nutritional diagnosis. The bioelectrical impedance vector analysis (BIVA) method appears as a feasible tool in clinical practice to define the physiological state of cirrhotic patients by assessing hydration and body cellularity. AIM: To evaluate body composition in cirrhotic patients using BIVA. METHODS: This retrospective cross-sectional study was carried out by following cirrhotic outpatients at a hospital in Porto Alegre, Brazil. A tetrapolar bioelectrical impedance analysis device was used to evaluate cellularity and hydration and to perform the BIVA. The BIVA graphic was elaborated by software and for statistical analysis a significance level of 5% (P ≤ 0.05) was considered. RESULTS: One hundred and ninety patients, 61.1% males, with a mean age of 56.6 ± 11.0 years, were evaluated. Of these, 56.3% had Child-Turcotte-Pugh (CTP) A score, and the prevalent etiology was hepatitis C virus (47.4%). The patients were classified according to cellularity and hydration by the quadrants and ellipses of the BIVA method, quadrant 1 (47.9%); quadrant 2 (18.9%); quadrant 3 (14.2%); and quadrant 4 (18.9%). Those classified in quadrant 1 and 2 had a higher phase angle compared to those in quadrants 3 and 4 (P < 0.001). Quadrant 2 patients had a lower average age than the other groups. The association with CTP score showed that patients in quadrant 2 had a higher proportion of CTP A, and those in quadrant 4 had a higher proportion of CTP C (P < 0.052). CONCLUSION: The BIVA method allows identification of the cellularity and hydration status of cirrhotic patients, and its association with clinical factors determines the disease severity, age and prognostic index.

THE COST OF ADULT LIVER TRANSPLANTATION IN A REFERRAL CENTER IN SOUTHERN BRAZIL.

BACKGROUND: Liver transplantation (LTx) is the primary and definitive treatment of acute or chronic cases of advanced or end-stage liver disease. Few studies have assessed the actual cost of LTx categorized by hospital unit. OBJECTIVE: To evaluate the cost of LTx categorized by unit specialty within a referral center in southern Brazil. METHODS: We retrospectively reviewed the medical records of 109 patients undergoing LTx between April 2013 and December 2014. Data were collected on demographic characteristics, etiology of liver disease, and severity of liver disease according to the Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores at the time of LTx. The hospital bill was transformed into cost using the full absorption costing method, and the costs were grouped into five categories: Immediate Pretransplant Kit; Specialized Units; Surgical Unit; Intensive Care Unit; and Inpatient Unit. RESULTS: The mean total LTx cost was US$ 17,367. Surgical Unit, Specialized Units, and Intensive Care Unit accounted for 31.9%, 26.4% and 25.3% of the costs, respectively. Multivariate analysis showed that total LTx cost was significantly associated with CTP class C (P=0.001) and occurrence of complications (P=0.002). The following complications contributed to significantly increase the total LTx cost: septic shock (P=0.006), massive blood transfusion (P=0.007), and acute renal failure associated with renal replacement therapy (dialysis) (P=0.005). CONCLUSION: Our results demonstrated that the total cost of LTx is closely related to liver disease severity scores and the development of complications.