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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.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Recidiva Local de NeoplasiaRESUMO
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.
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Inflamação/terapia , Cirrose Hepática/complicações , Melatonina/farmacologia , Estresse Oxidativo , Condicionamento Físico Animal , Músculo Quadríceps/efeitos dos fármacos , Sarcopenia/terapia , Animais , Antioxidantes/farmacologia , Inflamação/etiologia , Inflamação/patologia , Masculino , Músculo Quadríceps/patologia , Ratos , Ratos Wistar , Sarcopenia/etiologia , Sarcopenia/patologiaRESUMO
INTRODUCTION: Liver retransplantation (LReTx) is the therapeutic option for hepatic graft failure. Survival after LReTx is poorer than after primary liver transplantation. Given the organ shortage, it is essential to optimize the use of this resource. OBJECTIVE: To evaluate rates, indications and patient survival after LReTx and identify factors associated with mortality following LReTx. MATERIAL AND METHODS: We conducted a retrospective cohort study of all adults undergoing LReTx based on registry data from the Liver Transplantation Group (Complexo Hospitalar Santa Casa de Porto Alegre), southern Brazil. RESULTS: Between June 16, 1991 and July 19, 2011, 824 patients underwent 866 liver transplants. Forty-two procedures corresponded to LReTx (4.8% of all liver transplants performed). Thirty-eight patients who underwent a single LReTx procedure were included in this study. The leading indication for LReTx was hepatic artery thrombosis (HAT) (31.6%), followed by primary nonfunction (PNF) (18.4%). The main indication for early LReTx was PNF (58.3%) and for late LReTx was HAT (38.5%). During the follow-up period, 26 patients (68.4%) died after LReTx. Patient survival at 1 and 3 years after LReTx was 44.7% and 44.7%, respectively. Patients infected with hepatitis C virus, serum albumin < 2.5 g/dL and receiving mechanical ventilation immediately before LReTx had a significantly lower survival rate than the other patients. CONCLUSION: Considering the increased mortality when the graft loss is delayed, it is necessary to define the minimum acceptable results to indicate LReTx and identify the patients who would most benefit from this treatment.
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Arteriopatias Oclusivas/cirurgia , Artéria Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Disfunção Primária do Enxerto/cirurgia , Trombose/cirurgia , Adolescente , Adulto , Idoso , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/mortalidade , Brasil , Criança , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/mortalidade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Trombose/etiologia , Trombose/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: A systematic bias against women, resulting from the use of creatinine as a measure of renal function, has been identified in Model for End-stage Liver Disease (MELD)-based liver allocation. Correction of this bias by calculation of female creatinine levels using the Modification of Diet in Renal Disease (MDRD) formula has been suggested. MATERIAL AND METHODS: A cohort of 639 cirrhotic candidates for first-time liver transplantation was studied. Creatinine levels were corrected for gender using the MDRD formula. The accuracy of MELD, with or without creatinine correction, to predict 3-and 6-month mortality after inclusion in a transplant waiting list was estimated. RESULTS: Women exhibited significantly lower creatinine levels, glomerular filtration rate, and MELD scores than men. After creatinine correction, female MELD scores had a mean increase of 1.1 points. Creatinine correction yielded an increase of 3 points in the MELD score in 15.2% of patients, 2 points in 22.4%, and 1 point in 17.6% of patients. The likelihood of death at 3 and 6 months after enrollment in the transplant waiting list was similar in males and females and the likelihood of receiving a transplant, as assessed by Kaplan-Meier survival curves, was also similar in males and females. CONCLUSION: The survival or the likelihood of receiving a transplant while on the waiting list were similar in men and women in both pre- and post-MELD eras and creatinine correction did not increase the accuracy of the MELD score in estimating 3- and 6-month mortality in female candidates for liver transplantation.
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Creatinina/sangue , Indicadores Básicos de Saúde , Disparidades em Assistência à Saúde , Rim/fisiopatologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Seleção de Pacientes , Listas de Espera , Adulto , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo , Listas de Espera/mortalidadeRESUMO
BACKGROUND/AIMS: Liver diseases are responsible for metabolic disturbances and the loss of muscle mass and function. This study aims to correlate maximal oxygen uptake (VO2max) with the Model for End Stage Liver Disease (MELD) severity score and associate VO2max with mortality in patients with alcoholic cirrhosis. METHODOLOGY: This prospective study included 27 patients who had a diagnosis of alcoholic liver cirrhosis. All subjects were followed for 3 years and performed an exercise test to determine VO2max. RESULTS: The study included 18 men and 9 women. We observed a strong inverse correlation between VO2max and MELD (r=-0.91, p<0.001). In a survival analysis, individuals who had a VO2max less than 14mL/kg showed 60% mortality when compared with those who had a VO2max greater than 14mL/kg (p<0.0001; OR: 3.29; 95% CI: 1.44-5.25). CONCLUSIONS: The VO2max is directly associated with the survival of patients with alcoholic cirrhosis and demonstrates a strong inverse correlation with the MELD severity score.
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Cirrose Hepática Alcoólica/mortalidade , Consumo de Oxigênio , Trifosfato de Adenosina/análise , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática Alcoólica/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
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.
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[This corrects the article on p. 688 in vol. 13, PMID: 36160465.].
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BACKGROUND: Liver cancer is one of the most common malignancies in the world and at the moment, there is no drug intervention effective for the treatment of liver tumours. Investigate the effect of N-acetylcysteine (NAC), which has been studied for its antitumoural properties, on the toxicity of hepatocarcinoma (HCC) cells in vitro when used with the drug interferon alpha-2A (IFN), which is used clinically to treat HCC. RESULTS: NAC, IFN and NAC plus IFN reduced cell viability, as determined by MTT assay. More importantly, NAC potentiates the cytotoxic effect of IFN, with the best response achieved with 10 mM of NAC and 2.5 x 104 of IFN. These results were confirmed by Annexin/PI staining through flow cytometry and morphologic analyses. Co-treatment reduced the expression of the nuclear transcription factor kappa-B (NF-kB). In a similar way to NAC, RNAi against p65 potentiated the toxic effect of IFN, suggesting that, indeed, NAC may be enhancing the effect of IFN through inhibition of NF-kB. CONCLUSIONS: Our results support the notion that NAC may be an important drug for the treatment of liver tumours as primary or adjuvant therapy. IFN has a limited clinical response, and therefore, the anti-proliferative properties of NAC in the liver should be explored further as an alternative for non-responders to IFN treatment.
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Croton cajucara Benth is a plant found in Amazonia, Brazil and the bark and leaf infusion of this plant have been popularly used to treat diabetes and hepatic disorders. The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Croton cajucara Benth (1.5 mL of the C. cajucara extract i.g.) in rats with streptozotocin-induced diabetes. Croton cajucara Benth was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipid peroxidation and superoxide dismutase, catalase, and glutathione reductase activities were measured in the hepatic tissue, as well as the presence activation of p65 (NF-κB), through western blot. Phytochemical screening of Croton cajucara Benth detected the presence of flavonoids, coumarins and alkaloids. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hypoxanthine/xanthine oxidase assays. Liver lipid peroxidation increased in diabetic animals followed by a reduction in the Croton-cajucara-Benth-treated group. There was activation of p65 nuclear expression in the diabetic animals, which was attenuated in the animals receiving the Croton cajucara Benth aqueous extract. The liver tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. In conclusion the Croton cajucara Benth aqueus extract treatment effectively reduced the oxidative stress and contributed to tissue recovery.
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Croton/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Fígado/patologia , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Animais , Compostos de Bifenilo/metabolismo , Western Blotting , Ensaios Enzimáticos , Sequestradores de Radicais Livres/metabolismo , Concentração Inibidora 50 , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Picratos/metabolismo , Extratos Vegetais/farmacologia , Subunidades Proteicas/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo , Xantina Oxidase/metabolismoRESUMO
We evaluated the efficacy of pineapple juice with gadopentetate dimeglumine as a negative oral contrast agent for magnetic resonance cholangiopancreatography (MRCP). Images were obtained before and after the intake of a negative oral contrast agent. Images obtained from six different areas of the biliary tree were analyzed by three different radiologists, who were blind to the exams; scores regarding image quality were given to each area. The statistical analysis showed a significant difference between images before and after the use of the contrast agent (P < 0.001) for the three radiologists (R1-R3). Mean scores given by radiologists before the intake of the contrast agent were 2.49 ± 0.42 (R1), 2.62 ± 0.32 (R2), and 2.22 ± 0.46 (R3). After the intake, mean scores were 3.38 ± 0.62 (R1), 3.48 ± 0.55 (R2), and 2.89 ± 0.69 (R3). The ducts that showed the highest scores were the common bile duct and duct of Wirsung, the distal portion of the common bile duct and the cystic duct. We suggest herein that the contrast agent pineapple juice with gadopentate dimeglumine constitutes an efficient negative oral contrast agent for MRCP, for it efficiently eliminates the signal of the digestive tube in MRCP images.
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Ananas , Meios de Contraste , Gadolínio DTPA , Adolescente , Adulto , Idoso , Análise de Variância , Bebidas , Brasil , Colangiopancreatografia por Ressonância Magnética/métodos , Meios de Contraste/administração & dosagem , Estudos Cross-Over , Feminino , Gadolínio DTPA/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. OBJECTIVE: To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. MATERIAL AND METHODS: A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. RESULTS: Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002). CONCLUSION: The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Predisposição Genética para Doença , Hepatectomia , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/química , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Resultado do TratamentoRESUMO
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.
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Terapia por Exercício , Qualidade de Vida , Exercício Físico , Fadiga , Humanos , Cirrose Hepática , Projetos PilotoRESUMO
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.
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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 Ë .05), APACHE IV (P Ë .001), length of stay in the intensive care unit (P Ë .001), and death outcome (P Ë .001) were observed. The greatest workload was in checking vital signs, water balance, and administrative tasks (P Ë .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.
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Doença Hepática Terminal , Transplante de Fígado , Masculino , Humanos , Pessoa de Meia-Idade , APACHE , Carga de Trabalho , Transplante de Fígado/efeitos adversos , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Estudos de Coortes , Estudos Retrospectivos , Índice de Gravidade de Doença , Unidades de Terapia Intensiva , Tempo de InternaçãoRESUMO
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.
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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.
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Deficiência de Colina , Melatonina , Hepatopatia Gordurosa não Alcoólica , Alanina Transaminase , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aspartato Aminotransferases , Biomarcadores/metabolismo , Catalase/metabolismo , Colina/análise , Colina/metabolismo , Colina/farmacologia , Deficiência de Colina/complicações , Deficiência de Colina/metabolismo , Dano ao DNA , Dieta , Glutationa Peroxidase/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Metionina/análise , Metionina/genética , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
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Recurrent hepatitis C after liver transplantation is universal. Graft reinfection occurs rapidly, with chronic hepatitis and rapid evolution from end-stage liver disease. Within 5 years until 30% of patients with recurrent disease ultimately progress to cirrhosis, and survival of transplanted patients with recurrent hepatitis C virus has been shown to be lower than of patients transplanted for other indications. Antiviral therapy in this patient population is generally recommended, but indication, optimal timing, dose and duration of therapy are not clearly defined. There are two major indications of therapy in that patients: pre-transplant antiviral therapy aiming to prevent reinfection, and post-transplant therapy with the goal of eradicating the recurrent infection. The first is limited by poor tolerance and drug side effects, and the second achieves only sustained virologic response in 25-45% of patients. Combination therapy with PEG INF and ribavirin showed the better results. Dose reduction and interruption of therapy occurs in 30 to 60% by side effects. There are no prospective randomized trials with confidence of results. More efficacious and better tolerable antiviral therapies are needed.
Assuntos
Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Hepatite C/cirurgia , Transplante de Fígado/efeitos adversos , Antivirais/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Sobrevivência de Enxerto/efeitos dos fármacos , Hepatite C/diagnóstico , Humanos , Interferon-alfa/administração & dosagem , Guias de Prática Clínica como Assunto , Recidiva , Ribavirina/administração & dosagem , Resultado do TratamentoRESUMO
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.
RESUMO
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.