Evolución de los pacientes con enfermedad hepática crítica / Prognosis of patients with critical hepatic disease

INTRODUCTION: The acute liver failure on chronic (ACLF), is an entity, whose recognition is increasing. The ACLF and CLIF OF indexes have been recently presented with the objective of predicting mortality in this kind of patients. MATERIAL AND METHODS: All patients admitted to the Ramón y Cajal University Hospital diagnosed of acute liver failure on chronic during 2016 and 2017 were collected. We collect the scores: SOFA, CLIF, APACHE II, SAPS II and ACLF score in patients admitted to the ICU by comparing them with each other and define which stages have worse prognosis. RESULTS: A total of 46 patients were collected. The study presents an intra ICU mortality of 31% (15/46) and a six-month mortality of 59.6% (28/46). Patients classified as death, present ACLF values ​​at admission (49.5 vs 60 p = 0.001), and at three days (46.66 vs 59.4 p = 0.001) higher than survivors. In the analysis of the ROC curve, the area under the curve in relation to six-month mortality is higher in the ACLF index (0.8) compared to the MELD (0.69) SOFA (0.66) SAPS II (0.69) or APACHE II (0.65). Patients with ACLF indexes above 65 had an intra UCI mortality of 54%, however, mortality at 6 months is 90%. Patients with ACLF values ​​greater than 65 present mean values ​​of lactic acid, leukocytes, INR or bilirubin higher than those under 65 in a statistically significant manner. CONCLUSIONS: The data presented in this study suggest that the ACLF index works as an adequate predictor of intra-ICU mortality and at 6 months.

INTRODUCCIÓN: El fallo hepático agudo sobre crónico es una entidad cuyo reconocimiento va en aumento. Los índices ACLF y CLIF OF, han sido presentados recientemente con el objetivo de predecir la mortalidad en este tipo de enfermos. MATERIAL Y MÉTODOS: Se recogen todos los pacientes ingresados en una unidad de cuidados intensivos (UCI) de un hospital terciario universitario, diagnosticados de fallo hepático agudo sobre crónico durante 2016 y 2017. Recogemos los índices SOFA, CLIF, APACHE II, SAPS II Y ACLF en pacientes ingresados en UCI comparándolos entre sí. Definimos que estadios presentan peor pronóstico. RESULTADOS: Se analizan un total de 46 pacientes. El estudio presenta una mortalidad intra-UCI del 31% (15/46) y una mortalidad a los seis meses de 59,6% (28/46). Los pacientes clasificados como éxitus presentan valores ACLF al ingreso (49,5 vs 60 p = 0,001), a los tres días (46,66 vs 59,4 p = 0,001) superiores a los supervivientes. En el análisis de la curva COR, el área bajo la curva en relación a la mortalidad a los seis meses, es superior en el índice ACLF (0,8) en comparación con el MELD (0,69) SOFA (0,66) SAPS II (0,69) o APACHE II (0,65). Los pacientes con índices ACLF superiores a 65 presentaban una mortalidad intra-UCI del 54% sin embargo, la mortalidad a los 6 meses es del 90%. Los pacientes con valores ACLF superiores a 65 presentan a su vez valores medios de láctico, leucocitos, INR o bilirrubina mayores de forma estadísticamente significativa. CONCLUSIONES: Los datos presentados en este estudio sugieren que el índice ACLF funciona como un adecuado predictor de mortalidad intra-UCI y a los 6 meses.

Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis.

BACKGROUND AND AIMS: Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis. APPROACH AND RESULTS: This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96). CONCLUSIONS: Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

Prognostic value of hepatic encephalopathy for survival of patients with liver failure: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The aim of this paper was to evaluate the association of hepatic encephalopathy with survival of patients with liver failure. MATERIALS AND METHODS: We retrieved the relevant articles from the PubMed, Embase and Cochrane Library, up to May 2017. The pooled odds ratio (OR) as well as their 95% confidence intervals (CI) was calculated by the software of R package version 3.12. RESULTS: Total 13 studies with 2071 liver failure patients were included and reanalyzed in this meta-analysis. The results proved the prognostic value of hepatic encephalopathy for survival of patients with liver failure (OR=5.62, 95%CI=6.30-9.82, P<0.001). The subgroup analyses showed that the type of liver failure and the follow up duration may be the factor influencing the association between hepatic encephalopathy and survival of patients with liver failure. CONCLUSIONS: The results proved that hepatic encephalopathy was a prognostic factor of survival in patients with liver failure.

Low vitamin D at ICU admission is associated with cancer, infections, acute respiratory insufficiency, and liver failure.

OBJECTIVES: Vitamin D deficiency may be associated with comorbidities and poor prognosis. However, this association in patients in the intensive care unit (ICU) has not been fully elucidated. The aim of this study was to investigate whether the serum concentrations of 25-hydroxyvitamin D (25[OH]D) within the first 48 h after ICU admission are associated with prognostic indicators (Acute Physiology and Chronic Health Evaluation [APACHE] II, Sequential Organ Failure Assessment [SOFA] score, Charlson comorbidity index [CCI]), clinical complications, serum C-reactive protein (CRP) concentrations, mechanical ventilation duration, and mortality. METHODS: Seventy-one patients were admitted to the ICU, and their concentrations of 25(OH)D in the first 48 h were analyzed. To evaluate the prognostic factors in the ICU, APACHE II scores, SOFA scores, CCI questionnaires, mechanical ventilation time, CRP, and mortality were used. RESULTS: The mean concentration of 25(OH)D was 17.7 ± 8.27 ng/mL (range 3.5-37.5 ng/mL), with 91.6% presenting with deficiency at admission. Although no associations were found between serum 25(OH)D concentrations with mechanical ventilation time, CRP, mortality, and APACHE II and SOFA severity scores, we found associations with the CCI when adjusted by age (model 1: odds ratio [OR], 1.64; 95% confidence interval [CI], 1.14-2.34) and by age, sex and body mass index (model 2: OR, 1.59; 95% CI, 1.10-2.34). In addition, among the comorbidities present, 25(OH)D concentrations were inversely associated with cancer (crude model OR, 3.42; 95% CI, 1.21-9.64) and liver disease (crude model OR, 9.64; 95% CI, 2.28-40.60). CONCLUSION: We found a strong association between 25(OH)D concentrations and the prognostic indicator CCI and clinical complications (acute respiratory insufficiency, acute liver failure, and infections), but no associations with the prognostic indicators APACHE II and SOFA score, CRP, mechanical ventilation duration, or mortality. The main comorbidities associated with low 25(OH)D were cancer and liver disease, suggesting that the determination of 25(OH)vitamin D is relevant during the ICU stay.

The Effects of Gestational Alloimmune Liver Disease on Fetal and Infant Morbidity and Mortality.

OBJECTIVES: To evaluate pregnancy outcomes in pedigrees of neonatal hemochromatosis to determine the spectrum of gestational alloimmune liver disease (GALD) in a large cohort. STUDY DESIGN: We prospectively collected data from women with a prior offspring with proven neonatal hemochromatosis between 1997 and 2015 and analyzed pregnancy outcomes. RESULTS: The pedigrees from 150 women included 350 gestations with outcomes potentially related to GALD. There were 105 live-born infants without liver disease, 157 live-born infants with liver failure, and 88 fetal losses. Fetal loss occurred in 25% of total gestations. Ninety-seven pedigrees contained a single affected offspring, whereas 53 contained multiple affected offspring. Analysis of these 53 pedigrees yielded a per-pregnancy repeat occurrence rate of 95%. Notably, the first poor outcome occurred in the first pregnancy in 60% of pedigrees. Outcomes of the 157 live-born infants with liver failure were poor: 18% survived, 82% died. Of the 134 live-born infants with treatment data, 20 received intravenous immunoglobulin with or without double-volume exchange transfusion of which 9 (45%) survived; 14 infants (10%) received a liver transplant of which 6 (43%) survived. CONCLUSIONS: GALD is a significant cause of both fetal loss and neonatal mortality with a high rate of disease recurrence in untreated pregnancies at risk. Poor outcomes related to GALD commonly occur in the first gestation, necessitating a high index of suspicion to diagnose this disorder at first presentation.

Isoniazid Preventive Therapy for People With HIV Who Are Heavy Alcohol Drinkers in High TB-/HIV-Burden Countries: A Risk-Benefit Analysis.

BACKGROUND: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. METHODS: We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. RESULTS: In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. CONCLUSIONS: The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance.

Prognostic factors for death from visceral leishmaniasis in patients treated with liposomal amphotericin B in an endemic state in Brazil.

Objective: To characterize the clinical and epidemiological profiles of patients with visceral leishmaniasis (VL) treated with liposomal amphotericin B (LAmB) and to identify prognostic factors for death from VL in 2008-2012 in the state of Minas Gerais, Brazil. Methods: A historical cohort study was conducted using data obtained from treatment requests forms, Brazilian Notifiable Disease Information System and the Mortality Information System. Case-fatality rates of patients with VL treated with LAmB were compared with patients treated with other therapies. Logistic regression analysis was used to identify prognostic factors for death. Results: The overall case-fatality rate of the 577 patients treated with LAmB was 19.4%. Prognostic factors for death from VL were age between 35 and 49 years (OR 2.7; 95% CI 1.3-5.4) and above 50 years (OR 2.6; 95% CI 1.3-4.9), jaundice (OR 2.2; 95% CI 1.2-3.7), kidney disease (OR 2.8; 95% CI 1.6-4.9), presence of other infections (OR 2.4; 95% CI 1.5-4.1), edema (OR 2.0; 95% CI 1.1-3.4), platelet count below 50.000/mm3 (OR 3.6; 95% CI 2.1-6.0), AST higher than 100 U/L (OR 2.2; 95% CI 1.3-3.8), and assistance in non-specialized institutions (OR 1.9; 95% CI 1.0-3.5). Conclusions: Case-fatality rates were higher than that observed among patients with VL treated with other therapies. Identification of prognostic factors of death from VL may allow early diagnosis of patients prone to such outcome and prompt an expeditious and appropriate management of VL to reduce fatality rates.

Hemophilia Liver Transplantation Observational Study.

Hepatitis C virus (HCV) infection is the leading cause of liver disease in hemophilia patients. In those with human immunodeficiency virus (HIV)/HCV coinfection, the rate of liver disease progression is greater than in HCV monoinfected individuals. Despite antiretroviral therapy, which slows HCV liver disease progression, some require transplantation. Whether transplant outcomes are worse in hemophilic (H) rather than nonhemophilic (NH) candidates is unknown. In order to determine rates and predictors of pretransplant and posttransplant survival, we conducted a retrospective observational study using United Network for Organ Sharing national transplant registry data, comparing HCV+ H and NH candidates. We identified 2502 HCV+ liver transplant candidates from 8 US university-based transplant centers, between January 1, 2004 to December 31, 2010, including 144 HIV+ (6%) and 2358 HIV-; 36 H (1%) and 2466 NH; 1213 (48%) transplanted and 1289 not transplanted. Other than male predominance and younger age, each were P < 0.001. Baseline data were comparable between H and NH. In univariate analysis, 90-day pretransplant mortality was associated with higher baseline Model for End-Stage Liver Disease (MELD; hazard ratio [HR] = 1.15; P < 0.001), lower baseline platelet count (HR = 0.9 per 25,000/µL; P = 0.04), and having HIV/HCV+ hemophilia (P = 0.003). In multivariate analysis, pretransplant mortality was associated with higher MELD (P < 0.001) and was significantly greater in HIV+ than HIV- groups (P = 0.001). However, it did not differ between HIV+ H and NH (HR = 1.7; P = 0.36). Among HIV/HCV+, posttransplant mortality was similar between H and NH, despite lower CD4 in H (P = 0.04). In conclusion, this observational study confirms that hemophilia per se does not have a specific influence on transplant outcomes and that HIV infection increases the risk of mortality in both H and NH patients. Liver Transplantation 23 762-768 2017 AASLD.

Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis.

BACKGROUND: Glucose metabolism abnormalities frequently coexist with liver cirrhosis; however, the impact of these on liver-related outcomes has not been fully investigated. AIMS: We examined the influence of glucose abnormalities on overall mortality and liver-related complications in cirrhotic patients. METHODS: A prospective cohort of 250 subjects with compensated hepatitis C virus-related cirrhosis and without known diabetes underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks. RESULTS: At baseline, 67 (27%) had type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (sHR: 2.2, 95% CI: 1.04-4.6, P=0.04) and hepatic decompensation events (sHR: 1.9, 95% CI: 1.05-3.3, P=0.03) were significantly higher in diabetic patients. Subjects with a HOMA-IR >5 showed higher rates of mortality (sHR: 2.2, 95% CI: 1.03-4.8, P=0.04). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (sHR: 1.7, 95% CI: 1.04-2.9, P=0.03). Overall, 2h-plasma glucose was the most robust predictor of overall mortality (sHR: 2.5, 95% CI: 1.03-6, P=0.04) and decompensation (sHR: 2.7, 95% CI: 1.4-5.5, P<0.01). CONCLUSIONS: In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival and increased risk of hepatic decompensation.

The efficacy and safety of entecavir in patients with chronic hepatitis B- associated liver failure: a meta-analysis.

BACKGROUND: The effectiveness of nucleoside analogue (NA) treatment in patients with chronic hepatitis B (CHB) -associated liver failure is still controversial. Severe lactic acidosis has been reported during entecavir (ETV) treatment in patients with impaired liver function. AIM: To investigate the rescuing efficacy and safety of ETV in patients with CHB-associated liver failure. MATERIAL AND METHODS: A literature search was carried out to collect articles dated up to December, 2013 on ETV therapy for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was used as the primary efficacy measure. The safety of ETV was assessed. RESULTS: Six randomized controlled trials were selected. The overall analysis revealed ETV significantly improved survival at 4 weeks (RR = 1.35; 95% CI [1.16, 1.57]; p < 0.0001), 8 weeks (RR = 1.33; 95% CI [1.07, 1.64]; p = 0.009), 12 weeks (RR = 1.68; 95% CI [1.24, 2.28]; p = 0.0008). Pooled data also showed beneficial effects of antiviral therapy compared with control for HBV DNA negative change (RR = 5.35; 95% CI [2.06, 13.88]; p = 0.0006), TBIL and PTA improvement (TBIL: MD = -69.36; 95% CI [-134.37, -4.36]; p = 0.04. PTA: MD = 16.26; 95% CI [8.59, 23.94]; p < 0.0001). No adverse effect was identified in the examined studies. CONCLUSION: Our results showed that antiviral therapy with ETV improved the short-term survival of patients with CHB-associated liver failure. In addition, ETV was well tolerated during the treatment period. Further studies are still needed to strengthen these results.

Propranolol associated with endoscopic band ligation reduces recurrence of esophageal varices for primary prophylaxis of variceal bleeding: a randomized-controlled trial.

OBJECTIVE: The aim of this study was to compare the recurrence of esophageal varices (EVs) after endoscopic band ligation (EBL) associated with propranolol (PP) versus EBL alone. PATIENTS AND METHODS: Sixty-six cirrhotic outpatients (EBL group, n=32 and EBL+PP group, n=34) with high-risk EVs without previous bleeding were studied. MAIN OUTCOME MEASUREMENTS: The primary outcome was recurrence of EV. The secondary outcomes were EV eradication, bleeding before EV eradication, mortality, and adverse events. RESULTS: Demographic characteristics and the initial endoscopic findings were similar. EV eradication was achieved in all patients. Three patients presented gastrointestinal bleeding before variceal eradication, two in the EBL group and one in the EBL+PP group (P=0.13). Six patients died (liver failure), two in the EBL group and four in the EBL+PP group (P=0.27). Twelve (38%) patients in the EBL group and three (9%) patients in the EBL+PP group had variceal recurrence. The risk of recurrence of EVs after eradication was significantly higher among patients in the EBL group (P=0.003). CONCLUSION: EBL alone and EBL+PP were effective in the primary prophylaxis of bleeding from EVs in cirrhotic patients (EV eradication, bleeding before EV eradication, mortality, and adverse events were similar in both groups). However, variceal recurrence was lower in the EBL+PP group than band ligation alone.

Clinical and molecular characteristics of mitochondrial DNA depletion syndrome associated with neonatal cholestasis and liver failure.

OBJECTIVE: To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants with cholestasis and liver failure and to further clarify the clinical, biochemical, radiologic, histopathologic, and molecular features associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene mutations. STUDY DESIGN: We studied 20 infants with suspected hepatocerebral MDS referred to our tertiary care center between 2007 and 2013. Genomic DNA was isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard methods. Mitochondrial DNA copy number relative to nuclear DNA levels was determined in muscle and/or liver DNA using real-time quantitative polymerase chain reaction and compared with age-matched controls. Nuclear candidate genes, including polymerase γ, MPV17, and DGUOK were sequenced using standard analyses. RESULTS: We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period. All of the 11 patients manifested cholestasis that was followed by a rapidly progressive liver failure and death before 2 years of life. Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the 11 cases where tissue was available. Seven patients had mutations in the MPV17 gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel mutations). CONCLUSION: Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis.

Extended preoperative chemotherapy, extent of liver resection and blood transfusion are predictive factors of liver failure following resection of colorectal liver metastasis.

AIM: The aim of this study was to determine the incidence and prognostic factors of postoperative liver failure in patients submitted to liver resection for colorectal metastases. METHOD: Patients with CLM who underwent hepatectomy from 1998 to 2009 were included in retrospective analysis. Postoperative liver failure was defined using either the 50-50 criteria or the peak of serum bilirubin level above 7 mg/dL independently. RESULTS: Two hundred and nine (209) procedures were performed in 170 patients. 120 surgeries were preceded by chemotherapy within six months. The overall morbidity rate was 53.1% and 90-day mortality was 2.3%. Postoperative liver failure occurred in 10% of all procedures, accounting for a mortality rate of 9.5% among this group of patients. In multivariate analysis, extent of liver resection, need of blood transfusion and more than eight preoperative chemotherapy cycles were independent prognostic factors of postoperative liver insufficiency. This complication was not related with the chemotherapy regimen used. CONCLUSION: We conclude that postoperative liver failure has a relatively low incidence (10%) after CLM resection, but a remarkable impact on postoperative mortality rate. The amount of liver resected, the need of blood transfusion and extended preoperative chemotherapy are independent predictors of its occurrence and this knowledge can be used to prevent postoperative liver failure in a multidisciplinary approach.

Orthotopic liver transplantation without venovenous bypass: 125 cases from a single center.

AIM: This study analyzed a 10-year single-center experience in orthotopic liver transplantation (OLT) without venovenous bypass (VVB). METHODS: We retrospectively analysed a nonrandomized series (1999-2008) of 125 adult OLT patients without VVB. RESULTS: The main causes of liver failure were viral hepatitis (n = 39), alcoholic liver disease (n = 22), and liver cancer (n = 17). One-year survival was 76.4%. The most common postoperative complications were bile duct stenosis (n = 12), postoperative bleeding (n = 8), hepatic artery thrombosis (n = 7), and primary liver failure (n = 6). Twelve patients required hemodialysis and four underwent retransplantations of the liver. Fourteen patients died before postoperative day 30(th). Univariate analysis showed significant differences between patients who did and did not survive 30 days among donor death diagnoses (P = .05), red blood cell units transfused (P = .03), aspartate aminotranferase on the first postoperative day (P = .002), ABO type (P = .04), time of orotracheal intubation (P = .001), hemodialysis (P = .001), and period of postoperative vasoactive drug use (P = .006). The total length of orotracheal tube intubation showed a significant independent association with mortality before 30 days (P < .001). CONCLUSION: OLT without VVB can be safely performed even in severe cases of chronic liver failure.

Predictive factors of early graft loss in living donor liver transplantation.

CONTEXT: Living donor liver transplantation has become an alternative to reduce the lack of organ donation. OBJECTIVE: To identify factors predictive of early graft loss in the first 3 months after living donor liver transplantation. METHODS: Seventy-eight adults submitted to living donor liver transplantation were divided into group I with 62 (79.5%) patients with graft survival longer than 3 months, and group II with 16 (20.5%) patients who died and/or showed graft failure within 3 months after liver transplantation. The variables analyzed were gender, age, etiology of liver disease, Child-Pugh classification, model of end-stage liver disease (MELD score), pretransplantation serum sodium level, and graft weight-to-recipient body weight (GRBW) ratio. The GRBW ratio was categorized into < 0.8 and MELD score into >18. The chi-square test, Student t-test and uni- and multivariate analysis were used for the evaluation of risk factors for early graft loss. RESULTS: MELD score <18 (P<0.001) and serum sodium level > 135 mEq/L (P = 0.03) were higher in group II than in group I. In the multivariate analysis MELD scores > 18 (P<0.001) and GRBW ratios < 0.8 (P<0.04) were significant. CONCLUSIONS: MELD scores >18 and GRBW < 0.8 ratios are associated with higher probability of graft failure after living donor liver transplantation.

Predictive factors of early graft loss in living donor liver transplantation / Fatores preditivos da perda precoce do enxerto hepático em transplante hepático intervivos

CONTEXT: Living donor liver transplantation has become an alternative to reduce the lack of organ donation. OBJECTIVE: To identify factors predictive of early graft loss in the first 3 months after living donor liver transplantation. METHODS: Seventy-eight adults submitted to living donor liver transplantation were divided into group I with 62 (79.5%) patients with graft survival longer than 3 months, and group II with 16 (20.5%) patients who died and/or showed graft failure within 3 months after liver transplantation. The variables analyzed were gender, age, etiology of liver disease, Child-Pugh classification, model of end-stage liver disease (MELD score), pretransplantation serum sodium level, and graft weight-to-recipient body weight (GRBW) ratio. The GRBW ratio was categorized into < 0.8 and MELD score into >18. The chi-square test, Student t-test and uni- and multivariate analysis were used for the evaluation of risk factors for early graft loss. RESULTS: MELD score <18 (P<0.001) and serum sodium level > 135 mEq/L (P = 0.03) were higher in group II than in group I. In the multivariate analysis MELD scores > 18 (P<0.001) and GRBW ratios < 0.8 (P<0.04) were significant. CONCLUSIONS: MELD scores >18 and GRBW < 0.8 ratios are associated with higher probability of graft failure after living donor liver transplantation.

CONTEXTO: O transplante hepático intervivos constitui alternativa para amenizar a falta de doação de órgãos. OBJETIVO: Identificar os fatores preditivos da perda precoce do enxerto hepático nos 3 primeiros meses após transplante hepático intervivo. MÉTODOS: Setenta e oito adultos submetidos ao transplante de fígado intervivos foram divididos em grupo I com 62 (79,5%) doentes com sobrevivência do enxerto superior a 3 meses, e grupo II com 16 (20,5%) que faleceram e/ou apresentaram falha do enxerto até 3 meses após o transplante hepático. As variáveis analisadas foram: sexo, idade, origem da doença hepática, classificação de Child-Pugh, critério MELD, nível sérico de sódio pré-transplante e relação GRBW. O critério MELD foi categorizado em > 18 e a relação GRBW em < 0,8. Na avaliação dos fatores de risco para perda precoce do enxerto hepático foi utilizada a análise uni e multivariada. RESULTADOS: Critério MELD <18 (P = 0,001) e nível sérico de sódio >135 mEq/L (P = 0,03) foram maiores nos doentes do grupo II. A probabilidade de perda do enxerto no transplante hepático intervivos teve como variáveis independentes o índice MELD > 18 e a relação GRBW< 0,8. CONCLUSÃO: Os valores de MELD >18 e GRBW <0,8 estão associados com maior probabilidade de insucesso no transplante hepático intervivos.

Risk factors for long-term mortality in a large cohort of patients wait-listed for liver transplantation in Brazil.

Liver donor shortage and long waiting times are observed in many liver transplant programs worldwide. The aim of this study was to evaluate the wait list in a developing country, before and after the introduction of the MELD scoring system. In addition, the MELD score ability to predict mortality in this setting was assessed. A single-center retrospective study of patients wait-listed for liver transplantation between 1997 and 2010 was undertaken. There were 1339 and 762 patients on the list in pre-MELD and MELD era, respectively. A competitive risk analysis was performed to assess age, gender, disease diagnosis, serum sodium, MELD, Child-Pugh, ABO type, and body mass index. Also, MELD score predictive ability at 3, 6, 12, and 24 months after list enrollment was evaluated. The overall mortality rates on waiting list were 31.0% and 28.1% (P = 0.16), and the median waiting times were 412 and 952 days (P < 0.001), in pre and MELD eras, respectively. The competitive risk analysis yielded the following significant P values for both eras: HCC (0.03 and <0.001), MELD (<0.001 and 0.002), sodium level (0.002 and <0.001), and Child-Pugh (0.02 and <0.001). The MELD mortality predictions at 3, 6, 12, and 24 months were similar. In conclusion, in a liver transplant program with long waiting times, the MELD system introduction did not improve mortality rate. In either pre and MELD eras, HCC diagnosis, serum sodium, Child-Pugh, and MELD were significant predictors of prognosis. Short- and long-term MELD based mortality predictions were similarly accurate. Strategies for increasing the liver donor pool should be implemented to improve mortality.

Does pre-liver transplant HBV DNA level affect HBV recurrence or survival in liver transplant recipients receiving HBIg and nucleos(t)ide analogues?

BACKGROUND AND AIMS: The risk of recurrent hepatitis B virus (HBV) infection and prognosis of liver transplantation in patients with HBV has dramatically changed with the use of prophylaxis including hepatitis B immune globulin (HBIg) and antiviral agents. METHODS: This study analyzes the prognostic value of HBV DNA level before orthotopic liver transplantation (OLT) and the effect of HBV prophylaxis on rates of HBV recurrence and survival. Between 1988 and 2008, 859 patients underwent OLT in our center; 60 patients had HBV-related liver disease and in 49, HBV DNA was determined by real time-PCR before OLT. Survival and HBV recurrence were analyzed according to preoperative viral load (HBV DNA <10(3) IU/mL vs. HBV DNA ≥10(3)) and prophylaxis regimens (HBIg vs HBIg and antivirals). RESULTS: On multivariate analysis, prophylaxis with HBIg alone, but not HBV-DNA levels was independently associated with poor survival, with a relative risk (RR) of death of 6.5 (95% CI 2.1-19.8, P = 0.001). The risk of HBV recurrence, in this small series, was also associated with monoprophylaxis with HBIg (RR 27, 95% CI 5.2-147.2, P < 0.0001), but not with HBV-DNA levels. CONCLUSIONS: When prophylaxis with HBIg and antiviral agents was administered, survival and HBV recurrence were not influenced by HBV-DNA levels determined by real time-PCR prior to OLT.

Survival on waiting list for liver transplantation before and after introduction of the model for end-stage liver disease score.

BACKGROUND: Since July 2006, the Model for End-stage Liver Disease (MELD) score has served as the national basis for allocation of donor livers for transplantation in Brazil. Patients with higher MELD scores receive greater priority for allocation regardless of the time on the waiting list. PURPOSE: To investigate the impact of MELD score implementation on the survival of waiting list patients. METHODS: A retrospective study of patients registered at the national Organ Procurement Organization (OPO) for the liver transplantation waiting list between January 2004 and June 2006 (pre-MELD) and between July 2006 and December 2008 (post-MELD). RESULTS: We included listed patients awaiting liver transplantation in the pre-MELD era (n = 250, 48.4%) and in the post-MELD era (n = 266, 51.6%). The times awaiting transplant prior to and after the MELD system were 487.2 +/- 384.8 days and 183.9 +/- 157.2 days, respectively. Prior to the MELD score, waiting list survivals were greater when compared to rates in the current system. Early posttransplant patient survival rates were significantly reduced in the post-MELD era (83.4%) compared to the period before MELD implementation (93.2%). CONCLUSIONS: MELD score provides a transparent, objective system to drive allocation policy; however, it presents several important limitations. Constant need of changes and reevaluation are needed as an evolutionary process. Future changes in the present system may be addressed by adjusting the MELD system.

Survival before and after model for end-stage liver disease score introduction on the Brazilian liver transplant waiting list.

INTRODUCTION: To examine whether the official adoption of Model for End-Stage Liver Disease (MELD) as a criterion for organ allocation was effective, we studied risk factors for patient deaths and the accuracy of the MELD score to predict mortality. METHODS: Patients on the waiting list for liver transplantation were divided into two periods depending on whether they were on the waiting list before (period 1) or after (period 2) the MELD introduction in Brazil. The Kaplan-Meier method with log-rank tests were used to study patient survivals. Predictive factors were identified using the Cox regression method. A receiver operating characteristic (ROC) curve was used to analyze Child-Turcotte-Pugh (CTP) and MELD accuracy. RESULTS: We analyzed 295 patients in period 1 and 240 in period 2. The survivals after 3, 6, 9, and 12 months in periods 1 and 2, were 95.6%, 90.5%, 84.9%, and 69.6% vs 95.7%, 92.1%, 85.3%, and 83.3%, respectively (P = NS). Multivariate analysis showed CTP, MELD-Na, and albumin levels, besides spontaneous bacterial peritonitis (SBP), to be independent factors related to survival in period 1. In period 2, CTP, creatinine levels, international normalized ratio, besides spontaneous bacterial peritonitis, were the independent factors. The ROC curve for CTP was 0.676 and for MELD, 0.644 (P = .4) in period 1. In period 2, the ROC curve for CTP was 0.680 and for MELD, 0.718 (P = .4). CONCLUSION: Patient survival on the waiting list for liver transplantation did not change at 1 year after the introduction of the MELD.