Análisis del sistema de alistamiento y priorización para trasplante hepático de adultos en Chile

Background: In Chile, organ allocation for liver transplantation (LT) in adults is prioritized according to the MELD-Na score. Exceptions such as Hepatocellular Carcinoma (HCC) and other non-HCC exceptions receive a score called Operational MELD score. Aim: To evaluate the effectiveness of the MELD-Na score and the operational MELD score as a prioritization system for LT in Chile. Material and Methods: Retrospective analysis of the waiting list (WL) of adult candidates (≥ 15 years) for elective LT in Chile from 2011 to 2017. The probability of leaving the WL, defined by death or contraindication for LT was compared in three groups: 1) Cirrhotic patients prioritized according to their real MELD-Na score (CPM), 2) HCC and 3) other non-HCC exceptions. Results: We analyzed 730 candidates for LT, with a median age of 57 years, 431 (56%) were men. In the study period, 352 LT were performed (48%). The annual exit rate was significantly higher in the CPM group (45.5%) compared to HCC (33.1%) and non-HCC (29.3%), (p < 0.001). Post LT survival was 86% at 1 year and 85% at 5 years, without significant differences between groups. In the CPM group, post-transplant survival was significantly lower (p < 0.05) in patients with MELD-Na ≥ 30 at transplant (81% per year) compared to patients with patients with MELD-Na < 30 (91% per year). Conclusions: MELD-Na score can discriminate very well patients who have a higher risk of death in the short and medium term. However, the assignment of operational scores for situations of exception produces inequities in the allocation of organs for LT and must therefore be carefully adjusted.

Situación actual del trasplante hepático pediátrico por hepatopatías crónicas en Chile: Inequidades asociadas a la priorización por sistema MELD/PELD

Background: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. Aim: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. Material and Methods: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. Results: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. Conclusions: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

[Analysis of the organ allocation system for liver transplantation in Chile]. / Análisis del sistema de alistamiento y priorización para trasplante hepático de adultos en Chile.

BACKGROUND: In Chile, organ allocation for liver transplantation (LT) in adults is prioritized according to the MELD-Na score. Exceptions such as Hepatocellular Carcinoma (HCC) and other non-HCC exceptions receive a score called Operational MELD score. AIM: To evaluate the effectiveness of the MELD-Na score and the operational MELD score as a prioritization system for LT in Chile. MATERIAL AND METHODS: Retrospective analysis of the waiting list (WL) of adult candidates (≥ 15 years) for elective LT in Chile from 2011 to 2017. The probability of leaving the WL, defined by death or contraindication for LT was compared in three groups: 1) Cirrhotic patients prioritized according to their real MELD-Na score (CPM), 2) HCC and 3) other non-HCC exceptions. RESULTS: We analyzed 730 candidates for LT, with a median age of 57 years, 431 (56%) were men. In the study period, 352 LT were performed (48%). The annual exit rate was significantly higher in the CPM group (45.5%) compared to HCC (33.1%) and non-HCC (29.3%), (p < 0.001). Post LT survival was 86% at 1 year and 85% at 5 years, without significant differences between groups. In the CPM group, post-transplant survival was significantly lower (p < 0.05) in patients with MELD-Na ≥ 30 at transplant (81% per year) compared to patients with patients with MELD-Na < 30 (91% per year). CONCLUSIONS: MELD-Na score can discriminate very well patients who have a higher risk of death in the short and medium term. However, the assignment of operational scores for situations of exception produces inequities in the allocation of organs for LT and must therefore be carefully adjusted.

[Current situation of pediatric liver transplantation in Chile. Inequities associated with the MELD/PELD prioritization system]. / Situación actual del trasplante hepático pediátrico por hepatopatías crónicas en Chile: Inequidades asociadas a la priorización por sistema MELD/PELD.

BACKGROUND: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. AIM: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. MATERIAL AND METHODS: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. RESULTS: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. CONCLUSIONS: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.

[Liver transplantation: development, learning curve and results after the first 300 cases]. / Trasplante hepático: evolución, curva de aprendizaje y resultados después de los primeros 300 casos.

BACKGROUND: Liver transplantation (LT) is an option for people with liver failure who cannot be cured with other therapies and for some people with liver cancer. AIM: To describe, and analyze the first 300 LT clinical results, and to establish our learning curve. MATERIAL AND METHODS: Retrospective cohort study with data obtained from a prospectively collected LT Program database. We included all LT performed at a single center from March 1994 to September 2017. The database gathered demographics, diagnosis, indications for LT, surgical aspects and postoperative courses. We constructed a cumulative summation test for learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30 days, and actuarial 1-, and 5-year survival rate were analyzed. RESULTS: A total of 281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percent of patients were younger than 18 years old. The first, second and third indications for LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis and alcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in 51 cases (17%). The overall complication rate was 71%. Infectious and biliary complications were the most common of them (47 and 31% respectively). The LC-CUSUM curve shows that the first 30 patients corresponded to the learning curve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rates were 82 and 71.4%, respectively. CONCLUSIONS: Outcome improvement of a LT program depends on the accumulation of experience after the first 30 transplants and the peri-operative mortality directly impacted long-term survival.

Trasplante hepático: evolución, curva de aprendizaje y resultados después de los primeros 300 casos / Liver transplantation: development, learning curve and results after the first 300 cases

Background: Liver transplantation (LT) is an option for people with liver failure who cannot be cured with other therapies and for some people with liver cancer. Aim: To describe, and analyze the first 300 LT clinical results, and to establish our learning curve. Material and Methods: Retrospective cohort study with data obtained from a prospectively collected LT Program database. We included all LT performed at a single center from March 1994 to September 2017. The database gathered demographics, diagnosis, indications for LT, surgical aspects and postoperative courses. We constructed a cumulative summation test for learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30 days, and actuarial 1-, and 5-year survival rate were analyzed. Results: A total of 281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percent of patients were younger than 18 years old. The first, second and third indications for LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis and alcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in 51 cases (17%). The overall complication rate was 71%. Infectious and biliary complications were the most common of them (47 and 31% respectively). The LC-CUSUM curve shows that the first 30 patients corresponded to the learning curve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rates were 82 and 71.4%, respectively. Conclusions: Outcome improvement of a LT program depends on the accumulation of experience after the first 30 transplants and the peri-operative mortality directly impacted long-term survival.

Accuracy of the BAR score in the prediction of survival after liver transplantation.

INTRODUCTION AND AIM: The Balance of Risk (BAR) Score, a simple scoring system that combines six independent donor and recipient variables to predict outcome after liver transplantation (LT), was validated in a large U.S./European cohort of patients. This study aims to assess the performance of the BAR score to predict survival after liver transplantation and determine the factors associated with short and long-term survival in Latin-American patients. MATERIAL AND METHODS: A retrospective cohort study was performed in 194 patients [112 (55.4%) males; mean age 52±14 years] who underwent 202 LT during the period 2003-2015. Demographic, clinical, pathological and surgical variables, as well as mortality and survival rates, were analyzed. The BAR score was investigated through a receiver operating characteristics (ROC) curve with the calculation of the area under the curve (AUC) to evaluate the predictive score power for 3-month, 1 and 5-year mortality in a matched donor-recipient cohort. Youden index was calculated to identify optimal cutoff points. RESULTS: The AUC of BAR score in predicting 3-month, 1-year and 5-year mortality were 0.755 (CI95% 0.689-0.812), 0.702 (CI95% 0.634-0.764) and 0.610 (CI95% 0.539-0.678) respectively. The best cut-off point was a BAR score ≥15 points. In the multivariate analysis BAR score <15 was associated with higher survival rates at 3 months and 1 and 5-years. CONCLUSIONS: BAR score <15 points is an independent predictor of better short and long-term survival in Latin-American patients undergoing LT. The BAR scoring system has an adequate diagnostic capacity allowing to predict 3 and 12-month mortality.

Prioritization for liver transplantation using the MELD score in Chile: Inequities generated by MELD exceptions.: A collaboration between the Chilean Liver Transplant Programs, the Public Health Institute and the National Transplant Coordinator.

INTRODUCTION AND AIM: The MELD score has been established as an efficient and rigorous prioritization system for liver transplant (LT). Our study aimed to evaluate the effectiveness of the MELD score as a system for prioritization for LT, in terms of decreasing the dropout rate in the waiting list and maintaining an adequate survival post-LT in Chile. MATERIALS AND METHODS: We analyzed the Chilean Public Health Institute liver transplant registry of candidates listed from October 15th 2011 to December 31st 2014. We included adult candidates (>15 years old) listed for elective cadaveric LT with a MELD score of 15 or higher. Statistical analysis included survival curves (Kaplan-Meier), log-rank statistics and multivariate logistic regression. RESULTS: 420 candidates were analyzed. Mean age was 53.6±11.8 years, and 244 were men (58%). Causes of LT included: Liver cirrhosis without exceptions (HC) 177 (66.4%); hepatocellular carcinoma (HCC) 111 (26.4%); cirrhosis with non-HCC exceptions 102 (24.3%) and non-cirrhotic candidates 30 (7.2%). LT rate was 43.2%. The dropout rate was 37.6% at 1-year. Even though the LT rate was higher, the annual dropout rate was significantly higher in cirrhotic candidates (without exceptions) compared with cirrhotics with HCC, and non-HCC exceptions plus non-cirrhotic candidates (47.9%; 37.2% and 24.2%, respectively, with p=0.004). Post-LT survival was 84% per year, with no significant differences between the three groups (p=0.95). CONCLUSION: Prioritization for LT using the MELD score system has not decreased the dropout rate in Chile (persistent low donor's rate). Exceptions generate inequities in dropout rate, disadvantaging patients without exceptions.

Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH) / Liver transplantation in a patient with human immunodeficiency virus (HIV): case report

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

Current Status and Future Challenges of Liver Transplantation Programs in Chile.

Liver transplantation (LT) was performed for the first time in Chile in 1969, but only since the 1990s has it been systematically performed. Our health system is strongly centralized, which is a severe limitation for the patients who need to be evaluated and subsequently listed. Although proper human and technological resources are available and our results are comparable to international outcomes (overall patient survival at 1, 5, and 10 years of 82%, 70%, and 64%, respectively), we are limited because of a severe scarcity of grafts, which translates into an availability of approximately 7 organs per million persons and a wait-list dropout rate of 40% every year. Thus, our main challenge for the next few years is to improve access to LT among the populations from the extreme regions of the country and overall to improve the availability of grafts by increasing the awareness of physicians in intensive care units and emergency departments, to develop living donor LT programs, to educate the population in order to decrease family refusal, and to reinforce the system of potential donor detection. Although hard work is mandatory for these improvements, none of these tasks seem to be unreachable in the midterm.

[Liver transplantation in a patient with human immunodeficiency virus (HIV). Case report]. / Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH).

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

Validation of the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Chilean-Hispanic Patients.

INTRODUCTION AND AIM: In 2008 the International autoimmune hepatitis (AIH) Group proposed the simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers, but validation studies are scarce in Latin-America. The aim of this study is validate these criteria in Hispanic patients. MATERIAL AND METHODS: A retrospective cohort of patients undergoing percutaneous liver biopsy and follow-up of at least 12 months was recruited from a Chilean University hospital. Patients with previous immunosuppressive therapy and liver transplant recipients were excluded. The diagnostic accuracy was analyzed using as gold standard the clinical course during long-term follow-up. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the ROC curve (AUROC) were calculated. RESULTS: Four hundred eighty one patients were evaluated, 294 were included. 218 (74.15%) were female, mean age 48.5 (± 12.3) years, mean follow-up 34 (± 18) months. 66 patients had AIH or overlap syndrome (22.45%), 96 (32.65%) non-alcoholic steatohepatitis, 40 (13.61%) primary biliary cholangitis, 31 (10.54%) hepatitis C, 8 (2.72%) hepatitis B, 53 (18.02%) other etiologies. The AUROC for AIH simplified criteria was 0.976. Using a cutoff ≥ 6 and ≥ 7 points, the sensitivity was 86.4% and 54.6%; specificity, 98.7% and 99.6%; PPV, 95% and 97.3%; and NPV, 96.2% and 88.6%, respectively. CONCLUSION: Simplified criteria for the diagnosis of AIH have a high accuracy in our Chilean-Hispanic cohort. The female gender is strongly associated to AIH and could help in difficult cases. Further studies with a prospective design are necessary to confirm these observations.

Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus.

AIM: To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension. METHODS: A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded. RESULTS: Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described. CONCLUSION: Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.