WAITING LIST FOR LIVER TRANSPLANTATION: CLINICAL AND ECONOMIC BURDEN.

BACKGROUND: Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). OBJECTIVE: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. METHODS: The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. RESULTS: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). CONCLUSION: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

Lista de espera para transplante hepático: impacto clínico e econômico / Waiting list for liver transplantation: clinical and economic burden

ABSTRACT Background Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). Objective: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. Methods The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. Results: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). Conclusion: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

RESUMO Contexto O impacto da doença é um indicador relacionado ao estado de saúde. Dados epidemiológicos norte-americanos e europeus mostraram que, nas últimas décadas, o impacto da doença hepática crônica tem aumentado significativamente. Não há estudos que avaliem o impacto das descompensações da doença hepática crônica na lista de espera para transplante hepático (TxH) com doador falecido. Objetivo: Determinar o impacto clínico e econômico das descompensações da doença hepática nos pacientes em lista de espera sob a perspectiva do centro transplantador. Métodos Foram analisados, retrospectivamente, os prontuários de 104 pacientes incluídos em lista de espera para TxH com doador falecido entre outubro de 2012 e maio de 2016 e acompanhados integralmente no centro transplantador. Dados clínicos foram obtidos do prontuário eletrônico, enquanto dados econômicos foram coletados através de software de gestão hospitalar. A apropriação dos custos médicos diretos foi realizada sob duas metodologias: custeio por absorção pleno e microcusteio. Resultados: A descompensação com maior incidência foi a ascite refratária (20,2%) seguida de encefalopatia portossistêmica (12,5%). A média de internações por paciente foi de 1,37±3,42. A hemorragia digestiva alta varicosa foi a descompensação com maior tempo mediano de internação (18 dias), seguida da síndrome hepatorrenal (13,5 dias). A descompensação mais onerosa foi a síndrome hepatorrenal (custo médio de US$ 3.565), seguida encefalopatia portossistêmica (US$ 2.576) e a hemorragia digestiva alta varicosa (US$ 1.530). Conclusão O impacto da doença hepática crônica inclui um custo importante para os sistemas de saúde. Além disso, é provável que seja ainda maior em decorrência do curso insidioso da doença.

EVALUATION AND SELECTION OF CANDIDATES FOR LIVER TRANSPLANTATION: AN ECONOMIC PERSPECTIVE.

BACKGROUND: Over the next 20 years, the number of patients on the waiting list for liver transplantation (LTx) is expected to increase by 23%, while pre-LTx costs should raise by 83%. OBJECTIVE: To evaluate direct medical costs of the pre-LTx period from the perspective of a tertiary care center. METHODS: The study included 104 adult patients wait-listed for deceased donor LTx between October 2012 and May 2016 whose treatment was fully provided at the study transplant center. Clinical and economic data were obtained from electronic medical records and from a hospital management software. Outcomes of interest and costs of patients on the waiting list were compared through the Kruskal-Wallis test. A generalized linear model with logit link function was used for multivariate analysis. P-values <0.05 were considered statistically significant. RESULTS: The costs of patients who underwent LTx ($8,879.83; 95% CI 6,735.24-11,707.27; P<0.001) or who died while waiting ($6,464.73; 95% CI 3,845.75-10,867.28; P=0.04) were higher than those of patients who were excluded from the list for any reason except death ($4,647.78; 95% CI 2,469.35-8,748.04; P=0.254) or those who remained on the waiting list at the end of follow-up. CONCLUSION: Although protocols of inclusion on the waiting list vary among transplant centers, similar approaches exist and common problems should be addressed. The results of this study may help centers with similar socioeconomic realities adjust their transplant policies.

Avaliação e seleção de candidatos para transplante hepático: uma perspectiva econômica / Evaluation and selection of candidates for liver transplantation: an economic perspective

ABSTRACT BACKGROUND: Over the next 20 years, the number of patients on the waiting list for liver transplantation (LTx) is expected to increase by 23%, while pre-LTx costs should raise by 83%. OBJECTIVE: To evaluate direct medical costs of the pre-LTx period from the perspective of a tertiary care center. METHODS: The study included 104 adult patients wait-listed for deceased donor LTx between October 2012 and May 2016 whose treatment was fully provided at the study transplant center. Clinical and economic data were obtained from electronic medical records and from a hospital management software. Outcomes of interest and costs of patients on the waiting list were compared through the Kruskal-Wallis test. A generalized linear model with logit link function was used for multivariate analysis. P-values <0.05 were considered statistically significant. RESULTS: The costs of patients who underwent LTx ($8,879.83; 95% CI 6,735.24-11,707.27; P<0.001) or who died while waiting ($6,464.73; 95% CI 3,845.75-10,867.28; P=0.04) were higher than those of patients who were excluded from the list for any reason except death ($4,647.78; 95% CI 2,469.35-8,748.04; P=0.254) or those who remained on the waiting list at the end of follow-up. CONCLUSION: Although protocols of inclusion on the waiting list vary among transplant centers, similar approaches exist and common problems should be addressed. The results of this study may help centers with similar socioeconomic realities adjust their transplant policies.

RESUMO CONTEXTO: Nos próximos 20 anos, estima-se um aumento de 23% no número de pacientes em lista de espera para transplante de fígado (TxF) e de 83% nos custos no período pré-TxF. OBJETIVO: Avaliar os custos médicos diretos do período pré-TxF sob a perspectiva de um centro de atenção terciária. MÉTODOS: Foram incluídos no estudo 104 adultos em lista de espera para TxF, com doador falecido, entre outubro de 2012 e maio de 2016, tratados integralmente no centro transplantador do estudo. Dados clínicos e econômicos foram obtidos do prontuário eletrônico e do software de gestão hospitalar. Os desfechos de interesse e os custos dos pacientes em lista de espera foram comparados através do teste de Kruskal-Wallis. Um modelo linear generalizado com função de ligação logarítmica foi utilizado para a análise multivariável. Valores de P<0.05 foram considerados estatisticamente significativos. RESULTADOS: Os custos com pacientes submetidos a TxF (US$ 8.879,83; IC 95% 6.735,24-11.707,27; P<0,001) ou que morreram enquanto estavam em lista (US$ 6.464,73; IC 95% 3.845,75-10.867,28; P=0,04) foram maiores do que com pacientes excluídos da lista por qualquer motivo, exceto óbito (US$ 4.647,78; IC 95% 2.469,35-8.748,04; P=0,254) ou daqueles que permaneceram em lista de espera ao final do seguimento. CONCLUSÃO: Embora os protocolos de inclusão em lista de espera variem entre os centros transplantadores, existem condutas semelhantes e problemas comuns devem ser considerados. Os resultados deste estudo podem auxiliar os centros com realidades socioeconômicas semelhantes na adequação das suas políticas de transplante.

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

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

O custo do transplante hepático adulto em um centro de referência na região sul do Brasil / The cost of adult liver transplantation in a referral center in southern brazil

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

RESUMO CONTEXTO: O transplante hepático (TxH) é o principal e definitivo tratamento de casos agudos ou crônicos de doenças hepáticas avançadas ou terminais. Poucos estudos têm avaliado o custo real do TxH categorizado por setores hospitalares. OBJETIVO: Avaliar o custo do TxH categorizado por especialidade da unidade em um centro de referência na região sul do Brasil. MÉTODOS: Analisamos retrospectivamente os prontuários de 109 pacientes submetidos a TxH entre abril de 2013 e dezembro de 2014. Foram coletados dados sobre características demográficas, etiologia da doença hepática e gravidade da doença hepática de acordo com os escores Child-Turcotte-Pugh (CTP) e Model for End-stage Liver Disease (MELD) no momento do TxH. A conta hospitalar foi transformada em custo pelo método de custeio por absorção integral, e os custos foram agrupados em cinco categorias: Kit Pré-Transplante Imediato; Unidades Especializadas; Centro Cirúrgico; Unidade de Terapia Intensiva; e Unidade de Internação. RESULTADOS: O custo médio total do TxH foi de US$ 17.367. O Centro Cirúrgico, as Unidades Especializadas e a Unidade de Terapia Intensiva responderam por 31,9%, 26,4% e 25,3% dos custos, respectivamente. A análise multivariada demonstrou que o custo total do TxH se associou significativamente ao escore CTP classe C (P=0,001) e ao desenvolvimento de intercorrências (P=0,002). As seguintes intercorrências contribuíram para aumentar significativamente o custo do TxH: choque séptico (P=0,006), politransfusão sanguínea (P=0,007) e insuficiência renal aguda associada à terapia renal substitutiva (diálise) (P=0,005). CONCLUSÃO: Nossos resultados demonstraram que o custo total do TxH guarda uma estreita relação com os escores de gravidade da doença hepática e com o desenvolvimento de intercorrências.

Cost-effectiveness of whole-body bone scans in the pre-liver transplant assessment of patients with hepatocellular carcinoma in Southern Brazil.

BACKGROUND: Bone metastases (BM) are rare in patients with early-stage hepatocellular carcinoma (HCC). In many centers, liver transplantation (LTx) policies require patients with HCC to undergo bone scans (BSs). METHODS: We retrospectively assessed the benefit of BS for patients with a diagnosis of HCC wait-listed for LTx. RESULTS: BS was performed in 259 of 328 patients (78.9%) and was suggestive of BM in only one (0.4%). At follow-up, 276 patients had received LTx, of whom 207 had undergone BS. Histopathological examination of explants failed to confirm the presence of HCC in 20 patients from the BS group. The survival and recurrence rates of the 187 patients with confirmed HCC in the explant who underwent BS as part of pre-LTx assessment and 69 patients who did not undergo BS were compared. The one- and five-yr post-transplant survival rates were 81% and 69%, respectively, in the BS group vs. 78% and 62%, respectively, in patients who did not undergo BS (p = 0.25). The one- and five-yr post-LTx recurrence rates were 4.8% and 10.7%, respectively, in the BS group vs. 2.9% and 10.1%, respectively, in patients who did not undergo BS (p = 0.46). CONCLUSIONS: BS generated expenditures of US$39 296 and was not cost-effective.

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

BACKGROUND AND RATIONALE: The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS: Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS: APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

Impact of MELD score implementation on liver allocation: experience at a Brazilian center.

Introduction. Model for end-stage liver disease (MELD) is an accurate predictor of mortality in patients with cirrhosis, and has been used on liver allocation in Brazil since 2006. However, its impact on organ allocation, waiting list and post-transplant mortality is still poorly characterized. This study aimed to assess the impact of implementation of the MELD system on liver allocation and mortality after liver transplantation (LT) in Southern Brazil. Material and methods. Adult patients with chronic liver disease on the waiting list for primary deceased-donor LT were divided into two cohorts (pre- and post-MELD implementation) according to the date of waiting list placement. Disease severity, as assessed by MELD score at placement, was similar in both cohorts. Patients were followed for at least 18 months to assess the outcomes of interest (death/LT). Results. Higher MELD scores correlated with waiting list mortality, which increased 20% with each additional point (HR 1.2; 95%CI 1.14-2.26; p < 0.001). Waiting list mortality was 30.9% before and 21.7% after MELD implementation (nonsignificant). Transplant rate increased after MELD implementation (52 vs. 40%, p = 0.002). After excluding patients with hepatocellular carcinoma, mean MELD scores at LT were significantly higher in the MELD era (p < 0.01). There was no significant correlation between MELD scores at LT and post-LT survival. During 18-month follow-up, post-LT mortality rate was 25.4% before and 20% after MELD implementation (nonsignificant). Conclusion. MELD implementation was associated with a reduction in waiting list mortality. Although sicker patients received LT in the MELD era, post-transplant survival was similar in both periods.

Impact of creatinine values on MELD scores in male and female candidates for liver transplantation.

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.

Liver transplantation in HIV-positive patients: the position of the Brazilian groups.

BACKGROUND: Patients infected with the human immunodeficiency virus (HIV) have generally been excluded from consideration for liver transplantation. Recent advances in the management and prognosis of these patients suggest that this policy must be reevaluated. AIM: To identify the current position of Brazilian transplant centers concerning liver transplantation in asymptomatic HIV-infected patients with end-stage liver disease. METHODS: A structured questionnaire was submitted by e-mail to Brazilian groups who perform liver transplantation and were active in late 2003, according to the Brazilian Association of Organ Transplantation. RESULTS: Of the 53 active groups, 30 e-mail addresses have been found of professionals working in 41 of these groups. Twenty-one responses (70%) were obtained. Most of the professionals (62%) reported that they do not include HIV-infected patients in waiting lists for transplants, primarily on account of the limited world experience. They also reported, however, that this issue will soon be discussed by the group. Those who accept these patients usually follow the guidelines provided by the literature: patients must fulfill the same inclusion criteria as the other patients with end-stage liver diseases, present low or undetectable HIV viral load, and a CD4 count above 250/mm3. They reported that there are 10 HIV-infected patients in waiting list and that only one patient has received a liver transplant in the country. CONCLUSION: Most centers do not accept in waiting lists for liver transplantation patients with HIV infection, even asymptomatic ones. However, advances in the management of HIV-infected patients suggest that this policy must be reevaluated. In Brazil, there is practically no experience in liver transplantation in HIV-positive patients.

Liver transplantation in HIV-positive patients: the position of the Brazilian groups

RACIONAL: Pacientes infectados com o vírus da imunodeficiência humana (HIV) têm sido comumente excluídos dos programas de transplantes de fígado. Avanços recentes no tratamento e prognóstico desses pacientes sugerem que essa política deva ser reavaliada. OBJETIVO: Identificar a orientação atual dos transplantadores brasileiros em relação a transplante de fígado em pacientes infectados com HIV, assintomáticos, com doença hepática terminal. MÉTODOS: Envio de questionário estruturado, por correio eletrônico, para grupos que realizam transplante hepático e ativos no final de 2003, segundo Associação Brasileira Transplantes de Órgãos. RESULTADOS: Dos 53 grupos em atividade, identificou-se o endereço eletrônico de 30 profissionais, que atuam em 41 desses grupos. Foram recebidas 21 respostas (70%). A maioria dos profissionais (62%) informou não incluir pacientes anti-HIV reagentes em lista para transplante, fundamentalmente em razão da pequena experiência mundial. Contudo, relataram que o assunto será discutido brevemente pelo grupo. Profissionais que aceitam esses pacientes adotam, em geral, orientações sugeridas na literatura: devem preencher os critérios de inclusão que os demais pacientes com doenças hepáticas terminais, ter carga viral do HIV baixa ou negativa e contagem de CD4 >250/mm3. Informaram haver 10 pacientes anti-HIV reagentes em lista e que apenas 1 paciente foi transplantado no país. CONCLUSÃO: A maioria dos profissionais não aceita pacientes anti-HIV reagentes mesmo que assintomáticos, em lista de espera para transplante hepático. Contudo, os avanços no manejo de pacientes com HIV recomenda que essa posição seja reavaliada. Praticamente não há experiência em nosso país, com transplante hepático em pacientes anti-HIV reagentes.