Cost-effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation.

Background: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. Aims: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. Method: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment—resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. Results: Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8–6.1 months with an acceptable cost ($40 000/ year of life gained) for waiting lists ≥1 year whereas it was not cost effective ($74 000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2–6.7 months with a marginal cost of approximately $20 000/year of life gained in all cases, remaining cost effective for all waiting times. Conclusions: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage

Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases

Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as 'mild' or 'severe' based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART) analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC) curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903). Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival

Changes of liver hemodynamic and elastography parameters in patients with colorectal liver metastases receiving preoperative chemotherapy: 'a note of caution'

BACKGROUND: New systemic chemotherapy agents have improved prognosis in patients with colorectal liver metastases (CLM), but some of them damage the liver parenchyma and ultimately increase postoperative morbidity and mortality after liver resection. The aims of our study were to determine the degree of hemodynamic and pathological liver injury in CLM patients receiving preoperative chemotherapy and to identify an association between these injuries and postoperative complications after liver resection. METHODS: This is a prospective descriptive study of patients with CLM receiving preoperative chemotherapy before curative liver resection from November 2013 to June 2014. All patients had preoperative elastography and hepatic hemodynamic evaluation. We analyzed clinical preoperative data and postoperative outcomes after grouping the patients by chemotherapy type, development of sinusoidal obstructive syndrome (SOS), and development of major complications. RESULTS: Eleven from the 20 patients included in the study received preoperative oxaliplatin-based chemotherapy (OBC). Nine patients had SOS at pathological analysis and five patients developed major complications. Patients receiving preoperative OBC had higher values of hepatic venous pressure gradient (HVPG) and developed more SOS and major complications. Patients developing SOS had higher values of HVPG and developed more major complications. Patients with major complications had higher values of HVPG, and patients with a HVPG of 5 mmHg or greater had more major complications than those under 5 mmHg (20 vs 80%, p = 0.005). CONCLUSIONS: OBC and SOS impair liver hemodynamics in CLM patients. An increase in major complications after liver resection in these patients develops at subclinical HVPG levels

Laparoscopic versus open hemihepatectomy: comprehensive comparison of complications and costs at 90 days using a propensity method

Laparoscopic hemihepatectomy (LHH) may ofer advantages over open hemihepatectomy (OHH) in blood loss, recovery, and hospital stay. The aim of this study is to evaluate our recent experience performing hemihepatectomy and compare complications and costs up to 90 days following laparoscopic versus open procedures. Retrospective evaluation of patients undergoing hemihepatectomy at our center 01/2010-12/2018 was performed. Patient, tumor, and surgical characteristics; 90-day complications; and costs were analyzed. Inverse probability of treatment weighting (IPTW) was used to balance covariates. A total of 141 hemihepatectomies were included: 96 OHH and 45 LHH. While operative times were longer for LHH, blood loss and transfusions were less. At 90 days, there were similar rates of liver-specifc and surgical complications but fewer medical complications following LHH. Medical complications that arose with greater frequency following OHH were primarily pulmonary complications and urinary and central venous catheter infections. Complications at 90 days were lower following LHH (Clavien-Dindo grade≥III OHH 23%, LHH 11%, p=0.130; Comprehensive Complication Index OHH 20.0±16.1, LHH 10.9±14.2, p=0.001). While operating costs were higher, costs for hospital stay and readmissions were lower with LHH. Patients undergoing LHH experience a signifcant reduction in postoperative medical complications and costs, resulting in 90-day cost equity compared with OHH

DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma

Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HCC treated with surgical resection allowed us to generate a methylation-based prognostic signature using a training-validation scheme. Methylome profiling was done with the Illumina HumanMethylation450 array (Illumina, Inc., San Diego, CA), which covers 96% of known cytosine-phosphate-guanine (CpG) islands and 485,000 CpG, and transcriptome profiling was performed with Affymetrix Human Genome U219 Plate (Affymetrix, Inc., Santa Clara, CA) and miRNA Chip 2.0. Random survival forests enabled us to generate a methylation signature based on 36 methylation probes. We computed a risk score of mortality for each individual that accurately discriminated patient survival both in the training (221 patients; 47% hepatitis C-related HCC) and validation sets (n = 83; 47% alcohol-related HCC). This signature correlated with known predictors of poor outcome and retained independent prognostic capacity of survival along with multinodularity and platelet count. The subset of patients identified by this signature was enriched in the molecular subclass of proliferation with progenitor cell features. The study confirmed a high prevalence of genes known to be deregulated by aberrant methylation in HCC (e.g., Ras association [RalGDS/AF-6] domain family member 1, insulin-like growth factor 2, and adenomatous polyposis coli) and other solid tumors (e.g., NOTCH3) and describes potential candidate epidrivers (e.g., septin 9 and ephrin B2). Conclusions: A validated signature of 36 DNA methylation markers accurately predicts poor survival in patients with HCC. Patients with this methylation profile harbor messenger RNA-based signatures indicating tumors with progenitor cell features

Pilot study of living donor liver transplantation for patients with HCC exceeding Milan criteria

BACKGROUND & AIMS: A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. METHODS: In 2001 we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria - the BCLC expanded criteria- that expanded the conventional indications of transplantation: 1 tumor ≤ 7cm, 5 tumors ≤ 3cm, 3 tumors ≤ 5cm without macrovascular invasion or down-staging to Milan after loco-regional therapies. RESULTS: We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (17) or down-staging (5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age: 57yr old; males/female: 20/2, Child-Pugh A/B: 16/6, AFP <100ng/mL: 21. Twelve patients received neo-adjuvant loco-regional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow up of 81 months, the 1-, 3-, 5- and 10-year survival was 95.5%, 86.4%, 80.2% and 66.8%, respectively. Overall, seven patients recurred (range 9-108 mo), and the 5-y and 10-yr actuarial recurrence rate was of 23.8% and 44,4%, respectively. CONCLUSION: A proper selection of candidates for extended indications of living donor liver transplantation for HCC patients provide survival outcomes comparable

Bespoken nanoceria: A new effective treatment in experimental hepatocellular carcinoma

Background and aims: Despite the availability of new-generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeO2 NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2 NPs as therapeutic agents in HCC. Approach and results: HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2 NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2 NPs on tumor progression and animal survival was investigated. Hepatic tissue MS-based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2 NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2 NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2 NPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeO2 NPs reduced serum alpha-protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. Conclusions: These data indicate that CeO2 NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC. © 2020 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases

Psychometric characteristics of the Spanish version of instruments to measure neck pain disability

[EN] Background. The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ). Methods. Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed. Results. Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires [median, (P25, P75)]: NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: [ICC, (95%CI)]: NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92. Validity: Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15. Conclusion. Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistanceS

Características bioquímicas y factores pronósticos del rechazo agudo después del trasplante ortotópico de hígado en el adulto

El trasplante hepático es el tratamiento de elección en pacientes con hepatopatías en fase terminal. En la actualidad puede ofrecerse con esta terapéutica una supervivencia a los tres años que oscila entre el 60 y el 80%. Una vez superados los problemas de técnica quirúrgica y reanimación, los factores que pueden limitar el éxito del trasplante hepático son la presencia de rechazo y la aparición de infecciones. Se han buscado métodos para diagnosticar con prontitud el rechazo y se han tratado de encontrar factores que pudieran servir de predicción del rechazo. La gran variabilidad de los resultados y en otros casos la sofisticación de las técnicas o de la infraestructura necesaria para aplicarlas ha hecho que no se hayan adoptado de manera sistemática para diagnosticar el rechazo, Por otra parte la similitud que desde el punto de vista semiológico y bioquímico, presentan otras situaciones clínicas distintas del rechazo, hace que sea necesario asegurar el diagnóstico. Esto es particularmente importante, porque el aumento de los niveles de inmunosupresión puede aumentar el riesgo o la susceptibilidad de los pacientes frente a los agentes infecciosos, fundamentalmente víricos. La rapidez con que se inicia la administración de dosis crecientes de fármacos inmunosupresores puede ser vital a la hora de controlar el rechazo, pero también puede aumentar innecesariamente el riesgo de infección si en realidad el problema que presenta el paciente es otro. Estos precedentes, han acentuado la necesidad de obtener una biopsia hepática antes de iniciar el tratamiento. Sin embargo en situaciones especiales el tiempo que puede tardarse en "leer" la biopsia puede significar perder un tiempo precioso durante el cual el rechazo puede progresar. Con estas premisas se ha realizado una hipótesis de trabajo que pretende conocer si hay algunas alteraciones en los parámetros bioquímicos de función hepática o en otras variables que sean un índice seguro de rechazo, y asimismo conocer si existen datos en el donante o en el receptor que sirvan de predicción del rechazo. Esta tesis pretende a su vez concretar en una ecuación matemática la posibilidad de que una disfunción hepática sea un rechazo y establecer grupos de riesgo de presentar un rechazo a lo largo del tiempo. El estudio se realizó en los 100 primeros trasplantes realizados en el Hospital Clínic de Barcelona, entre junio de 1988 y Octubre de 1990. El seguimiento medio era de 11±8 meses, con un máximo de 30 meses y un mínimo de 3 meses. El 50% de los pacientes había superado los 10 meses de seguimiento. El estudio analiza el primer episodio de disfunción hepática tras el trasplante. Para el diagnóstico de rechazo se utilizaron criterios clínicos bioquímicos e histológicos. La biopsia fue considerada como el único criterio determinante para el diagnóstico de rechazo, e imprescindible para que el caso fuera incluido en el estudio. De esta manera quedaron configurados dos grandes grupos. El primero constituido por aquellos trasplantes en los que la biopsia mostró la existencia de un rechazo, y el segundo por los que la biopsia no demostró la presencia de un rechazo. A partir de este dato se recogió de cada trasplante una serie de variables obtenidas antes, durante o después del trasplante que fueron agrupados en las denominadas Variables Relacionadas con el donante, Variables Relacionadas con el Receptor, Variables relacionadas con el episodio de Rechazo y Variables que correlacionan Donante y Receptor. En total se han analizado en cada trasplante 33 variables. El estudio estadístico se realizó mediante un análisis bivariante con la variable dependiente Rechazo y las otras variables del donante y del receptor, seguidas de una regresión logística para identificar los parámetros con significación pronóstica independiente. Asimismo se analizó la probabilidad de presentar un rechazo a Jo largo del tiempo mediante la comparación de curvas de supervivencia mediante los test de Brelow y Mantel-Cox. Los resultados obtenidos permitieron contestar a modo de conclusión las preguntas planteadas en la hipótesis de trabajo: 1.- ¿Existen algunas alteraciones en los parámetros bioquímicos de función hepática o en otras "aria bies que se desprenden del estudio del donante y del receptor que sean un índice seguro de diagnóstico de rechazo? Sí. El estudio realizado permitió separar dos tipos de pacientes en función de la presencia o no de rechazo. El análisis entre los dos grupos demostró que existían algunas diferencias entre ellos que eran significativas desde el punto de vista estadístico. Después de realizar el estudio bivariable se han determinado unos puntos de corte de cada variable que con el estudio estadístico ofrecen una sensibilidad y especificidad alta con una probabilidad de diagnosticar correctamente entre el 81% y el 87% de los pacientes. Tras este estudio se realizó un estudio multivariable en el que se introdujeron las variables que habían resultado significativas en el estudio univariable y otras que razonablemente podían estar implicadas desde el punto de vista médico. En el modelo final resultaron ser significativas cuatro variables, tres de ellas cuantitativas como son el valor de bilirrubina, el valor de Gammaglutamiltranspeptidasa y la edad del receptor y una cualitativa que fue la compatibilidad entre donante y receptor a nivel del "locus" B del Complejo Mayor de Histocompatibilidad. 2.- ¿Existen algunos datos obtenidos del estudio del receptor que puedan servir de predicción de la aparición de un rechazo a lo largo del tiempo? Sí. El interés de esta tesis se centraba no sólo en el análisis del rechazo a partir del momento de su aparición sino también en considerar si existían factores que sirvieran de predicción de la aparición del rechazo. Estos factores se han definido en este estudio tras la realización de curvas de supervivencia. El único factor dependiente del receptor que tienen capacidad de predicción de la aparición del rechazo en nuestros trasplantes es el Diagnóstico por el que se indica el Trasplante. A través del estudio estadístico realizado se pudo establecer una gradación de mayor a menor rechazo en función del diagnóstico. Los pacientes con un trasplante realizado por una Insuficiencia Hepática Aguda, tienen una mayor incidencia de rechazo agudo. Este hecho no es dependiente de la compatibilidad ABO. La necesidad acuciante de un órgano hace que en estos pacientes no se respete la compatibilidad sanguínea. Por esta razón se podía suponer que este grupo de pacientes el rechazo agudo era una consecuencia de la trasgresión de la compatibilidad ABO. Esto no es así porque el número de pacientes con ABO incompatible es insignificante. Por otra parte se ha podido observar que los pacientes con Cirrosis de etiología alcohólica tienen una menor probabilidad de presentar un rechazo a lo largo del tiempo, significativamente menor que el que presentan los pacientes con Cirrosis de etiología no alcohólica como son las criptogenéticas o las post-hepáticas. 3.- ¿Existen algunos dalos obtenidos del estudio del donante que puedan servir de predicción de la aparición de un rechazo a lo largo del tiempo? Sí. Al igual que en la pregunta anterior de la hipótesis se han calculado curvas de supervivencia de cada parámetro hasta el momento en que los pacientes han presentado un rechazo. Se han encontrado dos parámetros dependientes del estudio del donante que podrían servir de predicción de la aparición de un rechazo, y que son el sexo del donante y también el tipo de Solución de Preservación utilizado. Los trasplantes realizados con donantes de sexo femenino tienen un tiempo libre de rechazo significativamente mayor que los de sexo masculino. Del mismo modo, los órganos preservados con el método que hemos denominado combinado tienen un mayor tiempo libre de rechazo que los preservados con Solución de Eurocollins o Solución de Wisconsin aisladas. 4.- ¿Podría concretarse en una ecuación matemática la probabilidad de que una determinada disfunción hepática, en un determinado receptor al que se le ha trasplantado un determinado hígado fuera un rechazo? Sí. Para contestar a esta pregunta planteada en la hipótesis hemos utilizado las variables que demostraren capacidad pronostica independiente para diagnosticar el rechazo. Los resultados se han concretado en la siguiente ecuación en la cual se tienen en cuenta estas variables en función de los puntos de corte y de los coeficientes de regresión: e(2.9971+edadx(-0.19868)+ MMBx2.7666 +Bix4.5203+GPTx5.6646) PROB= ----------------------------------------------------------------------------------------------- 1+e(2.9971+edadx(-0.19868)+MMBx2.7666+Bix4.5203+GPTx5.6646) Esta ecuación ofrece según el cálculo de probabilidades un valor global de alrededor del 90%. Se ha validado en un grupo de enfermos pertenecientes a la misma Unidad distintos de la serie inicial de 100 Trasplantes. Se han considerado tanto los primeros episodios como los segundos o terceros episodios de disfunción hepática. Los resultados obtenidos tras la validación demuestran que con esta ecuación es posible diagnosticar correctamente las tres cuartas partes de los episodios de disfunción hepática que aparecen tras el trasplante. 5.- ¿Sería posible establecer distintos grupos de riesgo de presentar un rechazo a lo largo del tiempo, en función de parámetros obtenidos del estudio del donante y del receptor? Sí. El estudio multivariable que se realizó con todos los factores significativos demostró que existía como único factor pronóstico independiente, el diagnóstico con el que se había realizado la indicación del trasplante. Existía una clara gradación en el sentido de que los pacientes con trasplante por Insuficiencia Hepática Aguda tienen un mayor probabilidad de presentar un rechazo o sea tienen un menor tiempo libre de rechazo. A continuación el grupo de las Enfermedades de predominio Colestásico constituidas en su mayor parte por Cirrosis Biliares Primarias. En tercer lugar se situaron los pacientes con Enfermedades de predominio hepatocelular en el que estaban incluidos los pacientes con cirrosis de variada etiología. Por último, como grupo en el que existe un mayor tiempo libre de rechazo están los pacientes con una hepatopatía alcohólica. Este hecho es un punto que debe unirse a las consideraciones éticas que se han invocado para que el grupo de los pacientes alcohólicos no sea discriminado a la hora de indicar un trasplante hepático.Rejection is one of the most important problems alter liver transplantation (OLT).The aim of the present study was to evaluate the possibility of diagnosis of rejection only by biochemical parameters. Besides to study different preoperative and postoperative factors that may influence in the incidence of rejection episodes. MATERIAL AND METHODS: From June 1988 to October 1990, 82 OLT were performed. 66p were male and 16 female. Triple therapy immunosuppresive regimen was used (Cyclosporine, Azathioprine and Prednisone). During the follow-up period, 89 fine-needle aspiration biopsies were performed due to liver graft dysfunction episodes. Variables considered were: Liver Function tests, donor and recipient age, sex, CMV status, ABO compatibility, HLA mismatch, Crossmatch, preservation solution, and indication for OLT (hepatocellular, cholestatic, fulminant hepatic failure , and retransplantation, Statistical Analysis: Univariate and Multivariate Methods (proportional hazard model with co-variates) were used. Only the first liver dysfunction episode was considered. According to histologic findings the samples were divided in Group 1: rejection present (60), Group 2: No signs of rejection (22). Median follow up was of 10 months (range from 3 to 28). RESULTS: Patients with rejection episodes significantly differed in the value of: Bilirrubín >2.5 mg%, AST>701.U, age (inverse related) and mismatch B. Regression model was used and applied in a formula where the above variables were considered. Overall diagnosis sensibility and specificity was around 75%. Incidence of rejection was equally distributed with respect to donor age (26.3 vs. 25.3) and recipient age (44.9 vs. 48.6) Patients without sex mismatch rejected in 54.7%, while patients with sex mismatch rejected in 45.2%. Donor/recipient CMV+/- did not influence on rejection. A total of 6 positive crossmatch were detected, only one in the group of no rejection episodes. With respect to HLA mismatch, most of our patients had 5 or 6 MM (55). Finally patients with alcoholic cirrhosis had a low incidence of rejection (5 out of 14). Multivariate analysis confirmed the predictive value of the type of cirrhosis on the incidence of rejection (X2=7.7, p<0.005). CONCLUSION: Using the formula here in proposed the possibility to diagnose rejection episodes over 75%. Out of the preoperative risk factors studied we have found that only patients with alcoholic cirrhosis have demonstrated a low risk for rejection

Cost-effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation.

Background: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. Aims: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. Method: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment—resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. Results: Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8–6.1 months with an acceptable cost ($40 000/ year of life gained) for waiting lists ≥1 year whereas it was not cost effective ($74 000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2–6.7 months with a marginal cost of approximately $20 000/year of life gained in all cases, remaining cost effective for all waiting times. Conclusions: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage