Fulminant hepatic failure after simultaneous kidney-pancreas transplantation: a case report / Insuficiência hepática fulminante após transplante simultâneo de rim-pâncreas: um relato de caso

Abstract We describe an unusual case of hyperacute hepatic failure following general anesthesia in a patient receiving a simultaneous kidney-pancreas transplant. Despite an aggressive evaluation of structural, immunological, viral, and toxicological causes, a definitive cause could not be elucidated. The patient required a liver transplant and suffered a protracted hospital course. We discuss the potential causes of fulminant hepatic failure and the perioperative anesthesia management of her subsequent liver transplantation.

Resumo Descrevemos um caso incomum de insuficiência hepática hiperaguda após a anestesia geral em uma paciente que recebeu um transplante simultâneo de rim-pâncreas. Apesar de uma avaliação agressiva das causas estruturais, imunológicas, virais e toxicológicas, uma causa definitiva não pôde ser identificada. A paciente precisou de um transplante de fígado que resultou em prolongamento da internação hospitalar. Discutimos as potenciais causas da insuficiência hepática fulminante e o manejo da anestesia no período perioperatório de seu subsequente transplante de fígado.

Paecilomyces variotii Fungemia in a Patient with Lymphoma Needing Liver Transplant.

Paecilomyces sp. are emerging pathogens in immunocompromised patients. We report here a case of Paecilomyces variotii fungemia, cured with amphotericin and anidulafungin, illustrating difficulties of early diagnosis and therapeutic choice in such rare fungal infection.

Alterations of Serum IP-10 and TARC in Patients with Early Acute Rejection after Liver Transplantation.

BACKGROUND/AIMS: To analyze alterations of interferon-γ-induced protein 10 (IP-10) and thymus and activation-regulated chemokine (TARC) levels in early acute liver transplantation rejection. METHODS: Thirty-six patients with early acute liver transplantation rejection were classified as non-, mild, moderate, and severe rejection groups. The levels of serum IP-10 and TARC were determined on days 3, 2, 1, and 0 before biopsy. RESULTS: The IP-10 activities in all rejection groups were significantly higher (p < 0.05) than those in the non-rejection group at all time points and correlated with the extent of rejection (p < 0.05). The differences in TARC among the three rejection groups were significant (p < 0.05), and its highest level was found in the mild rejection group at all observed time points, whereas its lowest level was detected in the severe rejection group. The analysis of the TARC/IP-10 ratio revealed that the volume was correlated with the rejection degree. This ratio in the moderate and severe rejection groups on days 2, 1, and 0 before biopsy were 20% lower than that before transplantation. CONCLUSION: Serum IP-10 showed an increasing trend during early acute liver transplantation rejection. IP-10 increase or TARC/IP-10 ratio decrease combining with abnormal hepatic enzymatic alteration could be a valuable and specific sign for early rejection of the transplanted liver.

Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-ß7 during Acute Graft-versus-Host Disease of the Liver.

Homing of allogeneic donor T cells to recipient tissue is imperative for the development of acute graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In this study we show that alteration of T cell homing due to integrin-ß7 deficiency on T cells or its ligand MAdCAM-1 in BMT recipients contributes to the pathophysiology of experimental GVHD. In contrast, lack of CC chemokine receptor 9 on donor T cells alters tissue homing but does not impact GVHD survival. We further demonstrate that MAdCAM-1 is aberrantly expressed in hepatic murine GVHD as well as in patients with active liver GVHD. However, infiltration of donor T cells in gut but not liver was dependent of MAdCAM-1 expression, indicating, that homing and/or retention of donor T cells rests on divergent molecular pathways depending on the GVHD target tissue.

Lack of association between CD40 polymorphisms and acute rejection in German liver transplant recipients.

CD40 and its ligand, CD154, are major costimulatory molecules whose interactions are important in alloreactive transplant rejection. The aim of this study was to examine the association of CD40 polymorphisms with the susceptibility to acute rejection episodes in liver transplantation. In total, 112 liver transplant recipients with biopsy proven acute rejections (BPAR), 97 without BPAR (WBPAR), and 112 healthy control individuals were enrolled in the study. Two single nucleotide polymorphisms (SNPs) of CD40 gene (rs1883832 and rs4810485) were genotyped by polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA). Both SNPs has been tested for a recessive and a dominant model. No significant differences were found in the genotype and allele frequencies of the SNPs rs1883832 and rs4810485 between BPAR liver recipients and WBPAR recipients. Our results do not suggest an important role of tested CD40 SNPs in the susceptibility to acute liver transplant rejection in a Caucasian population.

p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury.

BACKGROUND AND AIMS: The cyclin-dependent kinase inhibitor p21 has been implicated as a tumour suppressor. Moreover, recent genetic studies suggest that p21 might be a potential therapeutic target to improve regeneration in chronic diseases. The aim of this study was to delineate the role of p21 in chronic liver injury and to specify its role in hepatocarcinogenesis in a mouse model of chronic cholestatic liver injury. METHODS: The degree of liver injury, regeneration and tumour formation was assessed in Mdr2(-/-) mice and compared with Mdr2/ p21(-/-) mice. Moreover, the role of p21 was evaluated in hepatoma cells in vitro and in human hepatocellular carcinoma (HCC). RESULTS: Mdr2(-/-) mice developed HCCs as a consequence of chronic inflammatory liver injury. In contrast, tumour development was profoundly delayed in Mdr2/ p21(-/-) mice. Delayed tumour development was accompanied by markedly impaired liver regeneration in Mdr2/ p21(-/-) mice. Moreover, the regenerative capacity of the Mdr2/ p21(-/-) livers in response to partial hepatectomy declined with age in these mice. Hepatocyte transplantation experiments revealed that impaired liver regeneration was due to intrinsic factors within the cells and changes in the Mdr2/ p21(-/-) microenvironment. In human HCCs, a subset of tumours expressed p21, which was associated with a significant shorter patient survival. CONCLUSIONS: We provide experimental evidence that p21 is required for sustained liver regeneration and tumour development in chronic liver injury indicating that p21 needs to be tightly regulated in order to balance liver regeneration and cancer risk. Moreover, we identify p21 as a negative prognostic marker in human HCC.

[The role of transjugular hepatic biopsy in preparation of the patients for the large hepatic resection].

The results of transjugular hepatic biopsy (TJHB) were analyzed in 32 patients, in whom the performance of hepatic radical resection was planned for the focal hepatic diseases. The biopsy procedures have had succeeded in 100% of observations. The severe complications were absent. The specimen length have constituted 12 mm at average, fragmentation was noted in 32% of observations. All the specimen were recognized as affordable for histological studying. In 24 patients in terms of 2-4 weeks after biopsy the embolization of lobar branches of portal vein was performed with the objective to enhance the assumed residual hepatic volume. In all the patients in terms of 2-8 weeks the spacious radical hepatic resection was succeeded. The data obtained witness that application of TJHB is expedient in the patients, who are prepared for spacious radical hepatic resection, for estimation of the organ parenchyma state and prognostication of postoperative hepatic insufficiency.

Liver transplantation in the 21st century: expanding the donor options.

Over the past decade, use of ECD organs for OLT has allowed many transplant programs to afford patients access to an otherwise scarce resource and to maintain center volume. Although overall posttransplant outcomes are inferior to results with optimal, whole-liver grafts, aggressive utilization of ECD and DCD organs significantly lowers median wait-times for OLT, MELD score at OLT, and death while awaiting transplantation. It is incumbent on the transplant community to provide continued scrutiny of the many factors involved in ECD organ utilization, evaluate the degree of risk and benefit such allografts may impart on particular recipients, and thereby provide suitable "matching" to maximize favorable outcomes. Transplant caregivers need to provide patients with evidence-based care decisions, be good stewards of a scarce resource, and maintain threshold survival results for their programs. This requires balancing the urgency with which a transplant is needed and the utility of such a transplant. There is a clear necessity to pursue additional donor research to improve use of these marginal grafts and assess interventions that enhance the safety of ECD livers.

Long-term management of the liver transplant recipient: pearls for the practicing gastroenterologist.

Liver transplantation is becoming more common and patients are surviving longer after transplantation. Special care must be paid to the long-term management of these patients because they are at increased risk for medical problems, malignancies, and adverse effects from immunosuppression. A stable and continuing relationship must be developed between the physician and the patient to optimize the long-term outcomes for these individuals.

[Therapeutic effect of autologous bone marrow stem cell transplantation in the treatment of severe liver damage].

OBJECTIVE: To evaluate the effect of autologous bone marrow stem cell transplantation in the treatment of severe liver damage. METHODS: Autologous bone marrow (50 ml) was harvested from 6 patients aged 44 to 69 years admitted for severe liver damage. Human bone marrow stem cells (HMSCs) were isolated and transplanted in to the patients' liver. At l, 4, 8, and 12 weeks after the transplantation, the changes in ALT, ALB, Cr, TB, PT and the clinical symptoms of the patients were observed. RESULTS: The transplantation of autologous bone marrow stem cells resulted in obvious improvement of the liver function. At 12 weeks after the transplantation, ALT was reduced from 98.4 IU/L to 41.5 IU/L, TB from 136.5 µmol/L to 78.4 µmol/L, Cr from 112.3 µmol/L to 72.1 µmol/L, and ALB rose from 23.3 g/L to 32.6 g/L. The survival of the patients was 100% at 12 weeks, but one patient died at 7 months after the transplantation. The symptoms of the patients were also alleviated after the transplantation. At 12 weeks after transplantation, 3 patients reported improved appetite, 3 showed recovery of physical strength, and 2 showed lessened abdominal swelling. No serious adverse complications in association with the transplantation were found in the in 4 patients available to the follow-up. CONCLUSION: Autologous bone marrow stem cell transplantation can improve the liver function of patients with severe liver damage without causing serious complications.

Assessing outcomes in liver disease patients: reliability and validity of the Spanish version of the Liver Disease Quality of Life Questionnaire (LDQOL 1.0).

OBJECTIVE: To assess the reliability and validity of a Spanish version of the LDQOL 1.0 (Liver Disease Quality of Life questionnaire). METHODS: Observational, cross-sectional study in Spanish patients awaiting liver transplantation (LT). Feasibility was assessed by analyzing administration times and missing responses. Ceiling and floor effects were calculated and reliability was tested by examining internal consistency (Cronbach's alpha). Convergent validity was tested by examining correlations between LDQOL disease-specific and Short Form health survey with 36 questions (SF-36) dimensions. Known groups' validity was tested by examining the LDQOL's capacity to discriminate between groups defined by etiology and Child-Turcotte-Pugh (CTP) scores. RESULTS: A total of 200 patients were included for analysis. Mean age (SD) was 52.6 (9.8) years and 73% of the sample were male. The most common indication for LT was liver cancer (34%). Mean (SD) time to complete the questionnaire was 35.8 minutes (21.2 minutes). Missing responses were highest on the dimensions of sexual functioning and symptoms of liver disease. Ceiling effects were over 20% on 7 of the LDQOL's 12 disease-specific scales. Cronbach's alpha coefficients were over 0.70 on all but 2 dimensions. Correlations between SF-36 and LDQOL disease-specific dimensions generally fulfilled the hypotheses, with 35 of the 40 highest and lowest correlations (87.5%) being in the expected direction. The LDQOL discriminated well between patients in CTP class A and C, and as hypothesized, hepatocarcinoma and alcoholic cirrhosis patients scored better on most dimensions than patients with hepatitis C virus or other etiologies. CONCLUSIONS: The Spanish version of the LDQOL 1.0 has shown satisfactory reliability and validity.

[Criteria of differential assignment of drugs with sorptive and disintoxication properties to patients with obturative icterus of non-tumoral genesis].

The article defines criteria of differential assignment of drugs with sorptive and disintoxication properties according an analysis of clinical signs of a mechanical icterus, results of biochemical, immunologic, biophysical, crystal optics methods. The results were assessed by points (high--a score 98-65; average--64-32 a point; low--not higher 31 points) that allowed to judge severity level of a patient condition with obturative icterus not tumoral genesis. Positive efficiency of treatment was defined by point estimation which was not lower than 10 times (severe and moderate degrees; moderate and mild degrees). The study has shown that consideration both clinical and laboratory characteristics of the course of obturative icterus allows raising results of the treatment due to individual therapy and to predict its efficiency based on dynamic definition of point assessment of severity level.

Endourological management of urolithiasis in hepatically compromised patients.

PURPOSE: Hepatic insufficiency is a medically debilitating disease state, resulting in coagulopathy, malnutrition and immunological suppression. Before and after liver transplantation patients are at increased risk for urolithiasis due to nutritional factors, acidosis and hyperoxaluria. MATERIALS AND METHODS: We retrospectively reviewed our experience with endourological procedures for nephrolithiasis in hepatic compromised patients awaiting transplants and recipients. A total of 16 patients, including 13 males and 3 females, with a mean age of 52.8 years (range 46 to 59) underwent a total of 24 endoscopic stone procedures at 23 anesthesia sessions. Procedures included 18 ureteroscopies (extraction with or without lithotripsy), 5 percutaneous nephrolithotomies and 1 cystoscopic stone manipulation. Of the patients 12 patients had significant hepatic insufficiency and were evaluated for transplantation. Four patients had a prior orthotopic liver transplant at surgery. The most common causes of cirrhosis were hepatitis C and ethanol abuse. Of 22 sessions 12 were preceded by the use of fresh frozen plasma, platelets, vitamin K, desmopressin or recombinant factor VIIa for reversing severe coagulopathy. In 4 patients procedures were preceded by transfusion for anemia. RESULTS: All 24 procedures were successfully accomplished. Average hospital stay was 2.8 days (range 0 to 8) with 5 patients treated on an outpatient basis. A total of 52 calculi with a mean size of 10.7 mm (range 2 to 40) were treated. Of the 17 evaluated stone analyses 15 revealed pure or mixed calcium oxalate calculi, while the remaining 2 were struvite. Morbidity included 2 postoperative transfusions and 1 rehospitalization for urinary tract infection. One death was due to multisystem organ failure in a pretransplant patient who underwent bilateral ureteroscopy. CONCLUSIONS: Endourological procedures may be accomplished in this morbid group of patients. Mandatory preoperative medical evaluation, selective prehospitalization with supportive services and pre-stenting patients for passive ureteral dilation have led to successful endourological outcomes. Our experience has led us to adopt protocols and apply a team approach for the successful endoscopic management of urolithiasis in this complicated group of patients.

Comparison of two methods of future liver remnant volume measurement.

BACKGROUND: In liver transplantation, a minimum graft to patient body weight (BW) ratio is required for graft survival; in liver resection, total liver volume (TLV) calculated from body surface area (BSA) is used to determine the future liver remnant (FLR) volume needed for safe hepatic resection. These two methods of estimating liver volume have not previously been compared. The purpose of this study was to compare FLR volumes standardized to BW versus BSA and to assess their utility in predicting postoperative hepatic dysfunction after hepatic resection. METHODS: Records were reviewed of 68 consecutive noncirrhotic patients who underwent major hepatectomy after portal vein embolization between 1998 and 2006. FLR (cubic centimeter) was measured preoperatively with three-dimensional helical computed tomography; TLV (cubic centimeter) was calculated from the patients' BSA. The relationship between FLR/TLV and FLR/BW (cubic centimeter per kilogram) was examined using linear regression analysis. Receiver operating characteristic (ROC) curve analysis was used to determine FLR/TLV and FLR/BW cutoff values for predicting postoperative hepatic dysfunction (defined as peak bilirubin level>3 mg/dl or prothrombin time>18 s). RESULTS: Regression analysis revealed that the FLR/TLV and FLR/BW ratios were highly correlated (Pearson correlation coefficient, 0.98). The area under the ROC curve was 0.85 for FLR/TLV and 0.84 for FLR/BW (95% confidence interval, 0.71-0.97). Sixteen of the 68 patients developed postoperative hepatic dysfunction. The ROC curve analysis yielded a cutoff FLR/BW value of

Trasplante hepático en adultos: casuística de Clínica Alemana de Santiago / Adult liver transplantation: a single center experience from Chile

Background: The success of orthotopic liver transplantation (OLT) has resulted in its widespread use for different liver diseases. Aim: To report our 8 years experience with adult OLT at Clinica Alemana de Santiago. Patients and methods: In all transplantations done at the center, we recorded patient's overall data and survival, postoperative medical and surgical complications and causes of death. Results: Between November 1993 and September 2001, 51 consecutive OLT were performed in 44 patients (22 females, median age 45 years old). Thirty eight patients presented with chronic and 6 with acute or sub-acute liver failure. Cryptogenic cirrhosis and hepatitis C infection were the most common causes for OLT. Postoperative bleeding and extra-hepatic biliary complications were seen in 17.6 and 21.5 percent of cases respectively. Acute rejection, bacterial infections, CMV infection or disease and post OLT hemodialysis were the most common medical complications (51, 31, 19.6 and 19.6 percent of cases respectively). The overall 1 and 5 years survival rates were 80 percent and 73 percent respectively. Considering exclusively the last 22 OLT performed since January 1999, the 1 year survival rate has improved to 91 percent. Conclusions: Liver transplantation in Chile provides a good long term survival with acceptable morbidity, due to a multidisciplinary approach management. The survival rates have improved over the last few years probably due to better surgical techniques, ICU care and immunosuppression. These overall results are comparable with those from other Centers in developed countries

Insuficiencia hepática fulminante / Fulminant hepatic failure

Fulminant hepatic failure (FHF) is an acute and eventually fatal illness, caused by a severe hepatocyte damage with massive necrosis. Its hallmarks are hepatic encephalopathy and a prolonged prothrombin time (<40 percent). FHF is currently defined as hyperacute (encephalopathy appearing within 7 days of the onset of jaundice), acute (encephalopathy appearing between 8 and 28 days) or subacute (encephalopathy appearing between 5 and 12 weeks). FHF can be caused by viruses, drugs, toxins, and miscellaneous conditions such as Wilson's disease, Budd-Chiari syndrome, ischemia and others. However, a single most common etiology is still not defined. Factors that are valuable in assessing the likelihood of spontaneous recovery are age, etiology, degree of encephalopathy, prothrombin time and serum bilirubin. The management is based in the early treatment of infections, hemodynamic abnormalities, cerebral edema, and other associated conditions. Liver transplant has emerged as the most important advance in the therapy of FHF, with a survival rate that ranges between 60 and 80 percent. The use of hepatic support systems, extracorporeal liver support and auxiliary liver transplantation are innovative therapies

Características clínicas y factores pronósticos en la insuficiencia hepática fulminante en adultos y niños / Clinical features and prognostic factors in fulminant hepatic failure in adults and children

La Insuficiencia Hepática Fulminante (IHF) es una entidad rápidamente fatal, secundaria a múltiples causas y se clasifica en hiperaguda, aguda y subaguda. El único tratamiento que modifica su pronóstico es el trasplante hepático ortotópico (THO). Objetivo: describir las características clínicas, manejo y evolución de pacientes adultos y niños con IHF. Pacientes y métodos: 51 casos de IHF, evaluando evolución, factores pronósticos, posible etiología y tratamientos realizados en el Hospital Clínico de la Universidad de Chile y Roberto del Río entre abril de 1990 y febrero del 2002. Resultados: 34 adultos (67 por ciento), edad de 46 ñ 17,6. Las causas principales fueron isquemia 29 por ciento, criptogénica 20 por ciento, drogas 14 por ciento y viral 11 por ciento. La presentación fue hiperaguda 53 por ciento, aguda 38 por ciento y subaguda 9 por ciento. Las complicaciones más frecuentes fueron respiratorias 67 por ciento, renal 67 por ciento, hematológicas 61 por ciento e infecciosas 55 por ciento. Diecisiete niños (33 por ciento), edad de 5 ñ 4,3. Las causas principales fueron viral 41,2 por ciento, criptogénica 29 por ciento, hepatitis autoinmune 17 por ciento. Las complicaciones más frecuentes fueron infecciosas 88 por ciento, cardiovascular 71 por ciento, respiratorias 65 por ciento y hematológicas 65 por ciento. Ingresaron a una Unidad de Pacientes Críticos 33 adultos y 17 niños. Sólo se transplantaron 3 (6 por ciento) pacientes (2 niños y un adulto), todos vivos hasta la fecha. La sobrevida sin transplante fue de 15 por ciento en los adultos y 20 por ciento en los niños. Conclusión: la IHF es una enfermedad de variada etiología y alta mortalidad, que requiere un manejo multidisciplinario y en que debería plantearse el THO como la única alternativa posible, si no hay contraindicación