Sherfield Dawson

Predictors of Survival After In Vivo Split Liver Transplantation: Analysis of 110 Consecutive Patients

ObjectiveTo determine the factors that influence patient survival after in vivo split liver transplantation (SLT). Summary Background DataSplit liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. MethodsDuring a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors’ in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. ResultsOverall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables—UNOS status and number of transplants per patient—were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. ConclusionsPatient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with hepatitis C

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha‐fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty‐four of 67 patients (36%) died during the follow‐up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC. (Liver Transpl 2004;10:1478–1486.)

Hyperlipidemia after liver transplantation : Natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin

This study was designed to determine the frequency of hyperlipidemia after orthotopic liver transplantation and whether treatment with a hydroxy-methylglutaryl coenzyme A reductase inhibitor was safe and efficacious. Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean +/- SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for patients on CsA [total n=22]: pre-Tx = 140+/-11, 1 month = 183+/-36,3 months = 221+/-12, 6 months = 211+/-11, 12 months = 202+/-14 [P<0.01 vs. pre-Tx]; FK506 [total n=23]: Pre-Tx = 151+/-13, 1 month = 187+/-22, 3 months = 188+/-10, 6 months = 184+/-13, 12 months = 164+/-9 [P=0.02 vs. CsA]). A separate cohort of patients with stable graft function, cholesterol >225 mg/dl, and two additional risk factors for coronary artery disease were started on pravastatin. Ninety-eight patients were enrolled. Sixteen patients (16%) discontinued the drug because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment = 251+/-7, 6 months = 220+/-7 [P=0.01 vs. pretreatment], 12 months = 224+/-8 [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251+/-17, 6 months = 219+/-17, 12 months = 208+/-17 [P=0.08 vs. pretreatment]). Natural killer cells isolated from normal volunteers (n=14) exhibited 27+/-9% specific lysis. Patients on FK506 or cyclosporine-based immunosuppression alone (n=11) exhibited 20+/-4% specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased lysis to 0.2+/-10% (P<0.02 vs. controls and standard immunosuppression). We conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver transplant patients than in renal or cardiac transplants; (2) pravastatin is safe and efficacious for cholesterol reduction in liver transplant patients; and (3) pravastatin coadministered with standard immunosuppression reduces natural killer cell-specific lysis in these recipients.

Early graft function after pediatric liver transplantation: Comparison between in situ split liver grafts and living-related liver grafts

Background. The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. Methods. A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. Results. There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P <0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P =0.745). In the surviving grafts, the early differences in liver function variables normalized. Conclusions. Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7–30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

Liver and Kidney Transplantation for Polycystic Liver and Kidney-renal Function and Outcome

Background. Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. Methods. Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. Results. Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8±25.4 ml/min/1.73m2. One year later, GFR was 37.2±8.3 ml/min/1.73m2. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7±54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4±68.6 months (n=9) (P=0.36). Conclusion. Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Calcineurin inhibitor-induced chronic nephrotoxicity in liver transplant patients is reversible using rapamycin as the primary immunosuppressive agent

Abstract: The purpose of this study was to determine whether calcineurin inhibitor (CNI)‐induced chronic nephrotoxicity in liver transplant patients is reversible by replacement of the CNI with rapamycin as the primary immunosuppressive agent. CNIs, while providing potent immunosuppression for liver transplant patients, exhibit nephrotoxicity as a major side‐effect. Whereas acute CNI‐induced nephrotoxicity is reversible by withdrawal of the CNI, chronic nephrotoxicity due to CNIs is a progressive process thought to be irreversible. Eight liver transplant patients with CNI‐induced chronic nephrotoxicity were converted to rapamycin as the primary immunosuppressive agent. The CNI was either discontinued (four patients) or the dosage lowered to maintain a subtherapeutic level (four patients). Renal function as assessed by serum creatinine was measured before and after conversion to rapamycin. Two patients progressed to dialysis dependence following conversion to rapamycin. These two patients had been on CNIs for a mean of 112 months (range 93–131 months) prior to conversion to rapamycin. Five patients experienced improvement in renal function. These patients had been on calcineurin inhibitors for a mean of 60 months (range 42–75 months) prior to conversion. One patient with chronic nephrolithiasis as a contributing factor to his renal dysfunction has progressed to dialysis dependence despite conversion to rapamycin following exposure to a CNI for 24 months. In the five patients with improved renal function, serum creatinine levels decreased significantly (2.4 ± 0.3 mg/dL to 1.5 ± 0.1 mg/dL, p < 0.05) by a mean of 7.2 months (range 5–10 months) after conversion from CNI to rapamycin‐based immunosuppression. Liver function remained stable after conversion to rapamycin. CNI‐induced chronic nephrotoxicity can be reversed upon withdrawal of the CNI. Rapamycin is an effective replacement agent as primary immunosuppressive therapy following withdrawal of CNIs in liver transplant patients with CNI‐induced chronic nephrotoxicity.

Radiofrequency thermal ablation of hepatocellular carcinoma before liver transplantation--a clinical and histological examination.

Abstract:  Background:  Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is an optional treatment for patients awaiting liver transplantation (LTX). The study evaluates the efficacy of RFA in the explanted liver and its effect on patient outcome.

Hepatocellular carcinoma: strategy for optimizing surgical resection, transplantation and palliation

Abstract: In December 1997, a prospective study with informed consent was initiated to test a neoadjuvant treatment of transcatheter hepatic arterial chemo‐embolization (TACE) and thermal or chemical ablation followed by transcatheter hepatic arterial chemo‐infusion (TACI) in patients with hepatocellular carcinoma (HCC) referred for transplantation (OLT) and for resection. Patients were staged with American Liver Tumor Study Group‐modified tumour‐node‐metastasis (TNM) staging classification using serial 3–6 month physical exam, alphafetoprotein (AFP), abdominal enhanced MRI, chest CT and bone scan. Sixty‐five patients with HCC, out of 508 patients referred for OLT, were divided into five clinical groups and an incidental HCC patient group (n = 8), diagnosed on post‐transplant explant pathology. The key focus of study was safety, site of HCC recurrence and tumour free survival. One hundred and thirty three ablation, infusion procedures were performed with an overall 24.8% morbidity, including two septic deaths. There were 13 (21.6%) HCC recurrences in 60 patients having one or more ablative treatments with only 23% hepatic HCC recurrences at 43 months of study. Eighteen HCC patients were listed for OLT (Group 3), with 12 patients transplanted after 29–424 d waiting. Two patients were removed from the OLT list due to HCC metastases, waiting a mean of 145 d. Two patients, post‐OLT, had their TNM score upgraded from T2, T3 to T4. No Group 3 post‐OLT patient has died or had HCC recurrence at mean follow‐up of 27 ± 15 months. No incidental HCC group post‐OLT patient has died or had HCC recurrence at mean follow‐up of 24 ± 14 months. This neoadjuvant protocol is safe and effective in reducing HCC recurrence prior to and after OLT and resection.

An outcome comparison between primary liver transplantation and retransplantation based on the pretransplant MELD score

Survival after liver retransplantation (RLTX) is worse than after primary liver transplantation (LTX). We studied retrospectively the 2‐year outcome in 44 patients who received RLTX more than 30 days after the primary transplant and in 669 after LTX performed between December 1993 and October 1999, focusing on the relation between the model for end‐stage liver disease (MELD) score immediately pretransplant and post‐transplant survival. A 2‐year survival for RLTX was inferior to LTX (65.9% vs. 82.9%, P ≤ 0.01). This difference was greatest with MELD scores < 25; survival within 2 years remained 11.3–18.2% less for RLTX than for LTX (6 months, P = 0.002; 12 months, P = 0.029, 24 months, P = 0.123). Mortality was mainly related to early vascular complications and sepsis. Two‐year survival after RLTX was 81.8% if RLTX occurred < 2 years after LTX and 50% if the interval between LTX and RLTX was > 2 years (P < 0.05). MELD scores were similar in 2‐year survivors and nonsurvivors after late RLTX (P = 0.82). Late RLTX is marked by poor survival regardless of the pretransplant MELD score. The MELD‐based allocation system may not benefit patients who undergo retransplantation.

Successful combined liver and kidney transplant for COACH syndrome and 5-yr follow-up

Abstract:  The COACH syndrome is a very rare disorder with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Nineteen cases with COACH diagnosis have been reported. Neurologic abnormalities are the first symptoms in most cases. Complications of the hepatopathy [portal hypertension, esophageal varices, and gastrointestinal (GI) bleeding] contribute extensively to the morbidity and lethality in the course of the disease. We describe a 28‐yr‐old female with COACH syndrome resulting in chronic renal and hepatic insufficiency. The patient was found to have significant mental retardation, truncal ataxia, motor abnormality and occulomotor abnormality. She began to develop GI bleeding and encephalopathy because of biopsy‐confirmed cirrhosis. We performed combined liver and kidney transplant after challenging discussion. Her postoperative course was uneventful, and she was discharged on the ninth postoperative day (POD). She has not had any problems at 1, 3 and 5‐yr follow‐up with excellent liver and renal function. This is the first description of successful combined liver and kidney transplant with long‐term follow‐up. The decision for transplant is challenging because COACH syndrome is rare with only descriptive characterization and patients have non‐progressive ataxia and mental retardation. However, our case shows that liver and kidney transplant can be medically successful, and the individuals achieve long‐term success if they have a stable neurological condition and an excellent support system.