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/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. 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.

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 < or = 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.

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

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. MATERIAL AND METHOD: Forty-seven patients underwent RFA and were listed for transplant between January 1998 and May 2003. The patients were divided into two groups: transplanted and non-transplanted. Both groups were evaluated in terms of tumor characteristics, recurrence, mortality rate, and time on the waiting list. The ablation sites in the explanted livers were examined for percentage of necrosis by Hematoxylin & Eosin (H&E) stain and by TUNEL stain. RESULTS: Transplantation was carried out in 35 patients (74.5%). Ten patients (21.3%) died before transplant or were removed from the wait list, while two patients (4.2%) are still listed. Mortality and tumor-related mortality were significantly higher in the non-transplanted group. The time spent on the waiting list was longer in the non-transplanted patients (350 vs. 186 d average, p = 0.0345). Thirty-eight ablation sites were examined in the explanted livers. The percentage of tumor necrosis by TUNEL staining was 19.6% higher than that reported by H&E staining. After TUNEL staining, 28 sites (73.7%) had more than 90% necrosis, eight sites (21.0%) had 50-90%, and two sites (5.3%) had less than 50% necrosis. CONCLUSIONS: RFA and LTX can be used successfully in HCC patients, and in most cases, tumor necrosis can be achieved with ultrasound-guided RFA. H&E stain tends to under-represent the amount of tumor necrosis on the ablation sites. Survival of RFA patients after LTX is excellent.

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

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.

Comparison of two drug regimens upon clinical outcome among renal transplant recipients with positive flow cytometric crossmatches.

Renal transplant recipients with positive flow cytometric crossmatches (FCXM) face greater risk of early rejection and graft failure. It is clear that the pharmacologic needs of this high risk group have not been identified. We retrospectively compared the impact of two drug regimens upon early rejection and 5 yr actuarial survival among 324 primary cadaveric transplant recipients with positive and negative FCXM. Patients received either Regimen I (OKT3 induction, cyclosporine and steroids) or Regimen II (mycophenolate mofetil with cyclosporine or Prograf). Recipient gender, age, disease etiology, ethnic distribution and cytotoxic panel reactive antibody (PRA) were equivalent between regimens (p=ns). With Regimen I, the incidence of rejection was greater for FCXM positive vs. FCXM negative patients (51 vs. 21%, p=0.001). In contrast, with Regimen II the incidence of rejection for FCXM positive and FCXM negative patients was equivalent (18 vs. 12%, p=ns) and lower than patients treated with Regimen I (p < 0.01). Ethnic variation was only observed with Regimen I in which African Americans with positive FCXM had more rejections than Caucasians (60 vs. 45%, p < 0.05). Five-year actuarial survival was lower for FCXM positive vs. FCXM negative patients treated with Regimen I (40 vs. 75%, p=0.0006) or Regimen 2 (60 vs. 90%, p=0.001). Allograft survival was equivalent (p=ns) among FCXM positive individuals receiving Regimen I or II. However, allograft survival among FCXM negative individuals improved with Regimen II (p < 0.05). Ethnic variation in survival was not observed with either regimen (p=ns).

The Baylor Regional Transplant Institute: review of a twenty-year experience.

As the Baylor Regional Transplant Institute celebrates its 20-year anniversary and the transplant of its 2,500th liver, the program has continued to grow, reaching its highest yearly volume to date. Twenty years gives an excellent opportunity to see how the facets of our program have adjusted in response to changes in both society and our own field of transplantation. Our recipient and donor demographics have changed significantly, but despite older recipients, older and more marginal donors and the issues of disease recurrence, we have consistently improved survival of both the patient and graft, reduced rejection rates and minimized hospital and ICU stays. These survival improvements have been even more pronounced in patients transplanted for HCC. Because of constantly changing risk and complication patterns, we have continually analyzed and adapted our processes and protocols, adjusting them in response to patient outcomes and the best current scientific evidence when needed. The research at Baylor has always had a practical, clinical dimension, but with development of our "Genes of Health" program at the Baylor Institute of Immunology Research, we hope to expand more basic science transplant research and most importantly take the lead in translational research.

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

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.

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

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.

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.