Enhanced oral cyclosporine absorption with water-soluble vitamin E early after liver transplantation.

We evaluated the effect of Liqui-E, a water-soluble vitamin E preparation, on cyclosporin A (CyA) whole blood concentration in liver transplant recipients, and its impact on the cost of CyA. Patients were 26 liver transplant recipients (19 adults, 7 children) who were unable to achieve and maintain therapeutic CyA whole blood concentrations with the standard recommended oral daily dose in the early post-transplant period. Liqui-E 6.25 IU/kg orally was administered with CyA every 12 hours (median time of starting Liqui-E day 14.5). With Liqui-E, the daily oral CyA requirements (mean +/- SD) were decreased in adults from 22.6 +/- 8.9 to 16.2 +/- 7.3 mg/kg/day (p < 0.001) and in children from 78.6 +/- 34.1 to 53.7 +/- 35.0 mg/kg/day (p < 0.02); intravenous administration of CyA was unnecessary. The CyA trough concentrations (mean +/- SD) before and after Liqui-E were 670 +/- 186 and 1012 +/- 216 ng/ml, respectively, in adults (p < 0.001) and 732 +/- 187 and 1052 +/- 166 ng/ml, respectively, in children (p < 0.01). When given with Liqui-E, the daily cost of CyA decreased by 26% in both adults and children. No clinical or biochemical evidence of Liqui-E toxicity was observed. Thus its administration in the early post-transplantation period can enhance CyA absorption in adults and children who are unable to achieve adequate whole blood concentrations with the usual recommended oral dosages. In addition, a significant cost saving can be realized by coadministration.

Hepatic resection for malignancy in the elderly.

Although elderly patients are accounted for in all large series of major hepatic resections, the role of age as a determinant of outcome remains unclear. At Cedars-Sinai Medical Center, we review a series of 20 major hepatectomies for neoplasia performed in patients older than 66 years of age (4 of them > or = 80 years old) over a 5-year period. A retrospective comparison was conducted with a group of 22 hepatectomies for malignancy performed in 20 patients younger than 59 years of age during the same time period. The younger group had a significantly greater degree of liver resected (12 trisegmentectomies vs 3). Although one operative death (5% mortality) was observed in the elderly group, no statistically significant difference was noted, when compared to the younger group (Chi-square, P = 0.48). Likewise, no significant difference in the complication rate (20% vs 33%) was noticed (Chi-square, P = 0.8). Severe postoperative liver dysfunction was present in 2 cases (10%) in the elderly group and one (4%) in the younger group. These patients underwent a right trisegmentectomy (TS). Nine patients from each group were resected without red blood cell transfusion. We conclude that major hepatic resection in elderly patients without severe comorbid disease is a safe procedure that is not associated with an increased perioperative morbidity or mortality rate.

Improved method of porcine renal allografting for transplantation research.

This study presents a refined, reproducible, and clinically appropriate animal model of renal transplantation. A pair of kidneys are harvested from a donor pig and preserved in Euro-Collins' solution (4 degrees C). After a set period of preservation, the allografts are transplanted to two recipient pigs. The abdomen is entered through a midline incision. The right common iliac artery and vein are dissected and bilateral native nephrectomy is performed. Each allograft is then randomly assigned and transplanted to the recipients. Three minutes before unclamping, 100 mg of furosemide and 10 g of mannitol are given IV. Immediately after reperfusion, urine output is measured for 1 h. The allograft is biopsied and ureteroneocystostomy is created. Cystostomy is then placed using a 16F Foley catheter. The bladder neck is ligated to secure complete diversion of urine, and the abdomen is closed in layers. This kidney transplant model allows an absolutely paired study of the kidney allograft function from the same donor and also collection of pure urine at any time postoperatively, obviating the need for metabolic cages or sedation for urinary collection. This model and its unique modifications allow various transplant studies, including organ preservation, immunosuppressive protocol, and the prevention of reperfusion injury from oxygen free radicals.

Hepatic regeneration: current concepts and clinical implications.

Liver regeneration occurs as a result of hepatic tissue loss or injury. The process of liver regeneration is carefully regulated in a controlled biologic scheme with closely interactive relationships between hormones, free neurotransmitters, and nutrients; protooncogenes; and polypeptide and glycolipid growth factors. These relationships are now being studied at the molecular and cellular levels and attempts are being made to reconstruct the complete intricate process. Although significant breakthroughs have occurred in understanding the effects and regulation of several subsystems (such as insulin and its receptors; TGF-alpha and TGF-beta; HGF and its receptors), the integral process remains a mystery. Improved comprehension of the regeneration process will lead to rational treatment algorithms for now dreaded hepatic diseases.

Acute liver failure due to lymphoma. A diagnostic concern when considering liver transplantation.

Lymphomatous involvement of the liver may present as acute liver failure but is an absolute contraindication for liver transplantation. Therefore it is imperative to diagnose such patients since survival in this group is poor and recurrence is high. We describe two patients with acute liver failure referred for liver transplantation whose diagnostic testing revealed hepatic lymphoma. These cases underscore the importance of considering lymphoma in the differential diagnosis of acute liver failure prior to liver transplant.

Malignant vascular tumors of the liver presenting as liver failure and portal hypertension.

We describe three patients referred for orthotopic liver transplantation with liver failure and portal hypertension who were found to have malignant vascular tumors: two patients with angiosarcoma and one patient with epithelioid hemangioendothelioma. Their clinical presentation mimicked decompensated chronic liver disease. None had tumor masses on computed tomography and ultrasonography. Massive tumor involvement of the liver was identified in the two patients studied by magnetic resonance imaging. Pathological examination of the explanted liver at the time of transplantation in one patient and autopsy in a second patient showed angiosarcoma. Laparoscopic liver biopsies in the third patient showed epithelioid hemangioendothelioma. The vascular origin of the tumor was established by histopathologic examination and confirmed with immunohistochemistry. Malignant vascular tumors of the liver should be included in the differential diagnosis of liver failure of unclear etiology.

Detection of hepatitis C virus with RNA polymerase chain reaction in fulminant hepatic failure.

The role of hepatitis C virus (HCV) infection in fulminant hepatic failure is controversial. The frequency of serum HCV RNA positivity in previously reported patients with fulminant hepatic failure (FHF) of indeterminate cause ranged from 0 to 12% in the United States and Europe and from 43% to 59% in Asia. We assessed serum HCV RNA using polymerase chain reaction (PCR) and oligoprimers from the 5'UTR of the HCV genome in 26 consecutive patients with FHF. Another laboratory independently performed PCR on 21 of the serum samples using different oligoprimers from the 5'UTR and NS3 region of the HCV genome. Serum HCV RNA was detected in two of seven (28%) patients with hepatitis B, 9 of 15 (60%) with an indeterminate cause, and in none with hepatitis A (n = 2) or drug-induced hepatotoxicity (n = 2). HCV RNA PCR results were concordant between both laboratories in 17 of 21 (81%) of samples. In patients with an indeterminate cause, HCV RNA positivity was significantly associated with the transmission risk factor of low socioeconomic status and Hispanic ethnicity. Eighteen patients underwent liver transplantation (LT) and 15 (83%) survived. Among patients with FHF of indeterminate cause, recurrent or acquired HCV infection after transplantation occurred in three of five (60%) and one of four (25%) patients, respectively. Three of four (75%) patients with hepatitis C virus infection post-LT also developed histologic hepatitis. HCV appears to be the causative agent of a substantial number of cases of FHF classified as indeterminate in the Los Angeles area. Differences in patient populations or risk factors may explain the discordant incidences of HCV infection in FHF observed among different programs.