H. I. Wright

Autoimmune chronic active hepatitis (CAH-A) is a chronic liver disease of unknown etiology that is believed to have an autoimmune pathogenesis. The disease is slowly progressive until hepatic failure and portal hypertension develop and either death or liver transplantation occur. Currently, the only widely recognized therapy is the administration of glucocorticoids, which have both anti-inflammatory and immunosuppressive actions. Many patients cannot tolerate such therapy because of the psychiatric, osteoporotic, and weight-enhancing actions of steroids. Tacrolimus (FK 506) is a new macrolide antibiotic that has an immunosuppressive activity that is estimated to be 10-200 times greater than that of cyclosporine. Because of its greater immunosuppressive activity, we have used it in the treatment of 21 patients with autoimmune chronic active hepatitis. Before each subject was treated, a liver biopsy and a panel of hematological, serological, and biochemical parameters were assessed. The Tacrolimus was administered orally at 12-h intervals, and the dose was controlled by monitoring plasma FK trough levels. After 3 months of therapy at an oral dose of 3 mg twice a day, having achieved a median blood level of 0.5 ng/ml, the serum ALT level was reduced by 80%, and the AST level was reduced by 70%. Modest change in the white blood cell count and platelet count were noted. The median BUN level increased from a level of 12 to 18 mg/dl, and the serum creatinine increased from 0.9 to 1.3 mg/dl. These preliminary data demonstrate that: 1) Tacrolimus can be used to successfully treat CAH-A; 2) the response of CAH-A to Tacrolimus treatment is rapid and sustained; and 3) a minor increase in the serum BUN and creatinine levels occurs as a consequence of Tacrolimus treatment. It is anticipated that with continued treatment for periods of 1-2 yr, the natural history of CAH-A will be changed such that hepatic failure and the requirement for liver transplantation may be averted.

Liver biopsy is a frequently utilized diagnostic tool at a liver transplant center. It is occasionally utilized prior to OLTx to determine whether or not a potential recipient either has tumor or a disease process that has some chance of spontaneous recovery without OLTx. Following OLTx, it is often utilized to determine the need to alter a recipient's immunosuppression regimen or gauge the response to a recent change in immunosuppression. At the University of Pittsburgh Medical Center, adult liver transplant patients have been biopsied using 3 different techniques based upon the physician's (Tru-cut needle) or surgeon's (suction needle) personal choice and whether or not it has been the intent of the biopsy to obtain tissue from a focal lesion within a liver. In the latter cases, ultrasound guidance and an automated biopsy needle are used. In the former, either a suction-type needle (Jamshidi) or a cutting needle (Tru-cut) has been used. During the period between January 1, 1989, and December 31, 1991, a total of 12,750 liver biopsies have been done on patients admitted to the adult transplant service at this institution. Of these, 8500 were performed with a suction needle, 4195 were performed using a cutting needle, and 55 were performed under ultrasound guidance using an automated cutting needle. A total of 26 major complications occurred--19 with the suction needle (0.22%); 6 with the cutting needle (0.14%), and 2 using ultrasound guidance and an automatic cutting needle (3.6%). Nine of these 26 complications required surgical intervention consisting of a thoracotomy or laparotomy; 4 required the insertion of a chest tube and two required hepatic artery embolization. Based upon these data obtained at a large transplant center, it can be concluded that, in general: (1) a liver biopsy can be done safely in liver transplant recipients; (2) an overall low rate of major complications occurs varying from 0.1 to 3.6% depending upon the type of needle and other circumstances relating to the biopsy procedure; (3) complications, when they occur, are morbid and often necessitate either additional surgical or interventional radiologic procedures.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is a common complication of advanced cirrhosis. Thus many potential transplant recipients will experience this problem while waiting for a liver donor. The minimal amount of time with the use of appropriate antibiotics after which a potential recipient can be transplanted safely is not currently known. We examined the effect of pretransplant SBP on subsequent post-transplant outcome. MATERIALS AND METHODS: A retrospective review of the records of 100 liver transplant recipients having an episode of spontaneous bacterial peritonitis within 30 days of their transplant was performed. The records of transplant controls without an episode of spontaneous bacterial peritonitis were reviewed to compare the outcome between the two groups in terms of sepsis during the initial 30 post-transplant days. RESULTS: Post-transplant sepsis occurred in 8.8% of the cases and 10% of the controls (NSO). Only one episode in the study group could be ascribed to the pre-transplant episode of spontaneous bacterial peritonitis and it occurred in an IgA deficient recipient. CONCLUSIONS: These data suggest that SBP prior to liver transplantation does not lead to an increased rate of postoperative sepsis if 4 or more days of appropriate treatment for SBP are administered prior to liver transplantation.

As a potent immunosuppressive agent, Tacrolimus is widely used in organ transplantation. Although complications due to chronic Tacrolimus use are rather well recognized, little is known about acute overdose and its treatment. Phenytoin, an anti-convulsant agent, can induce the Cytochrome P450 enzyme in the liver, which metabolizes Tacrolimus. Therefore, it can be considered as a potential treatment option for acute Tacrolimus toxicity. We hereby report two cases of acute Tacrolimus overdose after Orthotopic Liver Transplantation and the treatment with Phenytoin. Probable mechanisms of metabolism and interactions of these two drugs are discussed and the literature is reviewed.

Liver transplantation (OLTx) has become a common procedure at many centers in Europe and North America. The 1 and 5 year survival of patients receiving liver transplants at most centers is 75-85% and 60-65% respectively. As such, many physicians, in addition to those at transplant centers, will be called upon to see and care for recipients surviving liver transplants. The gastrointestinal tract is a common site of post-transplantation problems. These problems involve all components of the gastrointestinal tract. Many have characteristic, if not unique, presentations and clinical courses. They are reviewed for the physician in clinical practice who does not practice at a transplant center.