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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.

Recipients of solid organ allografts require lifelong immunosuppression in order to prevent graft rejection and to maintain graft function. In general, such immunosuppression greatly impairs the cellular immune system, as this level of the immune system is principally responsible for self and non-self recognition. The consequences of allograft transplantation in terms of patient and graft survival when transplants are given to individuals who have a preexisting humoral immune deficiency characterized by a deficiency of the serum levels of one or more of the major Ig classes have not yet been reported. From February 1, 1981 through December 31, 1990, a total of 43 adult patients with a deficiency of 1 or more Ig classes received a ABO-matched liver allograft at this institution. This sample represents 2.5% of a total of 1684 adults transplanted during this interval. These 43 liver graft recipients could be divided into 3 major groups based upon the presence of an IgG, IgM, or IgA deficiency. IgG deficiencies were defined as levels less than 50 mg/dl. Patient and graft survival for the IgA-deficient group was significantly reduced (P less than 0.04 and P less than 0.009, respectively) compared with both the IgG- and IgM-deficient groups. The latter two groups did not differ from controls without an Ig deficiency for these same two endpoints. The major causes of death in the IgA-deficient group were sepsis and opportunistic infection. A third of the deaths in the IgA-deficient group occurred in the perioperative period (first 30 days) while greater than 50% of the deaths occurred within the first 3 months, and all deaths occurred before the first year. Based upon these data, the following conclusions can be made: (1) serum IgA deficiency but not IgG or IgM deficiency is associated with an increased post-OLTx death and graft loss rate; (2) the majority of these deaths are due to sepsis or an opportunistic infection; and (3) most of the deaths occur early. These data suggest that recognition of a deficiency of IgA prior to organ grafting necessitates meticulous attention to the prevention of infection in the immediate perioperative period if patient and graft survival of these patients is to be improved.

Gastrointestinal infection due to cytomegalovirus occurs frequently in liver transplant recipients. Upper gastrointestinal cytomegalovirus infection is associated with subjective complaints of nausea, a sense of abdominal fullness, and occasionally emesis and/or dysphagia. In order to determine whether these symptoms reflect a disruption of the normal motility of the stomach, the following study was performed. Eleven individuals who were evaluated for liver transplantation were prospectively recruited and studied as follows: (1) upper gastrointestinal endoscopy with biopsy of the gastric antral mucosa; (2) viral culture of the gastric mucosa; (3) a histologic examination of the gastric mucosa; and (4) a radionuclide gastric emptying study was obtained before and 4-8 weeks following successful liver transplantation. Prior to liver transplantation, none had symptoms of nausea, vomiting, or epigastric fullness. All were culture-negative for cytomegalovirus. All had endoscopic and histologic evidence of portal hypertensive gastropathy but none had antral erosions or ulcers. All demonstrated normal gastric emptying of a liquid meal. Following liver transplantation, 6 remained free of gastric cytomegalovirus while 5 developed a culture-confirmed gastric cytomegalovirus infection. Those that developed a gastric cytomegalovirus infection also had more gastric symptoms, and more gastric histologic abnormalities. Moreover, those with a gastric cytomegalovirus infection demonstrated enhanced gastric retention of a liquid meal (P less than 0.01).

Currently, alpha interferon is the only recognized therapy for chronic viral hepatitis. As a result of its success in several multicenter trials, the agent was approved recently by the FDA for use in the clinical management of patients with chronic hepatitis C. FDA approval for its use in chronic hepatitis B is anticipated. Based upon this experience in nonimmunosuppressed individuals, the efficacy of alpha interferon therapy in patients who are recipients of liver allografts and are receiving chronic immunosuppression was assessed in a preliminary trial of the agent in 30 patients (13 with HBV, 11 with HCV, and 6 with hepatitis non A, non B, non C). Therapy was initiated at a dose of 3 X 10(6) units three times per week and continued for 6 months. Dose reduction in the amount of the alpha interferon administered was determined by a preestablished protocol. Nine percent of those with HCV and 18% of those with hepatitis non A, non B, non C experienced a full response to alpha interferon therapy. No full responses to alpha interferon therapy. No full responses were seen in those with HBV disease. Partial responses were common in all three groups but were most frequent in those with hepatitis non A, non B, non C and least frequent in those with HCV-related disease. This preliminary experience demonstrates the following: 1. Viral hepatitis following OLTx can be treated with alpha-2b-interferon. 2. The complications of alpha-2b-interferon therapy utilized prior to OLTx can be avoided by giving the therapy following successful OLTx. 3. The high rate of partial responses noted suggests that future studies should utilize either higher doses or longer durations of therapy or both. 4. The response rate was greatest for those having non A, non B, non C hepatitis and least for those with HCV hepatitis. 5. In this small preliminary series, no episodes of liver graft rejection could be ascribed to the use of alpha-2b-interferon in the patients so treated.

The prevalence of upper gastrointestinal CMV infection was determined in 90 adult transplant patients: 54 were evaluated prior to orthotopic liver transplantation (OLTx), while 36 were evaluated one to six weeks after OLTx. Upper gastrointestinal endoscopy, with biopsies of the stomach and duodenum for viral culture and histopathologic examination, was performed on each subject. Those without esophageal varices had their esophagus biopsied also for viral cultures and histopathologic examination. In addition, a gastric brushing for cytologic examination was obtained on all patients. All 90 patients studied were known to be CMV-sero-positive prior to transplantation. Therefore all infections were considered to be reactivation infections. Gastrointestinal CMV infection was more common in patients studied post-OLTx (33%) than it was in those studied pre-OLTx (2%) (P less than 0.001). The presence of gastrointestinal CMV infection was associated with a decreased T lymphocyte helper/suppressor ratio in peripheral blood. CMV duodenal infections were associated with the presence of endoscopic and histologic inflammation. Of the various diagnostic methods utilized, viral cultures of intestinal tissue were found to be the most useful in establishing a diagnosis of infection.

Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.