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We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non-A, non-B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure. None of these patients had evidence of a preexisting hematological disorder or infection with hepatitis C virus (as determined with a second-generation ELISA). Aplastic anemia was diagnosed at a median of 4 wk after the onset of hepatitis, with five cases seen before transplantation. Six patients received antithymocyte globulin to promote remission of aplastic anemia. Three children died (fungal infection in two, intracranial hemorrhage in one)--one at 43, one at 108 and one at 119 days after transplantation--without remission of aplastic anemia. Among the four surviving patients, with median follow-up of 25 mo, complete and partial remission of aplastic anemia have occurred in three and one, respectively. Liver allograft function is stable in all surviving patients. The data demonstrate that aplastic anemia is a common complication among children who undergo liver transplantation for fulminant non-A, non-B hepatitis. It is associated with a high rate of mortality, although most survivors appear to have full hematological recovery.

In this report we describe two cases of liver allograft primary non-function in which the donor organs were obtained from patients with a long-standing history of hypertension and placed in normotensive 2 recipients. Examination of these failed grafts showed marked luminal narrowing of the medium and large intrahepatic arteries along with extensive hepatocellular necrosis. No evidence of cellular allograft rejection was present. Preoperative frozen section evaluation of the donor liver failed to detect any pathological changes in the donor organs. Morphometric studies showed a statistically significant luminal narrowing of the medium arteries in these patients compared with controls with graft failure because of other causes (P < .0001). To our knowledge there are no previous reports describing this finding in the literature. We hypothesize that the arterial narrowing in these livers resulted in compromised blood flow to the organ after transplantation into a normotensive patient. Further studies are necessary to determine the frequency of these changes in the hypertensive population. Such studies may lead to the development of criteria that will identify potential donors who are likely to have such changes before organ procurement.

Liver biopsy is an important diagnostic tool in the management of patients following orthotopic liver transplant. We evaluated complications following percutaneous liver biopsy in a group of liver transplant patients who had Roux-en-Y choledochojejunostomies fashioned as part of their biliary reconstruction during liver transplantation. Complications were divided into two major groups: septic complications (including fever, symptomatic bacteremia, cholangitis, infected hematoma and hypotension related to sepsis) and bleeding (defined as hypotension requiring volume expansion greater than 500 cm3 or blood transfusion, hemothorax, intrahepatic or peritoneal hemorrhage and hemobilia occurring within 1 wk of liver biopsy). One hundred ninety-two biopsies were performed in 46 patients with choledochojejunostomies, and 118 biopsies were carried out in an age- and sex-matched control group of patients with choledochocholedochostomy biliary anastomosis. There were no septic complications in the choledochojejunostomy patients and one (0.32%) septic complication in the choledochocholedochostomy patients (NS). Eight bleeding complications occurred (2.6%) in eight patients (8.3%). Five (2.6%) occurred in five (10.8%) of the choledochojejunostomy patients, vs. three (2.5%) in three (6.5%) choledochocholedochostomy patients (NS). None of the bleeding complications required surgical intervention or was fatal. We conclude that liver biopsy in posttransplant patients with Roux-en-Y choledochojejunostomies is a safe procedure and that the incidences of complications were similar in our two groups. The negligible incidence of septic complications in the choledochojejunostomy patients does not appear to warrant the administration of prophylactic antibiotics, as has been previously suggested.

Graft-versus-host disease (GVHD) occurring after liver transplantation can pose a difficult diagnostic dilemma. Similar clinical and pathologic skin and gastrointestinal manifestations can result from other causes (i.e., drugs, infections). Treatment for each of these entities differs, and the high mortality associated with GVHD makes this distinction critical. GVHD has been assumed to result from the cotransplantation of donor lymphoid tissue along with the allograft. In most instances, the patient also receives blood products during the operation, and occasionally during the postoperative period, and the lymphoid cells in these products are also a potential source of concern. In this report, we describe a patient who developed GVHD after liver transplantation. Using molecular diagnostic techniques, we determined that the source for this GVHD was not the organ donor, but was most likely nonirradiated blood products received during the hospital course. Our results suggest that transplant recipients with concomitant hematopoietic dysfunction would benefit from irradiated blood products to reduce the likelihood of this complication.

Objectives: The purpose of this study was to review our experience with Epstein-Barr virus (EBV) hepatitis after liver transplantation., Methods: During a 68-month period, we performed 668 liver transplants and 585 patients. We identified 11 patients (2 percent), including 5 adults and 6 children with EBV hepatitis after liver transplantation. The diagnosis of EBV hepatitis was established by evaluating allograft biopsies. The histology was confirmed by the use of polymerase chain reaction technology., Results: The average time of diagnosis after liver transplantation was 45 days. Eight of eleven cases occurred within the first six months after transplantation. After the diagnosis of EBV hepatitis, treatment consisted of a decrease in immunosuppression plus antiviral therapy and intravenous immunoglobulin. The one-year actuarial survival for patients with EBV hepatitis, was 73 percent (8 of 11). Two patients died of progressive multi-organ EBV involvement. To determine the risk of developing EBV hepatitis, we reviewed our experience with the administration of antilymphocyte preparations in 585 patients. The patients found to have a significantly greater risk of developing EBV hepatitis included those receiving more than one course of antilymphocyte therapy or greater than a total dose of 70 milligrams of OKT3 in a single course., Conclusions: EBV hepatitis after liver transplantation is an infrequent event, which may be treated successfully. The occurrence of EBV hepatitis appears closely linked to the use of antilymphocyte preparations.

Bile acid metabolism and biliary secretion were characterized in the first 2 wk after orthotopic liver transplantation in 15 patients receiving cyclosporine and in five patients receiving FK 506. Analyses were performed on hepatic bile obtained by T-tube drainage; values obtained were compared with literature values for bile samples obtained in patients who had undergone cholecystectomy. Biliary bile acid output, which is equivalent to bile acid biosynthesis from cholesterol, was low (mean +/- S.E.M.) and increased with time: day 1, 0.50 +/- 0.1 mmol/day; day 3, 0.8 +/- 0.1 mmol/day; and day 6, 1.6 +/- 0.5 mmol/day. Chenodeoxycholic acid biosynthesis, as percent of total bile acid biosynthesis, was abnormally low in patients receiving cyclosporine (16.2 +/- 1.1) but not in patients receiving FK 506 (38.2 +/- 4.8) (p < 0.005). Before the T-tube was clamped, the proportion of deoxycholic acid (a secondary bile acid formed by bacterial 7-dehydroxylation of cholic acid) was low in both groups: cyclosporine, 0.4 +/- 0.1; FK 506, 4.8 +/- 2.5 (p < 0.01). The mean concentration of bile acids in hepatic bile between days 4 and 11 did not differ significantly between groups: cyclosporine, 7.7 +/- 1.3 mmol/L; FK 506 4.3 +/- 0.7 mmol/L (mean +/- S.E.M.). (These values are similar to those reported for patients who have undergone cholecystectomy.) Bile acid-dependent bile flow, expressed as apparent choleretic activity (microliters of bile per micromole of bile acid output), was markedly elevated: in patients receiving cyclosporine the value was 129, and in patients receiving FK 506 the value was 220. (In patients who have undergone cholecystectomy, this value is less than 30).(ABSTRACT TRUNCATED AT 250 WORDS)

Six transplantations of the liver were performed over a period of six years in five adult patients with Type I diabetes mellitus (DM). The diabetic group included two males and three females with a mean age of 36 years and a mean duration of DM of 20 years. Primary diseases of the liver included two instances of primary biliary cirrhosis, two instances of sclerosing cholangitis and one instance of autoimmune chronic hepatitis. Three patients also received a simultaneous whole organ pancreatic transplant. All patients were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. Patient and hepatic allograft survival rates were 80 and 67 percent, respectively, after a mean follow-up period of 4.7 years. One of the three pancreatic grafts was successful and resulted in euglycemia for two years. Three patients have subsequently undergone successful renal transplantation at one, two and one-half, and six and one-half years after hepatic transplantation. Although transplantation of the liver can be performed safely in carefully selected patients with Type I DM, these patients are still at risk for the development of progressive nephropathy. Renal transplantation is an acceptable therapeutic alternative when this occurs.

In summary, as our protocols of immunosuppression improve in selectivity and, more importantly, as we become more adept at tailoring the degree of immunosuppression to the needs of individual patients, both our enthusiasm and our success with organ transplantation in the elderly will improve. This has particular relevance as the average age of our population increases. Arbitrary age limits, largely the products of the 1970s and early 1980s, have now been abandoned. Nevertheless, the enthusiasm to demonstrate skill in treating the older patient must be tempered by an understanding of the extreme shortage of available donor organs. In terms of life-years saved, the older patient offers much less potential than younger patients. At some point, the co-existence of other life-threatening illnesses in older patients must influence our desire to save older lives. One cannot overlook the probability that Medicare coverage of kidney transplantation since 1972 and heart and liver transplantation since the end of the last decade has served as a tremendous stimulus to the enthusiasm for treating older patients. In anticipation of further limits being placed on the availability of dollars for health care, the need for responsible stewardship of our precious donor and health care dollar resources becomes ever more important.

Acute hepatic failure developed after 8-methoxypsoralen and ultraviolet irradiation for psoriasis in a patient with prior methotrexate-induced cirrhosis. Review of the literature and the temporal relationship between 8-methoxypsoralen and hepatic injury in our patient suggests it may be a direct hepatotoxin. In our report, submassive necrosis superimposed on cirrhosis appears to have produced hepatic failure.

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.

Despite improving results, the management of exocrine complications after pancreas transplantation remains problematic. During a 30-month period, we performed 65 pancreas transplants with bladder drainage. A total of 23 patients (35%) were managed with a long-acting somatostatin analogue (Sandostatin) for persistent hyperamylasemia or allograft pancreatitis. Sandostatin was begun at a mean of 29 days after transplant with a mean duration of therapy of 13 days. Sandostatin therapy was associated with significant reductions in the serum, urine, and peritoneal fluid amylase levels (p < 0.05). Sandostatin also caused a decrease in cyclosporine levels during oral cyclosporine use. In patients receiving Sandostatin, pancreas allograft survival was 83%. We conclude that pancreatitis remains a major cause of morbidity after pancreas transplantation. The selective use of Sandostatin can result in excellent graft salvage with low morbidity. Sandostatin appears to be safe and effective in reducing the exocrine output of the denervated pancreas allograft but also reduces cyclosporine levels.

Fulminant hepatic failure as a result of hepatitis A is a rarely diagnosed complication entity in developed countries. With the advent of specific serologic markers for acute hepatitis A virus infection, the incidence and pathology of fulminant hepatitis A can be more clearly defined. We describe four patients (one adult, three children; two males and two females, ages 2 1/2-58 years) referred to our institution for orthotopic liver transplantation subsequent to fulminant hepatic failure following hepatitis A infection. All of these patients had a history of residence in or travel to hepatitis A endemic areas. Hepatitis A infection was documented by the presence of serum IgM against hepatitis A virus prior to transplantation. Infection with hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus was excluded by clinical and specific serologic examinations. All patients presented with varying degrees of encephalopathy, progressing to coma. Coagulopathy in the form of prolonged prothrombin time and partial thromboplastin time was present in all patients. Peak liver parenchymal enzymes increased to greater than ten times the upper limit of the normal range. Total and direct bilirubin levels increased to > 20 and 10 mg/dl, respectively. Histologic evaluation of the explanted livers showed a spectrum of changes ranging from periportal hepatocellular necrosis with focal parenchymal collapse and prominent bile duct proliferation to massive necrosis with complete loss of hepatic architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Currently, diabetes mellitus is the most common cause of renal failure in adults. However, combined pancreatic and renal transplantation (PRT) remains controversial when compared with renal transplantation alone (RTA) in diabetic recipients. We analyzed the results and morbidity in four age-matched groups--31 patients with Type I diabetes undergoing PRT before dialysis, 30 patients with diabetes who are dependent of dialysis undergoing PRT, 31 concurrent and historic patients with Type I diabetes undergoing RTA and 31 concurrent patients without diabetes undergoing RTA. All patients received cadaver donor organs and were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. The four groups were comparable with respect to age, weight, gender, duration and severity of diabetes, dialysis type, number of retransplants, degree of sensitization, preservation time and matching. The groups differed with regard to duration of dialysis and period of follow-up evaluation, pretransplant blood transfusions, racial distribution and OKT3 induction therapy. PRT was associated with a greater morbidity rate as evidenced by a slightly higher incidence of rejection, infections and reoperations. The number of readmissions and hospitalization period during the first 12 months was also greater after PRT versus RTA. However, none of these differences were significant. No detrimental effect was noted on renal allograft function at one year; patient and graft survival was actually higher in the PRT groups. Quality of life was improved in nearly 90 percent of PRT recipients. Although the improved results after PRT may be attributed to selection bias, only lesser differences were noted among the four study groups. The aforementioned data suggest that appropriate patient selection can overcome the morbidity associated with PRT, resulting in excellent patient and graft survival with the potential for complete rehabilitation.

The University of Pittsburgh policy for procuring organs from non-heart-beating cadaver donors recognizes the potential for conflicts of interest between caring for a "hopelessly ill" patient who has forgone life-sustaining treatment and caring for a potential organ donor. The policy calls for a separation between those medical personnel who care for the gravely ill patient and those involved with the care of transplant recipients. While such a separation is possible in theory, it is difficult or impossible to attain in practice. However, such a separation of duties would be unnecessary if an arbitrator were appointed to monitor the proceedings as they take place on a case-by-case basis. In this way, the biases--real or potential--of the individuals involved could be identified, and the harmful effects of the unavoidable conflicts of interest could be minimized.

This report describes the clinical characteristics and demographics of patients enrolled into this rescue trial for patients experiencing refractory rejection after liver transplantation. Actuarial graft and patient survival at 12 months postconversion was 50% and 72%, respectively. Actual treatment success at 3 months postconversion was 70%. Karnofsky scores and liver function tests were significantly improved for patients continuing on therapy indicating clinical benefit in these patients. The safety profile of FK 506 is acceptable for such a high-risk group of patients. These preliminary clinical results support the conclusion that FK 506 can effectively control and reverse refractory rejection in a majority of liver transplantation patients.

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.

From more than 900 articles in the medical literature, published between August 1, 1991 and July 31, 1992, 46 were selected for review. During the year of review, major international symposiums were held on a new drug, FK506, and intestinal transplantation. In addition, at least one new attempt at a unifying hypothesis regarding graft adaptation was proposed. Other studies included living related donor transplantation, results with transplantation for alcoholics, and the controversy regarding the role of liver transplantation for the treatment of Budd-Chiari syndrome. Concerns regarding the recurrence of both hepatitis and primary hepatic malignancy following liver transplantation were also addressed. Two innovative approaches to the treatment of acute liver failure offer exciting promise for the future. Other subjects include histologic evaluation of renal dysfunction in patients with liver disease, quality of life after transplantation, and the proper distribution of precious donor livers.

Extracorporeal liver perfusion (ECLP) has been used for detoxifying blood in patients in class IV hepatic encephalopathy. Palliation of the moribund patient utilizing extracorporeal devices with cross-circulation of a cadaver liver has been documented for over three decades. Common problems associated with this procedure which appear in the literature include cadaver liver distention, increased resistance to blood flow, and limited time of extracorporeal support due to cadaver liver failure. This report summarizes the experiences of the perfusion team in utilizing an extracorporeal circuit with an otherwise nontransplantable cadaveric liver, to support the decompensating hepatic patient as a bridge to transplantation. Between January and July 1992, three patients were supported for hepatic failure with ECLP. Two patients were placed on ECLP with a modified circuit containing two positive displacement pumps and one centrifugal pump. The third patient was placed on ECLP with a circuit that contained two centrifugal pumps and one positive displacement pump. Patient age ranged from 6 to 38 years and length of support ranged from 24 to 72 hours. In all three patients, a centrifugal pump was placed in the suprahepatic inferior vena cava line to facilitate cadaver liver drainage and decompression. Intensive monitoring of both patient and cadaver liver hemodynamics, hepatic function, and hematological status was performed. All three patients were successfully weaned from ECLP. Two patients received successful orthotopic liver transplantation. The third died of complications unrelated to ECLP after support was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors describe a case of orthotopic liver transplantation (OLT) in a patient with an infantile form of choledochal cyst that progressed to severe hepatic failure. Choledochal cyst must be included in the differential diagnosis of extrahepatic biliary obstruction in infants; it represents an additional reason to consider early exploratory laparotomy, both for diagnosis and to perform definitive excision. In the event that end-stage liver disease develops, OLT should be considered.

The lack of an artificial liver makes liver retransplantation a unique, life-saving procedure when all the other alternatives to save a failed graft have been exhausted. On the other hand, the shortage of donors in line with the increasing number of end-stage liver disease patients who are waiting in long recipient lists represents a dilemma and raises the question of most appropriate recipient selection. In this report, we retrospectively analyzed the results of 350 primary, 48 secondary, and 5 tertiary hepatic transplants performed between July 1985 and January 1990 at University of Nebraska Medical Center. The same immunosuppression protocol was used in each case and the maintenance immunosuppressive therapy consisted of a cyclosporine (CyA) and steroids. The overall survival rate of 80.5% at 1 year which was achieved in the primary grafting group was significantly better than the secondary grafting group (63.0%, p less than 0.05). However, this difference was not significant in pediatric patients and their rates were 73.8% and 71.6% in primary and secondary grafting groups, respectively. When the retransplanted patients were considered as deaths unless secondary grafting was performed, the overall patient survival rate of 69.7% in primary grafting group at 1 yr increased to 77.8% in the retransplanted group and this difference was significant (p less than 0.05). Blood loss and operating time were found to be lower in the retransplanted group. Furthermore, the decrease of the operating time in the retransplanted pediatric patients reached statistical significance (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective randomized study was conducted to assess the effectiveness of clotrimazole troches and nystatin suspension to prevent oral candidiasis in immunosuppressed orthotopic liver transplant patients. Thirty-four patients received either clotrimazole troches, 10 mg, five times daily, or nystatin suspension, 500,000 units, four times daily. Prophylaxis was initiated after extubation after transplantation and continued throughout the hospitalization. One of 17 patients in each treatment group developed clinical and microscopic evidence of an oropharyngeal Candida infection. This gave an intragroup and an overall infection rate of 5.9%. It appears that either nystatin or clotrimazole may be used for candidiasis prophylaxis in orthotopic liver transplant patients.

An unusual type of diffuse biliary tract injury after liver transplantation that is characterized by multiple intrahepatic biliary strictures, ductal dilatations, fluid collections, or intrahepatic abscesses has been identified. Over a 5-year period, a total of 10 patients (2%) developed diffuse intrahepatic biliary injury with established vascular patency and no obvious source for their biliary tract pathology. All patients received livers preserved in University of Wisconsin solution with a mean preservation time of 16 hours. This biliary tract injury was associated with the presence of severe preservation injury and Roux limb biliary reconstruction. Of the 10 patients, 5 were treated nonoperatively with multiple stricture dilations and stent placements, 3 underwent retransplantation, 1 was treated operatively with hepaticojejunostomy, and 1 died of sepsis. This study suggests that this complication appears to be related to preservation injury and that the etiology may be ischemic in origin.

Cyclosporine is used in the postoperative management of rejection in liver allograft recipients. Despite its efficacy in the treatment of allograft rejection, the drug exhibits toxicity at elevated whole blood concentrations including nephrotoxicity with associated histologic changes, and evidence of hepatotoxicity as determined by liver function studies. To date, there have been few published reports describing histologic changes in liver biopsies from patients with elevated blood cyclosporine levels. In the present study, we retrospectively examined biopsies from 16 liver allograft recipients, seven patients with elevated whole blood cyclosporine levels (> 1000 ng/ml) and nine control patients who had whole blood cyclosporine levels in the therapeutic range (558 to 993 ng/ml). In each case, frozen liver biopsy tissue was available to measure tissue levels of cyclosporine and metabolites. The blood and tissue drug levels were then correlated with the histologic changes present in the biopsy specimens. Patients with increased cyclosporine levels displayed histologic changes consisting of hypertrophy of the bile ductal epithelium with cytoplasmic vacuoles and the presence of "foamy" material within the hepatic sinusoids that were either absent or occurred less frequently in the control group. The histologic changes correlated best with cyclosporine metabolite levels rather than tissue levels of native drug. When liver function studies were correlated with cyclosporine levels, only gamma glutamyl transpeptidase (GGT) demonstrated a significant positive correlation with the histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

The benefits of pancreas transplantation (PT) must be weighed against the morbidity associated with the operative procedure and long-term immunosuppression. Over a 32-month period, we performed 73 PTs including 61 combined pancreas-kidney transplants (PKT) and 12 solitary PTs. In the PKT group, 25 reoperations were performed in 18 patients (29.5%) at a mean of 39 +/- 12 days after transplant. In the solitary PT group, 16 reoperations were performed in 8 recipients (66.7%, p = 0.03) at a mean of 87 +/- 12 days after PT (p < 0.01). In the PKT group, pancreas allograft survival was 93.4%. Vascular thrombosis resulted in the loss of two pancreas allografts. In the solitary PT group, pancreas allograft survival was 50% (p < 0.001), with 6 transplant pancreatectomies performed for either infectious (5) or vascular (1) complications. Surgical complications after PT are common (35.6% in this series), occur earlier in patients who undergo PKT, and are more frequent and morbid in patients undergoing solitary PT, especially after a previous kidney transplant. An aggressive surgical approach can lead to a high rate of pancreas allograft salvage without jeopardizing either the patient or the renal allograft.

Background: Extensive destruction of the extrahepatic biliary system after liver transplantation can be a catastrophic event. We present our experience with the use of intrahepatic cholangiojejunostomy (IHCJ) in this setting., Methods: From July 1985 through December 1991, 668 liver transplantations were performed in 583 patients. Seven patients required IHCJ. This technique involves creating an anastomosis between the jejunal mucosal and hepatic parenchyma/capsule with the use of a Roux-en-Y limb of bowel. There were four adults and three children. The clinical presentation included bile leak (n = 4), subhepatic abscess (n = 2), and intrahepatic abscess (n = 1). The probable cause of these events included hepatic arterial thrombosis (n = 4), occult bile leak (n = 2), and fungal cholangitis (n = 1)., Results: After IHCJ, six of the seven patients are currently alive, with a mean follow-up of 28 months. The current liver function test results include a mean bilirubin of 0.7 mg/dl (range, 0.4 to 1.9 mg/dl), serum glutamic pyruvic transaminase of 69 units/L (range, 32 to 118 units/L), and gamma-glutamyltranspeptidase of 118 IU/L (range, 111 to 265 IU/L)., Conclusions: These results suggest that IHCJ is a safe and effective alternative to retransplantation in liver recipients with extensive destruction of the extrahepatic biliary system.

We report the experience with Pneumocystis carinii lung infections in the 109 children undergoing liver transplantation at our hospital between August, 1985 and May, 1989. PCP developed in 9 of the 86 patients (10%) surviving > or = 6 weeks after transplantation and not receiving P carinii chemoprophylaxis. Of the 59 patients undergoing BAL 2 or more weeks after transplantation there were 16 specimens from 14 patients (24%) positive for P carinii. These patients had a spectrum of illness ranging from asymptomatic to severe pneumonia requiring mechanical ventilation. The mean interval from first transplantation to bronchoalveolar lavage positive for P carinii was 24.9 weeks and the mean interval to first PCP was 28.0 weeks. The earliest and latest occurrences of PCP were 7 weeks and 73 weeks, respectively, after transplantation. There were no complications attributed to BAL.

We initiated a policy of using RSLT in critically ill patients in June of 1988. Since that time we have performed 30 RSLTs in 29 patients, including 28 children and 1 adult. The mean age of the children was 27 months (range 1 month to 10 years) with 14 (52%) being 1 year of age or less. The mean weight was 11.3 kg (range 2-50 kg) with 20 being 10 kg or less. A total of 22 patients were in the intensive care unit at the time of RSLT including 9 who were intubated. Of the 30 RSLTs, 23 were performed as a primary transplant while 7 were retransplants. Indications for primary transplantation included biliary atresia (n = 11), fulminant hepatic failure (n = 5), neonatal hepatitis (n = 4) and others (n = 3). The RSLT was used in retransplantation for primary nonfunction (n = 2), hepatic artery thrombosis (n = 2), chronic rejection (n = 2), and herpetic hepatitis (n = 1). The size reductions included 18 left lobes, 7 left lateral segments, and 5 right lobes. This group includes the use of the split-liver technique, which was applied to 10 patients (5 livers). The median donor/recipient weight ratio for left lobe transplants was 2:1; left lateral segments was 7.3:1; and right lobes 1.6:1. One year actuarial patient and graft survivals were 68 and 65%, respectively, with a mean follow-up of 10.6 months. The number of children dying awaiting transplantation has been significantly reduced following the introduction of RSLD (3 of 115, 2.6% vs. 12 of 95, 13%; P less than 0.02).

Splanchnic venous inflow is considered mandatory to ensure graft survival after liver transplantation. Over a 68-month period, we performed 570 liver transplants in 495 patients. Portal vein thrombosis was present in 16 patients. At transplant, the extent of the occlusion included portal vein alone (n = 4), portal including confluence of the splenic and superior mesenteric veins (n = 8), portal, splenic, and distal superior mesenteric veins (n = 2), and the entire portal vein, splenic vein, and superior mesenteric vein (n = 2). The operative approach included thrombectomy alone (n = 5), anastomosis at the confluence of the splenic and superior mesenteric splenic veins (n = 8), and extra-anatomic venous reconstruction (n = 3). The mean operative blood loss was 22 +/- 22 units, and the mean operative time was 9.7 +/- 4.8 hours. The 1-year actuarial survival rate was 81%, with a mean follow-up of 12.5 months. In summary, with a selective approach and the use of innovative forms of splanchnic venous inflow, portal vein thrombosis is no longer a contraindication to liver transplantation.

The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n = 50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing non-cytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis.

Objective: To report a case of valproic acid (VPA)-induced hepatotoxicity and to discuss the incidence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this severe reaction., Data Sources: Case reports, review articles, and relevant laboratory studies identified by MEDLINE., Data Extraction: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors., Data Synthesis: The case of a 23-year-old woman with VPA-associated hepatic failure was successfully treated with orthotopic liver transplantation. Hepatic failure is a rare, often fatal, adverse effect of VPA. Most cases of VPA-associated hepatic failure have occurred within several months of initiation of therapy. Initial symptoms of presentation often include nausea and vomiting, lethargy, or loss of seizure control. Laboratory values to be monitored include serum concentrations of hepatic enzymes, and, in some patients, tests indicative of the liver's synthetic capabilities. The exact mechanism of VPA-associated hepatic failure has not been clearly established; however, it is postulated to involve the formation of toxic metabolites. Major risk factors include age less than two years and concomitant treatment with more than one anticonvulsant. Other significant risk factors include underlying metabolic or serious neurologic disorders., Conclusions: Caution should be taken when initiating VPA therapy and clinicians should be familiar with the risk factors and clinical presentation of this reaction.

In an analysis of surgical complications following 500 consecutive orthotopic liver transplants, we identified 12 patients who developed the syndrome of multiple bowel perforations that was not due to iatrogenic injury. All cases occurred in small children (mean weight: 9.0 kg), who represented 7% of the pediatric population. Each patient had a minimum of three perforations. The typical intraoperative findings were pin-point perforations in areas of normal-appearing bowel. With only one possible exception (a patient with cytomegalovirus enteritis), no specific etiology could be determined. Management was based on multiple exploratory laparotomies and individualized operative procedures. All patients are currently alive (mean follow-up: 34.9 months). The pathogenesis of the syndrome of multiple bowel perforations remains unclear but is possibly multifactorial or related to high doses of steroids. Aggressive surgical management with semiopen treatment of peritonitis and frequent explorations has afforded excellent results.