Clinicopathological review of 18 cases of liver allografts lost due to bile duct necrosis.

Clinical, radiographic, and pathological features of 18 patients with biliary necrosis in their explanted liver allografts were reviewed. Twelve patients were men and ages ranged from 27 to 72 years. Indications for initial liver transplant (LT) were viral hepatitis (n = 7), steatohepatitic cirrhosis (n = 3), cryptogenic cirrhosis (n = 3), secondary sclerosing cholangitis (n = 2), primary sclerosing cholangitis (n = 1), biliary atresia (n = 1), and nodular regenerative hyperplasia (n = 1). Donor age ranged from 16 to 75 years. Duct-to-duct biliary anastomoses were fashioned in 13 cases; warm and cold ischemia times were not significantly different from general LT population. Seventeen allograft biopsies after recirculation had no significant findings. Post-LT, clinical and radiographic evaluation indicated biliary strictures (n = 7), bile leak (n = 7), intrahepatic abscess (n = 1), and duodenal perforation (n = 1). Radiographic vascular studies suggested hepatic arterial thrombosis or stenosis in 11 cases. Biopsies prior to retransplantation were performed on 17 patients and showed acute rejection (n = 10), biliary outflow impairment (n = 4), normal histology (n = 2), and centrilobular necrosis (n = 1). Retransplantation was performed 14 to 334 days after initial LT. Pathological examination of explants revealed perihilar duct necrosis in all cases, with bacterial colonies (n = 10) and fungal organisms (n = 2). Arterial thrombi were seen in 10 cases, and two had prominent arteriosclerosis. Infarction and centrilobular necrosis were seen in 9 and 13 cases, respectively. Four explants showed features of biliary outflow impairment. Twelve patients were alive 6 to 18 months following retransplantation. We conclude that post-LT biliary necrosis is associated with ischemia, and such a complication is rarely evident in allograft biopsies. Biliary and vascular imaging studies are essential in evaluating patients for this complication.

Review of 31 cases of morphologic hepatitis in liver transplant patients not related to disease recurrence.

AIMS: We examined the clinical and pathologic features of morphologic hepatitis occurring after liver transplantation (LT) that is unrelated to disease recurrence. METHODS: Between February 1998 and December 2003, 704 primary LTs were performed at our center. Patients transplanted for diagnoses with low risk of disease recurrence were considered for our study (n = 282). Those with hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those with morphologic hepatitis comprised our case series and had medical records reviewed for clinical associations, duration, and outcome. RESULTS: Thirty-one cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13), steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2), and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8 months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and moderate in 12. Associated conditions were identified in 19 patients (57%) with 3 categories being identified: probable drug toxicity (n = 7), systemic infection (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the index biopsy, 10 cases had resolution and 15 cases had persistence of the infiltrate. One patient had evidence of de novo HBV infection. CONCLUSIONS: Morphologic hepatitis occurred in 11% of patients at low risk for disease recurrence. Associated conditions could be grouped into three categories: drug toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases did not appear to progress or improved over time, with no allograft loss occurring as a result of chronic hepatitis.

Liver transplantation for massive hepatic haemangiomatosis causing restrictive lung disease.

A 34-yr-old man with hepatic haemangiomatosis presented for orthotopic liver transplantation. His massively distended abdomen caused thoracic compression and severe restrictive lung disease. Respiratory failure was the principal indication for transplantation. Increased airway pressures, pulmonary hypertension, systemic hypotension caused by aorto-caval compression, and blood loss, complicated the intra-operative anaesthetic management. Weaning from mechanical ventilation was impaired by acute and chronic metabolic alkalosis, and diaphragmatic laxity.

Hepatic localization of endothelin-1 in patients with idiopathic portal hypertension and cirrhosis of the liver.

Endothelin-1 (ET-1) may mediate increased resistance to hepatic sinusoidal blood flow. We evaluated the hepatic distribution of ET-1 in patients with idiopathic portal hypertension (IPH), in which liver architecture may be normal, and in patients with cirrhosis, in which distortion of hepatic sinusoidal architecture is prominent. Immunohistochemistry and in situ hybridization were used to localize ET-1 in hepatic tissue of patients with IPH and cirrhosis. ET-1 was measured in plasma from a peripheral vein, the hepatic vein, and the portal vein of patients with cirrhosis of the liver and controls. On immunohistochemistry and in situ hybridization, ET-1 was localized to periportal hepatocytes and sinusoidal cells in patients with IPH and cirrhosis. Minimal positive staining for ET-1 was observed in control livers. Plasma ET-1 levels were significantly greater in patients with cirrhosis than in controls. In patients with cirrhosis, ET-1 was greater in the hepatic vein compared with the portal vein. However, the level of plasma ET-1 in patients with cirrhosis did not correlate with either the presence of ascites or portacaval pressure gradient. We conclude that in IPH, ET-1 is localized to sites in which it can modulate intrahepatic resistance. In late stages of cirrhosis, ET-1 may not modulate resistance. We speculate that vascular resistance in late stages of cirrhosis probably results from distortion of hepatic architecture.

Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma.

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma.

A case of bilateral optic neuropathy in a patient on tacrolimus (FK506) therapy after liver transplantation.

PURPOSE: To report a case of bilateral optic neuropathy in a patient receiving tacrolimus (FK 506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) for immunosuppression after orthotropic liver transplantation. METHOD: Case report. In a 58-year-old man receiving tacrolimus after orthotropic liver transplantation, serial neuro-ophthalmologic examinations and laboratory studies were performed. RESULTS: The patient had episodic deterioration of vision in both eyes, with clinical features resembling ischemic optic neuropathies. Deterioration of vision occurred despite discontinuation of the tacrolimus. CONCLUSION: Tacrolimus and other immunosuppressive agents may be associated with optic nerve toxicity.

Late recurrence and rapid evolution of severe hepatopulmonary syndrome after liver transplantation.

Recurrence of hepatopulmonary syndrome (HPS) after orthotopic liver transplantation (OLT) in an adult has never been reported. We describe a 23-year-old woman who initially underwent OLT because of debilitating and severe HPS associated with nonalcoholic steatohepatitis (NASH). Although the clinical resolution of HPS was well documented day 117 post-OLT, the reappearance of NASH was documented by liver biopsy. Severe hypoxemia because of recurrent HPS rapidly evolved beginning approximately day 700 post-OLT. Retransplantation was attempted, but the patient died post-OLT of sepsis and/or multiorgan failure.

No evidence of hepatitis G virus in fulminant hepatic failure in children.

BACKGROUND: The cause of fulminant hepatic failure in children remains unknown, but a viral origin has been suspected in most cases. The recently discovered blood-borne virus, hepatitis G, has been suggested as a possible causative agent. METHOD: Six consecutive children who underwent liver transplantation for fulminant hepatic failure were studied. The children were tested for hepatitis G virus antibodies and hepatitis G virus RNA by polymerase chain reaction after excluding other causes of fulminant hepatic failure. RESULTS: No evidence of hepatitis G virus infection was found in these patients. CONCLUSION: Hepatitis G virus is unlikely to be a common cause of fulminant hepatic failure in pediatric patients from the upper midwestern United States.

Recurrence of primary sclerosing cholangitis following liver transplantation.

Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.

Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer?

BACKGROUND/AIMS: The risk of cholangiocarcinoma in primary sclerosing cholangitis is widely recognized to be 8-30%, whereas the risk of acquiring hepatocellular carcinoma in primary sclerosing cholangitis is unknown. As in other chronic liver diseases, the presence of hepatocellular carcinoma in a patient with primary sclerosing cholangitis undergoing evaluation for orthotopic liver transplantation would clearly impact on the candidacy, diagnostic evaluation, and alternative treatment options. Thus, the aim of our study was to determine the prevalence of hepatocellular carcinoma in patients undergoing liver transplantation for primary sclerosing cholangitis. METHODS: The records of the 520 patients undergoing orthotopic liver transplantation at our institution between 1985 and May 1995 were reviewed. Of the 134 patients with primary sclerosing cholangitis, three (2%) had hepatocellular carcinoma. In the 386 patients without primary sclerosing cholangitis undergoing orthotopic liver transplantation, 22 (6%) had hepatocellular carcinoma. RESULTS: Neither the duration of primary sclerosing cholangitis (range 7-23 years) nor the presence of ulcerative colitis (two of three patients) distinguished those patients with primary sclerosing cholangitis plus hepatocellular carcinoma from those with primary sclerosing cholangitis alone. None of the three patients with primary sclerosing cholangitis plus hepatocellular carcinoma had evidence for hepatitis B or C, alpha-1-antitrypsin deficiency, or hemochromatosis. None of the tumors was of the fibrolamellar variety of hepatocellular carcinoma. CONCLUSIONS: The prevalence of hepatocellular carcinoma in patients with primary sclerosing cholangitis undergoing orthotopic liver transplantation is 2%. These data suggest that patients with advanced cirrhotic-stage primary sclerosing cholangitis are at increased risk for developing hepatocellular carcinoma and should be screened for hepatocellular carcinoma as well as for cholangiocarcinoma prior to orthotopic liver transplantation.

Neoral compared to Sandimmune is associated with a decrease in histologic severity of rejection in patients undergoing primary liver transplantation.

BACKGROUND: In a randomized, controlled study we investigated the clinical efficacy of the microemulsion formulation of cyclosporine (Neoral) in comparison with Sandimmune (SIM) in the treatment of patients who underwent primary orthotopic liver transplantation (OLT). METHODS: In total, 33 patients were randomized in a double-blind fashion before undergoing primary OLT to receive either Neoral or SIM. All 33 patients initially received intravenous cyclosporine, but as soon as it was tolerated, the oral study drug was initiated (median time, 3.6 days) and 17 patients received Neoral and 16 SIM (for both drugs, 10 mg/kg/day). Both groups were comparable with regard to age, sex, etiology of chronic liver disease, and hepatic biochemical profile. Episodes of rejection were diagnosed histologically and characterized as mild, moderate, or severe using criteria from the National Institute of Diabetes and Digestive and Kidney Diseases. RESULTS: Patients were followed for 1 year. Four patients in each group were discontinued prematurely. The reason for discontinuation of cyclosporine was drug-related complications in two of the NEO patients and in three of the SIM group; the other three were non-drug-related. Rejection episodes occurred in 9 of 17 patients (52.90%) in the Neoral group and in 9 of 16 patients (56.3%) in the SIM group. The total number of rejection episodes in each group was 14. However, in evaluating the severity of rejection histologically, nine episodes of rejection were characterized as moderate/ severe in the SIM group compared with only three in the Neoral group (P=0.027). Five of the nine moderate/severe rejection episodes in the SIM group occurred within the first 2 weeks after transplant. In contrast, moderate/severe rejection did not occur in the Neoral group in this early period. Two patients in the SIM group and no patients in the Neoral group required treatment with OKT3 for steroid-resistant rejection. There were no differences in mean doses or trough levels when comparing the two study groups. The incidence of adverse effects was similar in the two groups. CONCLUSIONS: Neoral is a safe and efficacious drug in the treatment of primary OLT patients. Given comparable doses of cyclosporine in each group over 1 year, there was no significant difference in the total number of rejection episodes between study groups. However, patients treated with Neoral had a lower incidence of moderate/severe histologic rejection and were free of steroid-resistant rejection when compared with SIM-treated patients.

Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database.

BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS: During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS: Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Liver transplantation for cryptogenic cirrhosis.

End-stage liver disease secondary to cryptogenic cirrhosis is the indication for orthotopic liver transplantation (OLT) in 7% to 14% of recipients. However, there are no reports documenting the outcome of OLT for this indication. The aim of this study was to determine (1) survival and (2) the incidence of histological recurrence of cryptogenic cirrhosis after OLT. Between March 1985 and December 1994, 560 OLTs were performed at our institution. Of these, 39 transplants for cryptogenic cirrhosis were in patients who met the following criteria: antinuclear antibody < 1:40; negative anti-smooth muscle antibody, antimitochondrial antibody, polymerase chain reaction for hepatitis C virus, and hepatitis B surface antigen results; normal ceruloplasmin and alpha-1 antitrypsin phenotype; transferrin saturation < 65%; and liver biopsy specimen not suggestive of hemochromatosis or other known disorders. Histological recurrence was assessed with protocol liver biopsies in all patients who survived longer than 6 months. The mean age of cryptogenic recipients at the time of transplantation was significantly lower (40.6 years; range, 3 to 63 years) than that of noncryptogenic recipients (48.5 years; range, 1-70; P < .03). Median modified Child's-Pugh score was slightly higher for cryptogenic recipients at the time of transplantation (10.0 + 0.08 standard error of mean [SEM]), than for the noncryptogenic recipients (9.0 + 0.03 SEM; P < .02). Actuarial survival was 72% (+ 0.07 SEM) at 1 and 58% (+ 0.08 SEM) at 5 years for cryptogenic recipients compared with 89% at 1 and 80% at 5 years for noncryptogenic recipients. The difference in survival was significant (P < .001) at both 1 and 5 years. Among the 27 cryptogenic recipients surviving more than 6 months (mean follow-up, 5.5 years), 6 have persistent hepatitis histologically without apparent infectious, vascular, biliary, or drug origins. Four patients (15%) had chronic active hepatitis, and 2 (7%) had steatohepatitis. No cases of recurrent cryptogenic cirrhosis were seen. OLT for cryptogenic cirrhosis is associated with a poor outcome compared with other indications, hepatitis of uncertain origin occurred in 22% of cryptogenic recipients surviving longer than 6 months, and no evidence of recurrence of cryptogenic cirrhosis was seen thus far in follow-up.

Combined orthotopic heart and liver transplantation for genetic hemochromatosis.

A 47-year-old man with cirrhotic liver disease complicated by encephalopathy and class IV congestive heart failure caused by genetic hemochromatosis underwent combined orthotopic heart and liver transplantation. The patient remains well, working full time, 4 years after operation. Combined heart and liver transplantation is an effective therapy for selected patients with concurrent heart and liver failure caused by systemic iron overload.

A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease.

We studied the outcome of 436 patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) who underwent orthotopic liver transplant (OLT) at three major liver transplant centers. Univariate predictors of outcome included age, Karnofsky score, Child's class, Mayo risk score, United Network for Organ Sharing (UNOS) status, nutritional status, serum albumin, serum bilirubin, international normalized ratio, and the presence of ascites, encephalopathy, renal failure (serum creatinine > 2 mg/dL), and edema refractory to diuretics. Using these predictors, we developed a four variable mathematical prognostic model to help the liver transplant physician predict the following: 1) the amount of intraoperative blood loss; 2) the number of days in the intensive care unit (ICU); and 3) severe complications after surgery. The model uses age, renal failure, Child's class, and United Network for Organ Sharing status. This study is the first to model the outcome of liver transplant in patients with a specific etiology of chronic liver disease (PBC or PSC). The model may be used to help select patients for OLT and to plan the timing of their transplantation.

In situ neural isolation of the entire canine upper gut: effects on fasting and fed motility patterns.

BACKGROUND: Multiorgan upper gut transplantation is becoming clinically feasible; however, the effects of multivisceral transplantations on gastrointestinal motility are unknown. Our aim was to determine the neural and hormonal mechanisms controlling motility patterns after complete extrinsic denervation of the upper gut as a model of multivisceral upper gut autotransplantation. METHODS: Seven dogs successfully underwent in situ neural isolation of the stomach, entire small intestine, proximal colon, liver, and pancreas by transecting all connections (distal esophagus, midcolon, all nerves, lymphatics) to this multivisceral complex except the celiac artery, superior mesenteric artery, and the suprahepatic and infrahepatic vena cava; these vessels were meticulously stripped of adventitia under optical magnification. Blood flow was not disrupted to prevent confounding effects of ischemia-reperfusion injury. After 1- to 2-week recovery, myoelectric and manometric recordings of stomach and myoelectric recordings of small bowel were obtained from conscious animals. RESULTS: During fasting the characteristic cycling migrating motor complex (MMC) was observed in the stomach and small intestine. The gastric component of the MMC was absent in one of the seven dogs. Regular cycling of the MMC during fasting, however, was intermittently disrupted and replaced by a noncyclic pattern of intermittent contractions in two of seven dogs 43% of the recording time. A small meal (50 gm liver) did not abolish the MMC as occurs in normal dogs; in contrast, a large meal (500 gm liver) did abolish the MMC. CONCLUSIONS: Extrinsic innervation to the upper gut modulates but is not requisite for interdigestive and postprandial motility of the stomach. Because relatively normal global motility patterns are preserved, multivisceral upper gut transplantation should be a viable option in selected patients.

Enhanced liver calpain protease activity is a risk factor for dysfunction of human liver allografts.

Our aim was to determine whether calpain protease activity is increased in liver tissue from allografts that have poor graft function postoperatively. Liver tissue was obtained from 36 patients at 1 hr after recirculation. The patients were divided into two groups: (1) 30 patients with good graft function; and (2) six patients with immediate poor graft function. Calpain protease activity was increased 1.6-fold in biopsy specimens from patients with immediate poor function as compared with those with excellent graft function. There was no difference between the two groups with regard to cold ischemic time for organ storage, donor age, recipient age, United Network for Organ Sharing status of the recipient, or fatty infiltration of the donor liver. In summary, enhanced calpain protease activity present in the liver 1 hr after reperfusion is a risk factor for graft dysfunction.

Hepatopulmonary syndrome with progressive hypoxemia as an indication for liver transplantation: case reports and literature review.

In the hepatopulmonary syndrome (HPS), a pulmonary vascular complication of liver disease, severe hypoxemia due to pulmonary vascular dilatation can be extremely debilitating. Determining whether patients with advanced liver disease and HPS should be considered for liver transplantation is difficult. We describe three patients with progressive and severe hypoxemia who underwent successful liver transplantation and had resolution of their arterial hypoxemia. In these patients, the progressive pulmonary deterioration accelerated the need and was considered an indication for liver transplantation rather than being considered an absolute or relative contraindication. In addition, we review the literature on 81 pediatric and adult patients with HPS who underwent liver transplantation and specifically highlight mortality, morbidity, syndrome resolution, and prognostic factors. Posttransplantation mortality (16%) was associated with the severity of hypoxemia (mean arterial oxygen tension [PaO2] in 68 survivors was 54.2 +/- 13.2 mm Hg and in 13 nonsurvivors was 44.7 +/- 7.7 mm Hg; P<0.03). Patients with a pretransplantation PaO2 of 50 mm Hg or lower had significantly more frequent mortality (30%) in comparison with those with a PaO2 greater than 50 mm Hg (4%; P<0.02). Pulmonary recommendations that address the severity of hypoxemia and candidacy for liver transplantation are discussed.

Causes and outcome of seizures in liver transplant recipients.

Previous studies found that seizures in orthotopic liver transplantation (OLT) herald a catastrophic neurologic event, but the studies were done of patients who later died and came to autopsy. We studied 630 OLT patients. Laboratory values, electroencephalography, neuroimaging, and levels of cyclosporine or FK506 were reviewed. Neurotoxicity from immunosuppression was considered a trigger for seizures when toxic blood level or increases > or = to 100% were documented, or when white matter lesions or confusional state or tremors were present. Generalized tonic-clonic seizures occurred in 28 of 630 patients (4%). In 7 patients seizures were part of an agonal event (central nervous system infection [n = 3], anoxic encephalopathy [n = 1], cerebral edema with fulminant hepatic failure [n = 1], intracranial hemorrhage [n = 1], and sepsis [n = 1]. In 17 patients cyclosporine (n = 11) or FK506 (n = 6) could be implicated. Remaining causes were acute uremia (n = 1), meningioma (n = 1), and unknown (n = 2). All patients were initially treated with anticonvulsants. Median follow-up of 2 years did not reveal seizure recurrence after discontinuation of anticonvulsants. We conclude that the majority of new-onset seizures after OLT are not indicative of a poor prognosis. Immunosuppression neurotoxicity is the most frequent cause. Anticonvulsant therapy is not necessary for favorable long-term outcome.