Transplantation of a small liver into a large patient may cause problems with correct reperfusion of the graft because of torsion of the hepatic pedicle, leading to malfunction of the transplanted organ. We describe the case of a 60-year-old man with alcoholic cirrhosis and hepatitis B virus who received a small-sized liver graft. Owing to the lack of adequate reperfusion of the transplanted organ arising from pedicular kinking caused by disparate sizes, a breast implant was placed behind the graft as a means of support, thereby resolving the problem. The use of prosthetic materials for the correct placement of grafts with size incongruity is also discussed, and the literature is reviewed.

We report a successful living related liver transplantation from a donor with von Willebrand's disease. With proper preparation, a substantial liver resection can be performed safely in such patients, and the transplanted liver will function normally.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with an unpredictable course and prognosis. The aim of this study is to describe our experience with liver resection, as well as transplantation, in the treatment of this tumor. We retrospectively analyzed the clinical features, pathological findings, and postoperative results in a series of 11 patients presenting between 1990 and 1998. Five patients (45%) presented with abdominal pain, 3 patients (27%) with jaundice and ascites, and the rest were asymptomatic. Computed tomography or magnetic resonance imaging showed localized lesions in 2 patients (18%) and multifocal disease in the others. Seven patients (64%) had extrahepatic lesions, detected either by preoperative imaging or discovered at exploration. Two resections of apparently localized lesions were followed by rapid and aggressive recurrence. Five patients were treated with transplantation, including 1 patient who had previously undergone resection. Of these 5 patients, 2 patients are currently free of detectable disease, 1 patient who had severe ascites and jaundice is now asymptomatic with stable extrahepatic lesions, and 2 patients (including 1 who had previously undergone a resection) died of tumor recurrence. One patient with advanced tumor died while waiting for transplantation. The remaining 4 patients are free of symptoms and have stable hepatic and extrahepatic disease. HEHE is nearly always multifocal, and our results with resection were dismal. Because of the unpredictable nature of the tumor, the indications for transplantation in patients without liver-related symptoms should be carefully evaluated. Nevertheless, extrahepatic disease should not be an absolute contraindication for liver transplantation in patients with severe liver dysfunction.

Current protocols for prophylaxis against allograft reinfection after liver transplantation for chronic hepatitis B virus (HBV) infection include the administration of large doses of hepatitis B immune globulin (HBIG), with considerable associated economic costs. Monotherapeutic prophylaxis with lamivudine has been complicated by the development of resistant strains of HBV. We studied the effectiveness of a posttransplantation prophylaxis protocol using combination lamivudine and low-dose HBIG in 7 consecutive patients with chronic HBV infection, 4 of whom were serum HBV DNA positive before pretransplantation lamivudine therapy. All patients were serum HBV DNA negative at transplantation and received lamivudine, 100 mg/d, posttransplantation. HBIG, 2170 IU, was administered intramuscularly intraoperatively and daily for 14 days. Maintenance HBIG therapy consisted of 2170 IU intramuscularly twice weekly, tapered to every 2 to 4 weeks by 12 months posttransplantation. Target serum HBIG (HBV surface antibody) titers were less than 500 IU/L for 6 months, then greater than 300 IU/L until 12 months posttransplantation. Induction serum HBIG titers were determined daily in 5 patients, and both serum HBIG and hepatitis B surface antigen were determined every 4 weeks in all patients. One patient died 61 days posttransplantation; the surviving patients (n = 6) were followed up for a mean of 532 days (range, 395 to 648 days). No patient has developed allograft reinfection. In the induction period, a target HBIG titer of greater than 500 IU/L was not achieved until a mean of 6.8 days (range, 5 to 10 days). In the maintenance period, all patients achieved the target HBIG titer. This suggests combination lamivudine and low-dose HBIG is effective in preventing allograft reinfection by HBV.

Recurrent hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV reactivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant-associated HBV infection undergoing liver transplantation (n = 29). Outcomes were compared in three patient groups: group 1, precore mutant HBV infection not receiving lamivudine (n = 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n = 10); and group 3, HBV precore mutant patients undergoing liver transplantation and receiving lamivudine and low-dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9). In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow-up on lamivudine therapy was for a median of 11 months. Six of these 10 patients developed mutations in the HBV polymerase gene associated with lamivudine resistance. There were two liver failure-related deaths in this group. In group 3 patients, there was one death from graft-versus-host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low-dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.

We describe our use of a liver allograft from a donor who died of intracranial hemorrhage after brodifacoum ingestion. Because brodifacoum can remain in the human body for months, the recipient's posttransplantation coagulation profiles and serum brodifacoum levels were monitored closely. Her posttransplantation course was excellent, with no coagulation problem. At 15 months posttransplantation, she is well, with normal liver function and coagulation profile. We conclude that brodifacoum toxicity is not a strict contraindication to liver donation.

Tacrolimus is an effective immunosuppressant in the rescue of liver allograft patients in whom conventional immunosuppression failed. Efficacy and safety were examined in a multicenter trial of liver transplant recipients converted to tacrolimus because of rejection despite cyclosporine (CyA) therapy or intolerance to CyA. Six hundred seventy-seven patients were enrolled onto the study; 475 patients for rejection, 197 patients for intolerance, and 5 patients treated compassionately. The mean daily dose of tacrolimus was less in the intolerance (Int) patients throughout the study: 0.22 versus 0.17 mg/kg at 1 week and 0.14 versus 0.11 mg/kg at 24 months in rejection (Rej) and Int patients, respectively. Mean blood levels paralleled dosing in both groups, but were greater in the Rej patients (10.7 v 8.3 ng/mL at 18 months). Kaplan-Meier estimates of patient and graft survival were similar in the two groups. Patient survival rates were 80.1% and 81.5%, and graft survival rates were 72.7% and 73.9% at 24 months in the Rej and Int patients, respectively. Most adverse events occurred with a similar incidence in the two groups. Those with a 4% or greater incidence were fever, viral hepatitis, and pneumonia. The incidence of sepsis, gastrointestinal hemorrhage, kidney failure, and convulsion was greater in the Int group. The incidence of abnormal liver function test results, hyperglycemia, headache, and abnormal kidney function was greater in the Rej group. Mean liver function test results decreased with time postrescue in both groups. Mean serum creatinine level increased from baseline to 18 months postrescue in both groups (1.44 to 1.51 mg/dL for Int patients, 1.14 to 1.48 mg/dL for Rej patients). We conclude tacrolimus is safe and effective rescue in liver transplant recipients with rejection or CyA intolerance.

Patients with end-stage liver disease (ESLD) may be at increased risk for syncopal episodes based on their circulatory physiological state. Although a definitive cause for this is not known, several mechanisms have been proposed. In patients with ESLD, defecation syncope may result from a failure of short-term neurocirculatory adaptation to the Valsalva maneuver in the face of a hyperdynamic circulatory state and a decreased effective intravascular volume. We describe 2 patients with ESLD who had repeated episodes of defecation syncope before orthotopic liver transplantation (OLT). The most effective treatment of these syncopal episodes appears to be fluid administration and the use of a pressor agent, such as dopamine, to help maintain both an effective heart rate and intravascular volume. Correction of this altered circulatory physiological state through OLT prevented further syncopal episodes in both patients. A search of the literature failed to show previous reports associating ESLD and defecation syncope. Possible mechanisms favoring this association are reviewed.

Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.

Adrenomedullin (AM) is a potent vasodilating peptide that increases rat platelet cyclic adenosine monophosphate levels and acts on endothelial cells to stimulate nitric oxide release. Both mechanisms inhibit platelet function. Considering these effects, AM may have a role in cardiovascular regulation after orthotopic liver transplantation (OLT) and could have an antithrombotic effect. The aim of the present study is to investigate plasma AM levels in the early postoperative period after OLT and their relationship with vascular complications in OLT. We measured plasma AM levels in 35 patients with cirrhosis who underwent OLT at baseline and 1, 7, and 15 days postoperatively. We found that AM levels were significantly greater in patients with cirrhosis compared with healthy subjects. Of the 35 patients, 10 had vascular complications. In these 10 patients, AM concentrations were significantly greater than those observed in the nonthrombotic group in the early postoperative period. In addition, we also noticed in the nonthrombotic group a significant increase in AM levels from baseline to day 1, then a decrease to baseline levels in the early postoperative period. Our study shows that AM might act as a new humoral factor involved in the response to surgery in OLT and is significantly associated with vascular thrombosis in OLT.

Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

The occurrence of acute cellular rejection after orthotopic liver transplantation is common. At present, no allowance is made in immunosuppressive regimens for parameters other than weight. We investigated parameters in 121 consecutive patients receiving their primary allograft to determine if there are pretransplantation factors predicting the occurrence of acute cellular rejection after transplantation. The case notes and dietetic notes of these patients were reviewed for age at transplantation, cause of liver disease, preoperative albumin and creatinine levels, lymphocyte count, anthropometric measurements, donor age, HLA DR mismatch, and cold ischemia time. Acute cellular rejection was more likely to occur in younger patients, patients with Child's class A disease, and those with normal midarm muscle circumference. Acute rejection was increased in transplant recipients from donors aged younger than 30 and older than 50 years. Acute cellular rejection was less likely to occur in patients who underwent transplantation for alcoholic liver disease. Chronic rejection was significantly increased in women and those patients who experienced recurrent acute rejection. On multivariate analysis, the only significant predictor was the decreased likelihood of acute rejection in patients with depleted midarm muscle circumference. In conclusion, it may be possible to individualize immunosuppressive regimens on the basis of pretransplantation characteristics.

Wilson's disease is a hereditary defect in copper excretion leading to the accumulation of copper in the tissues, with subsequent tissue damage. The most serious sequela is that of progressive central nervous system involvement. The use of orthotopic liver transplantation (OLT) has been controversial for those patients with neurological symptoms attributed to Wilson's disease. The aim of this study is to determine the effectiveness of OLT for patients with Wilson's disease, including those with neurological involvement attributed to copper accumulation in the central nervous system. OLT was performed in 45 patients (19 men [42.2%], 26 women [57.8%]) with Wilson's disease between 1971 and 1993 who were followed up for at least 4 years. The age at diagnosis of Wilson's disease ranged from 3 to 41 years (mean, 17.7 +/- 7.4 years). The age at OLT ranged from 8 to 52 years (mean, 22.3 +/- 9.4 years). Nineteen patients (42.2%) were aged younger than 18 years at OLT. The indications for OLT included chronic hepatic failure in 15 patients (33.3%) and fulminant (FHF) or subfulminant hepatic failure in 30 patients (66. 6%). All but 1 of the 19 pediatric patients (94.7%) were in the latter group. Twenty-five patients (55.5%) were receiving D-penicillamine, 9 patients for more than 1 year; none of the patients treated long term presented as FHF. Thirty-three patients (73.3%) survived more than 5 years after OLT. Fourteen patients (31%) died during the posttransplantation period; 7 of the 14 patients (50%) were aged younger than 18 years. Twelve patients died during the first 3 months after OLT of complications of disease and surgery, 10 of whom underwent transplantation for FHF. The other 2 patients died 6 and 9 years after transplantation of infectious problems. Eleven patients (24.4%) required retransplantation because of a primary nonfunctioning graft (n = 6), chronic rejection (n = 4), and hepatic artery thrombosis (n = 1). Seventeen patients (37.7%) presented with neurological abnormalities; 14 patients with Wilsonian neurological manifestations and 3 patients with components of increased intracranial pressure. Ten of the 13 surviving patients with hepatic insufficiency and neurological abnormalities at OLT showed significant neurological improvement. Our experience shows OLT is a life-saving procedure in patients with end-stage Wilson's disease and is associated with excellent long-term survival. The neurological manifestation of the disease can improve significantly after OLT. Earlier transplantation in patients with an unsatisfactory response to medical treatment may prevent irreversible neurological deterioration and less satisfactory improvement after OLT.