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Background: Data on patient and liver graft survival comparing liver transplantation alone after listing for kidney with simultaneous liver kidney (SLK) transplantation are scanty., Methods: United Network Organ Sharing network database (1994-2011) queried for liver transplantation alone after being listed for kidney and SLK transplants., Results: Of 65,206 first liver transplants, 3549 were listed for simultaneous kidney. Of these, 422 (12%) received only liver (LIST) and differed from SLK recipients for the white race (64% vs. 57%; 0.005), diabetes (27% vs. 37%; P = 0.02), model for end-stage liver disease era (68% vs. 82%; P = 0.0001), serum creatinine (2.9±1.9 vs. 4.3±2.5; P < 0.0001), dialysis (35% vs. 64%; P < 0.0001), and donor risk index (1.6±0.4 vs. 1.5±0.3; P < 0.0001). Overall survival was poorer in the LIST group (55% vs. 76%; P < 0.0001). A higher proportion of patients died within 2 days of transplantation in LIST group (11% vs. 0.5%; P < 0.0001), mostly from cardiovascular causes. After excluding these patients, odds of patient mortality and liver graft loss were about 1.2-fold and twofold higher in the LIST group. A total of 103 (24%) patients needed a renal transplantation in the LIST group with 16 (4%) receiving kidney within first year after transplantation. After excluding patients receiving kidney within first year, about 33% recovered renal function to above estimated GFR of greater than 60 mL per min., Conclusion: Guidelines are needed for patient selection to list for and receipt of simultaneous liver kidney transplantation.

Background: The frequency of simultaneous liver kidney (SLK) transplantation is increasing. Data are scanty on outcomes of SLK transplants for liver disease etiology., Methods: Outcomes for liver and kidney grafts and patients survival at 5 years were compared for liver disease etiology among adults receiving SLK during 2002 and 2011 in the United States. Cox regression analysis models were built to determine the independent impact of liver disease etiology on outcomes., Results: A total of 2,606 patients (mean age 53 years, 69% males, 55% Caucasians) received SLK for primary biliary cirrhosis (PBC, n=76), primary sclerosing cholangitis (n=81), hepatitis C virus (HCV) (n=945), alcoholic liver disease (n=495), alcohol and HCV (n=152), cryptogenic cirrhosis (CC, n=289), nonalcoholic steatohepatitis (NASH) (n=221), hepatitis B virus (HBV) (n=98), and hepatocellular carcinoma (HCC) (n=249). HCV and NASH+CC contributed to about 44% and 9%, respectively, of all SLK transplants in 2002. Corresponding figures in 2011 were 34% and 22%, respectively. Compared to PBC, 5-year outcomes were worse for NASH, HCV, and HCC for liver graft (72%, 66%, and 72% vs. 82%; hazard ratio, HR: 2.5-3.1), kidney graft (71%, 65%, and 71% vs. 80%; HR: 2.3-2.8), and patient survival (74%, 69%, and 69% vs. 82%; HR: 2.4-2.7). Follow-up renal function assessed at 1, 3, and 5 years showed poor renal function among patients receiving SLK for HCV, NASH, CC, and HBV., Conclusions: Frequency of SLK transplants is increasing among NASH patients. Overall graft and patient outcomes are good. However, SLK for NASH, HCV, and HCC do worse. Strategies are needed to improve outcomes for SLK in HCV and NASH patients.

We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In the background of availability of better treatments for specific liver diseases and listing of nonalcoholic steatohepatitis (NASH) as an etiology for liver transplantation (LT), data are unclear on the impact of disease etiology on the frequency of LT and liver posttransplantation outcomes., Methods: The United Network for Organ Sharing database (1994-2009) was queried for adults receiving first LT for primary biliary cirrhosis (PBC; n=3052), primary sclerosing cholangitis (PSC; n=3854), hepatitis C virus (HCV; n=15,147), alcoholic cirrhosis (AC; n=8940), HCV+alcohol (n=6066), NASH (n=1368), cryptogenic cirrhosis (CC; n=5856), hepatitis B virus (HBV; n=1816), and hepatocellular carcinoma (HCC; n=8588). Graft and patient survival were compared and Cox models were built to determine independent prediction of outcomes by disease etiology., Results: The frequency of LT increased for NASH, HCC, and HCV+alcohol, remained stable for AC, and decreased for PBC, PSC, HCV, CC, and HBV. The proportion of simultaneous liver-kidney transplants increased from approximately 3% in 2001 to 10% in 2009. Compared with PBC, 5-year graft and patient survival were (a) similar for PSC, NASH, and HBV (80-85%), (b) poorer for AC and CC (hazard ratio, 1-1.5), and (c) worst for HCV, HCV+alcohol, and HCC (hazard ratio, 1.5-2.4). Five-year outcomes for HCV-associated HCC were poorer compared with HCC due to other etiologies., Conclusions: LT performed for NASH and HCC are increasing. Potent treatment options resulted in a decrease in number of transplants for HBV, HCV, and PBC. Better treatment modalities for HCV are expected to further reduce the number of LT for HCV. Excellent posttransplantation outcomes for NASH and AC are encouraging, resulting in wider acceptance of transplants for these etiologies.

Liver transplantation has enjoyed dramatic success as a treatment option for patients suffering from chronic end-stage liver diseases. It also serves as a definitive treatment for certain genetic conditions such as familial amyloidosis and primary oxalosis, and as a potential curative therapy in selected cases of primary liver cancer. Currently, over 50,000 patients are alive with functioning liver transplants. Liver transplantation owes its success to advances in surgical technique, improvements in anesthesia and critical care, and advances in treatment of post-transplant complications including improved therapies for cytomegalovirus infections. But perhaps the most important advances in liver transplantation arise in the context of improvements in our understanding of the molecular biology of transplant immunology and the development of new agents that allow for manipulation of immunological signaling pathways. These improvements in immunosuppressive therapy have dramatically increased both graft and patient survival.

To evaluate the impact of mycophenolate mofetil (MMF) on long-term outcomes of tacrolimus and corticosteroids, we analyzed data reported to the Scientific Registry of Transplant Recipients for 11,670 adult patients (3463 with hepatitis C [HCV]) who underwent primary, single-organ, liver transplantation between 1995 and 2001. Patients who were discharged from the hospital on tacrolimus-based immunosuppression with (n = 4466; n = 1323 HCV) or without MMF (n = 7204; n = 2140 HCV) were included in the analysis. Recipients treated at discharge with MMF, tacrolimus, and corticosteroids had significantly increased patient survival (81.0% vs. 77.0% at 4 years, P < 0.0001) and graft survival (76.4% vs. 72.9%, P < 0.0001), and lower rates of acute rejection (29.0% vs. 33.4%, P < 0.001) as compared to recipients treated at discharge with tacrolimus and corticosteroids alone. A trend toward lower rates of death from infection was observed (6.1% at 4 years for MMF vs. 7.1% at 4 years for tacrolimus and corticosteroids, P = 0.0508), but this result did not reach statistical significance. In multiple regression analyses, MMF triple therapy at discharge was associated with a reduced risk of death (hazard ratio [HR] = 0.77, P < 0.001), graft loss (HR = 0.81, P < 0.001), acute rejection (HR = 0.89, P = 0.002), and death from infectious complications (HR = 0.80, P = 0.007). Outcomes were similar for the cohort with HCV.In conclusion, the addition of MMF at discharge to tacrolimus-based immunosuppression is associated with improved long-term outcomes after liver transplantation in patients with and without HCV.

The Model for End-Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan-Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF-NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P =.0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P <.0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P =.41) and did not show a significant association between survival and OLT (P =.68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF-NA candidates.

Non-anastomotic biliary stricture (NAS) formation is a major complication of liver transplantation. We prospectively determined the time to development of responsiveness to treatment, and clinical outcomes following NAS formation. In addition, an extensive analysis of the association of recipient, donor, and clinical variables with NAS formation was performed. A total of 749 consecutive patients was studied in a prospective, protocol-based fashion. Seventy-two patients (9.6%) developed NAS at a mean of 23.6 +/- 34.2 weeks post-transplantation. Non-anastomotic biliary stricture formation resolved in only 6% of affected patients. Although patient survival was not affected, retransplantation and graft loss rates were significantly greater in recipients who developed NAS. In contrast to previous reports, a pretransplant diagnosis of HCV was associated with a low frequency of NAS formation. The incidence of NAS was independently associated with pretransplant diagnoses of PSC and autoimmune hepatitis. Hepatic artery thrombosis, and prolonged warm and cold ischemia times were also independent risk factors for NAS formation. We conclude that NAS developed in approximately 10% of primary liver transplant recipients. A pretransplant diagnosis of autoimmune hepatitis has been identified as a novel independent risk factor for NAS formation. Development of NAS significantly attenuates graft but not patient survival.

There is a paucity of data regarding hepatic allograft iron accumulation in patients undergoing orthotopic liver transplantation (OLT) in whom severe iron overload was present in the native explanted liver. Our aim is to evaluate the frequency and cellular distribution of stainable iron in early and late post-OLT hepatic allograft biopsy specimens from patients undergoing their first OLT who had excess iron in their native explanted liver. We compared iron-staining patterns in hepatic allograft biopsy specimens at approximately 1 month (early) and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater than 1.9 in the explanted liver (cases) with a selected group of matched controls without explant hemosiderosis. Our cases included 6 patients with a pre-OLT diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and secondary iron overload. Early iron deposition was mild in most cases, commonly affected Kupffer's cells, and was seen with similar frequency in cases and controls (41% v 27%; P =.29). Stainable iron was observed in 20 donor livers (12 cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic allograft biopsy specimens. Liver samples from 35 matched pairs were studied for late iron deposition. Iron deposition was observed in 43% of cases versus 17% of controls (P =.06). In conclusion, the frequency of stainable iron in early hepatic allograft biopsy specimens was not different between patients with versus without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late hepatic biopsy specimens.

The aims of this study are to assess the efficacy of hepatitis B virus (HBV) vaccination using an accelerated schedule and double dose of recombinant vaccine in liver transplant recipients and identify factors associated with seroconversion and persistence of antibody to hepatitis B surface antigen (anti-HBs). Three hundred fifty-six patients were enrolled. Exclusion criteria were previous HBV infection, fulminant liver failure, or less than 2 years of follow-up after orthotopic liver transplantation (OLT). The vaccination schedule was 0, 2 weeks, 4 weeks, and 6 months using double-dose recombinant vaccine. Seroconversion was evaluated prospectively by measuring anti-HBs on the day of OLT and 1 and 2 years after OLT. Quantitative analyses of anti-HBs were performed retrospectively on stored sera. Geometric mean concentrations (GMCs) were calculated using a standard formula. All patients completed the full vaccination schedule, and 129 patients (36%) completed the schedule before OLT. The overall prevalence of anti-HBs was 128 of 356 pre-OLT samples (36%) compared with 41 of 353 (11.6%) and 26 of 325 post-OLT samples (8%) 1 and 2 years after OLT, respectively (both P =.001). The pre-OLT GMC was 86.7 compared with 0.32 and 0.33 at 1 and 2 years after OLT, respectively (P =.001). Patients with high titers of anti-HBs before OLT were more likely to have persistence of antibodies 1 or 2 years after OLT. Younger age (P =.02), low Child-Pugh score (P =.02), underlying chronic hepatitis C (P=.03), and specific host HLA subtypes were most strongly associated with seroconversion and/or persistence of anti-HBs. Thus, (1) seroconversion before or after OLT using double-dose accelerated-schedule vaccination against HBV is low, (2) there is a rapid, significant decrease in antibody titer after OLT, (3) pre-OLT anti-HBs titer potentially may be useful in predicting persistence of protective antibodies after OLT, and (4) several factors (age, genetic predisposition, severity of liver disease, and underlying liver disease) may have a role in poor vaccine responsiveness.

Liver transplant recipients frequently have chronic liver diseases and should be considered for vaccination against hepatitis A virus (HAV). However, persistence of protective antibodies after orthotopic liver transplantation (OLT) has not been shown in this population, which may have implications for future vaccine recommendations. We evaluated the prevalence and epidemiological significance of immunoglobulin G (IgG) antibody to HAV (anti-HAV) in a nonvaccinated population before OLT (immunity from previous exposure) and determined the persistence of IgG anti-HAV at 1 and 2 years after OLT. One hundred consecutive patients were identified who underwent OLT and had at least 2 years of follow-up post-OLT. They were not vaccinated against HAV infection at any time. Clinical data were summarized from medical records, and stored sera were tested for IgG anti-HAV before OLT and at 1 and 2 years after OLT by a commercially available enzyme immunoassay. Of 100 patients, 24 had IgG anti-HAV before OLT. No epidemiological differences were noted between those with or without detectable IgG anti-HAV before OLT. Among patients with detectable IgG anti-HAV before OLT, 4 of 22 patients (18%) and 7 of 24 patients (29%) became negative for IgG anti-HAV at 1 and 2 years post-OLT, respectively. None of the patients with undetectable IgG anti-HAV before OLT became positive at any time. Most of our patients with end-stage liver disease had no serological evidence for immunity against HAV. A significant proportion of patients with detectable protective antibodies before OLT lost their antibodies at 2 years after OLT.

This report summarizes a recent meeting cosponsored by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases to formulate minimal criteria by which patients with severe liver disease will be placed on the waiting list for liver transplantation. The participants agreed that only patients in immediate need of liver transplantation should be placed on the waiting list. Patients should not be placed in anticipation of some future need for such therapy. It was agreed that minimal criteria could assist but not replace the clinical judgment of the transplant professionals at individual centers. The criteria will be summarized below for adult patients with acute or chronic liver disease. The most important non-disease-specific criterion for placement on the transplant waiting list was an estimated 90% chance of surviving 1 year. This translated into a Child-Pugh score of > or = 7 for patients with cirrhosis which places the patient in Child-Pugh class B or C. Cirrhotic patients who have experienced gastrointestinal bleeding caused by portal hypertension or a single episode of spontaneous bacterial peritonitis would meet the minimal criteria irrespective of their Child-Pugh score. There were disease-specific criteria also. These include a sole minimal criterion for patients with fulminant hepatic failure regardless of etiology of the onset of stage 2 hepatic encephalopathy. A requirement for 6 months abstinence from alcohol before placement on the transplant waiting list was considered appropriate for most patients with alcoholic liver disease. Exceptional cases could get access to the waiting list through a regional review process. Chronic cholestatic diseases present difficulties because of a different natural history than that of chronic hepatocellular diseases. The use of specific risk scores for primary biliary cirrhosis and primary sclerosing cholangitis will likely replace Childs-Pugh classification as the scoring systems become refined. Minimal criteria for any patient with a primary hepatocellular cancer would admit any patient with a tumor confined to the liver irrespective of size or number of tumors, after careful investigation had failed to show spread to lymph nodes, the portal vein, or distant organs. Unusual or rare indications for liver transplantation, including Budd-Chiari syndrome, Wilson's disease, and other hereditary disorders, were also discussed. Finally, it was agreed that there should be no absolute contraindications to placement of patients on the liver transplant waiting list. These criteria should be open to regular review to accommodate advances in the field.

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.

Objective: To review our experience with portosystemic shunts during the era of liver transplantation at the Mayo Clinic to provide insight into the selection of patients for these procedures., Design: We reviewed the charts of a cohort of 57 patients who underwent portosystemic shunting between 1985 and 1990 for the management of variceal bleeding. A follow-up survey by letter and telephone was also conducted., Setting: The Mayo Clinic, a tertiary referral center., Patients: These patients were not considered transplantation candidates at the time of the shunt because of active alcoholism, extensive portal vein thrombosis, coexistent myelodysplastic syndromes, or malignant neoplasms., Intervention: Portosystemic shunts; the exact type was at the surgeon's discretion., Outcome: Survival after shunt surgery among patients with various liver diseases., Results: Twenty-two patients died during follow-up after being shunted for bleeding, and one of the shunted patients subsequently required liver transplantation. Comparison of Kaplan-Meier survival curves between various groups of patients indicated that patients who were actively alcoholic had a poorer chance of survival (P < .003) than did those who were abstinent. Patients with portal vein obstruction or chronic cholestatic liver disease appeared to do better after shunt surgery than did patients with other causes of portal hypertension. Other factors such as age, Child-Pugh score, or presence of malignant neoplasms did not reliably predict outcome from portosystemic shunts., Conclusions: In well-selected patients who may not be deemed candidates for liver transplantation, portacaval shunts can be effectively employed to prevent bleeding from esophageal varices that are resistant to obliteration by sclerotherapy.

The study determined predictive factors for postoperative complications and outcome after ileal pouch-anal anastomosis in patients with ulcerative colitis and primary sclerosing cholangitis. Patients with ulcerative colitis and primary sclerosing cholangitis treated by colectomy and ileostomy are at high risk of troublesome bleeding from peristomal varices. Postoperative complications and outcome were assessed in 40 patients with ulcerative colitis and sclerosing cholangitis who received in ileal pouch-anal anastomosis between January 1981 and February 1990. Immediate postoperative and remote ileoanal anastomosis-related complications were high but related directly to the severity of liver disease. No patient had perianastomotic and bleeding. In patients with both ulcerative colitis and primary sclerosing cholangitis, ileal pouch-anal anastomosis is safe and is not associated with perianastomotic bleeding.

Hepatic allograft rejection is presently classified into acute and chronic rejection based on histological features, timing and reversibility. However, because features of both types of rejection can occur at any time, and in many combinations, the terms "acute" and "chronic" seem inappropriate in some instances. Thus the term "cellular rejection" better defines the histological features of portal hepatitis, nonsuppurative destructive cholangitis and endotheliitis, which are independent of time and response to therapy. Similarly, because progressive bile duct destruction leading to a decrease in the number of interlobular and septal bile ducts is the major histological feature of "chronic rejection," the term "ductopenic rejection," defined as the loss of bile ducts in 50% or more of portal tracts independent of time and reversibility, seems more appropriate. The pathogenesis of cell-mediated rejection has not been completely explained; however, direct immunocytic attack on small bile ducts and small arteries appear to be the major feature. The process may lead to bile duct loss ("ductopenia"). The pathogenetic role of foam-cell arteritis resulting in ischemic bile duct injury and the role of humoral mechanisms in causing ductopenic rejection awaits further clarification. In the past, irreversible ductopenic rejection occurred in approximately 10% of all patients who underwent their first liver transplantation; this figure, however, appears to be decreasing. The clinical features of irreversible rejection include persistent and progressive cholestasis; rising serum levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase; and a decrease in hepatic synthetic function. Ductopenic rejection can occur early (2 to 5 wk after liver transplantation) but most often develops between 6 wk and 6 mo after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection.

Fulminant hepatic failure is the rapid onset of life-threatening hepatic decompensation in patients who have no previous history of liver disease. This condition has a multifactorial etiology, including viral hepatitis and drug toxicity. At this time there is no specific therapy for FHF. However, early diagnosis and treatment of the complications--in particular, cerebral edema--may prolong survival and prevent irreversible neurologic complications. Once the diagnosis has been made, patients with FHF should promptly be transferred to a specialized liver care unit where liver transplantation is available. Liver transplantation is now the treatment of choice for patients with clinical characteristics suggesting a poor chance of survival.

When Wilson's disease presents as fulminant hepatic failure, it may be extremely difficult to differentiate from other causes of hepatic insufficiency. A recently described diagnostic biochemical profile (elevated serum and urine copper levels, mild transaminase elevation, very high bilirubin levels, and low hemoglobin with intravascular hemolysis) was employed to diagnose this form of Wilson's disease prior to death in a young woman without Kayer-Fleischer rings and with a normal serum ceruloplasmin level. Since hepatic transplantation now offers a possible cure for this previously uniformly fatal form of Wilson's disease, it should be considered the treatment of choice for this disease entity. Combined with the availability of hepatic transplantation, this patient's temporary improvement and unusually long survival of four months further emphasizes the importance of this diagnostic profile in recognizing Wilson's disease quickly and accurately when it presents as fulminant hepatic failure.

Monoclonal antibodies were used to identify T-helper cells (TH) and T-suppressor/cytotoxic cells (TS/C) in biopsy specimens obtained 7, 21, 90, 180, and 365 days postoperatively, and during episodes of graft dysfunction, from 34 consecutive liver transplant patients treated with cyclosporine and steroids. Rejection was diagnosed by the presence of appropriate laboratory and light microscopic findings and at least 8 weeks of follow-up to exclude other causes of graft dysfunction. Four immunohistologic patterns were seen--no labeled cells (No), only lobular TS/C, only portal TH, and a portal mixture of TH and TS/C (mix). Of 36 specimens with the No or only lobular TS/C pattern, 29 were not associated with rejection. Of the 39 specimens with the portal TH or portal Mix pattern, 33 were associated with a rejection episode. In addition, in nine specimens from patients with no biochemical or routine histologic evidence of rejection, the presence of portal TH or a portal mix indicated immunologic rejection 5 days to 5 weeks before biochemical and routine histologic evidence of it was manifested. Immunohistologic labeling appears to be an early indicator of liver allograft rejection.