The impact of proposed changes in liver allocation policy on cold ischemia times and organ transportation costs.

Changes to the liver allocation system have been proposed to decrease regional variation in access to liver transplant. It is unclear what impact these changes will have on cold ischemia times (CITs) and donor transportation costs. Therefore, we performed a retrospective single center study (2008-2012) measuring liver procurement CIT and transportation costs. Four groups were defined: Local-within driving distance (Local-D, n = 262), Local-flight (Local-F, n = 105), Regional-flight <3 h (Regional <3 h, n = 61) and Regional-Flight >3 h (Regional >3 h, n = 53). The median travel distance increased in each group, varying from zero miles (Local-D), 196 miles (Local-F), 384 miles (Regional <3 h), to 1647 miles (Regional >3 h). Increasing travel distances did not significantly increase CIT until the flight time was >3 h. The average CIT ranged from 5.0 to 6.0 h for Local-D, Local-F and Regional <3 h, but increased to 10 h for Regional >3 h (p < 0.0001). Transportation costs increased with greater distance traveled: Local-D $101, Local-F $1993, Regional <3 h $8324 and Regional >3 h $27 810 (p < 0.0001). With proposed redistricting, local financial modeling suggests that the average liver donor procurement transportation variable direct costs will increase from $2415 to $7547/liver donor, an increase of 313%. These findings suggest that further discussion among transplant centers and insurance providers is needed prior to policy implementation.

What liver transplant outcomes can be expected in the uninsured who become insured via the Affordable Care Act?

Our study objective is to measure the survival impact of insurance status following liver transplantation in a cohort of uninsured "charity care" patients. These patients are analogous to the population who will gain insurance via the Affordable Care Act. We hypothesize there will be reduced survival in charity care compared to other insurance strata. We conducted a retrospective study of 898 liver transplants from 2000 to 2010. Insurance cohorts were classified as private (n = 640), public (n = 233) and charity care (n = 23). The 1, 3 and 5-year survival was 92%, 88% and 83% in private insurance, 89%, 80% and 73% in public insurance and 83%, 72% and 51% in charity care. Compared to private insurance, multivariable regression analyses demonstrated charity care (HR 3.11, CI 1.41-6.86) and public insurance (HR 1.58, CI 1.06-2.34) had a higher 5-year mortality hazard ratio. In contrast, other measures of socioeconomic status were not significantly associated with increased mortality. The charity care cohort demonstrated the highest incidence of acute rejection and missed clinic appointments. These data suggest factors other than demographic and socioeconomic may be associated with increased mortality. Further investigations are necessary to determine causative predictors of increased mortality in liver transplant patients without private insurance.

Human primary gastric dendritic cells induce a Th1 response to H. pylori.

Adaptive CD4 T-cell responses are important in the pathogenesis of chronic Helicobacter pylori gastritis. However, the gastric antigen-presenting cells that induce these responses have not yet been identified. Here we show that dendritic cells (DCs) are present in the gastric mucosa of healthy subjects and are more prevalent and more activated in the gastric mucosa of H. pylori-infected subjects. H. pylori induced gastric DCs isolated from noninfected subjects to express increased levels of CD11c, CD86 and CD83, and to secrete proinflammatory cytokines, particularly interleukin (IL)-6 and IL-8. Importantly, gastric DCs pulsed with live H. pylori, but not control DCs, mediated T-cell secretion of interferon-gamma. The ability of H. pylori to induce gastric DC maturation and stimulate gastric DC activation of Th1 cells implicates gastric DCs as initiators of the immune response to H. pylori.

17beta-estradiol differentially activates mitogen-activated protein-kinases and improves survival following reperfusion injury of reduced-size liver in mice.

Ischemia-reperfusion injury (I/R-I), which is unavoidable in liver transplantation, impairs liver regeneration and predisposes to liver failure. The three major mitogen-activated protein-kinases (MAPKs): ERK, p38, and JNK, are critical in the transmission of signals triggered by proinflammatory cytokines, by stress, and by growth factors. JNK and p38alpha activation have been associated with apoptosis; p38beta with cell survival; and ERK with proliferation. Previous studies have demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. Female mice are protected to a much greater extent from I/R-I than male mice. We assessed the effects of 17beta-estradiol (17beta-E) on liver function, host survival, and cellular activation of MAPK in a murine model of I/R-I in reduced-size livers. C57BL/6 mice were subjected to 45 minutes of warm ischemia (70% of the liver mass). After reperfusion, the nonischemic lobes were excised. Vehicle, 17beta-E or the estrogen receptor antagonist ICI-182780, was delivered 1 hour before the injury. We evaluated AST and apoptosis as well as activation of JNK, p38, and ERK. Female mice showed a lower level of hepatocellular injury (AST = 445 +/- 82 IU/L) after I/R-I compared with male mice (AST = 1400 +/- 210). 17beta-E decreased the liver injury in male mice (AST = 522 +/- 77), an effect that was partially reversed by ICI-182,780 (910 +/- 92). A higher rate of apoptosis was observed in male animals given saline (enrichment factor = 7.22 +/- 0.8) versus those treated with 17beta-E (5.85 +/- 0.3, P < .05). A significant increase in liver regeneration, as assessed by the percentage of liver weight/body weight was demonstrated in females (184% +/- 24%) and male mice given 17beta-E (168% +/- 22%) compared with male mice given vehicle (9% +/- 4%). 17beta-E significantly down-regulated JNK and p38alpha activities, whereas I/R-I promoted p38beta and ERK activation. These results suggest that the cytoprotective effects of 17beta-E on I/R-I to reduced-size livers are associated with selective modulation of MAPK kinases.

Radio-frequency ablation in cirrhotic patients with hepatocellular carcinoma.

Current surgical treatments for hepatocellular carcinoma (HCC) include radio-frequency ablation (RFA), resection, and orthotropic liver transplant (OLT). RFA is particularly attractive in these high-risk patients because surgery is associated with high mortality and there is a relative scarcity of organs available for those in need of transplants. This study was performed to evaluate the management of cirrhotic patients with HCC undergoing RFA at a single Western institution. A retrospective study from March 1999 to June 2002 was performed to evaluate the clinicopathologic and treatment-related variables in cirrhotic patients with HCC. Forty-nine lesions in 26 patients with HCC and cirrhosis underwent RFA. Data was analyzed for safety and overall survival as the main endpoints. The mean age was 60.4 +/- 11 years, 19 patients were male, 5 had hepatitis B virus, and 19 had hepatitis C virus. The Child classification was 26 per cent, 39 per cent, and 35 per cent for A, B, and C; the number of lesions was 1 in 62 per cent, 2 in 23 per cent, and more than 2 in 15 per cent. The approach was laparoscopic in 58 per cent, percutaneous in 15 per cent, and open in 27 per cent. There were no mortalities and only 1 complication. Average hospital stay was 2.7 +/- 2 days. Subsequent to RFA, 9 patients underwent an OLT within a median of 4.1 months. The median follow-up of the whole group was 13 months and the disease-free survival 9.3 months. Tumor recurrence was identified in 3 previously ablated lesions, nonablated liver in 11, and as pulmonary metastases in 3. Overall survival (P = 0.03) was prolonged for those treated with RFA + OLT over RFA alone. We conclude that RFA is a safe ablative technique in high-risk cirrhotic patients with HCC. This technique may provide a bridge to OLT; however, it remains to be proven whether it prolongs survival in those who do not undergo OLT.

Gene transfer of the Bcl-2 gene confers cytoprotection to isolated adult porcine pancreatic islets exposed to xenoreactive antibodies and complement.

BACKGROUND: Exposing adult porcine pancreatic islets (PI) to xenoreactive natural antibodies (XNA) induces brisk inflammatory injury that involves activation of the complement system. Gene transfer of Bcl-2 has been shown to protect PI from apoptosis and necrosis in several models. In this study, we investigated the effect of Bcl-2 gene transfer on protection of PI from primate XNA and complement-mediated injury. METHODS: The PI were isolated from adult female sows. Only islet preparations that exhibited >90% viability and purity were used. Fresh rhesus monkey serum served as the XNA source. Gene transfer of Bcl-2 was achieved with an adenoviral vector (AdBcl-2) at 500 particle forming units (pfu)/cell. The Bcl-2 expression was confirmed by Western blot technique. Untransfected and transfected PI were incubated in 50% fresh complete serum (CS) or heat-inactivated (HI) rhesus serum for 24 hours. The PI viability was analyzed with acridine orange and ethidium bromide staining. Antibody and complement-mediated cytotoxicity were tested by intracellular lactate dehydrogenase (LDH) release. The PI function was assessed in vitro by static incubation studies and in vivo after intraportal transplantation in diabetic severe combined immunodeficiency (SCID) mice. RESULTS: The AdBcl-2 gene transfer resulted in Bcl-2 gene expression in >90% of PI cells. Following exposure to XNA, <15% of the untransfected cells were viable. Similar results were obtained in PI transfected with a similar recombinant adenovirus encoding the reporter gene E coli beta-galactosidase (AdLacZ), an irrelevant gene. A significant increase in LDH release was observed in control PI after exposure to CS compared with PI that overexpressed Bcl-2 (82.89% +/- 7.78% vs 34.31% +/- 5.4%, P <.005). Higher insulin release was observed in vitro in PI transfected with Bcl-2 compared with untransfected PI or islets transfected with AdLacZ (stimulation index of 0.9 +/- 0.31, 0.9 +/- 0.3 vs 2.67 +/- 0.4, respectively). Only PI treated with AdBcl-2 were able to achieve euglycemia after exposure to XNA and complement after transplantation. CONCLUSIONS: Transfer of the antiapoptotic and antinecrotic Bcl-2 gene into PI can reduce primate XNA and complement-mediated lysis. Cytoprotection of PI with Bcl-2 has potential to improve survival of PI xenotransplants.

Cytoprotection of pancreatic islets before and soon after transplantation by gene transfer of the anti-apoptotic Bcl-2 gene.

Isolated pancreatic islet transplantation is a promising alternative to conventional insulin-dependent diabetes treatment but is not yet a practical clinical therapy. In the first few days after pancreatic islet transplantation, substantial donor pancreatic islet dysfunction and apoptosis commonly occur. Islet apoptosis has been documented after extracellular matrix disruption and exposure to proinflammatory cytokines, and during hypoxia before islet revascularization and rejection. These studies show that targeting the apoptosis pathway by adenoviral-mediated gene transfer of the anti-apoptotic Bcl-2 gene exerts a major cytoprotective effect on isolated macaque pancreatic islets. Bcl-2 transfection ex vivo protects these islets from apoptosis induced by disruption of the islet extracellular matrix during pancreatic digestion. Additionally, overexpression of Bcl-2 confers long-term, stable protection and maintenance of functional islet mass after transplantation of macaque islets into diabetic severe combined immunodeficency mice. Notably, genetic modification of pancreatic islets also reduced the islet mass required to achieve stable euglycemia. Ex vivo gene transfer of anti-apoptotic genes has potential as a therapeutic approach to both minimize loss of functional islet mass after transplant and reduce the high donor islet requirement currently needed for successful stable reversal of insulin-dependent diabetes.

Successful reversal of streptozotocin-induced diabetes with stable allogeneic islet function in a preclinical model of type 1 diabetes.

The recent focus on islet transplantation as primary therapy for type 1 diabetes has heightened interest in the reversal of type 1 diabetes in preclinical models using minimal immunosuppression. Here, we demonstrated in a preclinical rhesus model a consistent reversal of all measured glycemic patterns of streptozotocin-induced type 1 diabetes. The model used single-donor islet transplantation with induction of operational tolerance. The term "operational tolerance" is used to indicate durable survival of single-donor major histocompatibility complex (MHC)-mismatched islet allografts without maintenance immunosuppressive therapy and without rejection or loss of functional islet mass or insulin secretory reserve. In this operational tolerance model, all immunosuppression was discontinued after day 14 posttransplant, and recipients recovered with excellent health. The operational tolerance induction protocol combined peritransplant anti-CD3 immunotoxin to deplete T-cells and 15-deoxyspergualin to arrest proinflammatory cytokine production and maturation of dendritic cells. T-cell deficiency was specific but temporary, in that T-cell-dependent responses in long-term survivors recovered to normal, and there was no evidence of increased susceptibility to infection. Anti-donor mixed lymphocyte reaction responses were positive in the long-term survivors, but all showed clear evidence of systemic T-helper 2 deviation, suggesting that an immunoregulatory rather than a deletional process underlies this operational tolerance model. This study provides the first evidence that operational tolerance can protect MHC nonhuman primate islets from rejection as well as loss of functional islet mass. Such an approach has potential to optimize individual recipient recovery from diabetes as well as permitting more widespread islet transplantation with the limited supply of donor islets.

Combined cardiac surgery and liver transplantation.

During evaluation for liver transplantation, a 63-year-old man with cirrhosis secondary to hepatitis C was diagnosed with severe aortic stenosis (aortic valve area, 0.87 cm(2)) and coronary artery disease. A combined procedure involving aortic valve replacement (pericardial xenograft), coronary artery bypass surgery, and orthotopic liver transplantation was performed. Convalescence was uneventful, and at 2 years after the procedure, the patient has normal cardiac function, good prosthetic valve function, and biochemically normal liver function.

Multimodality treatment for patients with hepatocellular carcinoma: analysis of prognostic factors in a single Western institution series.

There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including orthotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham from January 1990 through December 1999. Clinicopathologic and treatment factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or IV tumors. The median follow-up for survivors was 22 months. The 1-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial 1-, 3-, and 5-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.

Experience with renal transplantation in the nonhuman primate: a modified ureteroneocystostomy to prevent urologic complications.

Nonhuman primates provide an optimal model for the evaluation of tolerance in the preclinical setting. Transplantation and management of nonhuman primates are technically demanding, and the purpose of this article is to review our extensive experience in renal transplantation in non-human primates, with particular emphasis on modifications of surgical techniques on urologic complications. We retrospectively reviewed our results with 329 renal transplants in rhesus monkeys over an 18-year period. The surgical technique and, in particular, the ureteroneocystostomy have evolved over this period of time. This review extensively details our current technique, the surgical and urologic complications, and their management. There were 329 renal transplants performed. There were 85 early deaths, or animals euthanized, within 30 days of the transplant operation. In the first 15 years, there were 27 (10.68%) surgical complications that required euthanasia, and in the last 3 years the complication rate has been reduced to 5 (7.3%, p < .05). The routine use of microsurgical techniques has reduced the incidence of arterial thrombosis (6.2% vs. 2.9%, p < .05). The incidence of ureteral strictures (15 vs. 0, p < .005) has been reduced by a modification of the ureteroneocystostomy technique detailed in the text. Renal transplantation in small rhesus monkeys is technically demanding. The routine use of microsurgical techniques and a modified ureteroneocystostomy has reduced the incidence of surgical complications.

Durable donor-specific T and B cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic allograft nephropathy.

Tolerance induction can prevent acute kidney allograft rejection without chronic immunosuppression. It is uncertain whether specific tolerance can prevent chronic allograft nephropathy (CAN), which involves both nonimmune and immune injury. This report provides evidence that immunologically tolerant macaques, induced with immunotoxin and deoxyspergualin, developed neither acute rejection nor CAN. Long survivors, bearing MHC-mismatched grafts without chronic immunosuppression for 0.8 to 3.4 years, exhibited general immune competence with donor-specific T and B cell tolerance and no functional or histological evidence of CAN. Stringent criteria for tolerance were satisfied by specific prolongation of donor skin grafts with rapid rejection of third-party skin, followed by indefinite acceptance of a second donor kidney graft and establishment of microchimerism. Primate tolerance with documented absence of CAN may give impetus to the clinical application of tolerance.

The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients.

BACKGROUND: Induction therapy with daclizumab has been shown to be efficacious in the prevention of acute rejection in kidney transplant patients. The routine use of antibody induction therapy in liver transplantation has not gained widespread acceptance, except in the cases of renal insufficiency. The recent approval of daclizumab prompted us to initiate this pilot study using induction therapy in those patients at risk for developing posttransplant renal insufficiency. METHODS: This nonrandomized study examined the use of daclizumab in 39 of the last 97 liver transplants performed at the University of Alabama in Birmingham. The daclizumab group received 2 mg/kg intravenously before organ engraftment, and 38 of the 39 received 1 mg/kg intravenously on postoperative day 5. The control group consisted of the remaining 58 contemporary patients. Additional immunosuppression consisted of steroids, tacrolimus, or microemulsion cyclosporine in all patients and mycophenolate mofetil in selected patients. RESULTS: Pretransplant demographics were not significantly different between the groups. In the induction group there were significantly fewer males, 14 (36%) vs. 34 (59%) (P=0.03). They had greater renal insufficiency at the time of transplant, serum creatine 1.9+/-0.37 mg/dl vs. 0.8+/-0.5; P=0.0009, and more patients were at higher acuity (status 1 and 2A): 12 (31%) vs. 3 (5%) P=0.0006 than in the noninduction group. By postoperative day 7, renal function improved in the induction group such that it was not significantly different from the noninduction group and remained similar throughout the rest of the follow-up. The induction group also experienced significantly less acute rejection, 7 (18%) vs. 23 (40%) (P=0.02) than in the noninduction group in the first 6 months. The 1-, 3-, and 6-month patient survival rates were similar in the induction group, 97.4%, 97.4%, and 97.4%, vs. non-induction 94.8%, 93.0%, and 93% (P=NS). The incidence of cytomegalovirus, in the first 6 months, in the induction group was four (10%) vs. five (9%) (P=NS) in the noninduction group. CONCLUSION: In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.

Liver transplantation in the era of cost constraints.

BACKGROUND: The issue of containing cost has had a significant impact on organ transplantation. After our institution's 500th liver transplant, we critically examined the impact of the changing health care environment on liver transplantation. METHODS: We retrospectively analyzed 500 consecutive liver transplants done in the period of 1989 to 1998. RESULTS: Comparing the first 100 liver transplants to the last 100, patient demographics did not change significantly; however, mean waiting times increased significantly, from 30.4 days to 146.7 days, and median hospital stay decreased from 20.2 days to 10.9 days. One-year patient and graft survivals were not significantly different, 93.6% versus 96.5% and 88.0% versus 95.7%, respectively. CONCLUSIONS: Despite transplants in patients at higher risk and discharging patients sooner after transplantation, surgical results and patient survivals remained excellent. This was accomplished through improvements and modification of immunosuppression, outpatient treatment of uncomplicated acute rejection, and emphasis on close outpatient follow-up.

Long-term functional islet mass and metabolic function after xenoislet transplantation in primates.

BACKGROUND: Pancreatic islet transplantation (PIT) is an attractive alternative for patients with type I diabetes mellitus. PIT is not yet an effective clinical reality due in part to the high incidence of rejection and early loss of functional islet mass. In addition, current immunosuppressive drugs have toxic effects on islets and increase the risk of morbidity and mortality. In the present study, the effects of PIT on glycemic parameters were assessed in spontaneously diabetic primates. METHODS: Five insulinopenic nonhuman primates (three Macacca fascicularis, one Ceropithecus aethiops, and one Macacca mulatta) were studied. All required twice-daily treatment with 4-10 U of insulin. For immunosuppression, the animals received anti-CD3-immunotoxin (100 microg/kg(initially infused 2 hr before transplantation and again on day +1), cyclosporine (CsA) (20 mg/kg(i.v./2 hr before transplantation), cyclosporine microemulsion (Neoral) 60 mg/kg/b.i.d. on days +1 to +3 with dose adjusted by blood levels, and methylprednisolone (15 mg/kg day 0 to +3). Three recipients were given islets from a single donor (M mulatta). The islets were prepared by a semiautomated technique using Liberase. A mean of 13,136 islet equivalents/kg was infused into the portal vein. Two animals (M fascicularis and M mulatta) were used as a diabetic, nontransplanted control. Several metabolic parameters were evaluated. RESULTS: All monkeys that underwent transplantation experienced reversal of diabetes mellitus with normalization of all diabetic glycemic parameters. In the nontransplanted primates given the same immunosuppression but no PIT, diabetic metabolic parameters were unchanged after 9 months of follow-up. In contrast, all three PIT recipients established fasting and nonfasting euglycemia within 1-2 weeks, and none required exogenous insulin after day 10. Normal intravenous glucose tolerance tests were observed at day 15, and no significant differences in the glucose disappearance rate (Kg) were observed at days 15, 45, 190, and 365 days after transplantation. The acute insulin response to glucose indicated no significant reduction of functional islet mass. CONCLUSIONS: PIT in severely insulinopenic type I diabetes mellitus primates resulted in restoration of normal glycemic parameters and durable islet mass. Operational tolerance was achieved with only 4 days of drug administration, sparing the animals from chronic exposure to potentially diabetogenic immunosuppressive drugs. These results offer an exciting new potential for type I diabetes mellitus treatment.

Improved outcomes in cadaveric renal allografts with pulsatile preservation.

BACKGROUND: Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation pulsatile perfusion (PP) versus cold storage (CS) is debated. METHODS: Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( < or = 20 min, 21-40 min, or > 40 min) and total ischemic time (TIT) ( < or > or = 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. RESULTS: There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). CONCLUSIONS: Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

Role of ERCP in asymptomatic orthotopic liver transplant patients with abnormal liver enzymes.

OBJECTIVE: The safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in the evaluation and management of biliary tract complications after orthotopic liver transplantation (OLT) have been previously demonstrated. However, the role of ERCP in evaluating asymptomatic OLT patients with abnormal liver enzymes with a previously normal biliary tree remains poorly defined. We sought to assess the utility of ERCP in this subset of patients. METHODS: A retrospective analysis of-asymptomatic OLT patients with abnormal liver enzymes evaluated by ERCP was undertaken. In addition to ERCP, all these patients had a diagnostic abdominal Doppler ultrasound, and a percutaneous liver biopsy. All patients had choledochocholedochostomy at the time of transplant and normal T-tube cholangiograms 3 months postoperatively. A radiologist, blinded to clinical findings, interpreted the ultrasound as normal, biliary dilation, or vascular abnormalities. The same radiologist interpreted ERCP findings. A pathologist, blinded to clinical findings, graded liver biopsies as normal, diagnostic, or abnormal but nondiagnostic. RESULTS: Twenty-two patients underwent 23 ERCPs. Twenty-two of the 23 ERCPs were normal (96%), and one abnormal ERCP finding did not explain the liver enzyme abnormality. Liver biopsy was diagnostic in 13 of 22 (57%) and in each case the ERCP was normal. The remaining 10 liver biopsies were abnormal but nondiagnostic. Ultrasound was abnormal in five of 22 cases, but in the three cases suggesting biliary dilation, the ERCP was interpreted as normal. CONCLUSION: Routine use of ERCP in evaluation of asymptomatic OLT patients with liver function test abnormalities and normal cholangiograms at 3 months was not diagnostically useful. In this subset of patients, liver biopsy was usually abnormal and frequently diagnostic and should be the initial invasive diagnostic procedure.