Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart-Liver Transplantation.

When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart-liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune-mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol- and indication-specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell-mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor-specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody-mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0-0.02; p < 0.0001), antibody-mediated rejection (OR 0.04, 95% CI 0-0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07-0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients.

Combined liver transplantation and gastric sleeve resection for patients with medically complicated obesity and end-stage liver disease.

Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post-LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post-LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post-LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post-LT metabolic complications. Long-term follow-up is needed.

Impact of MELD on waitlist outcome of retransplant candidates.

Under the current allocation system for liver transplantation (LTx), primary and retransplantation (ReTx) are treated identically. The aims of this study were (1) to compare the risk of death between ReTx and primary LTx candidates at a given MELD score and (2) to gauge the impact of the MELD-based allocation system on the waitlist outcome of ReTx candidates. Based on data of all waitlist registrants in the United States between 2000 and 2006, unique adult patients with chronic liver disease were identified and followed forward to determine mortality within six months of registration. There were a total of 45,943 patients waitlisted for primary LTx and 2081 registered for ReTx. In the MELD era (n = 30,175), MELD was significantly higher among ReTx candidates than primary LTx candidates (median, 21 vs. 15). Within a range of MELD scores where most transplantation took place, mortality was comparable between ReTx and primary candidates after adjusting for MELD. The probability for LTx increased significantly following implementation of the MELD-based allocation in both types of candidates. We conclude that by and large, primary and ReTx candidates fare equitably under the current MELD-based allocation system, which has contributed to a significant increase in the probability of LTx.

Daclizumab induction therapy in liver transplant recipients with renal insufficiency.

BACKGROUND: The role of interleukin 2 (IL-2) receptor antibodies to avoid the nephrotoxic effects of calcineurin inhibitors in the early post-liver transplant (LT) period is not well defined. AIM: To examine the use of daclizumab induction in LT recipients with renal insufficiency. METHODS: Between 2002 and 2005, 62 patients (median pre-LT creatinine 2.4 mg/dL, IQR 1.9-3.7) received daclizumab induction with tacrolimus being administered when serum creatinine was <2.0 mg/dL. A concurrent comparison group (n = 221, 2002-2005) received tacrolimus-based immunosuppression without daclizumab (median pre-LT creatinine 1.1 mg/dL, IQR 0.9-1.4). A second historical comparison group (n = 103, 1995-2005) not receiving daclizumab was matched to the daclizumab patients by pre-LT serum creatinine (2.2 mg/dL, IQR 1.8-3.1). All patients received mycophenolate mofetil and steroids. RESULTS: Serum creatinine improved in the daclizumab group (-1.0 mg/dL, IQR -2.2 to -0.4) and worsened in the concurrent comparison group (+0.2 mg/dL, IQR 0-0.5) from pre-LT to 4 months. However, there was no difference when daclizumab group was compared with the historical comparison group matched on pre-LT creatinine (median change: -0.8 mg/dL vs. -0.7 mg/dL). Daclizumab induction was not associated with improvement in renal function at 4 months (P = 0.34) after adjusting for pre-LT creatinine, age, gender, hepatitis C status and simultaneous liver kidney transplantation. CONCLUSION: The incremental benefit offered by induction therapy with IL-2 receptor antibodies to preserve renal function is questionable.

Long-term management of the liver transplant patient: recommendations for the primary care doctor.

No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.

Insulin resistance, serum adipokines and risk of fibrosis progression in patients transplanted for hepatitis C.

In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR 1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01-1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV.

Influence of coronary artery disease on outcomes after liver transplantation.

Patients with coronary artery disease (CAD) who undergo liver transplantation (OLT) have been previously identified as a high-risk group. Since that identification, the management of CAD has undergone significant changes as has the cardiovascular screening and selection of patients for OLT. We retrospectively identified 42 patients with known CAD who underwent OLT to compare outcomes with a control group of 42 patients without CAD who were matched for gender, age, and primary liver disease. Mortality rates were higher in the CAD than the control group at 1 year (5 vs 1) and 3 years (11 vs 3; P < .05) although lower than previously reported (at 3 years, 26% vs 50%). New cardiovascular morbidity was also more frequent among the CAD than control group at 1 year (11 vs 3; P < .05) and 3 years (16 vs 4; P < .05). Although outcomes for patients with CAD undergoing OLT are improved from historical levels, they are still worse than those in patients without CAD despite current management and selection strategies.

Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups.

To determine the natural history of portopulmonary hypertension (POPH), a retrospective screening-right heart catheterization-survival analysis of patients was performed. We categorized patients by three treatment subgroups: (1) no therapy for pulmonary hypertension (PH) or liver transplantation (LT), (2) therapy for PH alone and (3) therapy for PH followed by LT. Seventy-four patients were identified between 1994 and 2007. Nineteen patients received no therapy for PH and no LT representing the natural history of POPH. Five-year survival was 14%, and 54% had died within 1 year of diagnosis. Five-year survival in 43 patients receiving therapy for PH but no LT was 45%, and 12% had died within 1 year of diagnosis. Twelve patients underwent LT and 5-year survival for the nine receiving therapy for PH was 67% versus 25% in the three who were not pretreated with prostacyclin therapy. The survival of untreated patients with POPH was poor. Subgroups of patients selected to medical treatment with or without LT had better long-term survival. Mortality did not correlate with baseline hemodynamic variables, type of liver disease or severity of hepatic dysfunction. Medical therapy for POPH should be considered in all patients with POPH, but the treatment effects and impact on those considered for LT still requires well-designed, prospective study before practice guidelines can be suggested.

Surgery for cholangiocarcinoma: the role of liver transplantation.

UNLABELLED: Liver transplantation alone for unresectable hilar cholangiocarcinoma (CCA) is fraught with frequent recurrence and poor long-term survival. The Mayo Clinic developed a novel therapeutic protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) in 1993 to treat patients with unresectable hilar CCA or CCA arising in the setting of PSC. AIM: We recently reviewed our experience over the past 14 years with the specific aim to evaluate the long-term outcomes of CCA patients treated according to our study protocol. METHODS: We analyzed data from all patients enrolled in the Mayo Clinic liver transplant protocol since 1993. Statistical data analysis of recurrence and survival rates was performed using the Kaplan-Meier method. RESULTS: 148 patients were enrolled in the protocol. Of 90 patients who completed neoadjuvant therapy and subsequent OLT, 71 are alive and 19 have died--only 8 due to recurrent CCA. Nineteen patients are awaiting OLT and 39 were removed from the protocol owing to disease progression or death. Overall, 1-, 3-, and 5-year patient survival was 82%, 63%, and 55%, respectively; 1-, 3-, and 5-year survival after OLT was 90%, 80%, and 71%. CONCLUSIONS: Neoadjuvant chemoradiation and OLT achieves significantly lower recurrence and higher long-term survival rates than resection, OLT alone, or medical treatment in hilar CCA. Additional experience at independent transplant centers is necessary to confirm these encouraging results, address the role of neoadjuvant therapy and liver transplantation versus conventional resection, determine appropriate inclusion/exclusion criteria, and define the risk of disease progression while awaiting transplantation.

Impact of pegylated interferon and ribavirin treatment on graft survival in liver transplant patients with recurrent hepatitis C infection.

Recurrent hepatitis C virus (HCV) infection is a major cause of morbidity and mortality after liver transplantation for HCV-related end stage liver disease. Although previous studies have shown a short-term effect of interferon-based treatment on fibrosis progression, it is unclear whether this translates to improved graft survival. We evaluated whether treatment of recurrent HCV leads to an improved graft survival. Cohort study included consecutive HCV patients who underwent liver transplantation between 1 January 1995 and 1 January 2005 in the Mayo Clinic, Rochester, MN. Two hundred and fifteen patients were included in the study. During a median follow-up of 4.4 years (interquartile range 2.2-6.6), 165 patients (77%) had biopsy-proven recurrent HCV infection confirmed by serum HCV RNA testing. Seventy-eight patients were treated. There were no differences in MELD-score, fibrosis stage or time towards HCV recurrence between treated and untreated patients at time of recurrence. There was a trend for greater frequency of acute cellular rejection among untreated patients. The incidence of graft failure was lower for patients treated within 6 months of recurrence compared to patients not treated within this time-period (log rank p = 0.002). Time-dependent multivariate Cox regression analysis showed that treatment of recurrent HCV infection was statistically significantly associated with a decreased risk of overall graft failure (hazard ratio 0.34; CI 0.15-0.77, p = 0.009) and a decreased risk of graft failure due to recurrent HCV (hazard ratio 0.24; CI 0.08-0.69, p = 0.008). In conclusion, although a cause and effect relationship cannot be established, treatment of recurrent HCV infection after liver transplantation is associated with a reduced risk of graft failure.

Clinical Trial of the Pan-Caspase Inhibitor, IDN-6556, in Human Liver Preservation Injury.

Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver transplantation. The aim of the current study was to assess the utility of the pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver transplantation. This report is a post hoc analysis of a Phase II, multi-center, randomized, placebo-controlled, double-blinded, parallel group study. Subjects were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo-Recipient: Placebo); Group 2 (Organ storage/flush: 15 microg/mL-Recipient: Placebo); Group 3 (Organ storage/flush: 5 microg/mL-Recipient: 0.5 mg/kg); and Group 4 (Organ storage/flush: 15 microg/mL-Recipient: 0.5 mg/kg). Liver cell apoptosis was assessed by serum concentrations of the apoptosis-associated CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry. Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver cell apoptosis were reduced in all groups receiving drug as compared to placebo. However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only consistently reduced in Group 2 (drug exposed to organ only). This reduction in serum transaminases was significant and observed across the study. In conclusion, IDN-6556 when administered in cold storage and flush solutions during liver transplantation offers local therapeutic protection against CI/WR-mediated apoptosis and injury. However, larger studies are required to confirm these observations.

Factor XII deficiency acquired by orthotopic liver transplantation: case report and review of the literature.

Transmission of congenital clotting factor deficiencies after orthotopic liver transplantation is rare. There are published reports of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia, protein S, factor VII and factor XI deficiencies. We report a case of transmission of factor XII deficiency with liver transplantation in a patient with Budd-Chiari syndrome. There was a persistent elevation of the activated partial thromboplastin time (aPTT), but no evidence of bleeding while the patient was maintained on warfarin. The presence of a persistently abnormal aPTT may raise suspicion for the presence of a clotting factor deficiency; however, deficiencies of other clotting factors may not be readily apparent on routine blood tests performed in a donor. Being aware of the possibilities of transmission of these inherited deficiencies of coagulation factors will aid in their early detection and management in the transplant donor and recipient.

Preoperative dobutamine stress echocardiography, intraoperative events, and intraoperative myocardial injury in liver transplantation.

INTRODUCTION: The appropriate method of screening for coronary artery disease in patients who present for liver transplantation is currently uncertain. METHODS: We assessed the utility of a screening protocol using dobutamine stress echocardiography (DSE) in 119 patients who underwent liver transplantation. Patients with cardiac risk factors had DSE performed, and those with positive results were referred for coronary angiography. Outcome was myocardial injury during liver transplantation determined by an elevation of cardiac troponin T measured after transplantation. RESULTS: Seventy-three patients had DSE performed; eight were reported as positive for inducible ischemia. Seven of these patients underwent coronary angiography, and one had significant coronary artery disease. Postoperative troponin elevation occurred in 14 patients. There was no significant difference in the prevalence of troponin elevation in those patients with positive DSE versus those with negative DSE. No significant difference was identified in the prevalence of troponin elevation when comparing those patients with cardiac risk factors who underwent DSE with those patients with no risk factors and no DSE performed. DSE had a sensitivity of 0.2 and a specificity of 0.9 for myocardial injury. The prevalence of intraoperative hemodynamic instability was significantly higher in patients who had evidence of myocardial injury, but hemodynamic instability was no more common in patients who had a positive DSE. CONCLUSION: When used in accordance with our protocol a positive DSE does not reliably identify patients at high cardiac risk during liver transplantation, but a negative DSE is strongly predictive of no myocardial injury.

Graft survival in pediatric liver transplantation.

BACKGROUND/PURPOSE: Liver transplantation is standard therapy for children with a variety of liver diseases. The current shortage of organ donors has led to aggressive use of reduced or split grafts and living-related donors to provide timely liver transplants to these children. The purpose of this study is to examine the impact of these techniques on graft survival in children currently treated with liver transplantation. METHODS: Data were obtained on all patients less than 21 years of age treated with isolated liver transplants performed after January 1, 1996 in an integrated statewide pediatric liver transplant program, which encompasses 2 high-volume centers. Nonparametric tests of association and life table analysis were used to analyze these data (SAS v 6.12). RESULTS: One hundred twenty-three children received 147 grafts (62 at the University of Florida, 85 at the University of Miami). Fifty-two (36%) children were less than 1 year of age at time of transplant, and 80 (55%) were less than 2 years of age. Patient survival rate was identical in the 2 centers (1-year actuarial survival rate, 88.4% and 87.1%). Twenty-five (17%) grafts were reduced, 28 (19%) were split, 6 were from living donors (4%), and 88 (60%) were whole organs. One-year graft survival rate was 80% for whole grafts, 71.6% for reduced grafts, and 64.3% for split grafts (P =.06). Children who received whole organs (mean age, 6.1 years) were older than those who received segmental grafts (mean age, 2.5 years; P <.01). Multifactorial analysis suggested that patient age, gender, and use of the graft for retransplant did not influence graft survival, nor did the type of graft used influence patient survival. CONCLUSIONS: The survival rate of children after liver transplantation is excellent independent of graft type. Use of current techniques to split grafts between 2 recipients is associated with an increased graft loss and need for retransplantation. Improvement in graft survival of these organs could reduce the morbidity and cost of liver transplantation significantly in children.

Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease.

Although nonalcoholic steatohepatitis (NASH) has generally been considered a benign condition, the increasing prevalence and severity of obesity has heightened concerns about the frequency with which NASH progresses to end-stage liver disease. The aim of this study is to determine the frequency, clinical features, and posttransplantation history of decompensated liver disease secondary to NASH. The frequency of NASH as a cause of end-stage liver disease was prospectively determined in patients evaluated for liver transplantation. NASH was considered to be the primary cause of liver disease in patients who had histological evidence of steatohepatitis and in whom chronic liver diseases other than NASH were excluded. Posttransplantation histological characteristics were also determined in patients with NASH and compared with those of patients with pretransplantation diagnoses of cholestatic liver diseases, alcoholic disease, and hepatitis C. Of 1,207 patients evaluated for liver transplantation during the study period, 31 patients (2.6%) had NASH as the primary cause of liver disease. In the same period, 546 liver transplantations were performed, 16 of which (2.9%) were for end-stage disease secondary to NASH. Posttransplantation steatosis was seen in 60% of transplant recipients with NASH versus 5% of those with cholestatic disease, 15% of those with alcoholic disease, and 15% of those with hepatitis C. Steatohepatitis recurred in 33% of transplant recipients with NASH, with progression to cirrhosis in 12.5%. NASH can progress to end-stage liver disease in a minority of affected patients and was the primary cause of liver disease in 2.9% of patients evaluated for liver transplantation at our center. Recurrence of steatosis and NASH is frequent and can be severe after liver transplantation.

Recurrent autoimmune hepatitis after orthotopic liver transplantation.

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 +/- 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 +/- 0.9 years of observation. Five-year patient (86% v. 82%; P =.9) and graft (86% v. 67%; P =.5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v. 40%; P =.008) and healthy subjects (100% v. 49%; P =.01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status.

Comparative allograft histology after liver transplantation for cryptogenic cirrhosis, alcohol, hepatitis C, and cholestatic liver diseases.

BACKGROUND: End-stage liver disease for which no cause can be identified, cryptogenic cirrhosis, is a common indication for liver transplantation. Allograft inflammation and fibrosis have been reported to recur with similar frequencies after liver transplantation for cryptogenic cirrhosis and hepatitis C (HCV). METHODS: We determined sequential posttransplant allograft histology in four groups of recipients: 31 transplanted for cryptogenic cirrhosis, 70 for cholestatic etiologies, 40 for alcoholic liver disease, and 56 for HCV. Modified hepatitis activity index (HAI) and fibrosis stage were determined at 4 months, 1 year, and at most recent biopsy posttransplantation. RESULTS: The prevalence of HAI > or = 2 among cryptogenic recipients was similar to that of cholestatic and alcoholic recipients at 4 months, 1 year, and at most recent evaluation (mean 45+/-17 months posttransplantation). For HCV-infected recipients, the frequency of HAI > or = 2 was more than for cryptogenic recipients at 1 year (52 vs. 29%, P=0.04) and at most recent evaluation (64 vs. 15%, P=0.003). Fibrosis scores for cryptogenic, cholestatic, and alcoholic recipients were similar at all timepoints. The proportion of HCV-infected recipients with fibrosis stage >2 was more than that of cryptogenic recipients at 4 months (29 vs. 12%, P=0.05), 1 years (46 vs. 7%, P=0.0002), and at most recent evaluation (42 vs. 15%, P=0.06). None of the cryptogenic recipients developed cirrhosis. RESULTS: The frequency of elevated HAI and fibrosis stage in recipients who undergo transplantation for cryptogenic cirrhosis is similar to that of recipients who undergo transplantation for cholestatic etiologies and significantly less than that of HCV-infected recipients. Fibrosis stage and HAI are generally stable after transplantation for cryptogenic cirrhosis. These data do not suggest a viral etiology of liver disease in the majority of patients with cryptogenic cirrhosis.

Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation.

In the setting of moderate to severe pulmonary artery hypertension, orthotopic liver transplantation (OLT) may be complicated by pulmonary hemodynamic instability and cardiopulmonary mortality. We retrospectively studied the relationship between cardiopulmonary-related mortality and initial (untreated) pre-OLT pulmonary hemodynamics in 43 patients with portopulmonary hypertension who underwent attempted OLT. Thirty-six patients were reported in 18 peer-reviewed studies, and 7 patients underwent OLT at our institution since 1996. Transplantation procedure outcome, mean pulmonary artery pressure (MPAP), pulmonary vascular resistance (PVR), cardiac output, pulmonary capillary wedge pressure, and transpulmonary gradient (TPG) are summarized. Overall mortality was reported in 15 of 43 patients (35%). Fourteen of the 15 deaths (93%) were primarily related to cardiopulmonary dysfunction. Two deaths were intraoperative, 8 deaths occurred during the transplantation hospitalization, and 4 patients died of cardiopulmonary deterioration posthospitalization. In 4 patients, the transplantation procedure could not be successfully completed. Cardiopulmonary mortality was associated with greater pre-OLT MPAP (49 +/- 14 v 36 +/- 7 mm Hg; P <.005), PVR (441 +/- 173 v 261 +/- 156 dynes.s.cm(-5); P <.005), and TPG (37 +/- 13 v 22 +/- 10 mm Hg; P <.005). MPAP of 50 mm Hg or greater was associated with 100% cardiopulmonary mortality. In patients with an MPAP of 35 to less than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater, the mortality rate was 50%. No mortality was reported in patients with a pre-OLT MPAP less than 35 mm Hg or TPG less than 15 mm Hg. Cardiopulmonary-related mortality in OLT patients with portopulmonary hypertension was frequent and associated with significantly increased pre-OLT MPAP, PVR, and TPG compared with survivors. Treated or untreated, we recommend intraoperative cancellation or advise against proceeding to OLT for an MPAP of 50 mm Hg or greater. Patients with an MPAP of 35 to less than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater appear to be at high risk for cardiopulmonary-related mortality after OLT. A prospective study is needed to define optimal pretransplantation treatments and pulmonary hemodynamic criteria that minimize OLT mortality associated with portopulmonary hypertension.