Thomas Bak

Impact of pretransplant diagnosis of hepatocellular carcinoma on cadveric liver allocation in the era of MELD

The allocation system based on the Model for End‐stage Liver Disease (MELD) has led to more patients diagnosed with hepatocellular carcinoma (HCC) being transplanted. We hypothesized that more patients misdiagnosed with HCC are also being transplanted, leading to inappropriate organ allocation. Therefore, we retrospectively analyzed all liver transplants at our center from July 14, 2000, to October 22, 2002 (N = 172; 129 pre‐MELD, 43 post‐MELD), comparing pretransplant HCC diagnosis to explant histology. Thirty patients met the United Network for Organ Sharing (UNOS) diagnostic criteria for pretransplant HCC diagnosis. There were 25 men (median age, 52.5 yr), and 80% had hepatitis C. The proportion of patients transplanted who had an HCC diagnosis increased from 12% (15/129) pre‐MELD to 35% (15/43) post‐MELD implementation (P < 0.01). Three of 15 (20%) transplanted pre‐MELD and 5 of 15 (33%) transplanted post‐MELD lacked HCC in the explant (P = 0.10). Of the three false‐positives pre‐MELD, one was Status 2B already, and two received living‐donor livers. Of the 5 false‐positives post‐MELD, three had score upgrades that led to early transplantation (13 to 29, 20 to 29, and 9 to 24) while two had MELD scores of 35 and 36 already. The percentage of organs that could have gone to patients with more advanced liver disease without HCC increased from 0% (0/129) pre‐MELD to 7% (3/43) post‐MELD (P < 0.01). Since the implementation of MELD, the proportion of patients transplanted who had an HCC diagnosis nearly tripled, and a small but significant proportion of organs are now going to patients misdiagnosed with HCC. More stringent HCC diagnostic criteria will be required to decrease the effect that misdiagnosis has on organ allocation. (Liver Transpl 2004;10:42–48.)

Hepatic Artery Chemoembolization for Hepatocellular Carcinoma in Patients Listed for Liver Transplantation

We retrospectively analyzed all listed patients having hepatic artery chemoembolization (HACE) for hepatocellular carcinoma (HCC) stage T2 or less. Outcomes were transplantation, waiting list removal, death, and HCC recurrence. Twenty patients (mean age 55.7 years; 15 males) were identified. Twelve (60%) were transplanted, seven (35%) were removed from the list and one (5%) remains listed. Fourteen (70%) are alive. All 12 transplanted patients are alive (mean 2.94 years); one of seven removed from the list is alive (mean 1.45 years). Survival was significantly higher for those transplanted or listed vs. removed from the list (100% vs. 14.3%, p = 0.0002). No HCCs recurred. Three patients (15%) were removed from the list after prolonged waiting times before MELD. Hepatic artery chemoembolization induced deterioration and removal from the list of one (5%) patient. Survival for those transplanted was excellent(100%), but overall survival was significantly lower (61.3%) at a mean 5.48 years. Hepatic artery chemoembolization for listed patients with ≤€ T2 stage HCC is beneficial, but must be weighed against decreased waiting times and risk of HACE‐induced deterioration. This balance is influenced greatly by the MELD systems determination of waiting times for HCC patients.

Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal.

Our center has attempted to minimize corticosteroid (CS) use in all of our orthotopic liver transplantation (OLT) recipients. Because patients with autoimmune hepatitis (AIH) typically require CSs after transplantation, we reviewed our experience in this cohort of patients to determine (1) patient outcomes including recurrent disease and (2) long‐term requirements for CS use in AIH patients. From 1988 to 2006, 1102 OLTs were performed in 1032 adult patients at the University of Colorado, of whom 66 (6%) with AIH received 68 allografts. Recurrence was defined by a clinically worsening examination and histological evidence from biopsy. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Twelve potential predictors of CS discontinuation were considered: age, gender, presence of inflammatory bowel disease (IBD), type of graft (cadaver or living donor), recurrence of AIH, warm ischemia time, follow‐up time (time since transplant), and immunosuppressants (cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil). Overall survival at 5 years was 91%. The 1‐ and 5‐year recurrence‐free survival was 88% and 59%, respectively. Risk (incidence) of recurrent AIH at 1, 3, and 5 years was 12%, 26%, and 36%, respectively. Disease recurred in 23 of 66 patients or 34.8%. Of the 23 patients who developed recurrent disease, none received a second transplant because of recurrent disease. CSs were withdrawn in 50% of patients at the time of review. Only 2 factors on multivariate analysis were strongly associated negatively with CS withdrawal: (1) an increasing dose of the immunosuppressant and (2) the presence of IBD. Controlling for these other factors, we found that recurrent disease did not strongly influence CS withdrawal. In conclusion, outcomes in AIH patients were quite favorable, and none of the patients required retransplantation for recurrent AIH. With a CS minimization approach, one‐half of the patients were able to remain CS‐free. Liver Transpl 14:1281–1286, 2008.

The role of TIPS for portal vein patency in liver transplant patients with portal vein thrombosis

The purpose of this research was to study the efficacy and outcomes of transjugular intrahepatic shunt (TIPS) in end‐stage liver disease (ESLD) patients with portal vein thrombosis (PVT) eligible for orthotopic liver transplant. Nine consecutive patients with PVT underwent TIPS as a nonemergent elective outpatient procedure. The primary indication for TIPS was to maintain portal vein patency for optimal surgical outcome. Eight patients underwent contrast enhanced computed tomography (CT) and 1 magnetic resonance imaging diagnosing PVT. Shunt creation was determined by available targets at the time of TIPS and by prior imaging. Patients were followed with portography, ultrasound, CT, or magnetic resonance imaging, and the luminal occlusion was estimated before and after TIPS. Primary endpoints were transplantation, removal from the transplant list, or death. Stabilization, improvement, or complete resolution of thrombosis was considered successful therapy. Failures included propagation of thrombosis or vessel occlusion, and poor surgical anatomy due to PVT. Of 9 patients with PVT, TIPS was successfully placed in all patients without complication or TIPS‐related mortality. Eight of 9 patients (88.8%) had improvement at follow‐up. One patient failed therapy and re‐thrombosed. Two patients (22.2%) were transplanted without complication and had no PVT at the time of transplant. Eight of 9 patients were listed for transplant at the time of their TIPS. Eight of 9 PVTs were nonocclusive. Four of 9 patients (44%) had evidence of cavernous transformation. Two patients expired during follow‐up 42 and 44 months after TIPS. Three patients remain on the transplant list. One patient has not been listed due to nonprogression of disease. One patient has been removed from the transplant list because of comorbid disease. In conclusion, TIPS is safe and effective in patients with PVT and ESLD requiring transplant. Patients can be successfully transplanted with optimal surgical anatomy. Liver Transpt 12:1544–1551, 2006.

Predictors of long‐term outcome following liver transplantation for hepatocellular carcinoma: a single‐center experience

Orthotopic liver transplantation (OLT) is increasingly being applied for cure in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC). In recipients with limited tumor burden, OLT achieves reasonable long‐term outcome. This study sought to identify clinical and pathologic variables predictive of long‐term disease‐free survival and the presence of vascular invasion. From 1992 to 2006, 130 patients underwent OLT for cirrhosis and HCC. Malignancy was diagnosed in 107 patients prior to OLT and in 23 patients on pathologic examination of the explant. Nine clinical and pathologic variables were considered including: TNM stage, nodularity, vascular invasion, Milan criteria, incidental lesion, differentiation, tumor size, preOLT transarterial chemoembolization (TACE), and administration of sirolimus‐based immunosuppression. The overall incidence of HCC recurrence was 17% with the majority (82%) being stage III. Cumulatively, tumor recurrence‐free survival (RFS) is 84, 74, and 67% at 1, 3, and 5 years respectively. Independent predictors of RFS included stage III and poorly differentiated lesions (P < 0.05). Furthermore, stage III tumors and those >3.5 cm in size were predictive of vascular invasion. Importantly, preOLT, TACE and postOLT sirolimus had no influence on survival. Pathologic variables including tumor stage and grade have a significant impact on outcome. Importantly, it seems that TACE and sirolimus had no beneficial effect.

Comprehensive cost comparison of adult-adult right hepatic lobe living-donor liver transplantation with cadaveric transplantion

Background. An important long-term consideration for living-donor liver transplantation (LDLT) is the expense compared with cadaveric-liver transplantation. LDLT is a more complex procedure than cadaveric transplantation and the cost of donor evaluation, donor surgery, and postoperative donor care must be included in a cost analysis for LDLT. In this study, we compare the comprehensive cost of LDLT with that of cadaveric-liver transplantation. Methods. All costs for medical services provided at our institution were recorded for 24 LDLT and 43 cadaveric recipients with greater than 1 year follow-up transplanted between August 1997 and April 2000. The donor costs include donors evaluated and rejected, donors evaluated and accepted, donor right hepatectomy costs, and donor follow-up costs (365 days postdonation). LDLT and cadaveric recipient costs include medical care 90 days pre-LDLT, recipient transplant costs, and recipient follow-up costs (365 days posttransplant) including retransplantation. Cost is expressed as an arbitrary cost unit (CU) that is a value between

Liver Transplantation for Primary Biliary Cirrhosis: Results of Aggressive Corticosteroid Withdrawal

500 to

Adult right lobe live donor liver transplantation without reconstruction of the middle hepatic vein: a single-center study of 109 cases.

1,500. Results. Total LDLT costs (evaluations of rejected donors+evaluations of accepted donors+donor hepatectomy+donor follow-up care for 1 year+pretransplant recipient care [90 days pretransplant]+recipient transplantation+recipient 1-year posttransplant care)= 162.7 CU. Total mean cadaveric transplant costs (pretransplant recipient care [90 days pretransplant]+recipient transplantation [including organ acquisition cost]+recipient 1-year posttransplant care)= 134.5 CU, (P =ns). Conclusions. The total comprehensive cost of LDLT is 21% higher than cadaveric transplantation, although this difference is not significant.

Pediatric liver transplantation.

INTRODUCTION A subset of patients with primary biliary cirrhosis (PBC) may require long-term corticosteroid (CS) therapy following liver transplantation (OLT) due to concern over the possibility of recurrence. Our center has attempted to minimize CS use in all of our OLT recipients. In this study, we review our experience in this cohort to determine (1) patient outcome including PBC recurrence following transplantation and (2) the long-term requirement for CS use in PBC patients. METHODS From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado, of which 70 patients (6.8%) with PBC received 74 allografts. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Thirteen potential predictors of CS discontinuation were considered: age, gender, body mass index (BMI), race, type of graft (cadaveric or living donor [LD]), recurrence of PBC, warm ischemia time, and immunosuppressant. RESULTS Overall survival at 5 years was 85%. The 1-, 5-, and 10-year recurrence-free survivals were 90%, 72%, and 54%, respectively. PBC recurred in 18 patients (25.7%). Of these, none received a second transplant due to disease recurrence. At the time of last follow-up, 73% of recipients were steroid free. Independent predictors of CS discontinuation are age (>54; P = .0059) and LD graft type (P = .0008). Conversely, cyclosporine (P = .0007), female gender (P = .0216), and BMI > 31 (P = .0306) were negatively associated with CS withdraw. Importantly, steroid discontinuation did not influence PBC recurrence. CONCLUSIONS While long-term outcomes in PBC patients are favorable, disease recurrence can generally be managed medically without the need for a second transplant. Using an aggressive CS minimization approach, nearly three-quarters of the patients were CS free at the time of last follow-up. Increasing age and LD grafts were associated with successful CS withdraw. Conversely, cyclosporine use, female gender, and increasing BMI were associated with unsuccessful steroid discontinuation.

Sirolimus and liver transplantation: clinical implications for hepatocellular carcinoma

We report our experience in adult-to-adult right hepatic lobe living donor liver transplantation (ALDLT) using extension of the hepatectomy transection line medially to incorporate the right middle hepatic vein branches into the donor graft. One hundred and nine ALDLT were performed at the University of Colorado from August 1997 to December 2005. Donors were screened preoperatively for hepatic venous anatomy compatible with this technique. Of the 109 ALDLT, the first 10 did not include the right middle hepatic vein branches in the graft. As such, three patients required retransplantation, two from graft loss because of venous congestion. Of the next 99 transplants, only 11 required retransplantation and none because of venous congestion. This approach allows adequate venous outflow through the right hepatic vein more than 1 cm, which is demonstrated by the absence of graft loss from venous congestion and superior graft survival.