Robert M. Goldstein

The use of marginal donors for liver transplantation: A retrospective study of 365 liver donors

A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and analyzed retrospectively to identify risk factors associated with poor graft function and to study the outcome of grafts retrieved from marginal donors. The donor mean age was 27.1 years (8-69 years). Mean ICU donor stay was 2.7 days (range 0 to 18 days), and the mean ischemic time was 8.6 hr (range 3 to 22 hr). The pancreas was retrieved in 39 donors. Donors weight above 100 kg was the only variable found to be associated with both significantly increased 3-month graft loss (P less than 0.01) and early hepatocellular damage--AST or ALT greater than 2000 U/ml, 1st day posttransplant (P less than 0.02). Prolonged stay in the ICU (greater than 3 days), although associated with a significantly increased rate of hepatocellular damage (P less than 0.05), did not affect early graft survival. A systolic blood pressure less than 90 mmHg despite the use of high-dose dopamine (greater than 15 micrograms/mg/min), but not each of these variables itself, was also associated with a significantly increase rate of hepatocellular damage (P less than 0.001). All other variables, including age greater than 50, ischemic time greater than 12 hr, combined liver-pancreas procurement, and liver function test abnormalities, did not affect the outcome. We conclude that extending our limits to accept donors of the higher age group and those who have moderately abnormal liver function tests or a prolonged ischemic time will not jeopardize our results. It is suggested to perform liver biopsy in overweight donors during the retrieval to prevent using grafts with severe fatty infiltration. It is hypothesized that hormonal changes, starvation, and increased risk to develop infection might jeopardize the outcome of grafts from donors with a prolonged ICU stay. Although 70% of the early hepatocellular injuries are reversible, the remaining 30% result in graft failure.

HEPATIC ARTERY STENOSIS AFTER LIVER TRANSPLANTATION-INCIDENCE, PRESENTATION, TREATMENT, AND LONG TERM OUTCOME1

Little is known about hepatic artery (HA) patency and patient clinical course when the nonthrombosed HA has been revised. We undertook this study to evaluate the risk factors in the development of HA stenosis and to assess the impact of HA revision on the outcome. A total of 857 adult consecutive OLT in 780 patients performed over a 6-year period were studied. Patients who underwent revision of their nonthrombosed but stenotic HA were reviewed for patient/graft survival, method of HA revision, incidence of biliary strictures, and long-term HA patency. Overall 39 patients (5%) with 41 allografts underwent HA revision for stenosis. Median time to diagnosis was 100 days posttransplant (range 1-1220 days). HA flow at the time of OLT was found to be the only significant variable of an anastomotic stenosis. No risk factor could be identified for the graft HA stenosis. Treatment methods included resection of the stenotic segment with primary reanastomosis (n = 17), aortohepatic iliac artery graft (n = 11), interposition vein graft (n = 4), vein patch angioplasty (n = 2), interposition artery graft (n = 1), and percutaneous transluminal balloon angioplasty (n = 6). Postrevisional HA patency was demonstrated in 32 (78%) cases. At a median follow-up of 25 months, 26 patients (67%) were asymptomatic with good liver function. Nine patients had developed biliary strictures. Seven patients had undergone retransplantation and 8 patients had died. The actuarial patient and graft survivals at 4 years in the patients with revised HA were 65% and 56%, respectively. HA stenosis requiring revision is an infrequent occurrence after OLT. Long-term patency of the revised HA is good. Revision of the HA may help prevent biliary strictures and allow for good long-term graft function in the majority of patients.

Limiting Hepatitis C Virus Progression in Liver Transplant Recipients Using Sirolimus-Based Immunosuppression

Hepatitis C virus (HCV) causes progressive liver fibrosis in liver transplant recipients and is the principal cause of long‐term allograft failure. The antifibrotic effects of sirolimus are seen in animal models but have not been described in liver transplant recipients. We reviewed 1274 liver recipients from 2002 to 2010 and identified a cohort of HCV recipients exposed to sirolimus as primary immunosuppression (SRL Cohort) and an HCV Control Group of recipients who had never received sirolimus. Yearly protocol biopsies were done recording fibrosis stage (METAVIR score) with biopsy compliance of >80% at both year one and two. In an intent‐to‐treat analysis, the SRL Cohort had significantly less advanced fibrosis (stage ≥2) compared to the HCV Control Group at year one (15.3% vs. 36.2%, p < 0.0001) and year two (30.1% vs. 50.5%, p = 0.001). Because sirolimus is sometimes discontinued for side effects, the SRL Cohort was subgroup stratified for sirolimus duration, showing progressively less fibrosis with longer sirolimus duration. Multivariate analysis demonstrated sirolimus as an independent predictor of minimal fibrosis at year one, and year two. This is the first study among liver transplant recipients with recurrent HCV to describe the positive impact of sirolimus in respect of reduced fibrosis extent and rate of progression.

Hepatocellular carcinoma: management of an increasingly common problem

Hepatocellular carcinoma (HCC) is a common cancer that typically occurs in the setting of cirrhosis and chronic hepatitis virus infections. Hepatitis B and C account for approximately 80% of cases worldwide. HCC is currently the fifth most common malignancy in men and the eighth in women worldwide; its incidence is increasing dramatically in many parts of the world. Recognition of those at risk and early diagnosis by surveillance with imaging, with or without serologic testing, are extremely important. Many highly effective and even curative therapies are now available and include resection, liver transplantation, and local ablation. Appropriate application of these interventions offers hope of prolonged survival to many patients with this otherwise lethal complication of liver disease.

Hepatorenal syndrome: A proposal for kidney after liver transplantation (KALT)

Hepatorenal syndrome (HRS) is a well‐recognized complication of end‐stage liver disease. Once thought to be a reversible condition with liver transplantation (LT) alone, HRS may directly contribute to the requirement for long‐term dialysis posttransplant. As a result, discussion has now focused on whether or when a kidney allograft should be considered for these patients. Using the International Ascites Club guidelines with a pretransplant serum creatinine (SCr) >2.0 mg/dL to define HRS, 130 patients undergoing LT over a 10‐yr period were identified, for an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%, and 68%, and 62%, respectively. Survival was significantly worse when compared to non‐HRS patients undergoing LT over the same study period (P = 0.0001). For patients presenting with type 2 HRS, 7 patients (6%) developed irreversible kidney failure posttransplant compared to 0.34% in the non‐HRS population (P < 0.0001). Five of these patients died within 1 yr with a median survival time of 139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS is not recommended. However, an improvement in outcome can be accomplished by addressing those patients who require dialysis greater than 60 days posttransplant. We propose a role for kidney after liver transplantation (KALT) in select HRS patients. Liver Transpl 13:838–843, 2007.

Alpha fetoprotein, ultrasound, computerized tomography and magnetic resonance imaging for detection of hepatocellular carcinoma in patients with advanced cirrhosis

Backgroundu2002 Serum alpha fetoprotein (AFP), ultrasound, computerized tomography scanning, and magnetic resonance imaging are commonly used to screen for hepatocellular carcinoma (HCC) in patients with cirrhosis.

Clinical outcomes from hepatic artery stenting in liver transplantation

Hepatic artery stenosis after liver transplantation may affect liver function and result in hepatic artery thrombosis. Surgical reconstruction has been the first choice for treatment. Interventional radiologic technique can be used, but there is no report on long‐term outcome. The aim of this paper is to assess current outcome and complications of hepatic artery stenting. Twenty‐six adult patients were stented for hepatic artery stenosis between 1998 and 2003. Nine patients had previous surgical reconstruction for hepatic artery stenosis. Seventeen patients suffered newly developed hepatic artery stenosis. Three patients were retransplanted. After stenting, the patients were followed by Doppler ultrasound at day 1, 1 month, and 6 months. Angiography was scheduled in 6 months. Four patients died within 2 months. The other 22 patients were followed for mean 31 ± 14 months (8‐71 months). One of 22 patients died from renal failure 2 years later. Twelve patients hepatic arteries looked normal after stenting. Restenosis was seen in 8 patients (36%). Other complications were artery thrombosis (n = 1) and long segment stricture (n = 1). In 2 patients (25%) restenosis resulted in thrombosis. Six of the 8 patients who developed recurrent stenosis were successfully treated interventionally: restent (n = 5) and balloon dilation (n = 3). However, 3 patients (38%) restenosed. Kaplan‐Meier complication‐free survival was 54% at 1 year after stenting. In conclusion, hepatic artery stenting is a viable treatment for hepatic artery stenosis with reasonable results. Stenting is useful as adjuvant treatment after surgical revision. Liver Transpl 12:422–427, 2006.

Readmission to the intensive care unit after liver transplantation

ObjectiveWe undertook this study to understand the factors at our transplant center that contribute to patients’ return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. DesignA retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. SettingA large metropolitan tertiary care center and adult liver transplant center. PatientsA total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. InterventionReadmission to the intensive care unit after adult liver transplantation and discharge from that unit. Main ResultsOnly recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. ConclusionsWe conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid hypervolemia is essential. Readmitted patients have a greater resource utilization and have lower survival rates.

A comparison of UW with eurocollins preservation solution in liver transplantation

Fifty consecutive liver transplants were performed using livers perfused with and stored in University of Wisconsin preservation solution. These grafts were compared with the preceding 55 consecutive transplants performed using livers perfused and preserved with Eurocollins solution. The purpose of the study was to determine if organs preserved with UW solution functioned better after transplantation than organs preserved with Eurocollins. Extensive retrospective analysis of prospectively accumulated data included enzyme levels through 30 days, cost and length of hospital stay, blood product usage, and ischemia time. Average age of patients in the UW group was 47.1 years compared with 39.6 years in the EC group (P less than 0.05); cold ischemia time was 7.21 hr in the UW group compared with 5.21 in EC (P = 0.0001). Total bilirubin values were significantly lower on days 0-6 and day 14, but not day 30, in the UW group. Aspartate aminotransferase was significantly lower in the UW group on days 0-1, 3-6, and 14, but not on day 3 or day 30. Prothrombin times were significantly lower in the UW group across all times (days 0-6, 14, and 30). Intraoperative and postoperative use of packed red blood cells and fresh frozen plasma was lower in the UW group (P less than or equal to .05). Also, total hospital days, intensive care unit days, and hospital cost to the patient were lower in the UW group (P less than or equal to .05). A second analysis was done comparing only nonemergent transplants from both groups. These results confirmed the initial analysis of a longer cold ischemia time in the UW group (P less than 0.001), and improved enzyme values in the TBR, AST, and PT in the UW group (P less than 0.05). Also, hospital cost in the UW group was again lower (P less than 0.05). In this nonrandomized study, the cold ischemia time was increased but kept close to that of the control group. We conclude that UW solution is an improved donor liver preservation solution on the basis of improved enzyme values, decreased blood usage, shorter hospital stay, and lower hospital charges.

Improved results of transplantation for hepatocellular carcinoma: A report from the international registry of hepatic tumors in liver transplantation

Improved outcome after liver transplantation (LTX) for hepatocellular carcinoma (HCC) made LTX a legitimate treatment of the disease. We analyzed trends of LTX for HCC with tumors known before transplantation in 902 patients in a large international registry across 3 periods: 1983–1990, 1991–1996, and 1997–2005. Patient survival improved gradually across eras, with 5‐year survival rates of 25.3%, 44.4%, and 67.8%, respectively (P < 0.0001), and the 5‐year tumor recurrence rate declined from 59% to 41.3% and 15%, respectively (P < 0.0001). The number of HCC nodules and tumor size decreased over time, and there were fewer moderately or poorly differentiated tumors. Tumors > 5 cm decreased from 54.5% to 31.7% and 11.7%, respectively (P < 0.0001), and LTX with ≥4 nodules decreased from 38.9% to 23.5% and 15.1%, respectively (P = 0.0044). Poorly differentiated tumors decreased from 37.2% to 31.8% and 20.3%, respectively (P = 0.0005). Tumor microvascular invasion remained at 21.2% to 23.8% despite changes in patient selection over time (P = 0.7124). Stepwise Cox regression analysis (n = 502) showed significant risk for tumor recurrence and patient survival for transplants before 1997 [hazard ratio (HR), 1.82 and 1.88, respectively], tumor size > 6 cm (HR, 2.09 and 1.76), microvascular invasion (HR, 1.75 and 1.69, respectively), and alpha‐fetoprotein > 200 (HR, 2.45 and 2.32, respectively). In conclusion, outcome after LTX for HCC has improved continuously over the past 20 years. Improved perioperative care and better patient selection may partially explain the improved outcome after LTX for HCC. Liver Transpl 15:574–580, 2009.