Adam E. Levy

Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis.

Background. Antiviral prophylaxis has been shown to decrease the incidence of cytomegalovirus (CMV) disease in organ transplant recipients, but whether CMV disease that occurs despite prophylaxis is associated with mortality remains unknown. Methods. The clinical features and risk factors for CMV disease in a cohort of liver transplant recipients who received antiviral prophylaxis were assessed retrospectively. Cox proportional hazard regression was used to assess the relationship of CMV to mortality during the first posttransplant year. Results. CMV disease developed in 37 of 437 (8.5%) recipients at a median of 4.5 (range, 2.5 to 12) months posttransplant and was associated only with donor-seropositive/recipient-seronegative serostatus in multivariate analysis (P<0.0001). Mortality at 1 year was 12% (51 of 437) and was infection-associated in 49% of cases. In multivariate analysis, CMV disease was independently associated with overall mortality at 1 year (HR, 5.1, P=0.002) and even more strongly with infection-associated mortality (HR 11, P=0.002). There was no association of CMV with noninfection-associated mortality (P>0.05). Conclusions. Late CMV disease is an important clinical problem in liver transplant recipients who receive antiviral prophylaxis, and is strongly and independently associated with mortality. Strategies to prevent late CMV disease are warranted.

Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors

The use of donation after cardiac death (DCD) donor hepatic allografts is becoming more widespread; however, there have been published reports of increased graft failure from specific complications associated with this type of allograft. The complication of ischemic cholangiopathy (IC) has been reported to occur more frequently after the use of DCD hepatic allografts. We report the results of 52 liver transplants from DCD donors and the factors that influenced the development of IC. We conducted a retrospective review of all DCD and donation after brain death (DBD) donor liver recipients from September 2003 through December 2006 at a single institution. Survival and complication rates were compared between the 2 groups. The Cox proportional hazards model was then used to identify recipient and donor factors that predict the development of IC in the DCD group. There was no difference in 1‐year patient or graft survival rates between the 2 groups. There was no incidence of primary nonfunction from the DCD allografts. Hepatic artery complications and anastomotic bile duct complications were comparable in the 2 groups. There was, however, an increased risk for the development of IC in the DCD group (13.7% versus 1%, P = 0.001). Donor weight >100 kg and total ischemia times ≥9 hours, in donors older than 50 years of age, predicted the development of IC in the DCD group. In conclusion, there is a higher incidence of IC in recipients receiving DCD donor livers; however, patient and graft outcomes with DCD donors remain comparable to those with DBD donors. Careful donor selection may improve utilization of these grafts. Liver Transpl 14:604–610, 2008.

Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: Implications for surveillance studies and new adjuvant therapies

The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We conducted a retrospective review of 834 consecutive liver transplants from 1/1/1996 to 12/31/2005 (mean follow‐up 1303 ± 1069 days) at one institution and 352 consecutive transplants from 1/2/2002 to 12/31/2005 (mean follow‐up 836 ± 402 days) at a second institution. The test cohort comprised patients identified with HCC in their explanted livers from 1/1/2001 to 12/31/2005 at the first institution. Explant pathology and donor and recipient characteristics were reviewed to determine factors associated with HCC recurrence. These predictors were validated in the remaining liver transplant recipients. The test cohort had 116 patients with findings of HCC in their explanted livers. Twelve patients developed recurrent HCC. Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (>4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well‐differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from −3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. In conclusion, patients transplanted for HCC with a PCRS of ≤0 have a low risk of recurrence. Patients with a PCRS of 1 or 2 have a moderate risk of recurrence, and those with a PCRS of ≥3 have a high risk for recurrence. Liver Transpl 14:956–965, 2008.

Acquiring basic surgical skills: is a faculty mentor really needed?

BACKGROUND We evaluated the impact of expert instruction during laboratory-based basic surgical skills training on subsequent performance of more complex surgical tasks. METHODS Forty-five junior residents were randomized to learn basic surgical skills in either a self-directed or faculty-directed fashion. Residents returned to the laboratory 2 days later and were evaluated while performing 2 tasks: skin closure and bowel anastomosis. Outcome measures included Objective Structured Assessment of Technical Skill, time to completion, final product quality, and resident perceptions. RESULTS Objective Structured Assessment of Technical Skill, time to completion, and skin esthetic ratings were not better in the faculty-directed group, although isolated improvement in anastomotic leak pressure was seen. Residents perceived faculty-directed training to be superior. CONCLUSIONS Our data provided minimal objective evidence that faculty-directed training improved transfer of learned skills to more complex tasks. Residents perceived that there was a benefit of faculty mentoring. Curriculum factors related to training of basic skills and subsequent transfer to more complex tasks may explain these contrasting results.

Transiently altered acetaminophen metabolism after liver transplantation

Background and objectives: Acetaminophen (INN, paracetamol) is metabolized to N‐acetyl‐p‐benzoquinone imine (NAPQI), a hepatotoxic metabolite, predominantly by cytochrome P450 (CYP) 2E1. Alterations in drug metabolism occur after organ transplantation. This study was designed to characterize acetaminophen disposition during the first 6 months after liver transplantation.

Rescue of Acute Portal Vein Thrombosis After Liver Transplantation Using a Cavoportal Shunt at Re-transplantation

Background: Portal vein thrombosis is a rare but devastating complication following orthotopic liver transplantation. Fulminant liver failure ensues with acute portal vein thrombosis after transplantation limiting the treatment options.

Human Liver Cytochrome P450 2D6 Genotype, Full-length Messenger Ribonucleic Acid, and Activity Assessed with a Novel Cytochrome P450 2D6 Substrate

The goal of this study was to develop and validate a cytochrome P450 (CYP) 2D6 probe substrate with improved sensitivity to elucidate the relationship of CYP2D6 ribonucleic acid transcript levels, genotype, and enzyme activity in human liver biopsy samples.