Faculty Bibliography

BACKGROUND & AIMS: Prevention of recurrent hepatitis C virus (HCV) following liver transplant (LT) with pre-LT antiviral therapy is limited by poor tolerability and efficacy. We aimed to evaluate the safety and efficacy of NS3/4A protease inhibitor (PI)-based triple therapy in patients awaiting LT. METHODS: Consecutive patients treated with triple therapy pre-LT from two centers were prospectively enrolled in an observational cohort. Overall 12 week sustained virological response (SVR12) was the primary outcome. Pre- and post-LT (pTVR) virological response rates and safety were secondary outcomes. RESULTS: Twenty-nine patients (mean age 57.9, 79% male, 66% prior non-responders) were treated with telaprevir (93%) or boceprevir-based (7%) triple therapy for a median (range) of 27 (3-50) weeks, including a pegylated-interferon and ribavirin lead-in in 18%. Median (range) MELD at treatment was 8 (6-16), 39% had hepatocellular carcinoma and all patients were Child-Turcotte-Pugh class A (62%) or B (38%). Twelve patients underwent LT, 75% with undetectable viral load. The overall SVR12 rate was 52%, including pre-LT SVR12 of 41% in patients who completed treatment and follow-up on the wait list and pTVR12 of 67% among transplanted patients. The pTVR12 rate was 89% among those patients with undetectable viral load at LT. Serious adverse events occurred in nine (31%) patients including one (3%) on-treatment death and eight (28%) hospitalizations. CONCLUSIONS: Overall SVR12 and pTVR12 rates are high among patients treated with PI-based triple therapy while awaiting LT, even in this difficult to treat population. However, caution is needed as early discontinuation and serious adverse events are common.

There is conflicting literature regarding the superiority of transarterial chemoembolization (TACE) versus bland transarterial embolization (TAE), and this has not been well studied before transplantation. Twenty-five TAE patients were matched in a 1:2 ratio with TACE patients by the initial radiographic tumor size and number in a retrospective, case-controlled study. The patients were otherwise treated according to the same protocols. The method of embolization was chosen on the basis of interventionalist practices at 2 sites within the program. Kaplan-Meier survival analyses at 1 and 3 years were the primary endpoints. There were no significant demographic differences between the groups. The mean adjusted Model for End-Stage Liver Disease scores at transplantation and waiting times were not significantly different between the TAE and TACE patients (MELD scores: 26 +/- 3 versus 24 +/- 3 points, P = 0.12; waiting times: 13 +/- 8 versus 11 +/- 10 months, P = 0.43). TAE patients (16%) were less likely than TACE patients (40%) to require 2 procedures (P = 0.04). Explant tumors were completely necrotic for 36% of the TAE patients and for 26% of the TACE patients. The 3-year overall survival rates were 78% for the TAE patients and 74% for the TACE patients (P = 0.66), and the 3-year recurrence-free survival rates were 72% for the TAE patients and 68% for the TACE patients (P = 0.67). On an intention-to-treat basis, there was no significant risk of wait-list dropout associated with TAE or TACE (P = 0.83). In conclusion, there were no significant differences in wait-list dropout or in overall or recurrence-free survival between HCC patients undergoing TAE and HCC patients undergoing TACE before transplantation.

Substantial evidence has linked ionizing radiation exposure (RE) to oncogenesis. Patients evaluated for transplantation undergo extensive diagnostic imaging and have increased baseline cancer risk factors. The objective was to examine exposure in a cohort of patients undergoing evaluation and liver transplantation. Radiation exposure from all diagnostic examinations and procedures were retrospectively recorded. Radiation exposure is reported in mSv, a standardized measure of the detrimental biologic effect of radiation which allows for population-level comparisons. Seventy-four patients (69% male, mean 57 years) were evaluated, of which 13 of 35 subsequently listed patients were transplanted; an additional 18 previously evaluated patients were also transplanted during 2010. The most common indications were hepatitis C (55%) and hepatocellular carcinoma (HCC) (30%). The median observation period was 14 months. In all, 1,826 imaging examinations were performed, of which 408 (22%) involved considerable ionizing radiation and were the focus of investigation. Median annualized effective RE was 51 mSv (interquartile range [IQR]: 19,126), with 10% exposed to almost twice the amount of radiation recommended for a 5-year period. Patients with HCC received significantly (P < 0.00001) higher median annualized effective RE than patients without HCC, 137 mSv (IQR: 87,259) versus 32 mSv (IQR: 13,57), respectively. Computed tomography (CT) abdomen (23%) and chest (16%) accounted for the most common exposures, with CT abdomen accounting for 46% of overall cohort RE. CONCLUSION: Patients undergoing evaluation and liver transplantation at our center are exposed to very high levels of ionizing radiation. Although long-term effects in these patients are yet to be defined, the theoretical increased risk of malignancy must be given its due consideration. Routine use of nonradiation imaging and reconsideration of indications may be preferred and justified in this population.

BACKGROUND: Lamivudine (LAM) has been shown to prevent de novo hepatitis B virus (HBV) infection in recipients of hepatitis B core antibody (HBcAb)-positive liver transplants (LT) but primarily in small studies with limited follow-up. METHODS: We conducted a retrospective cohort study of HBcAb+ graft recipients at our institution from October 1999 to August 2008. RESULTS: One hundred nineteen recipients without prior HBV were identified (median age, 54 years; 70% male), of which 62 received LAM. The median follow-up was 2.6 years overall and 5.3 years in the LAM group. Among LAM recipients, 44% were HBV naive (HBsAb-/HBcAb-) at LT, of which 6% developed HBsAb+ and 3% developed HBcAb+ after LT. Eight percent developed de novo HBV: two recipients became hepatitis B surface antigen positive at 70 and 23 months and three experienced breakthrough with HBV DNA more than 2000 IU at 1 to 9 months after LT. Sixty percent (3 of 5) were HBV naive. Four (6%) other recipients also had transiently detectable HBV less than 2000 IU, which did not require any changes to their prophylaxis regimen. When compared with recipients who received other nucleos(t)ide analogues, there was no difference in de novo rates: LAM 8% (5 of 62), adefovir 15% (5 of 33), tenofovir 0% (0 of 3), entecavir 0% (0 of 1), and 5% (1 of 20) for those not given prophylaxis (P=0.59). CONCLUSIONS: LAM monoprophylaxis was effective in preventing de novo HBV in the vast majority of recipients over long-term follow-up. Adefovir had a higher rate of de novo infections numerically, whereas tenofovir and entecavir had no cases and may be more effective, but this was limited by a small sample size.

BACKGROUND: ABO-incompatible organ transplantation typically induces hyperacute rejection. A2-to-O liver transplantations have been successful. This study compared overall and graft survival in O recipients of A2 and O grafts based on Organ Procurement and Transplantation Network data. METHODS: Scientific Registry of Transplant Recipients data were used. The first A2-to-O liver transplantation was entered on March 11, 1990; all previous transplantations were excluded. Between March 11, 1990, and September 3, 2010, 43,335 O recipients underwent transplanation, of whom 358 received A2 grafts. RESULTS: There were no significant differences in age, sex, and race between the groups. Recipients of A2 grafts versus O grafts were significantly more likely to be hospitalized at transplantation (45% vs. 38%, P