Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience.

OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Vibration Controlled Transient Elastography to Evaluate Steatosis in Candidate Living Donors for Liver Transplantation.

BACKGROUND: The ability of vibration controlled transient elastography (VCTE) to reliably exclude significant steatosis in living donor candidates could obviate the need for invasive liver biopsies, expedite the donor approval process, and reduce recipient wait time. We therefore aimed to determine whether VCTE controlled attenuation parameter (CAP) could be used to detect steatosis in potential living donors. METHODS: Living donor candidates who presented for evaluation between 2016 and 2019 underwent standard donor workup, VCTE, and liver biopsy if indicated. CAP scores were compared with MRI-Fat Fraction and, when available, histologic fat fraction from liver biopsy. Receiver operating characteristic curves were used to identify cutoffs with appropriate sensitivity and specificity for screening. Statistical analysis was conducted using R (version 3.6.0). RESULTS: Seventy-nine candidate living donors presented during the study period, of whom 71 were included in the final analysis and of whom 20 underwent liver biopsy. There was a positive correlation between MRI-Fat Fraction and CAP scores with an observed Spearman correlation coefficient of 0.424 ( P < 0.01). A CAP score of 271.5 dB/m or less was determined to have 89.8% sensitivity and 75% specificity for detecting <5% steatosis on MRI. The correlation between CAP and steatosis of available histologic samples had a Pearson correlation coefficient of 0.603 ( P = 0.005). A CAP cutoff of 276.0 dB/m demonstrated 66.7% sensitivity and 85.7% specificity for detecting <15% histopathologic steatosis and positive and negative predictive values of 71.5% and 82.7%, respectively. CONCLUSIONS: VCTE can be integrated into living donor evaluation to accurately screen for hepatic steatosis.

Can lightning strike twice? Wild-type transthyretin cardiac amyloidosis associated with rare liver disease.

Wild-type ATTR cardiac amyloidosis (ATTRwt-CA) is not as rare as previously thought to be. Patients with infiltrative cardiac amyloidosis often present with right-sided heart failure (HF) symptomatology. Clinically significant liver disease and cirrhosis has not been reported in ATTRwt-CA. We present two cases of ATTRwt-CA with right-sided HF and abnormal liver function tests initially thought to be secondary to congestive hepatopathy but found to have rare and unrelated liver disease. These cases highlight the importance of developing a broad differential diagnosis and leveraging a multidisciplinary team approach in evaluating patients for unusual causes of cirrhosis/other chronic liver diseases when ATTR cardiac amyloidosis patients present with congestive hepatopathy.

Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation in Children.

BACKGROUND: Despite high survival in pediatric living donor liver transplantation (LDLT), only 10% of liver transplants in children in the United States are from living donors, reflecting reluctance to embrace this approach. In addition to optimal timing and graft quality, LDLT may offer immunologic benefit because most donors are haploidentical parents. We sought to quantify the benefit of LDLT compared to deceased donor liver transplantation (DDLT) using granular clinical and immunologic outcomes over the long term. METHODS: A retrospective cohort of children (age <18 years) surviving 1 year or longer posttransplant was evaluated to determine the impact of donor type on graft survival and immunologic outcomes. RESULTS: Two hundred forty-one children (177 DDLT and 64 LDLT) were assessed. In multivariable analysis, LDLT was associated with a lower rate of acute cellular rejection (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98; P = 0.04), a lower rate of chronic rejection (HR, 0.12; 95% CI, 0.03-0.56; P = 0.007), better graft survival on monotherapy immunosuppression at 3 years posttransplant (87.7% vs 46.7%; odds ratio, 7.41; 95% CI, 2.80-19.66; P < 0.001), and a lower rate of graft loss (HR, 0.29; 95% CI, 0.10-0.88; P = 0.03). Graft type was not an independent predictor of posttransplant mortality (LDLT HR, 0.57; 95% CI, 0.16-2.01; P = 0.38). Maternal graft LDLT was associated with a lower rate of acute cellular rejection (HR, 0.13; 95% CI, 0.03-0.64; P = 0.01) and posttransplant lymphoproliferative disorder (HR, 0.04; 95% CI, 0.004-0.44; P = 0.008) compared with paternal grafts. CONCLUSIONS: This study demonstrates the potential benefit of LDLT, particularly with maternal grafts, for pediatric liver transplant recipients on multiple clinical parameters over long-term follow-up.

Fully laparoscopic left-sided donor hepatectomy is safe and associated with shorter hospital stay and earlier return to work: A comparative study.

Living donor liver transplantation has failed to become a major means of transplantation in the United States, where <5% of the transplants are performed with living donors. At least 30% to 50% of the complications of donor hepatectomy appear to be related to abdominal wall trauma, including hernia, bowel obstruction, and chronic abdominal discomfort. We analyzed our experience with laparoscopically procured donor hepatectomy. We compared 22 full laparoscopic donor hepatectomies to 20 open/hybrid hepatectomies over an 11-year period. Donor and recipient demographics, complications, and graft and recipient outcomes were analyzed. All 22 laparoscopically procured liver allografts were transplanted successfully. The laparoscopically procured grafts took longer to procure (7 hours 58 minutes versus 6 hours 38 minutes; P < 0.001). The laparoscopically procured cases had lower blood loss (177.3 versus 3753 cc; P < 0.001), a shorter length of stay, and significantly reduced days off work (P = .01). The 1-year graft survival was not different (90% in the laparoscopic group and 85% in the open group; P = 0.70). The 1-year patient survival was not different (95% in the laparoscopic group and 85% in the open group; P = 0.32). There was a trend toward lower wound issues in the laparoscopic group, but this did not reach significance (the hybrid/open group had a 15% hernia rate versus 5% for the laparoscopic group). In experienced living donor centers, laparoscopic liver donation appears to be feasible for all pediatric recipients and some adult recipients. Outcomes for the recipients of laparoscopically procured grafts do not appear significantly different from outcomes with hybrid/open techniques.

High post-transplant virological response in hepatitis C virus infected patients treated with pretransplant protease inhibitor-based triple therapy.

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.

Bland embolization versus chemoembolization of hepatocellular carcinoma before transplantation.

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.

Exposure to ionizing radiation during liver transplantation evaluation, waitlist time, and in the postoperative period: a cause for concern.

UNLABELLED: 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.

Liver transplantation in HIV patients.

In the last three decades, the management of human immunodeficiency virus (HIV) has improved dramatically. The use of combination antiretroviral therapy (ART) has been successful at preventing death and the myriad infectious, malignant, and immune-mediated complications of HIV. Once considered to be a fatal disease, HIV is now considered by many to be a chronic disease; those affected may now live to experience complications of other coexistent diseases. Liver disease has been increasingly recognized as a leading cause of non-HIV/acquired immunodeficiency syndrome- (AIDS-) related morbidity and mortality in this population.Although liver transplantation offers the opportunity to prolong life, the transplant community has been slow to recognize the chronicity of HIV and potential for transplantation within this population. The experience with liver transplantation in HIV-positive patients is evolving and successful outcomes have been observed when specific criteria are used to select candidates.