Moving toward personalizing MELD exceptions in liver transplantation for hepatocellular carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150509/1/ajt15389_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150509/2/ajt15389.pd

Diminishing Use of Liver Biopsy among Liver Transplant Recipients for Hepatitis C.

Background and Aims: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality. Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy. The introduction of direct-acting antiviral agents (DAAs) has changed the management of recurrent HCV infection. This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs. Methods: A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV. The analysis included 475 adult liver transplants for hepatitis C performed at the University of California, Los Angeles from January 1, 2006 to October 1, 2015. Patients were divided into two eras, pre- and post-introduction of DAAs on December 1, 2013. Results: In the era before the introduction of DAAs, the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs. 26.9%, p < 0.001). Conclusions: The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV. Given that DAAs are well tolerated and have high efficacy, liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation

Reoperative Complications after Primary Orthotopic Liver Transplantation: A Contemporary Single-Center Experience in the Post–Model for End-Stage Liver Disease Era

BackgroundData on complications requiring reoperation after orthotopic liver transplantation (OLT) are limited. We sought to describe the spectrum of reoperative complications after OLT, evaluate the associations with graft and patient survival, and identify predictors of need for reoperation.Study designWe retrospectively studied adult patients who underwent primary OLT at our institution from February 2002 to July 2012. The primary outcomes included occurrence of a reoperative complication. Secondary outcomes were graft and patient survival. Multivariable logistic regression analysis was used to model the associations of recipient, donor, and operative variables with reoperation.ResultsOf 1,620 patients, 470 (29%) had complications requiring reoperation. The most common reoperative complication was bleeding (17.3%). Compared with patients not requiring reoperation, patients with reoperative complications had greater Model for End-Stage Liver Disease scores and need for pretransplantation hospitalization, mechanical ventilation, vasopressors, and renal replacement therapy; considerably longer cold and warm ischemia times and greater intraoperative blood transfusion requirements; and substantially worse 1-, 3-, and 5-year graft and patient survival rates. In multivariable analysis, predictors of reoperative complications included intraoperative transfusion of packed RBCs (odds ratio [OR] = 2.21; 95% CI, 1.91-2.56), donor length of hospitalization >8 days (OR = 1.87; 95% CI, 1.28-2.73), recipient pretransplantation mechanical ventilation (OR = 1.65; 95% CI, 1.21-2.24), cold ischemia time >9 hours (OR = 1.63; 95% CI, 1.23-2.17), warm ischemia time >55 minutes (OR = 1.58; 95% CI, 1.02-2.44), earlier major abdominal surgery (OR = 1.41; 95% CI, 1.03-1.92), and elevated donor serum sodium (OR = 1.17; 95% CI, 1.03-1.31).ConclusionsPatients who require reoperation for complications after OLT have high pretransplantation acuity and inferior post-transplantation survival. We identified factors associated with reoperative complications to guide perioperative donor-recipient matching and improve outcomes

A rapid, reproducible, noninvasive predictor of liver graft survival

BACKGROUND: Clinical and laboratory criteria are not reliable predictors of deceased donor liver graft quality. Intraoperative assessment of experienced surgeons is the gold standard. Standardizing and quantifying this assessment is especially needed now that regional sharing is the rule. We prospectively evaluated a novel, simple, rapid, noninvasive, quantitative measure of liver function performed before graft procurement. MATERIALS AND METHODS: Using a portable, finger-probe–based device, indocyanine green plasma disappearance rates (ICG-PDR) were measured in adult brain-dead donors in the local donor service area before organ procurement. Results were compared with graft function and outcomes. Both donor and recipient teams were blinded to ICG-PDR measurements. RESULTS: Measurements were performed on 53 consecutive donors. Eleven liver grafts were declined by all centers because of quality; the other 42 grafts were transplanted. Logistic regression analysis showed ICG-PDR to be the only donor variable to be significantly associated with 7-d graft survival. Donor risk index, donor age, and transaminase levels at peak or procurement were not significantly associated with 7-d graft survival. CONCLUSIONS: We report the successful use of a portable quantitative means of measuring liver function and its association with graft survival. These data warrant further exploration in a variety of settings to evaluate acceptable values for donated liver grafts

Optimal Timing of Administration of Direct-Acting Antivirals for Patients with Hepatitis C-Associated Hepatocellular Carcinoma Undergoing Liver Transplantation

Objective: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). Summary of Background Data: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. Methods: The United States HCC LT Consortium (2015–2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). Results: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). Conclusions: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results

Changes in liver transplant center practice in response to COVID‐19: Unmasking dramatic center‐level variability

The COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, has been devastating to health care delivery in many parts of the US and has had a significant impact on organ transplantation. With shelter‐in‐place orders, outpatient clinics transitioned to telemedicine, and the threat of hospitals being overrun with COVID‐19 patients, liver transplant programs have been faced with the challenge of balancing patient and staff safety while operating in a resource limited environment

Impact of the Share 35 Policy on Perioperative Management and Mortality in Liver Transplantation Recipients.

BACKGROUND The Share 35 policy was introduced in 2013 by the Organ Procurement and Transplantation Network (OPTN) to increase opportunities of sicker patients to access liver transplantation. However, it has the disadvantage of higher MELD score associated with adverse postoperative transplant outcomes. Early data after implementation of the Share 35 policy showed significantly poorer post-transplantation survival in some UNOS regions. We aimed to analyze the impact of Share 35 on demographics of patients, perioperative management, and perioperative mortality. MATERIAL AND METHODS A retrospective analysis of data was performed from an institutional liver transplantation cohort from 1 January 2008 to 31 December 2017. Adult patients who underwent liver transplantation before 2013 were defined as the pre-Share 35 group and the other group was defined as the post-Share 35 group. The MELD score of each patient was calculated at the time of transplantation. Perioperative mortality was defined as death within 30 days after the operation. RESULTS A total of 1596 patients underwent liver transplantation. Of those, 895 recipients underwent OLT in the pre-Share 35 era and 737 in the post-Share 35 era. The median MELD score was significantly higher in the post-Share 35 group (30 vs 26, P&lt;0.001) and 45.7% of the post-Share 35 group had MELD scores ≥35. In intraoperative management, patients required significantly more blood component transfusion, intraoperative vasopressor, and fluid replacement. Veno-venous bypass (VVB) usage was significantly higher in the post-Share 35 era (47.2% vs 38.1%, P&lt;0.001). In the subgroup of patients with MELD scores ≥35, the median waiting time was significantly shorter (18.5 vs 14.5 days, P=0.045). Overall perioperative mortality was not significantly difference between groups (P=0.435). CONCLUSIONS After implementation of the Share 35 policy, we performed liver transplantation in significantly higher medical acuity patients, which required more medical resources to obtain a result comparable to that of the pre-Share 35 era

Intestinal Stem Cell Organoid Transplantation Generates Neomucosa in Dogs

Intestinal stem cell organoid transplantation generates functional intestinal neomucosa and has been used therapeutically to improve nutrient absorption and cure bile acid malabsorption in rats. We hypothesized that intestinal organoids can be harvested and transplanted to generate intestinal neomucosa in a large animal model. In group 1, 2-month old beagles (n = 6) underwent autotransplantation of intestinal organoids prepared from a segment of their own ileum. In group 2, intestinal organoids were harvested from fetuses and allotransplanted into 10-month old mother animals (n = 4). Tissues were harvested after 4 weeks and analyzed by hematoxylin and eosin histology and fluorescent microscopy. Large numbers of viable organoids were harvested in both groups. In group 1, no neomucosal growth was identified in any of the engraftment sites after autotransplantation of juvenile organoids. In group 2, neomucosal growth with large areas of crypts and villi was identified in 11 of 12 polyglycolic acid scaffolds after allotransplantation of fetal organoids. The neomucosa resembled normal canine mucosa in structure and composition. Intestinal stem cell organoid transplantation can be used to generate neomucosa in dogs. This is the first report of successful generation of intestinal neomucosa using intestinal stem cell organoid transplantation in a large animal model