Practice patterns of the medical evaluation of living liver donors in the United States.

Living donor liver transplantation (LDLT) can help address the growing organ shortage in the United States, yet little is known about the current practice patterns in the medical evaluation of living liver donors. We conducted a 131-question survey of all 53 active LDLT transplant programs in the United States to assess current LDLT practices. The response rate was 100%. Donor acceptance rate was 0.33 with an interquartile range of 0.33-0.54 across all centers. Areas of high intercenter agreement included minimum age cutoff of 18 years (73.6%) and the exclusion of those with greater than Class 1 obesity (body mass index, 30.0-34.9 m/kg 2 ) (88.4%). Diabetes mellitus was not an absolute exclusion at most centers (61.5%). Selective liver biopsies were performed for steatosis or iron overload on imaging (67.9% and 62.3%, respectively) or for elevated liver enzymes (60.4%). Steatohepatitis is considered an exclusion at most centers (84.9%). The most common hypercoagulable tests performed were factor V Leiden (FVL) (88.5%), protein C (73.1%), protein S (71.2%), antithrombin III (71.2%) and prothrombin gene mutation (65.4%). At 41.5% of centers, donors were allowed to proceed with donation with FVL heterozygote status. Most programs discontinue oral contraceptive pills at least 28 days prior to surgery. At most centers, the need for cardiovascular ischemic risk testing is based on age (73.6%) and the presence of one or more cardiac risk factors (68.0%). Defining areas of practice consensus and variation underscores the need for data generation to develop evidence-based guidance for the evaluation and risk assessment of living liver donors.

Coagulopathy and hemostasis management in patients undergoing liver transplantation: Defining a dynamic spectrum across phases of care.

Patients with acute and chronic liver disease present with a wide range of disease states and severity that may require liver transplantation (LT). Physiologic alterations occur that are dynamic throughout all phases of perioperative care, creating complex management scenarios that necessitate multidisciplinary clinical care. Specifically, alterations in hemostasis in liver disease can be pronounced and evolve with disease progression over time. Recent studies and society guidance address this emerging paradigm and offer recommendations to assist with hemostatic management in patients with liver disease. However, patients undergoing LT are unique and diverse, often with unstable disease that requires specialized approaches. Our aim is to provide a focused review of hemostatic management of the LT patient, distinguish unique aspects of the three main phases of care (before LT, perioperative, and after LT), and identify knowledge gaps and critical areas of future research.

Liver transplantation for hepatocellular carcinoma: Management after the transplant.

Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.

Simeprevir and Sofosbuvir (SMV-SOF) for 12 Weeks for the Treatment of Chronic Hepatitis C Genotype 1 Infection: A Real World (Transplant) Hepatology Practice Experience.

OBJECTIVES: The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the "real world" experience. The goal of this study was to define SVR rates in a "real world" analysis and to explore predictors of treatment response with SMV and SOF. METHODS: This is a retrospective study examining the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol. RESULTS: The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African-American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort. CONCLUSIONS: Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease.

Preservation of quality of life with doxorubicin drug-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma: Longitudinal prospective study.

BACKGROUND AND AIM: The study aims to determine the effects of doxorubicin drug-eluting bead transarterial chemoembolization (DEB-TACE) therapies on health-related quality of life (HRQOL) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: This is a single-center, prospective study assessing HRQOL of consecutive patients with unresectable HCC who underwent DEB-TACE. Longitudinal assessment of HRQOL scores via Short-Form-36 (SF-36) was performed. Baseline HRQOL scores were evaluated for significant change (P < 0.05) pre-therapy, post-therapy, and at 6- and 12-month follow-up. Analysis of overall survival (OS) from HCC diagnosis and OS from first DEB-TACE was performed. Paired t-tests were used to compare HRQOL domain scores. RESULTS: One hundred eighteen patients (83 male; median age 60 years) were enrolled. Patients had lower baseline scores within all eight HRQOL domains of the SF-36 compared with US age-adjusted healthy norms. No significant changes in all eight domains were observed post-therapy and at 6- or 12-month follow-up compared with baseline (P > 0.05). No significant differences in all eight domains were observed between patients receiving ≥ 4 versus ≤ 3 DEB-TACE (P > 0.05). Both groups were similar for age at HCC diagnosis, gender, ethnicity, HCC etiology, Child-Pugh class and Eastern Cooperative Oncology Group Performance Status (P > 0.05). Patients receiving staged DEB-TACE demonstrated significantly greater median OS from HCC diagnosis (≥ 4 vs ≤ 3 DEB-TACE procedures, 31.9 vs 23.7 months, P = 0.04) and from first DEB-TACE (≥ 4 vs ≤ 3 DEB-TACE, 29.1 vs 20.2 months, P = 0.03). CONCLUSION: DEB-TACE therapy for HCC demonstrated long-term preservation of HRQOL. In addition, staged DEB-TACE with four or more therapies does not significantly impact long-term HRQOL compared with patients who received three or fewer therapies.

Discarding Dichotomization: Retrieving Data in the Service of Patient Care.

Content available: Author Interview and Audio Recording.

Locoregional Therapies for Hepatocellular Carcinoma: What Has Changed in the Past Ten Years?

The evolution of locoregional therapies in the last decade has been refined with improved patient selection and a development of a more personalized approach. In doing so, there has been associated improved outcomes and less toxicity. With the rapidly changing landscape of systemic therapy, the role of locoregional therapies alone or in combination for downstaging and curative intent will continue to evolve.

Liver Transplantation in the Obese Cirrhotic Patient.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

Management of de novo malignancies after liver transplantation.

Due to advances in medical and surgical expertise leading to significant improvements in graft and patient survival, there is an increased recognition of long term complications in survivors such as de novo malignancies, cardiovascular events and infections. Data show solid organ transplant recipients have 2-3 times the increased risk of developing a de novo malignancy compared to an age-matched and sex-matched general population and malignancy is expected to be the number one cause of mortality in long term transplant recipients in the next two decades. Risk factors include an aging transplant population, oncogenic viruses and the long term effects of immunosuppression in the development of carcinogenesis. This review summarizes common de novo malignancies occurring in the post liver transplant population and current strategies for their prevention and management. Unfortunately, due to limited evidence based data, robust screening guidelines for post transplant cancer prevention have yet to be implemented in this population.

Overview of immunosuppression in liver transplantation.

Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate peri- and post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.