Inferior Survival Is Associated With Socioeconomic Deprivation in Hepatocellular Carcinoma.

INTRODUCTION: Pernicious health disparities have been reported in patients with hepatocellular carcinoma (HCC). Few tools exist to screen patients in order to facilitate educational and outreach initiatives. We hypothesize that neighborhood-level socioeconomic metrics such as the Area Deprivation Index (ADI) can predict inferior outcomes in patients with early-stage HCC. METHODS: A single institution's retrospective review of patients with Surveillance, Epidemiology, and End Results Stage I HCC between 2000 and 2020 was conducted. Univariate and multivariate models were constructed to identify clinical and socioeconomic variables correlated with treatment-specific survival. Kaplan-Meier analysis was performed to compare survival differences between cohorts. RESULTS: A total of 558 patients were included in this study with newly diagnosed Surveillance, Epidemiology, and End Results Stage I HCC. Multivariate models demonstrated native model of end-stage liver disease, largest tumor size, insurance type, the distance to our transplant center, and the ADI score, a validated metric for a patient's socioeconomic status, are independent risk factors for worse overall survival (all P-values < 0.05). Concerningly, despite similar maximal tumor size, number of tumors, and native model of end-stage liver disease scores, patients from high ADI neighborhoods are 20% less likely to receive surgical treatment, especially liver transplantation. CONCLUSIONS: The ADI is a useful tool for identifying patients at the time of presentation who are at risk for inferior treatment for early stage HCC, and the ADI should be incorporated as a social vital sign.

Sofosbuvir-Based Therapy in the Pre-Liver Transplant Setting: The Canadian National Experience.

INTRODUCTION AND AIM: Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status. MATERIAL AND METHODS: A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status. RESULTS: 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported. CONCLUSIONS: SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list .

Survey of Living Organ Donors' Experience and Directions for Process Improvement.

INTRODUCTION: Understanding living organ donors' experience with donation and challenges faced during the process is necessary to guide the development of effective strategies to maximize donor benefit and increase the number of living donors. METHODS: An anonymous self-administered survey, specifically designed for this population based on key informant interviews, was mailed to 426 individuals who donated a kidney or liver at our institution. Quantitative and qualitative methods including open and axial coding were used to analyze donor responses. FINDINGS: Of the 141 survey respondents, 94% would encourage others to become donors; however, nearly half (44%) thought the donation process could be improved and offered numerous suggestions. Five major themes arose: (1) desire for greater convenience in testing and scheduling; (2) involvement of previous donors throughout the process; (3) education and promotion of donation through social media; (4) unanticipated difficulties, specifically pain; and (5) financial concerns. DISCUSSION: Donor feedback has been translated into performance improvements at our hospital, many of which are applicable to other institutions. Population-specific survey development helps to identify vital patient concerns and provides valuable feedback to enhance the delivery of care.

MicroRNA-494 is a master epigenetic regulator of multiple invasion-suppressor microRNAs by targeting ten eleven translocation 1 in invasive human hepatocellular carcinoma tumors.

UNLABELLED: Vascular invasion provides a direct route for tumor metastasis. The degree to which microRNA (miRNA) expression plays a role in tumor vascular invasion is unclear. Here, we report that miR-494 is up-regulated in human hepatocellular carcinoma (HCC) tumors with vascular invasion and can promote HCC cell invasiveness by gene inactivation of multiple invasion-suppressor miRNAs. Our results show that ten eleven translocation (TET) methylcytosine dioxygenase, predominantly TET1 in HCC cells, is a direct target of miR-494. The reduced 5'-hydroxymethylcytosine levels observed in the proximal cytosine-phosphate-guanine (CpG) regions of multiple invasion-suppressor miRNA genes are strongly associated with their transcriptional repression upon miR-494 overexpression, whereas enforced DNA demethylation can abolish the repression. Furthermore, TET1 knockdown shows a similar effect as miR-494 overexpression. Conversely, miR-494 inhibition or enforced TET1 expression is able to restore invasion-suppressor miRNAs and inhibit miR-494-mediated HCC cell invasion. CONCLUSIONS: miR-494 can trigger gene silencing of multiple invasion-suppressor miRNAs by inhibiting genomic DNA demethylation by direct targeting of TET1, thereby leading to tumor vascular invasion.

Robotic Assisted Transplant Nephrectomy: Case Series and Training Model for Improving Adoption.

Introduction: Open transplant nephrectomy for failed renal allograft is an invasive procedure associated with significant perioperative morbidity and mortality. Minimally invasive surgical approaches have improved a variety of patient outcomes for many surgeries. Thus, robotic assisted transplant nephrectomy (RATN) potentially offers significant patient benefit. Although previously reported, there remains a paucity of data on RATN outcomes and techniques. Methods: Four perfused, high-fidelity hydrogel models were created using previously described techniques and used for simulated RATN. Subsequently performed institutional cases were included for analysis. Intra- and postoperative variables along with patient demographics were retrospectively obtained through parsing of patient records. Results: Simulated nephrectomy time was 67.33 minutes (35.75 - 98.91). Five patients underwent RATN. There were four male and one female patients. The average age was 47 years. The most common indication was abdominal pain secondary to rejection (3/5). Mean blood loss was 188 mL; mean operative time was 243 minutes, and mean length of stay was 4.5 days. Intraoperatively there were two incidences of small cystotomies. One patient was readmitted within 30 days for intraabdominal abscess. Conclusion: This study adds to the growing literature around RATN, demonstrating the feasibility of the technique and reporting good outcomes for this cohort.

Saudi association for the study of liver diseases and transplantation position statement on the hepatology workforce in Saudi Arabia.

The field of hepatology has evolved significantly over the last two decades. Hepatology practice in Saudi Arabia (SA) was dominated by hepatitis B and C viruses but is now being overtaken by patients with non-alcoholic fatty liver disease. These patients require greater medical attention as their care is more complex compared to patients with viral hepatitis. In addition, liver transplantation (LT) has expanded significantly in SA over the last three decades. There is a necessity to increase the hepatology workforce to meet the demand in SA. The time has come to reinforce the transplant hepatology fellowship program, that was launched recently, and to develop a nurse practitioner practice model to meet these demands. In addition, SA is going through a health care reform to enhance health care delivery which may affect the financial compensation polices of various specialties including gastroenterology and hepatology. Therefore, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) established a task force to discuss the current and future demands in the hepatology workforce in SA, as well as to discuss different avenues of financial compensation for transplant hepatologists in LT centers.

Assessing the Effectiveness of a Primary Care Provider Office-Based Intervention for Increasing Organ Donor Registration Rates in Two New York State Counties.

Introduction: Despite strong public support, organ donor registration rates (RR) continue to lag while need only grows. In the United States, the traditional registration site is the Department of Motor Vehicles (DMV), however Primary care provider (PCP) offices have been considered as alternate locations for increasing RR. Methods: Twelve PCP offices across 2 New York Counties were subjected to a control week where participants received only a registration opportunity and an intervention week with the addition of a motivational poster and informational brochure. Zip code level sociodemographic data were obtained for each site. RR from the DMV over the same period served as historical control. Results: There were 1292 participants in the control phase and 1099 in the experimental phase. New registration rate for the control was 33.8% (289/897); experimental phase 7.88% (61/769); DMV registration 21.02% (1902/9050). The intervention was associated with a significant decrease in registrations (OR 0.181 (95% CI 0.135-0.244, P < 0.001)). Offices were clustered based on sociodemographic factors and regressed in 2 clusters. Lower educational attainment was associated with lower registration in the first but not second cluster (OR = 0.948 (0.923-0.974, P < 0.001)). Conclusions: This study provided evidence that PCP offices were a feasible site for organ donor registration and calls into question the efficacy of written materials-only interventions for increasing organ donor RR. It reiterated the negative effect of lower educational attainment on registration and suggested future studies focus on more active methods of engagement.

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

The Rochester Relapse Risk Scale: Developing a Standardized Approach to Predicting Substance Relapse in Liver Transplant Candidates.

OBJECTIVES: Substance abuse is a risk factor for nonadherence and graft failure after orthotopic liver transplant. This study aimed to evaluate the ability of an internally developed tool, the Rochester Relapse Risk Scale, to predict substance relapse in liver transplant candidates. MATERIALS AND METHODS: This single-center, retrospective, observational study included adult patients evaluated for orthotopic liver transplant using the Rochester Relapse Risk Scale. Primary outcome was rate of substance relapse, as measured by the risk scale, which stratified patients into relapse risk levels based on the number of factors present. RESULTS: In total, 303 patients (71.6% men, 90.4% White, median age of 55 years [interquartile range, 49-60 y]) were included. Median follow-up time was 212 days (interquartile range, 73-661 d). Seventy-four patients (24.4%) relapsed at 127 days (interquartile range, 55-461 d) after evaluation, with 60.8% who relapsed within 6 months. Relapse rates correlated with assigned risk level, with 8.3% relapsing at low, 19.0% at low-moderate, 25.3% at moderate, 33.8% at moderate-high, and 40.0% at high risk. High-risk cohorts had significantly shorter median time to relapse versus low-risk cohorts (104 vs 154 days; P = .001). CONCLUSIONS: Assignment of relapse risk level according to the Rochester Relapse Risk Scale aligned with rates of relapse. Additional studies are needed to refine the tool, assess inter-rater reliability, and confirm findings in prospective, multicenter studies.

The Effect of the Opioid Epidemic on Donation After Circulatory Death Transplantation Outcomes.

BACKGROUND: The opioid epidemic and the deaths of otherwise healthy individuals due to drug overdose in the United States has major implications for transplantation. The current extent and safety of utilization of liver and kidney grafts from donation after circulatory death (DCD) donors who died from opioid overdose is unknown. METHODS: Using national data from 2006 to 2016, we estimated the cumulative incidence of graft failure for recipients of DCD grafts, comparing the risk among recipients of organs from donors who died of anoxic drug overdose and recipients of organs from donors who died of other causes. RESULTS: One hundred seventy-nine (6.2%) of 2908 liver graft recipients and 944 (6.1%) of 15520 kidney graft recipients received grafts from donors who died of anoxic drug overdose. Grafts from anoxic drug overdose donors were less frequently used compared with other DCD grafts (liver, 25.9% versus 29.6%; 95% confidence interval [CI] for difference, -6.7% to -0.7%; kidney, 81.0% versus 84.7%; 95% CI for difference, -7.3% to -0.1%). However, the risk of graft failure at 5 years was similar for recipients of anoxic drug overdose donor grafts and recipients of other grafts (liver risk difference, 1.8%; 95% CI, -7.8% to 11.8%; kidney risk difference, -1.5%; 95% CI, -5.4% to 3.1%). CONCLUSIONS: In the context of the current opioid epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase the risk of graft failure and may help to address waitlist demands.

Comparison of outcomes between SBRT, yttrium-90 radioembolization, transarterial chemoembolization, and radiofrequency ablation as bridge to transplant for hepatocellular carcinoma.

PURPOSE: To evaluate and compare outcome of stereotactic body radiation therapy (SBRT), yttrium-90 radioembolization, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) as bridge to liver transplant (LT) in patients with hepatocellular carcinoma. METHODS AND MATERIALS: We retrospectively reviewed patients treated at our institution with SBRT, TACE, RFA, or yttrium-90 as bridge to LT between 2006 and 2013. We analyzed radiologic and pathologic response and rate of failure after bridge therapy. Toxicities were reported using Common Terminology Criteria for Adverse Events, 4.0. Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival after LT. RESULTS: Sixty patients with a median age 57.5 years (range, 44-70) met inclusion criteria. Thirty-one patients (50.7%) had hepatitis C cirrhosis, 14 (23%) alcoholic cirrhosis, and 8 (13%) nonalcoholic steatohepatitis cirrhosis. Patients received a total of 79 bridge therapies: SBRT (n = 24), TACE (n = 37), RFA (n = 9), and Y90 (n = 9). Complete response (CR) was 25% for TACE, 8.6% for SBRT, 22% for RFA, and 33% for Y90. Grade 3 or 4 acute toxicity occurred following TACE (n = 4) and RFA (n = 2). Transplant occurred at a median of 7.4 months after bridge therapy. Pathological response among 57 patients was 100% necrosis (n = 23, 40%), >50% necrosis (n = 20, 35%), <50% necrosis (n = 9, 16%), and no necrosis (n = 5, 9%). Pathologic complete response was as follows: SBRT (28.5%), TACE (41%), RFA (60%), Y90 (75%), and multiple modalities (33%). At a median follow-up of 35 months, 7 patients had recurrence after LT. DFS was 85.8% and overall survival was 79% at 5 years. CONCLUSION: All bridge therapies demonstrated good pathological response and DFS after LT. SBRT and Y90 demonstrated significantly less grade ≥3 acute toxicity. Choice of optimal modality depends on tumor size, pretreatment bilirubin level, Child-Pugh status, and patient preference. Such a decision is best made at a multidisciplinary tumor board as is done at our institution.