Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

Between-hospital care referrals for severe alcohol-related liver disease during the COVID-19 pandemic, 2020 to 2022.

Increased alcohol consumption during the coronavirus disease 2019 pandemic is projected to impact alcohol-related liver disease (ALD) morbidity and mortality. Inter-hospital escalation-of-care referral requests to our tertiary-care hepatology unit were analyzed from January 2020 through December 2022. Most requests to our center were for ALD with an increase in requests from intermediate care units, suggestive of higher acuity illness.

Patient reflections, challenges, and supports related to early liver transplant for severe alcohol-associated liver disease.

Transplant centers conventionally require at least 6 months of alcohol abstinence before offering liver transplants for alcohol-associated liver disease. However, early liver transplant (ELT)-proceeding with a transplant when clinically necessary without first meeting the conventional requirement-is increasingly gaining attention. In our study, we qualitatively assessed ELT recipients' perceived challenges and supports regarding alcohol-associated liver disease, transplant, and posttransplant survivorship. To diversify perspectives based on gender, race/ethnicity, age, time since ELT, and pretransplant abstinence duration, we purposively recruited ELT recipients and conducted semistructured interviews. Recruitment continued until data saturation. We analyzed transcripts using inductive thematic analysis. We interviewed 20 ELT recipients between June and December 2020 and identified themes within 3 participant-characterized time periods. Three themes emerged in life before severe illness: (1) alcohol as a "constant" part of life, (2) alcohol use negatively affecting relationships and work life, and (3) feeling "stuck" in the cycle of drinking. Two themes emerged during the severe illness period: (4) rapidity of health decline and (5) navigating medical care and the 6-month abstinence requirement. Finally, in life after transplant, 4 themes emerged: (6) feelings of shame or stigma and new self-worth, (7) reconnecting with others and redefining boundaries, (8) transplant as a defining point for sobriety, and (9) work-related challenges. Overall, participants expressed gratitude for receiving a gift of life and acknowledged their responsibilities to the new liver. ELT recipient experiences reveal complex psychosocial challenges related to addiction, inadequate support system, and stigma, particularly in the posttransplant period. The care of ELT recipients would be incomplete if focused solely on optimizing patient or graft survival.

Survival Benefit of Split-Liver Transplantation for Pediatric and Adult Candidates.

Patient and graft survival are similar following whole-liver transplantations (WLTs) versus split-liver transplantations (SLTs) among pediatric and adult recipients, yet SLTs are rarely used. We sought to determine the survival benefit associated with accepting a splittable graft offer for SLT versus declining and waiting for a subsequent offer using 2010 to 2018 Scientific Registry of Transplant Recipients (SRTR) data on 928 pediatric and 1814 adult liver transplantation candidates who were ever offered a splittable graft. We compared eventual mortality, regardless of subsequent transplants, between those patients who accepted versus declined a split liver offer with adjustments for Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease (MELD) scores, diagnosis, and weight among pediatric candidates and matching for MELD score, height, and offer among adult candidates. Among pediatric candidates ≤7 kg, split liver offer acceptance versus decline was associated with a 63% reduction in mortality (adjusted hazard ratio [aHR], 0.17 0.370.80 [P = 0.01]; 93.1% versus 84.0% 1-year survival after decision). Within 1 year of decline for those ≤7 kg, 6.4% died and 31.1% received a WLT. Among pediatric candidates >7 kg, there was no significant difference associated with acceptance of a split liver offer (aHR, 0.63 1.071.82 [P = 0.81]; 91.7% versus 94.4% 1-year survival after decision). Within 1 year of decline for those >7 kg, 1.8% died and 45.8% received a WLT. Among adult candidates, split liver offer acceptance was associated with a 43% reduction in mortality (aHR, 0.39 0.570.83 [P = 0.005]; 92.2% versus 84.4% 1-year survival after decision). Within 1 year of decline for adult candidates, 7.9% died and 39.3% received a WLT. Accepting split liver offers for SLT could significantly improve survival for small children and adults on the waiting list.

Multicenter study of racial and ethnic inequities in liver transplantation evaluation: Understanding mechanisms and identifying solutions.

Racial and ethnic disparities persist in access to the liver transplantation (LT) waiting list; however, there is limited knowledge about underlying system-level factors that may be responsible for these disparities. Given the complex nature of LT candidate evaluation, a human factors and systems engineering approach may provide insights. We recruited participants from the LT teams (coordinators, advanced practice providers, physicians, social workers, dieticians, pharmacists, leadership) at two major LT centers. From December 2020 to July 2021, we performed ethnographic observations (participant-patient appointments, committee meetings) and semistructured interviews (N = 54 interviews, 49 observation hours). Based on findings from this multicenter, multimethod qualitative study combined with the Systems Engineering Initiative for Patient Safety 2.0 (a human factors and systems engineering model for health care), we created a conceptual framework describing how transplant work system characteristics and other external factors may improve equity in the LT evaluation process. Participant perceptions about listing disparities described external factors (e.g., structural racism, ambiguous national guidelines, national quality metrics) that permeate the LT evaluation process. Mechanisms identified included minimal transplant team diversity, implicit bias, and interpersonal racism. A lack of resources was a common theme, such as social workers, transportation assistance, non-English-language materials, and time (e.g., more time for education for patients with health literacy concerns). Because of the minimal data collection or center feedback about disparities, participants felt uncomfortable with and unadaptable to unwanted outcomes, which perpetuate disparities. We proposed transplant center-level solutions (i.e., including but not limited to training of staff on health equity) to modifiable barriers in the clinical work system that could help patient navigation, reduce disparities, and improve access to care. Our findings call for an urgent need for transplant centers, national societies, and policy makers to focus efforts on improving equity (tailored, patient-centered resources) using the science of human factors and systems engineering.

Inter-Hospital Escalation-of-Care Referrals for Severe Alcohol-Related Liver Disease with Recent Drinking During the COVID-19 Pandemic.

Alcohol sales and consumption have increased during the coronavirus disease 2019 pandemic, but their downstream effects on alcohol-related liver disease (ALD) are unclear. We analyzed inter-hospital escalation-of-care referrals to our tertiary care inpatient liver unit across 18 months through December 2020. There was a significant rise in severe ALD with recent unhealthy drinking in our regional community during the pandemic.

Early Liver Transplantation in Acute Alcoholic Hepatitis.

Alcohol-related liver disease (ALD) is currently the leading indication for liver transplantation in the United States. Among patients with ALD, those with acute alcoholic hepatitis who do not respond to medical treatment have a 6-month mortality of 70% without transplantation. Despite the high mortality, the majority of patients will not be eligible for transplant, given that most centers follow the 6-month abstinence rule. A handful of centers in Europe and the United States perform early liver transplantation (< 6 months abstinence) in these patients, as it provides a substantial survival benefit. Short-term outcomes for these recipients are favorable, and relapse rates parallel those seen in alcoholic cirrhosis transplant recipients who have completed the 6-month wait period. Moving forward, studies examining long-term outcomes and candidate selection are necessary for this growing subset of liver transplant candidates.

Temporal trends in utilization and outcomes of steatotic donor livers in the United States.

Steatotic donor livers (SDLs) (macrosteatosis ≥30%) represent a possible donor pool expansion, but are frequently discarded due to a historical association with mortality and graft loss. However, changes in recipient/donor demographics, allocation policy, and clinical protocols might have altered utilization and outcomes of SDLs. We used Scientific Registry of Transplant Recipients data from 2005 to 2017 and adjusted multilevel regression to quantify temporal trends in discard rates (logistic) and posttransplant outcomes (Cox) of SDLs, accounting for Organ Procurement Organization-level variation. Of 4346 recovered SDLs, 58.0% were discarded in 2005, versus only 43.1% in 2017 (P < .001). SDLs were always substantially more likely discarded versus non-SDLs, although this difference decreased over time (adjusted odds ratio in 2005-2007:13.15 15.2817.74 ; 2008-2011:11.77 13.4115.29 ; 2012-2014:9.87 11.3713.10 ; 2015-2017:7.79 8.8910.15 , P < .001 for all). Conversely, posttransplant outcomes of recipients of SDLs improved over time: recipients of SDLs from 2012 to 2017 had 46% lower risk of mortality (adjusted hazard ratio [aHR]: 0.43 0.540.68 , P < .001) and 47% lower risk of graft loss (aHR: 0.42 0.530.67 , P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: 0.90 1.041.21 , P = .6) and graft loss (aHR: 0.90 1.041.20 , P = .6) to recipients of non-SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool.

Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report.

The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.

Multicenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates.

OBJECTIVE: To determine if the association of frailty and waitlist mortality varies by candidate age. BACKGROUND: Frailty, a construct developed in geriatrics, is a state of decreased physiologic reserve, and is associated with mortality while awaiting liver transplantation (LT). However, older candidates have high comorbidity burden and less physiologic reserve, so the relationship between frailty and waitlist mortality may vary by candidate age. METHODS: We studied adults listed for LT at 2 transplant centers. The liver frailty index (grip strength, chair stands, balance) was measured at evaluation, with frailty defined as liver frailty index  ≥ 4.5. We compared the prevalence of frailty in older (≥65 yr) and younger (18-64 yr) candidates. We studied the association between frailty, age, interaction between the 2, and waitlist mortality using competing risks regression adjusted for sex, BMI, and MELDNa. RESULTS: Among 882 LT candidates, 16.6% were ≥ 65 years. Older candidates were more likely to be frail (33.3% vs 21.7%, P = 0.002). Older age [adjusted subhazard ratio (aSHR): 2.16, 95% CI: 1.51-3.09, P < 0.001] and frailty (aSHR: 1.92, 95% CI: 1.38-2.67, P < 0.001) were independently associated with higher risk of waitlist mortality. However, the association between waitlist mortality and frailty did not vary by candidate age (aSHR of frailty for younger patients: 1.90, 95% CI: 1.28-2.80, P = 0.001; aSHR of frailty for older patients: 1.98, 95% CI: 1.07-3.67, P = 0.03; P interaction = 0.9). CONCLUSIONS: Older candidates experienced higher rates of frailty than younger candidates. However, regardless of age, frailty was associated with nearly 2-fold increased risk of waitlist mortality. Our data support the applicability of the frailty concept to the whole LT population and can guide the development of prehabilitation programs targeting frailty in LT patients of all ages.

Validation of predictive models identifying patients at risk for massive transfusion during liver transplantation and their potential impact on blood bank resource utilization.

BACKGROUND: Intraoperative massive transfusion (MT) is common during liver transplantation (LT). A predictive model of MT has the potential to improve use of blood bank resources. STUDY DESIGN AND METHODS: Development and validation cohorts were identified among deceased-donor LT recipients from 2010 to 2016. A multivariable model of MT generated from the development cohort was validated with the validation cohort and refined using both cohorts. The combined cohort also validated the previously reported McCluskey risk index (McRI). A simple modified risk index (ModRI) was then created from the combined cohort. Finally, a method to translate model predictions to a population-specific blood allocation strategy was described and demonstrated for the study population. RESULTS: Of the 403 patients, 60 (29.6%) in the development and 51 (25.5%) in the validation cohort met the definition for MT. The ModRI, derived from variables incorporated into multivariable model, ranged from 0 to 5, where 1 point each was assigned for hemoglobin level of less than 10 g/dL, platelet count of less than 100 × 109 /dL, thromboelastography R interval of more than 6 minutes, simultaneous liver and kidney transplant and retransplantation, and a ModRI of more than 2 defined recipients at risk for MT. The multivariable model, McRI, and ModRI demonstrated good discrimination (c statistic [95% CI], 0.77 [0.70-0.84]; 0.69 [0.62-0.76]; and 0.72 [0.65-0.79], respectively, after correction for optimism). For blood allocation of 6 or 15 units of red blood cells (RBCs) based on risk of MT, the ModRI would prevent unnecessary crossmatching of 300 units of RBCs/100 transplants. CONCLUSIONS: Risk indices of MT in LT can be effective for risk stratification and reducing unnecessary blood bank resource utilization.

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Projected 20- and 30-Year Outcomes for Pediatric Liver Transplant Recipients in the United States.

BACKGROUND: Observed long-term outcomes no longer reflect the survival trajectory facing pediatric liver transplant (LT) recipients today. We aimed to use national registry data and parametric models to project 20- and 30-year post-transplant outcomes for recently transplanted pediatric LT recipients. METHODS: We conducted a retrospective cohort study of 13,442 first-time pediatric (age <18) LT recipients using 1987 to 2018 Scientific Registry of Transplant Recipients data. We validated the proposed method (ie, to project long-term patient and graft survival using parametric survival models and short-term data) in 2 historic cohorts (1987-1996 and 1997-2006) and estimated long-term projections among patients transplanted between 2007 and 2018. Projections were stratified by raft type, recipient age, and indication for transplant. RESULTS: Parsimonious parametric models with Weibull distribution can be applied to post-transplant data and used to project long-term outcomes for pediatric LT recipients beyond observed data. Projected 20-year patient survival for pediatric LT recipients transplanted in 2007 to 2018 was 84.0% (95% confidence interval 81.5-85.8), compared to observed 20-year survival of 72.8% and 63.6% among those transplanted in 1997 to 2006 and 1987 to 1996, respectively. Projected 30-year survival for pediatric LT recipients in 2007 to 2018 was 80.1% (75.2-82.7), compared to projected 30-year survival of 68.6% (66.1-70.9) in the 1997 to 2006 cohort and observed 30-year survival of 57.5% in the 1987 to 1996 cohort. Twenty- and 30-year patient and graft survival varied slightly by recipient age, graft type, and indication for transplant. CONCLUSIONS: Projected long-term outcomes for recently transplanted pediatric LT recipients are excellent, reflective of substantial improvements in medical care, and informative for physician-patient education and decision making in the current era.

Survival benefit of accepting livers from deceased donors over 70 years old.

Livers from older donors (OLDs; age ≥70) are risky and often declined; however, it is likely that some candidates will benefit from OLDs versus waiting for younger ones. To characterize the survival benefit of accepting OLD grafts, we used 2009-2017 SRTR data to identify 24 431 adult liver transplant (LT) candidates who were offered OLD grafts eventually accepted by someone. Outcomes from the time-of-offer were compared between candidates who accepted an OLD graft and matched controls within MELD ± 2 who declined the same offer. Candidates who accepted OLD grafts (n = 1311) were older (60.5 vs. 57.8 years, P < .001), had a higher median MELD score (25 vs. 22, P < .001), and were less likely to have hepatitis C cirrhosis (14.9% vs. 31.2%, P < .001). Five-year cumulative mortality among those who accepted versus declined the same OLD offer was 23.4% versus 41.2% (P < .001). Candidates who accepted OLDs experienced an almost twofold reduction in mortality (aHR:0.45 0.520.59 , P < .001) compared to those who declined the same offer, especially among the highest MELD (35-40) candidates (aHR:0.10 0.240.55 , P = .001). Accepting an OLD offer provided substantial long-term survival benefit compared to waiting for a better organ offer, notably among candidates with MELD 35-40. Providers should consider these benefits as they evaluate OLD graft offers.

Liver transplantation and waitlist mortality for HCC and non-HCC candidates following the 2015 HCC exception policy change.

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non-HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013-2017 SRTR data, we identified 39  350 adult, first-time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non-HCC candidates before (October 8, 2013-October 7, 2015, prepolicy) and after (October 8, 2015-October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non-HCC candidates with the same calculated MELD, HCC candidates had a 3.6-fold higher rate of DDLT prepolicy (aHR = 3.49 3.69 3.89 ) and a 2.2-fold higher rate of DDLT postpolicy (aHR = 2.09 2.21 2.34 ). Compared to non-HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = 0.54 0.63 0.73 ) and a comparable risk of mortality/dropout postpolicy (asHR = 0.81 0.95 1.11 ). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest-first liver allocation, the revised policy seems to have established allocation equity for HCC and non-HCC candidates.

Liver transplantation for alcoholic hepatitis.

While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.

Expansion of the Liver Donor Supply Through Greater Use of Split-Liver Transplantation: Identifying Optimal Recipients.

The increased use of split-liver transplantation (SLT) represents a strategy to increase the supply of organs. Although outcomes after SLT and whole liver transplantation (WLT) are similar on average among pediatric recipients, we hypothesized that the relationship between graft type and outcomes may vary depending on patient, donor, and surgical characteristics. We evaluated graft survival among pediatric (<18 years) deceased donor, liver-only transplant recipients from March 2002 until December 2015 using data from the Scientific Registry of Transplant Recipients. Graft survival was assessed in a Cox proportional hazards model, with and without effect modification between graft type and donor, recipient, and surgical characteristics, to identify conditions where the risk of graft loss for SLT and WLT were similar. In a traditional multivariable model, characteristics associated with graft loss included donor age >50 years, recipient weight <10 kg, acute hepatic necrosis, autoimmune diseases, tumor, public insurance, and cold ischemia time (CIT) >8 hours. In an analysis that explored whether these characteristics modified the relationship between graft type and graft loss, many characteristics associated with loss actually had similar outcomes regardless of graft type, including weight <10 kg, acute hepatic necrosis, autoimmune diseases, and tumor. In contrast, several subgroups had worse outcomes when SLT was used, including recipient weight 10-35 kg, non-biliary atresia cholestasis, and metabolic disease. Allocation score, share type, or CIT did not modify risk of graft type and graft failure. Although one might anticipate that individuals with higher rates of graft loss would be worse candidates for SLT, data suggest that these patients actually have similar rates of graft loss. These findings can guide surgical decision making and may support policy changes that promote the increased use of SLT for specific pediatric recipients.

Hepatitis C-positive donor liver transplantation for hepatitis C seronegative recipients.

BACKGROUND: The opioid crisis has led to an increase in hepatitis C virus-positive donors in the past decade. Whereas historically hepatitis C seropositive organs were routinely discarded, the advent of direct-acting antiviral agents has notably expanded the utilization of organs from donors with hepatitis C. There has been growing experience with liver transplantation (LT) from hepatitis C seropositive donors to hepatitis C seropositive recipients. However, data remain limited on LT from hepatitis C seropositive or hepatitis C ribonucleic acid positive donors to hepatitis C seronegative recipients. METHODS: We performed a retrospective study of 26 hepatitis C seronegative recipients who received hepatitis C seropositive donor livers followed by preemptive antiviral therapy with direct-acting antiviral treatment at the Johns Hopkins Hospital Comprehensive Transplant Center from January 1, 2017, to August 31, 2019. RESULTS: Twenty-five of the 26 recipients are alive with proper graft function; 20 of them received livers from hepatitis C nucleic acid testing positive donors. All 12 recipients who completed their direct-acting antiviral courses and have reached sufficient follow-up for sustained virologic response have achieved sustained virologic response. Nine of our recipients have either completed direct-acting antiviral treatment without sufficient follow-up time for sustained virologic response or are undergoing direct-acting antiviral treatment. One patient is awaiting antiviral treatment initiation pending insurance approval. Of note, 11 of 12 patients with sustained virologic response received a hepatitis C nucleic acid testing positive donor liver. CONCLUSION: Hepatitis C seronegative patients who receive a hepatitis C seropositive or hepatitis C nucleic acid testing positive liver allograft can enjoy good short-term outcomes with hepatitis C cure following direct-acting antiviral treatment.

The Role of Liver Transplantation in Alcoholic Hepatitis.

Acute alcoholic hepatitis is a syndrome of jaundice and hepatic decompensation that occurs with excessive alcohol consumption. The diagnosis can be made with a combination of clinical characteristics and laboratory studies, though biopsy may be required in unclear cases. Acute alcoholic hepatitis can range from mild to severe disease, as determined by a Maddrey discriminant function ≥32. Mild forms can be managed with supportive care and abstinence from alcohol. While mild form has an overall good prognosis, severe alcoholic hepatitis is associated with an extremely high short-term mortality of up to 50%. Additional complications of severe alcoholic hepatitis can include hepatic encephalopathy, gastrointestinal bleeding, renal failure, and infection; these patients frequently require intensive care unit admission. Corticosteroids may have short-term benefit in this group of patients if there are no contraindications; however, a subset of patients do not respond to steroids. New emerging therapies, which target hepatic regeneration, bile acid metabolism, and extracorporeal liver support, are being investigated. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Recent studies have demonstrated that early liver transplantation in carefully selected patients with severe alcoholic hepatitis who fail medical therapy can provide a significant survival benefit and yields survival outcomes comparable to liver transplantation for other indications, with 6-month survival rates ranging from 77% to 100%. Alcohol relapse posttransplantation remains an important challenge, and heavy consumption can contribute to graft loss and mortality. Future investigation should address the substantial post-liver transplantation recidivism rate, from improving selection criteria to increasing posttransplantation substance abuse treatment resources.