Yang, Liu

Cirrhosis remains a major global cause of morbidity and mortality, with rapidly evolving etiologic drivers. This review summarizes the contemporary global epidemiology of cirrhosis, highlighting regional patterns and major transitions in underlying causes to inform prevention and policy. In 2021, cirrhosis and chronic liver disease accounted for ~1.4 million deaths worldwide. Although age-standardized mortality rates have declined in many regions, the absolute burden continues to rise due to population growth and aging. Reductions in hepatitis B and C–related cirrhosis, driven by vaccination, screening, and antiviral therapy, have been offset by a growing contribution from steatotic liver disease. High–sociodemographic index (SDI) regions exhibit lower mortality but increasing prevalence, reflecting improved survival and expanding metabolic risk, whereas low- and lower-middle–SDI regions continue to experience high mortality. Addressing the global burden of cirrhosis will require sustained public health investment focused on viral hepatitis elimination, alcohol-associated harm reduction, metabolic risk management, and equitable access to early detection and care.

Hepatic steatosis, characterized by the accumulation of triacylglycerol in hepatocytes, complicates liver transplantation by increasing the risk of ischemia-reperfusion injury (IRI), leading to suboptimal graft outcomes. This condition has become a major cause of liver graft discarding, exacerbating the ongoing organ shortage for transplantation. Recent advances in ex vivo normothermic perfusion machines (NMPs) have provided promising solutions for reconditioning and preserving steatotic liver. NMP supports cellular metabolism and mitigates IRI by maintaining the physiological conditions. In addition, pharmacological strategies to reduce hepatic steatosis have been explored to increase graft viability. In this review, we summarize current insights into hepatic lipid metabolism and the molecular mechanisms underlying steatosis, while discussing emerging pharmacological defatting approaches. These interventions have the potential to address the challenges posed by hepatic steatosis, improve graft quality, expand the availability of transplantable livers, and enhance clinical outcomes of transplant candidates. Finally, we highlight current limitations and outline directions for future research and clinical applications.

Despite European colorectal liver metastases (CRLM) transplant trials having been performed entirely using deceased donor liver transplant (DDLT), there has been speculation about whether similar results can be achieved in the United States, given the lack of MELD score prioritization. A formal transplant protocol for unresectable CRLM was implemented in our center at the start of 2022 with the plan to utilize DDLT. Between 2022 and 2025, 86 patients with CRLM were referred to our program, and 19 patients underwent a formal transplant evaluation. Median time from listing until transplant was 31 days (range 3–115 d). Median allocation MELD was 8 (range 6–15). The donor livers were from DCDs, older donors, or National Share livers, which had been declined by all other centers. All but 2 of the cases underwent advanced perfusion. There were no cases of primary nonfunction, postreperfusion syndrome, acute kidney injury, hepatic artery thrombosis, or ischemic cholangiopathy. The length of stay for the median posttransplant was 5 days. Graft and patient survival were 100% at the time of maximal follow-up. Recurrence developed in 3 recipients (25.0%), 1 of whom was treated and has no evidence of disease. These findings support the viability of DDLT for CRLM using advanced perfusion, contingent on strict protocol adherence. Center-specific waitlist dynamics must inform the choice between DDLT and living donor liver transplant (LDLT).

Objective: To develop and validate a risk score for predicting post-transplant recurrence in perihilar cholangiocarcinoma (pCCA) patients. Background: pCCA is an aggressive malignancy with a poor prognosis. Although neoadjuvant chemoradiation (CRT) followed by liver transplantation (LT) offers a potential cure for patients with unresectable, early-stage de novo or primary sclerosing cholangitis (PSC)-associated pCCA, post-transplant recurrence negatively impacts survival. Currently, no risk stratification tools exist. Methods: This retrospective study included consecutive patients with unresectable de novo or PSC-associated pCCA who underwent neoadjuvant CRT followed by LT at Mayo Clinic (1993–2024). Predictors of post-transplant recurrence were identified using multivariable Cox regression with LASSO variable selection. The Perihilar Cholangiocarcinoma Risk Estimation of Tumor Recurrence after Transplant (PRETREAT) risk score was created by assigning points from model coefficients. Score performance was evaluated by discrimination (c-statistic), internally validated with 10-fold cross-validation, and externally validated in a separate cohort. Survival outcomes were compared across 3 PRETREAT risk groups and between 2 time periods. Results: This study included 399 patients (development: 301; validation: 98). The 5-year cumulative incidence of post-transplant recurrence was 29.7% in the development cohort and 27.6% in the validation cohort. Multivariable analysis identified 4 independent predictors: macroscopic residual tumor on explant [hazard ratio (HR): 12.4], vascular encasement (HR: 2.18), lymphovascular invasion (HR: 2.04), and radial tumor diameter (HR: 1.02/mm). The PRETREAT score (0–22), based on these factors, demonstrated excellent performance in both internal and external validation (C-index 0.83 and 0.85, respectively). Patients were stratified into low-risk (0–7), moderate-risk (8–15), and high-risk (16–22) groups. The 5-year recurrence-free survival rates significantly differed across low-risk, moderate-risk, and high-risk groups (89.0%, 38.3%, and 15.4%, respectively; P<0.001). Over the last decade, overall survival improved significantly only in moderate-risk patients (70.4% vs 46.9%, P=0.024), without significant improvement in recurrence-free survival. Conclusions: The PRETREAT score provides a valuable tool for guiding post-transplant management of pCCA, enabling risk-stratified surveillance, and laying the foundation for future clinical trials.

Abstract Disclosure: A.L. McKenna: None. Y. Huang: None. L. Yang: None. N. Loo: None. C. Ritchie: None. A. Metcalfe: None. R. Nakhleh: None. M. Krishna: None. S. Thota-Kammili: None. J. Eleazer: None. A.Y. Chang: None. Hepatocellular adenomas (HCA) are uncommon, benign epithelial tumors of the liver. Risk factors include exogenous estrogen or androgen use, and genetic and metabolic syndromes. Management of HCA is delineated by sex assigned at birth; Observation is recommended in an HCA less than 5 cm in an individual assigned female at birth, while resection of an HCA in an individual assigned male at birth is recommended no matter the size due to risk of malignant transformation. What is not known is whether risk is different for individuals with gender incongruence on gender affirming hormone therapy (GAHT). There is limited data on the risk of HCA in this population. One case report of a transgender man who continued GAHT after diagnosis of an HCA though no follow-up information was available. We present follow-up on a transgender man assigned female at birth with multiple hemorrhagic HCA that was re-initiated on GAHT after stabilization of adenomas off GAHT. Unlike prior cases, the molecular profile showed ß-catenin negative, estrogen and androgen receptors positive. This is the first case report to our knowledge reporting detailed follow-up after restarting masculinizing GAHT after diagnosis of HCA. A 24-year-old transgender man presented to the emergency department with right upper quadrant pain. Initial labs were notable for ALT of 239 units per liter (U/L) and AST 165 U/L. Magnetic resonance imaging (MRI) of the abdomen and liver elastogram revealed multiple bilobar hepatic masses, the largest measuring 9.9 cm concerning for hemorrhagic HCA which was subsequently confirmed on liver biopsy. Immunostains were positive for estrogen and androgen receptors. The patient had no history of alcohol or illicit drug use, tattoos, or family history of liver disease. The patient had been treated with 100 mg of intramuscular testosterone cypionate weekly for the past six years for gender incongruence locally. No testosterone concentrations were available from prior to or during acute presentation. Discontinuation of hormone therapy was recommended along with conservative management with frequent MRI. Over the next 19 months, monitoring revealed improvement/resolution of the auto infarcting adenomas with the last MRI noting two stable HCA measuring 2.1 cm and 0.8 cm without new or enlarging liver lesions. Due to gender dysphoria off GAHT, reinitiation of hormone therapy with low dose AndroGel 1.62% topically was prescribed at 18 months after presentation. The patient has been monitored with labs monthly and plans to obtain MRI abdomen every three months. To date, the patient has tolerated reinitiation of therapy. This case demonstrates that patients on masculinizing GAHT who develop HCA can be conservatively managed and monitored based on pathology and that testosterone does not necessarily explain sex differences in the presentation/malignant transformation of HCA cisgender men as opposed to cisgender women. Presentation: 6/3/2024

Background. Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. Methods. Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. Results. Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin–tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ–space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10–20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs (P = 0.5), whereas surgical leak (P<0.001) and reoperation (P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. Conclusions. The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

INTRODUCTION: Liver disease is a significant public health problem in the United States, with notable racial disparities in mortality. This study examines liver disease mortality trends among Black and White populations during 1999–2020. METHODS: We used CDC WONDER database to ascertain liver disease age-standardized mortality rates in Black and White Americans. Annual percent change was calculated. Age-standardized absolute rate difference and rate ratios were computed by subtracting and dividing the White population's rate from that of the Black population. RESULTS: Liver diseases accounted for 171,627 Black and 1,314,903 White deaths during 1999–2020. Age-standardized mortality rates for Blacks decreased from 22.5 to 20.1 per 100,000 person-years (annual percentage change −0.4%, −0.6% to −0.2%), whereas an increase was observed for Whites, from 17.9 to 25.3 per 100,000 person-years (annual percentage change 1.4%, 1.4% to 1.7%). The rate ratio decreased from 1.26 (1.22–1.29) in 1999 to 0.79 (0.78–0.81) in 2020. This pattern was evident in all census regions, more pronounced among the younger (age 25–64 years) than older (age 65+ years) population and observed across different urbanization levels. The pattern may be attributable to increasing alcohol-related liver disease and metabolic dysfunction–associated steatotic liver disease–related deaths in Whites and tapering in viral hepatitis and primary liver cancer–related deaths in Blacks. Despite notable improvement, racial disparities persist in primary liver cancer and viral hepatitis among the Black population. DISCUSSION: The rise in alcohol-related liver disease and metabolic dysfunction–associated steatotic liver disease–related deaths among Whites, and enduring liver cancer and viral hepatitis disparities in the Black population, underscores the urgent need for tailored public health interventions.

Background: Graft-versus-host disease (GVHD) is a common complication of hematopoietic cell transplantation, and its incidence is low in liver transplantation (LT). Estimating the incidence of GVHD after LT is challenging due to the paucity of available data from the United Network for Organ Sharing. This is the first national analysis of the incidence and risk factors of GVHD after LT. Methods: This retrospective cohort study used the National Readmission Database to calculate the incidence rate of GVHD within 1 year of LT using survival analysis. The predictors of GVHD were identified using univariate and multivariate Cox regression analyses. Results: From 2010 to 2020, of 88,433 LTs, 383 cases of GVHD occurred within 1 year after LT, resulting in an incidence rate of 1.0% (95% CI: 0.8%–1.3%). We observed no statistically significant change in the incidence of GVHD after LT from 2010 to 2020 (beta-coefficient, −0.07%; 95% CI: −0.17% to 0.04%, p = 0.188). Interestingly, alcohol-associated liver disease was associated with a lower risk of GVHD (adjusted HR, 0.57; 95% CI: 0.36–0.91, p = 0.018), whereas a higher risk was found to be related to a secondary diagnosis of COVID-19 on index admission. Conclusion: Our study found that the incidence rate of GVHD within 1 year of LT in the United States was 1.0% and remained stable from 2010 to 2020. The predictors associated with GVHD include alcohol-associated liver disease and COVID-19. Our study provides valuable insights into the incidence, risk factors, and outcomes of GVHD after LT.

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P<0.001). Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.