Takotsubo cardiomyopathy following liver transplantation: A multicenter cohort study.

Takotsubo cardiomyopathy (TCM) is an acute, stress-mediated, reversible cardiomyopathy that occurs in the absence of hemodynamically significant coronary artery disease. We aimed to investigate the characteristics and outcomes of patients who developed TCM following liver transplantation (LT) in a multicenter study. Adult patients from 6 centers across the United States who developed TCM according to Mayo Clinic criteria following LT between 2008 and 2023 were included. Demographics, perioperative and long-term outcomes, and treatment modalities were assessed. Fifty-five patients were included. The center incidence of TCM ranged from 0.1% to 0.5%. The majority were female (54.5%) and Caucasian (87.2%), and the median age at transplant was 59 years. The primary etiologies for LT were alcohol-associated cirrhosis (49.1%) and metabolic dysfunction-associated steatotic liver disease cirrhosis (21.8%). The median time from LT to TCM diagnosis was 4 days. TCM was associated with a 60.9% reduction in left ventricular ejection fraction (LVEF) from a pretransplant median LVEF of 64.0%-25.0%. The most common treatment for TCM was diuretics (67.3%) and afterload reduction (54.5%), with only 27.3% of patients requiring vasopressor support. At a median follow-up of 31.5 months, 1-year and 3-year overall survivals (OSs) were 86.3% and 69.4%, respectively. A repeat echocardiogram performed at a median of 84 days demonstrated that 45/55 patients (81.8%) had recovered LVEF ≥50%. Patients with LVEF recovery to ≥50% had significantly improved OS compared to those without LVEF recovery >50% (106.4 vs. 12.2 mo, p = 0.001). TCM following LT is associated with a significant reduction in LVEF; however, the majority of patients recover LVEF to >50% with minimal perioperative mortality. Importantly, follow-up assessment of LVEF has significant implications as lack of recovery is associated with worse OS.

Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors on major liver outcomes in metabolic dysfunction-associated steatotic liver disease.

AIM: To compare the effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) with dipeptidyl peptidase-4 inhibitors (DPP4is) on major liver outcomes (MLO) in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: We included adult patients with T2D and MASLD, using metformin without specific liver conditions or surgeries, from the Merative MarketScan database. Patients initiating SGLT2is or DPP4is from 1 January 2014 to 31 December 2022 were identified. The primary outcome was time to MLO diagnosis. Overlap weighting balanced covariates, integrated with a Cox proportional hazards model for survival analysis. RESULTS: Among 44 651 patients, 22 100 initiated SGLT2is, and 22 551 began DPP4is. After weighting, the incidence rate of MLO in the SGLT2i group was 3.8 per 1000 person-years, and it was 3.9 per 1000 person-years in the DPP4i group, resulting in an adjusted hazard ratio (aHR) of 0.82 (95% CI, 0.60-1.10). SGLT2i initiation was not associated with cirrhosis (aHR: 0.77; 95% CI, 0.55-1.06) or hepatocellular carcinoma (aHR: 0.99; 95% CI, 0.47-1.83) separately. Subgroup and sensitivity analyses did not yield significant results. CONCLUSIONS: In patients with T2D and MASLD, SGLT2is did not show a lower risk of MLO compared with DPP4is. Clinicians should consider the overall patient conditions and the additional benefits of SGLT2is to support the decision to switch from DPP4is.

Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND & AIMS: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032). CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies.

Financial toxicity in living donor liver transplantation: A call to action for financial neutrality.

After 2 decades of limited growth, living donor liver transplant (LDLT) has been increasingly accepted as a promising solution to the growing organ shortage in the US. With experience, LDLT offers superior graft and patient survival with low rates of rejection. However, not all waitlisted patients have equal access to LDLT, with financial toxicity representing a substantial barrier. Potential living liver donors face indirect, direct, and opportunity costs associated with donation as well as insurance-based discrimination and variable employer leave policies. There are multiple potential national, local, and patient-centered solutions to address some of the cost-related issues associated with living LDLT. These include standardization of employer leave policies, creation of federal and state-led tax relief programs, optimization of National Living Donor Assistance Center use, engagement of independent living donor advocates, creation of financial toolkits, and encouragement of recipient or donor-led fundraising. In this piece, members of the North American Living Liver Donation Group, a consortium of 37 LDLT programs, explore these financial challenges and discuss solutions to achieve financial neutrality, where individuals can donate free from financial constraints or gains. As a community, it is imperative that we confront factors driving financial toxicity to improve equity and access to LDLT.

Opioid use and risks in candidates and recipients of liver transplant.

Opioid use is extremely prevalent among patients with cirrhosis and those who received liver transplant (LT), despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and patients before and after LT specifically. As a result, there is significant center-level variability in opioid-related practices and policies. The existing data-largely based on retrospective observational studies-do suggest that opioids are associated with increased health resource utilization pre-LT and post-LT and that they may precipitate HE in patients with cirrhosis and increase the risk of graft loss and death after LT. The strongest predictor of opioid use after LT is opioid use before transplant; thus, a focus on safe opioid use in the pretransplant and peritransplant periods is essential for minimizing opioid-related harms. We describe 3 strategies to guide LT providers including (1) improved characterization of pain, mental health symptoms, and opioid and polysubstance use; (2) minimization of opioid prescriptions for those at highest risk of adverse events; and (3) safe prescribing strategies for those who do use opioids and for the management of opioid use disorder. Ultimately, our goal is to improve the quality of life and transplant outcomes among patients with cirrhosis and those who received LT, particularly those living with concurrent pain, mental health, and substance use disorders.

Esophageal Lichen Planus: A Descriptive Multicenter Report.

GOALS: To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP). BACKGROUND: ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series. STUDY: A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States. RESULTS: Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers. CONCLUSIONS: Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.

EUS-guided coil injection therapy in the management of gastric varices: the first U.S. multicenter experience (with video).

BACKGROUND AND AIMS: Despite the significant morbidity associated with gastric variceal bleeding, there is a paucity of high-quality data regarding optimal management. EUS-guided coil injection therapy (EUS-COIL) has recently emerged as a promising endoscopic modality for the treatment of gastric varices (GV), particularly compared with traditional direct endoscopic glue injection. Although there are data on the feasibility and safety of EUS-COIL in the management of GV, these have been limited to select centers with particular expertise. The aim of this study was to report the first U.S. multicenter experience of EUS-COIL for the management of GV. METHODS: This retrospective analysis included patients with bleeding GV or GV at risk of bleeding who underwent EUS-COIL at 10 U.S. tertiary care centers between 2018 and 2022. Baseline patient and procedure-related information was obtained. EUS-COIL entailed the injection of .018 inch or .035 inch hemostatic coils using a 22-gauge or 19-gauge FNA needle. Primary outcomes were technical success (defined as successful deployment of coil into varix under EUS guidance with diminution of Doppler flow), clinical success (defined as cessation of bleeding if present and/or absence of bleeding at 30 days' postintervention), and intraprocedural and postprocedural adverse events. RESULTS: A total of 106 patients were included (mean age 60.4 ± 12.8 years; 41.5% female). The most common etiology of GV was cirrhosis (71.7%), with alcohol being the most common cause (43.4%). Overall, 71.7% presented with acute GV bleeding requiring intensive care unit stay and/or blood transfusion. The most common GV encountered were isolated GV type 1 (60.4%). A mean of 3.8 ± 3 coils were injected with a total mean length of 44.7 ± 46.1 cm. Adjunctive glue or absorbable gelatin sponge was injected in 82% of patients. Technical success and clinical success were 100% and 88.7%, respectively. Intraprocedural adverse events (pulmonary embolism and GV bleeding from FNA needle access) occurred in 2 patients (1.8%), and postprocedural adverse events occurred in 5 (4.7%), of which 3 were mild. Recurrent bleeding was observed in 15 patients (14.1%) at a mean of 32 days. Eighty percent of patients with recurrent bleeding were successfully re-treated with repeat EUS-COIL. No significant differences were observed in outcomes between high-volume (>15 cases) and low-volume (<7 cases) centers. CONCLUSIONS: This U.S. multicenter experience on EUS-COIL for GV confirms high technical and clinical success with low adverse events. No significant differences were seen between high- and low-volume centers. Repeat EUS-COIL seems to be an effective rescue option for patients with recurrent bleeding GV. Further prospective studies should compare this modality versus other interventions commonly used for GV.

Intersection of Coronavirus Disease 2019 and Alcohol-associated Liver Disease: A Review of Emerging Trends and Implications.

PURPOSE: This review will provide an overview of alcohol use and alcohol associated liver disease (ALD) prior to the coronavirus disease 2019 (COVID-19) pandemic and the impact of the pandemic on alcohol use and ALD. Furthermore, this review will explore strategies to mitigate the growing disease burden of AUD and ALD. METHODS: A search using PubMed was performed for articles on topics related to alcohol use, ALD, and COVID-19. The literature was reviewed and pertinent sources were used for this narrative review. FINDINGS: In the United States (US), excessive alcohol use is the third leading cause of preventable death. Prior to the COVID-19 pandemic, the increasing prevalence of alcohol use disorder (AUD) and ALD in the US had already constituted a public health crisis given the association between alcohol misuse, AUD, and ALD with significant medical, economic, and societal burdens. The COVID-19 pandemic led to increased alcohol consumption and downstream consequences, including increased prevalence of AUD, ALD, ALD-related hospitalization and death, and liver transplantation for ALD. IMPLICATIONS: There is a critical need for additional, multi-pronged interventions to mitigate the mortality and morbidity linked to ALD.

Incidental Finding of Hepatic Inflammatory Pseudotumor Immunoglobulin G4-Related Disease With Underlying Chronic Hepatitis C.

Immunoglobulin G4-related disease (IgG4-RD) is a unique immunological disease that can impact multiple organs including a formation of a hepatic inflammatory pseudotumor (IPT). We present a case of a 67-year-old male with a history of chronic viral hepatitis C infection who had an accidental finding on magnetic resonance imaging (MRI) of a liver arterially enhancing lesion. With an extensive work-up, immunohistochemical stains for immunoglobulin G of the liver lesion was performed and showed markedly increased IgG4-positive plasma cells (> 50/HPF), which was consistent with hepatic inflammatory pseudotumor related to IgG4-RD. The patient was treated with prednisone with a complete resolution of the hepatic lesion. The diagnosis of hepatic IPT and IgG4-RD requires a high degree of clinical suspicion and coordination with a multi-disciplinary team, including pathologists. Early tissue acquisition and staining for IgG4 was essential for the early diagnosis and treatment in this case. We also provide a comprehensive summary of published reports of IgG4-RD presenting with IPT.

High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States. METHODS: Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients' 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use. RESULTS: A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively). CONCLUSIONS: Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention.

Type of donor liver transplant does not affect pregnancy outcomes-a systematic review and meta-analysis.

Liver transplant (LT) has become increasingly common among reproductive-aged women. The effect of the type of liver donor, either a living donor LT (LDLT) or a deceased donor LT, on pregnancy outcomes is unknown. As such, we aim to review the available literature and assess obstetric, pregnancy, or delivery outcomes in LDLT. We conducted a comprehensive literature review of MEDLINE, EMBASE, Cochrane, and Scopus databases. Random-effect meta-regression assessed the association between the percentage of women who underwent LDLT (independent variable) and the proportion of outcomes. Meta-regression results were expressed as a regression coefficient, which transforms the proportion of outcomes of interest associated with a 1% increase in the percentage of LDLT patients. A value of 0 denotes no relationship between the outcomes and LDLT. A total of 6 articles (438 patients) were included, with a total of 806 pregnancies. Eighty-eight (20.09%) patients underwent LDLT. None of the studies segregated the data based on the type of donor LT. The median time from LT to pregnancy was 4.86 (4.62-5.03) years. Twelve (1.5%) stillbirths were reported. LDLT was statistically significantly associated with a higher rate of stillbirths (coefficient 0.002, p < 0.001; I 2 0%). The type of donor LT was not associated with an increased risk of other obstetric, pregnancy, or delivery complications. This is the first meta-analysis to evaluate the effect of the type of donor LT on pregnancy outcomes. This study highlights the lack of robust literature addressing this important topic. The results suggest that pregnancy outcomes after LDLT and deceased donor LT are comparable. Despite LDLT being statistically significantly associated with a higher rate of stillbirths, the association is weak and is unlikely to be clinically significant.

Long-term clinical outcomes of patients with COVID-19 and chronic liver disease: US multicenter COLD study.

BACKGROUND: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. METHODS: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19. RESULTS: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31-462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n=1332), patients with CLD with COVID-19 had worse long-term survival [p<0.001; hazards ratio (HR): 1.69; 95% CI: 1.19-2.41] and higher rate of hospitalization (p<0.001, HR: 2.00, 1.62-2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p=0.05, HR: 2.45, 1.01-2.11), Hispanic ethnicity (p=0.003, HR: 1.94, 1.26-2.99), and severe COVID-19 requiring mechanical ventilation (p=0.028, HR: 1.74, 1.06-2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n=470) of patients with CLD and history of COVID-19, of whom, 70% (n=326) had received the COVID-19 vaccine. CONCLUSIONS: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems.

Cost and value in liver disease guidelines: 2011-2022.

BACKGROUND: Chronic liver disease (CLD) is associated with rising health care utilization and cost. We aimed to describe the frequency of cost/value (C/V) statements in CLD-related clinical guidance documents (CGDs). METHODS: CGD with a focus on CLD published between January 2011 and February 2022 from 3 US societies [Association for the Study of Liver Diseases (AASLD), American College of Gastroenterology (ACG), and American Gastroenterological Association (AGA)] were analyzed. FINDINGS: Forty-five CGDs were identified. Eighty of 1334 guidance statements were C/V statements (6%). Only 1.1% reported patient-level costs and none reported out-of-pocket costs. Despite the increased importance of incorporating cost and value into care, the proportion of C/V statements in CGDs related to liver disease is low.