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

After two decades of limited growth, LDLT has been increasingly accepted as a promising solution to the growing organ shortage in the U.S. 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 liver transplant candidates and recipients.

Opioid use is extremely prevalent among cirrhosis and liver transplant (LT) patients, 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 pre- and post-LT patients specifically. As a result there is significant center-level variability in opioid-related practice and policies. The existing data-largely based on retrospective observational studies-does suggest that opioids are associated with increased health resource utilization pre- and post-LT, and that they may precipitate hepatic encephalopathy (HE) in patients with cirrhosis and increase risk of graft loss and death post-LT. The strongest predictor of opioid use post-LT is opioid use prior to transplant; thus, a focus on safe opioid use in the pre- and peri-transplant periods is essential for minimizing opioid-related harms. We describe three 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 management of opioid use disorder (OUD). Ultimately, our goal is to improve quality of life and transplant outcomes among cirrhosis and LT patients, 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.

Hepatocellular Carcinoma from a Hepatologist's Perspective.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, represents a growing health challenge worldwide. The incidence of HCC is rising, which, in turn, has led to a corresponding increase in the associated number of deaths. HCC will become the third leading cause of cancer-related deaths in the United States by 2030. HCC usually develops in the setting of chronic liver disease. Individuals at increased risk of HCC are recommended to undergo surveillance with ultrasound every 6 months along with serum α-fetoprotein testing. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered alternatives based on specific patient factors. Lesions suspicious for HCC are recommended to undergo a diagnostic testing, which includes contrast-enhanced multiphase CT or MRI and liver biopsy when findings are indeterminate. The Barcelona Clinic Liver Cancer prognosis and treatment strategy is the most used assessment for patients with HCC ( Fig. 2 ). Curative therapies include resection, liver transplantation, and ablation. Locoregional therapies, such as transarterial chemoembolization and radioembolization, can be used for patients with intermediate-stage HCC. For patients with advanced-stage HCC, systemic therapy is often used. This review aims to provide an overview of HCC from a hepatologist's perspective, including epidemiology, screening, surveillance, diagnosis, and management.

Rates of timely paracentesis for patients admitted to hospital with cirrhosis and ascites remain low but are unaffected by the COVID-19 pandemic.

For the first 6 months of the novel coronavirus-19 (COVID-19) pandemic, the hospital medicine procedure service at our center was temporarily unavailable. We assessed paracentesis rates and clinical outcomes for patients admitted with cirrhosis and ascites before and during the COVID-19 pandemic. Two hundred and twenty-four and 131 patients with cirrhosis and ascited were admitted to hospital before and during COVID-19 respectively. Approximately 50.9% and 49.6% of patients underwent a paracentesis within 24 h pre- and mid-pandemic, p = .83. No differences were observed for length-of-stay or 30-day readmissions. GI consultation was associated with higher rates of paracentesis in both eras (p < .001 pre-COVID-19, and p = .01 COVID-19). Changes due to the COVID-19 pandemic did not result in changes to rates of timely paracentesis in patients admitted with cirrhosis and ascites. While involvement of gastroenterology may increase rates of paracentesis, further efforts are needed to optimize rates of timely paracentesis to positively impact clinical outcomes.