Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients.

BACKGROUND & AIMS: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings. METHODS: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis. The primary outcome was time to alanine aminotransferase (ALT) normalization (≤40); secondary outcomes included time to ALT ≤100 U/L and time to death. To account for confounding by indication, inverse probability of treatment weighting was applied to perform Cox regression. A sensitivity analysis was performed excluding patients with grade 4 hepatitis. RESULTS: One hundred and sixty-six patients (56.5%) were hospitalized for a median of 6 (interquartile range, 3-11) days. On inverse probability of treatment weighting Cox regression, hospitalization was not associated with time to ALT normalization (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.86-1.43; P = .436) or time to ALT ≤100 U/L (HR, 1.11; 95% CI, 0.86-1.43; P = .420). In the sensitivity analysis limited to patients with grade 3 hepatitis, hospitalization was also not associated with time to ALT normalization (HR, 1.11; 95% CI, 0.83-1.50; P = .474) or time to ALT ≤100 U/L (HR, 1.19; 95% CI, 0.90-1.58; P = .225). In a subgroup analysis of 152 patients with melanoma, hospitalization was not associated with reduced risk of all-cause death (HR, 0.93; 95% CI, 0.53-1.64; P = .798). Notably, despite their Common Terminology Criteria for Adverse Events classification of high-grade hepatitis, 94% of patients had "mild" liver injury based on International Drug-Induced Liver Injury Criteria. CONCLUSIONS: Hospitalization of patients with high-grade ICI hepatitis was not associated with faster hepatitis resolution and did not affect mortality. Routine hospitalization may not be necessary in all patients with high-grade ICI hepatitis and Common Terminology Criteria for Adverse Events criteria may overestimate severity of liver injury.

Pancreatitis and Hyperlipasemia in the Setting of Immune Checkpoint Inhibitor Therapy.

BACKGROUND: Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges from asymptomatic hyperlipasemia to symptomatic acute pancreatitis (AP). The proportion of pancreatic injury while receiving ICIs that is attributable to therapy remains unclear. We evaluated the etiology of hyperlipasemia in patients receiving ICIs, and the clinical characteristics, management, and outcomes of ICI-PI. PATIENTS AND METHODS: We assessed 6,450 consecutive adult patients with cancer who received ICI doses between 2011 and 2019, 364 of whom had at least 1 instance of elevated serum lipase after ICI initiation and were included in our trial. Primary outcomes were the development of ICI-PI and ICI-induced acute pancreatitis (ICI-AP). RESULTS: Pancreatic injury was attributable to ICI use in 105 individuals (29% of those with hyperlipasemia; 1.6% overall). Of 27 patients with ICI-AP, 4 (15%) presented asymptomatically with hyperlipasemia and pancreatic inflammation on imaging. In multivariable regression, the presence of other immune-related adverse events was positively associated with ICI-AP (≥2 events: odds ratio, 5.43; 95% CI, 1.47-26.03). Compared with patients with other ICI-PI, those with ICI-AP more frequently required steroids (74% vs 4%), intravenous fluids (85% vs 10%), hospitalization (89% vs 9%), and permanent cessation of ICIs due to pancreatic injury (70% vs 3%), and less frequently continued therapy uninterrupted (0% vs 40%) (P<.01 for all). Of the 105 patients, 3 (3%) developed exocrine insufficiency and 9 (9%) developed endocrine insufficiency, which were concentrated among those with ICI-AP. CONCLUSIONS: A minority of occurrences of pancreatitis and hyperlipasemia in patients receiving ICIs are due to these therapies, supporting NCCN recommendations to exclude alternative etiologies. Because a notable proportion of patients with ICI-AP were asymptomatic but warranted treatment per current guidelines, abdominal imaging is diagnostically valuable in those with significant hyperlipasemia. Patients with ICI-AP should be monitored for exocrine pancreatic insufficiency. Many with hyperlipasemia who do not meet the criteria for AP can continue therapy uninterrupted.

Early Liver Specialist Consultation is Associated With Faster Biochemical Resolution of Severe Immune Checkpoint Inhibitor-Induced Hepatitis.

BACKGROUND: We evaluated the impact of gastroenterology/hepatology consultation, as recommended by guidelines, on the management of severe immune checkpoint inhibitor (ICI)-induced hepatitis. METHODS: We conducted a multicenter, retrospective cohort study of 294 patients who developed grade ≥3 (alanine aminotransferase [ALT] >200 U/L) ICI-induced hepatitis, with early gastroenterology/hepatology consultation defined as occurring within 7 days of diagnosis. The primary outcome was time to ALT normalization (≤40 U/L), and the secondary outcome was time to ALT improvement to ≤100 U/L. RESULTS: A total of 117 patients received early consultation. In the 213 patients with steroid-responsive hepatitis, early consultation was not associated with faster ALT normalization (hazard ratio [HR], 1.12; 95% CI, 0.83-1.51; P=.453). A total of 81 patients developed steroid-refractory hepatitis, with 44 (54.3%) receiving early consultation. In contrast to the patients whose hepatitis responded to steroid treatment, early consultation in those with steroid-refractory disease was associated with faster ALT normalization (HR, 1.89; 95% CI, 1.12-3.19; P=.017) and ALT improvement to ≤100 U/L (HR, 1.72; 95% CI, 1.04-2.84; P=.034). Notably, additional immunosuppressive therapy for steroid-refractory disease was initiated sooner after diagnosis in the early consult group (median 7.5 vs 13.0 days; log-rank P=.001). When time to additional immunosuppression was added as a covariate to the Cox model in mediation analysis, early consultation was no longer associated with time to ALT normalization (HR, 1.39; 95% CI, 0.82-2.38; P=.226) or with time to ALT improvement to ≤100 U/L (HR, 1.25; 95% CI, 0.74-2.11; P=.404). Time to additional immunosuppression remained associated with faster ALT normalization and faster ALT improvement to ≤100 U/L in the model, suggesting that the faster hepatitis resolution in the early consultation group was primarily attributable to earlier initiation of additional immunosuppression. CONCLUSIONS: Early gastroenterology/hepatology consultation is associated with faster resolution of biochemical abnormalities in patients with steroid-refractory hepatitis. This beneficial effect appears to be mediated by earlier initiation of additional immunosuppressive therapy in those receiving early consultation.

Immune checkpoint inhibitor gastritis is often associated with concomitant enterocolitis, which impacts the clinical course.

BACKGROUND: Gastrointestinal immune-related adverse events are frequently caused by immune checkpoint inhibitors (ICIs) and often require interruption of cancer treatment. Compared with ICI colitis and enteritis, limited information exists about ICI gastritis. This study characterized clinical features and treatment outcomes of ICI gastritis. METHODS: Consecutive cancer patients who received ICIs and underwent endoscopy with gastric biopsies while on ICIs from 2011 to 2021 were retrospectively assessed. Specific histopathologic features identified ICI gastritis. RESULTS: Of 6450 ICI-treated patients, 162 (2.5%) underwent endoscopy with gastric biopsies. ICI gastritis was identified in 54 (33%) biopsied patients; 38 (70%) had concurrent ICI enteritis/colitis and 16 (30%) had isolated ICI gastritis. Dyspepsia (38%) and bloating (25%) were the most frequent symptoms of isolated ICI gastritis. Compared with patients with concomitant enteritis/colitis, patients with isolated gastritis were less likely to have diarrhea (13% vs 68%; p < .001) or abdominal pain (19% vs 47%; p = .07). Patients with isolated ICI gastritis less frequently required glucocorticoids (69% vs 92%; p = .04) and had lower incidence of ICI hold/withdrawal (13% vs 42%; p = .06). There was no association between severity or extent of luminal inflammation and antitumor response (p = .85 and p = .44, respectively). Endoscopically, gastric mucosa appeared normal in 11 (20%) patients with biopsy-proven ICI gastritis. CONCLUSION: ICI gastritis may present alone or more commonly with concurrent enteritis/colitis, which may differentiate its clinical course. Gastric biopsies are required to diagnose a substantial minority of endoscopically normal, clinically significant cases. Most patients with isolated gastritis can continue ICI therapy uninterrupted, but a notable proportion require glucocorticoids. PLAIN LANGUAGE SUMMARY: Immune checkpoint inhibitors are effective anticancer treatments, but can cause inflammatory toxicities, including of the stomach (gastritis), intestine, and colon. Limited information is available on gastritis triggered by these agents. Adult patients with cancer who were treated with immune checkpoint inhibitors and had an upper gastrointestinal endoscopy with biopsies of the stomach were examined. More than two-thirds (70%) of people with checkpoint inhibitor gastritis also had inflammatory changes of the small intestine and/or colon. Compared with patients with isolated checkpoint gastritis, the subgroup with concomitant enteritis/colitis more frequently had abdominal pain, diarrhea, needed steroids, and/or needed to pause or stop antitumor therapy.

Quantitative Analysis of Liver Disease Using MRI-Based Radiomic Features of the Liver and Spleen.

BACKGROUND: Radiomics extracts quantitative image features to identify biomarkers for characterizing disease. Our aim was to characterize the ability of radiomic features extracted from magnetic resonance (MR) imaging of the liver and spleen to detect cirrhosis by comparing features from patients with cirrhosis to those without cirrhosis. METHODS: This retrospective study compared MR-derived radiomic features between patients with cirrhosis undergoing hepatocellular carcinoma screening and patients without cirrhosis undergoing intraductal papillary mucinous neoplasm surveillance between 2015 and 2018 using the same imaging protocol. Secondary analyses stratified the cirrhosis cohort by liver disease severity using clinical compensation/decompensation and Model for End-Stage Liver Disease (MELD). RESULTS: Of 167 patients, 90 had cirrhosis with 68.9% compensated and median MELD 8. Combined liver and spleen radiomic features generated an AUC 0.94 for detecting cirrhosis, with shape and texture components contributing more than size. Discrimination of cirrhosis remained high after stratification by liver disease severity. CONCLUSIONS: MR-based liver and spleen radiomic features had high accuracy in identifying cirrhosis, after stratification by clinical compensation/decompensation and MELD. Shape and texture features performed better than size features. These findings will inform radiomic-based applications for cirrhosis diagnosis and severity.

Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.

BACKGROUND AND AIMS: Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. APPROACH AND RESULTS: We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or <1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p < 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p < 0.001) steroid doses than the 128 patients in the <1.5 mg/kg group. There was no difference between the higher versus lower-dose groups in development of steroid-refractory hepatitis (OR 1.22, 95% CI 0.79-1.89, p = 0.365) on IPTW-logistic regression. In patients with steroid-responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72-1.45, p = 0.903) or IPTW-Cox regression (HR 1.09, 95% CI 0.78-1.51, p = 0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2-5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5-6.0, p = 0.001). CONCLUSIONS: In patients with high-grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications when compared with higher-dose regimens.

Association of Terry Nails With Liver Cirrhosis.

INTRODUCTION: We looked at the association between Terry nails and liver cirrhosis in an ambulatory population from hepatology and gastroenterology clinics. METHODS: We prospectively investigated the prevalence and determinants of Terry nails in 1,000 consecutive patients from hepatology and gastroenterology clinics at 2 institutions between May 2016 and February 2020. RESULTS: A total of 117 subjects manifested Terry nails, with a 25.6% prevalence in patients with cirrhosis. When adjusted for age, heart failure, diabetes mellitus type 2, and chronic liver disease, cirrhosis was the only significant correlate (odds ratio 5.7 [95% confidence interval 3.3-9.8]), irrespective of liver disease etiology, with a strong association with hepatic fibrosis stage (P < 0.0001). DISCUSSION: Sensitivity and specificity of Terry nails for cirrhosis (25.8%, 92.7%) was similar to palmar erythema but less than spider angioma.

MRI-based radiomic feature analysis of end-stage liver disease for severity stratification.

PURPOSE: We aimed to develop a predictive model of disease severity for cirrhosis using MRI-derived radiomic features of the liver and spleen and compared it to the existing disease severity metrics of MELD score and clinical decompensation. The MELD score is compiled solely by blood parameters, and so far, it was not investigated if extracted image-based features have the potential to reflect severity to potentially complement the calculated score. METHODS: This was a retrospective study of eligible patients with cirrhosis ([Formula: see text]) who underwent a contrast-enhanced MR screening protocol for hepatocellular carcinoma (HCC) screening at a tertiary academic center from 2015 to 2018. Radiomic feature analyses were used to train four prediction models for assessing the patient's condition at time of scan: MELD score, MELD score [Formula: see text] 9 (median score of the cohort), MELD score [Formula: see text] 15 (the inflection between the risk and benefit of transplant), and clinical decompensation. Liver and spleen segmentations were used for feature extraction, followed by cross-validated random forest classification. RESULTS: Radiomic features of the liver and spleen were most predictive of clinical decompensation (AUC 0.84), which the MELD score could predict with an AUC of 0.78. Using liver or spleen features alone had slightly lower discrimination ability (AUC of 0.82 for liver and AUC of 0.78 for spleen features only), although this was not statistically significant on our cohort. When radiomic prediction models were trained to predict continuous MELD scores, there was poor correlation. When stratifying risk by splitting our cohort at the median MELD 9 or at MELD 15, our models achieved AUCs of 0.78 or 0.66, respectively. CONCLUSIONS: We demonstrated that MRI-based radiomic features of the liver and spleen have the potential to predict the severity of liver cirrhosis, using decompensation or MELD status as imperfect surrogate measures for disease severity.

Bleeding Outcomes Following Transesophageal Echocardiography in Patients With Cirrhosis and Esophageal Varices.

Despite scant evidence, current guidelines indicate that esophageal varices are a relative contraindication to transesophageal echocardiography (TEE). The aim of this study is to compare the risk of gastrointestinal bleeding following TEE among cirrhotic patients with and without endoscopically-documented esophageal varices. This is a retrospective analysis of patients with cirrhosis who underwent upper endoscopy within 4 years of TEE at five institutions between January 2000 and March 2020. Primary outcome was overt gastrointestinal bleeding. Secondary outcomes were hemoglobin decline by at least 2 g/dL or blood transfusion within 48 hours following TEE. Of the 191 patients, 79 (41.4%) had esophageal varices (30.4% large). No patient experienced a primary outcome. Secondary outcomes occurred in 52 (27.2%): 28 (35.4%) with esophageal varices and 24 (21.4%) without varices. After propensity-score covariate adjustment, the odds ratio for a secondary outcome in patients with esophageal varices was 1.49 (95% confidence interval 0.74-2.99). Restricting analysis to those who underwent endoscopy within 1 year of TEE did not significantly alter results. The risk of a secondary outcome was identical between patients who had upper endoscopy prior (27.5%) versus subsequent (26.7%; P = 1.00) to TEE. Conclusions: Among patients with cirrhosis, there was no overt gastrointestinal bleeding after TEE. The likelihood of a 2 g/dL decline in hemoglobin or blood transfusion within 48 hours following TEE was not significantly higher in patients with esophageal varices after controlling for confounders. Patients who underwent upper endoscopy before TEE did not manifest a lower risk of secondary outcomes versus those who had endoscopy after TEE, suggesting that routine preprocedural endoscopy is of marginal utility.

Gastroparesis Following Immune Checkpoint Inhibitor Therapy: A Case Series.

BACKGROUND: Immune checkpoint inhibitors (ICI) have improved outcomes in patients with various malignancies; however, they can cause immune-related hepatitis and enterocolitis. Patients on ICI may also develop upper gastrointestinal symptoms and undergo measurement of gastric emptying. AIMS: Our aim was to review records of patients with gastroparesis following ICI therapy at two medical centers. METHODS: We performed a retrospective review of all patients at Mayo Clinic and Brigham and Women's/Dana-Farber Cancer Center (BWH/DFCC) who underwent gastric scintigraphy for the assessment of symptoms of gastroparesis following ICI treatment up to January 2020. Clinical presentation, medical history, laboratory evaluation, imaging, treatment, and outcomes were retrieved from the records. Gastroparesis was diagnosed as delayed gastric emptying (GE) measured by gastric scintigraphy. RESULTS: At Mayo Clinic, 2 patients (median age 59 years, 1 male [M], 1 female [F]) had delayed GE, while 4 patients (median age 53 years, 3M, 1F) had normal GE following ICI use. Of those with delayed GE (diagnosed after 38 and 2 months of ICI initiation), 1 patient was treated for non-Hodgkin's lymphoma and melanoma with ipilimumab; a second patient with breast cancer was treated with pembrolizumab. At BWH/DFCC, 2 patients (median age 56 years, 1M, 1F) had normal GE after ICI treatment, while a 62-year-old female with non-small cell lung cancer developed gastroparesis 3 months following initiation of nivolumab. CONCLUSION: This report documents gastroparesis as a potential adverse effect of ICI. Further studies should explore the potential for ICI therapy to damage anti-inflammatory macrophages that preserve the enteric neurons.

Outcomes after resumption of immune checkpoint inhibitor therapy after high-grade immune-mediated hepatitis.

BACKGROUND: In the current study, the authors assessed the risks and outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with resolved grade 3 to 4 ICI hepatitis because current guidelines recommend permanent ICI discontinuation in these patients. METHODS: The authors performed a retrospective cohort study from 2010 through 2019 of patients with melanoma who were treated with ≥1 ICIs and who recovered from grade 3 to 4 ICI hepatitis. The primary outcome was hepatitis recurrence and the secondary outcome was the development of any immune-related adverse event (irAE) requiring the discontinuation of ICI rechallenge. Best overall response and time to all-cause death were compared between the patients who did and those who did not undergo ICI rechallenge. Grading was performed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: Of the 102 patients with melanoma who developed high-grade ICI hepatitis, 31 underwent ICI rechallenge. Although 15 of 31 patients (48%) developed an irAE of any grade, only 6 patients (19%) required ICI discontinuation due to irAE severity (4 of 29 patients [14%] rechallenged with anti-PD-1 or anti-PD-L1 and 2 of 2 patients [100%] rechallenged with ipilimumab). Recurrent hepatitis accounted for 4 of these 6 cases. Rechallenged patients who did not require ICI discontinuation were found to be significantly less likely to receive ipilimumab rather than anti-PD-1 or anti-PD-L1 monotherapy (0% vs 33%; relative risk (RR), 0.1 [95% CI, 0.1-0.3; P = .032]) and significantly less likely to be rechallenged with their original ICI (8% vs 50%; RR, 0.2 [95% CI, 0.1-0.7; P = .038]). There was no difference noted with regard to best overall response or time to death between rechallenged and non-rechallenged patients. CONCLUSIONS: ICI therapy can be resumed in patients with melanoma who have recovered from grade 3 to 4 ICI hepatitis with a modest risk of serious irAEs. It remains unclear whether ICI retreatment improves clinical outcomes.

EUS-guided biliary drainage is equivalent to ERCP for primary treatment of malignant distal biliary obstruction: a systematic review and meta-analysis.

Background and study aims Although endoscopic retrograde cholangiopancreatography (ERCP) is standard of care for malignant biliary obstruction, endoscopic ultrasound-guided biliary drainage (EUS-BD) as a primary treatment has become increasingly utilized. The aim of this study was to perform a systematic review and meta-analysis to evaluate the effectiveness and safety of EUS-BD for primary treatment of malignant biliary obstruction and comparison to traditional ERCP. Methods Individualized search strategies were developed through November 2018 using PRISMA and MOOSE guidelines. A cumulative meta-analysis was performed by calculating pooled proportions. Subgroup analysis was performed for studies comparing EUS-BD versus ERCP. Heterogeneity was assessed with Cochran Q test or I 2 statistics, and publication bias by funnel plot and Egger's tests. Results Seven studies (n = 193 patients; 57.5 % males) evaluating primary EUS-BD for malignant biliary obstruction were included. Mean age was 67.4 years (2.3) followed an average of 5.4 months (1.0). For primary EUS-BD, pooled technical success, clinical success, and adverse event (AE) rates were 95 % (95 % CI 91 - 98), 97 % (95 % CI 93 - 100), and 19 % (95 % CI 11 - 29), respectively. Among EUS-BD and ERCP comparator studies, technical and clinical success, and total AEs were not different with lower rates of post-ERCP pancreatitis and reintervention among the EUS-BD group. Conclusion Primary EUS-BD is an effective treatment with few AE. Comparing EUS-BD versus ERCP, EUS-BD has comparable efficacy and improved safety as a primary treatment for malignant biliary obstruction. Further randomized trials should be performed to identify patient populations and clinical scenarios in which primary EUS-BD would be most appropriate.

Being accompanied to liver discharge clinic: An easy measure to identify potential liver transplant candidates among those previously considered ineligible.

BACKGROUND: Patients with cirrhosis deemed ineligible for liver transplantation are usually followed in general hepatology or gastroenterology clinics, with the hope of re-evaluation once they meet the appropriate criteria. Specific strategies to achieve liver transplant eligibility for these patients have not been studied. AIM: To assess clinical and sociodemographic factors associated with future liver transplant eligibility among patients initially considered ineligible. METHODS: This is a retrospective study of patients with cirrhosis considered non-transplant eligible, but without absolute contraindications, who were scheduled in our transitional care liver clinic (TCLC) after discharge from an inpatient liver service. Transplant candidacy was assessed 1 year after the first scheduled TCLC visit. Data on clinical and sociodemographic factors were collected. RESULTS: Sixty-nine patients were identified and the vast majority were Caucasian men with alcoholic cirrhosis. 46 patients (67%) presented to the first TCLC visit. Seven of 46 patients that showed to the first TCLC visit became transplant candidates, while 0 of 23 patients that no-showed did (15.2% vs 0%, P = 0.08). Six of 7 patients who showed and became transplant eligible were accompanied by family or friends at the first TCLC appointment, compared to 13 of 39 patients who showed and did not become transplant eligible (85.7% vs 33.3%, P = 0.01). CONCLUSION: Patients who attended the first post-discharge TCLC appointment had a trend for higher liver transplant eligibility at 1 year. Being accompanied by family or friends during the first TCLC visit correlated with higher liver transplant eligibility at 1 year (attendance by family or friends was not requested). Patient and family engagement in the immediate post-hospitalization period may predict future liver transplant eligibility for patients previously declined.

Advance Care Planning for Patients with Cirrhosis in a Structured Inpatient/Outpatient Hepatology Program.

Background: Patients with end-stage liver disease (ESLD) have high mortality, but low utilization of palliative care. A transitional care liver clinic (TCLC), bridging inpatient hepatology care to outpatient clinics, should offer the ideal setting for advance care planning (ACP). Objective: To examine ACP and related outcomes for TCLC patients who died within one year of the initial TCLC visit. Design: Retrospective chart review. Setting: Nontransplant eligible ESLD patients, seen in TCLC postdischarge from an inpatient liver unit. Measurements: Charts were reviewed for demographics, clinical data, ACP discussions, code status, location of death, and palliative care consultations. Results: Of the 58 patients who showed for the initial TCLC visit, 18 (31%) died within one year. Most patients were men (67%) with alcoholic cirrhosis (72%), Child-Pugh class C (55.5%) and median age of 56 years (37-72 years). There were no ACP discussions in any TCLC visits even after subsequent hospitalizations. Until their terminal hospitalization, 17 patients (94%) remained full code. Palliative care was consulted for 10 patients (56%). Despite late initiation, within two weeks of death for 6 of those 10 patients, palliative care consultation facilitated arrangements for out-of-hospital death: at home or inpatient hospice (70% vs. 12%, p = 0.01). Conclusions: Despite a structured program for ESLD patients, there were no ACP discussions until the terminal hospitalization. These findings support the need to integrate palliative care interventions in the management of ESLD patients, especially taking advantage of postdischarge visits.