Association between bridging therapy and posttransplant outcomes in patients with HCC within Milan criteria: A systematic review and meta-analysis.

Liver transplantation is the curative therapy of choice for patients with early-stage HCC. Locoregional therapies are often employed as a bridge to reduce the risk of waitlist dropout; however, their association with posttransplant outcomes is unclear. We conducted a systematic review using Ovid MEDLINE and EMBASE to identify studies published between database inception and August 2, 2023, which reported posttransplant recurrence-free survival and overall survival among patients transplanted for HCC within Milan criteria, stratified by receipt of bridging therapy. Pooled HRs were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 38 studies, including 19,671 patients who received and 20,148 patients who did not receive bridging therapy. Bridging therapy was not associated with significant differences in recurrence-free survival (pooled HR: 0.91, 95% CI: 0.77-1.08; I2 =39%) or overall survival (pooled HR: 1.09, 95% CI: 0.95-1.24; I2 =47%). Results were relatively consistent across subgroups, including geographic location and study period. Studies were discordant regarding the differential strength of association by pretreatment tumor burden and pathologic response, but potential benefits of locoregional therapy were mitigated in those who received 3 or more treatments. Adverse events were reported in a minority of studies, but when reported occurred in 6%-15% of the patients. Few studies reported loss to follow-up and most had a risk of residual confounding. Bridging therapy is not associated with improvements in posttransplant recurrence-free or overall survival among patients with HCC within Milan criteria. The risk-benefit ratio of bridging therapy likely differs based on the risk of waitlist dropout.

Psychiatric diagnoses are common after liver transplantation and are associated with increased health care utilization and patient financial burden.

Psychiatric disorders after liver transplantation (LT) are associated with worse patient and graft outcomes, which may be amplified by inadequate treatment. We aimed to characterize the burden of psychiatric disorders, treatment patterns, and associated financial burden among liver transplantation recipients (LTRs). IQVIA PharMetrics (R) Plus for Academics-a large health plan claims database representative of the commercially insured US population-was used to identify psychiatric diagnoses among adult LTRs and assess treatment. Multivariable logistic regression analysis identified factors associated with post-LT psychiatric diagnoses and receipt of pharmacotherapy. Patient financial liability was estimated using adjudicated medical/pharmacy claims for LTRs with and without psychiatric diagnoses. Post-LT psychiatric diagnoses were identified in 395 (29.5%) of 1338 LTRs, of which 106 (26.8%) were incident cases. Treatment varied, with 67.3% receiving pharmacotherapy, 32.1% psychotherapy, 21.0% combination therapy, and 21.5% no treatment. Among 340 LTRs on psychotropic medications before transplant, 24% did not continue them post-LT. Post-LT psychiatric diagnoses were independently associated with female sex, alcohol-associated liver disease (ALD), prolonged LT hospitalization (>2 wk), and pre-LT psychiatric diagnosis. Incident psychiatric diagnoses were associated with female sex, ALD, and prolonged LT hospitalization. Patients with a post-LT psychiatric diagnosis had higher rates of hospitalization (89.6% vs. 81.5%, p <0.001) and financial liability (median $5.5K vs. $4.6K USD, p =0.006). Having a psychiatric diagnosis post-LT was independently associated with experiencing high financial liability >$5K. Over 1 in 4 LTRs had a psychiatric diagnosis in a large national cohort, yet nearly a quarter received no treatment. LTRs with psychiatric diagnoses experienced increased health care utilization and higher financial liability. Sociodemographic and clinical risk factors could inform high-risk subgroups who may benefit from screening and mitigation strategies.

Active coping, resilience, post-traumatic growth, and psychiatric symptoms among early and late liver transplant survivors.

Understanding survivorship experiences at different stages postliver transplantation (poat-LT) is essential to improving care. Patient-reported concepts including coping, resilience, post-traumatic growth (PTG), and anxiety/depression, have been implicated as important predictors of quality of life and health behaviors after LT. We aimed to descriptively characterize these concepts at different post-LT survivorship stages. This cross-sectional study featured self-reported surveys measuring sociodemographic, clinical characteristics, and patient-reported concepts including coping, resilience, PTG, anxiety, and depression. Survivorship periods were categorized as early (1 y or below), mid (1-5 y), late (5-10 y), and advanced (10 y or above). Univariable and multivariable logistic and linear regression modeling examined factors associated with patient-reported concepts. Among 191 adult LT survivors, the median survivorship stage was 7.7 years (interquartile range: 3.1-14.4) and median age was 63 years (range: 28-83); most were male (64.2%) and Caucasian (84.0%). High PTG was more prevalent in the early survivorship period (85.0%) than late survivorship (15.2%). High trait resilience was only reported by 33% of survivors and associated with higher income. Lower resilience was seen among patients with longer LT hospitalization stays and late survivorship stages. About 25% of survivors had clinically significant anxiety and depression, which was more frequent among early survivors and females with pre-LT mental health disorders. In multivariable analysis, factors associated with lower active coping included survivors ≥65 years, non-Caucasian race, lower levels of education, and nonviral liver disease. In a heterogeneous cohort including early and late LT survivors, there was variation in levels of PTG, resilience, anxiety, and depression at different survivorship stages. Factors associated with positive psychological traits were identified. Understanding determinants of LT survivorship has important implications for how we should monitor and support LT survivors.

The financial burden after liver transplantation is significant among commercially insured adults: A large US National Cohort.

Liver transplantation (LT) is lifesaving for patients with cirrhosis; however, the resultant financial burden to patients has not been well characterized. We aimed to provide a nationally representative portrayal of patient financial burden after LT. Adult recipients of LT from 2006 to 2021 were identified using IQVIA PharMetrics® Plus for Academics-a large nationally representative claims database of commercially insured Americans. Patient financial liability (ie, what patients owe) was estimated using the difference between allowed and paid costs for adjudicated medical/pharmacy claims. Descriptive statistics were provided stratified by the financial liability group within 1 year after LT. Multivariable logistic regression modeling identified factors associated with high/extreme liability adjusting for covariates. Potential indirect costs of post-LT care were estimated based on hourly wages lost for care. Among 1412 recipients of LT, financial liability was heterogeneous-~3% had no liability and 21% had extreme liability > $10K for 1-year post-LT care; most (69%) paid between $1 and 10K, with 48% having liability >$5K. Factors associated with >$5K liability included older age, insurance/enrollment type, US region, history of HCC, and simultaneous liver-kidney transplant (for liability >$10K). Medication costs comprised ~30% of outpatient financial liability. Potential indirect costs from wages lost were $2,201-$6,073 per person, depending on an hourly wage. In a large national cohort of commercially insured recipients of LT, financial liability was highly variable across sociodemographic and clinical characteristics; nearly 1 out of 2 recipients of LT owed >$5K for 1 year of post-LT care. Transplant programs should help patients anticipate potential costs and identify vulnerable populations who would benefit from enhanced financial counseling.

Early Survivorship After Liver Transplantation: A Qualitative Study Identifying Challenges in Recovery From the Patient and Caregiver Perspective.

Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions.

Antiplatelet Medications Are Associated With Bleeding and Decompensation Events Among Patients With Cirrhosis.

BACKGROUND: In an aging population with cardiovascular comorbidities, anticoagulant (AC), antiplatelet (AP), and nonsteroidal anti-inflammatory drug (NSAID) use are increasing. It remains unclear whether these agents pose increased bleeding risk in cirrhosis. This study aimed to assess the association between these medications and bleeding and portal hypertension complications in cirrhosis. METHODS: The IMS PharMetrics database was used to identify privately insured adults diagnosed with cirrhosis from 2007 to 2015, stratified as compensated or decompensated based on the presence of portal hypertensive complications 1 year before cirrhosis diagnosis. Bleeding or decompensation outcomes were assessed 6 to 18 months after cirrhosis diagnosis using a landmark analysis design. Multivariable Cox proportional hazards regression modeling assessed associations between AC, AP, and NSAID drug exposures and outcomes adjusting for covariates. RESULTS: A total of 18,070 cirrhosis patients were analyzed; 57% male; 74% ages 50 to 64 years; 34% with a prior decompensation. Overall, 377 (2%) had claims for ACs; 385 (2%) APs; and 1231 (7%) NSAIDs. APs were associated with increased bleeding [adjusted hazard ratio (aHR)=1.31; 95% confidence interval (CI): 1.00, 1.72] and decompensation events (aHR=1.44; 95% CI: 1.06, 1.95) in a 9-month landmark analysis. NSAIDs were significantly associated with bleeding events (aHR=1.29; 95% CI: 1.06, 1.57) on 3-month landmark analysis. No statistically significant associations were seen between ACs and bleeding or decompensation outcomes in adjusted analyses. CONCLUSIONS: AP use was associated with increased bleeding and decompensation events among privately insured patients with cirrhosis. NSAID use was associated with significant early bleeding, but not decompensations. Lastly ACs were not associated with bleeding or decompensation outcomes.

What Survivorship Means to Liver Transplant Recipients: Qualitative Groundwork for a Survivorship Conceptual Model.

Survivorship is a well-established concept in the cancer care continuum with a focus on disease recurrence, quality of life, and the minimization of competing risks for mortality; however, survivorship has not been well studied in liver transplantation (LT). We investigated what survivorship means to LT patients and identified motivations and coping strategies for overcoming challenges after LT. A total of 20 in-depth home interviews were conducted among adults 3 to 6 months after LT. Interviews were conducted by trained qualitative research experts and coded and analyzed using an inductive approach. A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a "second chance" at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%). LT recipients and caregivers identified multiple strategies to cope with post-LT challenges, including relying on a large network of community, spiritual, and virtual support. These findings informed a conceptual model of LT survivorship based on socioecological theory, which identified the following variables influencing survivorship: (1) pretransplant experiences, (2) individual attributes and challenges, (3) interpersonal relationships with caregivers and other social support, (4) community relationships, and (5) large-scale factors including neighborhood and financial issues. LT recipients identified themselves as survivors, and post-LT identities were greatly influenced by pre-LT experiences. These perspectives informed an in-depth conceptual model of survivorship after transplantation. We identified sources of motivation and coping strategies used in LT recovery that could be targets of survivorship interventions aimed at improving post-LT outcomes.

Complications Associated With Anesthesia Services in Endoscopic Procedures Among Patients With Cirrhosis.

BACKGROUND AND AIMS: Anesthesia services for endoscopic procedures have proliferated with the promise of increased comfort and safety. Cirrhosis patients are higher risk for sedation, yet limited data are available describing anesthesia complications in this population. APPROACH AND RESULTS: This cross-sectional study utilized the National Anesthesia Clinical Outcomes Registry, a multicenter quality-improvement database from 2010 to 2015. Patients with cirrhosis undergoing an endoscopy were identified by International Classification of Diseases, Ninth Revision (ICD-9)/Current Procedures Terminology (CPT) codes. The outcome of interest was serious anesthesia-related complication defined as cardiovascular, respiratory, neurological, drug related, patient injury, death, or unexpected admission. A mixed-effects multivariate logistic regression model determined odds ratios (ORs) between variables and serious complications, adjusting for potential confounders. In total, 9,007 endoscopic procedures were performed among patients with cirrhosis; 92% were esophagogastroduodenoscopies. The majority (81%) were American Society of Anesthesiologists (ASA) class ≥3, and 72% had a history of hepatic encephalopathy, ascites, varices, hepatorenal syndrome, or spontaneous bacterial peritonitis identified by ICD-9/CPT codes. In total, 87 complications were reported, 33 of which were serious. Frequency of serious complications was 0.4% or 378.6 per 100,000 procedures (95% confidence interval [CI], 260.8, 531.3). The majority of serious complications were cardiovascular (21 of 33), including 15 cardiac arrests. Serious complications were significantly associated with ASA 4/5 (OR, 3.84; 95% CI, 1.09, 13.57) and general anesthesia (OR, 4.71; 95% CI, 1.20, 18.50), adjusting for age, sex, ASA class, anesthesia type, inpatient status, portal hypertension history, and variable complication reporting practices. CONCLUSIONS: Anesthesia complications among endoscopic procedures in cirrhosis are rare overall. Serious complications were predominantly cardiac and associated with sicker patients undergoing general anesthesia. The complexity of end-stage liver disease may warrant more intensive care during endoscopic procedures, including anesthesia monitoring.

Complications of Anesthesia Services in Gastrointestinal Endoscopic Procedures.

BACKGROUND & AIMS: Despite the increased use of anesthesia services for endoscopic procedures in the United States, the risks of anesthesia-directed sedation (ADS) are unclear. We analyzed national data from multiple centers to determine patterns of use of anesthesia services and risk factors for serious complications. METHODS: We performed a cross-sectional study using the National Anesthesia Clinical Outcomes Registry, a national quality improvement database. Univariable and bivariate analyses investigated frequencies and relationships between predefined variables and serious complications of anesthesia (cardiovascular, respiratory, neurologic, drug-related, patient injury, death, or unexpected admission). A multivariable mixed-effects model determined the odds ratios between these variables and serious complications, adjusting for confounders and varying reporting practices. RESULTS: In total, 428,947 endoscopic procedures of adults were performed using ADS from 2010 to 2015. The population was 54.9% female with a mean age of 59.1 years, and predominantly American Society of Anesthesiologists classes 2 and 3 (74.4%). More than half of the procedures were colonoscopies (51.4%); 37.4% were esophagogastroduodenoscopies and 6.5% were endoscopic retrograde cholangiopancreatographies. A total of 4441 complications (1.09%) were reported; 1349 were serious complications (0.34%). In multivariable analysis, older age, American Society of Anesthesiologists classes 4 and 5, esophagogastroduodenoscopy, general anesthesia, cases performed on an overnight shift, and longer cases were associated independently and significantly with serious complications. CONCLUSIONS: In an analysis of data from the National Anesthesia Clinical Outcomes Registry, we found ADS during endoscopy to be safe, with few serious complications (<1% of procedures). Risk of ADS complications increased with older age, more severe disease, procedure type, and case complexity.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018.

BACKGROUND & AIMS: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States. METHODS: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases. RESULTS: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed. CONCLUSIONS: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing.

The impact of post-transplant diabetes mellitus on liver transplant outcomes.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is common after liver transplantation (LT). Yet, how PTDM relates to graft outcomes and survival needs elucidation as more individuals are transplanted for nonalcoholic fatty liver disease (NAFLD). METHODS: This single-center, retrospective study of adult LT recipients (2003-2016) identified PTDM incidence and associations with graft steatosis, rejection, and post-LT patient survival. Multivariable analysis investigated predictors of PTDM. Kaplan-Meier curves depicted patient survival 5 years post-LT. RESULTS: Among 415 adult LT recipients, 23% had pre-LT DM and 13% were transplanted for NAFLD. PTDM incidence was 34.7%, 46.9%, and 56.2% and overall survival was 90%, 80.9%, and 71.7% at 1, 3, and 5 years, respectively. Over a third of non-NAFLD patients developed PTDM. Half of PTDM cases developed by 6 months and 75% by 12 months. The PTDM group had more rejection episodes compared to no PTDM (31.9% vs 21.8%, P = 0.055), with trends toward worse patient survival 5 years post-LT (log-rank test P = 0.254). Age was the only significant predictor of PTDM. CONCLUSIONS: Post-transplant diabetes mellitus occurs rapidly in the post-LT period and is a significant problem for both NAFLD and non-NAFLD LT recipients. Age is a significant risk factor for PTDM. Outcomes trended toward increased rejection and worse survival among PTDM individuals, suggesting the benefit of early strategies targeting glucose control.

Controversies in clinical trials for alcoholic hepatitis.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease, contributing to significant morbidity and mortality. Yet, the only available therapies that improve survival are corticosteroids and liver transplantation, with no new drugs successfully developed for decades. This article briefly describes the current state of affairs in AH therapy and examines the practical and ethical challenges of conducting controlled trials in patients with severe AH. While prednisolone is considered standard of care in severe AH, this recommendation remains controversial given the marginal benefits and questionable long-term safety of steroids. Placebo-controlled trials without steroids may be necessary and ethically justified in certain populations with AH who have not been adequately investigated. Ultimately, we suggest that the field will advance with the development of a plausible animal model of true AH, a consensus on a composite clinical endpoint that does not rely solely on mortality, as well as the adoption of the NIAAA Alcoholic Hepatitis Consortia recommendations regarding standard definitions and when to request a liver biopsy prior to study entry.

Should living donor liver transplantation be an option when deceased donation is not?

When a liver transplantation candidate is declined for listing to receive a deceased organ, sometimes a loved one comes forward and offers to be a living donor. This raises the ethical question of whether a patient who is not eligible for deceased donor liver transplantation should be eligible for living donor liver transplantation. We compare living organ donation in kidney and liver transplantation and explore key ethical concepts of justice, fairness, and societal trust. Ultimately, because there is no alternative life-preserving therapy in end-stage liver disease, and because transplantation with a living donor organ does not involve removing a resource from the common pool of transplant organs, we argue that a standard of "slightly less benefit" than that required for deceased transplantation should be used to determine the acceptability of living donor liver transplantation.

Medication adherence and rejection rates in older vs younger adult liver transplant recipients.

A growing number of older adults are undergoing liver transplantation (LT) in the United States. In some settings, it is thought that adherence declines with age. This retrospective study examined adherence and clinical outcomes in older vs younger adult LT recipients. Medical records of adult LT recipients from 2009 to 2012 from a single urban center were reviewed. The medication level variability index (MLVI) was the predefined primary outcome, with nonadherence defined as MLVI >2.5. The secondary outcome was incidence of rejection. Outcomes were evaluated starting 1 year post-LT until 2015. A total of 42 of 248 patients were ≥65 at transplant. Older adults had significantly better adherence than younger ones (65%≥65 were adherent vs 42% younger adults; chi-square two-tailed P=.02). Survival analyses of rejection between age groups censored by time since transplant showed no difference among the four age groups (χ2 =0.84, P=.84). Older age was not found to be a risk factor for reduced adherence or graft rejection in patients surviving at least 1 year post-LT.

Financial burden in a US cohort of patients with HCC.

BACKGROUND: High financial burden for patients has been reported for multiple types of cancer, but there are limited data in those with HCC. We aimed to describe the financial burden for patients diagnosed with HCC and identify correlates of high financial burden. METHODS: We used the IQVIA PharMetrics Plus for Academics database to identify commercially insured patients diagnosed with HCC between 2006 and 2021. Patient financial liability was defined as the difference between allowed and paid amounts from adjudicated insurance claims. We reported total and HCC-related financial liabilities (i.e., cost for HCC-related claims), with high total financial liability defined as ≥$3000 annually and high HCC-related financial liability as ≥$1000 annually. We used multivariable logistic regression modeling to identify factors associated with high total and HCC-related financial liability. RESULTS: Among 11,609 patients with HCC, the median total financial liability during the year after HCC diagnosis was $2955 (Q1-Q3: $972-$6293). Nearly half (45%) of patients experienced high total financial liability, with the greatest liability incurred in the 3-month period immediately following HCC diagnosis. Older age, increased comorbidity, and cirrhosis-related complications were associated with higher total patient liability. Patient liability also varied by type of HCC treatment, with systemic therapy and liver transplantation having the highest financial liability in multivariable analysis. However, only 66.7% of the patients experienced HCC-related liability. CONCLUSIONS: Patients with HCC experience significant financial liability underscoring a need for price transparency as well as financial counseling in this population.

Psychiatric disorders in patients with hepatocellular carcinoma: A large US cohort of commercially insured individuals.

BACKGROUND/AIMS: Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre-existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time. METHODS: Using IQVIA PharMetrics® Plus for Academics-a nationally representative claims database of the commercially insured US population-we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment. RESULTS: Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19-1.49]), pre-existing psychiatric diagnoses (aOR 9.12 [8.08-10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66-2.77]; locoregional therapies: aOR 1.74 [1.52-1.99]; hospice: aOR 2.43 [1.79-3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006-2009 to 21.1% in 2018-2021 (p < 0.001). In almost 20% of patients with pre-existing psychiatric conditions, therapy was discontinued after HCC diagnosis. CONCLUSIONS: Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC.