Statewide Survey of Primary Care and Subspecialty Providers on Hepatocellular Carcinoma Risk-Stratification and Surveillance Practices.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. AIMS: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. METHODS: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics. RESULTS: After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification. CONCLUSIONS: In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance.

Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis. METHODS: We searched PubMed, Web of Science, Embase, and Cochrane Library from January 1, 2014 to December 31, 2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after direct-acting antivirals. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity. RESULTS: We included 31 studies involving 27,711 patients with cirrhosis (mean follow-up, 2.1 years) and 11 studies involving 32,123 patients without cirrhosis (mean follow-up, 2.6 years). HCC incidence was 2.99/100 person-years (95% confidence interval [CI], 2.52-3.54; I2 = 75%) in patients with cirrhosis, 0.47/100 person-years (95% CI, 0.32-0.70, I2 = 71%) in patients without cirrhosis, and 0.63/100 person-years (95% CI: 0.34-1.20, I2 = 0%) in stage 3 (F3) fibrosis. Among patients with cirrhosis, HCC incidence was highest in studies with <1 year of follow-up (6.17/100 person-years [95% CI, 3.73-10.19]) and progressively lower in studies with longer follow-up (1-2 years: 2.75/100 person-years [95% CI, 2.48-3.06]; 2-3 years: 2.90/100 person-years [95% CI, 1.90-4.44]; ≥3 years: 1.83/100 person-years [95% CI, 0.88-3.80]). CONCLUSION: Pooled HCC incidence after SVR in patients with cirrhosis was very high (2.99/100 person-years) but may be declining as longer time accrues after SVR. In patients without cirrhosis, including F3 fibrosis, HCC incidence was lower than thresholds associated with cost-effective HCC screening. In patients with F3 fibrosis, the lack of between-study heterogeneity provides strong evidence that HCC screening may not be warranted.

A Pilot Study of Accelerometer-Based Biometric Data Collection among Patients Undergoing Locoregional Therapies.

This study evaluated the feasibility of measuring patient recovery after locoregional therapies (LRTs) using a wearable activity tracker (WAT). Twenty adult patients with cancer were provided with a WAT device to wear for a minimum of 7 days prior to their procedure (baseline) and for up to 30 days after their procedure (recovery). Daily step counts were continuously recorded. Patient responses to the Short Form 36-Item Health Survey (SF-36) were also collected before and after LRT. Analysis of WAT data demonstrated a mean of 4,850 daily steps taken at baseline, which decreased to 2,000 immediately after LRT and then rapidly increased to approximately 4,300 daily steps over an average of 10 days (P < .001). No significant changes were observed in SF-36 responses between baseline and follow-up assessments (P > .10). These results suggest that WAT devices capture dynamic periprocedural data not reflected in survey-based assessments and may be used to monitor patient recovery after interventional oncologic procedures.

Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

The COVID-19 Pandemic Highlights Opportunities to Improve Hepatocellular Carcinoma Screening and Diagnosis in a National Health System.

INTRODUCTION: We evaluated the coronavirus disease 2019 (COVID-19) pandemic's impact on hepatocellular carcinoma (HCC) screening and diagnosis among patients with cirrhosis in the Veterans Health Administration. METHODS: Rates and predictors of screening and diagnosis were reviewed September 1, 2019-February 29, 2020 ("pre-COVID-19," N = 94,612) and April 1, 2020-September 30, 2020 ("post-COVID-19," N = 88,073). RESULTS: Screening and diagnosis rates declined by 44% and 13%, respectively, after the COVID-19 pandemic. Screening declined irrespective of liver disease severity, but diagnosis declined only in Model for End Stage Liver Disease-Sodium score <20 or Fibrosis-4 score <3.25. Fibrosis-4 score ≥3.25 and HCC risk ≥1.5%/year strongly predicted HCC diagnosis but only moderately predicted receipt of screening. DISCUSSION: Screening and diagnosis rates declined after the COVID-19 pandemic. Prioritizing screening for patients at greatest risk for HCC may reduce delays in diagnosis.

Health Within Reach-a Patient-Centered Intervention to Increase Hepatitis B Screening Among Asian Americans: a Randomized Clinical Trial.

BACKGROUND: There are few studies to date of interventions to increase viral hepatitis screening among Asian Americans, who have high rates of chronic hepatitis B (HBV) infection. OBJECTIVE: To develop, implement, and test the efficacy of a mobile application (Hepatitis App) delivered in four languages to increase HBV screening among Asian Americans. DESIGN: Cluster-randomized clinical trial. PARTICIPANTS: Four hundred fifty-two Asian American patients ≥ 18 years of age, who had no prior HBV testing, and received primary care within two healthcare systems in San Francisco, CA. INTERVENTIONS: The intervention group received the Hepatitis App, delivering interactive video education on viral hepatitis in English, Cantonese, Mandarin, or Vietnamese and a provider printout (Provider Alert) and Provider Panel Notification. The comparison group received a mobile application delivering nutrition and physical activity education and Provider Panel Notification. MAIN MEASURES: Primary outcomes were patient-provider discussion about HBV and documentation of a HBV screening test within 3 months post-intervention. Secondary outcome was documentation of an order for a HBV screening test. KEY RESULTS: Participants had a mean age of 57 years and were 64% female, 80% foreign-born, and 44% with limited English fluency. At post-visit, over 80% of intervention participants reported they liked using the Hepatitis App. At 3-month follow-up, the intervention group was more likely than the comparison group (all P < 0.001) to have discussed HBV with their provider (70% vs.16%), have a HBV test ordered (44% vs.10%), and receive a HBV test (38% vs.8%). In multivariable analyses, the intervention odds ratio for HBV test ordering was 7.6 (95% CI: 3.9, 14.8) and test receipt was 7.5 (95% CI: 3.6, 15.5). CONCLUSIONS: A multi-lingual educational intervention using a mobile application in primary care clinics was well received by Asian American patients, enhanced patient-provider communication about HBV, and increased HBV screening. Technology can improve healthcare quality among Asian Americans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02139722 ( https://clinicaltrials.gov/ct2/show/NCT02139722 ).

PM2.5 air pollution exposure and nonalcoholic fatty liver disease in the Nationwide Inpatient Sample.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Particulate matter air pollution <2.5 µm in diameter (PM2.5) is a ubiquitous exposure primarily produced from fossil fuel combustion. Previous epidemiologic studies have been mixed. The objective of this study was to examine the association between ambient PM2.5 exposure and NAFLD among hospitalized patients in the Nationwide Inpatient Sample (NIS). METHODS: We conducted a cross-sectional analysis of hospitalizations from 2001 to 2011 using the NIS, the largest nationally representative all-payer inpatient care administrative database in the United States. Average annual PM2.5 exposure was estimated by linking census tracts (based on NIS-provided hospital ZIP Codes) with a spatiotemporal exposure model. Clinical conditions were identified using hospital discharge diagnosis codes. Multivariable logistic regression incorporating discharge weights was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PM2.5 exposure and odds of NAFLD among hospitalized patients adjusting for age, sex, race/ethnicity, year, individual- and area-level socioeconomic status, urbanicity, region, obesity, diabetes, metabolic syndrome, impaired fasting glucose, dyslipidemia, hypertension, obstructive sleep apnea, and smoking. RESULTS: There were 269,705 hospitalized patients with NAFLD from 2001 to 2011 (total unweighted n = 45,433,392 hospitalizations). Higher ambient PM2.5 exposure was associated with increased odds of NAFLD among hospitalized patients (adjusted OR: 1.24 per 10 µg/m3 increase, 95% CI 1.15-1.33, p < 0.01). There were statistically significant interactions between PM2.5 exposure and age, race/ethnicity, diabetes, smoking, and region, with stronger positive associations among patients who were aged ≥45 years, non-Hispanic White or Asian/Pacific Islander, non-diabetics, non-smokers, or in the Midwest and West regions, respectively. CONCLUSIONS: In this nationwide cross-sectional analysis of the NIS database, there was a positive association between ambient PM2.5 exposure and odds of NAFLD among hospitalized patients. Future research should examine the effects of long-term historical PM2.5 exposure and incident NAFLD cases.

Rates and Predictors of Undergoing Different Hepatocellular Carcinoma Screening Tests in Patients With Cirrhosis.

INTRODUCTION: We aimed to assess rates and predictors of hepatocellular carcinoma (HCC) screening among patients with cirrhosis. METHODS: We reviewed electronic health records of 11,361 patients with cirrhosis from 11 U.S. Veterans Health Administration facilities for receipt of HCC screening in the 6 months preceding October 1, 2019. RESULTS: Nearly half of the cohort (46%) received HCC screening over a 6-month period. Screening rates and modalities (ultrasound, computed tomography, magnetic resonance imaging, serum alpha fetoprotein) varied by facility. Screening was associated with race/ethnicity, body mass index ≥ 25, cirrhosis etiology, thrombocytopenia, Fibrosis-4 ≥ 3.25, and lower Model for End-Stage Liver Disease-Sodium. DISCUSSION: HCC screening rates varied by facility. Higher risk patients were more likely to receive screening.

Impact of exposure to patients with COVID-19 on residents and fellows: an international survey of 1420 trainees.

OBJECTIVES: To determine how self-reported level of exposure to patients with novel coronavirus 2019 (COVID-19) affected the perceived safety, training and well-being of residents and fellows. METHODS: We administered an anonymous, voluntary, web-based survey to a convenience sample of trainees worldwide. The survey was distributed by email and social media posts from April 20th to May 11th, 2020. Respondents were asked to estimate the number of patients with COVID-19 they cared for in March and April 2020 (0, 1-30, 31-60, >60). Survey questions addressed (1) safety and access to personal protective equipment (PPE), (2) training and professional development and (3) well-being and burnout. RESULTS: Surveys were completed by 1420 trainees (73% residents, 27% fellows), most commonly from the USA (n=670), China (n=150), Saudi Arabia (n=76) and Taiwan (n=75). Trainees who cared for a greater number of patients with COVID-19 were more likely to report limited access to PPE and COVID-19 testing and more likely to test positive for COVID-19. Compared with trainees who did not take care of patients with COVID-19 , those who took care of 1-30 patients (adjusted OR [AOR] 1.80, 95% CI 1.29 to 2.51), 31-60 patients (AOR 3.30, 95% CI 1.86 to 5.88) and >60 patients (AOR 4.03, 95% CI 2.12 to 7.63) were increasingly more likely to report burnout. Trainees were very concerned about the negative effects on training opportunities and professional development irrespective of the number of patients with COVID-19 they cared for. CONCLUSION: Exposure to patients with COVID-19 is significantly associated with higher burnout rates in physician trainees.

Disseminated adenovirus infection after autologous stem cell transplant.

Adenovirus is an infrequent but challenging viral complication of transplantation that is rarely reported after autologous stem cell transplant. We present a case of disseminated adenovirus infection in a woman who received an autologous stem cell transplant for treatment of multiple sclerosis. After presenting with post-transplant episodic diarrhea and viremia, endoscopic biopsies and immunohistochemical staining confirmed the diagnosis of disseminated adenovirus infection. Her symptoms and viremia resolved after treatment with cidofovir. This case demonstrates that a high index of suspicion, a systematic clinical approach, and immunohistochemical tissue staining are necessary to diagnose disseminated adenovirus infection in an unexpected host.

Race and Hepatitis C Care Continuum in an Underserved Birth Cohort.

BACKGROUND: Birth cohort screening is recommended for hepatitis C virus (HCV) and underserved populations are disproportionally affected by HCV. Little is known about the influence of race on the HCV care continuum in this population. OBJECTIVE: To assess the cascade of HCV care in a large racially diverse and underserved birth cohort. DESIGN: Retrospective cohort study using electronic medical record data abstracted until August 31, 2017. PATIENTS: 34,810 patients born between 1945 and 1965 engaged in primary care between October 1, 2014, and October 31, 2016, within the safety-net clinics of the San Francisco Health Network. MAIN MEASURES: Rate of hepatitis C testing, hepatitis C treatment, and response to therapy. RESULTS: Cohort characteristics were as follows: median age 59 years, 57.6% male, 25.5% White (20.6% Black, 17.7% Latino, 33.0% Asian/Pacific Islander (API), 2% other), and 32.6% preferred a non-English language. 99.7% had an HCV test (95.4% HCV antibody, 4.3% HCVRNA alone). Among HCV antibody-positive patients (N = 4587), 22.9% were not tested for confirmatory HCVRNA. Among viremic patients (N = 3673), 20.8% initiated HCV therapy, 90.6% achieved sustained virologic response (SVR) and 8.1% did not have a SVR test. HCV screening and treatment were highest in APIs (98.7 and 34.7% respectively; p < 0.001). Blacks had the highest chronic HCV rate (22.2%; p < 0.001). Latinos had the lowest SVR rate (81.3%; p = 0.01). On multivariable analysis, API race (vs White, OR 1.20; p = 0.001), presence of HIV co-infection (OR 1.58; p = 0.02), presence of chronic kidney disease (OR 0.47; p < 0.001), English (vs non-English) as preferred language (OR 0.54; p = 0.002), ALT (OR 0.39 per doubling; p < 0.001), and HCVRNA (OR 0.83 per 10-fold increase; p < 0.001) were associated with HCV treatment. CONCLUSIONS: Despite near-universal screening, gaps in active HCV confirmation, treatment, and verification of cure were identified and influenced by race. Tailored interventions to engage and treat diverse and underserved populations with HCV infection are needed.

Direct Acting Antivirals Improve HCV Treatment Initiation and Adherence Among Underserved African Americans.

INTRODUCTION AND AIM: Adherence to hepatitis C (HCV) care was suboptimal in the interferon era among underserved African Americans (AA), but adherence data in the era of direct acting antivirals (DAA) is lacking in this population. We aimed to evaluate the impact of DAA on HCV care in underserved AA. MATERIAL AND METHODS: Clinical records of AAs undergoing HCV evaluation attending a safety net health system liver clinic were reviewed from 2006 to 2011 (pre-DAA), and January 1, 2014 to December 31, 2016 (post-DAA). RESULTS: 291 patients were identified (129 pre-DAA, and 162 post-DAA). Median age was 58, 66% were male, 91% had HCV genotype 1, and 70% had fibrosis ≥ stage 2. Post-DAA patients were older (60 vs. 53 years; p < 0.001), had higher rates of insurance (98 vs. 88%; p < 0.001), liver fibrosis ≥ stage 2 (77 vs. 61%; p = 0.048), ≥ 2 medical comorbidities (19 vs. 0.8%; p < 0.001), and median baseline log10 HCV RNA (6.07 vs. 5.81 IU/mL; p < 0.001), but lower median ALT (46 vs. 62 U/L; p < 0.001). Post-DAA, fewer patients were treatment ineligible (5.6 vs. 39%; p < 0.001) and more initiated therapy (71 vs. 8.5%; < 0.001), were adherent to HCV care (82 vs. 38%; p < 0.001), and achieved cure (95.7 vs. 63.6%, p < 0.001). Availability of DAA was independently associated with improved adherence to HCV care (OR 10.3, 95% CI 4.84-22.0). CONCLUSION: Availability of DAA is associated with increased treatment eligibility, initiation, adherence to HCV care, and cure in HCV-infected underserved AAs; highlighting the critical role of access to DAA in this population.

Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure.

Importance: The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking. Objective: To evaluate the association of HCC screening after HCV cure with overall survival. Design, Setting, and Participants: This cohort study evaluated patients with HCV cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. Data analysis occurred from October 2023 to January 2024. Exposures: The percentage of time spent up to date with recommended HCC screening was calculated by year of follow-up and during the 4 years preceding HCC diagnosis (the detectable asymptomatic phase). Main Outcomes and Measures: The primary outcome was overall survival after HCC diagnosis and was compared by percentage of time spent up to date with screening using Kaplan-Meier analyses and Cox proportional hazards regression. Early-stage HCC at diagnosis and curative treatment were secondary outcomes assessed using logistic regression. Results: A total of 16 902 individuals were included (median [IQR] age, 64.0 [60.5-67.4] years; 16 426 male [97.2%]), of whom 1622 developed HCC. The cumulative incidence of HCC declined from 2.4% (409 of 16 902 individuals) to 1.0% (27 of 2833 individuals) from year 1 to year 7 of follow-up. Being up to date with screening for at least 50% of time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening was associated with a 3.2% decrease in the hazard of death (hazard ratio, 0.97; 95% CI, 0.95-0.99). There was a statistically significant interaction between time since HCV cure and screening, with no association observed among those who received a diagnosis of HCC more than 5 years after HCV cure. Each 10% of time spent up to date with screening was associated with a 10.1% increased likelihood of diagnosis with early-stage HCC (95% CI, 6.3%-14.0%) and a 6.8% increased likelihood of curative treatment (95% CI, 2.8%-11.0%). Conclusions and Relevance: In this cohort study of persons with HCV-related cirrhosis who achieved HCV cure and subsequently developed HCC, remaining up to date with screening was associated with improved overall survival, supporting the screening of eligible individuals.

Hepatocellular carcinoma risk decreases as time accrues following hepatitis C virus eradication.

BACKGROUND: It is unclear whether the risk of hepatocellular carcinoma (HCC) decreases over time following hepatitis C virus (HCV) eradication. AIM: To determine if patients who have accrued longer time since sustained virologic response (SVR) have a lower risk of HCC than those with less time since SVR METHODS: We conducted a retrospective cohort study of all HCV-infected Veterans Affairs patients who achieved SVR before 1 January 2018 and remained alive without a diagnosis of HCC as of 1 January 2019 (n = 75,965). We ascertained their baseline characteristics as of 1 January 2019 (time zero), including time accrued since SVR and followed them for the subsequent 12 months for incident HCC. We used multivariable Cox proportional hazards regression to determine the association between time since SVR and HCC risk after adjusting for age, race/ethnicity, sex, diabetes, hypertension, body mass index, alcohol use, Charlson Comorbidity Index, Fibrosis-4 score, HCV genotype, hepatitis B virus co-infection and HIV co-infection. RESULTS: 96.0% were male; mean age was 64.6 years. Among those with cirrhosis (n = 19,678, 25.9%), compared to patients who had accrued only ≥1 to 2 years since SVR (HCC incidence 2.71/100 person-years), those who had accrued >2 to 4 years (2.11/100 person-years, aHR 0.80, 95% CI 0.63-1.01) and >4 to 6 years (1.65/100 person-years, aHR 0.61, 95% CI 0.41-0.90) had progressively lower HCC risk. However, HCC risk appeared to plateau for those with >6 years since SVR (1.68/100 person-years, aHR 0.70, 95% CI 0.46-1.07). Among those without cirrhosis, HCC risk was 0.23-0.27/100 person-years without a significant association between time since SVR and HCC risk. CONCLUSIONS: Among patients with cirrhosis and cured HCV infection, HCC risk declined progressively up to 6 years post-SVR-although it remained well above thresholds that warrant screening. This suggests that time since SVR can inform HCC surveillance strategies in patients with cured HCV infection and can be incorporated into HCC risk prediction models.

In-situ tumor vaccination by percutaneous ablative therapy and its synergy with immunotherapeutics: An update on combination therapy.

Percutaneous tumor ablation is now a widely accepted minimally invasive local treatment option offered by interventional radiology and applied to various organs and tumor histology types. It utilizes extreme temperatures to achieve irreversible cellular injury, where ablated tumor interacts with surrounding tissue and host via tissue remodeling and inflammation, clinically manifesting as post-ablation syndrome. During this process, in-situ tumor vaccination occurs, in which tumor neoantigens are released from ablated tissue and can prime one's immune system which would favorably affect both local and remote site disease control. Although successful in priming the immune system, this rarely turns into clinical benefits for local and systemic tumor control due to intrinsic negative immune modulation of the tumor microenvironment. A combination of ablation and immunotherapy has been employed to overcome these and has shown promising preliminary results of synergistic effect without significantly increased risk profiles. The aim of this article is to review the evidence on post-ablation immune response and its synergy with systemic immunotherapies.

Maximizing utility of nondirected living liver donor grafts using machine learning.

Objective: There is an unmet need for optimizing hepatic allograft allocation from nondirected living liver donors (ND-LLD). Materials and method: Using OPTN living donor liver transplant (LDLT) data (1/1/2000-12/31/2019), we identified 6328 LDLTs (4621 right, 644 left, 1063 left-lateral grafts). Random forest survival models were constructed to predict 10-year graft survival for each of the 3 graft types. Results: Donor-to-recipient body surface area ratio was an important predictor in all 3 models. Other predictors in all 3 models were: malignant diagnosis, medical location at LDLT (inpatient/ICU), and moderate ascites. Biliary atresia was important in left and left-lateral graft models. Re-transplant was important in right graft models. C-index for 10-year graft survival predictions for the 3 models were: 0.70 (left-lateral); 0.63 (left); 0.61 (right). Similar C-indices were found for 1-, 3-, and 5-year graft survivals. Comparison of model predictions to actual 10-year graft survivals demonstrated that the predicted upper quartile survival group in each model had significantly better actual 10-year graft survival compared to the lower quartiles (p<0.005). Conclusion: When applied in clinical context, our models assist with the identification and stratification of potential recipients for hepatic grafts from ND-LLD based on predicted graft survivals, while accounting for complex donor-recipient interactions. These analyses highlight the unmet need for granular data collection and machine learning modeling to identify potential recipients who have the best predicted transplant outcomes with ND-LLD grafts.

Addressing racial and ethnic disparities in US liver cancer care.

HCC, the most common form of primary liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC disproportionately affects racial and ethnic minorities in the United States. A practical framework is needed to organize the complex patient, provider, health system, and societal factors that drive these racial and ethnic disparities. In this narrative review, we adapted and applied the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to the HCC care continuum, as a step toward better understanding and addressing existing HCC-related disparities. We first summarize the literature on HCC-related disparities by race and ethnicity organized by the framework's 5 domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) and 4 levels (individual, interpersonal, community, and societal) of influence. We then offer strategies to guide future research initiatives toward promotion of health equity in HCC care. Clinicians and researchers may help mitigate further inequities and better address racial and ethnic disparities in HCC care by prioritizing the following in HCC research: (1) increasing racial and ethnic minority representation, (2) collecting and reporting HCC-related data by racial and ethnic subgroups, (3) assessing the patient experience of HCC care by race and ethnicity, and (4) evaluating HCC-specific social determinants of health by race and ethnicity. These 4 priorities will help inform the development of future programs and interventions that are tailored to the unique experiences of each racial and ethnic group.

Factors Associated With Liver Transplant Referral Among Patients With Cirrhosis at Multiple Safety-Net Hospitals.

Importance: A high proportion of underserved patients with cirrhosis receive care at safety-net hospitals (SNHs). While liver transplant (LT) can be a life-saving treatment for cirrhosis, data on referral patterns from SNHs to LT centers are lacking. Objective: To identify factors associated with LT referral within the SNH context. Design, Setting, and Participants: This retrospective cohort study included 521 adult patients with cirrhosis and model for end-stage liver disease-sodium (MELD-Na) scores of 15 or greater. Participants received outpatient hepatology care at 3 SNHs between January 1, 2016, and December 31, 2017, with end of follow-up on May 1, 2022. Exposures: Patient demographic characteristics, socioeconomic status, and liver disease factors. Main Outcomes and Measures: Primary outcome was referral for LT. Descriptive statistics were used to describe patient characteristics. Multivariable logistic regression was performed to evaluate factors associated with LT referral. Multiple chained imputation was used to address missing values. Results: Of 521 patients, 365 (70.1%) were men, the median age was 60 (IQR, 52-66) years, most (311 [59.7%]) were Hispanic or Latinx, 338 (64.9%) had Medicaid insurance, and 427 (82.0%) had a history of alcohol use (127 [24.4%] current vs 300 [57.6%] prior). The most common liver disease etiology was alcohol associated liver disease (280 [53.7%]), followed by hepatitis C virus infection (141 [27.1%]). Median MELD-Na score was 19 (IQR, 16-22). One hundred forty-five patients (27.8%) were referred for LT. Of these, 51 (35.2%) were wait-listed, and 28 (19.3%) underwent LT. In a multivariable model, male sex (adjusted odds ratio [AOR], 0.50 [95% CI, 0.31-0.81]), Black race vs Hispanic or Latinx ethnicity (AOR, 0.19 [95% CI, 0.04-0.89]), uninsured status (AOR, 0.40 [95% CI, 0.18-0.89]), and hospital site (AOR, 0.40 [95% CI, 0.18-0.87]) were associated with lower odds of being referred. Reasons for not being referred (n = 376) included active alcohol use and/or limited sobriety (123 [32.7%]), insurance issues (80 [21.3%]), lack of social support (15 [4.0%]), undocumented status (7 [1.9%]), and unstable housing (6 [1.6%]). Conclusions: In this cohort study of SNHs, less than one-third of patients with cirrhosis and MELD-Na scores of 15 or greater were referred for LT. The identified sociodemographic factors negatively associated with LT referral highlight potential intervention targets and opportunities to standardize LT referral practices to increase access to life-saving transplant among underserved patients.