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Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. The Cancer Prevention and Research Institute of Texas has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate HCC research, education, and advocacy activities with the overall goal of reducing HCC mortality in Texas through coordination, collaboration, and advocacy. On September 17, 2022, TeCH co-sponsored a multi-stakeholder conference on HCC with the Baker Institute Center for Health and Biosciences. This conference was attended by HCC researchers, policy makers, payers, members from pharmaceutical industry and patient advocacy groups in and outside of Texas. This report summarizes the results of the conference. The goal of this meeting was to identify different strategies for preventing HCC and evaluate their readiness for implementation. We call for a statewide (1) viral hepatitis elimination program; (2) program to increase nonalcoholic steatohepatitis and obesity awareness; (3) research program to develop health care models that integrate alcohol associated liver disease treatment and treatment for alcohol use disorder; and (4) demonstration projects to evaluate the effectiveness of identifying and linking patient with advanced fibrosis and cirrhosis to clinical care. [ABSTRACT FROM AUTHOR]

Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are "TACE unsuitable" and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research. [ABSTRACT FROM AUTHOR]

In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors. We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs <30 kg/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint effects of these risk factors on risk of developing HCC using Cox regression with competing risks. Mean age was 59.6 years, 64.3% were male, 28.7% were Hispanic, 18.3% were non-Hispanic Black, 50.9% were obese, 6.2% had current heavy alcohol consumption, and 58.4% harbored at least 1 PNPLA3 G-allele. One hundred sixteen patients developed HCC. Compared with PNPLA3 noncarriers without heavy alcohol consumption, HCC risk was 2.65-fold higher (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.20–5.86) for carriers who had current heavy alcohol consumption. Compared with noncarrier patients without obesity, HCC risk was higher (HR, 2.40; 95% CI, 1.33–4.31) for carrier patients who were obese. PNPLA3 and alcohol consumption effect was stronger among patients with viral etiology of cirrhosis (HR, 3.42; 95% CI, 1.31–8.90). PNPLA3 improved 1-year risk prediction for HCC when added to a clinical risk model. The PNPLA3 variant may help refine risk stratification for HCC in patients with cirrhosis with heavy alcohol consumption or obesity who may need specific preventive measures. [Display omitted] [ABSTRACT FROM AUTHOR]

Efforts to assess and improve the effectiveness of Barrett's esophagus (BE) screening and surveillance are ongoing in the United States. Currently, there are limited population-based data in the United States to guide these efforts. We performed a retrospective cohort study using data from large commercial and Medicare Advantage health plans in the United States from 2004 – 2019. We identified individuals with BE and analyzed the proportion who developed EAC. EACs were classified as prevalent EAC (diagnosed within 30 days of index endoscopy), post-endoscopy esophageal adenocarcinoma (PEEC, diagnosed 30 – 365 days after index endoscopy), and incident EAC (diagnosed 365 days or more after index endoscopy). Using this cohort, we performed a nested case-control study to identify factors associated with prevalent EAC at BE diagnosis and study healthcare utilization prior to BE diagnosis. We identified 50,817 individuals with incident BE. Of the 366 who developed EAC, 67.2%, 13.7%, and 19.1% were diagnosed with prevalent EAC, PEEC, and incident EAC respectively. Factors positively associated with prevalent EAC versus BE without prevalent EAC included male sex, dysphagia, weight loss, and Charlson-Deyo comorbidity score. In those with prevalent EAC, most patients with dysphagia or weight loss had their symptoms first recorded within three months of EAC diagnosis. Healthcare utilization rates were similar between those with and without prevalent EAC. Two-thirds of EACs among individuals with BE are diagnosed at the time of BE diagnosis. Additionally, PEEC accounts for 14% of these EACs. These results may guide future research studies that investigate novel BE diagnostic strategies that reduce the morbidity and mortality of EAC. [ABSTRACT FROM AUTHOR]

The use of forceps for removal of nondiminutive polyps is associated with incomplete resection compared with snare polypectomy. However, few studies have characterized the frequency of forceps polypectomy for nondiminutive polyps or identified strategies to improve this practice. To address this gap, we estimated the prevalence and predictors of forceps polypectomy in clinical practice and examined the effectiveness of a multicomponent intervention to reduce inappropriate forceps polypectomy. We retrospectively reviewed all colonoscopies with polypectomies performed at 2 U.S. health systems between October 1, 2017, and September 30, 2019. We used a mixed-effects logistic regression model to examine the effect of a multicomponent intervention, including provider education and a financial incentive, to reduce inappropriate forceps polypectomy, defined as use of forceps polypectomy for polyps ≥5 mm. A total of 9968 colonoscopies with 25,534 polypectomies were performed by 42 gastroenterologists during the study period. Overall, 8.5% (n = 2176) of polyps were removed with inappropriate forceps polypectomy. Inappropriate forceps polypectomy significantly decreased after the intervention (odds ratio [OR], 0.34, 95% confidence interval [CI], 0.30–0.39), from 11.4% (n = 1539) to 5.3% (n = 637). Predictors of inappropriate forceps polypectomy included inadequate bowel prep (OR, 1.25; 95% CI, 1.06–1.47), polyps in the right colon (vs left: OR, 1.29; 95% CI, 1.09–1.51), and number of polyps removed (OR, 0.96; 95% CI, 0.94–0.97). Inappropriate forceps polypectomy also varied by gastroenterologist (median OR, 3.43). In a post hoc analysis, the proportion of polyps >2 mm removed with forceps decreased from 50.0% before the intervention to 43.0% after it (OR, 0.62; 95% CI, 0.58–0.68). Inappropriate forceps polypectomy is common but modifiable. The proportion of nondiminutive polyps removed with forceps polypectomy should be considered as a quality measure. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a wasting syndrome associated with functional impairment and reduced survival that impacts up to 50% of patients with gastrointestinal cancers. However, data are limited on the prevalence and clinical significance of cachexia in patients with hepatocellular carcinoma (HCC). We performed a retrospective cohort study of patients diagnosed with HCC at 2 United States health systems between 2008 and 2018. Patient weights were recorded 6 months prior to and at time of HCC diagnosis. Cachexia was defined as >5% weight loss (or >2% weight loss if body mass index <20 kg/m2), and precachexia was defined as 2% to 5% weight loss. We used multivariable logistic regression models to identify correlates of cachexia and multivariable Cox proportional hazard models to identify factors associated with overall survival. Of 604 patients with HCC, 201 (33.3%) had precachexia and 143 (23.7%) had cachexia at diagnosis, including 19.0%, 23.5%, 34.7%, and 34.0% of patients with Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. Patients with cachexia were less likely to receive HCC treatment (odds ratio, 0.38; 95% confidence interval, 0.21–0.71) and had worse survival than those with precachexia or stable weight (11.3 vs 20.4 vs 23.5 months, respectively; P <.001). Cachexia remained independently associated with worse survival (hazard ratio, 1.43; 95% confidence interval, 1.11–1.84) after adjusting for age, sex, race, ethnicity, Child Pugh class, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and HCC treatment. Nearly 1 in 4 patients with HCC present with cachexia, including many with compensated cirrhosis or early stage tumors. The presence of cancer-associated weight loss appears to be an early and independent predictor of worse outcomes in patients with HCC. [ABSTRACT FROM AUTHOR]

Cirrhosis is the terminal stage of progressive liver fibrosis, affecting 1%–2% of the global population and accounting for 1.3 million deaths annually.1,2 Median survival for persons with compensated cirrhosis is approximately 12 years, compared with only 2 years for those with hepatic decompensation. Accurate prediction of hepatic decompensation is an unmet need to enable identification of patients with cirrhosis who could benefit from close monitoring and timely medical interventions. Besides, risk stratification of patients with cirrhosis could help inform patient selection for trials evaluating therapies to prevent hepatic decompensation. Although various clinical scores, such as the albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) indices (ALBI-FIB4 score) have been proposed to predict long-term risk of hepatic decompensation, 3 external validation has often shown suboptimal prognostic capability and revealed room for improvement.4 [ABSTRACT FROM AUTHOR]

The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States; however, HCC incidence and mortality are not equally distributed among racial and ethnic groups. Our aim was to characterize the direction and magnitude of racial and ethnic disparities in overall survival and early tumor detection among patients with HCC. We searched MEDLINE, EMBASE and Cochrane databases from inception through August 2020 for studies reporting HCC outcomes (early stage presentation and overall survival) by race and ethnicity. We calculated pooled hazard ratios (HRs) and odds ratios (ORs) for each racial and ethnic group (White, Black, Hispanic, Asian) using the DerSimonian and Laird method for a random-effects model. We identified 35 articles comprising 563,097 patients (53.0% White, 17.3% Black, 18.4% Hispanic, 5.0% Asian). Compared with White patients, Black patients had worse survival (pooled HR 1.08; 95% CI, 1.05 – 1.12), whereas Hispanic (pooled HR 0.92; 95% CI, 0.87 – 0.97) and Asian (pooled HR 0.81; 95% CI, 0.73 – 0.88) patients had better survival. Among articles reporting tumor stage (n = 20), Black patients had lower odds of early stage HCC compared with White patients (OR, 0.66; 95% CI, 0.54 – 0.78). Conversely, there was no difference in odds of early HCC detection for Asian (OR, 1.01; 95% CI, 0.97 – 1.05) or Hispanic patients (OR, 0.87; 95% CI, 0.74 – 1.01) compared with White patients. The most common limitation of studies was risk of residual confounding from socioeconomic status and liver dysfunction. There are significant racial and ethnic disparities in HCC prognosis in the United States, with Black patients having worse overall survival and Hispanic and Asian patients having better overall survival compared with White patients. Interventions are needed to reduce disparities in early HCC detection to improve HCC prognosis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) continues to have a dismal prognosis, with 5-year survival below 20%. This poor prognosis can be in part attributed to failures along the cancer screening process continuum such as underuse of screening in at risk patients and appropriate treatments for patients with HCC. Better understanding these process failures, and how they compare to those seen in other cancer types, can help inform potential intervention targets and strategies to reduce HCC-related mortality. Herein, we outline a conceptual model with several discrete steps in the HCC screening process continuum including risk assessment, screening initiation, follow-up of screening results, diagnostic evaluation, and treatment evaluation. The conceptual model illustrates how each step in the screening process is prone to delays or failure, resulting in worse outcomes such as late stage diagnosis or poor survival, and how factors at the patient, provider, and health care system levels can contribute to these failures. We compare cancer screening processes for HCC with those employed in breast and colorectal cancer screening to identify opportunities for improvement. The Translational Liver Cancer consortium was recently established by the National Cancer Institute with the goal of improving early detection of HCC. Studies designed to address failures in the HCC screening process continuum will help accomplish this goal. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [Display omitted] [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC. We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We recorded imaging receipt in the year before HCC diagnosis: ultrasound plus α-fetoprotein (AFP), ultrasound alone, multiphasic contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI), and no liver imaging. We used multivariable logistic and Cox regression analysis to compare early tumor detection, curative treatment receipt, and overall survival between surveillance strategies. Among 2028 patients with HCC (46.7% Barcelona Clinic Liver Cancer stage A), 703 (34.7%) had ultrasound plus AFP, 293 (14.5%) had ultrasound alone, 326 (16.1%) had multiphasic CT/MRI, and 706 (34.8%) had no imaging in the year before HCC diagnosis. Over the study period, proportions without imaging were stable, whereas use of CT/MRI increased. Compared with no imaging, CT/MRI and ultrasound plus AFP, but not ultrasound alone, were associated with early stage HCC detection and curative treatment. Compared with ultrasound alone, CT/MRI and ultrasound plus AFP were associated with increased early stage detection. HCC surveillance patterns vary in clinical practice and are associated with differing clinical outcomes. While awaiting data to determine if CT or MRI surveillance can be performed in a cost-effective manner in selected patients, AFP has a complementary role to ultrasound-based surveillance, supporting its adoption in practice guidelines. [Display omitted] [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and one of the few cancers with a rising mortality in the United States. There are opportunities for intervention along the cancer care continuum (CCC), which includes risk assessment, primary prevention, detection (ie, screening initiation and follow-up of screening results), diagnosis, and treatment.1 Each step is prone to failures that are influenced by factors at multiple socioecological levels (ie, patient, provider, health delivery system, community, and policy levels).2 We recently described a conceptual model of the steps and interfaces along the CCC that are required for effective implementation of HCC screening in clinical practice.3 Herein, we present a conceptual model for the implementation and evaluation of interventions at each of the socioecological levels using implementation strategies that promote optimal delivery and uptake. We focus on early steps in the CCC, including risk assessment, primary prevention, and early detection (ie, secondary prevention), because these have the greatest potential to reduce HCC mortality. [ABSTRACT FROM AUTHOR]

Accurate estimates for the contemporary burden of chronic liver disease (CLD) are vital for setting clinical, research, and policy priorities. We aimed to review the incidence, prevalence, and mortality of CLD and its resulting complications, including cirrhosis and hepatocellular carcinoma (HCC). We reviewed the published literature on the incidence, prevalence, trends of various etiologies of CLD and its resulting complications. In addition, we provided updated data from the Centers for Disease Control and Global Burden of Disease Study on the morbidity and mortality of CLD, cirrhosis, and hepatocellular carcinoma (HCC). Lastly, we assessed the strengths and weaknesses of available sources of data in hopes of providing important context to these national estimates of cirrhosis burden. An estimated 1.5 billion persons have CLD worldwide and the age-standardized incidence of CLD and cirrhosis is 20.7/100,000, a 13% increase since 2000. Similarly, cirrhosis prevalence and mortality has increased in recent years in the United States. The epidemiology of CLD is shifting, reflecting implementation of large-scale hepatitis B vaccination and hepatitis C treatment programs, the increasing prevalence of the metabolic syndrome, and increasing alcohol misuse. The global burden of CLD and cirrhosis is substantial. Although vaccination, screening, and antiviral treatment campaigns for hepatitis B and C have reduced the CLD burden in some parts of the world, concomitant increases in injection drug use, alcohol misuse, and metabolic syndrome threaten these trends. Ongoing efforts to address CLD-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. [ABSTRACT FROM AUTHOR]

The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021. We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73–0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65–0.85) at 1 year and 0.77 (95% CI, 0.71–0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification. [ABSTRACT FROM AUTHOR]

Advanced liver disease, which includes fibrosis and cirrhosis, has been reported to be more prevalent in Hispanics patients at the time of diagnosis of chronic hepatitis C virus (HCV) infection than non-Hispanic black or non-Hispanic white patients. We performed a propensity score-matched analysis to determine whether metabolic risk factors contribute to this disparity. We collected data from persons with 748 HCV infection (22% Hispanic, 53% non-Hispanic black, and 26% non-Hispanic white; 23% with advanced liver disease), born from 1945 through 1965, diagnosed at 6 health care systems in Texas. Advanced liver disease was defined as a FIB-4 index score above 3.25. We examined the association between advanced liver disease and race or ethnicity, metabolic risk (based on diabetes mellitus and body mass index [BMI]) and heavy alcohol use in propensity score-matched analyses. In propensity-score matched models, among those who were obese (BMI ≥30) with a diagnosis of diabetes, the adjusted odds ratio of advanced liver disease for Hispanics vs non-Hispanic black was 7.89 (95% CI, 3.66–17.01) and adjusted odds ratio = 12.49 (95% CI, 3.24–48.18) for Hispanic vs non-Hispanic white patients (both P <.001). HCV-infected Hispanics with obesity and diabetes have a far higher risk for advanced liver disease than other racial or ethnic groups. These findings highlight the need for HCV treatment and management of probable concurrent fatty liver disease. Even after we accounted for metabolic risk factors, Hispanics were still at higher risk for advanced liver disease, indicating the potential involvement of other factors such as genetic variants. [ABSTRACT FROM AUTHOR]

The Liver Imaging Reporting And Data System (LI-RADS) was created with the support of the American College of Radiology (ACR) to standardize the acquisition, interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). A comprehensive and rigorous system developed by radiologists, hepatologists, pathologists, and surgeons, LI-RADS addresses a wide range of imaging contexts. Currently, 4 algorithms are available publicly on the ACR website: ultrasound for HCC surveillance, computed tomography and magnetic resonance imaging for HCC diagnosis and tumor staging, contrast-enhanced ultrasound for HCC diagnosis, and computed tomography/magnetic resonance imaging for treatment response assessment. Each algorithm is supported by a decision tree, categorization table, lexicon, atlas, technical requirements, and reporting and management guidance. Category codes reflecting the relative probability of HCC and malignancy are assigned to imaging-detected liver observations, with emerging evidence suggesting that LI-RADS accurately stratifies HCC and malignancy probabilities. LI-RADS is an evolving system and has been updated and refined iteratively since 2011 based on scientific evidence, expert opinion, and user feedback, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Concurrent with its most recent update, LI-RADS was integrated into the American Association for the Study of Liver Diseases HCC guidance released in 2018. We anticipate continued refinement of LI-RADS and progressive adoption by radiologists worldwide, with the eventual goal of culminating in a single unified system for international use. [ABSTRACT FROM AUTHOR]

Background & Aims Low rates of hepatocellular carcinoma (HCC) surveillance are primarily due to provider-related process failures. However, few studies have evaluated primary care provider (PCP) practice patterns, attitudes, and barriers to HCC surveillance at academic tertiary care referral centers. Methods We conducted a web-based survey of PCPs at 2 tertiary care referral centers (133 providers) from June 2017 through December 2017. The survey was adapted from pretested surveys and included questions about practice patterns, attitudes, and barriers to HCC surveillance. We used the Fisher exact and Mann–Whitney rank-sum tests to identify factors associated with adherence to HCC surveillance recommendations, for categoric and continuous variables, respectively. Results We obtained a provider-level response rate of 75% and clinic-level response rate of 100% (133 providers). Whereas most PCPs performed HCC surveillance themselves, one-third deferred surveillance to subspecialists and referred patients to a hepatology clinic. Providers believed the combination of ultrasound and α-fetoprotein analysis to be highly effective for early stage tumor detection and reported using the combination for assessment of most patients. However, PCPs were more likely to use computed tomography– or magnetic resonance imaging–based surveillance for patients with nonalcoholic steatohepatitis or decompensated cirrhosis. Most providers believed HCC surveillance to be efficacious for early tumor detection and increasing survival. However, they desired increased high-quality evidence to characterize screening benefits and harms. Providers expressed notable misconceptions about HCC surveillance, including the role for measurement of liver enzyme levels in HCC surveillance and cost effectiveness of surveillance in patients without cirrhosis. They also reported barriers, including not being up to date on HCC surveillance recommendations, limited time in the clinic, and competing clinical concerns. Conclusions In a web-based survey, PCPs reported misconceptions and barriers to HCC surveillance. This indicates the need for interventions, including provider education, to improve HCC surveillance effectiveness in clinical practice. [ABSTRACT FROM AUTHOR]

Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P =.14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P <.001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P =.16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28–1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99–1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50–5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78–2.30). With the availability of DAA therapy, racial disparities in post-LT survival have improved. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has an increasing mortality in the United States and is a leading cause of morbidity and mortality in patients with cirrhosis. We aimed to estimate the financial burden related to HCC in a large nationally representative United States cohort. We used the Surveillance, Epidemiology, and End Results program (SEER)-Medicare database to identify 4525 adult patients who were diagnosed with HCC between 2011 and 2015. We generated a 1:1 propensity score-matched cohort of patients with cirrhosis but no HCC as a comparator group to define incremental HCC-specific costs beyond costs related to underlying cirrhosis. Our main outcomes were patient liabilities and Medicare payments in the first year after HCC diagnosis. Compared with patients with cirrhosis, those with HCC had higher incremental patient liabilities (median +$7166; interquartile range, $2401–$16,099) and Medicare payments (+$50,110; interquartile range, $142,42–$136,239; P <.001 for both) in the first year after diagnosis. Patients with HCC had significantly higher inpatient, outpatient, and physician service costs compared with the matched cohort with cirrhosis (P <.001 for all). Patients with early-stage HCC had lower incremental patient liabilities (median, $4195 vs $8238; P <.001) and Medicare payments (median, $28,207 vs $59,509; P <.001) than those with larger tumor burden. In multivariable median regression analysis, incremental patient liabilities and Medicare payments were significantly associated with the National Cancer Institute comorbidity index, nonalcoholic fatty liver disease etiology, presence of ascites, and presence of hepatic encephalopathy. Patients with HCC suffer from cancer-related financial burden, highlighting a need for policy interventions and financial support systems. [ABSTRACT FROM AUTHOR]

Hepatocellular cancer (HCC) surveillance is associated with increased curative treatment and improved survival, underscoring its importance in patients with cirrhosis.1 Surveillance is 1 step in a larger HCC screening continuum, and those with abnormal screening results must undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI).2 The Liver Imaging Reporting and Data System (LI-RADS) classifies liver observations in at-risk patients based on risk of malignancy and HCC, with LR-5 observations having a positive predictive value exceeding 95% for HCC. However, indeterminate liver nodules (ie, LR-3 or LR-4) are commonly observed in clinical practice, associated with heterogenous HCC risk, and have large variations in practice management.3,4 We previously reported the natural history of LR-3 observations in a multicenter cohort of patients with cirrhosis, demonstrating a high annual incidence for HCC development of 8.4 cases per 100 person-years;5 however, the natural history of LR-4 observations remains uncertain. Herein, we aimed to characterize clinical outcomes in patients with LR-4 observations in a multicenter cohort. [ABSTRACT FROM AUTHOR]

Failures have been reported across the cancer care continuum in patients with hepatocellular carcinoma (HCC); however, the impact of treatment delays on outcomes has not been well-characterized. We described the prevalence of treatment delays in a racially and ethnically diverse cohort of patients and its association with overall survival. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients diagnosed with HCC between 2001 and 2015. We performed multivariable logistic regression analysis to identify factors associated with treatment delay (ie, receipt of HCC-directed therapy >3 months after diagnosis). Cox proportional hazards regression analysis with a 5-month landmark was used to characterize the association between treatment delay and overall survival, accounting for immortal time bias. Of 8450 patients with treatment within 12 months of HCC diagnosis, 1205 (14.3%) experienced treatment delays. The proportion with treatment delays ranged from 6.8% of patients undergoing surgical resection to 21.6% of those undergoing liver transplantation. In multivariable analysis, Black patients (odds ratio, 1.96; 95% confidence interval [CI], 1.21–3.15) and those living in high poverty neighborhoods (odds ratio, 1.55; 95% CI, 1.25–1.92) were more likely to experience treatment delays than white patients and those living in low poverty neighborhoods, respectively. Treatment delay was independently associated with worse survival (hazard ratio 1.15, 95% CI, 1.05–1.25). Nearly 1 in 7 patients with HCC experience treatment delays, with higher odds in Black patients and those living in high poverty neighborhoods. Treatment delays are associated with worse survival, highlighting a need for interventions to improve time-to-treatment. [ABSTRACT FROM AUTHOR]

Patients with cirrhosis are high risk for developing hepatocellular carcinoma (HCC) and warrant surveillance using abdominal ultrasound and α-fetoprotein.1 Those with positive surveillance results should undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI). The LI-RADS system is an evidence-based system to classify observations on CT or MRI in at-risk patients, ranging from LR-1 (definite benign) to LR-5 (definite HCC), with LR-3 and LR-4 observations being intermediate risk for HCC.2 LR-3 and LR-4 observations are observed on CT or MRI in more than one-fourth of patients undergoing HCC surveillance and have a high, yet variable, risk for progression to HCC.3 Approximately one-third of patients with LR-3 observations and more than two-thirds of LR-4 observations develop HCC, and surveillance strategies vary widely in practice.4,5 Variation in radiographic appearance and natural history of these observations suggests that this may be a heterogeneous group of patients; however, their histopathology has not been well described. Herein, we correlated imaging findings and explant histopathology from liver transplant recipients with at least 1 LR-3 or LR-4 observation on CT or MRI within 6 months preceding transplantation. [ABSTRACT FROM AUTHOR]

Patient navigation interventions can improve health outcomes in underserved, low-income, and racial and ethnic minority groups, who often experience health disparities. We examined the effectiveness of patient navigation to improve linkage to hepatitis C virus (HCV) treatment receipt in a socioeconomically disadvantaged, racially diverse patient population. We performed a pre-post analysis evaluating the effectiveness of a patient navigation program among baby boomers who tested positive for HCV in a safety-net health system. The usual care group (June 2013 to May 2015) and patient navigation group (January 2016 to December 2017) were balanced using a stabilized inverse probability of treatment weighting approach. We used logistic regression analyses to evaluate associations between patient navigation and linkage to care for HCV treatment evaluation, treatment initiation, and sustained virologic response. Among 1353 patients (62% black, 61% uninsured, 16% homeless), 769 were in the usual care group, and 584 were in the patient navigation group. The patient navigation group had significantly higher odds of linkage to care (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.9–4.8) and treatment initiation (OR, 3.2; 95% CI, 2.3–4.2) within 6 months. The patient navigation group continued to have increased linkage to care (OR, 3.4; 95% CI, 2.7–4.3) and treatment initiation (OR 2.3; 95% CI, 1.7–3.0) at 12 months. However, there was no significant difference in sustained virologic response between the groups (86.9% vs 86.1%; P =.78). Patient navigation was associated with significantly increased linkage to care and treatment initiation among patients with HCV infection. Patient navigation programs can be used to promote HCV elimination among traditionally difficult-to-reach patient populations. [Display omitted] [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a leading cause of death in patients with cirrhosis and has a rising mortality rate in the United States.1 Racial and ethnic minorities experience a disproportionate burden of HCC, including higher incidence rates, more late-stage diagnoses, and worse survival.2,3 These disparities are complex in nature and can be attributed to many proximal, intermediate, and distal determinants, such as health literacy and behaviors, social support, social needs, social determinants of health, and access to health care.4 Prior studies have identified racial and ethnic differences in clinical factors, including receipt of HCC surveillance and tumor stage5; however, few studies have examined differences in patient-reported barriers that may partly explain observed disparities. Understanding these data is essential to inform interventions to address and mitigate disparities. Therefore, we described patient-reported barriers to medical care and examined differences in barriers by race and ethnicity in a large, diverse population of patients newly diagnosed with HCC. [ABSTRACT FROM AUTHOR]

Early hepatocellular cancer (HCC) detection is associated with curative treatment and improved survival.1 The American Association for the Study of Liver Diseases recommends semiannual ultrasound and α-fetoprotein (AFP) in patients with cirrhosis, and those with abnormal results should undergo diagnostic multiphase computed tomography (CT) or magnetic resonance imaging (MRI).2 The Liver Imaging Reporting and Data System (LI-RADS) was devised to standardize reporting of liver observations in at-risk individuals, ranging from LR-1 ("definitely benign") to LR-5 ("definitely HCC''), with indeterminate observations classified as LR-3 ("intermediate probability of malignancy").3 A study among 999 cirrhosis patients found that indeterminate liver observations are common, being reported on diagnostic CT or MRI in 98 (38.3%) of 256 patients with abnormal ultrasound results.4 Prior studies have reported a wide range in HCC risk, from 4% to 31%, for LR-3 observations, so there is insufficient evidence to recommend a standardized strategy for monitoring LR-3 observations.5,6 [ABSTRACT FROM AUTHOR]

The extent to which nonalcoholic fatty liver disease (NAFLD) contributes to hepatocellular carcinoma (HCC) prevalence in contemporary practices and whether there are any etiologic differences in surveillance receipt, tumor stage, and overall survival (OS) remain unclear. We aimed to estimate the burden of NAFLD-related HCC and magnitude of associations with surveillance receipt, clinical presentation, and outcomes in a contemporary HCC cohort. In a cohort of HCC patients from the Surveillance, Epidemiology and End Results–Medicare database between 2011 and 2015, we used multivariable logistic regression to identify factors associated with surveillance receipt, early-stage tumor detection, and curative treatment. Cox regression was used to identify factors associated with OS. Among 5098 HCC patients, NAFLD was the leading etiology, accounting for 1813 cases (35.6%). Compared with those with hepatitis C–related HCC, NAFLD was associated with lower HCC surveillance receipt (adjusted odds ratio, 0.22; 95% confidence interval [CI], 0.17–0.28), lower early-stage HCC detection (adjusted odds ratio, 0.49; 95% CI, 0.40–0.60), and modestly worse OS (adjusted hazard ratio, 1.20; 95% CI, 1.09–1.32). NAFLD subgroup analysis showed that early-stage HCC, absence of ascites/hepatic encephalopathy, surveillance, and curative treatment receipt were associated with improved OS. NAFLD patients with coexisting liver disease were more likely to have surveillance, early-stage detection, curative treatment, and improved OS than NAFLD patients without coexisting liver diseases. NAFLD is the leading etiology of HCC among Medicare beneficiaries. Compared with other etiologies, NAFLD was associated with lower HCC surveillance receipt, early-stage detection, and modestly poorer survival. Multifaceted interventions for improving surveillance uptake are needed to improve prognosis of patients with NAFLD-related HCC. [ABSTRACT FROM AUTHOR]