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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]

Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumours at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomised-controlled trial in patients with chronic HBV infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i.e. increased early tumour detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts. To address these issues, ILCA (the International Liver Cancer Association) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies. [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]

Somatic mutations in non-malignant tissues are selected for because they confer increased clonal fitness. However, it is uncertain whether these clones can benefit organ health. Here, ultra-deep targeted sequencing of 150 liver samples from 30 chronic liver disease patients revealed recurrent somatic mutations. PKD1 mutations were observed in 30% of patients, whereas they were only detected in 1.3% of hepatocellular carcinomas (HCCs). To interrogate tumor suppressor functionality, we perturbed PKD1 in two HCC cell lines and six in vivo models, in some cases showing that PKD1 loss protected against HCC, but in most cases showing no impact. However, Pkd1 haploinsufficiency accelerated regeneration after partial hepatectomy. We tested Pkd1 in fatty liver disease, showing that Pkd1 loss was protective against steatosis and glucose intolerance. Mechanistically, Pkd1 loss selectively increased mTOR signaling without SREBP-1c activation. In summary, PKD1 mutations exert adaptive functionality on the organ level without increasing transformation risk. [Display omitted] • Sequencing of cirrhotic liver tissues revealed recurrent somatic mutations in PKD1 • PKD1 loss promotes regeneration, but not cancer development • PKD1 loss protects against fatty liver disease • In hepatocytes, Pkd1 loss increased insulin sensitivity and mTOR signaling Zhu et al. show that somatic mutations in PKD1 are selected for in chronically damaged livers because they promote clone and tissue fitness without driving carcinogenesis. [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]

There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis. We performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios (RRs) and hazard ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for random effects models. We identified 59 studies including 145,396 patients with HCC, which was detected by surveillance in 41,052 (28.2%) cases. HCC surveillance was associated with improved early-stage detection (RR 1.86, 95% CI 1.73–1.98; I2 = 82%), curative treatment receipt (RR 1.83, 95% CI 1.69–1.97; I2 = 75%), and overall survival (hazard ratio 0.67, 95% CI 0.61–0.72; I2 = 78%) after adjusting for lead-time bias; however, there was notable heterogeneity in all pooled estimates. Four studies examined surveillance-related physical harms due to false positive or indeterminate surveillance results, but no studies examined potential financial or psychological harms. The proportion of patients experiencing surveillance-related physical harms ranged from 8.8% to 27.5% across studies, although most harms were mild in severity. HCC surveillance is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there was heterogeneity in pooled estimates. Available data suggest HCC surveillance is of high value in patients with cirrhosis, although continued rigorous studies evaluating benefits and harms are still needed. There has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed. [Display omitted] • HCC surveillance was associated with improved early-stage detection, curative treatment receipt, and prolonged survival. • Semi-annual surveillance intervals were associated with improved early HCC detection and overall survival. • Few studies evaluated surveillance outcomes in post-SVR or NAFLD patient populations; thus, future research is warranted. • Few studies characterized surveillance-related harms, although available data suggest surveillance harms are mild in severity. [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]

There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein–based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein–based surrogate FPS was associated with the development of decompensation in cirrhosis patients. The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development. [Display omitted] Liver- and serum-based fibrosis progression signature assays were developed to predict future liver fibrosis progression and monitor response to antifibrotic therapies in patients with chronic liver disease. [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]

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of developing hepatocellular carcinoma (HCC), especially among those who have cirrhosis or advanced fibrosis, but 20–30% of cases of NAFLD-related HCC occur in the absence of advanced fibrosis. The prevalence of NAFLD-related HCC is increasing in most countries worldwide. There are few direct data to support or refute the efficacy or effectiveness of HCC surveillance in NAFLD or to guide its application. We use evidence on surveillance in other conditions and studies on the clinical course of patients with NAFLD to arrive at recommendations for rational approaches to HCC surveillance in this growing cohort of patients. We also outline gaps in research and practice, including opportunities to advance the field. [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 burden of hepatocellular carcinoma (HCC) is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. With the implementation of hepatitis B vaccination and hepatitis C treatment programmes worldwide, the epidemiology of HCC is shifting away from a disease predominated by viral hepatitis – an increasing proportion of cases are now attributable to non-alcoholic steatohepatitis. Surveillance using ultrasound, with or without alpha-fetoprotein, every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. Herein, we review the current state of HCC surveillance and highlight areas for future research, including improved risk stratification of at-risk patients, surveillance tools with higher sensitivity and specificity for early HCC, and interventions to increase surveillance utilisation. [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]