Patients with cirrhosis are at high risk for hepatocellular carcinoma (HCC), but few undergo guideline-recommended semi-annual screening. Randomized clinical trials (RCTs) demonstrate that mailed outreach can increase screening versus visit-based screening. We estimated the costs and cost-effectiveness of an outreach strategy versus usual care.

We built a 10-year Markov chain Monte Carlo microsimulation model to conduct a cost-effectiveness analysis comparing a mailed outreach program versus usual care for HCC screening in a cohort of 10,000 patients with cirrhosis. Model inputs were based on literature review (2005-current), and costs were based on inflation-adjusted estimates from Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data. We conducted one-way sensitivity analyses for HCC incidence, outreach costs, efficacy of the outreach strategy to increase screening, and efficacy of curative (versus palliative) HCC treatments.

Mailed outreach was estimated to cost $32.45 per patient in the first year and $21.90 per patient in subsequent years. The outreach program increased the number of HCC patients detected at an early stage by 48.4% and increased quality-adjusted life years (QALYs) by 300. Cost savings from these increases offset the costs of mailed outreach. Mailed outreach remained cost-effective across a wide range of HCC incidence rates, outreach costs, efficacy of the outreach strategy to increase screening, and the efficacy of curative HCC treatments. Annual out-of-pocket patient costs in the outreach arm were low at $13 per year.

Mailed outreach to encourage HCC screening in patients with cirrhosis dominates usual care and should be considered for implementation in routine practice.

National Cancer Institute and Cancer Prevention Research Institute of Texas.

Prognosis in patients with HCC is largely determined by stage at diagnosis, highlighting the importance of effective early detection strategies. HCC surveillance is associated with increased early detection and reduced HCC-related mortality and is currently recommended in patients with cirrhosis or chronic HBV infection.

We performed a targeted literature review to identify limitations of current HCC surveillance practices and strategies for improvement.

Semi-annual ultrasound continues as the cornerstone modality for HCC surveillance but has limited sensitivity for detecting early-stage HCC, particularly in patients with obesity and non-viral etiologies. Although sensitivity for early-stage HCC can be improved by using ultrasound with alpha fetoprotein, this strategy misses over one-third of HCC at an early stage. Emerging imaging and biomarker-based surveillance strategies currently remain in varying stages of validation and are not yet ready for routine use in practice. The cost-effectiveness of surveillance in patients with non-cirrhotic liver disease related to hepatitis C or metabolic dysfunction-associated steatotic liver disease continues to be debated, although subgroups with advanced fibrosis may warrant surveillance. Finally, the effectiveness of surveillance is diminished by underuse in clinical practice, particularly in racial minority and low-income groups, highlighting a need for interventions to increase utilization.

Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting.

A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006-2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates.

Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36-2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23-1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71-2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified.

Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.

The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis.

We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses.

Of 125 patients diagnosed with hepatocellular carcinoma (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan criteria. Early tumor detection did not statistically significantly differ between the outreach and usual care arms (64.2% vs 79.3%; P = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%; P = .95) with 5.9% in both arms having mild harms; 4.0% and 3.8%, respectively, with moderate harms; and 0.9% and 1.0%, respectively, with severe harms.

Most patients enrolled in hepatocellular carcinoma screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not increase early hepatocellular carcinoma detection or physical harms compared with usual care.

NCT02582918 and NCT03756051.

Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score (gender, age, α-fetoprotein [AFP] L3, AFP, and des-γ carboxyprothrombin) has been shown to have excellent sensitivity and specificity for HCC in phase 2 studies. We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC.

This is a prospective study of patients with cirrhosis enrolled at 7 centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per American Association for the Study of Liver Diseases guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis. All analyses were conducted by an unblinded statistician in the Early Detection Research Network data management and coordinating center.

A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%. The areas under the curve for AFP and GALAD within 12 months before HCC were 0.66 and 0.78 (P < .001), respectively. Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001).

GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis.

Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic.

We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date.

Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS.

Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.

Orthotopic liver transplantation is the recommended treatment option for patients with early-stage hepatocellular carcinoma and concomitant cirrhosis. Waitlist candidacy can be affected by social determinants of health that vary across races and ethnicities. Our study sought to evaluate whether racial/ethnic disparities exist in access to orthotopic liver transplantation in patients with hepatocellular carcinoma.

The National Cancer Database participant use file was used to analyze data between 2004 and 2020. Patients 18-70 years of age with TNM clinical stage I and II hepatocellular carcinoma who received either orthotopic liver transplantation or liver directed/nonsurgical therapies were included. Baseline demographic variables and treatment modalities were collected. Patients were assigned fixed categories on the basis of race and ethnicity. Descriptive statistics, multivariable logistical regressions, effects modification analysis, and propensity matching were used.

There were 23,313 non-Hispanic White, 5,215 non-Hispanic Black, 5,581 Hispanic, and 2,768 other patients included in this analysis. Significant socioeconomic variation was observed across races. Non-Hispanic White patients were more likely to undergo orthotopic liver transplantation than non-Hispanic Black patients. The proportion of patients insured by Medicare was the same between non-Hispanic White and non-Hispanic Black patients. There was a graeter proportion of non-Hispanic Black patients with Medicaid compared with non-Hispanic White patients, whereas a lower proportion of non-Hispanic Black patients were insured via private insurance compared with non-Hispanic White patients. Effect modification analysis showed the non-Hispanic Black patients were less likely to undergo orthotopic liver transplantation for those with private and Medicare coverage compared with non-Hispanic White patients. Propensity matching showed a significantly decreased rate of orthotopic liver transplantation in non-Hispanic Black patients compared with non-Hispanic White patients.

Non-Hispanic Black patients were less likely to undergo orthotopic liver transplantation for early-stage hepatocellular carcinoma, despite adjusting for cancer stage and socioeconomic factors, compared with non-Hispanic White patients. Social determinants of health were associated with the probability of undergoing orthotopic liver transplantation. Understanding disparities related to social determinants of health will help guide health policy changes and improved access to care.

Given suboptimal performance of ultrasound-based surveillance for early hepatocellular carcinoma (HCC) detection in patients with cirrhosis, there is interest in alternative surveillance strategies, including blood-based biomarkers. We aimed to evaluate the cost-effectiveness of biomarker-based surveillance in patients with cirrhosis.

We constructed a decision-analytic model to compare ultrasound/alpha-fetoprotein (AFP) and biomarker-based surveillance strategies in 1,000,000 simulated patients with compensated cirrhosis. Model inputs for adherence, benefits, and harms of each strategy were based on literature review, and costs were derived from the Medicare fee schedule. Primary outcomes were quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) of the surveillance strategies, with cost-effectiveness assessed at a threshold of USD 150,000 per QALY. We performed sensitivity analyses for HCC incidence, test performance characteristics, surveillance adherence, and biomarker costs.

In the base case, both ultrasound/AFP and biomarker-based surveillance were cost-effective versus no surveillance, with ICERs of USD 105,620, and USD 101,295, per QALY, respectively. Biomarker-based surveillance was also cost-effective versus ultrasound/AFP, with an ICER of USD 14,800 per QALY. Biomarker sensitivity exceeding 80%, cost below USD 210, or adherence exceeding 58% were necessary for biomarker-based screening to be cost-effective versus ultrasound/AFP. In two-way sensitivity analyses, biomarker costs were directly related with test sensitivity and adherence, whereas sensitivity and adherence were inversely related. In a probabilistic sensitivity analysis, biomarker-based screening was the most cost-effective strategy in most (65%) simulations.

Biomarker-based screening appears cost-effective for HCC screening, but results are sensitive to test sensitivity, adherence, and costs.

Age and comorbidity are key factors in assessing patient prognosis and informing stopping rules for cancer screening eligibility, but their impact has not been rigorously evaluated in patients with hepatocellular carcinoma (HCC).

We conducted a retrospective cohort study of patients diagnosed with HCC at 2 health systems between January 2010 and February 2023. We used multivariable logistic regression and Cox proportional hazards models to evaluate the associations between older age (≥65 years) and comorbidity burden (Charlson Comorbidity Index) with early-stage presentation, curative treatment receipt, and overall survival. We performed subgroup analyses in patients with early-stage HCC.

We identified 2002 patients with HCC (median age, 61 years; 76% male; 21% early-stage), with a median survival of 15.7 months. In adjusted analyses, curative treatment receipt was associated with higher comorbidity but not older age. Conversely, overall survival was significantly associated with older age (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.06-1.47) but not high comorbidity (HR, 0.92; 95% CI, 0.77-1.09). Older age continued to be associated with worse survival among patients with early-stage HCC (HR, 1.99; 95% CI, 1.45-2.73) and those who underwent curative treatment (HR, 1.52; 95% CI, 1.10-2.10). Median survival for younger versus older individuals was 20 versus 14 months overall, 65 versus 49 months for patients with early-stage HCC, and 113 versus 60 months for those with curative treatment.

Older age but not comorbidity burden is associated with worse survival, including among patients with early-stage HCC. Further studies are needed to define the role of comorbidity in HCC prognostication.

Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis.

Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses.

All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage.

Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions.

NCT02582918.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in India. This review explores the epidemiological trends and the landscape of systemic therapy for HCC in the Indian context, acknowledging the recent shift in etiology from viral hepatitis to lifestyle-associated factors. A comprehensive review of the literature was conducted, including data from the Global Cancer Observatory and the Indian Council of Medical Research, along with a critical analysis of various clinical trials. The article investigates systemic therapies in-depth, discussing their mechanisms, efficacy, and adaptation to Indian healthcare framework. Progression-free survival with a hazard ratio of ≤0.6 compared to sorafenib, overall survival of ∼16-19 months, and objective response rate of 20-30% are the defining thresholds for systemic therapy clinical trials. Systemic therapy for advanced HCC in India primarily involves the use of tyrosine kinase inhibitors such as sorafenib, lenvatinib, regorafenib, and cabozantinib, with sorafenib being the most commonly used drug for a long time. Monoclonal antibodies such as ramucirumab and bevacizumab and immune-checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, are expanding treatment horizons. Lenvatinib has emerged as a cost-effective alternative, and the combination of atezolizumab and bevacizumab has demonstrated superior outcomes in terms of overall survival and progression-free survival. Despite these advances, late-stage diagnosis and limited healthcare accessibility pose significant challenges, often relegating patients to palliative care. Addressing HCC in India demands an integrative approach that not only encompasses advancements in systemic therapy but also targets early detection and comprehensive care models. Future strategies should focus on enhancing awareness, screening for high-risk populations, and overcoming infrastructural disparities. Ensuring the judicious use of systemic therapies within the constraints of the Indian healthcare economy is crucial. Ultimately, a nuanced understanding of systemic therapeutic options and their optimal utilization will be pivotal in elevating the standard of HCC care in India.

Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients presented at an early stage (Barcelona Clinic Liver Cancer stage 0/A). In fully adjusted models, there were persistent Black-White disparities in early-stage presentation (OR: 0.63, 95% CI: 0.45-0.89) but not Hispanic-White disparities (OR: 0.93, 95% CI: 0.70-1.24). Median survival was 16.2 (IQR: 5.8-36.8) months for White patients compared to 15.7 (IQR: 4.6-34.4) months for Hispanic, 10.0 (IQR: 2.9-29.0) months for Black, and 9.5 (IQR: 3.4-31.9) months for Asian/other patients. Black-White disparities in survival persisted after adjusting for individual demographics and clinical factors (HR: 1.30, 95% CI: 1.09-1.53) but were no longer observed after adding HCC stage and treatment (HR: 1.05, 95% CI: 0.88-1.24), or in fully adjusted models (HR: 0.97, 95% CI: 0.79-1.18). In fully adjusted models, Hispanic-White (HR: 0.87, 95% CI: 0.73-1.03) and Asian/other-White (HR: 0.85, 95% CI: 0.63-1.15) differences in survival were not statistically significant, although patients in high-SES neighborhoods had lower mortality (HR: 0.69, 95% CI: 0.48-0.99).

In a multicenter cohort of patients with HCC, racial and ethnic differences in HCC prognosis were explained in part by differences in tumor stage at diagnosis and neighborhood SES. These data inform targets to intervene and reduce disparities.

The impact of clinical factors and social determinants of health on treatment patterns and health care costs among patients with HCC is unknown.

Using 100% Medicare Fee-For-Service claims and a commercial multipayor claims database, we identified patients diagnosed with HCC from January 1, 2017, to December 31, 2020. Surveillance receipt was defined 12 months prior to HCC diagnosis, whereas treatment and health care costs were assessed post-HCC diagnosis. Multinomial logistic regression was used to assess the association between demographics, social determinants of health, and surveillance or HCC treatment. Multivariable generalized linear regression was used to identify factors associated with total health care costs.

Of the 32,239 patients with HCC (mean age 68 y, 67% male, 73% White), 70% received surveillance and only half (51%) received any treatment. Curative treatment receipt was higher among those with prior surveillance (24% with CT/MRI and 18% with ultrasound vs. 9% with no surveillance). Curative treatment was independently associated with HCC surveillance and inversely associated with Black race, lower education level, and diagnosis in the year 2020 (COVID-19 year). Higher health care costs were independently associated with Black race, low English proficiency, living alone, and diagnosis in 2018-2020, and inversely associated with CT/MRI-based surveillance.

Race and social determinants of health were independently associated with curative treatment receipt and health care costs. Increasing access to high-quality HCC surveillance may improve treatment receipt and reduce health disparities among patients with HCC.

Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice.

The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5.

The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel.

NCT06084234.

The TRACER Study is actively enrolling.

Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear.

We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks.

Of 307 patients with ILNs, 208 had LR-3 lesions, 83 had LR-4 lesions, and 16 had both LR-3 and LR-4 lesions. HCC incidence rates for patients with LR-3 and LR-4 lesions were 110 (95% CI 70-150) and 420 (95% CI 310-560) per 1,000 person-year, respectively. In multivariable analysis, incident HCC among patients with LR-3 lesions was associated with older age, thrombocytopenia (platelet count ≤150 ×10 9 /L), and elevated serum alpha-fetoprotein levels. Among those with LR-4 lesions, incident HCC was associated with a maximum lesion diameter >1 cm. Although most patients had follow-up computed tomography or magnetic resonance imaging, 13.7% had no follow-up imaging and another 14.3% had follow-up ultrasound only.

ILNs have a high but variable risk of HCC, with 4-fold higher risk in patients with LR-4 lesions than those with LR-3 lesions, highlighting a need for accurate risk stratification tools and close follow-up in this population.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, leading to poor prognosis. This narrative review explores novel biomarkers for early HCC detection. We conducted a comprehensive literature review analyzing protein, circulating nucleic acid, metabolite, and quantitative proteomics-based biomarkers, evaluating the advantages and limitations of each approach. While established markers like alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and AFP-L3 remain relevant, promising candidates include circulating tumor DNA, microRNAs, long noncoding RNAs, extracellular vesicle, and metabolomic biomarkers. Multi-biomarker panels like the GALAD score, Oncoguard, and Helio liver test show promise for improved diagnostic accuracy. Non-invasive approaches like urine and gut microbiome analysis are also emerging possibilities. Integrating these novel biomarkers with current screening protocols holds significant potential for earlier HCC detection and improved patient outcomes. Future research should explore multi-biomarker panels, omics technologies, and artificial intelligence to further enhance early HCC diagnosis and management.

Primary liver cancer is among the most common cancers globally. It is the sixth-most common malignancy encountered and the third-most common cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for about 90% of primary liver cancers. The majority of HCCs occur in patients with underlying cirrhosis, which results from chronic liver diseases such as fatty liver, hepatitis B and hepatitis C infections, and chronic alcohol use, which are the leading causes. The obesity pandemic has led to an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which leads to nonalcoholic steatohepatitis and could progress to cirrhosis. As HCC is among the most common cancers and occurs in the setting of chronic liver disease in most patients, screening the population at risk could help in early diagnosis and management, leading to improved survival. Screening for HCC is performed using biochemical marker testing such as α-fetoprotein (AFP) and cross-sectional imaging. It is critical to emphasize that HCC could potentially occur in patients without cirrhosis (non-cirrhotic HCC), which can account for almost 20% of all HCCs. The lack of cirrhosis can cause a delay in surveillance, which could potentially lead to diagnosis at a later stage, worsening the prognosis for such patients. In this article, we discuss the diagnosis of cirrhosis in at-risk populations with details on the different modalities available for screening HCC in patients with cirrhosis, emphasizing the role of abdominal ultrasounds, the primary imaging modality in HCC screening.

Cirrhosis is a prevalent, chronic condition with an asymptomatic compensated phase, in which patients may feel well, and a decompensated phase that begins with the onset of complications (eg hepatic encephalopathy, ascites, and/or variceal bleeding). Because patients with cirrhosis may appear healthy with normal liver enzymes, alkaline phosphatase, and serum bilirubin levels, awareness of clinical signals is important. For example, patients with thrombocytopenia should be evaluated for chronic liver disease and cirrhosis. Early recognition and management of cirrhosis-related complications (eg hepatic encephalopathy, ascites, and/or variceal bleeding) are important, given their association with hospitalization and poor prognosis (eg increased odds of short-term mortality). Hepatic encephalopathy can be the most subtle cirrhosis-related complication and associated cognitive impairment may be misdiagnosed. Because hepatic encephalopathy can be associated with hospital readmissions, reducing readmission rates after hepatic encephalopathy-related hospitalizations is critical. This includes incorporating ongoing therapy (eg rifaximin plus lactulose) in postdischarge management plans to reduce the risk of hepatic encephalopathy recurrence. Strategies that mitigate cirrhosis progression and prevent the development of cirrhosis-related complications are key to improving patient outcomes.

Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people's main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg's Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening.

We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention.

The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations.

Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes.

In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality.

The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score.

Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems.

Hepatocellular carcinoma (HCC) is a highly lethal cancer with few treatment options available to patients. Most HCC cases in Arizona, a state with a high proportion of Hispanic adults, have not been included in recent reports of HCC incidence. This study describes trends in HCC incidence and stage at diagnosis among Arizona residents between 2009-2017 and reports on racial and ethnic disparities for these outcomes.

The Arizona Cancer Registry was used to identify Arizonans aged 19 or older diagnosed with liver cell carcinoma diagnosed between 2009-2017. A total of 5043 cases were examined. Adjusted annual and 3-year HCC incidence rates (per 100,000) were examined for non-Hispanic White (NHW) and Hispanic adults.

The total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017.

Whe total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017.

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.

To evaluate the association of HCC screening after HCV cure with overall survival.

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.

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).

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.

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%).

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 (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.

To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers.

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.

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.

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.

Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in west Africa, yet data on the incidence of HBV-related hepatocellular carcinoma remain scarce. We aimed to describe the uptake and early outcomes of systematic ultrasound-based hepatocellular carcinoma screening in SEN-B, which is a prospective HBV cohort in Senegal.

In this prospective cohort study, we included treatment-naive, HBsAg-positive individuals who were referred to the two infectious diseases clinics (the Department of Tropical and Infectious Diseases and Ambulatory Treatment Center) at Fann University Hospital of Dakar, Senegal, between Oct 1, 2019, and Oct 31, 2022. All participants resided within the Dakar region. Participants underwent abdominal ultrasound, transient elastography, and clinical and virological assessments at inclusion and every 6 months. Liver lesions at least 1 cm in diameter on ultrasound were assessed using four-phase CT, MRI, or liver biopsy. Adherence to hepatocellular carcinoma surveillance was measured using the proportion of time covered, calculated by dividing the cumulative months covered by abdominal ultrasound examinations by the overall follow-up time, defined as the number of months from the date of cohort entry until the last recorded visit, hepatocellular carcinoma diagnosis, or death. Optimal adherence was defined as a proportion of time covered of 100%.

Overall, 755 (99·6%) of 758 participants had at least one abdominal ultrasound performed. The median age of the enrolled participants was 31 years (IQR 25-39), 355 (47·0%) of 755 participants were women, and 82 (10·9%) had a family history of hepatocellular carcinoma. 15 (2·0%) of 755 individuals were HBeAg positive, 206 (27·3%) of 755 individuals had HBV DNA of more than 2000 IU/mL, and 27 (3·6%) of 755 had elastography-defined liver cirrhosis. Of ten (1·3%) participants with a focal lesion at least 1 cm at initial assessment, CT or MRI ruled out hepatocellular carcinoma in nine, whereas imaging and subsequent liver biopsy confirmed one patient with hepatocellular carcinoma. Two further patients with hepatocellular carcinoma were diagnosed at study presentation due to the presence of portal thrombosis on ultrasound. Excluding the three participants with hepatocellular carcinoma identified at baseline, 752 participants were eligible for screening every 6 months. Median follow-up time was 12 months (IQR 6-18) and the median number of ultrasounds per patient was 3 (2-4). During 809·5 person-years of follow-up, one incident hepatocellular carcinoma was reported, resulting in an incidence rate of 1·24 cases per 1000 person-years (95% CI 0·18-8·80). Overall, 702 (93·0%) of 755 participants showed optimal hepatocellular carcinoma surveillance, but this proportion decreased to 77·8% (42 of 54 participants) after 24 months.

Hepatocellular carcinoma screening is feasible in HBV research cohorts in west Africa, but its longer-term acceptability needs to be evaluated. Long-term hepatocellular carcinoma incidence data are crucial for shaping tailored screening recommendations.

Swiss National Science Foundation, the Swiss Cancer Research Foundation, the National Cancer Institute, and Roche Diagnostics.

For the French translation of the abstract see Supplementary Materials section.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival.

The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations.

A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI).

A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al.

Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.

Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes.

To evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis.

This survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19-related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023.

HCC surveillance knowledge was assessed with 6 questions querying the respondent's ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic-related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians.

Overall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P < .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P < .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P < .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays.

In this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system-level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Hepatocellular carcinoma (HCC) surveillance is associated with improved early tumor detection, but effectiveness is limited by underuse. We characterized adherence to HCC surveillance using proportion of time covered (PTC) and estimated its association with clinical outcomes among patients with cirrhosis.

We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We characterized PTC by imaging in the 12 and 24 months before HCC diagnosis. We used multivariable logistic and Cox regression analyses to assess the association between PTC and early HCC detection, receipt of curative treatment, and overall survival.

Among 2,027 patients with HCC, 331 (51.4% Barcelona Clinic Liver Cancer 0/A) had been followed up for at least 12 months before diagnosis. The median PTC was 24.9% (interquartile range 1.1%-50.7%), with only 16.0% having semiannual imaging and 42.0% having annual surveillance. Semiannual and annual surveillance decreased to 6.3% and 29.6% when assessed over 24 months, although the median PTC remained unchanged at 24.9%. Receipt of gastroenterology/hepatology care had the strongest association with PTC, with median PTC of 36.7% and 3.8% for those with and without gastroenterology/hepatology care, respectively. PTC was independently associated with improved early HCC detection, curative treatment receipt, and overall survival. The median survival was 15.7, 26.8, and 32.7 months among those with PTC of <25% (n = 168 patients), PTC 25%-50% (n = 69 patients), and PTC >50% (n = 94 patients), respectively.

The proportion of time covered by HCC surveillance in patients with cirrhosis remains low, highlighting a need for multilevel interventions.

Eliminating hepatitis B virus (HBV) is a significant worldwide challenge requiring innovative approaches for vaccination, screening, disease management, and the prevention of related conditions. Programs that support patients in accessing needed clinical services can help optimize access to preventive services and treatment resources for hepatitis B.

Here, we outline a coordinator-supported program (HBV Pathway) that connects patients infected with HBV to laboratory testing, imaging, and specialty care for treatment initiation and/or liver cancer surveillance (screening of high-risk patients for liver cancer). This study describes the HBV Pathway steps and reports sociodemographic factors of patients by initiation and completion.

Results showed a 72.5% completion rate (defined as completing all Pathway steps including the final specialty visit) among patients who initiated the Pathway. Differences in completion were observed by age, race, ethnicity, and service area, with higher rates for younger ages, Asian race, non-Hispanic ethnicity, and lower rates for patients within one service area. Of those who completed the specialty visit, 59.5% were referred for hepatocellular carcinoma surveillance.

The HBV Pathway offers dual benefits- care coordination support for patients to promote Pathway completion and a standardized testing and referral program to reduce physician burden. This program provides an easy and reliable process for patients and physicians to obtain updated clinical information and initiate treatment and/or liver cancer screening if needed.

Racial and ethnic disparities in hepatocellular carcinoma (HCC) prognosis exist, partly related to differential failures along the cancer care continuum. We characterized racial and ethnic disparities in treatment receipt among patients with HCC in the United States.

We searched Medline, Embase, and CINAHL databases to identify studies published between January 2012 and March 2022 reporting HCC treatment receipt among adult patients with HCC, stratified by race or ethnicity. We calculated pooled odds ratios for HCC treatment using random effects models.

We identified 15 studies with 320,686 patients (65.8% White, 13.9% Black, 10.4% Asian, and 8.5% Hispanic). Overall, 33.2% of HCC patients underwent any treatment, and 22.7% underwent curative treatment. Compared with White patients, Black patients had lower odds of any treatment (OR 0.67, 95% CI 0.55-0.81) and curative treatment (OR 0.74, 95% CI 0.71-0.78). Similarly, Hispanic patients had lower pooled odds of curative treatment (OR 0.79, 95% CI 0.73-0.84).

There were significant racial and ethnic disparities in HCC treatment receipt, with Black patients having lower odds of receiving any and curative treatment while Hispanic patients having lower odds of curative treatment.

Racial and ethnic differences in treatment receipt serve as an intervention target to reduce disparities in HCC prognosis.

Hepatocellular carcinoma (HCC) incidence and outcomes vary across populations in the United States, but few studies evaluate local drivers of observed disparities. We measured HCC incidence at the community level and assessed community-level HCC risk factors with the goal of informing resource allocation to improve early case detection, which is associated with improved outcomes.

Clinical and demographic data including census tract of residence for all adults diagnosed with HCC in the Connecticut Tumor Registry between 2008 and 2019 were combined with publicly available U.S. Census and Centers for Disease Control and Prevention (CDC) data at the ZIP Code tabulation area (ZCTA) level. The average annual incidence of HCC was calculated for each ZCTA and associations between community-level characteristics, HCC incidence, stage at diagnosis, and survival were evaluated.

Average annual HCC incidence during the study period was 8.9/100,000 adults and varied from 0 to 97.7 per 100,000 adults by ZCTA. At the community level, lower rates of high school graduation, higher rates of poverty, and rural community type were associated with higher HCC incidence. Persons with HCC living in the highest incidence ZCTAs were diagnosed at a younger age and were less likely to be alive at 1, 2, and 5 years after diagnosis.

Community-level socioeconomic factors are strongly associated with HCC incidence and survival in Connecticut.

This reproducible geo-localization approach using cancer registry, Census, and CDC data can be used to identify communities most likely to benefit from health system investments to reduce disparities in HCC.

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.