Hepatocellular Carcinoma Screening Research Articles

Analysis of four long non-coding RNAs for hepatocellular carcinoma screening and prognosis by the aid of machine learning techniques

Hepatocellular carcinoma (HCC) represents a significant health burden in Egypt, largely attributable to the endemic prevalence of hepatitis B and C viruses. Early identification of HCC remains a challenge due to the lack of widespread screening among at-risk populations. The objective of this study was to assess the utility of machine learning in predicting HCC by analyzing the combined expression of lncRNAs and conventional laboratory biomarkers. Plasma levels of four lncRNAs (LINC00152, LINC00853, UCA1, and GAS5) were quantified in a cohort of 52 HCC patients and 30 age-matched controls. The individual diagnostic performance of each lncRNA was assessed using ROC curve analysis. Subsequently, a machine learning model was constructed using Python’s Scikit-learn platform to integrate these lncRNAs with additional clinical laboratory parameters for HCC diagnosis. Individual lncRNAs exhibited moderate diagnostic accuracy, with sensitivity and specificity ranging from 60 to 83% and 53–67%, respectively. In contrast, the machine learning model demonstrated superior performance, achieving 100% sensitivity and 97% specificity. Notably, a higher LINC00152 to GAS5 expression ratio significantly correlated with increased mortality risk. The integration of lncRNA biomarkers with conventional laboratory data within a machine learning framework demonstrates significant potential for developing a precise and cost-effective diagnostic tool for HCC. To enhance the model’s robustness and prognostic capabilities, future studies should incorporate larger cohorts and explore a wider array of lncRNAs.

Low level of hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in compensated cirrhotic patients

BACKGROUND Whether patients with compensated cirrhosis and low-level viremia (LLV) of hepatitis B should receive antiviral therapy (AVT) is still controversial, and published results are inconsistent. AIM To investigate the link between LLV in compensated cirrhosis and prognosis concerning hepatocellular carcinoma (HCC), decompensation, and liver-related events. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched up to March 5, 2023. Outcomes of interest were assessed by pooled hazard ratios (HRs). The study was registered with PROSPERO (CRD42023405345). RESULTS Six cohort studies representing 3155 patients were included. Compared with patients with undetectable HBV DNA, patients with LLV was associated with increased risk of HCC (HR: 2.06, 95%CI: 1.36-3.13; Q -statistic-P = 0.07, I 2 = 51%) regardless of receiving AVT or not (AVT group: HR: 3.14; 95%CI: 1.73-5.69; Q -statistic-P = 0.60, I 2 = 0%; un-AVT group: HR: 1.73, 95%CI: 1.09-2.76; Q -statistic-P = 0.11, I 2 = 50%). The pooled results showed no statistical association between LLV and decompensation of cirrhosis (HR: 2.06, 95%CI: 0.89-4.76; Q -statistic-P = 0.04, I 2 = 69%), and liver-related events (HR: 1.84, 95%CI: 0.92-3.67; Q -statistic-P = 0.03, I 2 = 72%), respectively. Grading of Recommendations Assessment, Development and Evaluation assessment indicated moderate certainty for HCC, very low certainty for decompensation of cirrhosis and liver-related clinical events. CONCLUSION LLV in compensated cirrhotic patients is associated with increased risk of HCC, higher tendency for hepatic decompensation and liver-related events. Closer screening of HCC should be conducted in this population.

The methylation signature of hepatocellular carcinoma trajectory based on pseudotime and chronological time for predicting precancerous patients.

Early screening of hepatocellular carcinoma (HCC) is strongly recommended for hepatitis B virus (HBV)-infected patients. We aimed to develop and validate a predictive nomogram based on HCC occurrence trajectory for screening precancerous patients with HCC. Peripheral blood mononuclear cells (PBMC) samples from 22 patients with HCC with their precancerous stage (n = 55) and 18 healthy controls were measured using HumanMethylation EPIC BeadChip assay. HCC trajectory was assessed by pseudotime based on TimeAx algorithm and chronological time. The 43 candidate CpG sites were selected from the methylation signature and measured using multiplex bisulfite sequencing in a retrospective cohort of HBV-infected patients (n = 604). A 5-CpG-classifier was built using the LASSO Cox regression model, based on the association between the methylation level of every CpG and the duration from enrollment to HCC occurrence of individual patient. We validated the risk stratification and predictive accuracy of this classifier in both the primary cohort (n = 300) and independent validation cohort (n = 304). Pseudotime and chronological time of HCC trajectory analysis revealed that the PD-1/PD-L1 pathway underwent changes in the precancerous stage. Based on the trajectory of methylation signature, we built a 5-CpG-classifier which remained powerful and independent predictive efficiency after stratified analysis by clinicopathological risk factors in both primary cohort and independent validation cohort. A predicting nomogram including the 5-CpG-classifier was constructed after multivariate analysis. One-year cumulative hazard of HCC in low- and high-risk groups of HBV-infected patients was 3.0% (0.1%-5.8%) and 17.90% (11.00%-24.3%) (P < .0001) in primary cohort, 4.5% (1.20%-7.80%) and 27.3 (18.90-34.90) (P < .0001) in the independent validation cohort. One-year before HCC was a critical period of transitional time when parts of the methylation profile underwent shifting toward HCC like. The nomogram could identify precancerous stage patients with HCC who should be screened for early diagnosis and intervention.

Impact of Screening on Mortality for Patients Diagnosed with Hepatocellular Carcinoma in a Safety-Net Healthcare System: An Opportunity for Addressing Disparities.

Purpose: We describe the impact of screening on outcomes of patients diagnosed with hepatocellular carcinoma (HCC) in an urban safety-net healthcare system compared to a non-screened cohort diagnosed with HCC. Methods: Patients diagnosed with HCC at John Peter Smith Health Network were identified by querying the hospital tumor registry and allocated to the screened cohort if they had undergone any liver imaging within one year prior to HCC diagnosis, while the remainder were allocated to the non-screened cohort. Kaplan-Meier methods and log-rank tests were used to compare 3-year survival curves from an index date of HCC diagnosis. Cox proportional hazard models were used to calculate unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Duffy adjustment was used to address lead-time bias. Results: A total of 158 patients were included (n = 53 screened, n = 105 non-screened). The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9-NA) and that for the non-screened cohort was 5.4 months (95% CI: 3.7-8.5) [HR death (non-screened vs. screened) = 2.4, 95% CI: 1.6-3.6; log rank p < 0.0001]. The benefit of screening remained after adjusting for lead-time bias (HR 2.19, 95% CI 1.4-3.3, p = 0.0002). Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients diagnosed with HCC outside of a screening protocol.

Phase 3 validation of PAaM for hepatocellular carcinoma risk stratification in cirrhosis

Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis. Molecular (Prognostic Liver Secretome signature with alpha-fetoprotein) and clinical (aMAP score) variable-based scores were integrated to develop PAaM, which was subsequently validated in two phase 3 biomarker validation studies: the statewide Texas HCC Consortium (THCCC) and nationwide HCC Early Detection Strategy (HEDS) prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation (PRoBE) design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events. Of 2,156 cirrhosis patients in THCCC, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared to low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios (sHRs) for incident HCC of 7.51 (95% confidence interval [CI], 4.42-12.8) and 4.20 (95%CI, 2.52-7.01), respectively. Of 1,328 cirrhosis patients in HEDS, PAaM identified 201 (15%) high-risk, 540 (41%) intermediate-risk, and 587 (44%) low-risk patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate risk groups were associated with sHRs for incident HCC of 6.54 (95%CI, 3.85-11.1) and 1.77 (95%CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease (MASLD) and cured hepatitis C infection. PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.

Risk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis

Hepatocellular carcinoma (HCC) is typically detected only at advanced stages when treatment options are limited. Most of the current HCC risk models focus on patients with viral hepatitis or diagnosed cirrhosis or require variables not routinely available in clinical care. To identify modifiable HCC risk factors in the general population and to develop a risk score to inform HCC screening and risk-factor modification interventions for high-risk individuals without viral hepatitis or decompensated cirrhosis. This cohort study analyzed demographic, clinical, laboratory, and diagnostic data from the US Department of Veterans Affairs (VA) electronic health records. Data were divided into development and validation samples. Veterans aged 30 to 95 years were included, and those with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC were excluded. Patients were followed up until the occurrence of HCC diagnosis, death, or December 31, 2021. A Cox proportional hazards regression model for 10-year risk of HCC was developed and used to create an HCC risk score, and performance in development and validation samples and in patient subgroups was evaluated. One outpatient visit date per person at least 18 months after VA entry, between October 1, 2007, and March 31, 2020, was randomly selected and used as the index date for the start of follow-up. Analyses were performed from March 2023 to May 2024. Age, sex, race and ethnicity, body mass index, liver fibrosis (detected with Fibrosis-4 Index [FIB-4]), diabetes status, smoking status, and alcohol use. First HCC diagnosis during follow-up. This information was ascertained from VA national cancer registry topography and histology codes and from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for the inpatient or outpatient visits. This study of 6 509 288 veterans included 6 048 917 males (92.9%), with a median (IQR) age of 65 (54-74) years, who identified as being of Hispanic (5.3%), non-Hispanic Black (15.0%), non-Hispanic White (68.9%), or other (4.6%) race and ethnicity. Overall, 15 142 patients (0.2%) developed HCC, 69.5% of whom had FIB-4 of 3.25 or lower at baseline. While FIB-4 was the most important variable, age, sex, race and ethnicity, body mass index, diabetes, smoking, and alcohol use were also informative. Discrimination in the development sample was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82-0.85] vs 0.79 [95% CI, 0.77-0.80]). The HCC risk score performed consistently well in the validation sample and in all subgroups. A FIB-4 threshold of 3.25 would screen 5.0% of the cohort at a cost of 28 false-positives for every true-positive; a model risk score of 58 would screen 4.7% of the cohort at a cost of 23 false-positives for every true-positive. Results of this study suggest that a multivariable risk score that uses routinely available clinical data outperforms FIB-4 alone in identifying patients at risk of HCC who do not have viral hepatitis or hepatic decompensation at baseline.

Community-Based Point-of-Care Screening for Hepatitis B Virus and Hepatocellular Carcinoma in Rural Tanzania.

Sub-Saharan Africa has a high burden of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC). The lack of surveillance programs has led to low rates of diagnosis and treatment, particularly in rural areas. We conducted mobile HBV-HCC screening clinics in rural Tanzania between March 2021 and February 2023. After undergoing informed consent, patients completed a questionnaire about HBV. A rapid point-of-care (POC) assay measured HBV surface antigen (HBsAg), and HBsAg-positive patients underwent POC ultrasound to screen for HCC and POC hepatitis C (HCV) antibody testing. The primary outcome was number of HBV diagnoses, and the secondary outcome was prevalence of liver masses in HBsAg-positive individuals. Data were analyzed with descriptive statistics. Five hundred and one patients were screened for HBV; 63% (n = 303) were female with median (interquartile range [IQR]) age of 40 (28-55) years. Only 6% (n = 30) reported being vaccinated against HBV, 92% (n = 453) reported no vaccination, and 2% (n = 12) did not know their vaccination status. Seventy-six percent (n = 340) did not know they should get vaccinated, and 4% (n = 16) reported that vaccination was too expensive. Two percent (n = 11) of patients were positive for HBsAg, with 55% (n = 6) of those being female with median (IQR) age of 36 (34-43) years. None of the HBsAg-positive patients reported being vaccinated against HBV, and all were negative for HCV. On ultrasound, one patient had a liver mass, and another had ascites. We demonstrated that community-based HBV and HCC screening can be implemented in Africa with local partnerships, and this model could be used to promote awareness and improve early detection of disease.

Neighborhood opportunity is associated with completion of hepatocellular carcinoma surveillance prior to the diagnosis of hepatocellular carcinoma in patients with cirrhosis

BackgroundThe Ohio Opportunity Index (OOI) is a multidimensional metric used to quantify neighborhood-level resources to access a wide array of factors that influence health. This study examined the relationship between neighborhood opportunity and completion of guideline-concordant hepatocellular carcinoma (HCC) screening in patients with cirrhosis. MethodsThis retrospective study included patients with cirrhosis and HCC who received care at The Ohio State University Wexner Medical Center between 1/1/2015 and 12/31/2021. High opportunity was defined as a score greater than the third quartile of the study cohort. Modified Poisson regression models with robust variance examined the association, on the prevalence ratio (aPR) scale, between guideline-concordant HCC screening and high neighborhood opportunity status. ResultsThis study included 157 cirrhosis patients newly diagnosed with HCC. Only 25.5 % of the patients completed HCC surveillance within 6 months prior to diagnosis. The OOI was a significant predictor of adherence in all models. For every ten-percentile increase in OOI score, there was a consistent increase in the prevalence ratio (PR) of pre-diagnosis HCC surveillance (PR=1.37, 95 % CI 1.10–1.71). This effect remained significant after controlling for sociodemographic, clinical, and cirrhosis-related variables (adjusted PR=1.38, 95 % CI 1.02–1.85. Compared to those with high OOI (i.e.,≥Q3), patients in the lowest opportunity quartile had a 64 % lower prevalence of HCC screening (PR=0.36, 95 % CI 0.26–0.50). ConclusionNeighborhood opportunity status has a dose-dependent effect on HCC surveillance adherence in patients with cirrhosis. Future studies should identify neighborhood-level interventions to reduce socioeconomic disparities in HCC diagnosis and outcomes.

Risk-stratified hepatocellular carcinoma screening according to the degree of obesity and progression to cirrhosis for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD) in Japan: a cost-effectiveness study.

To evaluate the cost-effectiveness of risk-stratified hepatocellular carcinoma (HCC) screening in diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A state-transition model from a healthcare payer perspective on a lifetime horizon. Japan. A hypothetical cohort of 50-year-old diabetic patients with MASLD risk-stratified according to degree of obesity and progression to cirrhosis. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis (MASH) and MASH cirrhosis are progressive manifestations of this specific type of liver disease. Abdominal ultrasound (US), US with alpha-fetoprotein (AFP), US with AFP and lectin-reactive alpha-fetoprotein (AFP-L3), CT, extracellular contrast-media-enhanced MRI (ECCM-MRI), gadoxetic acid-enhanced MRI (EOB-MRI) and no screening. Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), early-stage HCC cases, advanced-stage HCC cases and HCC-related deaths. EOB-MRI is the most cost-effective screening method for non-obese diabetic patients with MASH cirrhosis and for obese diabetic patients with MASH and MASH cirrhosis. Cost-effectiveness was sensitive to HCC incidence in non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH, and the adherence rate of HCC screening in obese diabetic patients with MASH. When the semiannual HCC incidence was between 0.008 and 0.0138 in non-obese diabetic patients with MASH cirrhosis, US with AFP was more cost-effective than EOB-MRI. Cost-effectiveness acceptability curves showed that EOB-MRI was 50.7%, 96.0% and 99.9% cost-effective in obese diabetic patients with MASH and non-obese diabetic patients with MASH cirrhosis, and obese diabetic patients with MASH cirrhosis at a willingness-to-pay level of $50 000 per QALY gained. Compared with no screening in 100 000 non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH cirrhosis, EOB-MRI reduced total costs by US$69 million and by US$142 million, increased lifetime effectiveness by 12 546 QALYs and by 15 815 QALYs, detected 17 873 and 21 014 early-stage HCC cases, and averted 2068 and 2471 HCC-related deaths, respectively. Of all HCC screening methods for diabetic patients with MASH cirrhosis, EOB-MRI yields the greatest cost-saving with the highest QALYs, detects the greatest number of early-stage HCC cases and averts the greatest number of advanced-stage HCC cases and HCC-related deaths. The findings provide important insights for the precise implementation of risk-stratified HCC surveillance to reduce morbidity and mortality and improve the quality of life in diabetic patients with MASLD.

Bridging the Gap Between Imaging and Molecular Characterization: Current Understanding of Radiomics and Radiogenomics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related deaths. Imaging plays a crucial role in the screening, diagnosis, and monitoring of HCC; however, the potential mechanism regarding phenotypes or molecular subtyping remains underexplored. Radiomics significantly expands the selection of features available by extracting quantitative features from imaging data. Radiogenomics bridges the gap between imaging and genetic/transcriptomic information by associating imaging features with critical genes and pathways, thereby providing biological annotations to these features. Despite challenges in interpreting these connections, assessing their universality, and considering the diversity in HCC etiology and genetic information across different populations, radiomics and radiogenomics offer new perspectives for precision treatment in HCC. This article provides an up-to-date summary of the advancements in radiomics and radiogenomics throughout the HCC care continuum, focusing on the clinical applications, advantages, and limitations of current techniques and offering prospects. Future research should aim to overcome these challenges to improve the prognosis of HCC patients and leverage imaging information for patient benefit.

Hepatocellular Carcinoma in Acute Hepatic Porphyria: A Meta-Analysis of Observational Studies.

Hepatocellular carcinoma (HCC) is a long-term complication of acute hepatic porphyria (AHP) inclusive of acute intermittent porphyria [AIP], variegate porphyria [VP], or hereditary coproporphyria [HCP]. Data on HCC risk in AHP patients are limited and heterogeneous. We performed this meta-analysis with aims to (a) determine incidence of HCC in AHP and specific subtypes of AHP and (b) examine high-risk groups for HCC. Data from studies reporting HCC development in AHP patients were pooled and reported per 100 person years with 95% confidence intervals (CI). 12 observational (5 prospective) studies (11 Europe and 1 US) on 2735 patients (mean age 54.8 yrs., 62% females) with AHP (80% AIP) were analyzed. 115 HCC cases were observed with HCC incidence per 100 person years of 0.3 (0.2-0.5) in AHP, 0.4 (0.2-0.6) in AIP, 0.3 (0-0.4) in VP, and 0.2 (0.1-0.6) in HCP. The risk was 0.4 (0.2-0.6) in females, 0.3 (0.1-0.5) in males, 0.9 (0.1-1.7) in symptomatic, and 0.5 (0-1.6) in asymptomatic patients. Analyses were heterogeneous with publication bias. AHP patients with HCC were older females with a higher prevalence of cirrhosis, alcohol use, and viral hepatitis. The annual incidence of HCC in AHP patients is 0.3%, with higher risk in AIP, older females, symptomatic patients, and those with other risk factors of liver disease. Future studies pooling individual patient data and overcoming limitations of the current meta-analysis are needed as a basis for deriving a effective screening and surveillance approach for HCC in patients with AHP.

Role of Imaging in Screening for Hepatocellular Carcinoma.

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.

B-323 Measurement of PIVIKA II Blood Level in Patients with Liver Diseases by Immunoassays

Abstract Background Liver diseases are the most common diseases globally and can be complicated to cirrhosis and cancer and lead to death if not managed. It is crucial to prevent patients with liver diseases to reach the level of complications in particular liver cancer or hepatocellular Carcinoma (HCC). There are many screening lab tests to monitor and evaluate patients with liver disease such as alpha fetoprotein (AFP), however, it lacks optimal sensitivity and specificity. Another promising screening test is Prothrombin Induced by Vitamin K deficiency or antagonist- II (PIVKA-II) to complements AFP in screening of HCC. The aim of this study was to evaluate two PIVKA-II immunoassays and compare it to AFP in blood samples of patients with liver diseases. Methods Blood samples were collected from 56 patients with liver diseases, chronic hepatitis B (n=14), chronic hepatitis C (n=18), liver cirrhosis (n=14), and HCC (n=10) at King Abdulaziz medical city, Riyadh, SA. Measurement of PIVKA-II levels were performed on all samples by Snibe and Abbott analyzers. Clinical data was collected from the HIS BestCare. AFP was performed on Abbott analyzer. Statistical analysis was carried by Excel sheet Microsoft and p value was set at 0.05. Results There was an excellent correlation (R2= 0.9327) between the PIVKA-II two immunoassays from Snibe and Abbott among patients with HCC (p=0.1384). The diagnostic sensitivity PIVKA-II for Abbott and Snibe were calculated to be 78% and 90% respectively among HCC patients at cutoff 32 mAU/mL with specificity of 16% and 44.4% respectively. This was corresponding to sensitivity of 90% and specificity of 67% on AFP at cutoff 10 ng/mL. Conclusions The two PIVKA-II two immunoassays were perfectly correlated among the samples of HCC patients. The sensitivity of both assays was high but with lower specificity. Snibe assay has superior sensitivity and specificity among patients with HCC.

B-333 Optimizing AFP Cutoffs for Hepatocellular Carcinoma Screening: Insights from the National Cancer Screening Program in Korea

Abstract Background The incidence rate and mortality rate of liver cancer were 11.6 (ranked 8th among cancers) and 10.7 (4th) per 100,000 individuals respectively globally in 2020, whereas in Korea, they were higher at 29.5 (7th) and 20.6 (2nd) per 100,000 individuals. The National Cancer Screening Program (NCSP) in Korea conducts biannual concurrent liver ultrasound and serum alpha-fetoprotein (AFP) measurement for hepatocellular carcinoma (HCC) surveillance in high-risk groups, including those with chronic hepatitis B and C, and liver cirrhosis. The effectiveness of surveillance is impacted by varying AFP cutoffs; however, within the NCSP, different cutoffs are being used, and it is not clear which cutoffs are being employed. Harmonization of AFP test results by major reagent manufacturers have been achieved, enabling the adoption of a uniform threshold. This study aims to assess the variation of AFP cutoffs among institutions within the NCSP and suggest a unified and optimal AFP threshold. Methods This study examined HCC screening results from the NCSP between 2018 and 2020, investigating unit and cutoff usage for AFP test across institutions each year (number of institutions were 4452 for 2018, 4754 for 2019, and 4847 for 2020). To determine the optimal AFP cutoff for HCC screening, datasets comprised unique patient results from 2018 to 2020 (number of patients = 819,644). Receiver operating characteristic (ROC) curve analyses were conducted for determine best AFP cutoffs. Cancer diagnosis was defined by billing records indicating HCC within one year post-screening. Results More than 96% of institutions used ng/mL as a unit of AFP test. Among institutions using ng/mL, the most frequently used AFP cutoff was 7 ng/mL, with frequency percentages of 75.7%, 72.2%, and 62.2% in 2018, 2019, 2020, respectively. The percentiles (1st, 10th, 90th, 99th) of AFP cutoff usage for the years 2018, 2019, and 2020 were (7, 7, 8.8, 15), (7, 7, 8.9, 15), and (7, 7, 9, 15) respectively. The AUC of ROC was 0.824 and some cut-off points with their sensitivity and specificity values were as follows: 5 ng/mL (0.648, 0.874); 10 (0.457, 0.976); 20 (0.327, 0.993); 40 (0.246, 0.997); 100 (0.169, 0.998); 200 (0.123, 0.999); 400 (0.084, 1). Conclusions Different cutoffs observed across institutions in NCSP. Our study cautiously suggests that the optimal AFP value for screening HCC in NCSP may range from 10 to 20 ng/mL, considering sensitivity and specificity when AFP is combined with ultrasound in regions with a high prevalence of HCC. For a more suitable AFP cutoff recommendation, additional analyses based on ultrasound findings and underlying diseases should be considered.

Impact of screening on mortality for patients diagnosed with hepatocellular carcinoma at a safety-net hospital: An opportunity for addressing disparities.

140 Background: Hepatocellular carcinoma (HCC) is a common and deadly cancer with a rising incidence in the US. HCC almost always develops on a background of chronic liver disease, which disproportionately affects individuals of lower socioeconomic status (SES), perpetuating existing disparities. Compounding these disparities, individuals of lower SES are less likely to participate in recommended cancer screening exams. Here, we describe the outcomes of patients diagnosed with HCC at a large urban safety-net hospital primarily serving the underserved. Methods: We identified patients diagnosed with HCC at John Peter Smith Hospital in Fort Worth, Texas from January 1, 2018, to March 31, 2021 to determine the impact of screening on survival. Patients were allocated to the screened cohort if they had undergone liver imaging within one year prior to HCC diagnosis. Kaplan-Meier methods and log-rank test were used to illustrate and compare 3-year survival curves from an index date of diagnosis until death. Cox proportional hazards model were used to calculate unadjusted and adjusted hazards ratios (HR) and 95% confidence intervals (CI). Lead time bias was adjusted in a sensitivity analysis using the Duffy adjustment and a sojourn time of 70 days and 140 days. Results: A total of 158 patients were included (n=53 screened, n=105 unscreened). The mean age was 62 years; 144 (91%) had cirrhosis, 78% were male, 34% were non-Hispanic white, and 8.2% had private insurance. Those in the unscreened cohort had more severe liver dysfunction (as measured by the ALBI grade) and produced higher levels of AFP, but were less likely to have cirrhosis than the screened cohort. The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9-NA) and 5.4 months (95% CI: 3.7-8.5) in the unscreened cohort (HR death (unscreened v screened) = 2.4, 95% CI: 1.6-3.6; log rank P &lt;0.0001). After adjusting for ALBI grade, AFP, hepatitis C, insurance status and initial treatment, there was a statistical difference in hazard of death in the three years (HR: 2.3; 95% CI: 1.5-3.6), favoring the screened cohort. The benefit for screening remained after adjusting for lead-time bias. With a mean sojourn time of 70 days, the HR death was 2.19 (95% CI 1.4-3.3, P =0.0002) and was 2.09 (1.4-3.2, P =0.0005) with a 140-day sojourn time. Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients with incidentally-diagnosed HCC. Altogether, this implies that earlier diagnosis and institution of treatment can positively improve survival for patients with newly diagnosed HCC in a population of patients evaluated at a safety-net hospital. Development of screening programs in accordance with accepted guidelines with outreach to high-risk individuals represents an area of high value care for safety-net hospitals.

S1751 Advanced Liver Disease Detected by Abdominal Imaging Does Not Lead to Linkage to Care in Hepatology Clinics or Uptake of Hepatocellular Carcinoma Screening in an Urban Center

S1751 Advanced Liver Disease Detected by Abdominal Imaging Does Not Lead to Linkage to Care in Hepatology Clinics or Uptake of Hepatocellular Carcinoma Screening in an Urban Center

Abstract B074: Qualitative assessment of knowledge gaps and barriers to Hepatitis B and liver cancer screening in high-risk U.S. communities

Abstract Background: Up to 2.4 million people in the US live with chronic hepatitis B (HBV) infection (Wong et al., 2021). Foreign-born communities are most impacted, particularly those from Asia, the Pacific Islands, the Caribbean, and sub-Saharan Africa (Conners et al., 2023). Individuals with unmanaged HBV have a 15-40% lifetime risk of dying prematurely from cirrhosis or hepatocellular carcinoma (HCC) (McMahon, 2009). Low awareness, cultural norms, and misperceptions about HBV, HCC, and their connection contribute to low screening and care rates in affected communities. A more robust and comprehensive understanding of these barriers is needed to design effective awareness campaigns to improve HBV screening and care and prevent HCC. To this end, this study aimed to learn about existing knowledge and misconceptions about HBV and its relationship to HCC in high-risk communities, identify barriers to screening, and use the findings to develop effective communication strategies that raise awareness and dispel myths. Methods: Fifteen focus groups and two key informant interviews with community members, leaders, and public health experts were conducted to assess beliefs and attitudes about HBV and HCC and to identify preferred communication strategies. Results: The link between HBV and HCC remains poorly understood, and myths persist about the transmission and outcomes of both conditions. Multiple barriers to HBV and HCC screening exist, including concerns about insurance and immigration status, language barriers, cultural and religious beliefs, lack of general health literacy, lack of resources to cope with a positive diagnosis, widespread distrust of Western medicine, and fear of stigma and isolation. Ideas for effective communication methods included employing community health educators, primary care providers, ethnic media outlets and personal testimonials for delivery of information, and tailoring communications by community, age, and gender. These findings were used to create a suite of culturally and linguistically appropriate educational materials for use in each of twelve communities. Conclusions: Many challenges to increasing screening persist in groups most impacted by HBV and HCC, including a need for increased awareness about their connection. Community engagement is essential to overcoming these challenges, as are specific, targeted messaging and dissemination to improve the uptake of HBV screening and management. Behavioral and Social Science: Community-based Participatory Research Citation Format: Beatrice Zovich, Fiona Borondy-Jenkins, Suzanne Block, Kate Moraras, Thomas Chen, Chari Cohen. Qualitative assessment of knowledge gaps and barriers to Hepatitis B and liver cancer screening in high-risk U.S. communities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B074.

The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients.

This study aimed to investigate the expression and clinical significance of syncytin-1 in the serum exosomes of hepatocellular carcinoma (HCC) patients. Serum samples were collected from 61 patients with newly diagnosed HCC and 61 healthy individuals. Exosomes were extracted from serum samples and identified using transmission electron microscopy and Western blot. The relative expression levels of syncytin-1 in exosomes were determined by real-time quantitative PCR. The protein expression levels of alpha-fetoprotein and syncytin-1 in HCC patients were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to evaluate the sensitivity and specificity of serum exosomal syncytin-1 in diagnosing HCC. The relationships between syncytin-1 expression and clinical pathological features were analyzed using receiver operating characteristic curve analysis. The results showed that the expression level of syncytin-1 in the serum of patients with newly diagnosed HCC was significantly higher than that in the normal control group (P < 0.0001). Using pathological diagnosis as the gold standard, the sensitivity and specificity of syncytin-1 for the auxiliary diagnosis of HCC were 91.3% and 75.5%, respectively, which were significantly higher than those of alpha-fetoprotein (P < 0.0001). The relative expression level of serum exosomal syncytin-1 was significantly associated with lymph node metastasis, degree of differentiation, and CNLC staging of HCC patients (P < 0.05). In conclusion, syncytin-1 in serum exosomes has high sensitivity and specificity for diagnosing HCC and can serve as a novel tumor marker for early screening, detection, and staging of HCC.

Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial.

The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC 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 HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not 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 HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. NCT02582918 and NCT03756051.

Comparing barriers to early stage diagnosis of hepatocellular carcinoma between safety net hospitals and academic medical centers: An analysis from the United States Safety-Net Collaborative.

Early detection of hepatocellular carcinoma (HCC) is associated with improved survival. However, a greater proportion of patients treated at safety net hospitals (SNHs) present with late-stage disease compared to those at academic medical centers (AMCs). This study aims to identify barriers to diagnosis of HCC, highlighting differences between SNHs and AMCs. The US Safety Net Collaborative-HCC database was queried. Patients were stratified by facility of diagnosis (SNH or AMC). Patient demographics and HCC screening rates were examined. The primary outcome was stage at diagnosis (AJCC I/II-"early"; AJCC III/IV-"late"). 1290 patients were included; 50.2% diagnosed at SNHs and 49.8% at AMCs. At SNHs, 44.4% of patients were diagnosed late, compared to 27.6% at AMCs. On multivariable regression, Black race was associated with late diagnosis in both facilities (SNH: odds ratio 1.96, p = 0.03; AMC: 2.27, <0.01). Screening was associated with decreased odds of late diagnosis (SNH: 0.46, p = 0.04; AMC: 0.37, p < 0.01). Black race was associated with late diagnosis of HCC, while screening was associated with early diagnosis across institutional types. These results suggest socially constructed racial bias in screening and diagnosis of HCC. Screening efforts targeting SNH patients and Black patients at all facilities are essential to reduce disparities.