Hepatocellular Carcinoma Surveillance Program Research Articles

Chronic hepatitis B care in regional Australia: implications for clinical practice and public health policy.

Australia is struggling to meet its National Hepatitis B Strategy care targets, particularly in nonmetropolitan settings. It is vital to engage priority populations and improve their access to recommended care to reach these targets. This retrospective study examined people living with chronic hepatitis B (CHB) in regional North Queensland, Australia, and determined whether their care adhered to current national CHB management guidelines. The analysis aimed to identify gaps in care that might be addressed to improve future outcomes. All individuals referred to the gastroenterology clinic at the Townsville University Hospital in regional North Queensland, Australia, for CHB care between January 2015 and December 2020 were identified. Their linkage to care, engagement in care and receipt of guideline-recommended CHB care were determined. Of 255 individuals, 245 (96%) were linked to care; 108 (42%) remained engaged in care and 86 (38%) were receiving guideline-recommended care in 2021. There were 91/255 (36%) who identified as Indigenous Australians. Indigenous status was the only independent predictor of not being linked to care (odds ratio (OR): 0.13 (95% confidence interval (CI): 0.03-0.60), P = 0.01), not being engaged in care (OR: 0.19 (95% CI: 0.10-0.36), P < 0.0001), not receiving guideline-recommended CHB care (OR: 0.16 (95% CI: 0.08-0.31), P < 0.0001) or not being engaged in a hepatocellular carcinoma surveillance programme (OR: 0.08 (95% CI: 0.02-0.27), P < 0.0001). Current approaches are failing to deliver optimal CHB care to Indigenous Australians in regional North Queensland. Targeted strategies to ensure that Indigenous Australians in the region receive equitable care are urgently needed.

Surgical resection for hepatocellular carcinoma: a single-centre's one decade of experience.

Liver cancer is the third leading cause of global cancer deaths, and hepatocellular carcinoma is its most common type. Liver resection is one of the treatment options for hepatocellular carcinoma (HCC). This study aims to explore our hospital's more than a decade of experience in liver resection for HCC patients. This is a retrospective cohort study on HCC patients undergoing resection from 2010 to 2021 in a tertiary-level hospital in Jakarta, Indonesia. Mortality rates were explored as the primary outcome of this study. Statistical analysis was done on possible predictive factors using Pearson's χ2. Survival analysis was done using the Log-Rank test and Cox Regression. Ninety-one patients were included in this study. The authors found that the postoperative mortality rates were 8.8% (in hospital), 11.5% (30 days), and 24.1% (90 days). Excluding postoperative mortalities, the long-term mortality rates were 44.4% (first year), 58.7% (3 years), and 69.7% (5 years). Cumulatively, the mortality rates were 46.4% (1 year), 68.9% (3 years), 77.8% (5 years), and 67.0% (all time). Significant predictive factors for cumulative 1-year mortality include large tumour diameter [odds ratio (OR) 14.06; 95% CI: 2.59-76.35; comparing <3cm and >10cm tumours; P<0.01], positive resection margin (OR 2.86; 1.17-77.0; P=0.02), and tumour differentiation (P=0.01). Multivariate analysis found hazard ratios of 6.35 (2.13-18.93; P<0.01) and 1.81 (1.04-3.14; P=0.04) for tumour diameter and resection margin, respectively. The mortality rate of HCC patients undergoing resection is still very high. Significant predictive factors for mortality found in this study benefit from earlier diagnosis and treatment; thus, highlighting the importance of HCC surveillance programs.

Serologic Detection of Hepatocellular Carcinoma: Application of Machine Learning and Implications for Diagnostic Models.

The gender, age, lens culinaris agglutinin-reactive fraction of alphafetoprotein, alphafetoprotein, des-gamma-carboxyprothrombin (GALAD) score is a biomarker-based statistical model for the serologic diagnosis of hepatocellular carcinoma (HCC) that has been developed and validated using the case-control approach with a view to early detection. Performance has, however, been suboptimal in the first prospective studies which better reflect the real-world situation. In this article, we report the application of machine learning to a large, prospectively accrued, HCC surveillance data set. Models were built on a cohort of 3,473 patients with chronic liver disease within a rigorous surveillance program between 1998 and 2014, during which 459 patients with HCC were detected. Two random forest (RF) models were trained. The first RF model uses the same variables as the original GALAD model (GALAD-RF); the second is based on routinely available clinical and laboratory features (RF-practical). For comparison, we evaluated a logistic regression GALAD model trained on this longitudinal prospective data set (termed GALAD-Ogaki). Models were evaluated using a repetitive cross-validation approach with the metrics averaged over 100 independent runs. As judged by area under the receiver operator curve (AUROC) and F1 score, the GALAD RF model significantly outperformed the original GALAD model. The RF-practical model also outperformed the original GALAD model in terms of both AUROC and F1 score, and both models outperformed the individual biomarkers. An online web application that implemented the GALAD-RF and RF-practical models is presented. RF-based models improve on the diagnostic performance of the original GALAD model in the setting of a standard HCC surveillance program. Further prospective validation studies are warranted using these models and could be expanded to offer prediction of risk of HCC development over defined periods of time.

Sonographic appearance of focal liver lesions and likelihood of hepatocellular carcinoma in adult Thais with chronic hepatitis B virus infection.

The objective of our study was to study and compare the sonographic findings of hepatocellular carcinoma (HCC) and benign liver lesions, and apply these to an HCC surveillance program in patient with chronic hepatitis B virus (HBV). Sonographic findings of HCC and benign liver lesions were retrospectively reviewed following diagnosis based on either computer tomography or magnetic resonance imaging from July 2010 to December 2020. Multiple sonographic features were analyzed, including internal echogenicity, rim characteristics, and posterior acoustic enhancement. Associations between sonographic characteristics and HCC were assessed using uni- and multi-variate logistic regression analyses. Of the focal liver lesions in 337 chronic HBV patients, there were 25 HCC and 410 benign lesions, with median sizes of 1.6 and 1.0 cm, respectively. Three ultrasound patterns, homogeneous hypoechogenicity, heterogeneous echogenicity, and hypoechoic rims were more frequently found in HCC than in benign lesions. Moreover, the hypoechoic rim feature was the only sonographic pattern independently associated with HCC (Odds ratio, 68.05; 95% confidence interval, 7.37-628.10; p-values < 0.001). In a subgroup analysis of the lesions sized 2 cm or smaller, no sonographic findings were associated with HCC. A hypoechoic rim was a sonographic feature independently associated with HCC. These findings may aid in improving HCC detection and guiding management during HCC screening and surveillance with ultrasound.

Implementation of a Hepatocellular Carcinoma Surveillance Program in a Community-Based Integrated Health System in Patients With Hepatitis C Cirrhosis.

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 surveillance in Australia: current and future perspectives.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and is increasing in incidence in Australia. For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6-monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. While HCC surveillance almost certainly reduces cancer-related mortality, the potential harms of surveillance are incompletely understood. Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. Improved case-finding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic. HCC prediction models and novel surveillance tools such as biomarker panels, computed tomography and magnetic resonance imaging may have a future role in personalised HCC surveillance. Analyses suggest surveillance may be cost-effective, but Australian data remain limited. A centralised HCC surveillance program may ultimately have a role in delivering improved and more equitable care.

The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during the surveillance of patients with cirrhosis.

HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance. We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC. Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study.

Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Identifying individuals at higher risk of developing hepatocellular carcinoma (HCC) is pivotal to improve the performance of surveillance strategies. Herein, we aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine HCC risk stratification. Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programmes (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). The predictive ability of two clinical scores (a routine non-genetic model determined by multivariate analysis and the external aMAP score) with/without the GRS was evaluated by C-indices. The standardised net benefit was derived from decision curves. Among 1,145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into three groups with progressively increased 5-year HCC incidence (Group 1 [n= 627, 5.4%], Group 2 [n= 276, 10.7%], and Group 3 [n= 242, 15.3%]; p <0.001). The multivariate model identified age, male sex, diabetes, platelet count, gamma-glutamyltransferase levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-year HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Indices of 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit. Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and the Wnt-β-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores. The identification of patients at higher risk of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalised screening strategies.

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhotic or non-cirrhotic hepatocellular carcinoma (HCC), and is currently recognized as the fastest growing cause of HCC worldwide. Accordingly, professional society guidelines recommend HCC surveillance in patients with cirrhosis from any etiology, and some may consider it beneficial in subgroups with non-cirrhotic NAFLD at higher risk for HCC. Notably, patients with NAFLD-related HCC are more likely to have HCC diagnosed at more advanced stages and have poorer outcomes when compared to other etiologies, and suboptimal effectiveness of HCC surveillance programs is a major culprit. In this review, we summarize the current guidelines for HCC surveillance and discuss its benefits versus potential harms for NAFLD patients. We also address the unique challenges of HCC surveillance in NAFLD, including higher proportion of NAFLD-related HCC without cirrhosis, poor recognition of at-risk patients, lack of consensus regarding the value of surveillance in non-cirrhotic NAFLD, subpar effectiveness of surveillance tools related to NAFLD phenotype, and preponderant surveillance underuse among NAFLD patients. Finally, we examine the effectiveness of currently used surveillance tools (i.e., ultrasound and alpha fetoprotein) and outline future perspectives including emerging risk stratification tools, imaging surveillance strategies (e.g., abbreviated magnetic resonance imaging protocols), blood-based biomarkers (e.g., GALAD and circulating tumor DNA panels), and interventions to improve surveillance adherence.

THU244 - Could a multi-target blood test make hepatocellular carcinoma surveillance programs more effective? A modelling-based virtual trial

THU244 - Could a multi-target blood test make hepatocellular carcinoma surveillance programs more effective? A modelling-based virtual trial

Influence of hepatocarcinoma surveillance programs on cirrhotic patient’s survival: a real life study.

Resumen Background: Hepatocellular carcinoma (HCC) represents 75%-85% of all primary liver cancers and the third most common cause of cancer-related death worldwide. Cirrhosis is the most relevant risk factor for HCC with 70%-90% of cases diagnosed at end-stage liver disease. Several studies have revealed that early diagnosis of HCC under surveillance improves both prognosis and availability of major curative options. Aim:to determine current HCC surveillance impact on survival at a university hospital. Methods: we retrospectively gathered all HCC diagnosed between Jan 2012 and May 2018 at a university hospital in Málaga(Spain). Inclusion criteria were all space-occupying lesions (SOL) diagnosed at our centre and exclusion criteria were all non-HCC SOL and HCC diagnosed before or after the given dates. Epidemiological, etiological, liver-function, clinical, tumor-related, therapeutic and response-to-treatment variables were collected. Results: 159 patients were finally included. 92.5% of HCC were diagnosed on cirrhotic patients. Following the Barcelona Clinic Liver Cancer (BCLC) staging classification, 73% of patients who underwent surveillance were diagnosed on 0, A or B stages, whereas 38% of patients who didn’t perform surveillance were diagnosed on given stages. The surveillance-applying cluster had a 33 months survival median while the not-surveillance cohort showed a survival of 6 months. The median survival on early stages (0 and A) [50 months], stage B (20 months), stage C (10 months) and stage D (2 months) showed statistically significant differences. Conclusions:HCC surveillance programs allow early diagnosis on favorable tumor stages, increasing chances of major treatment options, and life expectancy of patients.

Multi-target blood test to improve the performance of hepatocellular carcinoma surveillance programs: A modeling-based virtual trial.

405 Background: Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer mortality in the United States. Although clinical guidelines recommend ultrasound (U/S), with or without the serum biomarker alpha fetoprotein (AFP) for HCC surveillance in at-risk patients, only 24% of patients adhere to surveillance and only one-third of HCCs are detected before developing symptoms. A multi-target HCC blood-based test (mt-HBT) was recently shown to have promising sensitivity for early HCC detection and may help improve surveillance adherence given its blood-based nature. Our objective was to evaluate the comparative clinical effectiveness of mt-HBT with the current standard-of-care surveillance strategy in patients with cirrhosis. Methods: We simulated a virtual trial by developing a microsimulation model of the natural history of HCC in patients with compensated (Child Pugh A) cirrhosis over a 30-year horizon. To inform model parameters, we used published data on tumor progression, competing risks of mortality, and real-world HCC surveillance adherence. Test performance characteristics were informed by a network meta-analysis. We simulated the life course of 51-year-old patients with cirrhosis and compared no surveillance with biannual surveillance using (1) AFP only, (2) U/S only, (3) U/S+AFP, (4) mt-HBT, and (5) mt-HBT with improved adherence. We assumed a blood-based test—without U/S—would improve surveillance adherence by 10% compared with current adherence (̃4% absolute improvement). Results: Per 100,000 cirrhosis patients, mt-HBT detected 6,220 more early-stage HCC than no surveillance, 2,250 (+57%) more than AFP, 1080 (+21%) more than U/S, and 200 (-3%) less than U/S+AFP. mt-HBT with improved adherence detected 210 (+3%) more early-stage HCC than U/S+AFP (Table). The remaining HCC cases were either symptomatic or the patients died per other competing causes prior to detection. The number of screening tests needed to detect one HCC were 296 for AFP, 287 for U/S, 253 for U/S+AFP, 254 for mt-HBT and 262 for mt-HBT with improved adherence. The number of diagnostic MRI/CT needed to detect one HCC were 40 for AFP, 38 for U/S, 45 for U/S+AFP, 37 for mt-HBT, and 38 for mt-HBT with improved adherence. Conclusions: mt-HBT detects more early-HCC cases than U/S and similar number of early-HCC cases with U/S+AFP. By decreasing surveillance barriers and increasing adherence, mt-HBT could improve early HCC detection and could be promising option for HCC surveillance in patients with cirrhosis. [Table: see text]

Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.

Simple SummaryNon-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC) in the near future. In this article, we review the current knowledge about the epidemiology, risk factors, pathogenesis, clinical presentation and diagnostic approach to HCC in NAFLD. Knowledge of these facts is of great importance to improve the early identification of patients that are at risk, allowing for early detection of HCC and, thus, an improvement in clinical outcomes. This is especially important given that around 30% of NAFLD-related HCCs develop in a non-cirrhotic liver. The presence of diabetes, male sex, older age and Hispanic race, in addition to liver cirrhosis, are the most important risk factors for HCC in this setting. In summarising the current knowledge of genetic susceptibility, metabolic derangements and immunological mechanisms involved in the pathogenesis of NAFLD-related HCC, we illustrate the need for further research on this intriguing topic.Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of liver morbidity worldwide and, as such, represents the pathogenic background for the increasing incidence of hepatocellular carcinoma (HCC). The annual incidence of NAFLD-related HCC is expected to increase by 45–130% by 2030. Diabetes mellitus is the most important risk factor for HCC development in NAFLD, with the risk further increased when associated with other metabolic traits, such as obesity, arterial hypertension and dyslipidemia. The highest risk of HCC exists in patients with advanced fibrosis or cirrhosis, although 20–50% of HCC cases arise in NAFLD patients with an absence of cirrhosis. This calls for further investigation of the pathogenic mechanisms that are involved in hepatocarcinogenesis, including genetics, metabolomics, the influence of the gut microbiota and immunological responses. Early identification of patients with or at risk of NAFLD is of utmost importance to improve outcomes. As NAFLD is highly prevalent in the community, the identification of cases should rely upon simple demographic and clinical characteristics. Once identified, these patients should then be evaluated for the presence of advanced fibrosis or cirrhosis and subsequently enter HCC surveillance programs if appropriate. A significant problem is the early recognition of non-cirrhotic NAFLD patients who will develop HCC, where new biomarkers and scores are potential solutions to tackle this issue.

Clinical Presentation of Hepatocellular Carcinoma in African Americans vs. Caucasians: A Retrospective Analysis.

Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.

Screening for Hepatocellular Carcinoma in Chronic Hepatitis B: An Update.

(1) Background: Hepatocellular carcinoma (HCC) is an important cause of mortality in individuals with chronic hepatitis B infection, with screening of high-risk groups recommended in all major international guidelines. Our understanding of the risk factors involved has improved over time, encouraging researchers to develop models that predict future risk of HCC development. (2) Methods: A literature search of the PubMed database was carried out to identify studies that derive or validate models predicting HCC development in patients with chronic hepatitis B. Subsequently, a second literature search was carried out to explore the potential role of novel viral biomarkers in this field. (3) Results: To date, a total of 23 models have been developed predicting future HCC risk, of which 12 have been derived from cohorts of treatment-naïve individuals. Most models have been developed in Asian populations (n = 20), with a smaller number in Caucasian cohorts (n = 3). All of the models demonstrate satisfactory performance in their original derivation cohorts, but many lack external validation. In recent studies, novel viral biomarkers have demonstrated utility in predicting HCC risk in patients with chronic hepatitis B, amongst both treated and treatment-naïve patients. (4) Conclusion: Several models have been developed to predict the risk of HCC development in individuals with chronic hepatitis B infection, but many have not been externally validated outside of the Asian population. Further research is needed to refine these models and facilitate a more tailored HCC surveillance programme in the future.

Effect of Hepatocellular Carcinoma Surveillance Programmes on Overall Survival in a Mixed Cirrhotic UK Population: A Prospective, Longitudinal Cohort Study.

Introduction: Surveillance for hepatocellular carcinoma (HCC) is recommended by national and international guidelines. However, there are no trial data on whether surveillance improves clinical outcomes in a UK cirrhosis population of mixed aetiology. Our aim was to determine the impact of, and adherence to, surveillance on overall survival. Methods: We prospectively collected data on consecutive patients diagnosed with HCC between January 2009 and December 2015 at two large UK centres. We assessed outcomes depending on whether they had been entered into an HCC surveillance programme, and if they had adhered to that. Results: Out of 985 patients diagnosed with HCC in this study, 40.0% had been enrolled in a surveillance programme. Of these, 76.6% were adherent with surveillance and 24.4% were not. Adherence to surveillance was significantly associated with improved overall survival, even when accounting for lead-time bias using different approaches (HR for 270 days lead-time adjustment 0.64, 0.53 to 0.76, p < 0.001). Conclusions: When adjusted for lead-time bias, HCC surveillance is associated with improved overall survival; however, the beneficial effect of surveillance on survival was lower than reported in studies that did not account fully for lead-time bias.

Hepatocellular carcinoma amongst Aboriginal and Torres Strait Islander peoples of Australia.

BackgroundLiver disease and hepatocellular carcinoma (HCC) are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. However, there is a lack of population based high quality data assessing the differences in HCC epidemiology and outcomes according to Indigenous status. The aim of this study was therefore to perform a large epidemiological study of HCC investigating differences between Indigenous and non-Indigenous Australians with HCC.MethodsStudy design was a retrospective cohort study. Data linkage methodology was used to link data from cancer registries with hospital separation summaries across three Australian jurisdictions during 2000–2017. Cumulative survival (Kaplan-Meier) and the differences in survival (Multivariable Cox-regression) by Indigenous status were assessed.FindingsA total of 229 Indigenous and 3587 non-Indigenous HCC cases were included in the analyses. Significant epidemiological differences identified for Indigenous HCC cases included younger age at onset, higher proportion of females, higher rurality, lower socioeconomic status, and higher comorbidity burden (all p < 0.001). The distribution of cofactors was also significantly different for Indigenous Australians including higher prevalence of alcohol misuse, hepatitis B, and diabetes and more frequent presence of multiple HCC cofactors (all p < 0.001). Indigenous Australians received curative HCC therapies less frequently (6.6% vs. 14.5%, p < 0.001) and had poorer 5-year survival (10.0% vs. 17.3%, p < 0.001; unadjusted hazard ratio (HR) =1.42 96%CI 1.21–1.65) compared to non-Indigenous Australians. The strength of the association between indigenous status and survival was weaker and statistically non-significant after adjusting for rurality, comorbidity burden and lack of curative therapy (adjusted-HR=1.20 95%CI 0.97–1.47)InterpretationSuch data provide a call to action to help design and implement health literacy, liver management and HCC surveillance programs for Indigenous people to help close the liver cancer mortality gap.

Utilization of hepatocellular carcinoma surveillance programs in patients with cirrhosis: A systematic review and meta-analaysis.

e16141 Background: Patients with cirrhosis are advised to undergo hepatocellular carcinoma (HCC) surveillance every six months. Routine screening is associated with early tumor detection and improved survival. However, surveillance is underutilized. We aimed to characterize the impact of HCC surveillance interventions on patient uptake and concomitant detection of HCC. Methods: We performed a comprehensive literature search of major databases (from inception to October 2020) to identify studies which assess the impact of HCC surveillance programs in patients with cirrhosis. Our primary endpoint was uptake of screening defined as having an abdominal sonogram every at least every 6 months. Secondary endpoint was the detection of HCC following screening. Pooled data was assessed using a random-effects model expressed in terms of odds ratio (OR) and 95% confidence interval (CI). Results: Nine studies were included for meta-analysis which involved 5,021 patients with cirrhosis. Patients with a history of hepatitis B or C accounted for 40.5% of the study cohort. Comparing both screening and control groups, patients were 5 times more likely to undergo abdominal sonography if they participated in surveillance programs versus usual care (OR 4.69; CI: 2.41 – 9.13, I2: 94%). Overall, the mean difference in patients who did undergo screening versus those who did not participate in surveillance was 30.6% (CI: 19.2% – 41.9%, P &lt; 0.001). Comparing both screening and control groups, patients were 1.5 times more likely to be diagnosed with HCC if they participated in surveillance programs (OR 1.49; CI: 0.57 – 3.89, I2: 65%). On subgroup analysis, comparing type of intervention program, dedicated surveillance programs showed a higher uptake compared to clinical reminders, though not statistically significant (dedicated programs OR 62.6, CI: 1.53 – 2559.5 vs clinical reminders OR 2.63, CI: 1.82 – 3.79). Conclusions: Patient uptake in HCC surveillance remains underutilized. Interventions such as dedicated surveillance programs and clinical reminders systems can significantly increase uptake of abdominal sonography and cancer detection.

Assessing risk scores for predicting hepatocellular carcinoma in Thai patients with chronic hepatitis B.

Chronic hepatitis B (CHB) infection-associated hepatocellular carcinoma (HCC) is a major health problem in Asian countries. Several HCC risk prediction models have been developed using either treated or untreated CHB patients. However, there is limited validation of these risk scores in a treated and untreated mixed CHB patient cohort. This study analysed and validated HCC risk scores among 2208 CHB patients who enrolled in the HCC surveillance programme in Thailand during July 2010. The baseline clinical and radiologic data of these CHB patients were applied to calculate various HCC risk scores. There were 20 patients (0.9%) with HCC development at the 5.9-year follow-up. The areas under the receiver operating characteristic curves (AUROCs) predicting HCC risk at 5years were 0.80 (0.68-0.91), 0.73 (0.60-0.85), 0.79 (0.67-0.91), 0.70 (0.58-0.82), 0.72 (0.59-0.85), 0.76 (0.63-0.87) and 0.77 (0.64-0.89) for the GAG-HCC, CU-HCC, REACH-B, PAGE-B, mPAGE-B, CAMD and AASL scores, respectively. The overall HCC risk scores were accurate and comparable. However, the subgroup analysis revealed better HCC-risk-predictive performance in the treated patients, while performance was less helpful in those not fulfilling criteria for antiviral therapy. Clinicians should be aware of these data when using the HCC risk score in untreated CHB patients.