Hepatocellular Carcinoma Surveillance Research Articles

Role of biomarkers in the diagnosis and management of HCC.

For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha fetoprotein (AFP) remains one of the few validated biomarkers for patients with hepatocellular carcinoma (HCC). Although AFP has shown potential for each of these steps, its performance when used alone has often been suboptimal. There continues to be discordant recommendations about AFP's value when combined with ultrasound for surveillance as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for selection of liver transplant candidates. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies to evaluate the role of these emerging biomarkers in clinical practice are currently ongoing.

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

External validation of models to predict hepatocellular carcinoma in Hepatitis C Virus cured F3-F4 patients.

Several hepatocellular carcinoma (HCC) risk-models have been developed to individualise patient surveillance following sustained viral response (SVR) in Hepatitis C Virus patients. Validation of these models in different cohorts is an important step to incorporate a more personalised risk assessment in clinical practice. We aimed at applying these models to stratify the risk in our patients and potentially determine cost-saving associated with individualised HCC risk-stratification screening strategy. Patients with baseline F3-4 fibrosis treated with new oral direct-acting antivirals who had reached a SVR were regularly followed as part of the HCC surveillance strategy. Six models were applied: Pons, aMAP, Ioannou, HCC risk, Alonso and Semmler. Validation of the models was performed based on sensitivity and the proportion of patients labelled as "high risk". After excluding 557 with less than 3 fibrosis, 12 without SVR, 18 with a follow up (FU)<1year, 17 transplant recipients, 16 lost to FU and 31 with HCC at time of antiviral therapy, our cohort consisted of 349 F3-4 SVR patients. Twenty-three patients (6.6%) developed HCC after a median FU of 5.12years. The sensitivity of the different models varied between 0.17 (Semmler7noalcohol) and 1 (Alonso A and aMAP). The lowest proportion of high-risk patients corresponded to the Semmler-noalcohol model (5%). Sixty-three and 90% of the Alonso A and aMAP patients, respectively were labelled as high risk. The most reliable HCC risk-model applied to our cohort to predict HCC development is the Alonso model (based on fibrosis stage assessed by liver stiffness measurements or Fibrosis-4 index (FIB-4) at baseline and after 1year, and albumin levels at 1year) with a-100% sensitivity in detecting HCC among those at high risk and 63% labelled as high risk. The application of the model would have saved the cost of 1290 ultrasound no longer being performed in the 37% low-risk group. In our cohort, the Alonso A model allows the most reliable reduction in HCC screening resulting in safely stopping life-long monitoring in about a third of F3-F4 patients achieving SVR with DAAs.

Progression of chronic liver disease to hepatocellular carcinoma: implications for surveillance and management

BackgroundCurrent opinion holds that hepatocellular carcinoma (HCC) arises as a stepwise progression from chronic liver disease (CLD) to cirrhosis and then to HCC. However, some HCCs may develop in a non-cirrhotic liver, raising uncertainty about their origin.MethodsWe analysed a prospectively accrued cohort of 2592 CLD patients (median follow-up = 13 years) with no prior evidence of liver cirrhosis. To track the progression of liver fibrosis prior to HCC diagnosis, we examined serial measurements of Fib-4 (an index of liver fibrosis). We also evaluated fibrosis progression in response to antiviral treatment in patients with hepatitis C (HCV) and hepatitis B (HBV). Recognising the limitations of serologic fibrosis assessment, we correlated Fib-4 and fibrosis histology within this cohort.ResultsAmong HCC patients, 28% had no indication of cirrhosis prior to HCC diagnosis. Only 31% of HBV-related HCC cases followed the cirrhotic pathway. HCV patients who achieved sustained virological response (SVR) developed cirrhosis approximately 7 years before HCC diagnosis.ConclusionsOur analysis challenges the notion of cirrhosis as an obligatory stage of HCC development in CLD patients. We affirm HBV’s direct oncogenic potential and find that achieving SVR does not universally prevent HCC development. Our findings have major implications for HCC surveillance.

Diagnostic accuracy of serological and imaging tests used in surveillance for hepatocellular carcinoma in adults with cirrhosis: a systematic review protocol

Background Liver cirrhosis is the largest risk factor for developing hepatocellular carcinoma (HCC), and surveillance is therefore recommended among this population. Current guidance recommends surveillance with ultrasound, with or without alpha-fetoprotein (AFP). This review is part of a larger project looking at benefits, harms and costs of surveillance for HCC in people with cirrhosis. It aims to synthesise the evidence on the diagnostic accuracy of imaging or biomarker tests, alone or in combination, to identify HCC in adults with liver cirrhosis in a surveillance programme. Methods We will identify studies through a 2021 Cochrane review with similar eligibility criteria, and a database search of MEDLINE, Embase and the Cochrane Database of Systematic Reviews. We will include diagnostic test accuracy studies with adult cirrhosis patients of any aetiology. Studies must assess at least one of the following index tests: ultrasound (US), magnetic resonance imaging (MRI), computerised tomography (CT), alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), a genomic biomarker, or a diagnostic prediction model incorporating at least one of the above-mentioned tests. We will assess studies for risk of bias using QUADAS-2 and QUADAS-C. We will combine data using bivariate random effects meta-analyses. For tests evaluated across varying diagnostic thresholds, we will produce pooled estimates of sensitivity and specificity across the full range of numerical thresholds, where possible. Where sufficient studies compare two or more index tests, we will perform additional analyses to compare the accuracy of different tests. Where feasible, we will stratify all meta-analyses by tumour size and patient characteristics, including cirrhosis aetiology and liver disease severity. Discussion This review will synthesise evidence across the full range of possible surveillance tests, using advanced statistical methods to summarise accuracy across all thresholds and to compare the accuracy of different tests. PROSPERO registration CRD42022357163

Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance

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.

The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance.

Abdominal US is currently the best-validated surveillance strategy for hepatocellular carcinoma (HCC) in at-risk patients. It is the only modality shown to have completed all five phases of validation and can achieve high sensitivity and specificity for HCC detection, especially when conducted by expert sonographers in high-volume centers. However, US also has limitations, including operator dependency and varying sensitivity in clinical practice. Further, the sensitivity of US for early-stage HCC detection is lower in patients with obesity or nonviral liver disease, increasingly common populations undergoing surveillance. Imaging-based and blood-based surveillance strategies, including abbreviated MRI and biomarker panels, may overcome some limitations of US-based surveillance. Both strategies have promising test performance in phase II and phase III biomarker studies and are undergoing prospective validation. Considering the variation in HCC risk and test performance between patients, there will likely be a shift away from a one-size-fits-all approach and toward precision screening, in which the "best" test is selected based on individual patient characteristics. In this upcoming era of precision HCC screening among patients with cirrhosis, US will likely continue to have an important, albeit reduced, surveillance role.

Metabolomics biomarkers of hepatocellular carcinoma in a prospective cohort of patients with cirrhosis

Background & AimsThe effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance of the screening modalities. MethodsWe developed a multicenter prospective cohort of cirrhotic patients undergoing surveillance with MRI, and applied global untargeted metabolomics to 612 longitudinal serum samples from 203 patients. Among them, 37 developed HCC during follow-up. ResultsWe identified 150 metabolites with significant abundance changes in samples collected prior to HCC (Cases) compared to samples from patients who didn’t develop HCC (Controls). Tauro-conjugated bile acids and gamma-glutamyl amino acids were increased, while acyl-cholines and deoxycholate derivatives were decreased. Seven amino acids including serine and alanine, had strong associations with HCC risk, while strong protective effects were observed for N-acetylglycine and glycerophosphorylcholine. Machine learning using the 150 metabolites, age, gender, patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TMS6SF2) SNPs, identified 15 variables giving optimal performance. Among them, N-acetylglycine had the highest AUC in discriminating Cases and Controls. When restricting Cases to samples collected within 1 year prior to HCC (Cases-12M), additional metabolites including microbiota-derived metabolites were identified. The combination of the top 6 variables identified by machine learning (alpha-fetoprotein, 6-bromotryptophan, N-acetylglycine, salicyluric glucuronide, testosterone sulfate and age) had good performance in discriminating Cases-12M from Controls (AUC=0.88 [0.83-0.93]). Finally, 23 metabolites distinguished Cases with Liver Imaging Reporting and Data System (LI-RADS)-3 lesions from Controls with LI-RADS-3 lesions, with reduced abundance of acyl-cholines and glycerophosphorylcholine-related lysophospholipids in Cases-LR3. ConclusionsThis study identified N-acetylglycine, amino acids, bile acids and choline-derived metabolites as main biomarkers of HCC risk, and microbiota-derived metabolites as main contributors to HCC development. Impact and ImplicationsThe effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited. There is an urgent need for improvement in risk stratification and new screening modalities, blood biomarkers in particular. Longitudinal collection of paired blood samples and MRI images from cirrhotic patients is particularly valuable in assessing how early blood and imaging markers become positive during the period when lesions are observed to obtain a diagnosis of HCC. We generated a multicenter prospective cohort of patients with cirrhosis under surveillance with contrast MRI, applied untargeted metabolomics on 612 serum samples from 203 patients and identified metabolites associated with risk of HCC development. Such biomarkers may significantly improve early stage HCC detection for cirrhotic patients undergoing HCC surveillance, a critical step to increasing curative treatment opportunities and reducing mortality.

Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia.

Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.

Statewide Survey of Primary Care and Subspecialty Providers on Hepatocellular Carcinoma Risk-Stratification and Surveillance Practices.

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.

Hepatocellular carcinoma surveillance among people living with hepatitis B in Senegal (SEN-B): insights from a prospective cohort study

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.

The Influence of Medical Subspecialty on the Adherence to Hepatocellular Carcinoma Surveillance in Patients with Chronic Hepatitis B

Objective: This study aimed to determine the adherence rate of HCC surveillance in CHB patients at the largest tertiary hospital in Southern Thailand and identify patient and physician factors that influence it. Materials and Methods: This retrospective cohort study included patients with CHB who were followed up for more than 1 year between 2011 and 2019 at a tertiary care hospital in Thailand. Patients diagnosed with HCC within 6 months of their first visit were excluded. The rate of adherence with HCC surveillance was calculated using percentage of time up-to-date with HCC surveillance (PTUDS). Results: The mean age of 531 eligible patients at the time HCC surveillance started was 55.5 ± 9.26 years. The most common indications for surveillance were male over 40 years of age (41.2%), female over 50 years of age (28.9%), and cirrhosis (22.6%). The median PTUDS was 70.6% (interquartile range 55.1 – 81.4%). The highest PTUDS was for cirrhosis (74.0%). For physicians’ subspecialties, the median PTUDS was 71.8% for gastroenterologists (IQR 58.3 – 81.6%) and 41.7% for internists (IQR 31.4 – 65.8%). Factors associated with increased PTUDS by multivariable analysis were having ≥2 clinical visits per year (±18.4%, p&lt;0.001), civil servant reimbursement (±8.81%, p=0.001), cirrhosis (±6.06%, p=0.003), and being follow-up by gastroenterologists (±20.4%, p&lt;0.001). Conclusion: The adherence with surveillance program in patients with CHB being followed up at a tertiary care setting in Thailand was good. This finding underscores the importance of education regarding indications for HCC surveillance, particularly in patients without cirrhosis.

Three-Dimensional Structure of Novel Liver Cancer Biomarker Liver Cancer-Specific Serine Protease Inhibitor Kazal (LC-SPIK) and Its Performance in Clinical Diagnosis of Hepatocellular Carcinoma (HCC).

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3D structure, which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC; about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK's clinical performance was also studied in HCC patients with viral and non-viral cirrhosis, including cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84, while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK exhibits significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71-91% of HCC patients with false-negative AFP test results in viral-associated HCC and non-viral-associated HCC.

Abstract 4802: Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. In sub-Saharan Africa, HCC is the second most common cancer in men and the sixth in women. African patients present with HCC at a young age and at advanced stage of disease. Improved surveillance can increase early HCC detection. The GALAD score has good sensitivity in the diagnosis of HCC in Asia, Europe and North America, however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in Ghanaian patients. Methods: Clinical data from patients with cirrhosis (n=93) or HCC (n=78) from out-patient hepatology clinics at 3 teaching hospitals in Ghana were abstracted, and serum samples analyzed. A logistic regression model predicting HCC status based on GALAD score was constructed to obtain the Receiver Operating Characteristics (ROC) curve for GALAD. The area under the curve (AUC) with 95% confidence interval was calculated and used to assess the performance of the GALAD score in surveillance for HCC. Results: The median AFP (5010.2 vs. 3.4), L3% (28.3 vs. 0.3) and DCP (507.6 vs. 0.2) levels were all significantly higher among HCC cases than the controls (p&amp;lt;0.0001). The median GALAD score was also higher among HCC patients (8.0 vs. -4.1, p&amp;lt;0.0001). The AUC of the GALAD score in the diagnosis of HCC was 0.86 (95% CI 0.79 - 0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. In a re-fit of the logistic regression model, the most significant factors in the GALAD model in our cohort were AFP-L3% and log(DCP). The AUC of the new GALAD model after model selection was 0.89. Conclusion: The GALAD score can be used to detect HCC in Ghana and has the potential to improve HCC surveillance in low-resource settings in sub-Saharan Africa. Citation Format: Yvonne Ayerki Nartey, Ju Dong Yang, Tyler Zemla, Joshua Ayawin, Shadrack Osei Asibey, Mohamed El-Kassas, Sally Afua Bampoh, Amoako Duah, Adwoa Agyei-Nkansah, Yaw Asante Awuku, Mary Yeboah Afihene, Hiroyuki Yamada, Jun Yin, Amelie Plymoth, Lewis Rowland Roberts. Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4802.

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.

Non-contrast short MRI surveillance for HCC screening: the study protocol of the SMS-HCC prospective multicenter study

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective.Key points• The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.Graphical

Abbreviated magnetic resonance imaging in hepatocellular carcinoma surveillance: A review.

Hepatocellular carcinoma (HCC) is one of the most common primary malignancies of the liver and a leading cause for cancer-related deaths worldwide. HCC surveillance aims at early detection. The recommended strategy for screening HCC is biannual ultrasound with or without alpha-fetoprotein. However, this strategy is associated with sub-optimal sensitivity. Abbreviated magnetic resonance imaging (AMRI) is a promising alternative to ultrasound (US) for surveillance of HCC. The data regarding the role of AMRI in HCC screening is evolving. There are different AMRI protocols, each having its merits and disadvantages. In this review, we discuss the need for AMRI, protocols of AMRI and hindrances to widespread adoption of AMRI.

Proactive case finding of alcohol-related liver disease in high-risk populations: A systematic review.

Alcohol-related liver disease (ARLD) is often diagnosed at a late stage when mortality is unacceptably high. Earlier identification of ARLD may lead to reduced alcohol intake, participation in hepatocellular carcinoma surveillance and reduction in liver-related morbidity and mortality. People with alcohol use disorder (AUD) are at highest risk of ARLD. The aim of this systematic review was to understand the yield of proactive screening for ARLD amongst high-risk groups. Embase, Medline, Scopus and grey literature were searched for studies describing proactive assessment for alcohol-related liver disease in people with a history of alcohol excess or diagnosed AUD. Outcomes of interest were fibrosis and cirrhosis detection rates, clinical outcomes, portal hypertension evaluation, attendance at follow-up and cost-effectiveness. Fifteen studies were identified for inclusion from 1115 returned by the search. Four key settings for patient engagement were identified as inpatient addiction services, outpatient addiction services, general acute hospital admissions and community outreach. Of these, acute hospital admissions were the highest yield for cirrhosis at 10.8%-29.6% and community outreach the lowest was 1.2%-2.3%. Targeted fibrosis assessment of high-risk populations for ARLD is feasible to conduct and identifies a proportion of patients at risk of advanced liver disease. The highest yield is amongst inpatients admitted with AUD. Prospective work is needed to establish which are the most effective and acceptable screening methods and the impact on long-term outcomes.

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.

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.