Ultrasound is the primary imaging modality used for surveillance of patients at risk for HCC. In 2017, the American College of Radiology Liver Imaging Reporting and Data Systems (ACR LI-RADS) introduced US LI-RADS to standardize the performance, interpretation, and reporting of US for HCC surveillance, with the algorithm recently updated as LI-RADS US Surveillance v2024. The American Association for the Study of Liver Diseases (AASLD) recommends reporting both the examination-level LI-RADS US Category as well as the US Visualization Score. The US Category conveys the overall findings of the exam and primarily determines follow up recommendations. The US Visualization Score conveys the expected sensitivity of the test and stratifies patients into appropriate surveillance pathways. One of the goals of routine surveillance is the detection of HCC at an early, potentially curable stage. Therefore, optimizing US technique is of critical importance. Increasing North American and worldwide utilization of LI-RADS US Surveillance, which includes technical recommendations, through education and outreach will undoubtedly benefit patients undergoing US HCC surveillance.

Abbreviated MRI (AMRI) has been proposed as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance; however, comparative data for AMRI and ultrasound are needed. Thus, we evaluated the sensitivity and specificity of dynamic contrast-enhanced (DCE)-AMRI and ultrasound for early-stage HCC detection in patients with cirrhosis.

We conducted a multicenter retrospective case-control study among patients with cirrhosis (cases with early-stage HCC as per Milan Criteria; controls without HCC) who underwent an ultrasound and a DCE-MRI within a 6-month period between 2012 and 2019. HCC diagnosis was confirmed by imaging alone in 85% and by histopathology in 15% of patients. Dynamic AMRI examinations were simulated from the full MRI by selecting relevant sequences. Independent, blinded interpretations of ultrasounds and AMRI results were performed using Liver Imaging Reporting and Data System algorithms. Ultrasounds were considered positive if US-3 observations were detected. AMRI was considered positive if LR-4, LR-5, or LR-M were detected. Per-patient sensitivity and specificity for early-stage HCC detection were estimated, and cross-modality differences were tested.

We included 216 cases and 432 controls. Patient-level sensitivity and specificity of AMRI were significantly higher compared with ultrasound: 80.1% (95% CI 76.1-83.6) vs. 71.1% (95% CI 66.6-75.2), p <0.001, and 91.9% (95% CI 89.9-93.5) vs. 72.3% (95% CI 69.3-75.2), p <0.001, respectively. AMRI sensitivity was significantly higher compared with ultrasound among patients with Child-Pugh B cirrhosis (80.8% vs. 57.4%, p <0.001) but not among those with Child-Pugh A (84.7% vs. 78.6%, p = 0.07) or Child-Pugh C cirrhosis (52.6% vs. 68.4%, p = 0.18).

Dynamic AMRI may be more sensitive and specific for early-stage HCC detection in patients with cirrhosis compared with ultrasound, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis. Larger direct comparative data sets are needed, particularly among patients with Child-Pugh C cirrhosis who may benefit from alternative surveillance strategies.

Abbreviated MRI (AMRI) is increasingly recognized as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance. However, existing data are limited by single-center samples, spectrum bias, and lack of comparative data for AMRI vs. ultrasound. We found that AMRI had significantly higher per-patient sensitivity and specificity compared with ultrasound for the detection of early-stage HCC, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis, and both modalities underperformed in patients with Child-Pugh C cirrhosis. If sufficiently validated, AMRI could be adopted into practice guidelines for HCC surveillance and serve as a preferred alternative in select subgroups of patients.

Alcohol-related liver disease is the third leading cause of hepatocellular carcinoma worldwide and the leading cause in Europe. Additionally, the recent definition of metabolic dysfunction-associated steatotic liver disease with increased alcohol intake (MetALD) will enrich this population with a more nuanced phenotype, reflecting recent epidemiological trends. In these patients, the hepatocellular carcinoma diagnosis is often delayed and less frequently detected through screening programmes. Moreover, at the time of diagnosis, patients with alcohol-related hepatocellular carcinoma tend to have a poorer general condition, more severely impaired liver function, and a higher prevalence of comorbidities, leading to increased competitive mortality. However, when hepatocellular carcinoma is diagnosed during surveillance programmes in patients with alcohol-related liver disease or MetALD, the rate of allocation to first-line curative treatments is high (56%) and comparable to that of patients with virus-related hepatocellular carcinoma. As a consequence, the aetiology of the underlying cirrhosis cannot be considered an independent prognostic factor in patients with hepatocellular carcinoma. Instead, prognosis is driven by liver function, general condition, and tumour burden. This underscores the crucial role of early diagnosis through periodic surveillance in patients with alcohol- or MetALD-related cirrhosis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is the fastest growing cause of cancer death in the United States (U.S.) In the U.S., current national clinical practice guidelines from the 2023 American Association for the Study of Liver Diseases (AASLD) Practice Guidance and the recently updated Liver Imaging Reporting & Data Systems (LI-RADS) Ultrasound (US) Surveillance v2024 core recommend semi-annual serum α-fetoprotein and US screening of patients deemed to be high risk for developing HCC. In this article, we will explore the transition to a patient-centered approach to HCC surveillance, including the role of the new LI-RADS US Surveillance v2024 core and the use of visualization score for determining ultrasound quality, the known risk factors for poor US image quality, and the potential options for alternative surveillance strategies when US may not be a viable option for certain patients, including multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and several abbreviated MRI protocols.

MRI is a potential alternative to ultrasound for hepatocellular carcinoma (HCC) detection. We evaluated the impact of ultrasound and dynamic abbreviated MRI (AMRI) exam quality on early-stage HCC detection.

We conducted a multicenter case-control study among patients with cirrhosis (cases with early-stage HCC per Milan Criteria; controls without HCC) who underwent both a liver ultrasound and dynamic contrast-enhanced (DCE) AMRI within 6 months in 2012-2019. Two radiologists performed independent, blinded interpretations of both exams for HCC detection and scored exam quality as no/mild, moderate, or severe limitations. Associations between exam quality, patient characteristics, and HCC detection were assessed by odds ratios (OR).

Of 216 cases and 432 controls, severe limitations were reported in 7% and 8% of ultrasounds and DCE-AMRIs, respectively. Severe limitations at ultrasound were associated with obesity (OR 2.08, 95%CI [1.32-3.32]) and metabolic dysfunction-associated steatotic liver disease (MASLD) (OR 1.98 [1.12-3.44]) but not for DCE-AMRI. Decompensated cirrhosis (Child-Pugh C) was associated with severe limitations for both ultrasound (OR 2.54 [1.37-4.58]) and DCE-AMRI (OR 3.96 [2.36-6.58]). Compared to exams with no/mild limitations, exams with severe limitations had lower sensitivity for ultrasound (79.6% vs. 21.7%, P < 0.001) and AMRI (86.1% vs. 50.0%, P = 0.001). In patients in whom ultrasound was severely limited, DCE-AMRI had significantly higher odds of early-stage HCC detection than ultrasound (OR 8.23 [1.25-54.02]).

HCC detection by DCE-AMRI may be preferred in patients with severe limitations at ultrasound due to obesity and MASLD. Both modalities remain limited for patients with decompensated cirrhosis, for whom alternative strategies may be needed.

BACKGROUND. The LI-RADS Ultrasound Surveillance algorithm was updated in 2024, incorporating α-fetoprotein (AFP) and a visualization score of VIS-C into management recommendations after nonpositive results. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of LI-RADS Ultrasound Surveillance version 2017 (v2017) and version 2024 (v2024) for the detection of hepatocellular carcinoma (HCC) in at-risk patients and to identify predictors of VIS-C on follow-up surveillance examinations. METHODS. This retrospective analysis included 407 patients (230 men and 177 women; median age, 56 years) with cirrhosis who underwent rounds of semiannual surveillance ultrasound as part of a prospective trial from November 2011 to August 2014. Two radiologists independently assigned ultrasound categories to round 1 examinations and visualization scores to round 1 and round 2 examinations; a third radiologist adjudicated disagreements. The AFP level was considered positive if elevated or increasing from preenrollment values, per v2024 criteria. The reference standard for HCC was positive biopsy or an LR-5 observation on MRI. Diagnostic performance was compared between v2017 and v2024. Logistic regression analyses were performed to identify predictors of a round 2 VIS-C result, with attention given to risk factors for VIS-C described in v2024. RESULTS. HCC was diagnosed in 28 patients (6.9%). LI-RADS Ultrasound Surveillance v2024, in comparison with v2017, showed greater sensitivity for reader 1 (64.3% vs 42.9%, p = .03) and reader 2 (64.3% vs 39.3%, p = .02) and lower specificity for reader 1 (82.1% vs 92.6%, p < .001) and reader 2 (82.3% vs 92.9%, p < .001). All seven patients with HCC detected by v2024 but not v2017 by means of consensus assessments had increasing AFP; two also had elevated AFP. Among 299 patients who underwent round 2 ultrasound after negative round 1 v2024 surveillance results, the only independent predictor of a round 2 VIS-C result was a round 1 VIS-C result (adjusted OR = 21.04 [95% CI, 10.84-40.83], p < .001). For 88 of these patients with round 1 VIS-C, no v2024 risk factor showed a significant univariable association with repeat VIS-C. CONCLUSION. Compared with v2017, LI-RADS Ultrasound Surveillance v2024 had higher sensitivity but lower specificity for HCC detection, which was primarily related to increasing, rather than elevated, AFP. The only independent predictor of VIS-C on subsequent ultrasound was the initial VIS-C result. CLINICAL IMPACT. The findings support the use of LI-RADS Ultrasound Surveillance v2024 to improve HCC detection in at-risk patients.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Current international guidelines recommend 6-monthly ultrasound surveillance in all patients with cirrhosis and those with hepatitis B virus-related risk factors to detect early-stage HCC. However, it is unknown whether the benefits of surveillance are comparable across patient groups and underlying disease-related factors. We aimed to evaluate patient- and disease-related factors associated with HCC stage at diagnosis and survival in an ethnically diverse UK population.

This was a multicentre retrospective observational study including patients with newly diagnosed HCC between 2007 and 2020 from six UK centres. Cox proportional-hazards regression and multivariate logistic regression models were used.

Overall, 1,780 HCC patients comprising 20.9% with ArLD, 29.7% with NAFLD, and 31.0% with viral hepatitis were analysed. Surveillance was associated with improved survival in patients with viral hepatitis but not in patients with ArLD and NAFLD. Surveillance was also associated with early-stage disease (BCLC stage 0 or A) at presentation in viral hepatitis but not in patients with ArLD. Females with ArLD were 2.5-fold more likely to present with early-stage HCC than males. Patients with NAFLD were more likely to develop HCC in the absence of cirrhosis. Type 2 diabetes was not associated with mortality, but metformin use did show survival benefit. Patients of white ethnicity had improved survival and were less likely to present with late-stage HCC compared to other ethnicities.

HCC surveillance as currently delivered was less effective for detecting early-stage HCC in patients with non-viral and non-cirrhotic liver disease. Gender and ethnicity influences stage at presentation and outcomes. HCC surveillance strategies are needed to refine risk stratification particularly in patients with NAFLD or without cirrhosis.

Hepatocellular carcinoma (HCC) in Malaysia is a growing health concern, despite regular liver ultrasound and α-fetoprotein (AFP) surveillance. The GALAD model incorporates AFP, lens culinaris agglutinin- reactive α-fetoprotein (AFP-L3), protein induced by vitamin K antagonist-II (PIVKA-II), gender and age to predict the probability of HCC. Our objective was to evaluate the diagnostic ability of GALAD compared to AFP in HCC screening.

A single-centre, case control study recruited newly diagnosed HCC and cirrhotic patients. Serum biomarkers were quantified using a microfluidic-based automated immunoanalyzer. The diagnostic ability of AFP, AFP-L3, PIVKA-II and GALAD was assessed using receiver operating characteristic curve (ROC) and corresponding area under the curve (AUC) analysis.

Among the 44 HCC cases, GALAD score achieved the highest AUC value of 0.94 (95% confidence interval [CI]: 0.90-0.98, p < 0.0001) significantly surpassing AFP (0.89), AFP-L3 (0.84) and PIVKA-II (0.88). The GALAD score demonstrated 84.1% sensitivity and 93.8% specificity at the standard cut-off (-0.63) and 88.6%/92.2% at its best cut-off (-1.035) for detecting any stage of HCC, outperforming AFP (79.5%/92.2%), AFP-L3 (59.1%/94.9%) and PIVKA-II (79.5%/84.9%). The sensitivity of the GALAD score was 100% in earlystage HCC (BCLC0/A).

GALAD outperformed conventional biomarkers, facilitating early detection, improved treatment options and ultimately a higher survival rate for HCC patients.

Hepatocellular carcinoma (HCC) represents a significant portion of global cancer incidence and mortality. Screening with ultrasound with or without alpha-fetoprotein is recommended for those at high-risk. Although screening can lead to earlier treatment and better outcomes, existing screening paradigms have several flaws. Ultrasound does not capture all early lesions and has lower efficacy in specific populations such as patients with obesity or those with metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, individuals with noncirrhotic MASLD and chronic hepatitis C also develop HCC, although not at high enough rates to justify screening based on current standards. These individuals, however, represent a substantial proportion of new HCC cases given rising MASLD rates and the endemic nature of hepatitis C in certain regions. Risk-stratifying these populations may reveal subsets that are higher risk and warrant screening. Several imaging advances, including contrast-enhanced ultrasound and abbreviated MRI protocols, may improve detection compared with the current approach. Evaluation of risk stratification and validation of these new imaging methods via clinical trials would likely lead to adjusting screening guidelines. This narrative review provides a diagnostic and interventional radiology-focused summary of the HCC screening guidelines and their recent evolution and highlights emerging imaging methods as potential screening tools of the future.

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

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

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

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To estimate the diagnostic accuracy of des-gamma-carboxy prothrombin, GALAD (Gender, Age, Lens culinaris agglutinin-reactive AFP, AFP and DCP), and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma of any size, and at any stage, in adults with chronic liver disease, in either a surveillance programme or a clinical setting. We acknowledge the possibility that theoretically, the accuracy of the tests in a surveillance programme may differ from that in a clinical setting due to variation in inclusion criteria and the prevalence of the target condition. However, we do not plan a separate analysis for surveillance and clinical settings, as they are not clearly distinct in current clinical practice (Forner 2018; Poustchi 2011). In routine evaluation of people with chronic liver disease, index tests, as well as ultrasound, are already part of standard procedure. Given that HCC typically presents with no symptoms and is often asymptomatic, suspicion of the disease is typically based solely on the presence of advanced chronic liver disease. However, we do plan to consider the study setting as a potential source of heterogeneity. To compare the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP) alone or GALAD alone versus alpha-foetoprotein (AFP), for the diagnosis of hepatocellular carcinoma (HCC) of any size, at any stage; in adults with chronic liver disease, either in a surveillance programme or a clinical setting. Secondary objectives To estimate the diagnostic accuracy of DCP or GALAD versus AFP, for resectable HCC in people with chronic liver disease, in a surveillance programme and a clinical setting. To investigate the following predefined sources of heterogeneity for each of the index tests: study design (case-control studies compared to cross-sectional studies); inclusion of participants without cirrhosis (studies including more than 10% of participants without cirrhosis compared to studies including less than 10% of participants without cirrhosis); study location (population differences): studies conducted in North and South America and Europe compared to Asia and Africa; prevalence of the target condition (studies with hepatocellular carcinoma prevalence more than 10% compared to studies with hepatocellular carcinoma prevalence less than 10%); participant selection (participants recruited from planned surveillance programmes compared to clinical cohorts); different reference standards (histology of the explanted liver compared to liver biopsy compared to another reference standard); different aetiology: studies including at least 90% of participants with chronic viral hepatitis compared to studies including less than 90% of participants with chronic viral hepatitis.

This study aimed to evaluate the cost-effectiveness (CE) of 4 hepatocellular carcinoma (HCC) surveillance strategies in the United Kingdom, the GAAD algorithm, which combines Gender (biological sex) and Age with Elecsys® biomarker assays, alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (previously Des-γ-carboxy prothrombin); ultrasound (US); US + AFP and GAAD + US.

A de novo microsimulation state-transition Markov model was developed in Microsoft Excel® from the perspective of the United Kingdom National Health Service to calculate life-years, quality-adjusted life-years (QALYs), costs, incremental CE ratios, and net monetary benefits. Parameters were sourced from peer-reviewed published literature, national guidelines, and public cost databases. Sensitivity and scenario analyses were performed to evaluate the impact of parameter and structural uncertainty on the results.

In a simulated cohort of 100 000 patients, discounted costs and QALYs per patient were £8663 and 6·066 for US, £9095 and 6·076 for US + AFP, £8719 and 6·078 for GAAD alone, and £9114 and 6·086 for GAAD + US. At a CE threshold of £20 000/QALY, GAAD was the most cost-effective strategy; however, although most costly, GAAD + US was the most clinically effective. Sensitivity and scenario analyses indicated that HCC incidence along with costs associated with diagnostic performance influence CE.

Considering the cost of US and low incidence of HCC in the United Kingdom, this study suggests that GAAD alone or in combination with US are cost-effective surveillance strategies compared with US and US + AFP. Although GAAD + US showed the highest QALY increase, GAAD alone is considered preferable regarding CE; however, better performance estimates for GAAD + US are needed to confirm.

The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system that uses standardized terminology, technique, interpretation, and reporting of imaging studies for hepatocellular carcinoma surveillance, diagnosis, and locoregional treatment response assessment. Since its initial release in 2011, LI-RADS has evolved and expanded in scope. In this article, we discuss recent updates intended to address clinical needs and mitigate current challenges.

Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it the leading etiology of chronic liver diseases and a prime cause of liver-related mortality. MASLD can progress into steatohepatitis (termed MASH), fibrosis, cirrhosis, and ultimately cancer. MASLD is associated with increased risks of hepatocellular carcinoma (HCC) and also extrahepatic malignancies, which can develop in both cirrhotic and non-cirrhotic patients, emphasizing the importance of identifying patients with MASLD at risk of developing MASLD-associated malignancies. However, the optimal screening, diagnostic, and risk stratification strategies for patients with MASLD at risk of cancer are still under debate. Individuals with MASH-associated cirrhosis are recommended to undergo surveillance for HCC (e.g. by ultrasound and biomarkers) every six months. No specific screening approaches for MASLD-related malignancies in non-cirrhotic cases are established to date. The rapidly developing omics technologies, including genetics, metabolomics, and proteomics, show great potential for discovering non-invasive markers to fulfill this unmet need. This review provides an overview on the incidence and mortality of MASLD-associated malignancies, current strategies for HCC screening, surveillance and diagnosis in patients with MASLD, and the evolving role of omics technologies in the discovery of non-invasive markers for the prediction and risk stratification of MASLD-associated HCC.

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.

To investigate the utilization of MRI using a MRI liver protocol with extracellular contrast-enhanced series for hepatocellular carcinoma (HCC) surveillance in high-risk patients.

Consecutive high-risk patients of a western European cohort who underwent repeated liver MRI for HCC screening were included. Lesions were registered according to the Liver Reporting & Data System (LIRADS) 2018. HCC was staged as very early stage HCC (BCLC stage 0) and more advanced stages of HCC (BCLC stage A-D). Differences in time interval between MRI's for BCLC stage 0 and stage A-D were calculated with the Mann-Whitney U test. The HCC cumulative incidence at one-, three- and five years was calculated with the Kaplan Meier estimator.

From 2010 to 2019 a total of 240 patients were included (71% male; median age: 57 years; IQR: 50-64 years) with 1350 MRI's. Most patients (83 %) had cirrhosis with hepatitis C as the most common underlying cause. Patients underwent on average four MRI's (IQR: 3-7). Forty-two patients (17.5%) developed HCC (52 HCC lesions: 43 LIRADS-5, eight LIRADS-4, and one LIRADS-TIV). Eighteen patients (43%) had BCLC stage 0 HCC with a significant shorter screening time interval (10 months; IQR: 6-21) compared to patients with BCLC stage A-D (21 months; IQR: 10-32) (p = 0.03). Thirty seven percent of patients with a LIRADS-3 lesion (n=43) showed HCC development within twelve months (median: 7.4 months). One, three- and five-year HCC cumulative incidence in cirrhotic patients was 1%, 10% and 17%, respectively.

High-risk patients who underwent surveillance with contrast-enhanced MRI developed HCC in 17.5 % during a follow up period of over 4 years median. Very early stage HCC was seen in compensated cirrhosis after a median time interval of 10 months. Later stages of HCC were related to prolonged screening time interval (median 21 months).

To determine the frequency, characteristics and clinical significance of incidental pelvic findings reported on abdominopelvic CT performed for hepatocellular carcinoma (HCC) surveillance in at-risk patients.

This two-center retrospective study received institutional review board approval with a waiver of informed consent. The radiologic reports of the CT exams performed 1/1/2010-2/28/2023 for HCC surveillance were reviewed. Exams were obtained with intravenous contrast material and included hepatic arterial and portal venous phases of the abdomen; images of the pelvis were acquired during the portal venous phase. Reported imaging findings and imaging-related recommendations either by the radiologists or the corresponding caregiver, if present, were retrospectively tabulated. The patient's medical records were reviewed to determine if there were any recommendations that were considered clinically important and culminated in any further interventions or treatments.

259 adults (1st center: mean age, 60 ± 11 years, 49% male and 2nd center: 56.26 ± 6.2 years, 48% male) at risk for HCC underwent 327 abdominopelvic CT exams for HCC surveillance at two centers. A total of 622 pelvic findings (mean, 2.2/ exam) were reported, including 131 bladder, 120 alimentary tract, 133 vascular, 51 gynecologic, 37 prostate, 33 lymph node, 27 inguinal, 44 peritoneal, and 46 skeletal. 52 of 622 reported findings (8.3%) were associated with actionable recommendations. 24 of the 52 actionable recommendations/clinical suggestions were implemented as follows: five complimentary imaging, ten additional laboratory tests, and nine non-imaging recommendations. Of note, only eight applied recommendations culminated in a clinical outcome, which included four urinary tract infection treatments.

Pelvic CT findings were associated with a clinical benefit to the patient in 1.3% of exams. These results suggest that pelvic imaging should be omitted from CT-based HCC surveillance.

Without compromising valuable information, patients undergoing HCC surveillance-CT may not require additional pelvic coverage.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide including sub-Saharan Africa. The GALAD score, derived from Gender, Age, Lens culinaris agglutinin-reactive fraction of alpha fetoprotein, Alpha fetoprotein, and Des-carboxy-prothrombin, has high accuracy in diagnosing 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 sub-Saharan Africa. Clinical data from patients with cirrhosis (n = 93) or HCC (n = 78) from outpatient hepatology clinics at three teaching hospitals in Ghana were abstracted, and serum samples were analyzed. A logistic regression model predicting HCC status based on the GALAD score was constructed to obtain the ROC curve for GALAD. The AUC with 95% confidence interval (CI) was calculated. The median GALAD score was higher among patients with HCC versus cirrhosis controls (8.0 vs. -4.1, P < 0.01). The AUC of the GALAD score for HCC detection 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. The AUC (95% CI) was 0.87 (0.80-0.95) and 0.81 (0.67-0.94) in hepatitis B virus-positive and hepatitis B virus-negative patients, respectively. The GALAD score has a high accuracy for HCC detection. It has great potential to improve HCC surveillance in sub-Saharan Africa where imaging resources are limited. Significance: The GALAD score or its relevant modifications have the potential to aid in improving HCC surveillance efforts in low-resource settings in sub-Saharan Africa. This could enhance early detection rates of HCC and potentially improve survival rates in resource-limited settings.

A highly accurate diagnostic method is crucial to reduce mortality and increase hepatocellular carcinoma (HCC) survival. Current biomarkers have limited accuracy, and novel ones are needed. Fibroblast growth factor-19 (FGF-19) is overexpressed in HCC. This study aimed to assess FGF-19 as a potential novel diagnostic biomarker for HCC.

This case-control study involved 114 individuals divided into three equal groups: HCC (n=38), Cirrhosis (n=38), and Control (n=38). HCC biomarkers included alpha-fetoprotein (AFP), Des-γ-carboxy prothrombin (DCP), and FGF-19.

The three markers, FGF-19, DCP, and AFP, were significantly different between the three groups, except that DCP was comparable between HCC and Cirrhosis groups (p=1.000). All individuals in the control group had FGF-19 levels below the minimum level in the HCC group. Thus, FGF-19 had 100% sensitivity and specificity in differentiating HCC from healthy controls. FGF-19 can discriminate between HCC and Cirrhosis groups at a 140.8 pg/mL cutoff with sensitivity and specificity of 81.8% and 87.9%, respectively. The sensitivity of FGF-19 was higher than AFP, trending toward statistical significance (p=0.095). Combining FGF-19 with AFP, DCP, or both improved sensitivity but decreased specificity.

FGF-19 is a possible noninvasive serum biomarker for HCC. Its combination with AFP or DCP improves the sensitivity for detecting HCC.

Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction-associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.

To establish and validate a CT-based nomogram for accurately detecting HCC in patients at high risk for the disease.

A total of 223 patients were divided into training (n=161) and validation (n=62) cohorts between January of 2017 and May of 2022. Logistic analysis was performed, and clinical model and radiological model were developed separately. Finally, a nomogram was established based on clinical and radiological features. All models were evaluated using the area under the curve (AUC). DeLong's test was used to evaluate the differences among these models.

In the multivariate analysis, gender (p = 0.014), increased Alpha-fetoprotein (AFP) (p = 0.017), non-rim arterial phase hyperenhancement (APHE) (p = 0.011), washout (p = 0.011), and enhancing capsule (p = 0.001) were the independent differential predictors of HCC. A nomogram was formed with well-fitted calibration curves based on these five factors. The area under the curve (AUC) of the nomogram in the training and validation cohorts was 0.961(95%CI: 0.935~0.986) and 0.979 (95% CI: 0.949~1), respectively. The nomogram outperformed the clinical and the radiological models in training and validation cohorts.

The nomogram incorporating clinical and CT features can be a simple and reliable tool for detecting HCC and achieving risk stratification in patients at high risk for HCC.

Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are frequently obese and medically complex, posing challenges for clinical management. In this review, we discuss NASH-specific challenges and the associated implications, including benefits of minimally invasive operative approaches in obese patients; the value of y90 as a locoregional therapy; and the roles of weight loss and immunotherapy in disease management. The relevant literature was identified through queries of PubMed, Google Scholar, and clinicaltrials.gov. Provider understanding of clinical nuances specific to NASH-HCC can improve treatment strategy and patient outcomes.

Hepatocellular carcinoma (HCC) prognosis remains dismal due to late-stage diagnosis; surveillance has been demonstrated to increase early diagnosis rates and receipt of curative treatment. Acknowledging limitations in the evidence base for HCC surveillance, international professional bodies reiterate the recommendation for biannual HCC surveillance and NHS England supports measures aimed to increase surveillance uptake. The current ad hoc provision of HCC surveillance is prone to failures, evident by low surveillance uptake and high numbers of patients being diagnosed outside of surveillance. We discuss challenges related to HCC surveillance in the UK and potential solutions to addressing them. We highlight the requirements of a consistent and effective national surveillance process, and suggest pathways on how this can be achieved.

Biannual ultrasound (US) is recommended for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis. However, US has limited sensitivity for early-stage HCC, particularly in overweight cohorts, where hepatic visualisation is often inadequate. Currently there are no robust imaging surveillance strategies in patients with inadequate US visualisation. We investigated the ability of non-contrast, abbreviated magnetic resonance imaging (aMRI) to adequately visualise the liver for HCC surveillance in patients with previously inadequate US.

Patients undergoing US surveillance, where liver visualisation was inadequate (LI-RADS VIS-B and VIS-C), were prospectively recruited. Patients underwent non-contrast T2-weighted and diffusion-weighted aMRI. The images were reviewed and reported by an expert liver radiologist. Three independent, blinded radiologists assessed the aMRI visualisation quality using a binary score assessing five parameters (parenchymal definition, vascular definition, coverage of the liver, uniformity of liver appearance and signal-to-noise ratio).

Thirty patients completed the aMRI protocol. The majority (90%) had underlying cirrhosis and were overweight (93.3%), with 50% obese and 20% severely obese. A total of 93.3% of the aMRI scans were of satisfactory quality. Six patients (20%) had hepatic abnormalities detected with aMRI that were not seen on their US: one HCC, one haemangioma and three clinically insignificant lesions. For the aMRI visualisation quality assessment, the coverage of the liver, vascular definition and parenchymal definition were consistently rated to be of sufficient quality by all three radiologists.

Non-contrast aMRI provided good visualisation of the liver and detection of abnormalities in patients with inadequate US. aMRI should be further explored in a larger, prospective study as an alternative surveillance strategy in patients with inadequate US.

Ultrasound (US) is associated with severe visualization limitations (US Liver Imaging Reporting and Data System visualization score C) in one-third of patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis undergoing hepatocellular carcinoma (HCC) screening. Data suggest abbreviated MRI (aMRI) may improve HCC screening efficacy. This study analyzed the cost-effectiveness of HCC screening strategies, including an US visualization score-based approach with aMRI, in patients with NAFLD cirrhosis.

We constructed a Markov model simulating adults with compensated NAFLD cirrhosis in the United States undergoing HCC screening, comparing strategies of US plus visualization score, US alone, or no surveillance. We modeled aMRI in patients with visualization score C and negative US, while patients with scores A/B did US alone. We performed a sensitivity analysis comparing US plus visualization score with US plus alpha fetoprotein or no surveillance. The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Sensitivity analyses were performed for all variables.

US plus visualization score was the most cost-effective strategy, with an ICER of $59,005 relative to no surveillance. The ICER for US alone to US plus visualization score was $822,500. On sensitivity analysis, screening using US plus visualization score remained preferred across several parameters. Even with alpha fetoprotein added to US, the US plus visualization score strategy remained cost-effective, with an ICER of $62,799 compared with no surveillance.

HCC surveillance using US visualization score-based approach, using aMRI for visualization score C, seems to be the most cost-effective strategy in patients with NAFLD cirrhosis.

This study aimed to evaluate the efficacy of the aMAP score and compare it with other risk scores for predicting hepatocellular carcinoma (HCC) development in Thai patients with chronic hepatitis B (CHB). We retrospectively analyzed patients with CHB between 1 January 2008 and 31 December 2019. Data on demographics, clinical parameters, cirrhosis status, HCC imaging, and alpha fetoprotein surveillance were collected to calculate the aMAP score (0-100) based on age, sex, albumin-bilirubin level, and platelet count. Of the 1060 patients analyzed, 789 were eligible, of whom 51 developed HCC. The cumulative HCC incidences in the low-, moderate-, and high-risk groups at 3, 5, and 10 years were significantly different (log-rank, p < 0.0001). The area under the receiver operating characteristic curves (AUROCs) of the aMAP scores for predicting HCC at 3, 5, and 10 years were 0.748, 0.777, and 0.784, respectively. Among the risk scores, the CU-HCC score had the highest AUROCs (0.823) for predicting 5-year HCC development. The aMAP score is a valuable tool for predicting HCC risk in Thai patients with CHB and can enhance surveillance strategies. However, its performance is inferior to that of the CU-HCC score, suggesting the need for new predictive tools for HCC surveillance.

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

Ultrasound (US) surveillance is a cornerstone for early diagnosis of HCC, anyway US presentation has undergone significant changes. With the aim of evaluating the effects of US surveillance program in the real-world clinical practice, we wanted to evaluate US presentation of HCCs over the last 30 years and the differences of HCCs presentation according to etiology.

174 patients diagnosed between 1993 and 98 (G1), 96 between 2003 and 08 (G2), 102 between 2013 and 18 (G3), were compared. US patterns were: single, multiple or diffuse nodules. The echo-patterns: iso-, hypo-, hyper-echoic, or mixed. In G1, the HCC diagnosis was mainly histologic; in G2 by EASL 2001 and AASLD 2005, in G3 AASLD 2011, EASL 2012, and AISF 2013 guidelines.

HCV was the most frequent etiology, dropping between G1 (81%) and G3 (66%) (P < 0.01), metabolic increased between G1 (5%) and G3 (14%) (P < 0.01). Single HCC was more prevalent in G3 vs G1 (65.6% vs 40%) (P < 0.0001), multiple nodules in G1 (50%) vs G3 (33.3%) (P < 0.02) and diffuse in G1 (16%) vs G2 (2%) and vs G3 (1%) (P < 0.001). The most frequent echo-pattern was hypo-echoic G1 (50%) vs G2 (79%) and G1 vs G3 (65%) (P < 0.01). Iso-echoic pattern was the least frequent (7-12%). Mixed pattern decreased from G1 (28%) to G3 (12%) (P < 0.002). In G3 there were more multiple or diffuse HCCs in metabolic (P < 0.03).

US presentation became less severe due to surveillance programs. HCV remains the most frequent cause, an increase in metabolic etiology has been shown throughout the decades.

Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC.

A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP).

Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001).

HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

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.

Hepatic cancer is widely regarded as the leading cause of cancer-related mortality worldwide. Despite recent advances in treatment options, the prognosis of liver cancer remains poor. Therefore, there is an urgent need to develop more representative in vitro models of liver cancer for pathophysiology and drug screening studies. Fortunately, an exciting new development for generating liver models in recent years has been the advent of organoid technology. Organoid models hold huge potential as an in vitro research tool because they can recapitulate the spatial architecture of primary liver cancers and maintain the molecular and functional variations of the native tissue counterparts during long-term culture in vitro. This review provides a comprehensive overview and discussion of the establishment and application of liver organoid models in vitro. Bioengineering strategies used to construct organoid models are also discussed. In addition, the clinical potential and other relevant applications of liver organoid models in different functional states are explored. In the end, this review discusses current limitations and future prospects to encourage further development.

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.

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.

Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions.

Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not develop HCC. Manual and automated EPM signals of liver parenchyma between cases and controls were quantitatively validated on an independent patient set using cross validation with manual methods avoiding parenchyma with artifacts or blood vessels.

With manual EPM, RMSD of 0.37 was identified as a cutoff for distinguishing lesions that progress to HCC from background parenchyma with and without lesions on pre-diagnostic scans (median time interval 6.8 months) with an area under the curve (AUC) of 0.83 (CI: 0.73-0.94) and a sensitivity, specificity, and accuracy of 0.65, 0.97, and 0.89, respectively. At the time of diagnostic scans, a sensitivity, specificity, and accuracy of 0.79, 0.93, and 0.88 were achieved with manual EPM with an AUC of 0.89 (CI: 0.82-0.96). EPM RMSD signals of background parenchyma that did not progress to HCC in cases and controls were similar (case EPM: 0.22 ± 0.08, control EPM: 0.22 ± 0.09, p=0.8). Automated EPM produced similar quantitative results and performance.

With manual EPM, a cutoff of 0.37 identifies quantifiable differences between HCC cases and controls approximately six months prior to diagnosis of HCC with an accuracy of 89%.

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.

The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need.

This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs.

PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC.

In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels.

PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers.