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.

The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

The epidemiological landscape of hepatocellular carcinoma (HCC) in Europe is evolving. This study aims to provide an updated description of the current epidemiology of liver cancer in Spain.

This multicenter prospective study collected demographic and clinical data on primary liver cancer between October 2022 and January 2023. We conducted descriptive and comparative analyses with data collected in 2008 and 2014.

Of the 767 cases of primary liver cancer collected from 52 centers, 91% were diagnosed as HCC. The majority of patients were male (83.3%), average age 68 years, 80.7% had cirrhosis. The primary causes were alcohol (29.9% alone, 55% combined with other etiologies), liver disease related to metabolic syndrome (LDrMS, 23%) and hepatitis C (17.3%). Treatments included ablation (15.7%), systemic therapy (14.7%), and chemoembolization (14.6%). Data from 29 centers (n = 1,351) across three registries revealed a significant increase in LDrMS (from 4.9% to 24%) and HCC in non-cirrhotic livers (from 4.2% to 7.9%). Meanwhile, hepatitis C decreased sharply (from 43% to 17.5%). Alcohol-related cases remained stable. There was a slight increase in male patients and hypertension, diabetes, and obesity. Patients with cirrhosis diagnosed outside of screening programs presented with larger tumors and more advanced disease. This led to fewer evaluations for curative treatments.

Alcohol accounts for 30% of HCC cases and is the main etiology. The registry shows a decrease in hepatitis C-related HCC, an increase in LDrMS and HCC in non-cirrhotic livers. Surveillance was implemented in ∼80% of the recommended population. There is a need for improved screening and prevention strategies, particularly for alcohol abuse and LDrMS, to enhance HCC management.

Our study showcases the involvement of numerous reference centers across Spain and examines over 1,300 patients to track the changing epidemiology of hepatocellular carcinoma (HCC) over 14 years. In patients with known liver cirrhosis, more than 80% of HCC diagnoses were made through screening leading to early-stage identification and curative treatment opportunities. Notably, there has been a shift in HCC etiology within the registries from hepatitis C to liver disease related to metabolic syndrome, with an increase in cases without cirrhosis. Findings indicate a need for the prevention and early detection of HCC, particularly focusing on alcohol and liver disease related to metabolic syndrome, along with greater involvement of health authorities, to improve the participation of at-risk patients in screening programs.

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.

During its 2022 World Congress in New York the International Hepato-Pancreato-Biliary Association (IHPBA) launched the Legacy Initiative, aiming to create sustainable, positive impacts in host countries or regions by addressing critical healthcare challenges in the field of Hepato-Pancreato-Biliary surgery. The 2024 Legacy Initiative focused on hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA), a region disproportionately burdened by this disease due to a high incidence, limited healthcare infrastructure and resources, lack of screening programs, low awareness, and financial constraints. HCC, the sixth most common malignancy globally, is often diagnosed at advanced stages in SSA, leading to dismal outcomes. The initiative aims to improve management pathways and access to care through a multidisciplinary approach, emphasizing prevention, early diagnosis, curative treatments, potentially life-prolonging treatments, and palliative care. Key strategies include expanding healthcare infrastructure, implementing screening programs, raising awareness, and advocating for policy reforms. The IHPBA has partnered with the African Viral Hepatitis Convention and the African Palliative Care Association to address risk factors for developing HCC, in particular viral hepatitis, a major HCC risk factor. The initiative also highlights the need for capacity building, research, and collaboration with regional and international stakeholders. The 2024 Legacy Initiative aims to drive meaningful change, improve HCC outcomes, and reduce the disease burden in SSA, aligning with the IHPBA's mission to create long-lasting, positive impacts in global HPB healthcare.

Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide, with more than a doubling of incidence over the past two decades in the United States. Yet, the survival rate remains less than 20%, often due to late diagnosis at advanced stages. Current HCC screening approaches are serum alpha-fetoprotein (AFP) testing and ultrasound (US) of cirrhotic patients. However, these remain suboptimal, particularly in the setting of underlying obesity and metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH), which are also rising in incidence. Therefore, there is an urgent need for novel biomarkers that can stratify risk and predict early diagnosis of HCC, which is curable. Advances in liver cancer biology, multi-omics technologies, artificial intelligence, and precision algorithms have facilitated the development of promising candidates, with several emerging from completed phase 2 and 3 clinical trials. This review highlights the performance of these novel biomarkers and algorithms from a mechanistic perspective and provides new insight into how pathological processes can be detected through blood-based biomarkers. Through human studies compiled with animal models and mechanistic insight in pathways such as the TGF-β pathway, the biological progression from chronic liver disease to cirrhosis and HCC can be delineated. This integrated approach with new biomarkers merit further validation to refine HCC screening and improve early detection and risk stratification.

This study introduces HCC-Net, a novel wavelet-based approach for the accurate diagnosis of hepatocellular carcinoma (HCC) from abdominal ultrasound (US) images using artificial neural networks. The HCC-Net integrates the discrete wavelet transform (DWT) to decompose US images into four sub-band images, a lesion detector for hierarchical lesion localization, and a pattern-augmented classifier for generating pattern-enhanced lesion images and subsequent classification. The lesion detection uses a hierarchical coarse-to-fine approach to minimize missed lesions. CoarseNet performs initial lesion localization, while FineNet identifies any lesions that were missed. In the classification phase, the wavelet components of detected lesions are synthesized to create pattern-augmented images that enhance feature distinction, resulting in highly accurate classifications. These augmented images are classified into 'Normal,' 'Benign,' or 'Malignant' categories according to their morphologic features on sonography. The experimental results demonstrate the significant effectiveness of the proposed coarse-to-fine detection framework and pattern-augmented classifier in lesion detection and classification. We achieved an accuracy of 96.2 %, a sensitivity of 97.6 %, and a specificity of 98.1 % on the Samsung Medical Center dataset, indicating HCC-Net's potential as a reliable tool for liver cancer screening.

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 mortality worldwide. Early detection via surveillance plays a crucial role in enabling curative treatment and improving survival rates. Since the initial randomized controlled trial, biannual ultrasound (US) has been established as the standard surveillance method because of its accessibility, safety, and low cost. However, US has some limitations, including operator dependency, suboptimal sensitivity for early-stage HCC, and challenges such as a limited sonic window that may result in inadequate examination. Alternative imaging modalities, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), have demonstrated higher sensitivity for detecting very early-stage HCC. Recent advancements, such as low-dose CT with deep learning-based reconstruction, have enhanced the safety and feasibility of CT-based surveillance by reducing radiation exposure and amount of contrast media. MRI, particularly with gadoxetic acid or abbreviated protocols, offers superior tissue contrast and sensitivity, although its accessibility and cost remain challenges. Tailored surveillance strategies based on individual risk profiles and integration of advanced imaging technologies have the potential to enhance the detection performance and cost-effectiveness. This review highlights the recent developments in imaging technologies for HCC surveillance, focusing on their respective strengths and limitations.

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 HCC. Although AFP has shown potential for each of these steps, its performance, when used alone, has often been suboptimal. There continue 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 the selection of candidates for liver transplant. 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 are currently ongoing to evaluate the role of these emerging biomarkers in clinical practice.

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

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

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

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

National Cancer Institute and Cancer Prevention Research Institute of Texas.

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.

Background/Objectives: Ultrasound (US) imaging plays a crucial role in the early detection and treatment of hepatocellular carcinoma (HCC). However, challenges such as speckle noise, low contrast, and diverse lesion morphology hinder its diagnostic accuracy. Methods: To address these issues, we propose CSM-FusionNet, a novel framework that integrates clustering, SoftMax-weighted Box Fusion (SM-WBF), and padding. Using raw US images from a leading hospital, Samsung Medical Center (SMC), we applied intensity adjustment, adaptive histogram equalization, low-pass, and high-pass filters to reduce noise and enhance resolution. Data augmentation generated ten images per one raw US image, allowing the training of 10 YOLOv8 networks. The mAP@0.5 of each network was used as SoftMax-derived weights in SM-WBF. Threshold-lowered bounding boxes were clustered using Density-Based Spatial Clustering of Applications with Noise (DBSCAN), and outliers were managed within clusters. SM-WBF reduced redundant boxes, and padding enriched features, improving classification accuracy. Results: The accuracy improved from 82.48% to 97.58% with sensitivity reaching 100%. The framework increased lesion detection accuracy from 56.11% to 95.56% after clustering and SM-WBF. Conclusions: CSM-FusionNet demonstrates the potential to significantly improve diagnostic reliability in US-based lesion detection, aiding precise clinical decision-making.

The rising global burden of cancer drives increased demands for medical imaging, which is essential throughout cancer care. However, delivering medical imaging presents significant environmental challenges including high energy use, reliance on single-use supplies, and the production of environmental pollutants. Environmental factors, such as ultraviolet radiation, wildfire smoke, and carcinogenic pollutants contribute to rising cancer rates, while extreme weather events driven by climate change disrupt cancer care delivery-highlighting the close connection between patient and planetary health. This review explores opportunities to improve the environmental sustainability of oncologic imaging, emphasizing the importance of patient-relevant outcomes-such as quality of life and overall survival-as a guiding principle in cancer care. Key strategies include optimizing imaging schedules to reduce low-value imaging, selecting modalities with lower environmental impact where clinically appropriate, minimizing waste streams, and adopting energy-efficient practices. Artificial intelligence offers the potential to personalize imaging schedules and improve efficiency, though its benefits must be weighed against energy use. Mobile imaging programs and integrated scheduling reduce patient travel-related emissions while promoting health equity, particularly in underserved communities. Future research should focus on optimizing imaging intervals to address patient-relevant outcomes better, expanding the use of abbreviated imaging protocols, and the judicious deployment of artificial intelligence, ensuring its benefits justify energy use.

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.

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

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

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

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

NCT02582918 and NCT03756051.

The liver is one of the most frequent sites of primary malignancies in humans. Hepatocellular carcinoma (HCC) is one of the most prevalent solid tumors with poor prognosis. Current treatments showed limited efficacy in some patients, and, therefore, alternative strategies, such as immunotherapy, cancer vaccines, adoptive cell therapy (ACT), and recently chimeric antigen receptors (CAR)-T cells, are developed to offer better efficacy and safety profile in patients with HCC. Unlike other ACTs like tumor-infiltrating lymphocytes (TILs), CAR-T cells are equipped with engineered CAR receptors that effectively identify tumor antigens and eliminate cancer cells without major histocompatibility complex (MHC) restriction. This process induces intracellular signaling, leading to T lymphocyte recruitment and subsequent activation of other effector cells in the tumor microenvironment (TME). Until today, novel approaches have been used to develop more potent CAR-T cells with robust persistence, specificity, trafficking, and safety. However, the clinical application of CAR-T cells in solid tumors is still challenging. Therefore, this study aims to review the advancement, prospects, and possible avenues of CAR-T cell application in HCC following an outline of the CAR structure and function.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

This article reviews surveillance for the detection of early stage hepatocellular carcinoma, covering the rationale for surveillance, optimal selection of persons needing surveillance, methods and frequency of screening, strategies for addressing barriers to surveillance, and trends for future improvement in surveillance leading to more effective cancer control and improved patient outcomes. The importance of integrating liver cancer surveillance as a core component of national public health programs is emphasized. The impact of emerging technologies for identifying persons at risk, stratifying individual risk to improve the cost-effectiveness of surveillance programs, and improving the performance, accessibility, and convenience of surveillance are discussed.

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

This study aimed to compare ultrasonography (US) and noncontrast magnetic resonance imaging (MRI) in the surveillance of hepatic malignancy.

We conducted a randomized, nonblinded trial at a single center in South Korea. Eligible individuals were aged 20 to 70 years with liver cirrhosis, Child-Pugh class A, and no history of liver cancer or other recent malignancy. Participants were randomized 1:1 to receive up to 10 semiannual surveillance using US or noncontrast MRI with serum alpha-fetoprotein testing. The primary endpoints were the detection rates of Barcelona Clinic Liver Cancer (BCLC) stage 0 or A tumors, stage distribution at initial diagnosis, and false-positive referral rates.

From June 2015 to November 2017, 416 patients were screened, and 414 were enrolled and assigned to the US (n = 207) or MRI (n = 207) group. In total, 23 participants in the US group and 25 in the MRI group were diagnosed with liver cancer by November 2022. The detection rates of BCLC stage 0 or A tumors were not different between the US and MRI groups (7% [95% confidence interval (CI), 4%-11%] vs 12% [8%-17%]). BCLC stage 0 tumors were more frequently detected in the MRI group than in the US group (8% vs 2%). The MRI group had earlier BCLC stage (P = .014) and lower false-positive referral rate (0.7% [95% CI, 0.4%-1.2%] vs 3.1% [2.3%-4.1%], P < .001) compared with the US group.

Noncontrast MRI is a better alternative to US for the surveillance of cirrhotic patients offering earlier stage at initial diagnosis and lower false-positive referral rate. (ClincalTrials.gov, Number: NCT02514434.).

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer deaths worldwide. Six-month imaging along with alpha-fetoprotein (AFP) serum levels detection are the current gold standard to exclude HCC. Protein induced by vitamin K absence (PIVKA-II) has been proposed as a potential screening biomarker for HCC. This study was designed to evaluate the role of PIVKA-II as diagnostic HCC marker, and the correlation between PIVKA-II levels and HCC stage.

PIVKA-II levels were assessed on serum samples of Italian patients. The study population included 80 patients with HCC, 111 with liver cirrhosis (LC), and 111 with chronic hepatitis C (CHC).

PIVKA-II serum levels progressively increase from patients with CHC to patients with HCC. In the HCC group, PIVKA-II values are higher in the more advanced stages of the disease, assessed by the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC-B vs. BCLC-A vs. BCLC-0). Youden's index analysis identified a value >37 mAU/mL as the optimal threshold for the best combination of sensitivity and specificity (80% and 76%, respectively) and, at the best cut-off of 5.2 ng/mL, AFP yielded 53% specificity and 78% sensitivity. The combination of PIVKA-II and AFP reached positive and negative predictive values of 73.9% and 94.2%, respectively.

PIVKA-II levels are increased in the HCC patients, compared to control groups. The increase is more evident in patients with advanced HCC. The diagnostic performance of PIVKA-II seems more sensitive than AFP while the combination of PIVKA-II and AFP resulted in the best diagnostic accuracy, reaching 73.9% positive predictive value and 94.2% negative predictive value, thus improving the diagnostic capability of the single marker.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death, with a 5-year survival rate of 10%-12%. It usually develops in the setting of chronic liver disease (CLD), with chronic viral hepatitis, alcohol, and non-alcoholic fatty liver disease (NAFLD) being the most common risk factors. Some patients are at higher risk of developing hepatocellular cancer, so it is important to screen them regularly to diagnose the disease at an early stage and improve their chances for curative treatment. Six-monthly ultrasound with or without alpha-fetoprotein (AFP) is the currently recommended surveillance method. AFP has been used as a biomarker for liver cancer; however, it has low sensitivity and specificity, which necessitates the search for other, more accurate biomarkers. Promising biomarkers include lens culinaris agglutinin-reactive AFP, des-gamma-carboxy prothrombin, methylated DNA markers, plasma microRNA expression, circulating tumor DNA, and circulating tumor cells. In addition, combinations of biomarkers, like the GALAD score and the Doylestown algorithm, may help in the early detection of HCC. In this review, we summarize the screening tests for early detection of HCC that have been studied over the last decade.

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most prevalent liver disease worldwide. It is associated with an increased risk of developing hepatocellular carcinoma (HCC) in the background of cirrhosis or without cirrhosis. The prevalence of NAFLD-related HCC is increasing all over the globe, and HCC surveillance in NAFLD cases is not that common. In the present review, we attempt to summarize promising treatments and clinical trials focused on NAFLD, nonalcoholic steatohepatitis (NASH), and HCC in the past five to seven years. We categorized the trials based on the type of intervention. Most of the trials are still running, with only a few completed and with conclusive results. In clinical trial NCT03942822, 25 mg/day of milled chia seeds improved NAFLD condition. Completed trial NCT03524365 concluded that Rouxen-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) results in histological resolution of NASH without worsening of fibrosis, while NCT04677101 validated sensitivity/accuracy of blood biomarkers in predicting NASH and fibrosis stage. Moreover, trials with empagliflozin (NCT05694923), curcuvail (NCT06256926), and obeticholic acid (NCT03439254) were completed but did not provide conclusive results. However, trial NCT03900429 reported effective improvement in fibrosis by at least one stage, without worsening of NAFLD activity score (NAS), as well as improvement in lipid profile of the NASH patients by 80 or 100 mg MGL-3196 (resmetirom). Funded by Madrigal Pharmaceuticals, Rezdiffra (resmetirom), used in the clinical trial NCT03900429, is the first FDA-approved drug for the treatment of NAFLD/NASH.

There is significant variation in HCC management across different centers with poor adherence to evidence-based clinical practice guidelines as assessed in prior studies. In Australia, quality indicators (QIs) have recently been proposed by a multidisciplinary group of experts to help provide a framework to assess and monitor the quality of HCC care. In this review, we discuss the many areas where real-world practice deviates from evidence-based medicine, the role that QI sets play in addressing this gap, and the similarities and differences between Australian QIs and other leading treatment guidelines and QI sets from around the world. We focus on the utility of QI sets to identify opportunities for targeted improvement in the real-world clinical environment. We conclude with a discussion about the formation of a national clinical quality registry as a long-term measure to facilitate continual improvements in patient care within and across sites in order to optimize patient outcomes.

Most patients with cirrhosis have compensated disease and are cared for in primary care; however, the exact epidemiology within Australia remains largely unknown. The aim of this study was to assess cirrhosis care in an Australian primary care setting by evaluating rates of cirrhosis diagnosis, appropriate hepatocellular carcinoma (HCC) surveillance and specialist communication.

Electronic medical records in consenting general practices were reviewed using the "Liver Toolkit" to identify patients with an existing cirrhosis diagnosis. Individual cases were reviewed to identify outcomes of interest.

One hundred seventy-one patients with confirmed cirrhosis across nine general practices were identified (74% male, mean age: 61.2 years). There was significant variation in the rate of cirrhosis diagnosis between practices (range 31.7-637.9 per 100 000 patients, P < 0.0001). Patients with cirrhosis had predominately compensated disease (75% Child-Pugh A) and common etiologies of cirrhosis were alcohol (49%), hepatitis C (47%), and metabolic dysfunction-associated steatotic liver disease (29%). Forty-two patients (25%) had received appropriate HCC surveillance. Predictors of inadequate HCC surveillance were time from last specialist correspondence (odds ratio [OR] = 1.06 per month increase, 95% confidence interval [CI]: 1.02-1.10, P = 0.002) and hepatitis B (OR = 0.24, 95% CI: 0.06-0.98, P = 0.047). Specialist correspondence with primary care was older than 2 years or absent in 37% of cases.

There was a 20-fold difference in the rate of cirrhosis diagnosis between general practices within Sydney, suggesting a large proportion of patients remain undiagnosed. Three quarters of patients with diagnosed cirrhosis are not receiving appropriate HCC surveillance.

Primary liver cancers are tumors that develop from different liver cells. Hepatocellular carcinoma (HCC), which develops from hepatocytes, accounts for approximately 75-85% of primary liver cancers.HCC is the 6th leading cause of cancer worldwide and the 3rd leading cause of cancer-related death. Its incidence is low in northern Europe, but high in sub-Saharan Africa and the Far East, where both hepatotropic viruses and exposure to mycotoxins are. It complicates cirrhosis in over 90% of cases and is predominantly male.The prevalence of HCC is increasing due to improved diagnostic techniques and criteria, but also to the persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in adults. A worldwide increase in the incidence of steatopathy makes it the leading cause of liver disease worldwide, associated with alcohol abuse and/or steatohepatitis associated with metabolic dysfunction (MASH), including type 2 diabetes.Chronic hepatotropic viral infections, cirrhosis and chemical carcinogens combine to produce an annual incidence of 2-5% of hepatocellular carcinoma arising from cirrhosis. This justifies biannual surveillance of known cirrhosis, without which late diagnosis limits therapeutic options.Major advances have been made in curative treatment (liver transplantation, surgery, radiodestruction) and palliative treatment (chemo- or radioembolization, sorafenib chemotherapy or immunotherapy), depending on how early HCC is diagnosed (size, number of hepatic or extrahepatic lesions) and the severity of underlying liver disease and associated comorbidities.

In 2017, the American College of Radiology introduced the US Liver Imaging Reporting and Data System (LI-RADS) as a framework for US surveillance of patients at risk for developing hepatocellular carcinoma. This has aided in the standardization of technique, clinical reporting, patient management, data collection, and research. Emerging evidence has helped inform changes to the algorithm, now released as LI-RADS US Surveillance version 2024. The updated algorithm, the rationale for changes, and its alignment with the 2023 American Association for the Study of Liver Diseases Practice Guidance are presented.

Hepatocellular Carcinoma (HCC) is a malignant tumor with high morbidity and mortality worldwide, which represents a serious threat to human life, health and quality of life. Blood-based detection is essential for HCC screening, early diagnosis, prognosis evaluation, and surveillance. Current non-invasive detection strategy including serum alpha-fetoprotein (AFP), ultrasound, computerized tomography, and magnetic resonance imaging. The limited specificity of an AFP and the dependence on operator experience and diagnostic personnel for ultrasound have constrained their utility in early HCC diagnosis. In recent years, with the development of various detection technologies, there has been an increasing focus on exploring blood-based detection markers for HCC. The types of markers include protein markers, DNA mutation, DNA epigenetic modification, mRNA, miRNA, and so on. However, numerous methodological and biological factors limit the clinical sensitivity and generalization performance of these new biomarkers. In this review, we describe the state-of-the-art technologies for cfDNA analysis, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve HCC diagnostics and patient care.

Hepatocellular carcinoma (HCC) is often detected at advanced stages among patients with hepatitis B virus (HBV), underscoring the urgency for more precise surveillance tests. Here, we compare the clinical performance of the novel - GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], protein-induced by vitamin K absence-II [PIVKA-II]) and GALAD (gender [biological sex], age, AFP, Lens-culinaris AFP [AFP-L3]), PIVKA-II) algorithms to assess the utility of AFP-L3 for distinguishing HCC from benign chronic liver disease (CLD) in Chinese patients with predominantly chronic HBV infection. Eligible adults were enrolled, and biomarkers were measured using Elecsys (Cobas) or µTASWAKO assays. In total, 411 participants provided serum samples (HCC, n = 176 [early-stage, n = 110]; CLD, n = 136; specificity n = 101). HBV was the underlying disease etiology for most participants (HCC, 95%; benign CLD, 72%). For GAAD (Cobas), GALAD (Cobas), and GALAD (µTASWAKO), AUCs were 93.1% (95% CI: 90.0-96.2), 93.2% (90.0-96.3), and 92.7% (88.4-96.9) for early-stage, and 95.6% (93.6-97.6), 95.6% (93.6-97.7), and 95.8% (93.2-98.3) for all-stage HCC, versus CLD, respectively. Interestingly, both GAAD and GALAD algorithms demonstrated comparable diagnostic performance regardless of disease etiology (HBV vs. non-HBV), presence of cirrhosis, geographic region, and within pan-tumor specificity panels (p < 0.001), indicating AFP-L3 may have a negligible role in HCC surveillance.