Management of hepatocellular carcinoma prior to liver transplantation: latest developments.

Hepatocellular carcinoma (HCC) is a highly morbid malignancy that is a leading cause of death in patients with cirrhosis or chronic hepatitis B. Liver transplantation is considered a curative therapy for HCC, with 5-year survival rates exceeding 75%. Current allocation policy in the US restricts transplant to patients with early HCC, and priority for transplant is granted after 6 months on the waitlist, thus patients often require therapies for cancer control while awaiting liver transplantation.

Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified Delphi panel.

HCC surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on 21 statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities.

Utility-Based Dose Selection for Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma.

Purpose: Stereotactic body radiation therapy (SBRT) planning for hepatocellular carcinoma (HCC) typically prescribes the maximum dose associated with an acceptable risk of toxicity, relying on implicit trade-offs between efficacy and toxicity. To make this trade-off quantitative, we developed a utility-based approach to dose selection for SBRT in HCC and studied the expected effects on clinical outcomes.

Methods And Materials: Using a multi-institutional cohort of SBRT-treated patients, we developed predictive models for local progression, competing mortality, and liver toxicity, defined as an increase of 0.

The Contribution of Cirrhosis Progression in Liver Dysfunction After Stereotactic Body Radiation Therapy.

Purpose: Patients with cirrhosis and hepatocellular carcinoma (HCC) often have progressive liver dysfunction after stereotactic body radiation therapy (SBRT), but the relative contribution of direct radiation toxicity versus cirrhosis progression is unknown. Our goal was to estimate the proportion of post-SBRT deterioration in the albumin-bilirubin (ALBI) score that is due to cirrhosis progression versus radiation toxicity.

Methods And Materials: We first developed mixed-effects models to predict longitudinal ALBI trajectories among 6789 patients with cirrhosis within the University of Michigan system who did not have HCC.

Development of Histotripsy as a Local-Regional Liver Cancer Therapy: Preclinical to Clinical Translation.

Histotripsy is the first noninvasive, nonthermal, and nonionizing focused ultrasound ablative therapy that effectively destroys targeted tissue. Histotripsy research began as an early preclinical prototype that eventually underwent small- and large-animal preclinical testing to ensure safe clinical translation to human use. Small-animal studies demonstrated the efficacy of histotripsy in destroying liver tumors and generating immune responses, while large-animal studies in human-sized livers further refined the technology for clinical translation.

Real-world treatment patterns and outcomes in patients with early-stage HCC in the US treated with resection or ablation.

Aim: Real-world outcomes in early-stage hepatocellular carcinoma (eHCC) are not well characterized. We aimed to evaluate treatment patterns and long-term outcomes in patients with eHCC treated with resection or ablation in the United States.

Materials And Methods: We conducted a retrospective study with Optum's de-identified Market Clarity Data.

Causes of mortality among patients with early-stage hepatocellular carcinoma.

Background And Aims: Early detection of hepatocellular carcinoma (HCC) can reduce cancer-related mortality; however, there are often competing risks from comorbid conditions, including cirrhosis. Understanding causes of death among patients with early-stage HCC can inform strategies to improve surveillance effectiveness.

Approach And Results: We conducted a retrospective cohort study of patients with early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stages 0/A] at 4 U.

The association between stage migration and overall survival after radiation-based therapies in patients with hepatocellular carcinoma.

Background & Aims: Stereotactic body radiation therapy (SBRT) and transarterial radioembolization (TARE) are common locoregional therapies for hepatocellular carcinoma (HCC). However, lack of surrogate endpoints has limited the feasibility of conducting comparative effectiveness clinical trials.

Methods: We conducted a multicenter retrospective cohort study of adult patients with HCC who received SBRT or TARE as initial treatment between 2008 and 2019.

Evaluation of Living Liver Donors Using Dual-Contrast-Agent Magnetic Resonance Imaging (MRI) and Cholangiopancreatography (MRCP)-Technical Development.

The indications for liver transplantation continue to expand to meet the growing need of patients with end-stage liver disease and select hepatic malignancies. Living donor liver transplantation allows for access to transplant with recipient outcomes superior to deceased donor liver transplantation. To ensure absolute safety of the donor and optimal outcome of the recipient, potential liver donors are subjected to an exhaustive preoperative evaluation.

Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Background & Aims: Older adults have lower treatment eligibility and worse survival across cancer types; however, the association between age and outcomes in patients with hepatocellular carcinoma (HCC) has not been well characterized.

Methods: We performed a search of the PubMed, Ovid MEDLINE, and EMBASE databases from January 2000 to July 2022 to identify studies reporting tumor stage, curative treatment, and overall survival among patients with HCC, stratified by age. Using the DerSimonian and Laird method for a random-effects model, we calculated pooled risk ratios (RRs) for curative treatment receipt and hazard ratios (HRs) for overall survival among younger and older patients (per age thresholds in each study).

The Real-World Prevalence of Esophagogastric Varices, Bleeding, Emergency Room Visits, and Hospitalization Among Patients with Advanced Hepatocellular Carcinoma in the United States: A Retrospective Cohort Study.

Purpose: Esophagogastric varices (EGV) and upper gastrointestinal bleeding are common and potentially fatal complications in patients with advanced hepatocellular carcinoma (aHCC). We aimed to evaluate the real-world prevalence of EGV among the aHCC population in the United States.

Patients And Methods: This retrospective cohort study utilized IQVIA's PharMetrics Plus Health Plans Claims database between January 1, 2016, and July 31, 2021 (study period).

Immune-Related Adverse Events Are Associated With Improved Outcomes After Immune Checkpoint Inhibitor Treatment in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Introduction: Immune checkpoint inhibitors (ICIs) have become the first-line treatment of unresectable hepatocellular carcinoma (HCC). The prognostic value of immune-related adverse events (irAEs) in these patients remains controversial. We aimed to investigate the association between irAEs and clinical outcomes in patients with HCC treated with ICIs.

Direct-acting antivirals lower mortality and recurrence in HCV-related hepatocellular carcinoma post liver resection: A multicenter international study.

Background: The impact of treatment on hepatitis C virus with direct-acting antivirals on 90-day postoperative outcomes, overall survival, and recurrence-free survival in patients after liver resection for hepatocellular carcinoma is unknown.

Methods: We conducted a multicenter retrospective study. Adults who underwent liver resection for hepatitis C virus-related hepatocellular carcinoma between January 2000 and December 2018 were included from 7 international institutions.

Multicenter evaluation of abbreviated MRI and ultrasound for detecting early-stage hepatocellular carcinoma.

Background & Aims: 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.

Methods: 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.

Patient-Perceived Risk of Hepatocellular Carcinoma and Net Benefit of Surveillance: A Multicenter Survey Study.

Introduction: Hepatocellular carcinoma (HCC) surveillance is underused in clinical practice, and few contemporary data have assessed patients' perceptions of surveillance effectiveness and net benefit.

Methods: We conducted a survey study among adult patients with cirrhosis at 7 health systems in the United States. The survey was based on validated measures, when available, and assessed patient knowledge about HCC surveillance, attitudes regarding surveillance benefits and harms, perceived HCC risk, and trust in their doctors.

AI-based phenotyping of hepatic fiber morphology to inform molecular alterations in metabolic dysfunction-associated steatotic liver disease.

Background And Aims: Hepatic fiber morphology may significantly enhance our understanding of molecular alterations in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to comprehensively characterize hepatic fiber morphological phenotypes in MASLD and their associated molecular alterations using multilayer omics analyses.

Approach And Results: To quantify the morphological phenotypes of hepatic fibers, the artificial intelligence-based FibroNest algorithm (PharmaNest) was applied to 94 MASLD-affected liver biopsies, among which 12 (13%) had concurrent HCC.

The #HOPE4LIVER single-arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors: 1-year Update of Clinical Outcomes.

Objective: To evaluate the 1-year clinical outcomes of patients enrolled in the #HOPE4LIVER trial of hepatic histotripsy.

Summary Background Data: Histotripsy is a novel non-invasive, non-thermal focused ultrasound therapy that liquefies tissue at the focal point of the transducer. Following diagnostic ultrasound targeting, an automated treatment is performed via a robotic arm to treat a user-defined volume of tissue.

Comparative effectiveness of immunotherapy versus lenvatinib in advanced hepatocellular carcinoma: A real-world analysis using target trial emulation.

Background And Aims: Immunotherapy has emerged as an effective treatment for advanced HCC. We aimed to investigate the real-world effectiveness of immunotherapy compared to lenvatinib in HCC.

Approach And Results: From the TriNetX database, we used a target trial emulation framework and identified patients with HCC who received first-line treatment with immunotherapy (atezolizumab/bevacizumab or tremelimumab/durvalumab) or lenvatinib between or between August 2018 and December 2023.

A systematic review of noninvasive laboratory indices and elastography to predict hepatic decompensation.

Background: Hepatic decompensation carries profound implications for patient quality of life and risk of mortality. We lack comparative data on how noninvasive tools perform in risk stratification for those with compensated cirrhosis. We performed a systematic review to assess the performance of laboratory and transient elastography-based models for predicting hepatic decompensation in patients with compensated cirrhosis.

Testosterone Replacement Reduces Morbidity and Mortality for Most Patients With Cirrhosis.

Background & Aims: Many men with cirrhosis have low testosterone levels. This is associated with sarcopenia, anemia, and poor quality of life. Data are lacking, however, regarding the clinical impact of testosterone replacement.

The first international experience with histotripsy: a safety analysis of 230 cases.

Background: Histotripsy is a novel, noninvasive, nonionizing, and nonthermal approach that uses focused ultrasound waves to treat liver tumors. This technology received a de novo Food and Drug Administration grant in late 2023. This study aimed to provide the first report on post-trial real-world clinical safety data.

Tolerability and Effectiveness of Regorafenib Treatment in Patients with Unresectable Hepatocellular Carcinoma: Real-World Data from the United States.

Introduction: While several systemic therapies are available for unresectable hepatocellular carcinoma (uHCC), there is a lack of granular real-world evidence to support the efficacy and safety of these therapies. The REFINE study evaluated safety and effectiveness of regorafenib in a global population under real-world practice conditions. This sub-analysis describes the safety and effectiveness of regorafenib among the United States (US) subset of patients in the REFINE study relative to patients in the non-US subset.

Electronic Interventions to Improve Quality for Inpatient Cirrhosis Care: A Prospective Evaluation.

Introduction: Efforts to improve adherence to quality measures in cirrhosis care are encouraged by American Association for the Study of Liver Diseases (AASLD) to improve clinical outcomes.

Methods: We prospectively evaluated 2 best practice advisory (BPA) interventions to alert clinicians caring for patients with cirrhosis and acute variceal hemorrhage or spontaneous bacterial peritonitis.

Results: Our BPAs increased utilization.

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.