Hepatology Communications最新文献

Background: Although ultrasonography (US) is widely recommended for HCC surveillance, its limited sensitivity for early-stage HCC remains a concern. Gadoxetic acid-enhanced abbreviated MRI (HBP-AMRI) has demonstrated high diagnostic performance; however, its role in routine surveillance settings remains uncertain due to limited prospective comparative evidence. The AMRIUS study (Abbreviated MRI using gadoxetic acid versus Ultrasonography for Surveillance of early-stage HCC in high-risk patients) aims to prospectively compare the effectiveness of HBP-AMRI and US for HCC surveillance in high-risk patients with cirrhosis.

Methods: AMRIUS is a randomized controlled trial (RCT) enrolling 806 high-risk patients with cirrhosis, randomly assigned (1:1) to undergo either biannual HBP-AMRI or US for 2 surveillance rounds. The primary endpoint is the detection rate of early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0 or A]. Secondary endpoints include false referral rate of BCLC 0 or A HCC, detection and false referral rates for BCLC stage 0 and all-stage HCC, BCLC stage distribution at initial HCC diagnosis, and the rate of curative treatment. Structured imaging protocols and quality assessments will be implemented.

Discussion: AMRIUS is the first RCT designed to provide high-level evidence comparing HBP-AMRI and US for HCC surveillance. Its findings are expected to inform future guidelines and support risk-adapted strategies that prioritize early detection and curative treatment eligibility, particularly for patients likely to benefit from high-sensitivity imaging.

Trial registration: Registered at Clinical Research Information Service on May 22, 2022 (KCT0007417) and ClinicalTrials.gov on March 9, 2024 (NCT06312826). Participant recruitment began on August 26, 2022. Follow-up is ongoing.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease and is estimated to affect over a billion people worldwide. MASLD patients may progress to more severe forms, including metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC) with or without cirrhosis. Recent data demonstrated that HCC represents the fifth most common cancer and is the second leading cause of cancer-related death globally, and MASLD has been recognized as a rapidly emerging cause for this malignancy. Given that, diagnosis at the early stage and assessing the risks of progression to HCC are critically important for MASLD patients. However, the optimal screening strategies for patients with MASLD at risk of cancer are still under debate. Although various studies have shown potential for MASLD-related HCC (MASLD-HCC) treatment, the clinical therapeutics are still faced with huge challenges due to the complexity of the pathogenesis of the disease. Herein, we present an overview of the current advancements of early detection and risk evaluation for MASLD and MASLD-HCC patients, and the therapeutic approaches adopted in current clinical management.

Chronic liver disease (CLD) is a progressive condition marked by persistent inflammation and regeneration of hepatic tissue, often leading to cirrhosis and increased susceptibility to microbial infections. These infections not only trigger acute decompensation and acute-on-chronic liver failure but also contribute to poor clinical outcomes despite antibiotic treatment. Conversely, CLD itself exacerbates infection severity, forming a vicious cycle. Recent research has highlighted the diverse and coordinated roles of liver parenchymal and nonparenchymal cells in antimicrobial immunity. Hepatocytes control infection by producing a large number of antimicrobial peptides, opsonins, and inflammatory mediators. KCs are key to capturing and clearing blood-borne pathogens and orchestrating immune responses. LSECs facilitate immune cell trafficking, pathogen sensing, and modulation of neutrophil-mediated defense. HSCs are activated during bacterial infections and promote fibrosis through inflammasome and TGF-β signaling. Biliary epithelial cells serve as frontline defenders in the biliary tract, expressing pattern recognition receptors and secreting cytokines, chemokines, defensins, and IgA. Understanding the complex interplay between hepatocytes, liver nonparenchymal cells, and immune components is crucial for developing targeted therapies to improve infection control and outcomes in patients with chronic liver disease. Here, we provide a comprehensive summary of the roles played by different hepatic cell types during microbial infections with a focus on bacterial infection. The potential mechanisms underlying the increased susceptibility of CLDs to these infections are also briefly discussed.

Background: Although medical risk prediction tools are widely developed, few achieve sustained clinical adoption. In cirrhosis patients, surgical risk calculators have achieved broad utilization. We sought to identify key design and implementation factors that influence provider uptake of such tools, using the VOCAL-Penn score (VPS) as a case example.

Methods: We conducted a qualitative study of 22 diverse clinicians who care for patients with cirrhosis. Semi-structured interviews were guided by the Consolidated Framework for Implementation Research to explore factors influencing the adoption of risk prediction tools. Interviews were transcribed and analyzed using a combined grounded theory and deductive approach. Emergent themes were synthesized into a conceptual framework.

Results: Five recurrent themes emerged as central: efficiency, accessibility, transparency, accuracy, and generalizability. Clinicians emphasized the need for tools that are intuitive, require minimal inputs, and integrate seamlessly into existing workflows. Ensuring input variables were clinically meaningful and readily available was cited as critical to encouraging use. Transparency in model development was essential to building trust. Participants stressed the importance of comparative performance data relative to existing clinical standards, as well as published external validations, to support the tool's credibility. Finally, generalizability was key to equitable application across diverse patient populations.

Conclusions: Using the VPS as a grounding example, our findings identify 5 domains-efficiency, accessibility, transparency, accuracy, and generalizability-that inform the development and dissemination of future tools. By aligning tool design with real-world clinical needs, this framework may support broader adoption and more equitable implementation of medical risk prediction tools.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~30% of the US adult population, and its prevalence is increasing. Early-stage disease is often missed by clinicians as it is largely asymptomatic until cirrhosis develops. Recent advances in artificial intelligence (AI) have allowed for expanded electronic health record (EHR) identification of several diseases. We aimed to develop an algorithm that utilizes AI to identify patients with MASLD via a large-scale review within the EHR.

Methods: We created a natural language processing (NLP) algorithm that identifies patients with hepatic steatosis on abdominal imaging and selects for patients meeting MASLD criteria. Validation was carried out via manual review of monthly generated cohorts. The algorithm was then utilized to retrieve a MASLD cohort for initial analysis. Demographics were summarized, and additional variables pertaining to early MASLD management were analyzed.

Results: Our algorithm identified patients with MASLD with a positive predictive value (PPV) of over 93%. The NLP component of the algorithm identified hepatic steatosis in imaging reports with a PPV of up to 99.4% and excluded patients with alcohol use with a negative predictive value of ~95%. From a cohort spanning 6 months, 957 individuals with MASLD were identified by the algorithm, of which 14.6% (n=140) had a MASLD-related diagnosis code.

Conclusions: We developed an AI algorithm that can perform a large-scale review of electronic health records to identify patients with MASLD with >93% accuracy. Our initial analysis suggests that a substantial proportion of individuals meeting MASLD criteria do not yet carry a MASLD-related diagnosis. Our work can be adapted by other institutions to enhance the detection of MASLD and alcohol use patterns, allowing for targeted interventions to prevent disease progression and improve outcomes.

Background: Kupffer cells (KCs) are the tissue-resident macrophages of the liver, where they serve a critical role in maintaining liver tissue homeostasis and act as a filter for circulation. The composition of hepatic macrophages changes during metabolic dysfunction-associated liver disease (MASLD), with the loss of resident KCs being a hallmark of disease progression. The mechanism(s) and consequences of KC death in metabolic liver disease have yet to be defined. Transcription factor EB (TFEB) is a master regulator of lysosome function and lipid metabolism, which has been shown to protect macrophages from lipid stress in atherosclerosis. We hypothesized that TFEB would improve KC fitness in MASLD.

Methods: To investigate the potential beneficial effect of TFEB induction in KCs, we created a transgenic mouse in which TFEB was overexpressed specifically in KCs and evaluated its impact on disease pathogenesis in high-fat, high-sucrose (HFHS) and choline-deficient diet models of MASLD.

Results: We found that TFEB induction protected KCs from cell death in both models of MASLD. KC preservation through TFEB induction reduced liver steatosis with HFHS diet via mechanisms that were dependent on macrophage lysosomal lipolysis and mitochondrial fatty acid oxidation. Fibrosis was unchanged in choline-deficient diet studies. TFEB protected KCs from cell death by diminishing oxidative stress and reducing ferroptosis through a mechanism that involved enhanced NADPH levels.

Conclusions: TFEB induction promotes KC fitness upon lipid stress during MASLD. Preservation of lipid-adapted KCs demonstrates beneficial effects against liver steatosis and protects portal filtration during MASLD.

Background: Dietary interventions are key for managing metabolic dysfunction-associated steatotic liver disease (MASLD), yet optimal diets and the role of PNPLA3 in modulating response to diet remain unclear. We evaluated the efficacy of a Mediterranean diet (MD) versus a low-fat diet (LFD) on hepatic fat and fibrosis, assessing interactions with PNPLA3 genotype.

Methods: Two hundred fifty adults with MASLD with BMI ≥25 kg/m2 were randomized to a 12-week moderately hypocaloric MD or LFD intervention. Individuals with excess alcohol intake and other etiologies of steatosis were excluded. Subjects were genotyped for PNLPA3 single-nucleotide polymorphism. Anthropometric measures, blood tests, and liver assessments [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)] were conducted at baseline and follow-up. Essential food items were provided, and adherence was tracked using validated questionnaires. The primary outcome was CAP, analyzed using linear mixed models adjusted for age and metabolic syndrome.

Results: Both diets significantly reduced CAP, LSM, and body weight at follow-up, with no significant differences between groups. The mean difference between MD and LFD was -0.13 dB/m for CAP (p=0.976, 95% CI: -8.54, 8.28), -0.19 kPa for LSM (p=0.355, 95% CI: -0.58, 0.21), and 3.01 kg for weight (p=0.159, 95% CI: -7.21, 1.19). PNPLA3 genotype did not significantly interact with diet for CAP, LSM, or weight (p=0.286, p=0.464, p=0.622, respectively).

Conclusions: Weight reduction achieved by MD and LFD is similarly efficient in steatosis and fibrosis reduction, while PNPLA3 genotype does not affect the response to diet. Further studies investigating the impact of diet and nutrigenetics on liver-related outcomes are warranted.

Background: Group-based, telehealth behavioral interventions may be efficient, effective, and acceptable treatment modalities for patients with chronic liver diseases; however, pilot feasibility and patient satisfaction data are needed to justify efficacy trials. Given the poor quality of life, symptoms, and health risk factors, patients with chronic hepatitis C-associated liver disease (HCV-LD) may benefit from psychosocial interventions. A pilot feasibility study of a videoconferencing-delivered cognitive behavioral coping skills intervention ("VC-CBCS") was conducted to evaluate multiple indicators of feasibility, levels of patient satisfaction, and changes in patient-reported outcomes (PROs).

Methods: We pilot tested a 14-week, 90-minute VC-CBCS intervention by conducting a small randomized controlled trial. Thirty-two adults with HCV-LD and high stress/symptom levels were randomized to the protocolized VC-CBCS intervention (n=24) or standard of care (n=8), in 4 waves of 7-9 participants in 2020-2021.

Results: Based upon rates of approach to enrollment (60%), retention (84%), PRO data collection (99.4%), and session attendance (91%), a future efficacy trial appears highly feasible. Levels of participant satisfaction were encouraging for VC delivery, intervention content and structure, and group processes. Technological and behavioral issues were minor. Collection of in-home saliva testing was not feasible. Moderate to large pre-post-intervention effect sizes were observed for some mediators (perceived stress, coping, relaxation, self-efficacy, sleep hygiene), with some of these changes correlating with small to moderate improvements in mental health and symptoms (eg, depression, fatigue; effect size range: 0.23-0.47). No consistent patterns were evident between changes in eating and exercise behaviors and PROs.

Conclusions: A group-based VC-CBCS intervention appears feasible and may address unmet psychosocial needs in patients living with chronic liver disease.