Leon A. Adams

Description:Objective: Fibrosis-4 Index (FIB-4) is a non-invasive tool for assessing liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, its role of dynamic FIB-4 for assessing fibrosis progression and predicting clinical outcomes remains unclear. To examine the association between changes in FIB-4 and changes in liver stiffness, fibrosis progression, and outcomes in MASLD. Methods: Three cohorts were analyzed: VCTE-Prognosis cohort (n=10,203) for stiffness progression, Paired Liver Biopsy cohort (n=1,145) for fibrosis progression, and Wenzhou Real-World (WRW) cohort (n=41,105) for clinical outcomes. Stiffness progression was defined as an increase in liver stiffness measurement, and fibrosis progression by a 1-stage increase. Outcomes included all-cause mortality, cardiovascular and liver-related events (LRE). FIB-4 was dichotomized into low (<1.3) and high (≥1.3). Increases were defined as ≥20% rise and to ≥1.3 in the low FIB-4 group, and ≥20% rise in the high FIB-4 group. Results: In the VCTE-Prognosis cohort, stiffness progression was more likely with increasing vs. stable FIB-4 (adjusted OR=2.36, P<0.001) in those with low baseline FIB-4. In high FIB-4 group, stiffness progression rates increased from stable to increasing FIB-4 (adjusted OR=3.42, P<0.001). In the Paired Liver Biopsy cohort, fibrosis progression was more frequent with increasing FIB-4 (adjusted OR=2.20, P=0.004 in low FIB-4; adjusted OR=3.68, P<0.001 in high FIB-4). In the WRW cohort, an increase in dynamic FIB-4 was linked to higher risks for all-cause mortality, cardiovascular events and LRE (all P<0.001). Conclusions: Dynamic FIB-4 monitoring tracks fibrosis and stiffness progression and predicts clinical outcomes in MASLD.

Description:Aim: Poor outcomes in advanced hepatocellular carcinoma (HCC) coupled with potential significant treatment side effects underpin a strong rationale to assess health-related quality of life (HRQOL) in those treated with systemic therapies. This study is aimed at quantifying the effect of systemic therapies on HRQOL outcomes in HCC patients when compared to baseline or placebo, other systemic therapies, and transarterial radioembolisation (TARE). Methods: In May 2024, two independent reviewers searched PubMed, EMBASE, and Google Scholar for studies comparing postsystemic therapy HRQOL scores in adult patients with HCC to baseline or placebo, other systemic therapies, or to TARE. Narrative synthesis was used to synthesise results. Risk of bias was assessed using RoB 2 and ROBINS-I. This review was structured according to PRISMA guidelines and was prospectively registered in the PROSPERO register (CRD42024521699). Results: Twenty-nine studies with 10,472 patients using eight HRQOL instruments were included. Compared to baseline, patients on atezolizumab/bevacizumab and sorafenib both experienced significant declines in HRQOL, and lenvatinib nonsignificantly decreased HRQOL. HRQOL remained unchanged in patients on pembrolizumab or nivolumab. Atezolizumab/bevacizumab and lenvatinib both significantly delayed HRQOL deterioration compared to sorafenib. Compared to TARE, atezolizumab/bevacizumab delayed time-to-deterioration in HRQOL, whereas sorafenib had significantly worse HRQOL. Conclusion: Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezolizumab/bevacizumab and lenvatinib had superior HRQOL outcomes in comparison to sorafenib. Sorafenib significantly worsened HRQOL compared to TARE. As the majority of included studies included sorafenib, which has been largely superseded by newer therapies, further trials evaluating HRQOL with these newer therapies are required.

Description:Objective: Metabolic dysfunction- and alcohol-associated liver disease (MetALD) is a recently defined entity for individuals with liver steatosis, metabolic dysfunction, and increased alcohol intake. However, the current definition of MetALD poses multiple challenges in clinical practice and research. In this Delphi consensus, we provide practical recommendations for the clinical assessment and management of MetALD to address current clinical challenges in MetALD. Methods: We used a modified Delphi process, including 2 surveys involving a panel of 28 experts from 10 countries spanning 4 continents. We predefined consensus as requiring an ≥80% agreement. Results: The panel reached consensus on 28 statements. Recommendations emphasize the importance of a comprehensive assessment of patients with presumed MetALD, including the quantification of alcohol intake using validated questionnaires and the use of objective biomarkers of alcohol use, such as phosphatidylethanol. The need to reassess metabolic risk factors and liver disease after a period of alcohol abstinence was highlighted to distinguish the primary driver of liver injury. Noninvasive tests were recommended to assess liver disease severity, whereas routine liver biopsy was deemed unnecessary unless other diagnoses were suspected. Comprehensive management strategies should involve multidisciplinary care focusing on lifestyle modifications, alcohol reduction or cessation, weight loss, and exercise. Finally, the panel identified significant gaps in knowledge, advocating for standardized research protocols, longitudinal studies, exploration of pathophysiological mechanisms to inform precision medicine approaches, and the validation of quantitative alcohol biomarkers for identifying MetALD. Conclusions: This Delphi consensus provides clear recommendations for the clinical assessment and management of MetALD, addressing the unique challenges posed by this condition.

Description:Objective: Several predictive scores have been developed internationally to rationalise hepatocellular carcinoma screening in patients with chronic hepatitis B. This study evaluated the performance of these scores in a large Australian cohort. Methods: A retrospective analysis was undertaken on patients with chronic hepatitis B attending two tertiary hospitals from 1st January 2017 to 30th June 2023. Predictive scores were calculated at baseline and patients were followed for the development of hepatocellular carcinoma. Results: A total of 1080 patients were included. The average age was 48 years, 43% were female, 91% were non-cirrhotic, and 51% received antivirals. Most patients (62%) were of Asian ethnicity, 13% African, and 9% Caucasian. Twenty-one patients (1.9%) developed hepatocellular carcinoma during a median follow-up of 5.2 years. The calculated sensitivity was 90.5% for PAGE-B and modified PAGE-B, and 42.9% for REACH-B. Positive predictive values were below 4%, and negative predictive values exceeded 98% for all scores. The time-dependent area under the curve at 5 years for PAGE-B, modified PAGE-B, and REACH-B were 0.74, 0.80, and 0.68 respectively. The 5-year cumulative incidence of hepatocellular carcinoma for patients with low, intermediate, and high PAGE-B scores was 0.33%, 2.1% and 4.9% respectively (log-rank, p < 0.001) and for modified PAGE-B was 0.44%, 1.0% and 7.1% respectively (p < 0.001). REACH-B was unable to accurately stratify hepatocellular carcinoma risk (p = 0.19). Conclusions: In our Australian cohort of diverse ethnicity, cirrhosis and treatment status, both PAGE-B and modified PAGE-B scores performed well with respect to hepatocellular carcinoma risk stratification and identifying low-risk patients who may safely avoid screening.