Background: Multi-biomarker panels have shown promise to improve hepatocellular carcinoma (HCC) surveillance in patients with chronic liver disease; however, we lack comparative data on their relative performance for early-stage HCC detection. Methods: We conducted a systematic review of PubMed, Ovid MEDLINE, and Embase databases from January 2010 to November 2024 to identify studies evaluating the performance of three commercially available blood-based biomarker panels (GALAD, GAAD, and ASAP) for HCC surveillance. Pooled estimates were calculated using the DerSimonian and Laird method for a random-effects model. Results: Of 44 eligible studies (n = 33,100 patients) examining HCC surveillance, 37 studies evaluated GALAD, 12 GAAD, and 11 ASAP. Pooled sensitivities of the biomarker panels for early-stage HCC ranged from 70.1% to 74.1%, with pooled specificities ranging from 83.3% to 87.2%. Among studies directly comparing biomarker panels, sensitivity for early-stage HCC did not significantly differ for GALAD versus GAAD (RR 0.96, 95% CI: 0.80–1.15) or GALAD versus ASAP (RR 1.12, 95% CI: 0.79–1.60). The pooled sensitivity of GALAD for early-stage HCC was higher than that of ultrasound among studies directly comparing the two (79.0% [95% CI: 62.2–89.6] versus 73.3% [95% CI: 45.4–90.1], respectively); however, this difference was not statistically significant (RR 1.09, 95% CI: 0.78–1.51). Studies were limited by inclusion of patients with non-cirrhotic liver disease, varying biomarker cutoffs across studies, and high statistical heterogeneity (I2 >50%) for pooled estimates. Conclusion: Multi-biomarker panels including GALAD, GAAD, and ASAP demonstrate promising performance for early-stage HCC detection, supporting their prospective validation for HCC surveillance.
Background: Disaster disrupts the normal functioning of a community, causing significant damages and losses. In recent years, Lebanon faced multiple disasters, including one of the largest explosions ever recorded, the Beirut Blast, in August 2020. Limited studies in the literature have examined disaster medicine preparedness among healthcare professionals (HCPs). Objective: To examine the knowledge (K), attitude (A), readiness to practice (rP), and KArP associated with disaster medicine preparedness among HCPs in Lebanon. Methods: A cross-sectional observational study was conducted in Lebanon using data from participants answering an online survey. Participants enrolled in this study were HCPs (residents and faculty), medical students, and postdoctoral research scholars. Levels of knowledge, attitude, and readiness to practice were assessed and used to examine their association with participants’ socio-demographic characteristics. Results: A total of 195 participants (average age 30.6 ± 11.4 years) were included in this study. Participants reported moderate scores of knowledge, attitude, and readiness to practice. Older participants reported better readiness to practice and a KArP score. A significant difference was observed in all categories according to gender, with men having higher scores than women. No significant difference was observed between the level of education and knowledge, attitude, and total KArP scores. Conclusions: Our study’s findings showed that age and the level of education were positively correlated with readiness to practice. Men, compared to women, had significantly higher scores in all categories. Barriers to the KArP should be identified and targeted in future studies, as disaster preparedness at the institutional level may improve outcomes in future disaster encounters.
Background/Aim: The impact of myocardial stressors such as high-fat diet (HFD) and pressure overload has been extensively studied. Toll-like receptor 4 (TLR4) deficiency has been suggested to have a protective role in response to these stressors, although some conflicting data exist. Furthermore, there is limited information about the role of TLR4 on cardiac remodeling in response to long-term exposure to stressors. This study aims to investigate the effects of TLR4 deficiency on cardiac histology and physiology in response to chronic stressors. Methods: TLR4-deficient (TLR4−/−) and wild-type (WT) mice were subjected to either HFD or a normal diet (ND) for 28 weeks. Another group underwent abdominal aortic constriction (AAC) or a sham procedure and was monitored for 12 weeks. Inflammatory markers, histology, and echocardiography were used to assess the effects of these interventions. Results: TLR4−/− mice exhibited reduced cardiac hypertrophy and fibrosis after long-term HFD exposure compared to ND without affecting cardiac function. On the other hand, TLR4 deficiency worsened cardiac function in response to AAC, leading to decreased ejection fraction (EF%) and increased end-systolic volume (ESV). Conclusions: TLR4 deficiency provided protection against HFD-induced myocardial inflammation but impaired hemodynamic cardiac function under pressure overload conditions. These findings highlight the crucial role of TLR4 and its downstream signaling pathway in maintaining cardiac output during physiologic cardiac hypertrophy in response to pressure overload.
2 November 2025 in Expert Review of Gastroenterology & Hepatology
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is one of the few cancers with a 5-year survival below 25%, largely driven by frequent late-stage diagnoses. Historically, viral etiologies have been the leading causes of HCC; however, the rising prevalence of metabolic risk factors including obesity and diabetes, in parallel with increasing alcohol misuse, has resulted in increasing proportions of HCC due to non-viral etiologies. This review summarizes HCC prevention, including established approaches such as hepatitis B vaccination and antiviral therapies, as well as emerging strategies tailored to non-viral etiologies. The review also discusses existing surveillance modalities and highlights emerging strategies including blood-based biomarkers, imaging modalities, and artificial intelligence (AI) models. Traditional prevention strategies face challenges with the shifting liver disease patterns. Emerging approaches, including lifestyle modifications and pharmacological therapies, show promise but require further evaluation in contemporary populations. Advances in surveillance may help overcome underutilization, improve early-HCC detection, and increase curative treatment receipt.
Background: Abdominal ultrasound is prone to hepatocellular carcinoma (HCC) surveillance failure, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD), prompting growing interest in blood-based biomarkers as an alternative strategy. Methods: We conducted a case–control study evaluating two blood-based biomarker panels, GAAD and GALAD, for detection of early-stage HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 or A) in patients with MASLD or ALD cirrhosis. Blood specimens were collected within 6 months of HCC diagnosis (cases); controls were patients with cirrhosis but without HCC. GAAD and GALAD scores were measured using the Roche Elecsys platform, applying validated cutoffs of 2.57 and 2.47, respectively. Sensitivity and specificity were compared between the panels and versus ultrasound plus alpha fetoprotein (AFP) using McNemar’s chi square test. Results: Of 152 patients (56.6% men), 46.7% had HCC (54.9% BCLC 0/A) and 53.3% had cirrhosis without HCC. GAAD and GALAD each achieved a sensitivity of 87.2% for early-stage HCC, with specificities of 69.1% and 67.9%, respectively. In paired analyses (n = 90), GAAD had higher sensitivity for any-stage HCC (89.5% vs. 68.4%, p = 0.046) but lower specificity (71.8% vs. 93.0%, p = 0.006) than ultrasound plus AFP. GAAD and GALAD demonstrated consistently higher sensitivity than ultrasound plus AFP across subgroups by age, sex, cirrhosis etiology, and Child Pugh class. Conclusion: In this case–control study of patients with non-viral cirrhosis, GAAD and GALAD demonstrated high sensitivity for early-stage HCC. These findings highlight the potential of blood-based biomarkers to improve HCC surveillance in contemporary populations.
24 June 2026 in American Journal of Physiology-Gastrointestinal and Liver Physiology
The circadian clock and gut microbiome are integral regulators of metabolic homeostasis, with disruptions in either system contributing to obesity pathogenesis. Roux-en-Y gastric bypass (RYGB) effectively treats severe obesity, yet the mechanisms underlying its benefits remain incompletely characterized. We investigated the impact of RYGB on cecal gut microbial composition and function using 16S rRNA sequencing in relation to host circadian gene expression and metabolic parameters in diet-induced obese mice. Diet-induced obese mice underwent RYGB or sham surgery and were compared with lean controls across multiple circadian Zeitgeber time (ZT) points (ZT3, ZT9, ZT15, ZT21). Principal component analysis at the ASV level revealed significant differences in all ZT points (ZT3, ZT9, ZT15, and ZT21) in the lean and sham-operated mice; however, only a significant difference between ZT9 and ZT21 was observed in RYGB mice. Microbial gene counts and microbial pathways were also different between RYGB and sham-operated mice, with several correlating with hepatic Clock and Bmal1 gene expression. Notably, specific taxa showed differential associations with glucose homeostasis, independent of surgical intervention. These findings demonstrate that RYGB alters the gut microbiome and host circadian rhythms, suggesting an association between microbial remodeling, circadian gene expression, and metabolic improvement following bariatric surgery.