Background/Aims Cirrhotic patients with liver stiffness measurement (LSM) <20 kPa and platelet count ≥150×109/L (Baveno VI criteria), otherwise spleen stiffness measurement (SSM) ≤40 kPa (Baveno VI-SSM criteria) can avoid endoscopy screening; however, no prospective data for their hepatic outcomes.
Methods Compensated cirrhosis with HBV were prospectively enrolled from April 2019 to April 2022 and followed until July 2023. All patients underwent LSM, SSM and esophagogastroduodenoscopy assessment.
Results Among 1,224 patients enrolled with median follow-up of 30 months (interquartile range, 21–42), the incidence of decompensation was greater in 560 patients with unfavored Baveno VI criteria (0.5 vs. 20.4 per 1,000 person-years, P=0.0004) than that in 664 patients with favored Baveno VI-SSM criteria. The Baveno VI-SSM model identified more patients (54.2%) as low-risk for decompensation than Baveno VII-SSM model (single cutoff) (48.4%, P=0.004) and than Baveno VI criteria (34.6%, P<0.0001) did. Patients with high-risk varices diagnosed via endoscopy following Baveno VI-SSM model assessment had greater probability of decompensation compared to those identified by the Baveno VII-SSM model (single cutoff) (42.8 vs. 21.1 per 1,000 person-years, P=0.0088). Additionally, among the 493 patients who underwent endoscopic re-assessment, 242 patients with favored Baveno VI-SSM criteria had much lower incidence of EV progression (2.6 vs. 99.5 per 1,000 person-years, P=0.0004) and lower risk of decompensation compared to 140 patients with unfavored Baveno VI-SSM model (0 vs. 34.2 per 1,000 person-years, P=0.0256).
Conclusions Baveno VI-SSM model could identify HBV-related cirrhosis patients at low risk of decompensation, which was greatly improved upon Baveno VI-SSM reassessment.
Citations
Citations to this article as recorded by
Correspondence to editorial 1 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis” Haiyu Wang, Jinjun Chen Clinical and Molecular Hepatology.2026; 32(1): e58. CrossRef
Correspondence to editorial 2 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis” Haiyu Wang, Jinjun Chen Clinical and Molecular Hepatology.2026; 32(1): e62. CrossRef
Correspondence to editorial 3 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis” Haiyu Wang, Jinjun Chen Clinical and Molecular Hepatology.2026; 32(1): e65. CrossRef
Reply to correspondence on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis” Mathias Jachs, Mattias Mandorfer Clinical and Molecular Hepatology.2026; 32(1): e106. CrossRef
Background/Aims Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH.
Methods Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH.
Results Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression.
Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.
Citations
Citations to this article as recorded by
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Ferroptosis inhibits cementoblast mineralization via cGAS-STING/GPX4 axis Tian Wei, Dongyang Li, Jie Zhang, Zhe Zhou, Chunmiao Jiang Progress in Orthodontics.2026;[Epub] CrossRef
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Macrophage ATG16L1: Potential candidate for metabolic dysfunction-associated steatohepatitis treatment: Editorial on “Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy” Junjie Yu Clinical and Molecular Hepatology.2024; 30(4): 721. CrossRef
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