Metabolic-associated fatty liver disease (MAFLD) is a progressive metabolic disorder characterized by hepatic steatosis, inflammation, and fibrosis. Emerging evidence suggests that lactate-driven histone lactylation may contribute to its pathogenesis, but mechanisms remain unclear. C57BL/6 mice were fed HFD or CDHFD, and hepatocytes were treated with OAPA. Histone lactylation was assessed by IF and WB. CUT&Tag and RNA-seq identified downstream targets, while H4K16R mutation, PDK4 knockdown, and dichloroacetic acid (DCA) inhibition were applied in vitro and in vivo. Histone lactylation, especially H4K16la, was elevated in murine and human MASH and correlated with steatosis, inflammation, and fibrosis. H4K16la directly activated PDK4 transcription, forming a lactate-H4K16la-PDK4 feedback loop that exacerbated MAFLD. Genetic or pharmacologic inhibition reduced lactate, lipid accumulation, and liver injury. We identify a lactate-H4K16la-PDK4 axis that drives metabolic reprogramming and MAFLD progression. Targeting PDK4 may represent a therapeutic strategy for MAFLD/MASH.

Autoimmune liver diseases (AILD) have historically been considered uncommon in the Asia-Pacific region, where viral hepatitis has predominated as the leading cause of chronic liver disease. However, their recognition and clinical relevance have increased substantially in recent years, mirroring global epidemiologic trends. This proceedings report summarizes the educational course on AILD held during the 34th Annual Meeting of the Asian Pacific Association for the Study of the Liver (APASL) in 2025, highlighting contemporary insights into disease burden, diagnosis, and management across diverse populations. International experts presented updated evidence and region-specific considerations concerning autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis. Key advances in risk stratification, imaging, serology, patient-reported outcome measures (PROMs), and emerging therapeutics were synthesized. Important updates included improved understanding of acute presentations of AIH, evolving risk stratification and second-line pharmacologic approaches in PBC, and advances in PSC diagnostics incorporating novel imaging modalities and emerging autoantibodies. The unique clinical phenotype and steroid responsiveness of IgG4-related sclerosing cholangitis were also emphasized. Increasing incorporation of PROMs into clinical practice and trials, as well as progress in targeted therapies-such as peroxisome proliferator-activated receptor agonists, farnesoid X receptor agonists, and ileal bile acid transporter inhibitors-reflects a shift toward precision medicine and improved quality of life. AILD represents a growing clinical challenge in the Asia-Pacific region. Earlier recognition, individualized treatment strategies, and strengthened multinational collaboration are essential to address unmet diagnostic and therapeutic needs and to improve long-term outcomes.