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ADH: alcohol dehydrogenase AI: artificial intelligence AILI: acetaminophen-induced liver injury ALD: alcohol-related liver disease APAP: acetaminophen ATF6: activating transcription factor 6 BAD: bile acid diarrhea BAs: bile acids BMDM: bone marrow-derived macrophages BSHs: bile salt hydrolases CAFs: cancer-associated fibroblasts CCA: cholangiocarcinoma CDCA: chenodeoxycholic acid CDI: Clostridioides difficile infection CMA: chaperone-mediated autophagy CMS: consensus molecular subtypes CPT-1: carnitine palmitoyltransferase-1 CRC: colorectal cancer CVD: cardiovascular disease DAA: direct-acting antivirals DAMPs: damage-associated molecular patterns DILI: drug-induced liver injury eCCA: extrahepatic cholangiocarcinoma ecDNA: extrachromosomal DNA EOCRC: early-onset colorectal cancer ER: endoplasmic reticulum FAK: focal adhesion kinase FAO: fatty acid -oxidation FFAs: free fatty acids FGF: fibroblast growth factor FXR: farnesoid X receptor GLP-1 RAs: glucagon-like peptide 1 receptor agonists GPX4: glutathione peroxidase 4 GSH: glutathione HA: hyaluronic acid HB: hepatoblastoma HCC: hepatocellular carcinoma HO-1: heme oxygenase-1 HSC: hepatic stellate cells IBAT: ileal bile acid transporter IBD: inflammatory bowel disease iCCA: intrahepatic cholangiocarcinoma ICI: immune checkpoint inhibition iNOS: inducible nitric oxide synthase IR: insulin resistance JNK: c-Jun N-terminal kinase KCs: Kupffer cells LAMP-2A: lysosome-associated membrane protein type 2A LSECs: liver sinusoidal endothelial cells MACEs: major adverse cardiovascular events MAFLD: metabolic dysfunction-associated fatty liver disease MASH: metabolic dysfunction-associated steatohepatitis MASLD: metabolic dysfunction-associated steatotic liver disease MetALD: metabolic dysfunction-associated alcohol-related liver disease MIM: mitochondrial inner membrane MPT: mitochondrial permeability transition MRE: magnetic resonance elastography MSI: microsatellite instability NAFLD: nonalcoholic fatty liver disease NHANES: National Health and Nutrition Examination Survey NITs: non-invasive tests NO: nitric oxide Nrf2: nuclear factor erythroid 2-related factor 2 PBC: primary biliary cholangitis PDOs: patient-derived organoids PERK: protein kinase-like endoplasmic reticulum eukaryotic initiation factor-2 kinase PIIINP: procollagen III N-terminal peptide PLR: platelet-to-lymphocyte ratio PNPLA3 : patatin-like phospholipase domain-containing 3 PPARs: peroxisome proliferator-activated receptors PSC: primary sclerosing cholangitis pSWE: point shear wave elastography PV: perivenous PXR: pregnane X receptor RCD: regulated cell death RCT: randomized placebo-controlled trial RIPK: receptor-interacting serine/threonine-protein kinase ROS: reactive oxygen species S1PR2: sphingosine-1-phosphate receptor 2 SERCA: sarco/endoplasmic reticulum calcium ATPase SFAs: saturated fatty acids SGLT2is: sodium-glucose cotransport 2 inhibitors SREBPs: sterol regulatory element binding proteins STARD1: steroidogenic acute regulatory protein 1 T2D: type 2 diabetes TAA: thioacetamide TCA: taurocholic acid TCDCA: taurochenodeoxycholic acid TE: transient elastography TFAM: mitochondrial transcription factor A TFEB: transcription factor EB TGR5: Takeda G-protein receptor 5 THR-: thyroid hormone receptor beta TLR: Toll-like receptor TME: tumor microenvironment UDCA: ursodeoxycholic acid UFA: unsaturated fatty acid UPR: unfolded protein response VDR: vitamin D receptor VMP1: vacuole membrane protein 1 We would like to thank Dr

10.1182/blood-2010-08-303339 42 ElsbachP.LevyS

2.5 Real time-polymerase chain reaction Total RNA was isolated from brain (control tissue), or lenses collected at 10am using Trizol according to the manufacturers protocol (TRIzol reagent

Zhang, J., Nishimura, N., Okubo, A

In line with that, Rotterdam and Framinghams studies revealed that IGF-1 levels are negatively linked with the incidence of CV events (166, 167)