Disease

Updated histologic guidance for MASLD: refined definitions for steatosis, lobular inflammation, hepatocyte ballooning, and portal changes as they relate to fibrosis stage.

Zone 3 is the first site of steatosis and oxidative stress; Zone 1 shows insulin resistance phenotype; fibrosis spreads from Zone 3 outward as zonation breaks down.

Lipid droplet biology as the organizing framework for steatosis: droplet formation, storage, lipolysis, and lipophagy. Histologically visible as macro- and microvesicular change on H&E and PAS.

Semi-quantitative scoring for hepatocellular necrosis, vacuolization, steatosis, fibrosis, and collagen deposition in experimental models; standardizes the histologic language used at the bench.

Morphology of ballooning: swelling, intermediate filament collapse, mitochondrial swelling, membrane blebbing; distinguishes from lipid vacuolization; discusses scoring consistency.

Lipid droplets deform the nucleus and disrupt cytoskeletal networks; mechanobiological basis for how macrovesicular steatosis impairs hepatocyte function beyond simple lipid storage.

Bariatric surgery reduces steatosis grade, NAS score, and ballooning on paired biopsies; quantifies histologic reversibility in a clinical cohort.

HepG2 is metabolically aberrant; HepaRG, PHH, and iPSC-derived hepatocytes compared for MASLD modeling. PHH remain gold standard despite cost.

iPSC-derived hepatocytes recapitulate lipid accumulation, inflammation, and early fibrosis relevant to MASLD histology.

STING inhibition reduces lipotoxic cell death in hepatocytes during viral hepatitis; links innate immune signaling to lipid-driven hepatocyte injury in co-morbid disease states.

Modified isolation protocol for steatotic liver: lipid accumulation alters density-gradient separation; Percoll adjustments required to recover viable hepatocytes from MASLD-model mice.

hESC-derived polarized hepatocyte organoids treated with free fatty acids recapitulate MASLD: steatosis, lipotoxicity, inflammation markers. Platform validated for therapeutic compound screening.

EV protein signatures differ between PHH, liver organoids, and patient serum in MASH; each model captures distinct aspects of hepatocyte injury; complementary use recommended for biomarker discovery.

UBE2N is lost from human and mouse MASH hepatocytes; hepatocyte-specific deletion worsens MASH and fibrosis through failed K63-p62 mitophagy and PANoptosis, and overexpression reverses it. p62 proposed as a target. Mouse and human tissue; single study.

Liver-specific Prmt1 loss triggers compensatory PRMT6 methylation of METTL3, raising m6A, lowering Keap1 and switching on NRF2 in premalignant disease-associated hepatocytes; steatohepatitic HCC incidence rises. Mouse; single study.

Cardiolipin falls in human and mouse MASLD; hepatocyte-specific cardiolipin synthase knockout causes spontaneous MASH with fibrosis through electron leak at complexes III and II and loss of the I+III2+IV supercomplex. Mouse; single study.

Spatial transcriptomics on human ACLF liver biopsies shows the Zone 1-3 metabolic gradient collapses in ACLF; enzymatic zonation markers lost across the lobule; zonation failure proposed to contribute to organ failure severity. Human; single study.

Review: ferroptosis (iron-dependent lipid peroxidation-driven cell death) and accompanying immune activation are proposed as key drivers of MASH progression to HCC; reviews therapeutic targeting opportunities. Review.

C/EBPbeta links hyperglycemic conditions to accelerated hepatocyte glycolysis and HCC progression; diabetic plasma amplifies the pathway in vitro and in mouse models. Mouse and cell lines; single study.

Traditional Chinese herb pair BAP ameliorates MAFLD steatosis and insulin resistance via PI3K/Akt-GSK3β/FoxO1; validated in HFSW-fed mice, AML12 hepatocytes, and human iPSC-derived liver organoids. Mouse and organoid; single study.

Rat-derived HEV-C1 breaches species barrier to infect AG129 mice; single-cell sequencing shows tropism for liver macrophages and hepatocytes; mouse-adapted strain infects immunocompetent C57BL/6J; CD4+ T cell depletion drives chronic infection. Mouse; single study.

SOD-displaying bacterial extracellular vesicles reduce hepatic steatosis, serum transaminases, and inflammatory infiltration in a murine ALD model by activating the Nrf2/HO-1 antioxidant axis; show liver-targeting capability without secondary hepatic burden. Mouse ALD model; single study.

Optogenetically controlled mesenchymal stem cells deliver hepatoprotective factors on light-command; in the ConA immune hepatitis model spatiotemporal control reduces lobular inflammation and hepatocyte death. Mouse; single study.

Co-expression of glucose-6-phosphate dehydrogenase (pentose phosphate pathway) and secreted phosphoprotein 1 (osteopontin) marks an aggressive, immunosuppressive hepatocellular carcinoma subtype with poor prognosis; identifies a metabolic-immune vulnerability. Human HCC cohort.

HSC co-culture with hepatocellular carcinoma cells in 3D spheroids promotes compaction, extracellular matrix remodeling, and drug resistance; demonstrates stellate cell contribution to HCC microenvironment in vitro. Cell model; single study.

Soy protein concentrate substitution for fish meal induces hepatic steatosis and transcriptomic shifts in Totoaba liver; relevant as non-mammalian reference for dietary-induced hepatic lipid accumulation. Fish (Totoaba macdonaldi); single study.

In ovo acrylamide administration produces hepatocyte vacuolation, glycogen loss, and elevated plasma transaminases in chick liver; documents avian liver response to a widespread food-processing contaminant. Chicken; single study.

Spatial transcriptomics in a mouse breast-to-liver metastasis model shows atorvastatin reprograms the hepatic microenvironment, reducing inflammatory signaling in peri-metastatic hepatocytes and restricting outgrowth. Mouse; single study.

NADES-based ultrasound extraction optimized for paeonol and related polyphenols from Moutan Cortex; hepatoprotective activity evaluated in CCl4-injured hepatocyte models; extraction-to-bioactivity pipeline validation. Cell model; single study.

Deep eutectic solvent ultrasound extraction of Blumea balsamifera flavonoids; hepatoprotective activity evaluated against LPS/D-GalN-induced liver injury; identifies active fraction composition and proposed mechanism. Mouse and cell model; single study.

EGF reduces α-amanitin (death cap amatoxin) hepatocyte death via EGFR-mediated survival signaling; efficacy compared against silibinin (standard antidote); proposes EGF receptor axis as a hepatoprotective target in amatoxin poisoning. Cell model; single study.

Review of ERK, JNK, and p38 MAPK roles in DILI; JNK activation identified as a central driver of hepatocyte apoptosis and necrosis in toxic and idiosyncratic liver injury; discusses therapeutic targets. Review.

Review of mitochondrial dysfunction as driver of HCC pathogenesis: mtDNA mutations, ETC defects, metabolic rewiring (Warburg), ROS-driven genomic instability, and mitophagy deregulation; discusses drug resistance mechanisms and mitochondria-targeted therapeutic approaches.

Review of how steatosis-driven metabolic shifts (lipotoxicity, ER stress, altered bile acids) reprogram hepatic immune cells including Kupffer cells, hepatic stellate cells, and infiltrating lymphocytes; links zone-3 lipid accumulation to perivenular inflammation. JHEP Reports.

Spatial transcriptomics analysis of lobular zone-specific immune dysfunction in MASLD; maps how oxygen and nutrient gradients across zones 1-3 shape immune cell composition and pro-inflammatory signalling; zone-3 perivenular injury predominant.

Melatonin reduces hepatocyte death in experimental liver injury through PI3K/AKT pro-survival signalling and suppression of NLRP3 inflammasome; hepatocellular signalling axis with therapeutic relevance.

Review of non-invasive MASLD biomarkers: serum (ALT, CK-18, FGF-21, GDF-15), imaging (MRI-PDFF, MRE, CAP, LSM), and omics panels; discusses regulatory acceptance as surrogate endpoints in clinical trials.

Systematic review of non-nutritive and natural sweetener effects on hepatic steatosis and fibrosis risk; discusses fructose-sparing mechanisms, gut-liver axis effects, and evidence quality; directly relevant to dietary-metabolic inputs driving MASLD.

ALDH2 rs671 (inactive allele) modifies lipid profile responses in alcohol-abstinent adolescents with steatotic liver disease; links hepatocyte alcohol-detoxification enzyme status to metabolic risk.

Gut microbiota-derived hippuric acid activates hepatic NK cells via TLR2 signalling in HBV-MASLD co-morbidity; gut-liver metabolite axis linking MASLD metabolic milieu to antiviral immunity in the perivenular and mid-zonal compartments.

Tumour-derived HMGB1 induces neutrophil senescence and neutrophil extracellular trap (NET) formation; NETs suppress CD8+ T-cell cytotoxicity in the HCC tumour microenvironment; demonstrates how HCC escapes innate-adaptive immune crosstalk.

Systematic review assessing how concurrent MASLD affects cirrhosis progression, HCC risk, and treatment response in chronic HBV infection; highlights synergistic metabolic-viral hepatocyte injury.