Table 1.
Mechanistic role of NAFLD-HBV interplay in chronic liver disease progression.
| Mechanistic role/pathways | Effects on HBV infection | Chronic liver disease progression | References | |
|---|---|---|---|---|
| NAFLD | ↑TLR4/MyD88 pathway leads to ↑TNF-α, IL-1, IL-6, IL-8, TGF-β→ ↑HSCs activation | inhibition of HBV replication | progression to liver fibrosis, NASH and HCC | (24, 26, 28, 30, 33–42) |
| ↑TLR5→NF-κβ, MAPK | ||||
| ↑TLRs in NASH stage leads to ↑CD8+ T cells and NKT cells | ↑anti-viral immune responses, HBV clearance | ↓chronic liver injury | (15–21) | |
| ↑Th17, IL-21 | ||||
| ↑LPS/TLR4 and TLR2 signaling | ↑immune responses, inflammation | inflammation-fibrosis-carcinoma (IFC) sequence in viral hepatitis, steatosis, fibrosis-mediated portal hypertension | (42) | |
| metabolic stress, ↓PGC-1α | ↑HBV suppressed immunity | ↓HBV-related liver disease progression | (44–48) | |
| inhibition of HBV replication | ||||
| palmitic acid→ impaired DCs function | ↓HBV specific immunocytes | ↑severe HBV-related disease progression | (49–52) | |
| abnormal/insufficient immune responses | ||||
| Metabolic components ALT, FBS, TGL BMI and waist circumference | ↑positive correlation with fibrosis/cirrhosis and hepatic steatosis in CHB patients | (53) | ||
| CHRONIC HBV INFECTION | Mechanistic role/pathways | Effects on NAFLD | Chronic liver disease progression | References |
| HBV DNA transcription, TFs (FXR, RXR,C/EBP, CREB), interaction between TFs of activated immune cells | hepatic metabolism of glucose, lipids, bile acid, and xenobiotics | promotion of hepatic regeneration, inflammation, fibrosis, and neoplastic transformation | (54–62) | |
| IL-13 leads to ↑TGF-β1, activation/proliferation of myofibroblasts, ↑JAK/STAT pathway→CCL11 production→eosinophil recruitment | Hepatic steatosis and Fibrosis | (63–80) | ||
| G-CSF expression | ↓hepatic lipogenic genes, ↑b-oxidative genes, ↓SREBP-1c | |||
| IL-4 activates macrophage, M2 → breakdown of ECM, ↑MMP-12 | ||||
| ↑IL-6 by KCs | ↑HSCs proliferation and survival | |||
| [HBx-HNF3b-C/EBPa-PPARa] activates FAB1 | ↑fatty acid uptake | Hepatic Steatosis | (13, 81–93) | |
| HBx activates PPARs, PI3K/AKT pathway and LXR/SREBP pathway→activation of FAS, ACC, SREBP-1c, CYP7A1 | inhibition of apolipoprotein B secretion, ↑hepatic lipogenesis, oxidative corvension of cholesterol to bile acids, hepatic lipid homeostasis | |||
| Hbx interacts with TNFR→activation of NF-κβ pathway | ||||
| HBV pre-S1 binds to NCTP-impede bile acid uptake,↑ expression of cholesterol synthesis genes [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and LDL receptor] | altered hepatic cholesterol metabolism |