Hepatic inflammation and progressive liver fibrosis in chronic liver disease

Table 1 Anti-fibrotic actions and clinical outcomes of the conventional drug regimens

Conventional therapies	Possible anti-fibrotic actions	Clinical outcomes
Anti-viral agents	Prevent viral activation of HSC[72,74] Limit viral induction of ROS[74] Reduce HSC proliferation[72] Decrease pro-inflammatory signals[74] Reduce TGFβ1 and procollagen[72-74] Decrease lymphocyte recruitment[75]	No fibrosis at 96 wk in 68%[7] Less fibrosis after SVR in 33%[9] Fibrosis stable in non-responders[6,9] Reversal of cirrhosis possible[10] Fewer complications of cirrhosis[10] Better transplant-free survival[10]
Corticosteroids	Inhibit NF-κB by stimulating IκB[85] Deplete pro-inflammatory factors[86] Decrease adhesion molecules[84,87] Increase lymphocyte apoptosis[88] Reduce production of ROS[49] Suppress metalloproteinase inhibitors[90] Decrease TGFβ1 activity[91-93] Impair activation of HSC[94]	Less fibrosis in 57%[11] Reversal of cirrhosis[12,13] Less or stable fibrosis in 79%[14] Inflammation increases fibrosis[3,14] Cirrhosis survival improved[11,18,165]
Cyclosporine (calcineurin inhibitors)	Reduce cytokines and growth factors[162] Decrease lymphocyte proliferation[97,162] Inhibit TGFβ and interleukin-4[164]	Decreased hepatic fibrosis score[15] Reduced inflammation score[15]
Azathioprine	Deplete purine-based nucleotides[98-100] Impair lymphocyte proliferation[98] Increase lymphocyte apoptosis[105,106] Deplete NK cells[107] Suppress pro-inflammatory genes[108]	Conjectural anti-fibrotic effects[97] Used mainly with steroids[97,109] Possibly protective after relapse[110]
Mycophenolate mofetil	Inhibit lymphocyte proliferation[112,113] Increase lymphocyte apoptosis[112,113] Decrease adhesion molecules[112,113] Inhibit fibroblast proliferation[114] Reduce iNOS production[112,113]	Unproven anti-fibrotic effects[97]
Ursodeoxycholic acid	Limit apoptosis of hepatocytes[138] Decrease oxidative stress[139] Reduce TGFβ1 signaling in HSC[140]	Varied anti-fibrotic effects[118,120,125] Slows fibrosis progression[126]

BA: Bile acids; HSC: Hepatic stellate cells; IκB: Inhibitor of nuclear factor kappa B; NF-κB: Nuclear factor kappa B; NK: Natural killer; ROS: Reactive oxygen species; SVR: Sustained virological response; TGFβ1: Transforming growth factor beta 1.