Molecular targets in the treatment of alcoholic hepatitis

Table 1 Summary of mechanism of action and existing evidence about potential future molecular targets for the treatment of severe alcoholic hepatitis

Treatment	Mechanism of action	Clinical evidence
rhu IL-10	Suppression of pro-inflammatory cytokines, e.g., TNFα	Phase 2 study in severe AH with concomitant glucocorticoids showed no significant difference in mortality or levels of IL-8 and TNFα[74]
	Suppression of reactive oxygen species
rhu IL-22	Increased levels of anti-inflammatory IL-22 Reduced oxidative stress	Reduced liver injury in ethanol-fed rat model[76] and acute hepatitis mouse model[77]. No studies in human liver disease yet reported
Anti-IL-8 antibody	Reduced neutrophil recruitment to liver	Phase 2 studies in COPD demonstrated reduced dyspnea[103]. No studies in human liver disease have yet been reported
rhu hepatocyte growth factor	Reduced hepatocyte apoptosis	HGF levels correlate with outcome in severe AH[81]. Well tolerated in a small phase 1/2 trial in fulminant hepatitis but no clear clinical benefit was seen[104]
Basiliximab (anti-CD25 antibody)	Reduced T cell proliferation and subsequent pro-inflammatory cytokine production	Reverses in vitro glucocorticoid resistance in patients with severe AH[42]. No clinical trials yet conducted in liver disease
Secukinumab (anti-IL-17A antibody)	Reduced pro-inflammatory IL-17A	Well tolerated in patients with rheumatoid arthritis, psoriasis or uveitis[93]. No clinical benefit in crohn’s disease[94]. No clinical trial yet reported in liver disease
Anti-CXCL10 antibody	Reduced Th1 cell recruitment to liver	CXCR3 (receptor for CXCL10) is elevated in patients with chronic hepatitis C infection[95]. Phase 2 clinical trial is underway in patients with PBC

rhu: Recombinant human; AH: Alcoholic hepatitis; TNFα: Tumor necrosis factor-α; HGF: Hepatocyte growth factor; PBC: Primary biliary cirrhosis; IL: Interleukin; COPD: Chronic obstructive pulmonary disease.