Table 2.
New and future treatments for alcohol-related hepatitis
| Mechanism of action | Method | Evidence | Current trialsa |
|---|---|---|---|
| Inhibition of oxidative stress | N-acetyl cysteine (NAC) +corticosteroids | NAC (IV 5 days) + corticosteroids significantly reduced mortality at 1 month vs steroids alone | Current trial of intravenous NAC + corticosteroids vs corticosteroids alone NCT02971306 |
| S-adenosylmethionine | Promising in small studies only, trials required | ||
| Blockade of apoptosis | ASK-1 (apoptosis signal-regulating kinase-1) inhititor GS-4997/selonsertib | Current trial ASK-1 inhibitor +corticosteroids NCT02854631 | |
| Reducing inflammation | Anti-tumour necrosis factor alpha | Increased mortality in clinical trials | |
| Bile acids | Obeticholic acid (Farnesoid R receptor [FXR] analogue) | In mice models cholic acid stimulates liver growth, response lost in FXR-/- mice | |
| Regeneration | Granulocyte colony stimulating factor (GCSF) | Improved survival vs placebo in pilot trial | Current trials of GCSF alone, in combination with NAC, or in null/partial responders to corticosteroid |
| Recombinant human IL-22, F-652) | Cytokine IL-22 induces liver regeneration | Current trial (TREAT 008), NCT02655510 | |
| Stem cell transplant | No survival benefit / improvement in liver function in randomised controlled trial | ||
| Modulation of gut microbiota | Probiotics | Current trial NCT02335632 | |
| Rifaximin | NCT02485106 | ||
| Faecal transplant | NCT02458079 | ||
| Transplant | Early salvage liver transplant | Initial trial improved survival in patients with alcohol-related hepatitis not responding to steroids (77% vs 25% matched controls) | Current trial NCT01756794 |
| Prophylactic antibiotics | Amoxicillin/co-amoxiclav | Current trial NCT02281929 |
aTrial details can be found at ClinicalTrials.gov