Table 3.
Treatment | Mechanism of action | Clinical trial outcomes | Side effects | Additional considerations |
---|---|---|---|---|
Corticosteroids (prednisolone, prednisone, methyl-prednisolone) | Anti-inflammatory | Reduction in short- to medium-term mortality, but increased risk of infections and no long-term mortality benefit | Weight gain, indigestion, sepsis, gastro-intestinal hemorrhage, restlessness | Controversial due to risks of sepsis and hemorrhage; effectiveness limited to short-term |
Pentoxifylline | Hemorrhagic agent | Initially showed short-term benefits; recent studies show no benefit | Gastro-intestinal complaints, dizziness, headaches, flushing | Controversial due to initial positive results; however, recent results showed no benefit |
Bovine colostrum (IMM-124E) | IgG to LPS, reduces bacterial translocation | Decrease in serum endotoxin levels at 7 months | Gastro-intestinal complaints, rash, unpleasant taste | Phase II, not recruiting |
Lactobacillus rhamnosus GG | Changes in gut microbiome | Decreased liver injury 1 month post-LGG therapy | Rash, pruritis, swelling, dizziness, throat swelling | RCT |
Amoxicillin-clavulanate | Interference with bacterial cell wall synthesis | No difference to prednisolone alone | Gastro-intestinal complaints, rash | RCT |
Anakinra (+ zinc) | IL-1 receptor antagonist; anti-inflammatory; immunomodulation | Survival at 6 months; improved outcomes in combination but not statistically significant mortality benefit | Infection risks given immunomodulatory effect | Combined with zinc and pentoxifylline in trials; requires further investigation |
Selonsertib (GS-4997) | ASK-1 antagonist, inhibits MAPK, JNK, p38 | Safety and serious adverse events at 28 days plus 30 days | Headache, nausea | Phase II, completed |
Emricasan (IDN-6556) | Pan-caspase inhibitor | Survival at 28 days | High-blood-level concerns, headache, nausea, fatigue | Study terminated after five patients |
Larsucosterol | Epigenetic modulator inhibiting DNA methylation | Reduces risk of mortality (41% reduction, P = 0.07) among AH patients | No unexpected serious adverse events | May now enter a Phase 3 trial with the goal of Food Drug Administration (FDA) approval in the near future |
Obeticholic acid (INT-747) | FXR activation, bile acid agonist, anti-inflammatory | Change in MELD score at 6 weeks | Pruritus, fatigue, gastro-intestinal disorders | Phase II, completed |
Metadoxine | Antioxidant; promotes abstinence; increases hepatic glutathione concentrations | Survival at 30 days; improved survival and sobriety rates in small trials | Nausea, upset stomach, diarrhea | Phase IV, recruiting; dual effects on liver health and sobriety maintenance promising but require larger studies |
IL-22 (F-652) | Anti-inflammatory and hepatic regeneration | Safety and serious adverse events at 42 days; preliminary data showed efficacy signals in a small cohort study | Dermal inflammation, ancanthosis | Phase I completed; Phase IIb RCT underway |
G-CSF (filgrastim) | Increases neutrophils, hepatic regeneration | Survival at 2 and 6 months depending on CS response; mortality benefit in small clinical studies | Bone pain, injection-site reactions | Phase IV, active and recruiting; results from larger trials are eagerly awaited |
Infliximab | TNF-α inhibitor | Improvement in Maddrey's score; increased infection risk | Increased risk of infections | Not recommended due to serious infection risk |
Etanercept | TNF-α inhibitor | Similar mortality rates to placebo at 1 month; increased 6-month mortality | Higher rate of serious infections | Not effective; poses a risk of serious infections |
N-acetylcysteine (NAC) | Antioxidants | Some promise shown in combination with steroids | Dry mouth, nausea, vomiting | Encouraging data; further studies needed |
Rifaximin | Antibiotic with low systemic absorption; targeting gut–liver axis; reduces endotoxin levels | Decreased endotoxin levels and hepatic venous pressure gradient; trend toward benefit in small pilot study | Generally well tolerated with low systemic absorption | Positive effects on liver hemodynamics; pilot study |
Betaine | Antioxidant and methionine metabolite | Improvement in hepatic steatosis in case reports | Diarrhea, nausea | Needs further study |
Granulocytapheresis | Removes activated granulocytes and monocytes | No benefit in case series of severe AH patients | Well tolerated without hemodynamic compromise | No clinical benefit observed |
AH = alcohol-associated hepatitis, IgG = immunoglobulin G, LPS = lipopolysaccharide, IL1 = interleukin 1, ASK-1 = apoptosis signal regulating kinase 1, MAPK = mitogen activated protein kinase, JNK = jun N terminal kinase, FXR = farnesoid receptor X, IL-22 = interleukin 22, TNF-α = tumor necrosis factor alpha, G-CSF = granulocyte stimulating factor.