New treatment options for alcoholic hepatitis

Table 1 Potential new avenues for research and therapy in severe alcoholic hepatitis

Gut microbiota modification

Antibiotics (luminal, systemic)

Prebiotics and probiotics

Fecal microbiota transplantation (FMT)

Blockade of LPS and its downstream pathways e.g., PD-1 and TIM-3 inhibition

Immune modulation

Chemokines e.g., CCL20 inhibition

IL-8, IL-17 inhibition

Recombinant IL-22, recombinant human IL-10

Osteopontin inhibition

TNF-alfa superfamily receptor modulation

ADAMTS 13 enhancement

Inhibition of complement activation

Inhibition of inflammasome activation

Increasing steroid sensitivity

E.g., Basiliximab, Theophylline

Modification of genetic polymorphism of alcohol metabolizing enzymes

Epigenetic modification of alcohol induced liver damage

Liver regeneration and Early liver transplantation

Granulocyte colony stimulating factor (G-CSF)

Liver transplantation (DDLT/LDLT)

Setting up of alcohol units for post transplant support

Others

Extracorporeal liver support

Granulocytopheresis

Anti-oxidants - N-Acetyl Cysteine, S-Adenosyl Methionine

Table 2 Ongoing registered studies on newer treatment for alcoholic hepatitis

Treatment	Type of molecule/intervention	Mechanism of action	Identifier
ELAD	Extracorporeal, human cell-based liver support system	Supplement hepatic function	NCT01829347, NCT00973817, NCT01471028
Obeticholic acid	Biliary acid	Affect bile acid abnormalities	NCT02039219
Corticosteroids + Bovine + Colostrum	Protein supplement	Improving immunity	NCT02473341
IMM 124-E	Hyperimmune bovine colostrum	Improving immunity	NCT01968382
G-CSF	Liver regeneration/immunomodulation	improves liver regeneration and immunity in steroid non-responders	NCT02442180, NCT02451033, NCT01820208
Corticosteroids + N-acetyl cysteine	Anti-oxidant	Augments steroid function	NCT00863785
Amoxicillin + corticosteroid	Antibiotic	Decreases infections	NCT02281929
S-adenosyl-l-methionine	Antioxidant	decreasing oxidative stress	NCT02024295
Rifaximin	Luminal antibiotic	Improves gut dysbiosis	NCT02116556, NCT02485106
Ciprofloxacin	Antibiotic	Decreasing infections	NCT02326103
Emricasan/IDN-6556	Pan-caspase inhibitor	Reduces apoptosis	NCT01912404
Lactobacillus Rhamnosus GG	Probiotic	Improving dysbiosis	NCT01922895
MycophenolateMofetil and Rilonacept	Immunosuppressant and immune modulation	Decreasing hepatic inflammation	NCT01903798
Metadoxine	Anti-oxidant		NCT02161653
Fecal microbiota transplantation	Healthy microbiome replacement	Correction of dysbiosis	NCT02458079
Early liver transplantation	New liver	Liver transplant in patients unresponsive to medical treatment	NCT01756794
Anakinra	interleukin-1 receptor antagonist	Decreases hepatic inflammation	NCT01809132