Alcohol-related liver disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Larsucosterol

Larsucosterol, an endogenous epigenetic modulator, regulates gene expression patterns without affecting the DNA sequence.[145] It has been granted breakthrough therapy designation by the US Food and Drug Administration (FDA) for the treatment of patients with severe alcohol-associated hepatitis based on data from the phase 2B AHFIRM trial.[146][147] Larsucosterol showed a significant reduction in 90-day mortality, compared with placebo, and was well tolerated at different doses studied in the trial.[147]

Granulocyte-colony stimulating factor (G-CSF)

G-CSF is a glycoprotein that stimulates the bone marrow to release neutrophils and stem cells (CD34+) into the bloodstream. One open-label study of 57 patients with severe alcohol-related hepatitis found that G-CSF improves liver function and increases survival times compared with an 800-2000 kcal/day diet plus pentoxifylline.[148] One systematic review and meta-analysis reported improved 90-day survival with G-CSF compared with standard medical therapy.[149] Another systematic review and meta-analysis concluded that despite its ability to improve prognosis in patients with severe alcohol-related hepatitis, G-CSF is not recommended in Europe owing to high heterogeneity due to conflicting findings between Asian and European studies.[150] Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear. Further studies are needed to better define the utility of G-CSF in severe alcohol-related hepatitis.

Extracorporeal cellular therapy

In an extracorporeal cellular therapy (ELAD) study, hepatoblastoma-derived C3A cells (that express anti-inflammatory proteins and growth factors) failed to improve overall survival in patients with severe alcohol-related hepatitis.[151] Subgroup analysis suggested that further investigation of ELAD in younger patients (aged <46.9 years) with a model for end-stage liver disease (MELD) score of less than 28 may be warranted.

Faecal microbiota transplantation (FMT)

In one pilot study, one week of FMT (from healthy donors) improved indices of liver disease and survival (at 12 months) among patients with severe alcohol-related hepatitis who were ineligible for corticosteroid therapy.[152] Larger controlled studies with long-term follow-up are needed.

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