Hepatic encephalopathy - Emerging treatments

Polyethylene glycol

Evidence from randomised controlled trials suggests that polyethylene glycol and lactulose may be similarly efficacious for the management of acute HE.[44][45] Further studies are needed before this treatment can be recommended routinely.

Extracorporeal albumin dialysis

Extracorporeal albumin dialysis (ECAD) is an artificial liver support system that dialyses blood against an albumin-enriched dialysate to remove albumin-bound toxins, in addition to bilirubin, aromatic amino acids, and water-soluble substances. Randomised controlled trials of ECAD have reported improvements in HE and 30-day survival compared with usual care.[46][47] This therapy is investigational and not widely available.

Probiotics

One Cochrane review found that probiotics probably improve recovery from HE, but give rise to little or no difference in all-cause mortality compared with placebo or no intervention.[48] The review was unable to determine whether probiotics are more effective than lactulose for HE. Included studies were at high risk for systematic error and random error (i.e., of low quality).[48] [ ]

Faecal microbiota transplant

Patients with HE have an altered gut microbiome, with a reduction in beneficial bacteria and an increase in potentially pathogenic bacteria. One open-label randomised trial (n=20) compared faecal microbiota transplantation with usual care.[49] The donor material was rich in Lachnospiraceae and Ruminococcaceae; these bacteria produce short-chain fatty acids that contribute to normal intestinal barrier function. There were fewer hospitalisations in the faecal microbiota transplant group than in the usual care group, particularly for portal hypertensive complications. The faecal microbiota transplant group demonstrated an improvement in cognitive function scores from baseline following transplant. There was no increase in bacterial infections in the faecal microbiota transplant group. One phase 1 clinical trial has reported that faecal microbiota is safe and well-tolerated in patients with recurrent HE and is associated with improved duodenal mucosal bacterial diversity.[50]

L-ornithine phenylacetate

Ammonia scavengers, such as L-ornithine phenylacetate (OPA), provide an alternative pathway to urea for waste nitrogen excretion. L-ornithine acts as a substrate for glutamine synthesis from ammonia, and the resulting glutamine is conjugated and excreted as phenylacetylglutamine in the urine.[51] One small open-label study reported that OPA is safe and well-tolerated in patients with decompensated cirrhosis. Plasma ammonia decreased and urinary phenylacetate excretion increased in the treatment group.[52] One Cochrane review concluded that there is currently insufficient evidence to determine the effects of ammonia scavengers on the prevention and treatment of HE in adults with cirrhosis.[53]