Fecal Microbiota Transplantation in the Management of Mild Overt Hepatic Encephalopathy: A Case Report: Presidential Poster

Abstract

Background: Hepatic encephalopathy (HE) is one of the most common complications of end stage liver cirrhosis. Although the precise pathophysiology of HE is not well defined, data suggest that ammonia (NH3) generated by the enteric bacterial flora is the critical driver of this process. The microbiota in patients with liver cirrhosis is altered compared to healthy controls, and they have more urease-producing bacteria associated with increased NH3 production. The standard of care in patients who have recurrent HE is rifaximin and/or lactulose. Although effective, many patients continue to suffer from breakthrough HE. It is possible that fecal microbiota transplantation (FMT) may overcome the limitations of probiotics in reversing dysbiosis associated with HE, leading to clinical improvement. Methods: We treated a 57 year-old man suffering from low grade persistent HE with liver cirrhosis (MELD score of 10) secondary to alcohol and hepatitis C in this pilot study. He had previously responded well to lactulose and rifaximin. His rifaximin was stopped when Health Canada ended the compassionate release program. He had chronic Grade I-II HE despite being on lactulose, limiting his daily functionings. He was given 5 weekly FMT, with the first one administered by colonoscopy and the remaining 4 by retention enema. Changes in mental status were assessed by both inhibit control test (ICT) and Stroop test. Stool samples were obtained from the patient 1 day before FMT and 1 week following each FMT. A final sample was obtained at 7 weeks following the final FMT. Microbial DNA was extracted and used for whole genome shotgun sequencing. Results: Within the first week of treatment, objective measures of reaction time, Stroop test, serum ammonia level, patient reported cognition and appetite were significantly improved. Unfortunately he missed his 2nd FMT, and these parameters deteriorated. Following further 3 weekly FMT, he continued to improve, with ICT and Stroop test scores within normal range by week 4. Table 1 summarizes the changes in ICT, Stroop test and serum NH3 levels over time in relation to FMT. No adverse events or infectious complications related to FMT administration were observed. Fig 1A and 1B demonstrated the fecal microbial changes before and after FMT.Figure 1Table 1: Changes in ICT, Stroop test and serum NH3 levels over time in relation toConclusion: This proof-of-concept, pilot case study suggests that manipulating the gut microbiome through FMT can transiently reverse intestinal dysbiosis associated with HE, resulting in temporary cognitive improvement in persistent low grade HE. In addition, microbial analysis demonstrated decreased Bacteroidaceae and Streptococcaceae following FMT, both of which have been associated with hepatic encephalopathy and urease production. This finding is promising and warrants further investigation.Figure 2