H epatic encephalopathy (HE) is a common and debilitating complication of end-stage liver cirrhosis. It is associated with poor quality of life, a significant burden on health care, and increased mortality. Ammonia generated by the enteric bacteria is a critical driver of HE. 1 The current treatment is lactulose and/or rifaximin, both of which target the gut microbiota. 2,3 As dysbiosis is thought to contribute to HE, we hypothesized that manipulating the gut microbiome through fecal microbiota transplantation (FMT) could reverse intestinal dysbiosis and result in cognitive improvement in overt HE. Health Canada approval was obtained to proceed with the study.
Case ReportWe treated a 57-year-old man suffering from grade 1-2 HE with liver cirrhosis (Model for End-Stage Liver Disease score 5 10) secondary to alcohol and hepatitis C. He had previously responded well to lactulose and rifaximin but could no longer afford rifaximin when Health Canada ended its compassionate release program. His subjective baseline assessment by his caregivers and health care team found him lethargic, with sleep-wake cycle reversal, slow reaction time, and intermittent disorientation for time. After obtaining informed consent, he was given five weekly FMTs from a universal stool donor registered with our FMT program, the first administered by colonoscopy and the remaining four by retention enema. Subjective and objective changes in mental status were assessed weekly, including use of the inhibitory control test (ICT) and the Stroop test. Random serum ammonia levels were measured at each visit. The patient was instructed to keep his diet and lactulose dose similar during the study. Within the first week of treatment, objective measures of reaction time, Stoop test, serum ammonia, and quality of life all significantly improved. Subjectively the patient reported improved appetite, alertness, and overall well-being. Unfortunately, he missed his second FMT, and these parameters deteriorated. Following further FMT, he continued to improve as he became more alert, with better ability to concentrate and follow instructions and improved sleep-wake cycle. All of these changes were noted by the study team and corroborated by his caregivers. Objectively, his ICT and Stroop test scores normalized by week 4. The patient unfortunately developed gallstone pancreatitis and required hospitalization for pain control at week 10, when he was noticeably more encephalopathic. By week 14, his ICT and Stroop scores had reverted to baseline. Table 1 summarizes the changes in ICT, Stroop test, and random serum ammonia levels in relation to FMT. No adverse events or infectious complications related to FMT occurred.Stool samples were obtained from the patient before FMT and 1 week following each FMT. A final sample was obtained at 7 weeks. Microbial DNA was extracted using the FastDNA Spin kit for Feces (MP Biomedicals, Solon, OH) and used for whole genome shotgun sequencing. Metagenome libraries were constructed using the Nextera XT (Illumina) protocol. Libraries...
