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A single, oral treatment with fecal microbiota transplant was safe and well tolerated, and showed suggestive evidence of clinical improvement in patients with cirrhosis and recurrent hepatic encephalopathy in a phase 1 randomized study with 20 patients.

Mitchel L. Zoler/MDedge News
Dr. Jasmohan S. Bajaj

The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.

The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.


During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.

Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.

SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.

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A single, oral treatment with fecal microbiota transplant was safe and well tolerated, and showed suggestive evidence of clinical improvement in patients with cirrhosis and recurrent hepatic encephalopathy in a phase 1 randomized study with 20 patients.

Mitchel L. Zoler/MDedge News
Dr. Jasmohan S. Bajaj

The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.

The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.


During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.

Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.

SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.

A single, oral treatment with fecal microbiota transplant was safe and well tolerated, and showed suggestive evidence of clinical improvement in patients with cirrhosis and recurrent hepatic encephalopathy in a phase 1 randomized study with 20 patients.

Mitchel L. Zoler/MDedge News
Dr. Jasmohan S. Bajaj

The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.

The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.


During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.

Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.

SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.

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