Rare Liver Diseases: 8 recent reports on PSC, PBC, PFIC, biliary atresia

While many researchers and pharmaceutical companies focus attention in hepatology on diseases with the highest prevalence, such as viral hepatitis and complications related to fatty liver disease, others focus on rare liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, progressive familial intrahepatic cholestasis and biliary atresia.

In recognition of Rare Disease Day, Healio Gastroenterology and Liver Disease presents the following reports that include a safety study of fecal microbiota transplantation in patients with PSC, demographics that may affect ursodeoxycholic acid outcomes for PBC, the current PFIC pipeline, and risk factors in biliary atresia cases.

FMT safe for patients with PSC, may lower ALP

Fecal microbiota transplantation in patients with primary sclerosing cholangitis was safe and may improve alkaline phosphatase levels, according to a study from The American Journal of Gastroenterology.

“It has been postulated that bacteria may stimulate an aberrant immune response resulting in the perpetuation of the biliary inflammation seen in PSC,” Jessica R. Allegretti, MD, MPH, from the Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues wrote. “Restoration of the microbiome is a reasonable target for therapy in PSC because there is no treatment, given the complexity of PSC-[inflammatory bowel disease] and the known interactions between genes, mucosal immunity, immune cell tracking, and the microbiome.” Read more

PSC Partners joins Komodo Health to improve patient care systems

The nonprofit organization PSC Partners Seeking a Cure announced a partnership with Komodo Health to develop improved patient care for those with primary sclerosing cholangitis, according to a press release.

“As an organization advocating for patients and caregivers impacted by primary sclerosing cholangitis, we are excited to be working with Komodo Health, because we are eager to expand our outreach and increase our exposure to better serve our community,” Ricky Safer, CEO of PSC Partners, said in the release. “We anticipate that Komodo Health’s platform will enable us to make great strides in our search for improved treatments, and, eventually, a cure for PSC.” Read more

PBC recurrence after liver transplantation decreases survival rates

Primary biliary cholangitis recurrence after liver transplantation reduced the likelihood for graft and overall survival, according to a recently published study. Younger patients and those with a history of tacrolimus use and cholestasis were more likely to experience PBC recurrence posttransplant.

“Prior reports have also suggested that the development of PBC recurrence has no significant impact on long-term patient survival or need for a second LT, and thus its clinical impact has been questioned,” Aldo J. Montano-Loza, PhD, from the University of Alberta, and colleagues wrote. “Our results imply that patients at higher risk of recurrence of PBC should be considered for therapeutic strategies within the first year of LT to prevent occurrence of PBC recurrence.” Read more

Age, not sex affects UDCA response in patients with PBC

Older and increasing age among patients with primary biliary cholangitis correlated with a better response to ursodeoxycholic acid treatment and lower rates of liver transplantation and mortality compared with younger age, whereas sex did not affect outcomes, according to a recently published study.

“Our data suggests that younger patients should be monitored carefully, with early consideration for additional therapies, as they appear to be at greatest risk of biochemical non-response to UDCA, liver transplantation, and death,” Angela C. Cheung, MD, from the Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “The presence of more overt biochemical hepatic activity suggests a more aggressive and inflammatory phenotype in younger, compared to older patients.” Read more

Albireo receives FDA orphan drug designation for biliary atresia therapy

Albireo Pharma received FDA orphan designation for its lead product candidate A4250, an ileal bile acid transporter inhibitor for the treatment of biliary atresia, according to a press release.

A4250 previously received an orphan drug designation from the European Commission for biliary atresia and an orphan drug designation from both the FDA and European Commission for the treatment of progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome, and primary biliary cholangitis. Read more

VIDEO: Albireo CEO discusses cholestatic therapy pipeline

In this exclusive video perspective from The Liver Meeting 2018, Ron Cooper, president and CEO of Albireo Pharma, discusses the company’s ongoing research into treatments for pediatric cholestatic diseases, nonalcoholic steatohepatitis and bile acid malabsorption disease.

“Albireo Pharma is a company that’s focused in areas of high, unmet medical need in the liver and GI space,” Cooper told Healio Gastroenterology and Liver Disease. “We use our expertise in bile acids and bile acid modulation to produce some pretty interesting product candidates. Read more

Portal hypertension predicts variceal hemorrhage in biliary atresia

Results of a prospective longitudinal analysis showed that the incidence of gastroesophageal variceal hemorrhage in children with biliary atresia was lower than previously described, and that gastroesophageal variceal hemorrhage was more common in patients with features of portal hypertension, according to a presentation at Digestive Disease Week 2018.

“The limitations of previous studies of variceal hemorrhage in biliary atresia include the fact that they were often single center, of retrospective design, and previous mortality rates do not account for improvements in care of patients with biliary atresia with variceal hemorrhage,” Lee Bass, MD, from the Ann & Robert H. Lurie Children’s Hospital of Chicago, said in his presentation. “[Our network] provides the opportunity for further characterization of natural history and risk factors impacting variceal hemorrhage.” Read more

Young age, high MELD increases waitlist mortality in pediatric biliary atresia cases

MELD score higher than 20 and age younger than 6 months correlated significantly with 2-year mortality among pediatric patients with biliary atresia on the liver transplantation waitlist, according to recently published data.

“Biliary atresia (BA) is an obstructive cholangiopathy that usually arises in the perinatal period,” H.P.J. van der Doef, MD, PhD, from the University of Groningen, the Netherlands, and colleagues wrote. “The overall prognosis of BA patients is greatly affected by mortality before transplantation. We are confident that our prognostic model based on age and MELD score at listing allows a reliable classification of infants with BA into risk groups with different prognoses.” Read more

While many researchers and pharmaceutical companies focus attention in hepatology on diseases with the highest prevalence, such as viral hepatitis and complications related to fatty liver disease, others focus on rare liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, progressive familial intrahepatic cholestasis and biliary atresia.

In recognition of Rare Disease Day, Healio Gastroenterology and Liver Disease presents the following reports that include a safety study of fecal microbiota transplantation in patients with PSC, demographics that may affect ursodeoxycholic acid outcomes for PBC, the current PFIC pipeline, and risk factors in biliary atresia cases.

FMT safe for patients with PSC, may lower ALP

Fecal microbiota transplantation in patients with primary sclerosing cholangitis was safe and may improve alkaline phosphatase levels, according to a study from The American Journal of Gastroenterology.

“It has been postulated that bacteria may stimulate an aberrant immune response resulting in the perpetuation of the biliary inflammation seen in PSC,” Jessica R. Allegretti, MD, MPH, from the Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues wrote. “Restoration of the microbiome is a reasonable target for therapy in PSC because there is no treatment, given the complexity of PSC-[inflammatory bowel disease] and the known interactions between genes, mucosal immunity, immune cell tracking, and the microbiome.” Read more

PSC Partners joins Komodo Health to improve patient care systems

The nonprofit organization PSC Partners Seeking a Cure announced a partnership with Komodo Health to develop improved patient care for those with primary sclerosing cholangitis, according to a press release.

“As an organization advocating for patients and caregivers impacted by primary sclerosing cholangitis, we are excited to be working with Komodo Health, because we are eager to expand our outreach and increase our exposure to better serve our community,” Ricky Safer, CEO of PSC Partners, said in the release. “We anticipate that Komodo Health’s platform will enable us to make great strides in our search for improved treatments, and, eventually, a cure for PSC.” Read more

PBC recurrence after liver transplantation decreases survival rates

Primary biliary cholangitis recurrence after liver transplantation reduced the likelihood for graft and overall survival, according to a recently published study. Younger patients and those with a history of tacrolimus use and cholestasis were more likely to experience PBC recurrence posttransplant.

“Prior reports have also suggested that the development of PBC recurrence has no significant impact on long-term patient survival or need for a second LT, and thus its clinical impact has been questioned,” Aldo J. Montano-Loza, PhD, from the University of Alberta, and colleagues wrote. “Our results imply that patients at higher risk of recurrence of PBC should be considered for therapeutic strategies within the first year of LT to prevent occurrence of PBC recurrence.” Read more

Age, not sex affects UDCA response in patients with PBC

Older and increasing age among patients with primary biliary cholangitis correlated with a better response to ursodeoxycholic acid treatment and lower rates of liver transplantation and mortality compared with younger age, whereas sex did not affect outcomes, according to a recently published study.

“Our data suggests that younger patients should be monitored carefully, with early consideration for additional therapies, as they appear to be at greatest risk of biochemical non-response to UDCA, liver transplantation, and death,” Angela C. Cheung, MD, from the Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “The presence of more overt biochemical hepatic activity suggests a more aggressive and inflammatory phenotype in younger, compared to older patients.” Read more

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Albireo receives FDA orphan drug designation for biliary atresia therapy

Albireo Pharma received FDA orphan designation for its lead product candidate A4250, an ileal bile acid transporter inhibitor for the treatment of biliary atresia, according to a press release.

A4250 previously received an orphan drug designation from the European Commission for biliary atresia and an orphan drug designation from both the FDA and European Commission for the treatment of progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome, and primary biliary cholangitis. Read more

VIDEO: Albireo CEO discusses cholestatic therapy pipeline

In this exclusive video perspective from The Liver Meeting 2018, Ron Cooper, president and CEO of Albireo Pharma, discusses the company’s ongoing research into treatments for pediatric cholestatic diseases, nonalcoholic steatohepatitis and bile acid malabsorption disease.

“Albireo Pharma is a company that’s focused in areas of high, unmet medical need in the liver and GI space,” Cooper told Healio Gastroenterology and Liver Disease. “We use our expertise in bile acids and bile acid modulation to produce some pretty interesting product candidates. Read more

Portal hypertension predicts variceal hemorrhage in biliary atresia

Results of a prospective longitudinal analysis showed that the incidence of gastroesophageal variceal hemorrhage in children with biliary atresia was lower than previously described, and that gastroesophageal variceal hemorrhage was more common in patients with features of portal hypertension, according to a presentation at Digestive Disease Week 2018.

“The limitations of previous studies of variceal hemorrhage in biliary atresia include the fact that they were often single center, of retrospective design, and previous mortality rates do not account for improvements in care of patients with biliary atresia with variceal hemorrhage,” Lee Bass, MD, from the Ann & Robert H. Lurie Children’s Hospital of Chicago, said in his presentation. “[Our network] provides the opportunity for further characterization of natural history and risk factors impacting variceal hemorrhage.” Read more

Young age, high MELD increases waitlist mortality in pediatric biliary atresia cases

MELD score higher than 20 and age younger than 6 months correlated significantly with 2-year mortality among pediatric patients with biliary atresia on the liver transplantation waitlist, according to recently published data.

“Biliary atresia (BA) is an obstructive cholangiopathy that usually arises in the perinatal period,” H.P.J. van der Doef, MD, PhD, from the University of Groningen, the Netherlands, and colleagues wrote. “The overall prognosis of BA patients is greatly affected by mortality before transplantation. We are confident that our prognostic model based on age and MELD score at listing allows a reliable classification of infants with BA into risk groups with different prognoses.” Read more

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