Open AccessGamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis
Author(s) -
Deneau Mark R.,
Mack Cara,
Abdou Reham,
Amin Mansi,
Amir Achiya,
Auth Marcus,
Bazerbachi Fateh,
Marie Broderick Anne,
Chan Albert,
DiGuglielmo Matthew,
ElMatary Wael,
ElYoussef Mounif,
Ferrari Federica,
Furuya Katryn N.,
Gottrand Frederic,
Gupta Nitika,
Homan Matjaž,
Jensen M.K.,
Kamath Binita M.,
Mo Kim Kyung,
Kolho KaijaLeena,
Konidari Anastasia,
Koot Bart,
Iorio Raffaele,
Martinez Mercedes,
Mohan Parvathi,
Palle Sirish,
Papadopoulou Alexandra,
Ricciuto Amanda,
Saubermann Lawrence,
Sathya Pushpa,
Shteyer Eyal,
Smolka Vratislav,
Tanaka Atsushi,
Valentino Pamela L.,
Varier Raghu,
Venkat Veena,
Vitola Bernadette,
Vos Miriam B.,
Woynarowski Marek,
Yap Jason,
Miloh Tamir
Publication year - 2018
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1251
Subject(s) - medicine , ursodeoxycholic acid , primary sclerosing cholangitis , gastroenterology , liver transplantation , surrogate endpoint , clinical endpoint , gamma glutamyltransferase , adverse effect , biliary atresia , cohort , transplantation , clinical trial , disease , biochemistry , chemistry , enzyme
Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P = not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P = 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P = NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P < 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P = 0.005). Conclusion: A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.