TY - JOUR
T1 - Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis
AU - Deneau, Mark R.
AU - Mack, Cara
AU - Abdou, Reham
AU - Amin, Mansi
AU - Amir, Achiya
AU - Auth, Marcus
AU - Bazerbachi, Fateh
AU - Marie Broderick, Anne
AU - Chan, Albert
AU - DiGuglielmo, Matthew
AU - El-Matary, Wael
AU - El-Youssef, Mounif
AU - Ferrari, Federica
AU - Furuya, Katryn N.
AU - Gottrand, Frederic
AU - Gupta, Nitika
AU - Homan, Matjaž
AU - Jensen, M. K.
AU - Kamath, Binita M.
AU - Mo Kim, Kyung
AU - Kolho, Kaija Leena
AU - Konidari, Anastasia
AU - Koot, Bart
AU - Iorio, Raffaele
AU - Martinez, Mercedes
AU - Mohan, Parvathi
AU - Palle, Sirish
AU - Papadopoulou, Alexandra
AU - Ricciuto, Amanda
AU - Saubermann, Lawrence
AU - Sathya, Pushpa
AU - Shteyer, Eyal
AU - Smolka, Vratislav
AU - Tanaka, Atsushi
AU - Valentino, Pamela L.
AU - Varier, Raghu
AU - Venkat, Veena
AU - Vitola, Bernadette
AU - Vos, Miriam B.
AU - Woynarowski, Marek
AU - Yap, Jason
AU - Miloh, Tamir
N1 - Publisher Copyright:
© 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85062720274
U2 - 10.1002/hep4.1251
DO - 10.1002/hep4.1251
M3 - Article
AN - SCOPUS:85062720274
SN - 2471-254X
VL - 2
SP - 1369
EP - 1378
JO - Hepatology Communications
JF - Hepatology Communications
IS - 11
ER -