Goals of Therapy for ALGS

William F. Balistreri, MD: Jennifer, I’ll come back to you. We talked about the overall goals, growth, development, and progression of liver disease. Tell us a little about that and how that varies from patient to patient over the different age ranges.

Jennifer M. Vittorio, MD: The goals of therapy are so interesting when we talk about Alagille [syndrome] because one of the themes of this talk has been the wide variability that we see among these patients. Medical management early on is usually aimed at cholestatic liver disease, which sometimes can be of variable severity. There are a handful of patients in whom we see that this may stabilize or even resolve by the time they’re school age. But for those patients who go on to have unremitting cholestasis—Dr [Philip] Rosenthal has already mentioned the focus on fat malabsorption, failure to thrive, bone risks—it’s almost like there are 2 areas of focus: the optimization of medical health and the focus on quality of life. Sometimes the 2 are intertwined. We’ll get to pruritus in a bit, but a lot of us as providers have historically struggled to control those symptoms in a way that’s acceptable to our patients and their caretakers. Hopefully we’re looking at some changes coming.

When medical therapy fails, a lot of times conversations start to focus more on biliary diversion surgeries and liver transplantations. When we’re talking about quality of life, those are things that are sometimes unacceptable to many individuals. I’ve certainly had families that have been very hesitant, sometimes from personal experience—we talked about how this is a disease that’s inherited—so there may be some personal stories that have them skeptical or hesitant to undergo anything invasive. I sometimes look at this as a 2-wave hit, so to speak. Early on, it seems to be cholestatic disease. Then as they hit adolescence and maybe even young adulthood, we’re talking more about progressive portal hypertension and whatnot. We’ve already alluded to how, a little contrary to what we thought in the past, a lot of patients aren’t maintaining their own liver as they reach young adulthood. The rates of transplantation are much higher than we had appreciated before.

William F. Balistreri, MD: Then there’s the later onset of a renal injury, which is often not manifest early in life, except for maybe some mild RTA [renal tubular acidosis].

TRANSCRIPT EDITED FOR CLARITY