Table 6.

Treatment of Manifestations in Individuals with ATP8B1 Deficiency

Manifestation/ConcernTreatmentConsiderations/Other
Cholestasis Severe ATP8B1 deficiency PharmacotherapyIneffective
Surgical interruption of enterohepatic circulation 1, 2
  • Can incl partial/total external diversion, partial/total internal diversion, or ileal exclusion
  • Primary surgical therapy; can ↓ pruritus & slow or reverse progression to hepatic fibrosis
  • Consider LTX if cirrhosis is present.
LTX considered when liver disease progresses to decompensated cirrhosis
  • In some LTX constitutes definitive therapy; in others secretory diarrhea in absence of steatorrhea continues or worsens after LTX
  • Consideration of diversion at time of transplantation to mitigate post-transplant diarrhea & steatohepatitis 3
Mild-to-moderate ATP8B1 deficiency Nasobiliary drainage 4 & extracorporeal liver support 5May hasten end of episode of cholestasis
Surgical interruption of enterohepatic circulationBenefit is unknown
LTXDifficult to justify
Pruritus Severe ATP8B1 deficiency Choleretic agents (e.g., phenobarbital & UDCA, cholestyramine, rifampin, antihistamines, carbamazepine, sertraline, naltrexone, UVB light therapy, plasmapheresis)
  • Relatively ineffective & do not alter progression to end-stage liver disease.
  • Future efforts focusing on real-world experience w/recently FDA-approved IBAT inhibitors are needed. 6
Mild-to-moderate ATP8B1 deficiency Rifampicin, UDCA, sertraline, 7 naltrexone, 8 & bile acid binding resinMay be efficacious 9
Secretory diarrhea May require IV fluids
  • Bile acid chelators 10 may ameliorate diarrhea after LTX, as they may divert bile produced by allograft away from the native gut. 11
  • Clonidine has palliated diarrhea after LTX in some persons. 12
  • Consider diversion at time of transplantation to mitigate post-transplant diarrhea & steatohepatitis. 3
Poor growth Medium-chain triglyceride-based formulas
  • May prevent &/or treat growth failure
  • Nasogastric tube feeding has been helpful in some.
  • May not be responsive to LTX
Nutritional deficiencies (incl vitamins A, D, E, K) Fat-soluble vitamin supplementation to alleviate malabsorption of fat-soluble vitamins
  • Preparations of vitamin E (e.g., tocopheryl polyethylene glycol-1000 succinate) are useful in severe cholestasis.
  • Vitamin K administration in newborn period (1st 28 days of life) is essential.
Sensorineural hearing loss Habituation per treating audiologist
Pancreatitis or pancreatic exocrine insufficiency
  • Supportive care for acute pancreatitis episodes
  • Replacement therapy for insufficiency if documented

IBAT = ileal bile acid transporter; LTX = liver transplantation; UDCA = ursodeoxycholic acid

1.

In partial external biliary diversion the gallbladder apex is anastomosed to one end of a segment of bowel while the other end is used to create a cutaneous stoma from which bile is then drained and discarded, thus, interrupting the enterohepatic circulation of bile acids and reducing pruritus.

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From: ATP8B1 Deficiency

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