Treatment of Cholestatic Liver Diseases

Introduction to Cholestatic Liver Diseases

• Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), require specific treatment approaches to manage symptoms and slow disease progression 1, 2, 3

Diagnosis and Monitoring

• In neonatal hyperbilirubinemia, total bilirubin should be measured every 12 hours until levels <10 mg/dL are reached 1
• In chronic cholestasis, liver function tests should be performed every 3 months in stable patients 1
• Patients on UDCA therapy should be monitored with liver function tests every 3 months in stable patients, assessment of response at 12 months after initiation, and annual monitoring of fat-soluble vitamins (A, D, E, K), as stated by the American Gastroenterological Association 4

Treatment of Primary Biliary Cholangitis (PBC)

• The British Society of Gastroenterology recommends ursodeoxycholic acid (UDCA) be given lifelong at a dose of 13-15 mg/kg/day in patients with PBC to prevent recurrence after liver transplantation and improve long-term outcomes 2
• UDCA has been shown to improve biochemical parameters and histological characteristics, and delay disease progression in PBC, with the established first-line treatment being UDCA at 13-15 mg/kg/day, as recommended by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases 5
• UDCA therapy has been shown to significantly reduce liver transplantation or death in patients with PBC, with the most pronounced benefit in patients with moderate to severe disease, as recommended by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases 5
• UDCA works through several mechanisms in PBC, including protection of injured cholangiocytes against toxic effects of bile acids, stimulation of impaired hepatocellular secretion, enhancement of ductular alkaline choleresis, and inhibition of bile acid-induced hepatocyte and cholangiocyte apoptosis, according to the American Association for the Study of Liver Diseases 5
• UDCA therapy in PBC results in significant decreases in serum bilirubin, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), reduction in cholesterol and immunoglobulin M levels, as stated by the European Association for the Study of the Liver 5

Treatment of Primary Sclerosing Cholangitis (PSC)

• The British Society of Gastroenterology strongly recommends against routine use of UDCA in newly diagnosed PSC patients 3
• High doses (28-30 mg/kg/day) of UDCA may be harmful in PSC patients, as warned by the European Society of Gastrointestinal Endoscopy and the British Society of Gastroenterology 3
• Guidelines explicitly recommend against the routine use of UDCA for newly diagnosed PSC, as stated by the European Society of Gastrointestinal Endoscopy and the American Gastroenterological Association 3, 6

Treatment of Overlap Syndromes

• For PBC-AIH overlap syndrome, combined therapy with corticosteroids and low-dose UDCA (13-15 mg/kg/day) is recommended 7
• For PSC-AIH overlap syndrome, combined therapy with corticosteroids and low-dose UDCA has been endorsed, though evidence is limited 7

Treatment of Cholestasis in Pregnancy

• The American College of Radiology recommends considering ursodeoxycholic acid (UDCA) for the treatment of pruritus in pregnant women with serum bile acid concentrations >40 μmol/L to reduce the risk of spontaneous preterm birth and may protect against fetal death 1
• UDCA should be continued during pregnancy in women with PBC as it is safe in pregnancy and breastfeeding, according to the European Association for the Study of the Liver 1

Dosing and Administration of UDCA

• The recommended dose of UDCA in neonates is 10 mg/kg/día divided every 12 hours 1
• In adults with cholestasis, the recommended dose is 13-15 mg/kg/día 1
• Moderate doses of UDCA (10-15 mg/kg/day) are preferable to high doses, which have shown potential harm in other cholestatic conditions, as suggested by the European Association for the Study of the Liver 5, 3
• The Journal of Crohn's and Colitis suggests that the dose of UDCA should not exceed 20 mg/kg/día in chronic liver disease due to potential adverse effects 8

Second-Line Therapy and Management of Symptoms

• Obeticholic acid is approved as second-line therapy (in combination with UDCA) for patients with incomplete response or as monotherapy for those intolerant to UDCA, as stated by the American Gastroenterological Association 9
• UDCA has limited effect on symptoms like fatigue or pruritus, and additional management strategies are required, such as first-line use of Bezafibrate or cholestyramine for pruritus, as recommended by the American Association for the Study of Liver Diseases 4