What is the recommended treatment for Autoimmune Hepatitis (AIH) - Primary Sclerosing Cholangitis (PSC) overlap syndrome?

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Last updated: June 17, 2025View editorial policy

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From the Guidelines

The recommended treatment for Autoimmune Hepatitis (AIH) - Primary Sclerosing Cholangitis (PSC) overlap syndrome is a combination of immunosuppressive therapy and ursodeoxycholic acid (UDCA), as suggested by the most recent guidelines 1.

Treatment Approach

The treatment approach for AIH-PSC overlap syndrome involves a dual strategy:

  • Immununosuppressive therapy to target the autoimmune inflammatory component
  • UDCA to target the cholestatic component

Immununosuppressive Therapy

Patients should generally receive prednisone starting at 30-40 mg daily, gradually tapered to the lowest effective dose (often 5-10 mg daily), along with azathioprine at 1-2 mg/kg/day as a steroid-sparing agent.

UDCA Therapy

UDCA should be administered at 13-15 mg/kg/day divided into 2-3 doses.

Monitoring and Surveillance

Regular monitoring of liver enzymes, including transaminases and alkaline phosphatase, is essential to assess treatment response, with laboratory tests recommended every 3-6 months once stable. Patients should also undergo periodic endoscopic screening for varices and surveillance for cholangiocarcinoma with imaging and CA 19-9 levels, as the PSC component carries these risks despite treatment.

Rationale

This combined therapeutic strategy aims to control inflammation, slow disease progression, and manage symptoms, though it may not completely halt the progression of the biliary disease associated with PSC. The use of UDCA in combination with immunosuppressive therapy has been endorsed by EASL guidelines 1, and has been shown to improve liver biochemistry and transplant-free survival in patients with AIH-PSC overlap syndrome 1.

Key Considerations

  • The treatment approach should be individualized based on disease severity and clinical cholestasis.
  • Patients with AIH-PSC overlap syndrome may have a better prognosis and transplant-free survival compared to those with classical PSC 1.
  • Regular monitoring and surveillance are crucial to assess treatment response and detect potential complications.

From the Research

Treatment of AIH-PSC Overlap Syndrome

The recommended treatment for Autoimmune Hepatitis (AIH) - Primary Sclerosing Cholangitis (PSC) overlap syndrome is empiric and includes:

  • Immunosuppressive therapy with or without ursodeoxycholic acid 2
  • Treatment of the dominant clinical feature first, with therapy adjusted according to the response 3
  • Individualized therapy, which may not be static 3

Key Considerations

  • The diagnosis of overlap syndrome requires prominent features of classic AIH and secondary objective findings of PSC 2
  • Patients with AIH-PSC overlap syndrome may have a progressive course toward cirrhosis and liver failure without adequate treatment 2
  • Liver transplantation is indicated for patients who have end-stage liver disease 2

Treatment Approach

  • The use of ursodeoxycholic acid for the cholestatic component and immunosuppressive agents for the hepatitic component, either simultaneously or sequentially 3
  • The International Autoimmune Hepatitis Group (IAIHG) suggests that patients with autoimmune liver disease should be categorized according to the predominating feature(s) as AIH, PBC, and PSC/small duct PSC, respectively, and that those with overlapping features are not considered as being distinct diagnostic entities 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis and management of overlap syndromes.

Clinics in liver disease, 2015

Research

Overlap Syndromes.

Digestive diseases (Basel, Switzerland), 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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