Summary
Autoimmune liver disease overlap syndromes are conditions that manifest with features of more than one autoimmune liver disease, most commonly autoimmune hepatitis (AIH) with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). These syndromes are considered clinical descriptions rather than distinct pathological entities. The AIH-PBC overlap syndrome is more common in women, while the AIH-PSC overlap syndrome is more common in younger men and is strongly associated with inflammatory bowel disease (IBD). Diagnosis of AIH-PBC overlap requires features of both conditions, including elevated transaminases and cholestatic liver injury, specific autoantibodies, and histology findings of interface hepatitis and florid bile duct lesions. Diagnosis of AIH-PSC overlap requires probable or definite AIH, negative antimitochondrial antibodies (AMA), and cholangiographic evidence of PSC. AIH-cholestatic syndrome is an autoimmune liver disease characterized by AIH with cholestatic liver injury that does not meet the diagnostic criteria for PBC or PSC. Treatment is directed at the predominant disease, typically involving combination therapy with ursodeoxycholic acid and immunosuppressants (e.g., glucocorticoids). Overlap syndromes are associated with an increased risk of cirrhosis, treatment failure, and a need for liver transplant.
Diagnostic approach
General principles [1]
- Consider overlap syndromes in patients with confirmed or suspected AIH and features of PBC or PSC.
- Assess for elevated transaminases and cholestatic enzymes.
- Evaluate for IBD.
- Confirmatory criteria or liver biopsy are often required.
Initial studies [1]
Interpretation [1]
| Test | AIH-PBC overlap syndrome | AIH-PSC overlap syndrome | AIH-cholestatic syndrome |
|---|---|---|---|
| MRCP or ERCP |
|
|
|
| AMA |
|
|
|
| ASMA |
|
|
|
Overlap syndromes are identified based on serology (AMA, ASMA) and cholangiography (MRCP or ERCP) findings.
Autoimmune hepatitis-primary sclerosing cholangitis overlap syndrome
Definition
AIH-PSC overlap syndrome is an autoimmune liver disease characterized by clinical, serological, and cholangiographic features of both AIH and PSC.
Epidemiology
-
Prevalence among patients with PSC [1][4]
- Adults: 5–14% [1][4]
- Children: up to 35% [4]
-
Prevalence among patients with AIH [1][2]
- Adults: 2–10% [1]
- 41% in patients with concurrent ulcerative colitis [1]
- Children: up to 50% [1][2]
- Typically affects younger populations (mean age of 25 years) [1]
- ♂ > ♀
Etiology [1]
- The exact etiology is unknown but likely involves genetic predisposition, environmental triggers, and/or altered immune regulation.
- Strongly associated with IBD, especially ulcerative colitis
Clinical features [1]
- Patients are typically asymptomatic at diagnosis.
- When present, symptoms may include:
Diagnosis
General principles [1][4]
- Suspect AIH-PSC overlap syndrome in patients with AIH who have concurrent IBD, unexplained elevated cholestatic liver enzymes, and/or inadequate response to glucocorticoid therapy.
- Refer to hepatology or gastroenterology for diagnosis.
- Diagnostic confirmation requires:
- Probable or definite AIH
- Negative AMA
- MRCP findings of multifocal bile duct strictures
- Concurrent IBD is common but not required for diagnosis.
Laboratory studies [1][4]
- ↑ ALK and GGT
- ↑ AST and ALT
- ↑ IgG and IgM
- Positive ANA and/or anti-smooth muscle antibodies (characteristic of AIH) [3]
- p-ANCA may be present.
- Negative AMA
Imaging [4]
- First line: MRI with MRCP
- Findings: multifocal intrahepatic and/or extrahepatic strictures alternating with normal or slightly dilated segments
Liver biopsy [4]
- Indication: concern for overlap syndrome
- Findings include features of both conditions:
- PSC: periductal fibrosis (e.g., "onion skinning"), fibro-obliterative duct lesions, ductular reaction, bile duct loss
- AIH: lymphoplasmacytic interface hepatitis
Differential diagnoses [1][4]
- AIH without PSC
- PSC without AIH
- IgG4–related sclerosing cholangitis
- Secondary sclerosing cholangitis (e.g., infectious, ischemic, malignant)
Management [2][3][4]
- Refer to hepatology or gastroenterology for management.
- Combination therapy with immunosuppression (e.g., prednisone ± azathioprine) plus ursodeoxycholic acid is often used.
- Liver transplant is the definitive treatment for patients with advanced liver disease. [1]
Treatment is directed at the predominant disease. [3]
Prognosis
- Patients with AIH-PSC overlap have a poorer long-term survival than patients with AIH alone. [1]
- Patients with AIH-PSC overlap may have better survival outcomes compared to patients with PSC alone. [1]
- Overall 10-year survival rate [2]
- Children: 89%
- Adults: ∼ 67%