Overlap syndrome

Dr Yasser M Fouad

Professor of Gastroenterology and Hepatology

Head of Tropical Medicine Department

Minia University

Types of overlap syndromes

- Systemic sclerosis with other CT diseases

- Myelodysplasia/myeloproliferative disorder

- Atrial arrhythmia and Brughada syndrome

- Chronic Asthma and chronic obstructive sleep apnea syndrome

- Functional dyspepsia-IBS syndrome

- Hepatic overlap syndrome

Hepatic overlap syndromes

Variants of AIH or separate entities ?

PBC

AIH

PSC

AIH PBC or PSC

Immune mediated injury

Hepatocytes Bile ducts

Genetic susceptibility and environmental factors

Cellular immunity Humoral immunity

Overlap syndrome

Proposed explanations for overlap syndrome

- Coexistence or sequential presentation of two independent

diseases in a susceptible patient

- “Overlap syndromes” represent distinct entities

- “Overlap syndromes” are in the middle of a wide continuum of

manifestations, ranging from pure hepatitic to pure cholestatic

-“Overlap syndromes” are the result of heterogeneous

manifestations of a primary disorder

Features of AIH, PBC, PSCPSCPBCAIHvariable

30-5030-65All agesage

Predominantlymales

Predominantly females

Predominantlyfemales

sex

Normal or mild elevation

Normal or mild elevation

Marked elevationAST&ALT

Normal or elevatedNormal or elevatedNormal or elevatedBilirubin

Moderate to marked elevation

Moderate to marked elevation

Normal or mild elevated

ALP

Features of AIH, PBC, PSCPSCPBCAIHvariable

Ig M & Ig GIg M Ig Gimmunoglobulins

8-70%30%70-80%ANA

Variable (0-80%)May be present50%SMA

NegativeNegative3-4%LKM

Yes or noYes or no10-30%SLA

Features of AIH, PBC, PSCPSCPBCAIHvariable

May be present90-95%Occasionaly positive in low titre

AMA

26-94%-50-96%pANACA

Periductal fibrosisInflammatory biliary injury

Interface hepatitisLiver histology

Multifocal stricturingNormalnormalCholangiogram

80%

No effective TTT

Very rare

UDKA

3-10%

Immunosupressives

IBD

Treatment

Primary biliary cirrhosis AIH overlap syndrome

• ALP˃ 2 times or GGT ˃5 times ULN

• Positive AMA

• Histological evidence of bile duct injuryPBC

• ALT ˃ 5 times ULN

• Ig G ˃2 times ULN or positive SMA

• Liver biopsy: Moderate to severe Periportal or periseptal inflammation

AIH

Diagnosis require at least 2 out of 3 features in each component of the overlap

Autoimmune hepatitis – PSC overlap syndrome

AIH-PSC

Cholestatic biochemical alteration

Concurrence of IBD

Cholangiographic evidence of intra and or extrahepaticbiliary dilation

Histological evidence of ductpoenia and bile stasis

ANA or SMA seropositivity

+ Hypergamaglobulinemia + Interface hepatitis

Treatment

AIH –PBC

ALK LESS THAN 2 FOLDS ULN

• Prednisone or prednisolone:

• 30 mg 1 week

• 20 mg 1 week

• 15mg 2 weeks

• 10 mg daily

• Combined with Azathioprine 50 mg from start

AIH - PBC

• Same +

• Ursodeoxycholic acid 13-15 mg /kg/day

AIH-PSC

•Prednisone or prednisolone combined with azathioprine 50 -75 mg/day

• Ursodeoxycholic acid 13-15 mg /kg/day

Practical point #1

If you have a patients with AIH and overlap with PBC:

- No follow up changes

- You add a comfortable drug (UDCA) which may slow down the progression of the disease and reduces mortality

- Possible reduced life expectancy

Practical point #2

If you have a patients with AIH and overlap with PSC:

- substancial follow up changes( the patient more liable to cholangiocarcinoma, hepatoma, or gall bladder carcinoma)

- You add a comfortable drug (UDCA) but possibly ineffective to slow down the progression of the disease

- Possible reduced life expectancy

Practical point #3

IF BPC or PSC are preceding , making a diagnosis of AIH overlap syndrome :

- You will add a uncomfortable but very effective drug (immunosuppressive) to slow down the progression of the disease and

- Dramatically change life expectancy

Thank You