• Arzt

Alpha version ALDUEG 1.0

Abstract

Version 1.1 edited

The Mini-Guideline covers the diagnostic approach to the autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

Epidemiologie

  • Prevalence [1] [2] [3]
    • AIH: 15–25 / 100.000 in Europe
    • PBC: 1 / 1.000 women > 40 years worldwide
    • PSC: 5–6 / 100.000 inhabitants incidence (0.9-1.3 per 100000/year) and prevalence (8.5-14.2 per 100000)
  • Incidence
    • AIH: 0.7–2 / 100.000 inhabitants per year
    • PBC: 1–2 / 100.000 inhabitants per year
    • PSC: 0.7 / 100.000 inhabitants per year incidence (0.9-1.3 per 100000/year) and prevalence (8.5-14.2 per 100000) rates
  • Demographics (gender / age distribution)
    • AIH: > (∼ 3:1)
      • Peak diagnosis during childhood / teenage years and between 40–60 years
    • PBC: > (∼ 9:1)
      • No classic childhood occurrence
    • PSC: > (∼ 1:2)
      • Occurs in children as well in elderly

All disease can affect all populations and all age groups!

Concomitant autoimmune diseases

  • AIH
    • Most common: Hashimoto’s thyroiditis and Grave’s disease
    • Less common:
  • PBC
    • Sjögren disease / sicca complaints
    • Hashimoto’s thyroiditis
    • Systemic sclerosis
    • Celiac disease
  • PSC
    • Inflammatory bowel disease: up to 80% occurrence

Clinical features

Patients are often asymptomatic!
Most common symptoms:

  • Fatigue
  • Pruritis
  • Arthralgia
  • Flu-like symptoms
  • Abdominal pain
  • Jaundice
  • Pale stools
  • Steatorrhoea
  • Sicca-syndrome

Diagnostic approach

There is no gold standard for the diagnosis autoimmune liver disease. Diagnosis should always be established by taking multiple factors into account!

Interpretation of lab results

  • Hepatocellular pattern: Suggestive for AIH
  • Cholestatic pattern: Suggestive for PBC / PSC

Value of serological markers

  • AIH
    • IgG ↑ or γ-globulin ↑: In 85% of all patients.
    • IgA and IgM usually normal
    • ANA and SMA are markers of AIH type 1: Positiv in 75% of patients.
    • Anti-LKM1 (in 66% of patients) and/or anti-LC1 (in 53% of patients) are markers of AIH type 2
    • Anti-SLA/LP: Only disease specific auto-antibody in AIH! (in 30% of all patients)

No single pattern or combination of auto-antibodies is pathognomonic of AIH!

  • PBC
    • IgM
    • AMA positivity in ≥90% of patients
    • ANA present in 30% of PBC patients: Anti-sp100 and Anti-gp210
  • PSC
    • Routine autoantibody screening is not required to establish the diagnosis!
    • pANCA positivity reported in 26-94% of patients, low specificity

When to chose for imaging? (e.g. ultrasound / MRCP)

  • AIH
    • Radiological imaging is not needed in the diagnostic work-up!
  • PBC
    • Radiological imaging is not needed in the diagnostic work-up!
    • Abdominal ultrasound:
      • Rule out extrahepatic causes of cholestasis
      • Identification of focal liver lesions, portal hypertension, splenomegaly or ascites
  • PSC
    • MRCP: Detailed radiological assessment of the biliary tree is needed to establish a diagnosis of PSC
      • Characteristic findings: Irregular aspect and short strictures of the intra- and extrahepatic bile ducts (‘Beaded’ pattern)
      • Isolated intrahepatic disease: <25% of patients
      • Isolated extrahepatic disease: <5% of patients

To biopsy or not?

  • AIH
    • Liver biopsy is essential for the diagnosis of AIH
    • Should be performed before starting treatment
    • Typical histology:
      • Interface hepatitis (hepatitis at the portal-parenchymal interface)
      • Lymphoplasmocytic infiltrate
      • Hepatocellular rosette formation
  • PBC
    • Liver biopsy is not necessary for the diagnosis of PBC
      • Still essential when: PBC-specific auto-antibodies are absent or when suspicion of co-existent AIH / NASH
    • Findings:
      • Chronic inflammation around intralobular and septal bile ducts
      • Ductopenia
      • Collagen deposits
  • PSC
    • Liver biopsy is not necessary for the diagnosis of PSC
      • But should be performed to diagnose ‘small-duct’ PSC if MRCP is normal
      • Allows assessment of disease activity and fibrosis staging

Liver stiffness measurement (LSM)

  • AIH
    • Role of LSM is still unclear: A Fibroscan can never substitute a liver biopsy in the diagnostic process!
    • Recent studies suggest that LSM can be used in follow-up of the disease
  • PBC
    • LSM is a good surrogate marker for detection of cirrhosis or severe fibrosis in PBC
    • Values of LSM >9.6 kPa: Associated with increased risk of liver decompensation, liver transplantation and death.
  • PSC
    • Current guidelines do not advise on LSM
    • Recent data suggest that baseline LSM measurement has a good performance in detecting higher fibrosis stages [4]

Genetic testing

  • AIH: There is currently no role for genetic testing in the diagnosis of AIH
  • PBC
    • In genereal there is currently no role for genetic testing in the diagnosis of PBC
    • Exemption: To rule out rare forms of cholestatic liver disease genetic testing could be done in expert centers
  • PSC: There is currently no role for genetic testing in the diagnosis of PSC

Scores

Simplified AIH-Score (Hennes-Score)

  • Indication: Scoring system for assessing the probability of AIH-diagnosis with the results of laboratory tests, histology and patient's history
Diagnostic parameters Criteria Points
ANA or SMA Titer ≥1:40 1
ANA or SMA Titer ≥1:80 2
LKM-AK Titer ≥1:40 2
SLA/LP-AK Positive 2
Serum IgG-level > than normal value 1
>1,1-times the normal value 2
Liver histology Typical or compatible with AIH 1
Typical 2
Viral hepatitis ruled out Yes 2

Interpretation

  • Score ≥6 Points: AIH-diagnosis probable
  • Score ≥7 Points: AIH-diagnosis confirmed

GLOBE score for PBC[5]

  • Indications: Scoring system for risk stratification in PBC allowing to categorize patients in low or high risk patients
  • Diagnostic parameters
    • Assessment at initiation of UDCA therapy: Age
    • Assessment 1 year after UDCA therapy initiation