• Arzt

Alpha version ALDUEG 1.0

Abstract

United European Gastroenterology (UEG) aims to reduce the burden of digestive disease and improve digestive health in Europe. A step to reach this goal is to close the gap between guidelines and clinical practice in rare liver diseases, such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This mini-guideline in AMBOSS contains the most vital information from international PSC, PBC and AIH guidelines which makes it easy to use in clinical practice.

Epidemiologie

  • Prevalence [1] [2] [3]
    • AIH: 15–25 / 100.000 inhabitants in Europe
    • PBC: 2–40 / 100.000 inhabitants in Europe
    • PSC: 6/100.000 in Europe
  • Incidence
    • AIH: 0.7–2 / 100.000 inhabitants per year
    • PBC: 1–2 / 100.000 inhabitants per year in Europe
    • PSC: 0.7 / 100.000 inhabitants per year [4]
  • Demographics (gender / age distribution)
    • AIH: > (∼ 3:1)
      • Peak diagnosis during childhood / teenage years and between 40–60 years
    • PBC: > (∼ 9:1)
    • PSC: > (∼ 1:2)
      • Occurs in children as well in elderly, mean age around 40 years

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 [5]

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[6]

  • 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