UEG toolkit for autoimmune liver disease

The United European Gastroenterology (UEG) aims to reduce the burden of digestive disease and improve digestive health in Europe. A first step towards this goal is closing 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). The guideline synopsis presented here in AMBOSS distills the vital points from the international PSC, PBC and AIH guidelines into a single overview for easy reference in clinical practice.

• Prevalence ^{[1] [2] [3]}
  • AIH: 15–25/100.000 inhabitants in Europe
  • PBC: 2–40/100.000 inhabitants in Europe
  • PSC: 6/100.000 inhabitants in Europe
• Incidence
  • AIH: 0.7–2/100.000 inhabitants per year in Europe
  • PBC: 1–2/100.000 inhabitants per year in Europe
  • PSC: 0.7/100.000 inhabitants per year in Europe ^[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 individuals of all ages; peak diagnosis at approx. 40 years

All diseases can affect all populations and all age groups!

• AIH
  • Most common: Hashimoto thyroiditis and Graves disease
  • Less common:
    • Alopecia
    • Rheumatoid arthritis
    • Type 1 diabetes mellitus
    • Inflammatory bowel disease
    • Psoriasis
    • SLE
    • Celiac disease
• PBC
  • Sjogren disease/symptoms of sicca syndrome
  • Hashimoto thyroiditis
  • Systemic sclerosis
  • Celiac disease
• PSC
  • Inflammatory bowel disease: develops in up to 80%

Affected individuals are often asymptomatic!
Most common symptoms:

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

As there is no gold standard for the diagnosis of autoimmune liver diseases, establishing the diagnosis always requires taking multiple factors into account!

Laboratory studies

• Hepatocellular pattern: suggestive of AIH
  • ↑↑ ALT + ↑↑ AST (+ ↑ bilirubin)
  • Moderately elevated AP and GGT
• Cholestatic pattern: suggestive of PBC/PSC
  • ↑↑ AP + ↑↑ GGT and/or ↑ bilirubin
  • Moderately elevated ALT + AST

Serological markers

• AIH
  • ↑ IgG or ↑ γ-globulin: in 85% of all patients
  • IgA and IgM are usually normal.
  • ANA and SMA are markers of type 1 AIH: positive 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 autoantibodies is pathognomonic of AIH!

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

Imaging studies

• AIH
  • Work-up does not require imaging!
• PBC
  • Work-up does not require imaging!
  • Abdominal ultrasound:
    • To rule out extrahepatic causes of cholestasis
    • Identification of focal liver lesions, portal hypertension, splenomegaly, and 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 intrahepatic and extrahepatic bile ducts (Beaded pattern)
    • Isolated intrahepatic disease: < 25% of affected individuals
    • Isolated extrahepatic disease: < 5% of affected individuals

Histological studies

• AIH
  • Liver biopsy is essential for the diagnosis of AIH.
  • Typical histological findings:
    • Interface hepatitis (hepatitis at the portal-parenchymal interface)
    • Lymphoplasmacytic infiltrates
    • Hepatocellular rosette formation
• PBC
  • Liver biopsy is not necessary for the diagnosis of PBC.
    • Liver biopsy is, however, essential in the absence of PBC-specific autoantibodies or if there is suspicion of coexistent 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.
    • However, liver biopsy should be performed to diagnose small-duct PSC if MRCP is normal.
    • Allows for assessment of disease activity and fibrosis staging

Liver stiffness measurement (LSM)

• AIH
  • The role of LSM is still undetermined: A FibroScan^® cannot substitute a liver biopsy in the diagnostic process!
  • Recent studies suggest that LSM is useful in follow-up care.
• PBC
  • LSM is a good surrogate marker for detection of cirrhosis or severe fibrosis in PBC.
  • Values of LSM > 9.6 kPa are associated with an increased risk of liver decompensation and higher rates of liver transplantation and death.
• PSC
  • Current guidelines do not address LSM
  • Recent data suggest that baseline LSM measurement is useful in detecting advanced fibrosis ^[5]

Genetic testing

• Genetic testing plays no role in the diagnosis of AIH, PBC, or PSC. It is, however, useful for ruling out rare forms of cholestatic liver disease.

Simplified AIH-Score (Hennes-Score)

• Indication: scoring system for assessing the probability of AIH-diagnosis based on the results of laboratory tests, histology, and patient history

Interpretation

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

GLOBE score for PBC ^[6]

• Indications: scoring system for risk stratification in PBC, which allows categorization of individuals into low- and high-risk patients
• Diagnostic parameters
  • Assessment at initiation of UDCA therapy: Age
  • Assessment 1 year after UDCA therapy initiation
    • Total bilirubin level
    • Alkaline phosphatase level
    • Albumin
    • Platelet count