Autoimmune Hepatitis Flashcards
Autoimmune Hepatitis
Autoimmune hepatitis is condition of unknown aetiology which is most commonly seen in young females. Recognised associations include other autoimmune disorders, hypergammaglobulinaemia and HLA B8, DR3. Three types of autoimmune hepatitis have been characterised according to the types of circulating antibodies present
Pathophysiology:
- a T-cell mediated progressive necro-inflammatory process resulting in fibrosis and cirrhosis
- disease is characterised by IgG Hypergammaglobulinaemia
Type I Autoimmune Hepatitis
Anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)
Affects both adults and children
Type II Autoimmune Hepatitis
Anti-liver/kidney microsomal type 1 antibodies (LKM1)
Affects children only
Type III Autoimmune Hepatitis
Soluble liver-kidney antigen
Affects adults in middle-age
Autoimmune Hepatitis - Features and Associations
Features
may present with signs of chronic liver disease
acute hepatitis: fever, jaundice etc (only 25% present in this way)
amenorrhoea (common)
ANA/SMA/LKM1 antibodies, raised IgG levels
liver biopsy: inflammation extending beyond limiting plate ‘piecemeal necrosis’, bridging necrosis
Associations:
- Coeliac disease
- Pernicious anaemia
- Thyroiditis
- T1DM
Autoimmune Hepatitis - Mx
Management
steroids, other immunosuppressants e.g. azathioprine
liver transplantation
Autoimmune Hepatitis - Type I: Example Question
A 48 year-old woman attends the outpatient department with a four month history of myalgia, itching and malaise. She has no past medical history and no relevant family history. Apart from taking antihistamines for the itching, she takes no regular medication and has a 10 pack year history. She also drinks on average 5-10 units of alcohol per week.
Examination reveals mild jaundice, 3 spider naevi on her torso and 4 spider naevi on her face.
Blood tests reveal:
Bilirubin 132 µmol/l ALP 225 u/l ALT 192 u/l γGT 84 u/l Albumin 34 g/l Antismooth muscle antibodies Positive Antinuclear antibodies Positive HBsAg Negative HBsAb Positive HBcAb Negative
What is the most likely diagnosis?
Type 3 autoimmune hepatitis Viral hepatitis Primary sclerosing cholangitis Type 2 autoimmune hepatitis > Type 1 autoimmune hepatitis
Type 1 autoimmune hepatitis is normally associated with antismooth muscle and antinuclear antibodies. Type 2 autoimmune hepatitis is mainly associated with liver kidney microsomal type 1 antibodies and type 3 autoimmune hepatitis normally has positive antibodies against soluble liver antigen. There is usually a strong female predominance and the disease often mimics viral hepatitis, without the positive serology.
Autoimmune Hepatitis - Example Question
A 17-year-old female presents having noticed yellowness to her skin in recent weeks and symptoms of myalgia and fatigue. She is normally fit and well, drinks ten units of alcohol per week and does not report any high risk behaviour. On examination she is clinically jaundiced and has a tender hepatomegaly. Blood tests taken in the acute medical unit are as follows:
Haemoglobin 123 g/l
White cell count 10.0 *10^9/l
Neutrophils 7.0 *10^9/l
Platelets 358 *10^9/l
Bilirubin 85 µmol/l
Aspartate transaminase (AST) 140 u/l
Alanine aminotransferase (ALT) 180 u/l
Alkaline phosphatase 120u/l
Albumin 36 g/l
Anti-nuclear antibody (ANA) positive
Anti-Liver Kidney Microsomal-1 antibody (anti-LKM-1) positive
Anti-mitochondrial antibody negative
Hepatitis B surface antigen (HBsAg) negative
Hepatitis B surface antibody (anti-HBs) positive
Hepatitis B core antibody (anti-HBc) negative
What is the most likely diagnosis?
Primary biliary cirrhosis Primary sclerosing cholangitis Autoimmune hepatitis type I > Autoimmune hepatitis type II Chronic hepatitis B
Autoimmune hepatitis is a chronic disease of unclear cause which leads to progressive fibrosis and cirrhosis. It presents non-specifically and there are no pathognomonic features but typically there are raised transaminases with a normal or minimally raised alkaline phosphatase. Diagnosis rests on autoantibodies and liver biopsy.
It is sub-divided into type I and type II depending upon the antibodies present:
Type I Anti-smooth muscle antibodies or anti-nuclear antibodies; this constitutes 75% of patients
Type II Anti-LKM-1 or anti-liver cytosolic-1 antibodies
The AST/ALT ratio can give clues to the cause of hepatitis. If the ratio is greater than 2 it is suggestive of alcoholic liver disease whereas less than 1 suggests non-alcoholic liver disease.
Her hepatitis B serology results are indicative of immunity.
Autoimmune Hepatitis - Example Question
A 45-year-old female presents to the acute medical take with jaundice. She reports being tee-total and does not report any abdominal pain or recent travel. On examination, the patient is apyrexial. There is palpable tender hepatomegaly. The sclerae are icteric with no peripheral stigmata of chronic liver disease. An initial liver screen shows:
Bilirubin 141 µmol/l ALP 208 u/l ALT 635 u/l Albumin 36 g/l INR 1.2
On further questioning, the patient reports taking regular thyroxine post-thyroidectomy but takes no other prescription or over-the-counter medications and is generally fit and well. An ultrasound and viral hepatitis screen comes back as follows:
HBsAg Negative
HBc Ab Negative
HepC Ab Negative
Ultrasound Smooth hepatomegaly
Given the most likely diagnosis, which of the following is correct?
A full blood count will characteristically show lymphocytosis Serum AMA titres will often be raised Serum IgG levels will often be low Treated mortality is 80% at 10 years > Liver biopsy will show an interface hepatitis
The clue in the history comes from the previous thyroidectomy which suggests the possibility of autoimmune disease in this patient. Autoimmune hepatitis (AIH) is a rare cause of acute hepatitis. However, in the history many of the more common causes (alcohol, medications, viral infection) have been excluded.
The diagnosis is usually confirmed by a liver biopsy which shows an interface hepatitis (inflammation with lymphocytic infiltrate at the junction between hepatocytes and portal tracts). Note that chronic viral hepatitis may also show a interface hepatitis however the viral screen was negative in this patient.
Autoimmune hepatitis is associated with hypergammaglobulinaemia i.e. serum IgG levels will typically be high. Anti-mitochondrial antibodies (AMA) are present in primary biliary cirrhosis (PBC) so point away from a diagnosis of AIH. Treated mortality of AIH is 10% at 10 years. EBV hepatitis usually shows a lymphocytosis, however there are no features of infectious mononucleosis in the history.
