Flashcards in Hepatology - Autoimmune liver diseases Deck (23):
What is the definition of autoimmune hepatitis?
A chronic, progressive liver disease of unknown aetiology, characterised by autoantibodies, autoimmune T cells, hypergammaglobulinaemia and associated with other autoimmune conditions.
What is the epidemiology of autoimmune hepatitis?
2nd and 3rd decades of life
(can occur in any age in either sex)
What is the aetiology of autoimmune hepatitis?
Aetiology is unknown, but the disease is characterised by immunological abnormalities including hypergammaglobulinaemia with high IgG levels, the presence of circulating antibodies. Histologically there is interface hepatitis with portal plasma cell infiltration.
What conditions are associated with autoimmune hepatitis?
Coombs positive haemolytic anaemia
What is the history of autoimmune hepatitis?
The onset is usually insidious with fatigue, anorexia and jaundice. In about 25%, the onset is acute, resembling viral hepatitis but resolution does not occur. Acute presentation can lead to extensive liver necrosis and failure.
What are the important features on examination of a patient with autoimmune hepatitis?
Signs of chronic liver disease are often present, with palmar erythema,, spider naevi, hepatosplenomegaly, and jaundice. Features of other autoimmune conditions may be present.
Other symptoms include fever, arthalgia, vitiligo, epistaxis, and amenorrhoea.
How do I investigate autoimmune hepatitis?
Circulating autoantibodies* (antinuclear, smooth muscle, soluble liver antigen, liver/kidney microsomal antibodies) are present in most patients. There is also hypergammaglobulinaemia (particularly IgG).
Serum bilirubin and aminotransferases are elevated.
Histology shows non specific changes of chronic hepatitis, with interface hepatitis and often cirrhosis.
* ANA are most common, followed by anti SM
How do I treat autoimmune hepatitis?
Prednisolone 30mg daily is given for 2-3 weeks. A subsequent reduction in dose depending on clinical response, but maintenance doses of 10-15mg are usually required.
Azothioprine should be added as a steroid sparing agent and is usually continued lifelong. Mycophenolate, ciclosporin, and tacrolimus are used in treatment failures.
What is the prognosis in autoimmune hepatitis?
Steroid and azothioprine induce remission in 80% of individuals. Liver transplantation may be necessary if treatment fails although the disease can recur.
What is the definition of primary biliary cirrhosis (PBC)?
PBC is a chronic autoimmune disorder in which there is progressive destruction of intrahepatic bile ducts in the portal triads, causing cholestasis and eventually leading to cirrhosis.
What is the epidemiology of PBC?
Affects predominantly young women aged 40-50 years.
Associated with other autoimmune conditions.
There is increased risk of HCC.
What is the aetiology of PBC?
An inherited abnormality of immune regulation, leads to a T lymphocyte mediated attack on bile duct epithelial cells. It is thought that disease expression results from an environmental trigger, possibly infective, in genetically susceptible individuals. Anti-mitochondrial antibodies are present in most (>95%) of cases, but there role in disease pathogenesis is unclear.
What are the clinical features associated with PBC?
Pruritis with or without jaundice is THE single MC presenting complaint. In advanced disease, there is the addition of hepatosplenomegaly and xanthelasma (PBC is a cause of secondary hypercholesterolaemia. Asymptomatic patients may be discovered on routine examination or screening to have hepatomegaly, a raised serum alk phos or autoantibodies. Patients with advanced disease may have steatorrhoea and malabsorption of fat soluble vitamins owing to decreased biliary secretion of bile acids and the resulting low concentrations of bile acids in the small intestine. Other autoimmune disorders, e.g. Sjogrens, scleroderma, RA occur with increased frequency.
How do I investigate PBC?
A raised serum alkaline phosphatase is the only abnormality on liver biochemistry.
Serum AMAs are found in 95% of patients, and a titre of 1:160 or greater makes the diagnosis highly likely. M2 antibody is specific.
Serum IgM may be high.
Liver biopsy shows loss of bile ducts, lymphocyte infiltration of the portal tracts, granuloma formation in 40% and at a later stage fibrosis and eventually cirrhosis.
An USS is sometimes performed in the jaundiced patient to exclude extrahepatic biliary obstruction.
How is PBC managed?
Management is with lifelong ursodeoxycholic acid (10–15 mg/kg daily by mouth), a naturally occurring dihydroxy bile acid. It slows disease progression and reduces the need for liver transplantation. The mechanism of benefit is incompletely understood. It should be given early in the asymptomatic phase. Pruritus may be helped by colestyramine, and malabsorption of fat-soluble vitamins (A, D, K) is treated by supplementation. Liver transplantation is indicated for patients with advanced disease (serum bilirubin persistently >100 μmol/L).
Monitoring - regular LFTs, ultrasound, AFP
What is the definition of primary sclerosing cholangitis?
PSC is a cholestatic liver disease cause by diffuse inflammation and fibrosis that can involve the entire biliary tree. It leads to gradual obliteration or intrahepatic and extrahepatic bile ducts, and ultimately biliary cirrhosis, portal hypertension and hepatic failure.
What is the epidemiology of PSC?
PSC is twice as common in young men, most patients present between 25-40 years. There is a close associated with inflammatory bowel disease, particularly UC.
Cholangiocarcinoma develops in 10-30% of patients.
What is the diagnostic criteria for PSC?
Generalised beading and stenosis of the biliary system on cholangiography
Absence of choledocholithiasis (or any history of bile duct surgery)
Exclusion of bile duct cancer, by prolonged follow up
What are the clinical features of PSC?
Diagnosis is often made incidentally when persistently raised serum ALP is discovered in an individual with UC. Symptoms include fatigue, intermittent jaundice, weight loss, RUQ pain and pruritis. Physical signs, most commonly jaundice and hepato/splenomegaly are present in only 50% of cases.
How do I investigated PSC?
Serum biochemistry: usually indicates cholestasis. However ALP and bilirubin levels vary widely in individual patients during the course of the disease, sometimes spontaneously, sometimes with therapy. In addition to ANCA, low titres of ANA and anti-SM antibodies have been found in PSC but have no diagnostic significance.
Radiology: MRCP, usually diagnostic, shows multiple irregular stricturing and dilatation of the biliary tree. ERCP should be reserved for patients in whom therapeutic intervention is likely to be necessary and should follow MRCP.
Histology: characteristic early features of PSC are periductal "onion skin" fibrosis and inflammation.
How is PSC treated?
Treatment is usually limited to management of complications arising from chronic liver disease with eventual liver trans- plantation. Extrahepatic strictures may be amenable to dilatation at ERCP. High-dose ursodeoxycholic acid (30 mg/kg) may slow disease progression. Metabolic bone disease should be treated. Cholangiocarcinoma (bile duct cancer) occurs in up to 15% of patients. Sclerosing cholangitis secondary to Cryptosporidium infection in seen in patients with acquired immune deficiency syndrome (AIDS).
Surgical biliary reconstruction has a limited role in non-cirrhotic patients with dominant extrahepatic disease. Transplantation is the only surgical option in patients with advanced liver disease, but is contraindicated if cholangiocarcinoma is present. Colon carcinoma is increased in patients following transplant because of immune suppression, and enhanced surveillance should be instituted.
What are key diagnostic features of PBC?
Think of the rule of "M's":
Middle aged women
Anti Mitochondrial antibodies