Aetiologies and Pathophysiology of chronic liver disease Flashcards
What is chronic liver disease?
Duration greater than 6 months
Outcome - progression to cirrhosis
Pathology - recurrent inflammation and repair with fibrosis and regeneration
Name some causes of chronic liver disease?
Alcohol Hep C Primary biliary cirrhosis Autoimmune hepatitis Hep B NAFLD (non-alcoholic fatty liver disease)
What can chronic liver disease lead to?
Cirrhosis
What is NAFLD?
Fatty liver or stet-hepatitis in absence of other cause
Describe the 2 hit paradigm pathogenesis of NAFLD?
First hit - excess fat accumulation
Second hit - intrahepatic oxidative stress, lipid per oxidation, TNF-alpha, cytokine cascade
Describe how you might treat simple steatosis?
Diagnosis by ultrasound No liver outcomes Increased cardiovascular risks Treatment ***Weight loss & exercise
How would you treat NASH (non alcoholic steatohepatitis)?
Diagnosis at present by liver biopsy Risk of progression to cirrhosis Treatment ***Weight loss & exercise Other treatments experimental
Name some auto-immune liver diseases?
Primary biliary cholangitis Auto-immune hepatitis Primary sclerosing cholangitis Alcohol related liver disease Drug reactions
What does auto-immune mean?
relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body.
Describe the presentation of PBC?
Middle ages women
Usually asymptomatic
Fatigue
Itch without a rash
Xanthesalmas and xanthomas
How do you diagnose PBC?
2 of 3 of….
Positive AMA
Cholestatic LFTs
Liver biopsy
What is the treatment for PBC?
Urseodeoxycholic acid
Who is more likely to develop auto-immune hepatitis?
Women
Roughly how many people will develop cirrhosis from auto-immune hepatitis?
40%
Describe type 1 auto-immune hepatitis?
Females more common
Assoc with extra hepatic manifestions
What is the usual clinical presentation of auto-immune hepatitis?
Hepatomegaly
Jaundice
Stigmata of chronic liver disease
Elevated AST, ALT, PT
How do you diagnose auto-immune hepatitis?
Rule out other causes
Liver biopsy
Presence of autoimmune antibodies
How do you treat auto-immune hepatitis?
Corticosteroids
Azathioprine
What is usually the prognosis like with people who have auto-immune hepatitis?
40% develop cirrhosis
54% oesophageal varices
13-20% have spontaneous resolution
What is primary sclerosing cholangitis?
Autoimmune destructive disease of large and medium sized bile ducts.
Progressive fibrosis and obliteration of the biliary tracts
What does cholangitis mean?
Inflammation of the bile ducts
Who is primary sclerosing cholangitis more common in?
Males and people who also have UC
How do you diagnose primary sclerosing cholangitis?
Imaging of the biliary tree
What is the treatment of primary sclerosing cholangitis?
Maintain bile flow, monitor for cholangiocarcinoma and coli-rectal cancer
What is haemochromatosis?
Genetic iron overload syndrome
What gene mutations are responsible for haemochromatosis?
Mutations in the HFE gene
Is wilsons disease a recessive or dominant disorder?
autosomal recessive
What causes wilsons disease?
loss of function or loss of protein mutations in ceruloplasmin (copper binding proteins – loss of copper regulation leads to massive tissue deposition of copper, especially in liver and basal ganglia)
What is alpha 1 anti-trypsin deficiency?
Genetic, mutations in the A1AT genes
Commonly affects lungs (Emphysema) and liver
How do you treat A1AT deficiency?
Supportive
What is Budd-Chiari syndrome?
Hyper-coagulation in the hepatic vein causing clotting (thrombosis of the hepatic veins)
congenital webs
What might some of the clinical symptoms be in Budd-Chiari be?
Acute
- jaundice
- tender hepatomegaly
Chronic
- ascites
How do you diagnose Budd-Chiari?
U/S visualisation of hepatic veins - showing occlusion
How do you treat budd Chiari?
TIPS
Recanculisation
What is methotrexate usually used to treat?
Rheumatoid arthritis and psoriasis
What must you be careful about when using methotrexate?
Dose dependent liver toxin - can cause progressive fibrosis
What is cardiac cirrhosis?
Secondary to high right heart pressures
What are the clinical symptoms of cardiac cirrhosis?
CCF
Too much ascitites and or liver impairment
How do you treat cardiac cirrhosis?
Treat the cardiac condition