Aetiologies and pathophysiologies of chronic liver disease Flashcards
What is the flow/pathophysiology of chronic liver disease?
how would each stage present?
Causes of chronic liver disease - signs and symptoms of the casual cause
- -> Recurrent inflammation and the process of fibrosis
- ->Cirrhosis- compensated - stigmata of cirrhosis
- -> Cirrhosis decompensated, chronic liver failure, acute on chronic liver failure - signs and symptoms of liver failure
List causes of chronic liver disease and cirrhosis.
Alcohol NAFLD Hepatitis C Primary Biliary Cirrhosis Autoimmune Hepatitis Hepatitis B Haemochromatosis Primary Sclerosing Cholangitis Wilsons Disease alpha 1anti-trypsin Budd-Chiari Methotrexate
What is the difference between chronic diseases affecting the liver and chronic liver diseases?
Chronic liver diseases can lead to cirrhosis
What syndrome is non-alcohol fatty liver disease associated with?
Metabolic syndrome
What is NAFLD?
Steatohepatitis in the absence of any other cause
What percentage of the population have a) a fatty liver, b) NAFLD?
a) 10-20%
b) 20-30%
What has been suggested as a pathophysiology of NAFLD?
The 2 hit paradigm. 1st hit = excess fat accumulation 2nd hit = Intrahepatic oxidative stress Lipid peroxidation TNF-alpha, cytokine cascade
List some possible “2nd hits” in the pathophysiology of NAFLD?
Oxidative stress & lipid peroxidation MCD diets Pro-inflammatory cytokine release TNFalpha Lipopolysaccharide Ischeamia-reperfusion injury
How is NASH diagnosed?
Liver biopsy
What is the treatment for NASH?
Weight loss & exercise
Primary biliary cirrhosis almost exclusively affects men or women?
Women
What is the clinical presentation of primary biliary sclerosis?
Middle aged women (f:m 10:1) Usually asymptomatic/ Incidental Symptoms Fatigue Itch without rash Xanthesalma and xanthomas Complications
How is PBC diagnosed?
2of 3:
Positive AMA
Cholestatic LFTs
Liver Biopsy
What is the treatment for PBC?
Urseo deoxycholic acid
Urseo deoxycholic acid is a bile salt
Brings more water into the bile duct, flushes away toxic bile salts reducing damages
Does not cure the disease but slows its progression
What are the outcomes of PBC?
Most will not develop symptoms in their life time
The majority with PBC symptoms do not develop liver failure
Itch can be particularly problematic.
Many developing liver failure will be unfit for transplant
Still a common cause of liver transplantation
Does autoimmune hepatitis affect women or men more frequently?
Women
What percentage of patients with autoimmune hepatitis develop cirrhosis?
40%
What is the classic presentation of autoimmune hepatitis?
A jaundiced teenage girl
What are the extrahepatic manifestations associated with type 1 autoimmune hepatitis?
Autoimmune thyroiditis, graves disease, chronic UC
Less commonly with RA, pernicious anemia, systemic sclerosis, ITP, SLE
How do 40% of patients with type 1 autoimmune hepatitis present?
with acute onset of symptoms similar to toxic hepatitis or acute viral hepatitis
What is the clinical presentation of autoimmune hepatitis?
Hepatomegaly Jaundice Stigmata of chronic liver disease Splenomegaly Elevated AST and ALT Elevated PT Non-specific symptoms: malaise, fatigue, lethargy, nausea, abdominal pain, anorexia
How is autoimmune hepatitis diagnosed?
Elevated AST and ALT Elevated IgG Rule out other causes: Wilsons disease Alpha 1 antitrypsin deficiency Viral hepatitis (A, B, C) Drug induced liver disease (alcohol, minocycline, nitrofurantoin, INH, PTU, methyldopa, etc) NASH PBC, PSC, autoimmune cholangitis
Presence of autoimmune antibodies
Liver biopsy
What is a hallmark histological finding of autoimmune hepatitis?
Interface hepatitis
What is the treatment for autoimmune hepatitis?
Corticosteroids Azathioprine Children: azathioprine or 6MP Combination Therapy Prednisone + Azathioprine Prednisone: start at 30mg daily and taper down to 15mg at week 4, then maintain on 10mg daily until therapy endpoint Azathioprine 50-100mg daily
What is the prognosis of autoimmune hepatitis?
40% of all pts with AIH develop cirrhosis
54% develop esophageal varices within 2 years
Poor prognosis if has presence of ascites or hepatic encephalopathy
13-20% of patients can have spontaneous resolution
Of patients who survive the most early and active stage of disease, approximately 41% of them develop inactive cirrhosis.
Of patients who have severe initial disease and survive the first 2 years, typically survive long term.
How does primary sclerosing cholanagitis present clinically?
As recurrent cholangitis
How is primary sclerosing cholangitis diagnosed?
Imaging of the biliary tree
What is the treatment for primary sclerosing cholangitis?
maintain bile flow
monitor for cholangiocarcinoma and colo-rectal cancer
What does haemochromatosis cause?
Cirrhosis
cardiomyopathy
Pancreatic failure
What is the treatment for haemochromatosis?
Venesection
What is the treatment for Wilson’s disease?
copper chelation drugs
How is Budd chiari diagnosed?
U/S visualisation of hepatic veins
How is Budd chiari treated?
recanalization or TIPS
What is methotrexate?
Drug used to treat Rheumatoid arthritis and psoriasis
What is the effect of methotrexate on the liver?
Dose dependent liver toxin
Progressive fibrosis
What are the symptoms of liver fibrosis caused by methotrexate?
There are no clinical signs
Have to monitor the fibrosis
What is the treatment for the fibrosis caused by methotrexate?
Stop the drug
What is cardiac cirrhosis?
Cirrhosis secondary to high right heart pressures: Incompetent tricuspid valve Congenital Rheumatic fever Constrictive pericarditis
What is the clinical presentation of cardiac cirrhosis?
CCF, with too much ascites and or liver impairment
What is the treatment for cardiac cirrhosis?
Treat the cardiac condition
