Liver disease wip Flashcards
What is the vasculature entering and leaving the liver?
Incoming: Portal vein and hepatic artery
Outgoing: Hepatic vein
What is cirrhosis?
- End stage liver disease
* Diffuse process with fibrosis and nodule formation
What are the common presenting symptoms of liver disease?
- Jaundice: dark urine, light stool, itch
- Ankle swelling
- Abdominal swelling
- Right upper quadrant pain
- Nausea/vomiting
- Fever
- GI symptoms
What is a classical past medical history of someone with liver disease?
- Previous jaundice, previous cholecystectomy
- Type 2 diabetes mellitus
- Obesity
- thyroid disease and other autoimmune diseases
What is a classical social history of someone with liver disease?
- Drug use
* Alcohol use
What are the standard liver function tests?
- Bilirubin
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT)
- Gamma glutamylytransferase (GGT)
- Alkaline phosphatase (ALP)
- Albumin
What is elevated to indicate hepatic causes in LFTs?
- AST
- ALT
- GGT
- +/- bilirubin
What is elevated to indicate cholestatic causes of abnormal LFTs?
- ALP
- GGT
- +/- bilirubin
What is a non liver related cause of raised ALP
Bone
What is a non liver related cause of elevated AST?
Muscle
What is a non liver related causes of isolated raised bilirubin
Haemolysis
What is liver function best indicated by?
- Albumin
- Bilirubin
- Prothrombin time
What are the broad patterns of diffuse liver disease?
- Acute hepatitis
- Acute cholestasis or cholestatic hepatitis
- Fatty liver disease
- Chronic hepatitis
- Chronic bililary/cholestatic disease
- Genetic/deposition disease
- Hepatic vascular disease
What investigations should be carried out in acute liver disease?
- ultrasound - look for blockage
- Immunoglobulins look for raised IgG indicating autoimmune liver disease (autoimmune hepatitis)
- Check paracetamol levels/ look for other drug induced liver injury
What are the causes of acute cholestasis?
- Extrahepatic biliary obstruction
* Drug injury e.g. antibiotics
Describe histology in acute cholestasis
Bile stasis = brown bile pigment
Name two liver disease patterns that are very similar to a drug induced liver disease
- Acute hepatitis
* Acute cholestasis/cholestatic hepatitis
What is a specific feature of hepatitis B infection in histology?
Ground glass cytoplasm in hepatocytes due to an accumulation of surface antigen
What are the causes of chronic liver disease?
•Chronic viral hepatitis - HBV - HCV •Autoimmune liver disease - autoimmune hepatitis - primary biliary cholangitis - primary sclerosis cholangitis •Metabolic liver disease - haemochromatosis - Wilsons disease - alpha 1 antitrypsin deficiency
What are the symptoms of autoimmune hepatitis?
- 12-35% of cases asymptomatic
- Fatigue/ general ill health
- Lethargy
- Weight loss
- Mild right upper quadrant pain
- Acute jaundice arthralgia (joint stiffness)
- Unexplained fever
What are the investigative signs of autoimmune hepatitis?
- Elevated AST and ALT
- Elevated anti-smooth muscle antibody (SMA)
- Anti-liver kidney microsomal antibodies (LKM)
- Increased IgG
What is the treatment of autoimmune hepatitis?
- Corticosteroids (prednisolone; budesonide)
* Azathioprine/mycophenolate
What are the causes of chronic biliary disease?
- Primary biliary cholangitis
* Primary sclerosing cholangitis
Describe the histology of chronic biliary disease
- Focal
- Portal predominant inflammation and fibrosis with bile duct injury
- Granulomas
What is the most common chronic cholestatic liver disease?
Primary biliary cholangitis
What are the common associations of primary biliary cholangitis?
- Sjögren’s syndrome
- Systemic sclerosis
- Rheumatoid arthritis
- Lupus
- Hypothyroidism
- Coeliac disease
What biochemistry results are seen in early primary biliary cholangitis?
•Elevated gamma glutamyl transferase and alkaline phosphatase
What is seen in advanced primary biliary cholangitis?
•Elevation in bilirubin
What are the common symptoms of primary biliary cholangitis?
- Tiredness
- Itching
- In more advanced cases jaundice
What is the treatment of primary biliary cholangitis?
Ursodeoxycholic acid
What stain is used to test for haemochromatosis?
Perl’s stain
What are the genetic/deposition liver diseases?
- Haemochromatosis - iron
- Wilson’s disease - copper
- Alpha-1-antitrypsin deficiency
What is the cause of Wilson disease?
- ATP7B mutation
* failure to transport excess copper into the bile leading to copper accumulation
What is the inheritance of Wilson disease?
•Autosomal recessive
What is the presentation of Wilson disease?
- May present with chronic liver disease
- About half have neurological or psychiatric symptoms
- Parkinsonism with or without typical hand tremor
- Masked facial expressions
- Slurred speech
- Ataxia
- Kayser-fleischer rings
What is the treatment of Wilson disease?
- Copper chelation: penicillamine or Tridentine
* Oral zinc
Describe what haemochromatosis is and how it causes its effects
•Iron accumulation in tissues and organs: - liver - adrenal glands - heart - skin (bronze appearance) - gonads - joints - pancreas •Results in raised ferritin and transferrin saturation
What is the inheritance of haemochromatosis?
- Mutation of HFE gene
* Autosomal recessive
What is the treatment of haemochromatosis?
Venesection
What is the treatment of haemochromatosis?
Venesection
What are the differences between ArLD and non-alcoholic fatty liver disease?
- Greater alcohol intake in ArLD
- AST/ALT ratio is NAFLD <0.8 but >1.5 in ArLD
- AST elevated in arid and GGT is more markedly elevated as is MCV
Explain the spectrum of ArLD
- Normal liver
- Exposure of normal liver can lead to steatosis (fatty change, perivenular fibrosis)
- Severe exposure of normal or steatotic liver can lead to hepatitis
- Repeated attacks of hepatitis or chronic exposure to a liver experiencing steatosis can lead to cirrhosis (fibrosis and hyper plastic nodules)
What are the essential features for an alcoholic hepatitis?
- Excess alcohol within 2 months
- Bilirubin >80 µmol/l for less than 2 months
- Exclusion of other liver disease
- Treatment of sepsis or GI bleeding
- AST <500 (AST:ALT>1.5)
What are the characteristic features of alcoholic hepatitis?
- Hepatomegaly
- Fever
- Leucocytosis
- Hepatic bruit
What are the associations with NAFLD?
- Obesity
- Type 2 diabetes
- Hyperlipidaemia
What are the causes of acute hepatitis?
- Hepatitis viruses A, B, C, D, E
- Drug injury
- Autoimmune liver disease
What are the causes of acute cholestasis or cholestatic hepatitis?
- hepatitis viruses A, B, C, D, E
- Drug injury
- Extrahepatic biliary obstruction
What are the causes of fatty liver disease (steatosis and steatohepatitis)
- Drug injury
- Alcohol
- Metabolic syndrome e.g. obesity
What are the causes of chronic hepatitis?
- hepatitis virus esp B and C
- Autoimmune liver disease
- Genetic/deposition liver disease
What are the causes of hepatic vascular disease?
- Vascular disease
* Drug injury
What are the non invasive tests of liver fibrosis?
- Fibroscan to test transient elastogrpahy
* Commerically available blood tests: enhanced liver fibrosis test and fibro test
What is the clinical presentation of cirrhosis?
•Can be incidental: abnormal LFTs •Decompensation: advanced liver disease: - variceal haemorrhage - hepatic encephalopathy - ascites ± oedema - hepato-renal failure - hepatocellular carcinoma
What are the signs of chronic liver disease and/or portal hypertension?
- Spider naevi
- Palmar erythema
- Finger clubbing
- Gynaecomastia
- Testicular atrophy
- Dupuytrens contracture
- caput medusa
- foetor hepaticas
- flapping tremor
What are the laboratory features of chronic liver disease?
- Thrombocytopenia
- Prolonged prothrombin time
- Hypoalbuminaemia
What is the assessment of ascites?
Diagnostic tap
•>500 WBC/cm3 and/or >250 neutrophils suggest bacterial peritonitis
•Lymphocytosis suggests TB or peritoneal carcinoma
•Serum ascites albumin gradient >11g/l = portal hypertension
What is the treatment of Ascites?
•Low salt diet
•Diuretics:
- spironolactone (side effects e.g. gynaecomastia, hyperkalaemia, hyponatraemia, impotence)
- Furosemide side effects = hyponatraemia
•Large volume paracentesis
