What are the four components of normal liver structure?
Vasculature - incoming portal vein and hepatic artery - outgoing hepatic vein Parencyhmal liver cells Biliary system Connective tissue matrix - normally not that much
Which component of the liver increases in quantity during pathology?
Connective tissue matrix
- increases in cirrhosis
What is the interface (limiting plate)?
A border of hepatocytes that separates the portal tract from the parenchyma
What are the broad categories of causes of liver injury?
Drugs and toxins Abnormal nutrition/metabolism Infection Obstruction to bile or blood flow Genetic/deposition disease Neoplasia Others
What is the definition of acute inflammation?
An agent causes injury, but is then removed
- only lasts for days/weeks
N.B. - Fulminant - severe, acute and rapidly progressing towards liver failure
What is the definition of chronic inflammation?
An agent causes liver injury, and then persists
- lasts for months/years
e. g. alcohol or viral hepatitis
What is acute-on-chronic liver inflammation?
Chronic liver disease often presents with acute exacerbations plus evidence of underlying chronicity
- e.g. fibrosis
Which component of the liver is most commonly targeted by injurious agents?
- bile ducts and blood vessels are rarer main targets
- however, as they are all interconnected, damage to one component leads to damage of the rest
Simply, what is cirrhosis?
End-stage liver disease
What is the definition of cirrhosis?
- diffuse process with
- fibrosis and
- nodule formation
Outline the clinical approach to liver disease.
History, symptoms and signs by examination
- blood tests, LFTs, haematol, viral and autoimmune serology, metabolic tests
- radiology - at least US
Usually yields a firm diagnosis, or at least tell us whether it is diffuse or a space-occupying lesion
List the histological patterns of diffuse liver disease.
Acute hepatitis Acute cholestasis or cholestatic hepatitis Fatty liver disease Chronic hepatitis Chronic biliary/cholestatic disease Hepatic vascular disease Deposition/genetic causes
Describe the histology of autoimmune acute hepatitis .
Diffuse hepatocyte injury (swelling) Some dead cells (spotty necrosis) Inflammatory cell infiltrate in all areas - portal tract - interface - parenchyma
Describe the histology of a liver after paracetamol overdose.
Viable liver in some places
Some places undergo massive necrosis
What are the causes of acute cholestasis?
Extrahepatic biliary obstruction Drug injury (e.g. antibiotics) Hepatitis viruses (especially A&E)
Describe the histology of acute cholestasis.
Brown bilepigment seen in the bile ducts (bilirubin)
May have acute hepatitis
Describe the histology of hepatitis B in the liver.
Ground glass cytoplasm in hepatocytes
- accumulation of surface antigen
What are the main causes of chronic cholestatic disease?
Primary biliary cirrhosis
Primary sclerosing cholangitis
What is the histology of chronic biliary cholestatic disease?
Focal, portal-predominant inflammation and fibrosis with bile duct injury
PBC - granulomas
Name some causes of genetic/deposition liver disease.
Wilson’s disease (copper)
How can you test a liver for iron deposits?
Perl’s stain shows excess iron as blue
- normally no blue stain is present
Name some specific causes of diffuse liver disease.
Hepatitis viruses (A, B, C, D and E) Drug injury Extrahepatic biliary obstruction Autoimmune liver disease Alcohol Metabolic syndrome (obesity) Chronic biliar disease (e.g. PBC) Vascular disease (e.g. venous obstruction) Genetic/deposition (e.g. haemochromatosis)
Name some causes of acute hepatitis.
Hepatitis virus (all)
Autoimmune liver disease
Name some causes of fatty liver disease.
Metabolic syndrome (e.g. obesity)
Name some causes of chronic hepatitis.
Hepatitis viruses (all)
Autoimmune liver disease
Genetic/deposition disease (e.g. Wilson’s)
Name some causes of hepatic vascular disease.
- venous obstruction
What is the difference between grade and stage of liver disease?
- severity (activity of inflammation)
- severity of fibrosis (how close are they to cirrhosis)
What are the aims of management of diffuse liver disease?
Prevent or slow progression of fibrosis
What is the treatment of diffuse liver disease?
Specific treatment against cause
- e.g. removal or alcohol or drug, weight loss, optimal diabetic control, anti-virals or immunosuppression
- e.g for severe acute hepatitis or for cirrhosis in general
What is the issue with drug-induced liver disease?
It is very common but mimicks other liver diseases
- can cause almost any pattern of liver disease
- will be a differential for cause in most cases (especially acute hepatitis and acute cholestatic hepatitis)
What are the main differentials for masses (space-occupying or focal) within the liver?
Inflammatory Benign lesions Cancer - metastases - hepatocellular carcinoma
How do you categorise focal liver lesions/space-occupying lesions?
Non-neoplastic - developmental/degenerative e.g. cysts - inflammatory (e.g. abscess) Neoplastic - benign - malignant
What is the most common type of liver cyst?
Von Meyenberg complex
- simple biliary hamartoma
Name the benign types of focal liver lesions
Liver cell - hepatocellular adenoma Bile duct - bile adenoma (rare) Blood vessel - haemangioma
Name the malignanct types of focal liver lesion.
Liver cell - Hepatocellular carcinoma Bile duct - cholangiosarcoma Blood vessel - angiosarcoma Non-liver tissue - metastases
Briefly describe a hepatic adenoma.
Rare, benign tumour of the hepatocytes of the liver Mainly in young women - associated with hormonal therapy Risk of bleeding and rupture - large excision required
When does a hepatocellular carcinoma arise?
Associated with elevated serum alpha feto-protein
What are the normal functions of the liver?
Protein, carbohydrate and fat metabolism
Plasma protein and enzyme synthesis
Storage of proteins, glycogen, vitamins and metals
What are the signs and symptoms related to abnormal liver structure and function?
Abnormal biliary system - accumulation of bilirubin (jaundice) - accumulation of bile acids (pruritis) Abnormal parenchyma - RUQ pain - liver failure (once <25% of function) - hormonal changes in chronic disease Abnormal vasculature and abnormal connective tissue matrix - portal hypertension
What blood tests can effect liver function?
Liver function tests - ALT - AST - ALP - bilirubin - GGT - albumin Liver-related haematology tests - PT time Synthetic function - albumin - PT time Viral serology Autoimmune serology Tests for liver metabolic/genetic disease - iron - copper - alpha-1 antitrypsin
What liver imaging is available for imaging of masses?
US of abdomen
CT of abdomen
Describe the asymptomatic model of liver disease.
Abnormal upper abdominal imaging
Abnormalities incidental or on screening
Describe the symptomatic model of liver disease.
Symptoms likely to relate to the liver - jaundice - ascites (portal hypertension) General symptoms - pruritus - malaise - anorexia
Describe the presentation of acute hepatitis?
Short history of RUQ tenderness and malaise
Elevated AST/ALT (sometimes bilirubin)
What is the most common cause of liver disease in the Western world?
Fatty liver disease
How does fatty liver disease typically present?
Acute or chronic ‘hepatitis’
Asymptomatic abnormal LFTs
Name some drugs that can damage a liver.
Where is the pathology of hepatitis C often found?
In the portal tracts
- chronic inflammation with lymphoid aggregates
What is the definition of chronic hepatitis?
Liver inflammation (abnormal LFTs) for at least 6 months
When a biopsy of a liver with chronic hepatitis is taken, what is assessed and why?
- degree of inflammation (of the portal, interface and parenchyma)
- guides treatment
Stage (amount of fibrosis)
Numerical score assigned - fascilitates follow-up and monitoring of treatment
What is the clinical presentation of chronic cholestatic disease?
Chronic liver disease
- e.g. itch (symptoms of excess bile acids)
- mainly ALP and GGT (mild)
What is primary biliary cirrhosis?
An auto-immune disease with serum anti-mitochondrial antibodies (AMA) and high IgM
Not cirrhotic from outset, but usually progresses to fibrosis then cirrhosis over years
What is the treatment for primary biliary cirrhosis?
Ursodeoxycholic acid eases symptoms and slows progression
Liver transplantation - end-stage
How does alpha-1 antitrypsin deficiency cause genetic/deposition in the liver?
The deficiency is due to lack of secretion, not lack of production
- accumulation in hepatocytes
What is the main form of hepatic vascular disease?
Hepatic vein outflow obstruction
- e.g. hepatic vein thrombosis (often fatal)
- > prothrombotic tendancy predisposes
- > early identification permits anti-coagulation
- lesser degress are more common (e.g. nodular regenerative hyperplasisa
What can cause liver abscesses?
Other parasitic disease
What is cholangiocarcinoma?
Adenocarcinoma of the bile ducts
- either intra- or extra-hepatic
What is the prognosis of a cholangiocarcinoma?
What type of cancer commonly metastasises to the liver?
Adenocarcinoma (or any carcinoma)
- especially from the GI tract due to the portal blood supply
What is the treatment for metastatic liver cancer?
Single metastases may be resected