liver disease 1 - causes, symptoms etc

• what are the common causes of liver disease?

  • Alcohol
  • Non-alcoholic fatty liver disease
  • Viral hepatitis
  • Drugs and toxins
  • Inherited and metabolic disorders\
• what is the recommended alcohol intake per week?

  Recommended not to drink more than 14 units of alcohol/week, spread across 3 days or more. However there is no completely safe level of drinking.
• how can alcohol cause liver disease?

  Consistent high levels can lead to liver damage as the liver is unable to process the alcohol quickly enough. Over time this leads to inflammation, scarring and eventually cirrhosis and death. May not exhibit symptoms of liver disease until significant damage.
• not everyone who drinks excessively will develop liver damage
• what are the 2 main routes of alcohol metabolism?

  1. Alcohol metabolised (oxidation) to acetyl aldehyde. Acetylaldehyde is then metabolised to acetate by aldehyde dehydrogenase. Further metabolised to water, fatty acids and CO2.
  2. Activated when higher quantities of alcohol intake – microsomal ethanol oxidising system. Produces unstable free radicals
• what is NAFLD?

  Non-alcoholic fatty liver disease. Range of conditions caused by a build-up of fat in the liver.
• healthy liver = little to no fat
• risk factors of NAFLD...

  • Obesity
• Metabolic syndrome occurs in patients who have several factors associated with an increased cardiovascular risk such as insulin resistance, type 2 diabetes, hypertension, hypercholesterolaemia and an increased waist circumference.

  • It is therefore important to screen for and appropriately manage these conditions in patients with NAFLD and to check for the presence of NAFLD in patients with these conditions.
• what is NSAID also associated with?

  Chronic kidney disease, colorectal cancer, metabolic bone disease and other rare metabolic diseases.
• metabolism of fat...

  Fats including triglycerides are metabolised in the liver and form lipoproteins which are released into the circulation. An excess in the intake of triglycerides or a blockage in the release of lipoproteins will result in the build-up of fat in liver cells.
• In some patients, NAFLD can then lead to NASH which is when the presence of fat in the liver over a long period causes inflammation and fibrosis. This can progress to cirrhosis, loss of cell function and ultimately liver failure.
• stages processing to cirrhosis, loss of cell function and ultimately liver failure;

  four stages:

  1. Non-alcohol-related fatty liver (NAFL) or steatosis in which there is an accumulation of fat in the liver cells.
  2. Non-alcohol-related steatohepatitis (NASH) - inflammation due to fat accumulation.
  3. NASH with scarring (fibrosis) - inflammation has lead to scarring in the liver
  4. Irreversible liver damage - cirrhosis
• Hepatitis A;

  • most common infective hepatitis
  • enteric ally transmitted - faecal-oral route
  • often mild
  • doesn't progress to chronic liver disease or carrier status.
  • In adults - severe with large use in transaminases + commonly see cholestasis (reduction of bile flow)
• Hepatitis B;

  • Enveloped DNA virus
  • Highly contagious - present in the blood, saliva, urine, semen and vaginal fluids.
  • acute hep B vs chronic hep B
  • leading cause of hepatocellular carcinoma (primary liver cancer)
• Hepatitis D;

  • Can't occur on its own - can only replicate in the presence of the Hep B virus.
  • combination of HBV and HDV increases the risk of progression of liver disease
  • Can get HDV at the same time as HBV (co-infection) or at a later date (superinfection)
• Hepatitis C

  • Bone-borne virus (single-stranded RNA virus)
  • acute hep C vs chronic hep C
  • majority of these injected are undiagnosed - asymptomatic
  • slow, progressive disease - silent killer
• Hepatitis E;

  Similar clinical course to hep A

  enterically transmitted - faecal-oral route

  Often mild

  Doesn't progress to chronic liver disease or carrier status.
• Viral infections that specifically target the liver...

  All acute viral infections. Only B, C and D of chronic viral infections.
• Drug induces liver disease;

  • Lots of drugs are 'hepatotoxic'
  • Drugs can cause acute or chronic liver disease
  • A wide range of damage can occur
  • Generally drug withdrawal results in resolution - not always.
  • Need to be familiar with which drugs can cause hepatotoxicity and what the recommendations are regarding monitoring
  • Need to identify DILI and potential causes
• Generally accepted patients with pre-existing liver disease do not have an increased susceptibility to developing hepatotoxicity BUT effects hepatotoxicity may be more severe due to reduced hepatic reserve.
• what are the two types of reactions that can occur in response to drug exposure?

  Intrinsic reactions and Idiosyncratic reactions
• intrinsic vs idiosyncratic reactions

  A) predictable

  B) reproducible

  C) dose

  D) hours

  E) months

  F) cell death

  G) acute

  H) immunoallergic

  I) paracetamol

  J) any

  K) non-steriodal

  
• classification of liver disease;

  Classified according to both the time course over which damage occurs and the pattern of damage seen.
• time course: acute liver disease

  history of onset of symptoms does not exceed 6 months

  • Most common causes – viral hepatitis and drugs
  • Acute hepatitis – usually self-limiting with spontaneous recovery
  • Can go on to acute liver failure or chronic liver disease
• time course: chronic liver disease

  persists for more than 6 months.

  • Progressive and permanent structural
  • Commonest causes – alcohol and chronic viral hepatitis
• the pattern of damage;

  The main patterns of damage can be initially classified as cholestatic or hepatocellular. They are not distinct entities - overlap occurs. Both can lead to fibrosis and cirrhosis.
• pattern of damage: cholestasis

  Disruption of bile flow – stagnation of bile in bile ducts
• pattern of damage: hepatocellular

  • Injury to hepatocytes
  • Fatty infiltration – steatosis
  • Inflammation – hepatitis
• types of cirrhosis;

  • Compensated cirrhosis – enough hepatocyte capacity to perform functions
  • Decompensated cirrhosis – do not have enough capacity to perform required liver functions
• cirrhosis - child-push scoring system

  A) Bilirubin

  B) albumin

  C) INR

  
• what are the initial symptoms of liver disease?

  They may be unspecific.

  • Fatigue
  • General malaise (discomfort)
  • Fever
  • Nausea and vomiting
• many patients will be asymptomatic - there can be a long time interval between disease occurrence and detection.
• more specific signs and symptoms:

  • Pruritus
  • Pale stools
  • Dark urine
  • Spider naevi
  • Bruising and bleeding
  • Gynaecomastia
  • Finger clubbing
• what is jaundice?

  high levels of bilirubin
• what is pruritus?

  accumulation of bile salts under the skin as it's not being excreted - leads to bad itching
• what do pale stools indicate?

  Indicate biliary obstruction. Usually, bile is excreted into the intestine where converted to faecal pigment stercobilin. If obstruction, bile excretion is reduced, and less pigment produced.
• why is dark urine an indicator of liver disease?

  Obstruction, water-soluble conjugated bilirubin can’t be excreted in faeces and therefore body compensates by increasing renal excretion
• what is spider naevi?

  vascular changes - build-up of oestrogen
• what is gynecomastia?

  Enlargement of male breast tissue. Due to increased levels of oestrogen (reduced oestrogen degradation in CLD). Suggests impaired metabolic function. Can also get a side-effect of spironolactone (inhibition of testosterone production).