Conditions of the Liver Flashcards
How may liver failure be recognised?
By the development of coagulopathy (INR > 1.5) and encephalopathy
Sudden = acute liver disease
Background of cirrhosis = chronic liver failure
(Fulminant hepatic failure is a clinical syndrome resulting from massive necrosis of liver cells leading to severe impairment of liver function)
Signs of liver failure?
Jaundice, hepatic encephalopathy, fetor hepaticus (smells like pear drops), asterixis/flap
Signs of chronic liver disease suggests acute-on-chronic hepatic failure
What can cause liver failure?
Viral hepatitis (esp. B and C), yellow fever, drugs (e.g. paracetamol overdose), alcohol, fatty liver disease, PBC, PSC, haemochromatosis, autoimmune hepatitis, alpha-1-antitrypsin deficiency, Wilson’s disease
What is hepatic encephalopathy?
As the liver fails, nitrogenous waste (as ammonia) builds up in the circulation and passes to the brain, where astrocytes clear it (by processes involving the conversion of glutamate to glutamine)
This excess glutamine causes an osmotic imbalance and a shift of fluid into these cells— hence cerebral oedema
What are the 4 stages of hepatic encephalopathy?
Grade I: Irritability
Grade II: Confusion, inappropriate behaviour
Grade III: Incoherent, restless
Grade IV: Coma
What is cirrhosis?
Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver
IRREVERSIBLE liver damage
What are common causes of liver cirrhosis?
Alcoholic liver disease, non-alcoholic liver disease, Hepatitis (B & C)
What are some rarer causes of liver cirrhosis?
Autoimmune (primary biliary cholangitis; primary sclerosing cholangitis)
Drugs (e.g. amiodarone, methotrexate, sodium valproate)
Genetic disorders: haemochromatosis; alpha 1-antitrypsin deficiency; Wilson’s disease
What are signs of liver cirrhosis?
Jaundice
Hepatomegaly (will actually be small in late stage)
Leuconychia (white nails)
Palmar erythema (due to hyper dynamic circulation)
Spider Naevi
Gynaecomastia + testicular atrophy (due to endocrine dysfunction)
Ascites
Caput medusae (distended periumbilical veins due to portal hypertension)
Asterixis (flapping tremor in decompensated liver disease)
Complications of liver cirrhosis?
Hepatic failure:
- Coagulopathy - bruise more easily (abnormal clotting)
- Hypoalbuminaemia (oedema)
- Spontaneous bacterial peritonitis (infection of ascitic fluid)
Portal hypertension:
- Ascites
- Splenomegaly
- Varices (e.g. in oesophagus)
- Caput medusae
What is seen in the LFTs for cirrhosis?
LFTs
- Raised bilirubin
- Raised AST, ALT, ALP and gamma-glutamyl transferase (GGT)
- Albumin (is it low?) - indicates synthetic function worse
- raised PT/INR
In decompensated cirrhosis
What can be seen in the blood tests in cirrhosis?
Low WCC
Low platelets - can indicate hypersplenism
Ferritin
Low Na+ (hyponatraemia - indicates fluid retention in severe liver disease)
Enhanced Liver Fibrosis (ELF) blood test - first line in NAFLD and produces a result to indicate fibrosis of the liver
What would ultrasound show in liver cirrhosis?
Ultrasound
- Hepatomegaly or a small liver
- Splenomegaly
- Nodules
- Ascites
What is the FibroScan and who is it used for?
Check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis - called ‘transient elastography’
NICE recommends using it in people with:
- hepatitis C infection
- men who drink over 50 units of alcohol per week and women who drink over 35 units of alcohol per week
- diagnosed alcoholic liver disease
What other investigations can be done for liver cirrhosis?
Endoscopy - to assess and treat oesophageal varices (when portal HTN is suspected)
CT and MRI scans - to look for hepatocellular carcinoma, abnormal blood vessels and acsites
Liver biopsy - to CONFIRM diagnosis
What is the general management of cirrhosis?
Ultrasound and alpha-fetoprotein every 6 months for hepatocellular carcinoma
Endoscopy every 3 years in patients without known varices
High protein, low sodium diet
MELD score every 6 months (gives a percentage estimated 3 month mortality)
Consideration of a liver transplant
Managing complications as below
What does the term hepatitis mean?
Hepatitis describes inflammation in the liver
This can vary from a chronic low level inflammation to acute and severe inflammation that leads to large areas of necrosis and liver failure
What can cause hepatitis?
Alcoholic hepatitis Non alcoholic fatty liver disease Viral hepatitis (A, B, C, E) Autoimmune hepatitis Drug induced hepatitis (e.g. paracetamol overdose)
What is the most common viral hepatitis globally?
Hepatitis A - a RNA virus
Not common in the UK but common in the developing world
How does Hep A spread?
Faeco-oral spread
How to treat Hep A?
Immunise those at risk
- Travel
- Other liver disease
Treatment NOT needed (only needed in those with fulminant liver)
In terms of serology what is the significance of IgM and IgG
Raised IgM indicates acute infection
Raised IgG indicates chronic infection
How is Hepatitis B spread?
Blood (IVDU, medical, tattoo)
Sex
Vertical transmission - mother to newborn
How is Hep B treated?
Vaccination
Chronic - antiviral
Interferon (48 week course) - immune stimulation to develop long term immune response
What is the serology in Hep B?
Hepatitis B serology • Acute - EARLY RISE in anti-core IgM • Chronic ◦ Persistent HbsAg > 6/12 months ◦ HbeAg positive = immunotolerant ‣ High viral levels = infectious ‣ Normal LFTs ‣ Few liver problems ◦ HbeAb positive = immunoreactive ‣ Low viral levels = less infectious ‣ ALT raised ‣ Often fibrotic/cirrhotic
How is Hepatitis C spread?
Blood borne Medical IVDU - main cause in UK Sexual Vertical transmission
What is the disease course of Hep C?
1 in 4 fights off the virus and makes a full recovery
3 in 4 it becomes chronic -> increasing fibrosis -> cirrhosis
Complications: liver cirrhosis and associated complications and hepatocellular carcinoma
How is Hep C treated?
No vaccine
Curable with direct acting antiviral (Ribavirin) medication
Interferon
How is Hep C tested for?
Hepatitis C antibody is the screening test
Hepatitis C RNA testing is used to confirm the diagnosis of hepatitis C, calculate viral load and assess for the individual genotype
Why is Hep D (delta) an imperfect virus?
Hepatitis D is an RNA virus
It can only survive in patients who also have a hepatitis B infection
- It attaches itself to the HBsAg to survive and cannot survive without this protein
Worsens prognosis of Hep B
How is Hep D treated?
Treat hepatitis B - interferon
What is Hepatitis E?
Hepatitis E is an RNA virus. It is transmitted by the faecal oral route
Normally it produces only a mild illness, the virus is cleared within a month and no treatment is required
Similar to Hep A
What is Primary Biliary Cholangitis (PBC)?
Primary biliary cirrhosis is a condition where the immune system attacks the small bile ducts within the liver
The first parts to be affected are the intralobar ducts, also known as the Canals of Hering. This causes obstruction of the outflow of bile, which is called cholestasis
The back-pressure of the bile obstruction and the overall disease process ultimately leads to fibrosis, cirrhosis and liver failure
How is PBC treated?
Ursodeoxycholic acid reduces the intestinal absorption of cholesterol
Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids
What is Primary Sclerosing Cholangitis (PSC)?
Primary sclerosing cholangitis is a condition where the intrahepatic or extrahepatic ducts become strictured and fibrotic
This causes an obstruction to the flow of bile out of the liver and into the intestines. Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts
Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.
How is PSC treated?
ERCP can be used to dilate and stent any strictures
Ursodeoxycholic acid is used and may slow disease progression
Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids
What are the stages of alcoholic liver disease (progression)?
1) Alcohol related fatty liver - drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks
2) Alcoholic hepatitis
3) Cirrhosis
What is the CAGE questionnaire?
C - cutting down
A - annoyed (Do you get annoyed at others commenting on your drinking?)
G - guilt (ever feel guilty about drinking?)
E - eye opener (ever drink in the morning to help your hangover/nerves?)
What are the complications of alcohol consumption?
Alcoholic Liver Disease Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma Alcohol Dependence and Withdrawal Wernicke-Korsakoff Syndrome (WKS) Pancreatitis Alcoholic Cardiomyopathy
What blood investigations may be done for alcoholic liver disease?
FBC – raised MCV
LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT
- ALP will be elevated later in the disease
- Low albumin due to reduced “synthetic function” of the liver
- Elevated bilirubin in cirrhosis
Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver
U+Es may be deranged in hepatorenal syndrome.
What further investigations can be done for alcoholic liver disease?
Ultrasound
FibroScan
Endoscopy - assess for and treat oesophageal varices when portal hypertension is suspected
CT and MRI scans
Liver biopsy - should be considered in those undergoing steroid treatment
How may alcoholic liver disease be treated?
Stop drinking alcohol permanently Corticosteroid treatment (if they have severe alcohol-related hepatitis) - Only effective in improving survival in short term (1 month)
What is ‘delirium tremens’?
An acute confusional state which results when someone who drinks excess alcohol daily, suddenly stops drinking
- Untreated it results in seizures and even death
- This is why patients are advised to reduce their drinking gradually, which allows receptors in the brain to adapt, or they are started on detoxification regimens.
How to pharmacologically manage acute alcohol withdrawal?
Offer benzodiazepine (e.g. Chlordiazepoxide) or carbamazepine
Clomethiazole may be offered as an alternative
- CAUTION when used - only in inpatient settings
How to manage delirium tremens and alcohol withdrawal seizures?
Offer oral lorazepam as 1st line treatment
If symptoms persists off parenteral (non-oral) lorazepam
Seizures: quick-acting benzodiazepines (e.g. lorazepam)
What is Wernicke-Korsakoff Syndrome (WKS)?
Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency
What are the features of WKS?
Wernickes encephalopathy:
- Confusion
- Oculomotor disturbances (disturbances of eye movements)
- Ataxia (difficulties with coordinated movements)
Korsakoffs syndrome
- Memory impairment (retrograde and anterograde)
- Behavioural changes
