Liver disease Flashcards
How serious is the problem of liver disease in the UK.
How many cases are preventable
Liver disease is a major, under-recognised cause of preventable morbidity and mortality in the UK
It is the fifth largest cause of premature death in the UK
Only common chronic condition with an increasing death rate
More than 90% of liver disease is preventable
What are the 3 main causes of liver disease
Alcohol
Non-alcoholic fatty liver disease (NAFLD)
Viral hepatitis
Account for over 3/4 cases
Give some less comon causes of liver disease
Drugs and toxins
Inherited and metabolic disorders
Wilson disease
Glycogen storage disease
Immune disease of the liver
Autoimmune hepatitis
Primary Biliary
Cholangitis (PBC)
Primary Sclerosing Cholangitis (PSC)
Vascular abnormalities
Budd-Chiari syndrome
Veno-occlusive disease (VOD)
Cancer
Biliary tract disorders
Other Infections
Which blood supplies provide the liver with blood
Has 2 blood supplies:
Arterial blood – 20% hepatic artery
Venous blood - 80% portal vein
true/false - the liver is the largest single organ and can regenerate itself
true
What substances does the liver metabolise
Carbohydrate Protein Fat Steroid hormone Insulin Aldosterone Bilirubin Drugs!!
What substances does the liver synthesise
Proteins
Clotting factors
Fibrinogen
Cholesterol
25-OH of vitamin D
Glucose from fat and protein
What other roles does the liver fulfil (other than synthesis and metabolism)
Production of bile clearance homeastasis stroage immunological function
Why do we test bilirubin levels to help diagnose liver disease
Bilirubin is a product of red blood cell breakdown
Transported to the liver in the serum attached to albumin
Transformed into a water-soluble conjugate which is excreted via the bile into the intestine
Levels increased:
Haemolysis
Hepatocellular damage
Cholestasis
What is jaundice
An accumulation of bilirubin which causes skin discolouration
Why do we test for transaminases
They are enzymes fund in liver cells. When liver cells break down (as they’re damaged) these enzymes are released
Levels are increased in hepatitis, drugs, sepsis
Where do we find Aspartate transferase and Alanine transferase respectively
Aspartate transferase - AST (0-40 iu/L)
Found in liver, heart, skeletal muscle, pancreas, kidney and RBC
Alanine transferase - ALT (5-30 iu/L)
Often termed ‘Liver specific enzyme’
All patients with liver disease will have raised transaminase enzymes – true or false?
False, in some cases of severe liver disease there wont be raised transaminase levels as the liver cells are simply too damaged to produce them any more
Where are the alp and ggt enzymes found and what does increased levels of them in the blood show
Alkaline Phosphatase – ALP
Usual range 30-120 iu/L
Found in liver, bone, intestine and placenta
Level is increased in cholestasis, damage to biliary tree (bile ducts)
γ-Glutamyltransferase – GGT
Usual range 5-55 iu/L
Found in liver and biliary epithelial cells, pancreas, kidneys, prostate, intestine
Level is increased by enzyme inducers including alcohol, cholestasis, carcinoma of pancreas & GIT
What does a decrease in albumin levels show
Decreased level – oedema
Decreased in chronic liver disease - long half life so the problem is chronic
Whyis it often helpful to look at the prothrombin time and international normalised ratio
Prothrombin time (PT) is a blood test that measures how long it takes blood to clot The international normalised ratio (INR) is a laboratory measurement of how long it takes blood to form a clot. Calculated using prothrombin time
Clotting factors are produced (synthesised) by the liver and have a short half-life (2-3 days).
Fewer clotting factors are produced so the PT/INR are ↑ in acute and chronic liver disease (the blood is thinner)
Is there a single test which demonstrates
No - Usually at least two will be deranged if liver dysfunction
Trends not isolation
Which criteria do we use to classify liver disease
Classified according to both the pattern of damage seen and time course over which damage occurs
What are the names of the two patterns of liver damage and what can they lead to
The main patterns of damage can be initially classified as cholestatic or hepatocellular
These are not distinct entities – overlap occurs (most patientd have a combination of both)
Both of these can lead to fibrosis and cirrhosis
Define cholestasis damage
Cholestasis
Disruption of bile flow – stagnation of bile in bile ducts
They may be narrowed or damaged
Define hepatocellular damage
Hepatocellular
Injury to hepatocytes
Fatty infiltration – steatosis
Inflammation – hepatitis
What is fibrosis and cirrhosis
Persistent, extensive hepatocyte damage - active deposition of collagen formation of scar tissue – fibrosis
Disruption of blood flow
Erratic regeneration and nodules can form - cirrhosis
What is the usual cause of acute liver disease
Acute – 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
What is the usual cause of chronic liver disease
Progressive and permanent structural
Compensated – the patient still has enough hepatocyte capacity to perform basic functions
Decompensated – do not have enough capacity to perform required liver functions
Commonest causes – alcohol and chronic viral hepatitis
What is the childs pugh scoring system used for
A scoring system used to asses the severity of liver disease (cirrhosis)
Is used to determine how severe the disease is and how to treat the patient
The tests used to calculate it are the bilirubin, albumin and inr levels
What are the general signs and symptoms of liver disease
Many patients will be asymptomatic
Can be long time interval between disease occurrence and detection
Initial symptoms may be unspecific: Fatigue General malaise Fever Nausea and vomiting
What are some specific symptoms of liver disease
Jaundice – high levels of bilirubin
Pale stools – indicate biliary obstruction. Usually bile excreted into intestine where converted to faecal pigment stercobilin. If obstruction, bile excretion reduced, less pigment produced
Dark urine – obstruction, water soluble conjugated bilirubin can’t be excreted in faeces and therefore body compensates by increasing renal excretion
Pruritus- accumulation of bile salts under skin as not excreted
Spider naevi – vascular changes (accumulation of oestrogen)
Gynaecomastia – enlargement male breast tissue. Due to increased levels of oestrogen (reduced oestrogen degradation in CLD). Suggests impaired metabolic function. Can also get as side-effect of spironolactone (inhibition of testosterone production)
Ascites – presence of excess fluid in peritoneal cavity, leading to swollen abdomen
Varices – abnormally dilated collateral vessels due to increased portal vein pressure (portal hypertension)
Encephalopathy – spectrum of reversible neuropsychiatric changes
Bruising and bleeding (fewer clotting factors)
Liver palms - red hands
Finger clubbing
Name 3 complications of liver disease (as a consiquence of cirrosis)
Ascites
Encephalopathy
Varices and portal hypertension
What is ascites
Accumulation of fluid in the peritoneal cavity leading to swollen (or expanded) abdomen – “abdominal distension”
Abdominal distension occurs when substances, such as air (gas) or fluid, accumulate in the abdomen causing its expansion
May also have abdominal (stomach) pain
How do we treat ascites (which 2 drugs, why we use these drugs and how we monitor their action)
Diuretics
Spironolactone (aldosterone antagonist)
Furosemide (loop diuretic)
Rationale
Diuresis - induces negative fluid balance and reduction in the amount of ascites (free fluid in the abdomen)
Spironolactone (first line) is useful as it is an aldosterone antagonist and liver pts have high circulating levels of aldosterone (because they cant break it down)
Monitor
Daily weight – 0.5 - 1kg/day weight loss
Renal function, urea and electrolytes – especially sodium, potassium and creatinine
What non - drug based therapies do we use to treat ascites
Fluid/Sodium restriction. Too much salt = water retention
Paracentesis (drain the fluid) for large volume ascites
What is Spontaneous Bacterial Peritonitis and how do we diagnose it
Spontaneous Bacterial Peritonitis (SBP) is an infection of the ascitic fluid without intra-abdominal source of sepsis (frequent complication)
Patient may have severe pain, raised temperature and raised white-cell count
Diagnosis – take a sample of ascitic fluid. SBP diagnosed if the neutrophil count > 250 cells per mm3 (raised inflammatory markers)
Mortality rate is approx. 40%
How do we treat spontaneous bacterial peritonitis
SBP can be caused by gram-positive (or gram-negative) bacteria
Common causative organisms include E. coli and Streptococcus
Initially treat with a broad spectrum intravenous (IV as its such a serious infection) antibiotic e.g.
3rd generation cephalosporins such as ceftazidime 2 grams IV three times a day
Piperacillin with tazobactam 4.5 grams IV three times a day
Treatment for 5 days and review
Norfloxacin/Ciprofloxacin as prophylaxis if the infection is recurrent
What is Hepatic Encephalopathy (as a complication of liver disease)
Neuropsychiatric changes inc changes in mood & behaviour, confusion, delirium and coma
4 clinical grades dependent on clinical signs
Several theories - accumulation of toxins esp. ammonia crossing into the brain
Precipitants include ↑ protein load, accumulation of ammonia, electrolyte disturbance, drugs, infection
Symptoms similar to hypoglycaemia, alcohol intoxication or withdrawal
How do we treat Hepatic Encephalopathy using non - antibiotic methods
Strategies aimed at avoiding precipitants + reducing ammonia levels
Laxatives
Lactulose liquid 20-30mls twice to three times a day
Phosphate enema – once or twice daily
Rationale
Inhibits intestinal ammonia production by a number of mechanisms including changing the pH of the gut lumen (reduces absorption of ammonia in to blood stream and also favours growth of non-ammonia producing bacteria) and reducing colonic bacterial load
Monitoring
Aim 2-3 soft stools per day
Which antibiotics are used for Hepatic Encephalopathy
Antibiotics
Rifaxamin tablets 550mg twice daily
Rationale
low systemic absorption, high levels in faeces. This antibiotic kills gut bacteria to reduce ammonia levels (gut bacteria produce ammonia)
L-ornithine L-aspartate sachets (LOLA) (unlicensed)
Rationale
Increases removal ammonia - naturally occurning amino acids
Dietary protein restriction not recommended
What causes portal hypertension and varices
Portal hypertension is caused by increased resistance to flow due to:
disruption of hepatic architecture
compression of hepatic venules by regenerating nodules
Collateral vessels form – enable blood to bypass the liver and reduce the pressure on the main vessels. However, they are very weak and liable to burst
Which diagnostic tools and treatments do we use in an emergency for portal hypertension and varices
Resuscitation – fluids, blood transfusion
Endoscopy – banding, schlerotherapy (glue)
Terlipressin IV 1-2mg bolus then every 4-6 hours
Potent vasoconstriction
Antibiotics – infection is common. IV broad spectrum antibiotic for at least 5 days
Proton-pump inhibitor (PPI) - protects the stomach
The likelihood of a second bleed after the fist incidance of portal hypertension and varices is high. Which drugs can we use to lower this risk
Propranolol tablets 20-40mg twice daily - reduces the blood pressure around the liver
Non-selective beta-blocker - for areas found outside the heart
Splanchnic vasoconstriction (beta2 blockade)
Cardiac output results in reduced portal pressures (beta1 blockade)
How do we treat pruritis in liver disease caused by the build up of bile salts
Treatment options include:
Colestyramine (anion-exchange resin) - binds bile acids and prevents reabsorption
Ursodeoxycholic acid (UCDA)
Antihistamines - Chlorpheniramine, Hydroxyzine (sedating), Loratadine, cetirizine (non-sedating
Topical - Calamine lotion,
(Menthol 2% in Aq cream
Ondansetron
Rifampicin
Naltrexone, Naloxone)
How common is alcohol related liver disease in the uk
Most common cause of liver disease in UK
Increasing incidence in people under 30 and in females
North West of England has one of the highest incidences in the UK
What is the reccomended maximum levels of alcohol per week
Recommended not to drink more than 14 units/week
nb - Not everyone who drinks excessively will develop liver damage
How does alcohol affect the liver
Spectrum of liver damage is not uniform. 3 main histological stages, in reality these stages may overlap.
How do we metabolise alcohol
2 main routes alcohol metabolism:
- Alcohol metabolised (oxidation) to acetylaldehyde. Acetylaldehyde metabolised acetate by aldehyde dehydrogenase. Further metabolised to water, fatty acids and CO2.
- Activated when higher quantities alcohol intake – microsomal ethanol oxidizing system. Produces unstable free radicals
NB 2E1 induction will increase metabolism of alcohol and drugs metabolised via this route
How do we manage alcohol withdrawal in hospital (and why do we do it)
Treatment of acute alcohol withdrawal is with a combination sedatives and vitamin supplementation – Chlordiazepoxide + Pabrinex IV or oral vitamin B co strong and thiamine
Withdrawal symptoms can range from mild – severe (delirium tremens)
Delirium, marked tremor
Fear and delusions, restlessness and agitation
Fever
Rapid pulse
Dehydration
Seizures
How do benzodiazepines work to treat alcohol withdrawal (and which one is commonly used)
Main drug used - Chlordiazepoxide because it has a long half-life and slower onset action – less abuse potential. It also has a low potency
Rationale
Chlordiazepoxide
prevents withdrawal symptoms such as agitation and alcohol withdrawal seizures (sedative and anti-convulsant properties)
Mechansim
Benzodiazepines are cross-tolerant with alcohol and modulate anxiolysis by stimulating GABA-A receptors. During withdrawal from one agent, the other may serve as a substitute
Why do we use a detoxification regime for patients on benzodiazapines
We prescribe oral reducing regimen + as required dosing – known as detoxification regime which helps to reduce the dose over 5 days to manage their symptoms
Which vitamins are provided to patients who are coming off alcohol and why do we use them
Pabrinex given intravenously (IV) – 1-3 pairs twice – three times a day
Thiamine and vitamin B co-strong orally
Indication
Treat potential thiamine deficiency
Prevent development Wernicke’s encephalopathy (complication of alcohol withdrawal - confusion)
Rationale Likely to be vitamin deficient: Poor diet (high in carbohydrate, low in protein, vitamins and minerals) Alcohol prevents thiamine absorption - causes malabsorption in the intestinal mucosa
What is viral hepatitis
Viral infections that specifically target the liver
Theres at least five viruses that cause hepatitis (liver inflammation) without significant damage to other organs
Acute hepatitis or chronic hepatitis
How is hepA transmitted and what is the prognosis of a patient who has it
Hepatitis A (HAV)
Commonest form infective hepatitis
Primarily enterically transmitted - faecal-oral route
Often mild
Doesn’t progress to chronic liver disease or carrier status
What is HEPB and what is the prognosis of a patient who has it
Enveloped DNA virus (hepadnavirus) so is very difficult to eradicate.
Number of subtypes (genotypes)
Highly contagious - present in blood, saliva, urine, semen, vaginal fluids
Clinical course – dependent on age of infection
Progression of HBV – child doesn’t usually show signs of disease but most will go on to develop chronic infection with a sig proportion then going on to develop cirrhosis
Adult – show some signs of infection – increase transaminase and jaundice. Self-limiting for most but small proportion adults will get chronic infection
Treatment dependent on number of factors including age, extent of liver damage, virology and HBV DNA level
How do we treat chronic hepB
Chronic Hepatitis B Treatment
Oral antivirals – entecavir or tenofovir
Pegylated Interferon for some patients (short course)
Aiming for “functional cure” - virus level isnt replicating and causing further liver damage. Eradication is almost impossible
Treatment with oral antivirals is long-term for majority of patients
Treatment supported by NICE guidelines
Vaccination is available
What is HEPD and how is it related to hepB
Also known as delta virus
Can only replicate in presence of Hepatitis B virus
Can get HDV at same time as HBV (co-infection) or at a later date (superinfection)
Acquired in same way
Combination of HBV and HDV increase risk of progression to chronic hepatitis and cirrhosis
Is HEPE as severe as HEPB
No - Similar clinical course to HAV
Enterically transmitted - faecal-oral route
Often mild
Doesn’t progress to chronic liver disease or carrier status
What type of virus is HEPC, how do we diagnose it and is it curable
Single stranded RNA virus - Flaviviridae family
Blood-borne virus
Six major genotypes identified (1-6)
Diagnosis – include testing for Hepatitis C antibodies, HCV RNA and genotype
Majority of those infected are undiagnosed – asymptomatic
Slow (20 year infection!), progressive disease – “silent killer”
Hepatitis C is curable (aim of treatment is eradication)
What are the aims of the treatments of HEPC
A sustained virological response (SVR) – viral eradication
Number of different treatments available –8-12wk courses
Choice and duration dependent on genotype, extent of liver damage and treatment history
WHO target – eliminate HCV as public health threat by 2030
