Lec 2- Liver I

Question 1

Signs and symptoms- Specific

NB- usually to see after a period of time of dysfunction

Answer 1

• Jaundice (+/- Pruritus)- this can happen a lot quicker than the other changes- jaundice can occur quickly
• Pale Stool & dark urine
• Gynaecomastia
• Spider Naevi
• Ascites-albumin deficiency
• Varices
• Hepatic Encephalopathy- thiamine deficiency
• Dupuytren’s Contracture
• Hepatomegaly
• Splenomegaly
• Palmar erythema

Question 2

Signs and Symptoms- Non-specific

NB- more likely to have

Answer 2

• Malnutrition
• Peripheral oedema
• Bruising and bleeding
• Testicular atrophy
• White nail
• Splenomegaly
• Fatigue/Malaise
• Abdominal or RUQ pain
• Muscle cramps
• Finger clubbing

Question 3

Causes of liver disease

Answer 3

• Fatty liver- NAFLD (Non-Alcoholic Fatty Liver Disease), NASH (Non-Alcoholic SteatoHepatitis)
• Alcohol
• Viral- hepatitis A,B,C,D,E
• Malignancy- often the 2^ndary site of cancer (metastasis)
• Immunological- primary biliary sclerosis/ Billary artemisia
• Biliary tract disorders
• Hereditary and metabolic
• Drug-induced- MTX, Valproate, Anti-TB medicines, Amiodarone

Question 4

Non-Alcoholic Fatty Liver Disease (NAFLD)

Answer 4

• Histologically similar to alcoholic liver disease
• Risks: Obesity (central obesity), type 2 diabetes (insulin resistance) or dyslipidaemia, 40-60yrs
• Can progress to cirrhosis and portal HTN
• Asymptomatic or typically fatigue, malaise, ab pain (hardening of the liver)
• Hepatomegaly/Splenomegaly
• Often accidental diagnosis (during routine check-up)
• During irreversible phase= more spleen problems

Question 5

NAFLD- Diagnosis

Answer 5

• Presence of risk factors
• Exclude excess alcohol, and viral causes
• Liver ultrasound- check blood flow
• Fibroscan- use to check elasticity= more fibrous (Biopsy- less used now)
• Unexplained elevations in AST/ALT for >6/12- must be for a sustained time

Question 6

NAFLD- Prognosis

Answer 6

• Good if no complications

Question 7

NAFLD- Treatment

Answer 7

• Eliminate causes and reduce risk factors
• Exercise (give NICE guidance on obesity no matter what BMI)
• Stop any offending drugs
• Optimise treatment for diabetes and dyslipidaemia- (higher risk of diabetes if they don’t have) (also more likely to get arrhythmias/stroke)
• Fibrosis: pioglitazone or Vit E (unlicensed)

Question 8

Alcoholic liver disease

Answer 8

• Alcohol damages liver cells- Alcohol metabolised into acetyl aldehyde (formaldehyde)- kill liver cell which is replaced by non-functional fatty cells= decrease in function
• Fatty liver- hepatitis- fibrosis can progress to cirrhosis
• Often cycling in nature
• Need thiamine in order to metabolise alcohol (also needed for brain function= increased encephalopathy)- give oral thiamine
  
  • Depletion of thiamine is called Wernicke’s encephalopathy and can become permanent
• Management
  
  • STOP drinking
  • Acute withdrawal can be a big risk- higher risk of epilepsy
    
    • Reducing the regimen of BZ’s
  • Support referral
  • Steroids (a NICE pathway for criteria- NICE not very good look at specific hospital guidelines)

Question 9

Viral Hepatitis (acute)

Answer 9

• Not all hepatitis forms into chronic
• Diffuse liver inflammation caused by a specific but diverse group of virus
• Presentation
  
  • Non-specific: Viral illness, with anorexia, malaise, nausea, ab pain
• Most cases of acute viral hep resolve 4-8 weeks after symptoms onset- most are self-limiting
• Can progress to chronic- >6 months, or acute fulminant hepatitis
• LFTs and viral serology help diagnosis
• Vaccines and immunoglobulins can help pre-exposure and post-exposure

Question 10

Hepatitis A

Answer 10

• Most common, esp in children and young adults
• Vaccine for people travelling to underdeveloped countries
• Spread by faecal-oral route- poor hygiene
• Sporadic cases due to person to person contact faecal shedding of virus
• Infectivity occurs before symptoms begin
• Incubation period 15-45 days- foreign travel is a common cause
• Increased liver enzymes and Alk Phos and itching whilst inflammation regresses
• No carrier state, and does not cause chronic hepatitis or cirrhosis
• Resolves spontaneously

Question 11

Hepatitis B

Answer 11

• Characteristic and most complex- Wide spectrum of liver disease
• 5-10% of cases progress to chronic
• 2^nd most common cause of acute viral hepatitis
• Prevalence <0.5% in US and northern Europe, 10% in far east
• Transmitted via blood or contaminated blood products
  
  • Sexual intercourse, shared needles
• Contact with other bodily fluids by sexual contact
• Screening programmes
• Can be associated with extrahepatic disorders like connective tissue disease, membranous glomerular nephritis (steroid treatment)
• Vertical transmission- from mother to baby (can try and use immunoglobulin to prevent this)
• If you have this for a long time your at higher risk of liver cancer, therefore, start screening
• Chronic treatment: Anti-virals- similar to HIV

Question 12

Hepatitis C

Answer 12

• Six subtypes each vary- virulence, geographically and response to treatment
• The highest rate of chronicity with 20-30% progressing to cirrhosis (decades to appear) then possibly HCC
• A chronic state can be benign
• Bloodborne: needle sharing, body piercings, tattooing, donor blood
• Sexual and vertical transmission rare
• Associated with other systematic diseases e.g. cryoglobulinaemia, porphyria and glomerulonephritis
• Synergism to cause liver damage
• Chronic treatment: anti-virals and interferons- very expensive and specialist

Question 13

Hepatitis D, E

Answer 13

• Hepatitis D- only replicates in the presence of the Hep B virus. Uncommon co-infection with acute Hep B, or superinfection with chronic Hep B
  
  • Varies in prevalence geographically. IV needle transmission is high risk, but not sexual activity
• Hepatitis E- water-borne linked to faecal contamination in underdeveloped countries. Similar to Hep A, No chronic or carrier state
  
  • Test for E at the same time as A

Question 14

Pruritus (Itching)

Answer 14

• Patient-specific
• Accumulation of bile salts causing hyperbilirubinaemia- can’t stop itching
• Management
  
  • Colestyramine (binder- watch the timing of other medication) 2-8g BD. Ineffective in complete biliary obstruction
    
    • Anti-histamine- ineffective and sedating- older, more sedating classes generally more effective
    • Sedation can be dangerous- mask regression
  • UDCA- cholestasis- often used in pregnancy
  • Natural fabrics
  • The menthol in Aq cream

Question 15

Portal HTN

Answer 15

• Increased portal vein pressure- a back flow of pressure because blood can’t flow through the liver as it should do
• Varices and ascites
• Management
  
  • Propranolol- licensed reduced splenic blood flow (Make sure HR doesn’t drop below 60)
    
    • Can use unlicensed isosorbide mononitrate
  • 25% decrease in resting HR
  • TIPSS procedure (Transjugular intrahepatic portosystemic shunt)- this reduces first-pass metabolism (effect drug metabolism) also effects breakdown of ammonia compounds (this can lead to hepatic encephalopathy)- bypassing liver

Question 16

Variceal bleed

Answer 16

• Emergency situation
• High mortality
• Vomit large amounts of fresh blood
• Endoscopic banding (camera to locate the bleed)/sclerotherapy
• Vitamin K- patients can have a deranged blood clotting
• Terlipressin- vasoconstriction of varices
• Octreotide- constriction of blood vessels
• TIPSS
• Risk of SBP (Spontaneous Bacterial Peritonitis)

Question 17

Deranged clotting

Answer 17

• Vit K deficiency
• Decreased synthesis of clotting factors
• IV Vit K doses (phytomenadione)
• Partial response to Vit K in severe disease
• Water-soluble (menadiol) oral requires activation by the liver
• Fresh frozen plasma if they have lost a lot of blood

Question 18

Ascites

Answer 18

• Accumulation of excess fluid in the peritoneum
• Swollen ab, and SOB (lack of oncotic pressure lack of albumin)
• overactive RAS system- body thinks it is losing water
• • Variable severity
• Strict fluid balance
• Reduce salt intake
• ? restrict fluids
• Spironolactone (block aldosterone- RASS) titration 100mg- 400mg daily (+/- loop diuretic)
• Monitoring U&E’s, weight loss (No more then 0.5-1kg OD- too much will damage kidneys)
• Side effects: Increase K, Decrease Na
  
  • Gynaecomastia, impotence, libido loss
  • Paracentesis (only if there breathing is restricted)- drainage and albumin administration

Question 19

Spontaneous bacterial peritonitis

Answer 19

• Acute infection of ascitic fluid- common in cirrhosis
• Fever, nausea/vomiting, confusion, ab pain, worsening ascites, failure, encephalopathy
• Diagnostic ascitic tap- neutrophil count
• Empirical IV antibiotic to cover gram-negative bacteria, E.coli and K.pneumoniae e.g. piperacillin-tazobactam
• Increased risk of HRS
• Prophylactic antibiotics if high risk of SBP
  
  • E.g. variceal bleed where there is ascites, diuretic resistant ascites
  • often use quinolones for prophylaxis (periodic ascites- multiple will require regular drainage)

Question 20

Hepatorenal syndrome

Answer 20

• Renal failure in advanced liver disease
• Type 1 and 2
• Diuretics should be withheld esp. spironolactone
• Terlipressin (+/- albumin)- vasoconstriction and reverse circulatory changes- monitor cardiac death
• Close monitoring

Question 21

Hepatic encephalopathy

Answer 21

• Reduced clearing of ammonia compounds
• Means generalised brain dysfunction
• Altered mental and potentially physical state
• Changes can become permanent

Question 22

Encephalopathy

Answer 22

• Consider all causes
• Monitor symptoms
• Management
  
  • Hepatic
    
    • Laxative- lactulose, Phosphate enemas (keep bowel clear= remove waste = less likely to enter the brain)
    • Rifaximin- antibiotic
    • Low protein diet
  • Wernicke’s
    
    • Vit B (Thiamine) high dose
    • If intoxicated- go hard and fast (Large dose IV)
  • Metabolic
    
    • Correct abnormality
  • Infective
    
    • Antibiotic/Anti-virals
  • Uraemic
    
    • Correct kidney function/ dialysis/ transplant
  • Increased intracranial pressure
    
    • Diuretics/steroids/craniotomy/boreholes/ supportive care