Cirrhosis

Question 1

Define

Answer 1

End-stage of chronic liver damage with replacement of normal liver architecture with diffuse fibrosis and nodules of regenerating hepatocytes

• Decompensated when there are complications such as ascites, jaundice, encephalopathy or GI bleeding
• Greek kirrhos = yellow
• Histologically → loss of normal hepatic architecture with bridging fibrosis and nodular regeneration

Question 2

Causes

Answer 2

Chronic alcohol misuse (most common in the UK)

Chronic viral hepatitis (hep B/C - most common worldwide)

Autoimmune hepatitis

Drugs (e.g. methotrexate, hepatotoxic drugs)

Inherited

• a1-antitrypsin deficiency
• Haemochromatosis
• Wilson’s disease
• Galactosaemia
• Cystic Fibrosis

Vascular

• Budd-Chiari Syndrome
• Hepatic Venous Congestion
• Chronic Biliary Diseases
• PBC
• PSC
• Biliary atresia

Unknown: 5-10%

Non-Alcoholic Steatohepatitis (NASH)

• Associated with obesity, diabetes, total parenteral nutrition, short bowel syndromes, hyperlipidaemia and drugs (e.g. amiodarone, tamoxifen)

Question 3

Epidemiology

Answer 3

One of the top 10 causes of death worldwide

Question 4

Symptoms

Answer 4

Early non-specific symptoms:

• Anorexia
• Nausea
• Fatigue
• Weakness
• Weight loss

Symptoms due to decreased liver synthetic function:

• Easy bruising
• Abnormal swelling
• Ankle oedema

Symptoms due to reduced detoxification function:

• Jaundice
• Personality change
• Altered sleep pattern
• Amenorrhoea
• Galactorrhoea

Symptoms due to portal hypertension:

• Abdominal swelling
• Haematemesis
• PR bleeding or melaena

Question 5

Signs

Answer 5

Stigmata of chronic liver disease

• Leukonychia (white nails with lunulae un-demarcated, ↓Alb)  Terry’s nails (white proximally, reddened distally by telangectasias)
•  Clubbing, palmer erythema, Duptyren’s contracture
•  Hyper-dynamic circulation
•  Liver flap
•  Xanthelasma, parotid enlargement
•  Spider naevi , gynecomastia , atrophic testes , loss of body hair, bruising
•  Ascites (shifting dullness and fluid thrill)
•  Caput medusae
•  Hepatomegaly (or shrunken and small in late disease), splenomegaly (portal HTN)

Question 6

Investigations

Answer 6

Bloods

• FBC: low platelets + Hb = because of hypersplenism as a result of portal hypertension
• LFTs - may be normal but often get:
  
  • High AST, ALT, ALP, GGT and bilirubin
  • Low albumin
• Clotting: prolonged PT
• Serum AFP (alpha-fetoprotein = tumour marker for liver cancer):
  
  • Raised in chronic liver disease
  • High levels may suggest hepatocellular carcinoma

Investigations to determine CAUSE

• Viral serology
• a1-antitrypsin
• Caeruloplasmin
  
  • This is a copper-carrying complex that is LOW in Wilson’s disease
• Iron studies: serum ferritin, iron, total iron binding capacity (TIBC) - check for haemochromatosis
• Anti-mitochondrial antibody (PBC)
• ANA, ASMA (autoimmune hepatitis)

Ascitic Tap

• MC&S - check for infection
• Biochemistry (protein, albumin, glucose, amylase)
• Cytology
• IMPORTANT: ascitic tap with neutrophils > 250/mm3 = spontaneous bacterial peritonitis (SBP)

Liver Biopsy

• Performed either:
  
  • Percutaneously
  • Transjugular - if clotting deranged or ascitic
• Histopathological features of cirrhosis:
  
  • Periportal fibrosis
  • Loss of normal liver architecture
  • Nodular appearance
• Grade - indicates degree of inflammation
• Stage - degree of architectural distortion (from mild portal fibrosis –> cirrhosis)

Imaging

• US, CT or MRI - to detect complications such as:
  
  • Ascites
  • HCC
  • Hepatic or portal vein thrombosis
  • Exclude biliary obstruction
• MRCP (if PSC suspected)

Endoscopy

• To examine varices

Child-Pugh Grading - score for estimating the prognosis in chronic liver disease/cirrhosis. It is based on 5 factors:

• Albumin
• Bilirubin
• PT
• Ascites
• Encephalopathy

Cirrhosis can be divided into Classes using the Child-Push grading system:

Class A: 5-6

Class B: 7-9

Class C: 10-15

Question 7

Management

Answer 7

Treat the CAUSE if possible

• Avoid alcohol, sedatives, opiates, NSAIDs and drugs that affect the liver
• Nutrition is important
• Enteral supplements should be given
• NG feeding may be indicated

Treating Complications:

Encephalopathy

• Treat infections
• Exclude GI bleed
• Use lactulose and phosphate enemas
• Normally, the liver breaks down ammonia that is absorbed in the GI tract, however, in Cirrhosis the ammonia can go through the liver without being broken down and exert toxic effects on the brain

IMPORTANT: lactulose reduces the absorption of ammonia from the gut

• This helps prevent encephalopathy caused by ammonia reaching the brain
• Avoid sedation

Ascites

• Diuretics (spironolactone with/without furosemide)
• Dietary sodium restriction
• Therapeutic paracentesis (with human albumin replacement)
• Monitor weight
• Fluid restrict if plasma sodium < 120 mmol/L
• Avoid alcohol and NSAIDs

Spontaneous Bacterial Peritonitis

• Antibiotics (e.g. cefuroxime and metronidazole)
• Prophylaxis against recurrent SBP with ciprofloxacin

Surgical

• Consider TIPS (transjugular intrahepatic portosystemic shunt) - this helps reduce portal hypertension
• However, it may precipitate encephalopathy because it is providing a route for blood from the GI tract to bypass the liver

Liver transplantation is the only curative method

Question 8

Complication

Answer 8

• Portal hypertension with ascites
• Hepatic encephalopathy
• Variceal haemorrhage
• SBP
• HCC
• Renal failure (hepatorenal syndrome)
• Pulmonary hypertension (hepatopulmonary syndrome)

Question 9

Prognosis

Answer 9

Depends on aetiology and complications

Generally poor prognosis

• Overall 5 year survival = 50%
• If ascites, 2 year survival = 50%