Liver list (red, orange and some green)

Question 1

Liver cirrhosis (red)

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 1

1. Fibrosis and re-organisation of liver tissue into regenerative nodules. It is the final stage of chronic liver disease and come become permenant. It is in top 10 leading causes of death.
2. Alcohol is the most common in west, Hep B and C elsewhere. RF: alcohol, IV drug, unprotected intercourse, obesity.
3. Fibrosing, non-function liver tissue. There is micronodular (alcohol mainly) and macronodular (hepatitis mainly) cirrhosis

Question 2

Liver cirrhosis (red)

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 2

4. Abdominal distension (ascites), jaundice, pruritis, haematesis and black stool. Clubbing, palmar erythema, spider naevi, hepatomegaly and bruising.
5. LFTs (raised PTT and low albumin), y-GT, liver biopsy is gold standard. FBC shows thrombocytopenia.
6. Portal vein thrombosis

Question 3

Liver cirrhosis (red)

7. Management
8. Complications
9. Prognosis

Answer 3

7. Underlying cause (alcohol abstaining), flu vaccine. Treat complications of cirrhosis (restrict sodium and give diuretics). Lose weight if obese. Transplantation.
8. Jaundice, coagulopathy, Portal hypertension = variceal haemorrhage and ascites. There is peripheral vasodilation activating RAAS forming oedema (encouraged by hypoalbuminaemia and portal HTN). Also portoystemic encephalopathy and HCC.
9. Depends on cause, but survival is impaired.

Question 4

Gallstones (red)

1. Define (biliary colic, cholecystitis, ascending cholangitis /epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 4

1. Gallstones also called cholethiasis. Biliary colic - associated intermittent pain. Cholecystitis is inflammation of the gallbladder which only occurs if lodged in cystic duct. A cholangitis is infection of the CBD, usually secondary to gallstone. Gallstones very common, present in 10-20% of the population.
2. 80% are cholesterol gallstones (supersaturation or lithogenic bile), 20% are pigment stones (haemolysis). RF: increasing age, Female, FH, obesity, metabolic syndrome, diet (high in animal fat), liver cirrhosis, DM.
3. Covered really.

Question 5

Gallstones, biliary cholic, cholecystitis, cholangitis (red)

4. Clinical manifestations (of each)
5. Investigations
6. Differentials

Answer 5

4. Biliary colic - pain that comes when eating fatty meal and radiates to right shoulder. Acute cholecystitis has same symptoms as biliary colic but can cause localised RUQ pain, fever, tenderness and Murphy’s sign. . Acute cholangitis - classic is fever, jaundice and RUQ (Charcot’s triad).
5. US shows dilated CBD or visual stones. Serum LFT, FBC (increased WCC in cholecystitis and cholangitis - also blood cultures).
6. Peptic ulcer disease, gallbladder cancer

Question 6

Gallstones, biliary cholic, cholecystitis, cholangitis

7. Management
8. Complications
9. Prognosis

Answer 6

7. Gallbladder stone then laparoscopic cholecystectomy, CBD stone then ERCP and sphincterotomy with stent. Analgesics for biliary colic, IV fluids, IV antibiotics (acute cholecystitis), same but more serious in acute cholangitis (3 antibiotics - cephalosporin, cefotaxime and metronidazole).
8. Cholecystitis, cholangitis, pancreatitis (0.1-0.3%).
9. Good - small risk of recurrence.

Question 7

Portal HTN (red)

1. Presentation
2. Treatment
3. Complications

Answer 7

1. GI bleeding, usually from oesophagus, ascites too.
2. For portal HTN, propranolol may lower BP. To manage acute, bleeding varices, endoscopic treatment and stops 80% by band ligation and sclerotherapy. Give Terlipressin and somatostatin while waiting for endoscopy. Give propranolol as prophylactic as recurrence is very common.
3. Most patients with cirrhosis develop varices, but only a third bleed (mortality is as high as 50% if they do).

Question 8

Ascites (red)

1. Presentation
2. Treatment
3. Complications
4. Investigation

Answer 8

1. Fullness in flanks, may be peripheral oedema, pleural effusion and respiratory distress.
2. Treat cause (portal hyerptension - propranolol and isosorbide) and diuretics, dietary sodium restriction, furosemide or paracentesis with albumin IV.
3. Bacterial peritonitis (E.coli)
4. Diagnostic aspiration of ascitic fluid. High albumin suggests exudate (inflammation), while low transudate (cirrhosis complication)

Question 9

Hepatitis A (orange).

1. Transmission/ epidemiology
2. Chronic liver disease or Liver cancer?
3. Presentation
4. Investigation
5. Management
6. Prognosis

Answer 9

1. Faeco-oral. Worldwide, from contaminated food or water (children and adults).
2. No, No
3. Acute hepatitis (rarely fulminant). Early in disease there are non-specific symptoms (nausea, anorexia) then patients become jaundiced 2 weeks later (dark urine, aple stools) and improvement.
4. Serum transaminases (raised ALT), bilirubin (raised in jaundice), IgM anti-HAV (igG = previous)
5. No specific treatment - monitoring, usually self limiting
6. Rarely there is fulminant hepatitis, coma and death but it usually self limiting in 3-6 weeks.

Question 10

Hepatitis B (orange).

1. Transmission/ epidemiology
2. Chronic liver disease or Liver cancer?
3. Presentation
4. Investigation
5. Management
6. Prognosis

Answer 10

1. Blood borne, sexual, vertical. World wide (particularly africa, middle east). Very common cause of chronic liver disease.
2. Yes, yes
3. Can cause acute infection (similar to hep A - nausea, anorexia, later jaundice) where the body produces strong immune response clearing in 99%. If not, if it persists for >6months it is chronic (immunocompromised) which presents like cirrhosis (jaundice and pruritus)
4. Same has hep A. Serum transaminases (raised ALT), bilirubin (raised in jaundice), IgM anti-HBV (igG = previous)
5. Again, management is supportive. Antivrial treatment (interferon or oral nucleotides - Entacavir) is given to those particularly likely to get liver cirrhosis. There is a vaccine.
6. Complications are cirrhosis, HCC causing death. 50-90% patients each sustained viral suppression

Question 11

Hepatitis D (orange).

1. Transmission/ epidemiology
2. Chronic liver disease or Liver cancer?
3. Presentation
4. Investigation, Management and Prognosis are same as for Hep B.

Answer 11

1. Blood/blood products. Common in eastern europe, north africa.
2. Yes, rare.
3. Indistinguishable from HBV infection and often co-infection more likely to cause acute liver failure and more likely to cause cirrhosis.

Question 12

Hepatitis C (orange).

1. Transmission/ epidemiology
2. Chronic liver disease or Liver cancer?
3. Presentation
4. Investigation
5. Management
6. Prognosis

Answer 12

1. Blood/blood.
2. Yes, yes. Chronic infection causes liver inflammation and fibrosis and mainy patients develop cirrhosis over 20years. More common in Europe but also prevalent in the UK.
3. Most acute infections are asymptomatic but then symptoms of chronic (malaise, fatigue - rarely arthritis etc.)
4. HCV antibody enzyme immunoassay.
5. Directly activating antiviral therapy (Glecaprevir) but expensive and not available everwhere. No vaccine.
6. Can cause cirrhosis/HCC, 10 year surival is around 80%, worse if there is cirrhosis.

Question 13

Hepatitis E (orange).

1. Acute or chronic?
2. Spread?
3. Treatment

Answer 13

1. Most are acute asymptomatic and self limiting. Not chronic/HCC
2. Faecal-oral
3. Supportive treatment, consider Ribavirin.

Question 14

Acute liver damage to acute liver failure (ALF) (orange)

1. Describe
2. Causes.
3. Pathophysiology of a paracetamol DILI
4. Presentations
5. Investigations
6. Management
7. Complications
8. Prognosis

Answer 14

1. Acute damage to the liver can cause a rare condition called acute/fulminant liver failure causing jaundice, coagulopathy and hepatic encephalopathy. Either excessive damage or damage on top of underlying liver disorder
2. Mainly alcohol, DILI (paracetamol). Also infections (hepatitis), poisons
3. Glutathione depleted = more CYP450 NAPQI which is toxic.
4. Malaise, nausea, anorexia, Jaundice, confusion, bleeding, RUQ pain.
5. LFTs, PTT/INR, FBC, metabolic panel, drug history
6. Liver transplant and monitoring. Acetylcysteine for autoimmune or HSV. Aciclovir for acute fatty, N acetyl cysteine in paracetamol DILI. Support for coagulation defects, renal failure etc.
7. Hepatic encephalopathy, coagulopathy, infection, metabolic disorders, renal failure.
8. Most DILI resolve, ALF carries substantial risk of mortality but depends on cause.

Question 15

Metabolic liver disease - haemochromatosis (orange)

1. Define/epidemiology
2. Aetiology/ Pathophysiology
3. Presentation
4. Investigation
5. Management
6. Complications/ prognosis

Answer 15

1. Hereditary haemochromatosis (HH) is a multisystem disorder of dysregulated iron absorption and release. Comes with life threatening complications like cirrhosis, HCC, diabetes. HH affects 1 in 400 (varied penetrance, white males - women have periods)
2. Autosomal recessive mutation in HFE causing excess absorption from duodenum.
3. Asymptomatic, found on routine biocehmistry. May be hepatomegaly, lethargy, DM, heart failure etc.
4. Liver biochemistry is normal, elevated serum iron and ferritin is raised and TIBC is reduced. Take history to distinguish from chronic transfusion iron overload.
5. Venesection (500mL twice weekly) lifelong. Surveillance of HCC in patients with cirrhosis. Screen relatives.
6. HCC in cirrhosis is main complication. Normal life expectancy if venesection

Question 16

Metabolic liver disease - Wilson’s disease (orange)

1. Define/epidemiology
2. Aetiology/ Pathophysiology
3. Presentation
4. Investigation
5. Management
6. Complications/ prognosis

Answer 16

1. Rare, recessive disorder on enzyme which excretes copper into bile, causing increased copper. Rare - affects 1 in 40,000.
2. AR. Copper accumulates in the liver causing fulminant liver failure and cirrhosis. Can be dementia and Kayser Fleischer rings. High Cu causes damage by oxidant damage, and excess copper stored in liver causing cirrhosis.
3. Hepatitis, behavioural abnormalities, tremor, dysarthria, symptoms of Parkinson’s
4. LFTs, 24hr urine copper, blood caeruloplasmin
5. Treat with Penicillamine or trientene to chelate copper or zinc (reduces copper absorption). Maybe liver transplant.
6. Fulminant liver failure, if treatment begins early then good outlook

Question 17

Metabolic liver disease - A1-antitrypsin deficiency (orange)

1. Define/epidemiology
2. Aetiology/ Pathophysiology
3. Presentation
4. Investigation
5. Management
6. Complications/ prognosis

Answer 17

1. Rare cause of cirrhosis causing by mutations in a1-AT genecaused reduced hepatic output of a1-AT which normally inhibits neutropil elastase (proteolytic enzyme). 1 in 2500 in west.
2. Autosomal co-dominant, causing early emphysema and liver damage inlammation.
3. Early signs of COPD, symptoms of hepatic involvement are rare but include hepatomegaly and ascites, confusion.
4. Plasma a1-AT, pulmonary function testing, genotyping.
5. Plasma a1-AT, stop smoking, hepatitis vaccinations, standard COPD treatment.
6. HCC, early emphysema. No cure, but normal lifespans generally.