20. Chronic Liver Disease Flashcards
CLD is the 5th cause of death in the UK, and deaths from it are increasing. What two things are contributing to this?
Describe the stages of liver disease.
What are the 3 main causes of chronic liver disease?
List some other causes.
20-50% increase in U/week of alcohol in 10 yrs.
15-25% of pop raised BMI
Pts presenting and dying younger
[Pic] (N.B. not set in stone e.g. can get cancer even if don’t have cirrhosis)
Alcohol, HCV, NAFLD
HBV
Immune’ (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis)
‘Metabolic’ (haemochromatosis - Fe overload, Wilson’s - excessive Cu deposition, A1AT deficiency)
Other (Budd-Chiari - occlusion of hepatic veins, 2o biliary cirrhosis, IgG4-related cholangiopathy, inherited)
Why is AST>ALT in alcoholic liver disease, and what is the ratio?
What is GGT and the significance of testing for it?
What is NASH?
20-30% of people with NASH progress to cirrhosis. What can they do to reduce progression?
- *ETOH** increases AST synthesis, B6 deficiency inhibits ALT.
- *2:1 - 3:1** (AST < 300)
Liver enzyme, not diagnostic but if raised the pt may be consuming alcohol
Non-alcoholic steatohepatitis - the most severe form of NAFLD, it combines steatosis, inflammation and fibrosis. Common cause of elevated LFTs. Often pts have metabolic syndrome
Wt loss, lipid and diabetes control
What is primary biliary cholangitis (PBC)?
What would you test for?
What are the symptoms and tx?
Autoimmune disease of the liver, slow progressive destruction of small bile duct causing build up of bile and toxins in liver -> cholestasis. F:M = 6:1, AGE >40
ALP (increased), GGT (increased), AMA (anti-mitochondrial ab, specific for PBC)
Symptoms: jaundice (rare), pruritis, lethargy
Tx: ursodeoxycholic acid (slows progression), liver transplant
What is primary sclerosing cholangitis?
How would a pt present?
There is increased cancer risk with PSC - what 2 main cancer types?
List the symptoms and tx
Progressive cholestasis with bile duct inflammation and strictures
M>F, age 20 onwards, 50% have IBD (usually UC), large bile duct sclerosis and loss
Cholangiocarcinoma, colorectal cancer (so do colonoscopy/yr). Also gallbladder and liver cancers.
Symptoms: jaundice (usually present, due to infection/disease progression), pruritis +/- fatigue, cholangitis
Tx: UDCA (ursodeoxycholic acid), ERCP (for strictures in bile duct, put stents in), liver transplant
What is autoimmune hepatitis?
Does it predominantly affect male or females?
How would someone present?
Inflammatory liver disease of unknown cause characterised by suppressor T-cell defects with autoantibodies directed against hepatocyte surface antigens. Classification is by autoantigens (types 1-3)
M:F = 1:3
**40%** = **acute hepatitis** and **signs of autoimmune disease** *e.g. fever, malaise, urticarial rash, polyarthritis, pleurisy, pulmonary infiltration, glomerulonephritis.* Remainder = **asymptomatic/ gradual jaundice**
How would you diagnose autoimmune hepatitis?
How would you treat autoimmune hepatitis?
Serum bilirubin, AST, ALT and alk phos usually increased, hypergammaglobulinaemia, IgG increased, +ve autoantibodies (smooth muscle, ANA, LKM, ALSA - all non-specific), anaemia, WCC decrease, plt decrease -> hypersplenism. Liver bx: mononuclear infiltrate of portal and periportal areas and piecemeal necrosis +/- fibrosis, cirrhosis = worse prognosis. MRCP helps exclude PSC if alk phos disproportionately increased
Immunosuppressant: prednisolone, azathioprine (steroid-sparing agent), mycophenolate. Liver transplant
What is haemochromatosis?
What is the frequency of the genetics of it? What are the 2 most common mutations responsible?
How would the patient present?
Inherited autosomal recessive disorder of iron metabolism in which increased intestinal iron absorption leads to iron deposition in joints, liver, heart, pancreas, pituitary, adrenals and skin. High hepatocellular carcinoma risk
0.3-0.5% pop homozygous, 9% heterozygous, M>F. HFE gene found on short arm of chromosome 6: C282Y, H63D
Early: nothing/tired, arthralgia
Later: slate-grey skin pigmentation, signs of CLD, hepatomegaly, cirrhosis, dilated cardiomyopathy, osteoporosis
Endocrineopathies: DM ‘bronze diabetes’, hypogonadism from pituitary dysfunction, hypoaldosteronism
How would you investigate hereditary haemochromatosis?
How would it be treated?
Blood: LFT, serum ferritin and transferrin saturation increased, HFE genotype
Images: chondrocalcinosis, Liver MRI = Fe overload (ferriscan)
Liver bx: Perl’s stain quantifies iron loading and assesses disease severity
ECG/ECHO if cardiomyopathy suspected
Venesection (1 unit every 1-3w until ferritin ≤50ug/L). Consider desferrioxamine (Fe chelation therapy) if intoleratent. Monitor LFT and glucose. Low iron diet
What is Wilson’s disease?
What are the genetics of it?
What are the presenting features?
Rare (3/100,000) inherited autosomal recessive disorder of biliary copper excretion with too much copper in the liver and CNS (basal ganglia). Treatable
Gene on chromosome 13 that codes for a Cu transporting ATPase, ATP78. Many mutations, HIS1069GLU the commonest
Acute liver failure, cirrhosis. CNS signs (tremor, dysarthria, dyspahgia, dyskinsias, dementia, parkinsonism, ataxia/clumsiness), depression/mania, memory decrease, haemolytic anaemia, copper in iris (Kayser-Fleischer rings), grey skin
How would you diagnose Wilson’s disease?
How would you treat it?
What are some complications of liver cirrhosis?
Urine (Cu increase), LFT increase, serum copper <11, serum caeruloplasmin decrease, molecular genetic testing can confirm dx, KF rings in iris, liver bx (increae hepatic copper), MRI (degeneration of basal ganglia etc.)
Low Cu diet, lifelong penicillamine, Cu chelation therapy, liver transplant. Screen siblings
Decompensation: ascites (increased pressure in portal veins), encephalopathy (toxins bypass BBB due to opening of colaterals), sepsis, hepatorenal syndrome (cirrhosis = hypoperfused kidneys)
Portal HTN: variceal haemorrhages
Hepatocellular carcinoma
Coagulopathy
[Pic - nodular cirrhotic lvier]
What is portal hypertension?
What might it cause?
How would you treat a variceal haemorrhage?
What are some primary and secondary prophylaxis methods?
Increase of BP in portal venous system [Pic]
- *Splenomegaly** (backflow of portal pressure = spleen congestion -> enlarges, plt decrease. Pancytopenia)
- *Varices** (oesophageal, gastric, rectal)
Medical emg!
Abx, terlipressin (vasopressin analogue, vasoconstrictor works mostly in splenic circulation, decreases blood loss), banding, glue injection, TIPSS (transjugular intrahepatic portosystemic shunt)
1o: Propranolol - non specific B blocker, decreases portal pressure. If not well tolerated try carvidolol
2o: Banding to obliteration (+ B blockers)
How does TIPSS work to treat variceal haemorrhage?
How would you diagnose ascites?
How would you treat ascites?
Artificial channel in liver that establishes communication between the inflow portal vein and the outflow hepatic vein, decreasing vascular resistance and portal pressure. Can embolise varices too. [Pic]
Clinical = peripheral oedema, USS + doppler, ascitic tap (check fluid WCC and albumin to see if related to liver disease - if yes = transudate. If albumin high, may be other things at work e.g. cancer. Do cytology of fluid)
Low Na diet, diuretics (spironolactone, furosemide), paracentesis, TIPSS, liver transplant
How would you diagnose spontaneous bacterial peritonitis (occurs only in the presence of ascites) (SBP)?
How would you treat SBP?
Ascitic tap: WCC >250mm3, neutrophils >80%, gram -ve rods (+ enterococcus)
Clinical decompensation: encephalopathy, HRS (hepatorenal syndrome)
IV abx, HAS (human albumin solution - hypoperfusing kidneys so supports intravascular space and osmotic presence)
What is hepatorenal syndrome? (And the 2 types)?
How is it treated?
Progressive kidney failure seen in people with severe liver damage, most often caused by cirrhosis. Hepatic circulatory dysfunction. Type 1: preciptant e.g. SBP, acoholic hepatitis; Type 2: progressive - irreversible
HAS, terlipresin, liver transplantation
What is hepatic encephalopathy?
What are the precipitants (causes)?
How is it diagnosed and treated?
Altered level of consciousness resulting from liver failure, mild confusion to coma (Grade I - IV - west haven criteria)
Sepsis, GI bleeding, drugs (opioids, benzos), dehydration (diuretics), portal vein thrombosis (shunt)
Dx: clinical (confused/drowsy/coma), hepatic flap (asterixis), EEG (slow moving delta waves), serum ammonia (increase)
Tx: treat precipitants, lactulose (decreases ammonia absorption from bowel), rifaximin (abx), liver transplant
What is the main risk factor for hepatocellular carcinoma (HCC)?
How is it screened?
How is it diagnosed and treated (curative and palliative)?
Cirrhosis. (HBV, HCV, haemochromatosis)
Screened every 6m (USS) if cirrhotic, look for mass lesion. If yes = MRI/CT.
Dx: CT triple phase, MRI. Clinical decompensation
Tx: Curative = surgical resection, liver transplant (Milan criteria: 3 tumours <3cm or 1 <5cms), radiofrequency ablation
Palliative = transcatheter arterial chemoembolisation (TACE) [Pic], RFA, sorafenib (decreases growth of BV around tumour)
What are some indications for a liver transplant?
How does portal hypertension lead to ascites and hepatorenal syndrome?
Decompensated CLD, HCC, acute liver failure, variant syndrome. Lifelong immunosuppression needed
[Pic]
