Liver Cirrhosis Flashcards
Pathogenesis of liver cirrhosis
Any condition that causes chronic inflammation -> cirrhosis
Degree of fibrosis F0 - F4 -> bridging fibrosis and nodule formation
Primarily due to activation of hepatic stellate cells (liver macrophages) - involved in healing and repair after biliary/hepatocellular injury, chronic activation -> increased collagen and extra-cellular matrix
Increased intrahepatic vasoconstriction
Increased sphlanchnic vasodilation
Increased sodium retention
Increase in renal vasoconstriction -> decreased renal blood flow -> hepatorenal syndrome
Diagnosis of liver cirrhosis
Gold standard = liver biopsy (but only samples 1/50,000th of liver)
Elastography e.g. fibroscans -> measure of liver stiffness, >= F2 = significant fibrosis
Notes on Child Pugh Score
Mortality highest in patients with infection and renal failure, followed by GI bleeding and ascites
Notes on MELD score
Initially validated as tool for mortality assessment in TIPS, often used for transplant waitlists
Need bilirubin, INR, creatinine
Complications of liver cirrhosis
- Ascites
- Encephalopathy
- Varices
- Spontaneous bacterial peritonitis
- Hepatorenal syndrome
Consequence of portal hypertension
Notes on portal hypertension
Cirrhotic or non-cirrhotic
Cirrhotic
Increased vascular resistance
* Structural (distortion of liver vascular architecture by fibrosis/regen nodules)
* Dynamic (increased hepatic vascular tone due to endothelial dysfn & decreased NO bioavailability)
Can measure HVPG radiologically (uncommon)
Hepatic venous pressure gradient
* measures wedged hepatic venous pressure
o (difference in pressure of the hepatic vein when wedged and compared with free)
o Gives an impression of hepatic sinusoidal pressure but not pre-sinusoidal (eg: PVT)
* 3-5mmHg = normal
* >10 = likely to have clinical sequelae (>12 varices)
Initiating factor leading to portal HTN is an increase in intrahepatic vascular resistance (R), whereas the increase in portal blood flow (F) is a secondary phenomenon that maintains and worsens the increased portal pressure, giving rise
to the hyperdynamic circulation
Non-cirrhotic causes of portal hypertension
Pre-sinusoidal
1. Portal vein compression (lymphoma, carcinoma)
2. Intravascular clotting (polycythaemia)
3. Umbilical vein phlebitis
Intrahepatic
1. Sarcoid, lymphoma, leukaemic infiltrates
2. Congenital hepatic fibrosis
Post-sinusoidal
1. Hepatic vein outflow obstruction (Budd-Chairi) -> idiopathic, myeloproliferative disease, cancer (kidney, pancreas, liver), COCP, pregnancy, paroxysmal nocturnal haemoglobinuria, fibrous membrane, trauma, schistosomiasis (most common in developing world)
2. Veno-occlusive disease
3. Constrictive pericarditis
4. Chronic cardiac failure
Oesophageal varices -> prognosis and high risk features
In patients with varices, rate of haemorrhage ~12%
- 5% small varices
- 15% for large varices
High risk features:
Size
Red wale marks
Advanced liver disease (Child B/C)
1 year recurrence rate after a variceal haemorrhage is 15-20%
Worse with Child Pugh C patients (up to 30%)
All patients with cirrhosis should have a screening gastroscopy
* Primary prophylaxis: variceal banding v beta-blockers (propranolol/carvedilol)
* Secondary prophylaxis: variceal banding to eradication
Management of bleeding oesophageal varices
- AIM SBP>90 mmHg
- Aim Hb>70
- Blood/albumin preferable
- Avoid N/S and CSL
- Don’t forget aetiology of liver disease (eg: thiamine IV if alcoholic liver disease and still drinking)
- Early blood cultures and empirical iv abx (ceftriaxone)
- Terlipressin
- Endoscopy - generally banding, glue may be an option for gastric varices
Indications for transjugulat intrahepatic portosystemic shunt (TIPS)
Indications:
* Variceal bleeding unable to be treated endoscopically
* Diuretic refractory ascites or hepatic hydrothorax
* Budd-Chiari
MELD score initially developed to determine suitability for
TIPS1
Increased risk of HE; beware in right heart failure (TTE
preferable prior)
NEJM 2010 study recommending early TIPS for variceal
bleeding
359 patients screened, only 60 randomized
early TIPS a/w improved survival, less re-bleeding
Grading of hepatic encephalopathy and precipitants
Grading
Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction
Grade 2 - Lethargy or apathy; minimal disorientation for time/place; personality change, inappropriate behaviour
Grade 3 – somnolence to semistupor but responsive to verbal stimuli; confusion; gross disorientation
Grade 4 – Coma
**Preceipitants
Infection, bleeding, constiptation/diarrhoea, drugs -> opioid, benzodizepines, metabolic/electrolyte derangement
Management of hepatic encephalopathy
- No role in measuring ammonia levels
- Lactulose -> converted to lactic acid -> acetic acid in gut lumen -> acidification. Favours conversion of ammonia -> ammonium -> trapped in gut lumen. Reduced ammonia absorption. Gut acidification also inihibis ammoniagenic coliform bacteria
- Rifaximin -> greater time to first HE episode and first hospitalisation for HE compared to placebo
Notes on ascites - diagnosis and complications
Reflects renal Na and H20 retention via activation of renin-angiotensin-aldosterone
SAAG > 11 suggestive of portal HTN (serum albumin - ascites albumin)
Portal hypertension primary driver of ascites (not hypoalbuminaemia)
Causes of low gradient ascites (SAAG <11)
- Peritoneal carcinomatosis
- Tuberculosis
- Pancreatic ascites
- Nephrotic syndrome
Complications
1. Spontanous bacterial peritonitis -> ascites and abdominal pain +/- fever. Inflammatory markers not always elevated. Leucocytes >500, PMN >250 ascitic fluid. Treatment -> ceftriaxone. IV albumin load followed by daily administration (>2 bottles/day) for >3/7
2. Hepatic hydrothorax -> ascitic fluid leaking into pleural space, right sided. Need to replace with albumin if drained -> avoid leaving drains in (same risk of infection as SBP), poorly treatable by VATs/surgical
Management of ascites
1.Salt restriction -> 5g/day (more effective than fluid restriction). Avoid Nacl, CSL
2. Diuretics -> spironolactone 100mg (+furosemide 20mg)
- Aim 1kg weight loss/day
- Uptitrate if Na >130, not hyperkalaemic, kidney functino permitting
- Increment by spiro 100
3. Paracentesis - 20% concentrated albumin 100ml over 1 hour for each 2L ascites drained to prevent large volume paracentesis associated renal failure/hypotension. If required > fortnightly -> consider other options (TIPS, transplantation)
Preferred fluids in ascites
- 5% dextrose, 20% concentrated albumin, 4% albumin, blood if Hb <70
Diuretic resistant ascites (ANSWER Study):
Spirinolactone >200mg/day, furosemide >25mg/day - assigned to standard medical therapy v SMT + albumin as outpatient
- Significant improvement in survival and reduction in portal hypertension complications (except variceal bleeding)
