Cirrhosis Flashcards
List 3 red flags in labs that would suggest cirrhosis
1) Low platelets
2) Low albumin
3) High INR (one of the most sensitive markers for hepatic function)
What diet should you have in cirrhosis?
High protein diet (at least 1g/kg/day) as cirrhosis is a catabolic state
Low sodium diet only if ascites are present
What is the FIB-4?
=AgexplatAST x ALT
Probability of cirrhosis
Most useful at the margins (i.e. ruling out or confirming dx if the history is supportive). Indeterminate scores need biopsy.
<1.45 has NPV of 90% of advanced fibrosis
>3.25 has PPV of 65% of advanced fibrosis
In what situations is fibroscan or shear wave elastography most useful?
1) Diagnosing cirrhosis in thin patients with Hep C
2) Ruling out (High NPV) cirrhosis in obese patients with diabetes and/or fatty liver disease
Important screening in cirrhosis
1) Screen for varices in cirrhosis at the time of diagnosis, then every 1-3 years based on size with esophagogastroduodenoscopy (EGD)
2) Liver US every 6 months for hepatocellular carcinoma in cirrhosis
AFP is no longer recommended in the guidelines but some doctors still do it
7 hand findings of cirrhosis
1) Palmar erythema
2) Dupuytren’s contracture
3) Terry’s nails
4) Clubbing
5) Asterixis
6) Spider angiomas
7) Muscle wasting
How does cirrhosis cause thrombocytopenia?
Cirrhosis –> portal hypertension –> hypersplenism –> spleen sequestration of platelets
Indicates advanced disease
How does cirrhosis cause low albumin?
Liver makes albumin
How does cirrhosis cause prolonged INR? How does this affect coagulopathy?
Liver makes all coagulation factors except factor VIII (made by endothelial cells), but liver also makes all procoagulant and anticoagulant (protein C, protein S, anti-thrombin) so this is actually quite balanced. The only problem is it can tip either way pretty quickly.
INR tells us about liver function but cannot tell us about coagulopathy. INR tells us about the bleed, but NOT the anti-bleed side of the equation.
Indicates advanced disease
One of the most sensitive markers for hepatic function
Is ultrasound useful in cirrhosis?
Only able to show advanced fibrosis
Good for looking at vessels or any obvious lump/bumps
When do you do liver biopsy?
Still the gold standard
Do it when there is an indeterminate score on FIB-4
Limited by sampling bias (only sample like 1/50000th of liver)
List 3 ways cirrhosis can kill you
1) Liver failure
2) Variceal bleeding
- Patient with index variceal bleed has 1/4 chance of dying from variceal bleeding
3) Hepatocellular carcinoma
What’s the risk of liver cancer in cirrhosis?
3-5% per year
Rx for suspected variceal bleed
- x2 large bore IVs
- Aim SBP >90 (if BP too high, can increase bleed)
- Fluids (blood and albumin; avoid N/S and CSL).
- Gently transfuse blood. Aim Hb >70. If transfuse too aggressively, can increase portal hypertension and bleeding.
- Terlipressin reduces portal pressure
- Early blood cultures and IV ceftriaxone for 5 days
- Endoscopy for banding within 12 hours
- IV thiamine if still drinking
Define compensated, decompensated and late decompensated cirrhosis
Compensated: No ascites, encephalopathy, variceal bleeds.
Compensated cirrhosis can be broken down into those with and without varices, or with or without portal hypertension
Prognosis 10-20 years
Decompensated: ascites, variceal bleed, encephalopathy. Prognosis months-years.
Late decompensated: recurrent variceal bleeds, refractory ascites, hepatorenal syndrome, recurrent hepatic encephalopathy, or continuous jaundice.
Much poorer prognosis (survival is measured in months or less). Need to consider transplant.
Define acute on chronic liver failure
Underlying liver disease (doesn’t have to be cirrhosis, can be fatty disease, chronic hep C)
+
Development of liver failure (e.g. jaundice, elevated INR, elevated bilirubin compared to baseline)
+
≥1 extrahepatic organ failure (i.e. AKI, encephalopathy/CNS failure, hypotension)
50-70% mortality during acute admission
In someone with cirrhosis who presents with decompensation, what must you rule out?
Rule out infection! Especially if there is ascites
CXR to look for infection
Blood culture
Urine MCS
Diagnostic paracentesis
Is ammonia level useful in hepatic encephalopathy?
Not useful because they do not correlate with levels of hepatic encephalopathy
Encephalopathy is a clinical diagnosis in cirrhosis, not a lab diagnosis.
Consider checking ammonia in the encephalopathy patient without known liver disease or as a prognostic tool in patient with acute liver failure (can prognosticate who is at risk of acute brainstem herniation)
PPI for variceal bleeding?
PPIs DO NOT have efficacy for variceal bleeding since it’s a pressure phenomenon. However its commonly given since its difficult to know if its variceal bleeding or ulcer bleeding until you do endoscopy.
Proton-pump inhibitors may help prevent bleeding from post-banding ulcers
How does octreotide and terlipressin work in variceal bleeding?
Vasoconstricts mesenteric vasculature –> decreases portal flow –> decreases portal pressure –> stops bleeding
Terlipressin can also boosts BP
Approach to hepatic encephalopathy
What to look for?
1) History
2) Exam
3) Labs
ABC! Do they need intubation/drop in GCS?
1) History
- Dark stools, blood thinners, NSAIDs, sedating medications (BZDs, opioids), ETOH, recent history of falling (ICH)
2) Exam
- Look for ascites and pulmonary oedema
3) Labs
- Low sodium, elevated creatinine = hepatorenal syndrome
- Low Hb = upper GI bleed
List common precipitants of hepatic encephalopathy
Can be anything
Infection Constipation Bleeding (variceal or otherwise) Diarrhoea Metabolic/electrolyte derangement Drugs - opioids, BZDs, GABA-ergic medications Volume depletion Under medication with lactulose Increased shunting due to thrombosis or malignancy (get a liver doppler US!)
Pathophysiology of hepatic encephalopathy
Shunting!!
Can happen in cirrhosis and without but cirrhosis increases the risk
Rx of hepatic encephalopathy
When other causes have been ruled out, mainstay of treatment is lactulose (ask patients to titrate it themselves to ensure BOx3/day)
Lactulose PR if the patient is obtunded
Movicol is an alternative if lactulose is not tolerated
2nd line: rifaxamin
If don’t tolerate lactulose or recurrent encephalopathy despite lactulose
Very good drug. The only limiting factor is $$$$
Observation data suggests possible reduction in infection and mortality
Don’t typically start these medications until patient develops encephalopathy
Whats a TIPS procedure?
Transjugular intrahepatic portosystemic shunt
Placed by interventional radiology to artificially connect portal vein to hepatic vein
This creates a shunt so that blood can pass from portal vein to IVC without going through the fibrotic, high-pressure liver system
TIPS immediately decreases portal pressures to sub-bleeding levels (not necessarily to normal)
Downsides to the TIPS
If the patient has pulmonary HTN, TIPS can cause death from increased preload (do TTE beforehand)
30-40% will develop encephalopathy (due to blood bypassing the liver)
Primary prevention of variceal bleeding (never bled before)
1) Non-selective beta blockers
- Effective at reducing portal pressure and reducing risk of variceal bleeding
- Propanolol or carvedilol
- Start at low dose and increase as tolerated. Goal is to get the pulse down 50-60bpm or 25% reduction in basal heart rate.
- Stop if SBP <90, Na <120 or AKI
2) Variceal banding
Studies use propranolol 80mg BD which is rarely tolerated due to dizziness. Hence most gastro in VIC do banding > beta-blocker
What is the MELD score?
Initially developed to determine suitability for TIPS
Now helps to stratify severity of end stage liver disease, for transplant planning
Estimates 3 month mortality
Not useful in the acute setting
Components
- Creatinine
- Bilirubin
- INR
- Dialysis at least twice in the past week
- (+Na version too)
When to use the CLIF score?
Modified SOFA score
Predicts mortality in acute on chronic failure
Useful in ICU setting to assess the likelihood of improving clinical status with continued intervention
Should we use DVT prophylaxis in cirrhosis?
Probably yes (data is a little controversial) unless there is some other reason not to e.g. very low platelets <50-60
They are at risk of bleeding but this is more likely due to pressure-based phenomenon rather than a true coagulopathy. Clotting also happens more likely with portal venous thrombosis and DVTs.
Does fixing the INR improve bleeding in cirrhosis.
NO
Fixing the INR to normal range does not actually improve bleeding outcomes.
When you give just pro-coagulant factors to improve the INR to a level you are comfortable with, you ignore the anticoagulant deficiencies that are present in liver disease and therefore push the patient towards a pro-clotting picture. These patients may very well clot off their portal veins or mesenteric vasculature.
FFP, Factor VII, and Vitamin K (unless you suspect the patient is vitamin K deficient for some reason) are not helpful.
How much fluid to take off in paracentesis?
Low volume paracentesis 2-3L is all you need for diagnostics - to rule out SBP
Therapeutic large volume paracentesis is only for comfort. And if you have someone with poor renal function, you want to avoid taking too much fluid off at once.
Whats investigations to send in paracentesis?
1) SAAG (serum ascites - serum albumin gradient)
2) Cell count and differential
- To look for SBP
- If PMNs >250, that is diagnostic of SBP
What’s the pathophysiology of SBP?
Bacterial translocate out of the gut, into the blood, and seed the peritoneal space
Ascitic fluid can’t rid itself of translocated bacteria it is protein poor (and therefore IgG and complement poor) and cannot fight off infection
A) Why do you get low albumin (SAAG >11) and low protein in cirrhotic ascites?
B) why do you get low albumin (SAAG >11) and high protein in non-cirrhotic cirrhosis?
The liver sinusoid, which is the liver’s capillary, is built to keep albumin in the blood vessel. In cirrhosis, the liver becomes scarred and the sinusoids lose their fenestrations. After this occurs, albumin and small proteins are even less likely to make it out of the sinusoids. Thus, the ascitic fluid becomes increasingly protein poor.
A) Cirrhotic ascites is protein poor and albumin poor with high SAAG >11. The scarred down liver sinusoids don’t allow the escape of both albumin (large molecule) and other proteins (smaller molecule)
B) In non-cirrhotic ascites (e.g. cardiac ascites), fluid has low albumin (high SAAG) and high protein (smaller molecule). The sinusoids are normal and haven’t lost their fenestrations so small molecules like protein can still go through.
How does ascites form in cirrhosis?
Ascites is fluid that has seeped out of the sinusoids in the liver due to high portal pressures (portal hypertension)
This is further exacerbated by low serum albumin (made by liver) = low oncotic pressure
What does low SAAG <11 mean?
It means there is similar albumin levels in the serum and ascitic fluid
Means the ascites is from an extra-hepatic source
Causes include infection, peritoneal carcinomatosis, malignancy, renal failure, pancreatitis
What does high SAAG >11 mean?
It means the ascites has been pushed out of the liver sinusoids (capillaries) the to high portal pressures
This could be coming from the liver (cirrhosis) or post-hepatic causes (right heart failure, Budd chiari, pulmonary hypertension)
How do you differentiate between liver and non-liver causes of ascites in someone with SAAG >11?
Look at the protein level in the ascites
Proteins other than albumin are much smaller molecules and will get pushed out of the sinusoids if there is no fibrosis surrounding them (i.e. no cirrhosis). Hence you will get high protein in the ascites.
Conversely, if the sinusoids are abnormal and lose their fenestrations and are surrounded by fibrosis (i.e. cirrhosis), even the small proteins can’t get pushed out. Hence you will get low protein in the ascites.
Note: sinusoids are naturally built to keep albumin in the blood vessels hence it will never seep out like fluid or smaller proteins
How does SBP present?
Ascites + abdo pain +/- fever
However can present without fever, abdominal pain or other symptoms
Inflammatory markers not always elevated
Can also present as encephalopathy or variceal bleed or rapid worsening of kidney function
Prevalence of SBP in patients admitted to hospital with cirrhosis and ascites is 10-20%!
How to diagnose SBP?
1) Paracentesis - take 2-3L and send for SAAG, protein, cell count, MCS (also in BC bottle - increase yield by 30%)
2) Blood cultures
What kind of cell counts in ascitic fluid is diagnostic of SBP?
Leucocytes >500, PMN >250
And there is no other cause e.g. perforated viscous or another intra-abdominal infection
How to treat SBP?
1) Abx ASAP
- 5/7 IV ceftriaxone (tazocin if on norfloxacin/bactrim)
- Repeat paracentesis after abx treatment if you are concerned about incomplete resolution
- Patients will need lifelong secondary SBP prophylaxis (Bactrim or norfloxacin)
2) IV albumin
- Goal is to keep the blood in the vasculature instead of causing compartmental shifting with fluid removal after paracentesis
- Reduces mortality (SORT trial)
- IV conc albumin load followed by >2 bottles/day for >3/7
Pathophysiology of hepato-renal syndrome, hyponatraemia and hypotension in cirrhosis (circulatory dysfunction)
1) Cirrhosis and portal HTN is complicated by high levels nitric oxide –> blood pools in the dilated splanchnic (gut) circulation
2) Relative systemic hypoperfusion and low SBP
3) Leads to “high output state” = increased cardiac output
4) Release of ADH, renin, angiotensin, aldosterone lead to increased sodium and water retention
5) Leads to further overload of the splanchnic circulation
Net effects
- Hyponatraemia
- Systemic hypotension
- Hepatorenal syndrome (due to renal vasoconstriction in an attempt to raise BP and the kidneys “strangle themselves” off from their own supply –> renal failure)
What are the 2 types of hepato-renal syndrome?
Type 1 (can happen in SBP) - develop ARF over a few days. These patients need transplant for survival.
Precipitated by sepsis, bleeding, acute on chronic liver failure, SBP.
Mortality in days-weeks.
Potentially reversible.
Type 2 - slower, more insidious process. Patients may not have overt renal failure (or elevated creatinine). Often associated with refractory ascites. Mortality in months.
Rx ascites
1) low sodium diet 2000mg daily limit
- Low sodium diet alone is often enough to control mild ascites
2) diuretics
- Spironolactone +/- frusemide
- To stop the kidney from holding onto all the sodium and water
- Step 1 = 100mg spironolactone daily +/- 20mg frusemide daily (this ratio seems to maintain normokalaemia)
- Step 2 = Increase doses in increments to maintain 100:20mg ratio, aiming 1kg weight loss/day
- Stop increasing dose if Na <130 (WH if Na <125), hyperkalaemic, worsening kidney function (give conc albumin to make sure they’re perfusing their kidneys), side effects (painful gynaecomastia)
How does hepatic encephalopathy present?
Often vague presentation so be on the look out for it!
Reversal of sleep-wake cycle - up all night and sleep during the day
Slow to answer questions
Repetitive speech
Don’t check ammonia level! Just put them on lactulose and see if they feel better
Rx hepatorenal syndrome
- Avoid nephrotoxins
- Treat underlying precipitant
- WH diuretics
- Albumin - 1g/kg daily to maximum of 100g/day (need to fill them up so they can perfuse their organs)
- Terlipressin - splanchnic vasoconstriction. ?Bridge to transplant. Better than norad or octreotide.
Who needs SBP prophylaxis?
1) History of SBP - everyone
2) No history of SBP - need to be much more selective
Low-protein ascites + kidney disease OR
Low protein ascites + hospitalised/at risk for infection
Cirrhosis or fibrosis of the liver is due which cells?
Activation of hepatic stellate cells (liver macrophages)
Involved in healing and repair after biliary or hepatocellular injury –> increased collagen and extracellular matrix
How do fibroscans work?
Looks at the liver stiffness measurement (LSM)
F0-F4 grading based on LSM (kPA)
F0-1 = pretty good NPV for excluding cirrhosis F2-3 = hard to differentiate F4 = cirrhosis however beware that other things such as steatosis, hepatic congestion, hepatic inflammation can push the LSM up
What’s the child Pugh score?
Predicts 1 year and 2 year survival
Looks at 5 components
- Encephalopathy
- Ascites
- INR
- Albumin
- Bilirubin
Child Pugh A - compensated
Child Pugh B + C - developing decompensated disease, risk of complications
What is the hepatic venous pressure gradient and when would you measure it?
Hepatic venous pressure gradient (HVPG) can be measured radiologically but is not commonly done.
HVPG = difference in pressure of the hepatic vein when wedged (sinusoidal pressure) and when free 3-5mmHg = normal >10 = high >12 = varices
It tells us where the obstruction is. If HVPG is normal, it means the obstruction is probably pre-sinusoidal (e.g. portal venous thrombus). If HVPG is high, it means the obstruction is in the sinusoids (e.g. cirrhosis).
What is hepatic hydrothorax?
Ascitic fluid leaking into pleural space
Right sided
Rx hepatic hydrothorax
If symptomatic, may require drain
If drain, need to replace with conc albumin (20% conc albumin 100ml/hr for every 2L drained)
Avoid leaving drains in for >6-8h (risk of SBP)
Not amenable to VATS/surgical rx - don’t work and risk of complication
What fluids to use in someone with chronic liver disease?
5% dextrose
20% conc alb
4% albumin
Blood if Hb <70
Avoid normal saline and CSL - all the salt will retain water –> become more hypervolemic and more hyponatraemic
How much conc albumin to give with paracentesis?
100ml 20% conc albumin over 1/24 with every 2L drained
What is the West Haven Criteria?
To grade severity of hepatic encephalopathy
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
What are some high risk features of varices?
Size
Red wale marks
Advanced liver disease (child Pugh B or C)
Secondary prevention of variceal bleeding (bled before)
1) Variceal banding
2) TIPS
- High hepatic venous pressure gradients
- Very high portal HTN >20mmHg
- Childs B or C cirrhosis who is still bleeding after banding
Is banding or gluing better in variceal bleeds?
Banding is the mainstay of oesophageal varices or gastric-oesophageal varices
Glue is an option for gastric varices. Risk of flicking off a bit of glue into the pulmonary circulation –> PE
What is the Sengstaken-blakemore/minneosta tube?
Inserts like an NGT but it has a gastric and an oesophageal balloon on the end which can be inflated. Acts by tamponading the bleed.
Must be released in 24 hours. If not, risk of ulceration.
Indications of a TIPS procedure
Variceal bleeding despite banding
Diuretic refractory ascites or hepatic hydrothorax
Budd-Chiari
`
Side effects of terlipressin
Powerful vasoconstrictor targeting the splanchnic circulation
Headaches
Diarrhoea
Hypertension
Coronary/intestinal/peripheral vascular disease ischaemia
Beware in those with severe arterial disease and the elderly
