19 - Cirrhosis Flashcards
What does cirrhosis mean?
tawny, yellow/orange colour of diseased liver
Top 2 causes in western world
- chronic alcohol abuse
- chronic hepatitis C
Less common causes of cirrhosis
- nonalcoholic steatohepatitis (NASH)
- chronic hepatitis B
- medications (isoniazid, amiodarone, methotrexate)
Where does liver receive blood from?
hepatic artery and portal vein
Chronic liver disease can lead to liver scarring and cause ?
hepatic fibrosis
Cirrhosis causes blood flow to be _____
altered
Complications from cirrhosis
- portal hypertension
- esophageal and gastric varies with risk of variceal bleeding
- ascites
- spontaneous bacterial peritonitis (SBP)
- hepatic encephalopathy
- other: includes hepatorenal syndrome, hepatopulmonary syndrome
What is portal hypertension?
- increased blood pressure in the portal venous system
- hepatic venous pressure gradient (HVPG) > 5 mmgHg
What are 2 reasons why portal hypertension develops?
1) Scarring of liver causes mechanical obstruction of blood flow from portal vein to liver
2) Splanchnic (GI) arterial vasodilation and decreased response to vasoconstrictors increases blood flow to portal vein
What are varices?
- Portal hypertension with HVPG > 10 mmHG lead to esophageal and gastric varies
- Small veins in the lower esophagus and stomach become distended as blood is redirected
What is ascites?
- Portal hypertension can lead to a cascade of events resulting in ascites - accumulation of fluid in the peritoneal cavity
- Sodium retention, low serum albumin (decreased oncotic pressure), fluid leaks into peritoneal cavity
- Within 10 years, about half of all patients with cirrhosis develop ascites, and half of those patients die within 2 years
What is spontaneous bacterial peritonitis? (SBP)
- infection of ascitic fluid without an obvious surgically treatable source
- bacteria from GI tract end up in ascitic fluid
- exact mechanism has not been definitely elucidated (bacterial translocation? hematogenous transmission?)
- E. Coli, K. Pneumoniae, and pneumococci are most commonly isolated
- High mortality rate (<50% survival 1 year after 1st episode)
What is hepatic encephalopathy?
- Decreased liver function causes neurotoxins to accumulate, affects brain function
- Most commonly implicated: ammonia - increased levels in arterial blood due to decreased liver function, shunting of blood around liver
- Ammonia believed to play key role as attempting to lower levels improves HE, y et blood levels do not correlate with mental status
- Glutamine and endogenous benzodiazepines are among other substances that may play a role
____ is the most accurate way to confirm cirrhosis, but usually not necessary.
Biopsy
Biopsy is not necessary, can usually diagnose from ??
1) signs and symptoms
2) lab values/abnormal endoscopy/abnormal radiographic tests
Symptoms of cirrhosis?
- weight loss
- fatigue
- anorexia
- jaundice
- impotence/decreased libido in men
- abdominal distension
- confusion/mental status changes
- pruritis
- GI bleeding
- dark coloured urine (due to increased levels of bilirubin)
What signs on a physical exam would you see?
- Hepatomegaly
- Splenomegaly
- Spider angiomata
- Caput medusa
- Digital clubbing
- Gynecomastia and testicular atrophy in men
- Jaundice
- Asterixis
- Ascites
- Fetor hepaticas
What are some lab value abnormalities in cirrhosis?
- Moderately elevated aminotransferases (AST:ALT - 2:1 common in alcohol liver disease)
- Elevated alkaline phosphatase (2-3 times normal) with concomitant GGT rise
- Decreased serum albumin (test of liver function)
- Prolonged prothrombin time and elevated INR (test of liver function)
- Hyperbilirubinemia
- Thrombocytopenia, leukopenia, anemia
- Increased serum creatinine
- Hyponatremia
What are some abnormal radiographic tests ?
- Ultrasonography - can detect hepatic nodules and irregularities, ascites
- CT or MRI - can detect hepatic nodules, ascites, varices
What are the two tools for grading severity of liver disease?
1) Cild-Pugh Classification:
- used for recommending drug dosage adjustments in liver failure
- considered bilirubin, albumin, degree of ascites, degree of encephalopathy, degree of prolongation of PT
2) Model for End-Stage Liver Disease Score (MELD Score):
- Used in the allocation of liver transplants
- Considers creatinine, bilirubin, and INR
- Predicts 3 month mortality
* how you decide if someone is eligible for liver transplant
Treatment?
- Slow rate of progression, modify causative factors such as alcohol
- Treat complications
What are complications that may arise?
1) Varices
2) Ascites
3) Spontaneous Bacterial Peritonitis
4) Hepatic Encephalopathy
What are the 2 aspects to treating varices caused by portal hypertension ?
i) Primary prophylaxis of varices
ii) Treatment of acute variceal bleeding
iii) Secondary prophylaxis of varies
Describe primary prophylaxis of varices:
-No varices?
No treatment
Describe primary prophylaxis of varices:
-Small varices with no risk factors?
No treatment
Describe primary prophylaxis of varices:
-Small varices with risk factors for variceal hemorrhage (red wales, child-pugh score C) ?
Treat patient with nonselective beta-blocker
Describe primary prophylaxis of varices:
-Medium to large varices with no bleeding?
Treat patients with nonselective beta blocker
OR
endoscopic variceal ligation
What are some non-selective beta blockers?
- Propranolol - start at 20 mg PO BID
- Nadolol - start at 20 mg PO daily
- Carvedilol - start at 6.25 mg PO BID
-Titrate as tolerated - q3days to heart rate 55-60 ppm continue indefinitely except in ESLD
Mechanism of non-selective beta blockers ?
decrease portal venous inflow by decreasing cardiac output (beta-1) and by decreasing splanchnic blood flow (beta-2)
which decreases build up of blood into the varices
Describe treatment of acute variceal bleeding.
- Medical emergency (15-20% mortality)
- Need to maintain blood pressure with fluids, control/correct bleeding (RBCs, platelets as needed)
- Octreotide
- EVL in conjunction (band varices and then they fall off)
- Prophylaxis for SBP - up to 7 days ciprofloxacin or ceftriaxone
- If still bleeding with Octreotide and EVL, transjugular intrahepatic portosystemic shunt (TIPS)
Dosing and MOA of Octreotide
ASAP - 50 mcg IV x 1, then 50 mcg/hr IV continuous infusion x 3-5 days (inhibits vasodilatory glucagon and has local splanchnic vasoconstrive effect)
Why do we do secondary prophylaxis of varices ?
Why? More than half of patient re-bleed (even higher mortality rate with re-bleeding).
What is Tx for secondary prophylaxis of varices ?
nonselective beta-blocker (propranolol or nadolol) + chronic EVL
Secondary prophylaxis of varices:
If patient previously had ____, then possible liver transplant candidate.
TIPS
Treatment of ascites:
With new onset ascites, need a ____
diagnosis
Treatment of ascites:
What is diagnostic paracentesis?
measure cell count with differential, ascitic fluid total protein, ascitic fluid cultures
Treatment of ascites:
What is SAAG ?
serum-ascites albumin gradient
SAAG = [serum albumin] - [ascitic fluid albumin] (measure both on same day)
Treatment of ascites:
What level of SAAG is accurate for diagnosing ascites from portal hypertension?
SAAG > 11g/L is 97% accurate for diagnosing ascites from portal hypertension
Treatment of ascites:
What is the medication Tx?
- diuresis
- sodium restriction to 2g/day
(fluid restriction usually not necessary unless sodium < 120 mmol/L)
Treatment of ascites:
What diuretics do you use?
What ratio?
Furosemide (loop diuretic)
+
Spironolactone (K+ sparing diuretic)
in a 40mg:100mg ratio to maintain normokalemia
Treatment of ascites:
How do you titrate the diuretics (furosemide + spironolactone)?
Max dose ?
Titrate diuretics up every 3-5 days for goal of 0.5 kg weight loss daily (max dose 160 mg furosemide: 400mg spironolactone)
Treatment of ascites:
What do we monitor for with diuretics?
electrolytes (K+) and sCr
Treatment of ascites:
How do we treat ascites refractor to diuretics?
therapeutic paracentesis (can sometimes drain well over 5 L)
Treatment of ascites:
What medications should you avoid?
avoid NSAIDs, generally avoid ACEi/ARBs
- NSAIDs can cause fluid retention
- ACEi/ARB associated with increased mortality in cirrhosis
Treatment of ascites:
Can also use ____ _____ for varies, weight risk to benefit in refractory ascites
beta blockers
Presentation of SBP (spontaneous bacterial peritonitis)
-may be asymptomatic, but often presents with one or more of fever, abdominal pain, encephalopathy, confusion, renal failure
How is SBP (spontaneous bacterial peritonitis) diagnosed?
polymorphonuclear leukocyte (PMN) > 250 cells/mm^3 and positive ascitic fluid bacterial cultures
When do we treat SBP (spontaneous bacterial peritonitis) empirically?
if PMNs > 250 or if signs/symptoms of infection
What do we use to treat SBP (spontaneous bacterial peritonitis)?
- Broad spectrum antibiotics to cover E. coli, K. pneumoniae, and pneumococci
- 3rd gen cephalosporin preferred (cefotaxime 2g IV q8h)
- quinolone is second line (ciprofloxacin)
How long do we treat SBP (spontaneous bacterial peritonitis) ?
5 day Tx course (10 days usually not necessary)
Following episode of SBP, give long-term prophylaxis with ?
-quinolone
OR
-sulfa-trim
(lower dose than standard dose)
-can be once daily, 5 days/week, or weekly dosing
How can hepatic encephalopathy present?
- acutely (episodic)
- continually (persistent)
- recurring (more than 1 episode < 6 months apart)
What are precipitating factors for hepatic encephalopathy?
- electrolyte abnormalities (dehydration, diuretic overuse)
- infection
- GI bleeding
- constipation
What is the mainstay of therapy in treating hepatic encephalopathy?
reduce ammonia levels
List 3 treatments for hepatic encephalopathy
- Lactulose
- Rifaximin
- Neomycin/metronidazole
Describe Lactulose route of administration for treating hepatic encephalopathy
- can give orally (typically 15-30mL/dose), nasogastrically, or rectally
- prefer PO/NG (PR inconvenient - 300mL lactulose qs to 1L with H20, retain 1hr)
Describe lactulose metabolism and MOA for treating hepatic encephalopathy
- metabolized to acetic acid and lactic acid
- lowers ammonia by more than one mechanism, including: laxative effect = less time for systemic ammonia absorption from gut, decreased pH leaves NH4+ cations “trapped” in acidified colon
How do you give lactulose to treat hepatic encephalopathy?
Acutely can give q1h to initiate laxative effect, then titrate for approx 3 soft stools daily.
Monitor for improved mental status
Describe Rifaxamin for treating hepatic encephalopathy
- poorly absorbed synthetic antibiotic
- believed to reduce ammonia-producing bacteria in the gut
- Rifaximin 550 mg PO BID
- Part 3 EDS in Manitoba ($1000+ monthly in 2018) - use in conjunction with lactulose in overt recurrent HE not responding to maximum tolerated doses of lactulose alone
Describe neomycin/metronidazole for treatment of hepatic encephalopathy
not commonly used anymore, higher risk of side effects (neomycin - ototoxicity, nephrotoxicity; metronidazole - neurotoxicity)
