Cirrhosis Flashcards
What range of points are associated with each Child-Pugh grade?
Grade A = <7 points
Grade B = 7-9 points
Grade C = 10-15 points
What is the equation for the Mayo End-Stage Liver Disease (MELD) Score?
3.78[ln serum bilirubin (mg/dL)]
+ 11.29[ln INR]
+ 9.57*[ln serum creatinine (mg/dL)]
+ 6.43
same equation; just if you prefer reading it this way
3.78[ln serum bilirubin (mg/dL)] + 11.29[ln INR] + 9.57*[ln serum creatinine (mg/dL)] + 6.43
What are MELD scores used for?
To determine your place on the liver transplant waitlist (higher score = higher priority/more pronounced disease)
Cirrhosis Complications
- Ascites most common, 50% death rate w/in 5 years
- Portal HTN
- Variceal bleeding
- Spontaneous bacterial peritonitis (SBP)
- Hepatic encephalopathy
- Hepatorenal syndrome common cause of death for a lot of patients
Cirrhosis Lab Values
- Jaundice (high bilirubin)
- LFTs/ALT and AST (can be increased or decreased due to acute and chronic alcoholism, respectively)
- Low albumin
- High PT/INR (poor clotting)
- Low platelets
Cirrhosis Causes
- Chronic alcohol use #1 cause
- Hepatitis C
- Fatty liver disease
Portal HTN/Ascites Pathophys
Hepatocytes scar and die off, resulting in a narrowed sinusoidal space. The narrowing of this space increases pressure and causes fluid backup (wants to avoid high-pressure space)
Ascites Physical Exam Characteristics
- Full, dense abdomen
- Bulging abdomen
- Trouble breathing
Ascites Diagnosis
- Abdominal ultrasound followed by paracentesis (drainage of ascitic fluid)
- Serum ascites albumin gradient (SAAG): if serum albumin - ascitic albumin ≥ 1.1 then portal HTN is present
Ascites Treatments (Names)
- Na+ restriction
- Spironolactone
- Furosemide
- Midodrine
- Large volume paracentesis (LVP) conditional
Ascites Treatment: Na+ (Dose/Pearls)
- Restrict to 2g/day
- Do NOT fluid restrict
Ascites Treatment: Spironolactone
- 50-100mg titrated prn up to 400mg/day
- START BEFORE LOOP DIURETIC IF LOW BP
- AEs: gynecomastia, hyperkalemia
- Preferred over loop diuretics in cirrhotics (more diuresis for this patient population)
Ascites Treatment: Furosemide
- 40mg/day titrated prn up to 160mg/day
- Maintain 40:100 ratio of furosemide:spironolactone (dose optimization)
- AE: hypokalemia
Ascites Treatment: Midodrine
- Increases BP
- Used in pt w/ hypoTN
Ascites Treatment: Large Volume Paracentesis (LVP)
- Use when not responding to/tolerating diuretics and/or midodrine
- Remove 4-8L of fluid q2weeks
- Decreases BP and mortality
- If taking out >5L, give 8g IV albumin per L removed
TIPS Procedure (Transjugular Intrahepatic Portosystemic Shunt)
- Used when LVP cannot be tolerated AND failed diuretics
- Used for refractory variceal bleeding
- Restores blood flow from portal to hepatic vein via bypass stent placement
- AE: hepatic encephalopathy (bypassing reduces ammonium metabolism)
- Do NOT perform TIPS procedure if Hx of hepatic encephalopathy
Portal HTN/Variceal Bleeding Pathophys
More than appropriate blood flow leads to distention of GI vessels (which are not designed to hold high blood flow/BP)
Varices Diagnosis
- Esophagogastroduodenoscopy (EGD)
- Admission due to ascites
When to treat portal HTN?
When varices are present
Portal HTN (+ varices) Treatment Drug Class
Non-selective beta blockers
Portal HTN (+ varices) Treatment
- Propranolol 20-40mg BID
- Nadolol 20-40mg QD
- Carvedilol 3.125mg BID drops BP the most
- Titrate until 60bpm
- Hold BB if SBP <90mmHg, DBP <60mmHg, HR <60bpm
Acute Variceal Bleeding Patho/Pearls
- Blood vessel rupture (GI bleeding)
- Causes 1/3 of cirrhosis-related deaths
- Risk factor for SBP (peritoneal infection)
Acute Variceal Bleeding Treatments (Names)
- IV isotonic solution (+O2 supp)
- PRBCs if necessary
- Octreotide
- Endoscopic Variceal Ligation (EVL)
- SBP Prophylaxis conditional
- Non-selective BB conditional
Acute Variceal Bleeding Treatment: IV Isotonic Solution
- NS or LR
- Supplemental O2
Acute Variceal Bleeding Treatment: PRBCs
- Only if Hgb <8g/dL
- 1 unit = 1g/dL
Acute Variceal Bleeding Treatment: Octreotide
- IV bolus then infusion
- Vasoconstricts dilated splantic vessels
- Inhibits intestinal secretion
Acute Variceal Bleeding Treatment: Endoscopic Variceal Ligation (EVL)
- Banding of varix to kill it
Acute Variceal Bleeding Treatment: Non-Selective BB
- Admin only when bleed and vital signs stabilize
SBP (Spontaneous Bacterial Peritonitis) Patho
- SBP = “spontaneous bacterial peritonitis”
- Bacterial infection (enteric gram neg. and some pos.) in ascitic fluid
- Bleeding in GI tract = higher risk of bacterial in peritoneal space and BP drops
SBP Diagnosis
- Elevated WBC
- Malaise, weakness
- Abdominal pain
- Fever
- Paracentesis (takes 72hrs): PMN ≥ 250mm^3
PMN = WBC in ascitic fluid * %PMN
SBP Active Treatments
- 1st line: 3rd gen cephalosporin → ceftriaxone 2g x5days
- Ciprofloxacin x5 days if anaphylaxis to beta-lactams
- IV albumin 1.5g/kg on day 1 then 1g/kg on day 3 (decreases mortality)
- Repeat paracentesis 48hrs after ABX start to confirm efficacy/resistance
- If PMN does not drop >25% then go with broad-spec ABX (e.g. carbapenems) x5 days
SBP Prophylactic Treatment
If acute variceal bleeding…
- 1g ceftriaxone IV x7 days
- Ciprofloxacin x7 days if allergic
- Can de-escalate to PO when discharged
If indefinite prophylaxis (Hx of SBP):
- Ciprofloxacin 250-500mg QD for life
- Bactrim DS (double strength) QD for life
Hepatic Encephalopathy Pathphys
Decreased hepatic function and portosystemic shunting leads to a decrease in ammonia detoxification. The excess ammonia crosses the BBB and exhibits CNS effects.
Hepatic Encephalopathy Presentation
- Altered mental status (e.g slow responses, coma)
- Elevated ammonia levels (but does not correlate with mental status)
Hepatic Encephalopathy Treatments (Names)
- Remove precipitating factors
- Protein
- Lactulose
- Rifaximin
Hepatic Encephalopathy Treatment: Remove Precipitating Factors
- Psychotropic medications (e.g. benzos, anti-seizure meds, bipolar meds)
- Treat UTI (?)
Hepatic Encephalopathy Treatment: Protein
- Patients need protein (in catabolic state)
- Use dairy/vegetable sources w/ branched amino acids → less likely to cross BBB
Hepatic Encephalopathy Treatment: Lactulose
- Targets ammonia in GIT
- Cathartic effects
- Fermented/broken down by gut flora → prod. organic acids → lowers colonic pH → enhances movement of ammonia from blood into bowel → converted into ammonium and gets trapped in bowel → eliminated in stool
Acute HE:
- PO: 25mL q1-2h until ≥2 loose stools
- Enema: 300mL retention enema for 1 hour q6-12h
HE Prevention:
- 15-60mL q6-12h
- Titrate until 2-3 soft bowel movements qd
Hepatic Encephalopathy Treatment: Rifaximin
- Reduces bacteria that produces ammonia
- Add-on therapy to lactulose PRN
Acute HE:
- 400mg PO q8h
HE Prevention:
- 550mg PO BID
AEs: Well-tolerated
Hepatorenal Syndrome Pathophys
Splanchnic vasodilation due to portal HTN leads to reduced effective circulating volume. Decrease circulating volumes means less renal perfusion, which leads to AKI.
*High mortality rate (95% w/in 30 days)
Hepatorenal Syndrome Diagnosis
- Cirrhosis w/ ascites and SCr ≥ 0.3mg/dL increase from baseline in 48hrs
-OR-
- ≥50% increase in baselines SCr in last 7 days w/ no improvement of SCr after 2 days of diuretic cessation and IV albumin use
- If no improvement after 2 days → ESRD :(
Hepatorenal Syndrome Treatment
- IV norepinephrine
-AND- - IV albumin 1g/kg/day
Measures of efficacy:
- SCr decreases to 1.5mg/dL -OR- return within 0.3mg/dL of baseline over max 2 weeks
- If after 4 days of therapy SCr remains the same or rises then d/c (lack of efficacy)
PKPD Changes in Cirrhosis: Decreased Liver Blood Flow
- Portal HTN shunts blood away from liver
Impacts drugs w/ high first-pass (movement from GIT to liver) - Less first-pass and therefore higher systemic concentrations
- Propranolol - titrate to effect
- Morphine - titrate to effect or change to diff agent (e.g. Dilaudid/hydromorphone)
- Carvedilol (Coreg) - titrate to effect
- Decrease doses to compensate
PKPD Changes in Cirrhosis: Loss of Hepatocyte Function
- Decreased metabolic capacity
- Phase I (CYP450) more affected than Phase II (glucuronidation and sulfation)
- If drug is CYP-dependent → increased therapeutic effects/concentrations
Use agents metabolized by Phase II when possible
1. Benzos: lorazepam (Phase II) > diazepam (CYP)
PKPD Changes in Cirrhosis: Decreased Albumin Production
- Heavily protein bound drugs will have higher free concentrations (therefore higher therapeutic effect)
- Phenytoin: reduce dose if needed
PKPD Changes in Cirrhosis: Reduced Renal Function Due to Increased SCr
- Decreased renal perfusion possible
- Hepatorenal syndrome possible
- Monitor renal function
PKPD Changes in Cirrhosis: Increased Therapeutic Response
- Increased BBB permeability
- Drugs acting on CNS can have greater therapeutic effects
- Opioids
- Benzos
- Monitor effect and decrease doses prn
- If pt is completely out of it after a dose, decrease the dose but only readmin AFTER their mental status returns to normal
