Portal HTN & Complications of the Liver

cirrhosis

end stage of any chronic liver disease

Variceal hemorrhage is a complication of ____ cirrhosis

decompensated

Ascites is a complication of ____ cirrhosis

decompensated

hepatic encephalopathy is a complication of ____ cirrhosis

decompensated

recurrent variceal hemorrhage is a complication of ____ cirrhosis

late decompensation

refractor ascites is a complication of ____ cirrhosis

late decompensation

hyponatremia is a complication of ____ cirrhosis

late decompensation

HRS is a complication of ____ cirrhosis

late decompensation

recurrent hepatic encephalopathy is a complication of ____ cirrhosis

late decompensation

jaundice is a complication of ____ cirrhosis

late decompensation

Two types of cirrhosis

compensated and decompensated

clinical presentation of ascites

edema and abdominal swelling

two main categories of cirrhosis complications

portal hypertension and liver insufficiency

T/F: A patient with decompensated cirrhosis can develop portal hypertension AND liver insufficiency

True

Which cirrhosis complication can be caused by portal HTN and liver insufficiency

encephalopathy

Which cirrhosis complication is due solely to liver insufficiency?

jaundice

What is Portal HTN?

Increased pressure in the portal vein → increased portal venous blood flow or hepatic resistance → body responds by developing large veins or varices to reduce portal pressure

Most common cause of portal HTN

cirrhosis

Most common contributor to cirrhosis

chronic alcohol consumption

propranolol brand name

inderal

nadolol brand name

corgard

carvedilol brand name

coreg

name the NSBB we use in PAH

propranolol (Inderal), nadolol (corgard) and carvedilol (coreg)

NSBB CIs

• asthma (uncontrolled)

• diabetes (uncontrolled)

• peripheral vascular disease

NSBBs are primarily metabolized by CYP…

CYP2D6

How do NSBB work to tx Portal HTN?

• blocks B1 in the heart to decrease cardiac output

• blocks B2 to cause splanchic vasoconstriction→ reduces portal venous inflow

  • body compensates (in PAH) by forming varices → increase flow → increase pressure

Ascites

Accumulation of fluid in peritoneal space as a result of hypoalbuminemia (d/t decreased protein synthesis caused by Portal HTN)

Non-Pharm Management of ascites

• sodium (< 2g/day)

• water restriction (< 1L) if SX dilutional hyponatremia

  • low Na + ascites ± edema

• paracentesis: for large volume & refractory ascites

TX approach for ascites

• pericentesis → drain excess fluids from abdomen into vacutainers

• diuretics

• albumin → increase colloid pressure inside veins → brings water back into veins

• monitor vital signs & electrolytes

DOC for ascites

spironolactone

monitoring for spironolactone

hyperkalemia & gynecomastia

furosemide use in ascites

used in combination with spironolactone (cannot be used as monotx)

spironolactone:furosemide dosing

100mg:40mg

If you can only use one medication for ascites, what would you recommend?

spironolactone

albumin place in tx of ascites

prn for large volume paracentesis (> 5 L removed)

albumin MOA

binds to vasoconstrictors to expand fx plasma volume (may improve fx of vasopressors)

how to choose best albumin strength?

choose one with the less volume (high % too?)

PREFERRED tx for pt with Portal HTN and ascites

spironolactone ± furosemide

In what scenario would you want to stop albumin infusion early?

if pt is hypotensive

Which medication used for ascites would need to be d/c if CrCl < 10 mL/min (acute renal failure)?

spironolactone

Hepatorenal Syndrome (HRS)

rapid progressive renal dysfunction that occurs in conjunction w/ advanced cirrhosis, circulatory dysfunction and acute liver failure

Pathophysiology of HRS

Affected by various pathophys from diff organs

• GI: bacteria enters the gut and triggers release of proinflammatory cytokines

• Liver: activation of RAAS and SNS as a result of hypovolemia from cirrhosis and portal HTN (compensatory mechanism) → renal vascoconstriction & decreased renal blood flow and eGFR

• Heart: high output → HF → reduced cardiac output → hypovolemia

HRS-AKI criteria

• increase in SCr > 0.3 mg/dL w/in 48 H AND/OR

• UOP < 0.5 mL/kg for > 6 hours OR

• % increase in SCr > 50% baseline (using last available SCr lvl w/in past 3 months)

Causes of HRS-AKI

• bacterial infection

• acute liver injury

• alcohol/drug abuse

• hypovolemia d/t overuse of diuretics

• variceal bleeding

• nephrotoxic medications

Nephrotoxic medications that should be d/c in HRS-AKI

• diuretics

• NSAIDs

• vasodilators

• antihypertensive agents

• aminoglycosides

Volume replacement tx algorithm for hypovolemia

• d/c any diuretic or laxative

• initiate 25% IV albumin

Name the only curative tx for HRS-AKI and what is the problem

transplant - can take years to get off the list but pt needs transplant urgently

What do we give pts with HRS-AKI if we suspect spontaneous bacterial peritonitis (SBP)

3rd gen cephalosporins

What do we give pts with HRS-AKI if pt is having a GI bleed?

NSBB

T/F: albumin is the gold standard for HRS-AKI as monotherapy

False - needs to be coupled with a different agent (midodrine or ocreotide)

Midodrine vs ocreotide : which is in an oral formulation?

midodrine

Midodrine vs ocreotide : which is given IV or SQ?

ocreotide

Midodrine vs ocreotide : which is an alpha 1 agonist ?

midodrine

Midodrine vs ocreotide : which is a somatostatin analogue

ocreotide

ocreotide (sandostatin) ADRs

bradycardia, peripheral edema, hyperglycemia, nausea

ocreotide brand name

sandostatin

midodrine brand name

proamatine

norepinephrine brand name

levophed

terlipressin brand name

terlivaz

norepinephrine MOA

increases arterial blood volume and pressure → improves renal blood flow

terlipressin MOA

acts on vasopressin V1 receptors → vasoconstriction → increased arterial blood volume and MAP

which trial failed to demonstrate a difference in complete HRS reversal between terlipressin and placebo

REVERSE trial

which trial showed a higher rate of complete HRS reversal with terlpressin vs placebo

CONFIRM Trial

Severe Terlpressin ADR that would warrant d/c

acute respiratory failure

What SPO2 lvl would warrant waiting before initiation terlipressin?

< 90% - would wait till levels improve

When would NE be preferred over terlipressin?

when the pt is in the ICU and/or requires vasopressors

How should you modify tx for HRS-AKI if pt has an ischemic event?

d/c terlipressin

How should you modify tx for HRS-AKI if pt has hypoxemia

• do not initiate terlipressin until oxygenation improves

• d/c terlipressin if it occurs while on tx

How should you modify tx for HRS-AKI if pt has volume overload?

• reduce or d/c albumin or other sources of fluid

• judicious use of diuretics

• consider interupting or reducing terlipressin tx until volume overload reduces

midodrine + ocreotide place in tx for HRS-AKI

floor patients/outpatients as part of step up approach (aka if terlipressin is not available)

gold standard vasoconstrictor to add w/ albumin for HRS-AKI?

terlipressin

Variceal bleeding

varices form as a result of resistance of drainage of venous blood from the GI to the liver → varices are weak and easily damaged → GI bleeding

Agents used for fluid resuscitation in acute variceal bleeding

• colloids

• FFP/platelets if significant coagulopathy and/or thrombocytopenia

Ocreotide is preferred over what agent for management of bleeding in acute variceal bleeding

vasopressin - non-selective → increased risk of ADRs

What drug class should NOT be used in acute variceal bleeding and why?

B-blocker → decrease BP causes increased HR and may worsen bleeding risk.

Preferred agent for TX (of bleeding) of acute variceal bleeding

ocreotide (sandostatin) ; continue 24-72 H after bleeding has stopped

Ocretodide should be used in caution with pts on ___

hemodialysis (except acute variceal hemorrhage since that is urgent scenario)

Vasopressin should be admin with ___

IV nitroglycerin

Nitrates MOA

• decreases intrahepatic or port collateral resistance

• systemic hypotensive fx → decrease portal pressure is related to hypotension

which is the best NSBB? why?

carvedilol (d/t additional alpha blockage fx)

First line for prevention of variceal bleeding

NSBBs (propranolol or nadolol)

Alternative for prevention of variceal bleeding if pt cannot take NSBBs

endoscopic variceal ligation (EVL) followed by pantoprazole

T/F: Isosorbide mononitrate is the preferred first line tx for prophylaxis of variceal bleeding

False

Hepatic encephalopathy

Accumulation of ammonia (NH3) due to cirrhosis and results in neurological impairment and cognitive dysfunction.

• accumulation cause d/t liver damage as ammonia is converted to ammonium by the liver

T/F: NH3 levels do not correlate with degree of CNS impairment

True

First line agent for hepatic encephalopathy

lactulose (enulose, kristalose)

Lactulose (Enulose, Kristalose) MOA

decreases colonic pH to allow conversion of NH3 to NH4 → traps it in the GI lumen to be excreted

Lactulose ADRs

diarrhea

Explain recurrence that occurs w/ lactulose use

recurrence occurs in pts who are nonadherent (d/t GI tolerability ADRs such as diarrhea and abdominal pain)

Modifications to tx if refractory hepatic encephalopathy

replace lactulose with rifaximin OR add rifaximin to low dose lactulose

physician is considered neomycin, metronidazole or vancomycin for hepatic encephalopathy tx - is this ok?

no - rifaximin is the preferred ABX

Target diet for hepatic encephalopathy

• daily energy intake: 35-40 kcal/kg of ideal BW

• daily protein intake: 1.2-1.5 g/kg/day

• small meal or liquid nutritional supplements evenly distributed throughout the day

• late night snacks should be offered