end stage liver disease

cirrhosis

one of the stages of liver failure

late stage of progressive hepatic fibrosis w/ distortion of hepatic architecture + formation of regenerative nodules

causes of cirrhosis

alcoholism!

viral hep C

viral hep B

metabolic liver disease

immunologic disease

vascular disease

drug induced liver injury

cirrhotic liver

chronic and irreversible

diffuse, extensive fibrosis

regenerative nodules

vascular architecture - scarring

non specific sx of cirrhosis

anorexia, wt loss, weakness, fatigue

s/sx of hepatic decompensation

jaundice, pruritus, UGIB (upper gi bleed), abdominal distension (ascites), confusion (hepatic encephalopathy)

physical exam findings of cirrhosis

ascites, digital clubbing, spider angiomas, gynecomastia, asterixis, palmar erythema, jaundice, splenomegaly

dx tests/possible etiologies for cirrhosis

CMP → ALT, AST, alkaline phosphatase, bilirubin, albumin, gamma-glutamyl transpeptidase (GGT)

CBC + coagulation test

serology for HBV, HCV (viral hep)

alcoholism

obesity + hx of diabetes

antinuclear antibodies (autoimmune hepatitis)

serum iron + transferrin saturation (hemochromatosis)

what lab abnormalities show cirrhosis

increased serum bilirubin, AST, ALT, alkaline phosphate, GGT, PT, INR

hyponatremia, thrombocytopenia

what radiographic imaging shows cirrhosis

ascites, varices, splenomegaly, hepatic/portal vein thrombosis

what other test/procedure can you use to confirm dx of cirrhosis

liver biopsy (will defnitively confirm)

fibroscan/transient elastography/FIB-4

non-invasive ultrasound methods that measure amount of liver fibrosis (liver stiffness measurement, LSM)

fibrosis-4 (FIB-4) score of >3.25 predicts fibrosis

screening for hepatocellular carcinoma (HCC)

biannually, abdominal ultrasound + serum alpha-fetoprotein (AFP) improve early detection in pts w/ cirrhosis regardless of etiology

pt w/ cirrhosis + greater than 1 cm mass on screening ultrasound or with rising or elevated AFP level (>20 ng/ml) need further dx work up

solid lesion on multiphasic contrast imaging can be dx as HCC

compensated cirrhosis

asymptomatic!!

may include non-specific sx, fatigue, loss of appetite, wt loss

may have elevated hepatic venous pressure gradient (HVPG) and varices, but not experience complication of vericeal bleeding, ascites, SBP or encephalopathy

decompensated cirrhosis

symptomatic!!

ascites, variceal hemorrhage (hematemesis or melena), hepatic encephalopathy (confusion, lethargy, flapping, tremor, coma), jaundice (skin and sclera)

how does presence or absence of cirhosis affect survival rate in any chronic liver disease

lower survival rates in pts w/ chronic liver disease w/ cirrhosis

how is median survival affected in compensated vs decompensated cirrhosis

shortened <1.6 yrs once pt develops a decompensating event

child pugh classification

combo of physical and pab findings

grades disease severity and predicts long-term risk of mortality and qol

helps w/ drug dosing adjustment

one + two yr survival

A: 100% + 85%

B: 80% + 60%

C: 45% + 35%

model for end stage liver disease score (MELD)

predicts 90-day mortality risk

• meld 6 ~2% mortality

• meld 40 ~71% mortality

prioritize organ allocation for liver transplantation (“sickest first”)

MELD ≥ 15 or experiencing decompensating events are referred for transplant eval

also used as risk stratification for surgical procedure (MELD ≤ 12 have low peri op mortality risk)

what are some possible complications of cirrhosis

portal HTN → varices

ascites

hepatorenal syndrome

spontaneous bacterial peritonitis

hepatic encephalopathy

coagulopathy

what do you use to quantify hypertension

hepatic venous pressure gradient (HVPG) - gold standard for quantifying HTN → diff btwn wedge + free hepatic pressure

HVPG 1-5 mmhg → normal

HVPG >5 mmhg → portal htn (PH)

HVPG ≥ 10 mmhg → clinical significant PH (CSPH) → varices + decompensation may develop

what value of HVPG is a predictor of decompensation

≥ 10 mmhg → increases risk of ascites, variceal hemorrhage, HE

what is used for primary prophylaxis

NSBBs or EVL

what is used for acute management

resuscitation, vasoactive drugs, abx, urgent EVL

what is used for secondary prophylaxis

NSBBs, EVL

if there are no varices during screening/surveillance endoscopy

repeat endoscopy in 3 yrs (compensated) or yearly (decompensated)

if there are small varices during screening/surveillance endoscopy

check if there are also red signs or CTP class B/C cirrhosis

if yes → initiate BB

if no → repeat endoscopy in 1-2 yrs if BB is no initiated

if there are medium to large varices during screening/surveillance endoscopy

use a BB or EVL

which is first line for primary ppx of variceal bleeding

non-selective beta blockers (carvedilol, propranolol, nadolol)

• carvedilol preferred over propranolol for additional alpha blocking effects to reduce intrahepatic resistance

• NSBBs dose reduced or discontinued if persistent low SBP <90 or severe adverse effects

• can switch from carvedilol to propranolol or nadolol if experienced low arterial pressure

if a pt needs primary ppx for variceal bleeding but is intolerant to NSBBs

an EVL is to be performed at 2-4 weeks until variceal eradication surveillance

surveillance EGD intervals vary by clinical stage + disease activity (detect varices bleeding tx, repeat EVL sessions when band ligation is used)

non-selective beta blockers (NSBBs)

beta 1 blockage → decrease cardiac output

beta 2 blockage → decreased portal flow by splanchnic arterial vasoconstriction

alpha 1 blockage → decrease resistance by intrahepatic vasodilation (carvedilol only)

what is used as second line for primary ppx for variceal bleeding

EVL - for medium large EV + those who cant tolerate / have CI to NSBBs

• its as effective as NSBB in preventing 1st variceal bleeding but no effect on mortality

• carry risk of ligation-induced ulcer bleeding

absolute contraindications for NSBBs

asthma, 2nd + 3rd degree atrioventricular block (in absence of implants pacemaker), sick sinus syndrome, extreme bradycardia (<50 bpm)

relative contraindications for NSBBs

psoriasis, PAD, COPD, pulmonary artery htn (controversial), insulin dependent DM (interfere w/ sx of hypoglycemia), raynaud syndrome

moa of propranolol

beta 1 blockage → works to reduce HR, CO → which reduces blood flow into the splanchnic circulation

beta 2 blockade → splanchnic vasoconstriction, which reduces portal venous flow

starting dose and titration of propranolol

20-40mg bid

increase q2-3 days until goal

max dose of propranolol

without ascites: 320mg /d

with ascites: 160mg/d`

goal hr and bp of propranolol

hr: 55-60 bpm if tolerated

bp: ≥ 90

adverse effects of propranolol

fatigue, bradycardia, dyspnea, orthostasis, hypotension, constipation

monitoring for propranolol

bp, hr, renal impairment, hypotension, bradycardia, bronchospasm, hypoglycemia

moa of nadolol

beta 1 and 2 blockade

starting dose of nadolol

20-40mg qd

max dose of nadolol

w/o ascites: 160 mg/d

w/ ascites: 80 mg/d

moa of carvedilol

beta1 and 2 blockade

alpha 1 blockade → intrahepatic vasodilation → reducing intrahepatiic vascular resistance

starting dose and titration of carvedilol

6.25mg qd

increase to 6.25 mg bid after 3 days

max dose of carvedilol

12.5 mg/d

hr and sbp goal of carvedilol

no hr goal

sbp ≥ 90

endoscopic variceal ligation (EVL)

elastic bands deployed around the EV to occlude the vessels

lead to thrombosis + necrosis, sloughing + ultimately obliteration

endoscopic tx of choice

• controlling acute variceal hemorrhage

• prevent rebleeding

• replaced sclerotherapy (superior efficacy + less complications)

when do pts get acute management

variceal bleeding (emergency), tx failure, or no tx at all

when do pts get secondary ppx

hemostasis is achieved, helps to reduce the risk of bleeding

acute variceal bleeding

medical emergency, mortality rate 7-15%, required admission to ICU

goal: stabilize, control bleeding, prevent complications

uses multidisciplinary approach

initial tx for acute variceal bleeding

adequate blood volume resuscitation

protect airway from aspiration of blood

ppx against sbp + other infxn

control bleeding

prevent re-bleeding

preservation of liver fxn, prevention of HE

prevent acute kidney failure

which vasoactive agent is mainly used for acute variceal bleeding and why

octreotide, superior safety profile

moa of octreotide

somatostatin analog, splanchnic vasoconstriction

dosing for octreotide

50 mcg iv bolus, then infusion 25-50 mcg/hr for 2-5 days

may shorten to 2d in select pts w/ CP class A/B cirrhosis + no active bleeding at endoscopy

adverse effects of octreotide

hyperglycemia, vomiting, bradycardia, htn, arrhythmia, abd pain

moa of terlipressin

vasopressin analog

dosing of terlipressin

2 mg iv q4-6hr for 24-48hr then 1 mg iv q4-6hr x 2-5 days

adverse effects of terlipressin

abd pain, dyspnea, ischemia, respiratory failure

what black box warning does terlipressin have

fatal respiratory failure

what is terlipressin contraindicated in

hypoxia or worsening respiratory sxs

somatostatin dosing

250 mcg iv bolus, then 250-500mcg/hr x 2-5 d

adverse effects of somatostatin

diarrhea, abd pain, nausea

is vasopressin still used? if not why?

no longer advised d/t high risk of cardio

acute variceal bleeding infxn ppx

variceal hemorrhage increases risk for severe bacterial infxn + increase mortality

use short term abx!!

initiate abx after emergent endoscopy, w/in 12h of admission

abx to prevent sbp → ceftriaxone 1g iv q24h x7d (preferred), oral cipro, bactrim considered

when are pts deferred or contraindicated for acute variceal bleeding tx

hemodynamically instability w/o adequate resuscitation

pregnancy

malignancy, PV thrombosis

prior TIPS or surgical shunts - if portal decompression already achieved

when is TIPS used as an intervention

for salvage tx!

TIPS

stent placement btwn hepatic vein + portal vein

what is used for blood volume resuscitation

packed RBCs (goal 7-9 g/dl) + endoscopy w/in12h of admission

what is used for sbp ppx

short term abx → initiate after endoscopy (w/in 12h of admission)

what is used to control bleeding + prevent re-bleeding

vasoactive drug administration → improve 5 day hemostasis, reduce 7 day mortality, decrease transfusion requirements

what is effective for endoscopic + surgical intervention

EVL is the most effective!, TIPS is salvage!

what is the main tx choice for secondary ppx

combo of NSBB and EVL

how often is EVL needed for secondary ppx

q 2-4 wks until variceal obliteration, then surveillance endoscopy in 1-3 mon after eradication then every 6-12 mons thereafter

what tx is used for pts who fail primary ppx w/ NSBBs

consider carvedilol → better portal pressure reduction

add simvastatin 10-20 mg to NSBB + EVL → reduced mortality

add isosorbide mononitrate to NSBB → reduces portal pressure more than NSBB alone, no diff in rate of bleeding and w/ more SE (HA + lightheadedness)

when is TIPS used for secondary prevention

2nd line therapy

reserved for pts who rebleed despite NSBB + EVL

reduce rebleeding but no improvement in survival

increase risk of hepatic encephalopathy (HE)

1st line therapy in pts w/ refractory ascites

ascites

common 1st sign of decompensation

accumulation of excessive fluid w/in abdomen → bulging of abdomen w/ shifting flank dullness

what is ascites an indication of

advanced liver disease w/ poor prognosis → associated w/ reduction 5 yr survival from 80→30%

goals of ascites therapy

minimize ascitic fluid volume, decrease peripheral edema, w/o causing intravascular volume depletion

classification of ascites

based on amount of fluid accumulation and response to tx

grade 1- mild ascites

only detected by ultrasound

grade 2 - mod ascites

mod symmetric distension of abdomen

grade 3 - large or gross ascites

marked distension of abdomen

refractory ascites

failure to respond to maximal diuretics or intolerance of diuretics

responsive ascites

fully mobilized or limited to grade 1 w/ diuretics or dietary na+ restriction

recurrent ascites

recurs on at least 2 occasions w/in a 12 mon period despite dietary na+ restriction + adequate diuretic dosage

refractory ascites

cannot be mobilized or early recurrence after LVP cannot be satisfactorily prevented by medical therapy

initial evaluation of ascites

new onset needs dx paracentesis!

based on ascitic protein, ascitic fluid PMN count, culture
SAAG ≥ 1.1 g/dl

ascitic protein <2.5 g/dl

equation for SAAG

serum albumin - ascitic fluid albumin

general management of ascites

alc abstenence!!!

na+ restriction, monitor k+, renal fxn, daily wt

avoid meds: aceis, arbs, nsaids, bbs, nephrotoxic drugs

when should a paracentesis be performed

if tense ascites is present

what is the main pharmacologic tx for ascites

diuretics! → spironolactone and furosemide

grade 2 (moderate) ascites tx

sodium restriction (<2g/d)

diuretics: spironolactone 100-400mg/d ± furosmide 40-160mg/d (monitor wt, scr, electrolytes)

grade 3 (tense) ascites tx

large volume paracentesis (LVP) w/

iv albumin 6-8 g/l removed

na+ restriction + diuretics

what ratio should spironolactone and furosemide be administered together

100:40

spironolactone + furosemide titration

every 3-5 days

starting dose of spironolactone/furosemide tx

100 mg / 40 mg

max dose of spironolactone/furosemide tx

400 mg / 160 mg

alternative to spironolactone in ascites tx

amiloride

amiloride moa

k+ sparring diuretic, inhibits na+ reabsorption, promotes na+ and h2o excretion

amiloride dosing and titration

10 mg bid, titrate every 4 d in increments of 10 mg bid to a max of 30 mg bid or 10-40 mg qd per guidelines