Download Cirrhosis by Greg Nizialek

Cirrhosis Boot Camp
Gregory Nizialek
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Objectives
• Brief introduction to the pathophysiology of cirrhosis
• Evaluation of the patient with cirrhosis
• Evaluation and management of common complaints and
complications in cirrhotic patients
• Pre and post liver transplant patients
Pathophysiology of Cirrhosis
• Spectrum of liver disease from mild/temporary to cirrhosis.
• Degree of liver disease can be defined on biopsy based on the
METAVIR score, which has two main components:
• 1. activity or degree of active inflammation (grade 0-4)
• 2. degree of fibrosis (stage 0-4)
• Stage 4 (cirrhosis) - pathologic
diagnosis with bridging fibrosis and
regenerative nodule formation.
Etiologies of cirrhosis (in the
US)
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Alcohol
Viral hepatitis – primarily HCV
Non-alcoholic fatty liver disease or NAFLD
Autoimmune hepatitis
Metabolic : Hemochromatosis, A1AT deficiency, Wilson’s
disease
• Biliary : primary/secondary biliary cirrhosis, primary sclerosing
cholangitis
• Vascular: cardiac cirrhosis, Budd-Chiari,
History in cirrhotic patients
1. Important to know the underlying etiology of their cirrhosis!
2. Cirrhosis ROS questions which may be more pertinent: diet
(to assess sodium intake), medication compliance, recent
procedures (ie paracentesis), mental status changes,
obvious or occult GI bleeding
3. Also helpful to know if they have ever had any of the
common complications of liver disease (variceal bleeding,
SBP, etc).
4. Know if your patient follows in the transplant clinic (either
pre-transplant and possibly on the transplant list, or posttransplant) and their hepatologist.
Physical Exam in cirrhotic
patients
• V/S: can tend to be slightly hypotensive due to peripheral
vasodilation (nitric oxide vs prostacyclin mediated vs ? relative
adrenal insufficiency)
• Pertinent exam findings
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Asterixis
Ascites and LE swelling
Lung findings
Arteriovenous fistulas
• Less pertinent (on rounds) but sometimes interesting exam
findings: scleral icterus, spider angiomas, Terry’s nails, palmar
erythema, gynecomastia, caput medusa
Icterus
Ascites
Other exam findings in
cirrhosis
Spider angioma
Terry’s nails (proximal nail bed whitening)
Caput medusa
Laboratory evaluation in
cirrhosis
• In all cirrhotic patients, the basic lab workup should include a
CBC, RFP, LFTs, and coagulation panel (the “MELD labs”).
• Common lab findings include:
• Leukopenia, anemia, thrombocytopenia – often multifactorial,
including splenomegaly and splenic sequestration from portal
HTN, nutritional, volume overload
• Hyponatremia – often due to volume overload (hypervolemic
hyponatremia)
• Coagulopathy (elevated INR) – important to also rule underlying
nutritional/vitamin K deficiency, and also to remember that these
patients are both hypercoagulable and prone to clotting
• LFTs can be found in any pattern (ALT/AST can be low in “burned
out cirrhosis”) – does not rule in or rule out cirrhosis
MELD score
• Developed in 2000 at the Mayo clinic and initially used to
predict mortality after TIPS.
• Now used more broadly as a measure of severity of liver
disease, and also an important part of placement on the
transplant list.
• 3 components: INR, total bilirubin, and creatinine (with an
exception for patients on dialysis).
• There are a number of ways to get MELD exception points, which
come via the local UNOS board, including HCC, hepatopulmonary
syndrome, portopulmonary HTN, amyloid disease, and primary
hyperoxaluria.
• Can also appeal to the local UNOS board for additional exception
points for recurrent cholangitis, refractory ascites or
encephalopathy or pruritis
MELD calculator
MELD = 3.78×ln[serum bilirubin
(mg/dL)] + 11.2×ln[INR] +
9.57×ln[serum creatinine
(mg/dL)]
http://www.mayoclinic.org/medical-professionals/model-end-stage-liver-disease/meld-model-unos-modification
Child-Pugh-Turcotte Score
• More traditional method of predicting mortality in cirrhosis.
Decompensation of Cirrhosis/Complications
of Cirrhosis
Case 1a.
Patient X who has a known diagnosis of ETOH Cirrhosis without
prior complications presents with 1 months of increasing
abdominal distention.
The man’s abdomen is distended with a noticeble fluid wave. A
small umbilical hernia is present. His abd is nontender on
examination
Clinical Diagnosis? Additional Diagnostic Steps? Therapy?
Case 1a
• Ascites! A complication of cirrhosis all by itself. Liver
transplantation should be considered in patient’s with
cirrhosis and ascites (AASLD Class 1 recommendation)
• Diagnostic Paracentesis should be performed on all patients
with clinically apparent new onset ascites. (AASLD Class 1
Recommendation)
• Sodium restriction and Diuretics are first line therapy for
ascites 2/2 to liver disease (AASLD Class II recommendation)
Case 1a- Paracentesis
• Diagnostic vs Therapeutic paracentesis?
• Who should perform the paracentesis?
• Should you use ultrasound? Albumin?
Case 1a: Paracentesis labs
Labs to send
• Always send Cell count and diff, GS and culture, albumin,
protein.
• Cytology if concerned for malignancy or fluid appears
atypical (cloudy, bloody, cellular)
• Rarely send for Glucose, Bilirubin (bile leak?), Amylase
(pancreatitis or leak?), Triglycerides (cylous ascites?), Adenosine
deaminase and mycobacterial culture (TB?)
What are the important values to be obtained from ascites analysis?
Case 1a: Ascites analysis
• The serum ascites albumin gradient
SAAG= Serum albumin- Ascites albumin
High SAAG= >1.1 Likely secondary to portal hypertension.
Low SAAG= <1.1 Concerning for malignant or infectious causes
and should prompt further workup.
• Neutrophil count >250 consistent with SBP in the appropriate
clinical situation. To be discussed further later
Case 1a: Treatment of ascites
-Treatment of high SAAG ascites 2/2 to cirrhosis is mainly
with sodium restriction (2g daily) and Diuretics.
• Standard starting regimen of 100mg spironolactone and
40mg furosemide daily.
• Can be titrated up to maximum doses of 400mg
spironolactone and 160mg furosemide daily. AASLD
recommends increasing doses in a 100/40 ratio to maintain
normokalemia.
Case 1a: Refractory ascites
Refractory ascites can be treated with TIPS, peritoneovenous
shunts, and serial paracentesis.
TIPS: Transjugular intrahepatic portosystemic shunting
• Good control of refractory ascites but with risk of severe
encephalopathy.
Peritoneovenous Shunting- Complicated with risks of infection
Serial Paracentesis: may require weekly to biweekly procedures
to control ascites. May contribute to protein wasting.
Case 1B: X returns
• Patient X returns 2 weeks later to the ED with new onset
abdominal pain for 2 days. It is a diffuse pain and he has felt
subjective chills at home.
• V/S: 100.1, 100, 95/60, 20, 95% on RA
• Exam: notable for abdominal distension, + fluid wave/flank
dullness, and diffuse abdominal tenderness
• Labs: WBC 15.2, Hgb 12.5, Plt 95. BMP notable for BUN 40, Cr
1.8. LFTs at patient’s baseline. INR 1.4.
• Diagnosis? What is your next step?
Case 1b: Are you sure this is spontaneous?
• Don’t forget – patients with cirrhosis can have non-cirrhotic
causes for abdominal pain too: peptic ulcer disease, ischemic
colitis, pancreatitis, C diff or other infectious colitis, etc.
Secondary bacterial peritonitis is a very real thing….
• Abdominal exam can be difficult to interpret in the setting of
cirrhosis/ascites. Have a low threshold to pursue further
workup, whether further lab tests (amylase/lipase, lactate,
stool studies) or imaging (generally CT abd/pelvis).
• If we have a low suspicion for other etiologies what should we
do for diagnosis and treatment?
Case 1b: OK we think this might be
spontaneous
•
Paracentesis should be performed in ALL patients with ascites admitted to
the hospital and repeated should they develop signs of infection (AASLD
class 1 recommendation)
•
A diagnostic paracentesis takes 2 minutes to perform – gathering the
materials takes longer than the actual procedure. Do not hesitate to do a
diagnostic paracentesis, even in the middle of the night - a therapeutic
paracentesis can always wait until the morning. Unless the procedure is
unable to be accomplished safely a diagnostic paracentesis should be
performed at the time of admission if SBP is being considered prior to or
as soon as possible to after intiation of abx. Concert tickets and dinner
reservations are not contraindications.
Case 1b: Ascites analysis
-As stated previously PMN/Neutrophil count greater than
250cells/mm3 is consistent with SBP and empiric treatment
should be started.
-PMNs may be elevated in other conditions such as malignancy,
TB, and intraperitoneal hemorrhage.
- Most common organisms isolated include Escherichia coli,
Klebsiella pneumoniae, and Streptococcal pneumoniae
• Findings concerning for secondary bacterial peritonitis
include PMNs>5000. Multiple organsims growing in culture
(particuarly fungi). Total protein >1 and glucose <50.
Case 1b: Treatment
• Empiric treatment for SBP is generally a 3rd generation
cephalosporin. Major clinical trials used cefotaxime 2 g every
8 hours, although ceftriaxone is also appropriate. Oral
fluoroquinolones can also be used. Tailor treatment to
culture results. Treatment is for 5 days or longer if failure to
improve.
• In patients with SBP who have elevated Cr, BUN, or Bili
should get 1.5 g/kg albumin within 6 hours of detection and
1.0 g/kg on day 3
• If clinically indicated, repeat paracentesis at 48hrs can be
performed if verification of treatment response is needed.
PMNs should have decreased dramatically in appropriately
treated SBP.
Case 1b: Other times to treat/prevent SBP
Additional situations require the use of ABX in patients with
cirrhosis outside of acute SBP.
1.Prior SBP- Daily norfloxacin or Bactrim for long term
prophylaxis. (AASLD Class 1 rec)
2.Acute GI bleed in a cirrhotic- Ceftriaxone 1g/day or norfloxacin
for 7 days (AASLD Class 1 rec)
3.Ascitic fluid total protein <1.5 and renal impairment- Some
evidence suggests long term oral norfloxacin prevents SBP.
Case #2: GI bleeding
• Patient Y is a 60 yo F with PMH of HCV cirrhosis who presents
with a 12 hour history of hematemesis. She started to feel
sick, then had a couple episodes of frankly bloody emesis, but
none for the last 6 hours. She has never had an EGD before.
• V/S: 85/60, 100, 99.0, 18, 93% on RA
• Exam: in some distress, no blood in the oral cavity,
tachycardic, abdominal fullness without tenderness
• Labs: WBC 12.5, Hgb 8.8, Plt 65. BUN 28, Cr 0.9. INR 1.3.
• Diagnosis? Additional procedures? Management?
GI bleed in cirrhosis
• Causes of GI bleeding
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Esophageal varices
Gastric varices or gastric esophageal varices (aka GOV)
Portal hypertensive gastropathy (PHG)
Gastric antral vascular ectasia (GAVE)
Peptic ulcer disease
Esophagitis
Tumor
Dieulafoy lesion
And more…!
• Initial management is the same as with all GI bleeds –
stabilize ABCs (intubation if necessary), fluid and blood
resuscitation, reversal of coagulopathy, ICU transfer if
needed, GI consult.
Medical Management of GI
Bleed
• Until the patient undergoes EGD, it is difficult to know what is
the cause.
• Treatment includes:
1.
2.
3.
octreotide drip (50 mcg bolus, then 50 mcg/hour x72h or
more) to reduce portal hypertension and variceal pressure
PPI drip (80 mg bolus, then 8 mg/hr) for treatment of possible
PUD.
Antibiotics to prevent concurrent infection (7-23% will
develop SBP in setting of GI bleed if untreated) – as before,
generally 3rd generation cephalosporin or FQ for 5-7 days.
Esophageal Varices
•Can cause a profound loss of blood very quickly leading to hemodynamic
compromise. Acute bleeding from varices is associated with approximately 15 to 20 percent 30-day mortality
•Low chance of spontaneous resolution (<50% chance)
•Very high risk for recurrent bleeding
Variceal Treatment
•Octreotide- somatostatin analog decreases portal/variceal pressures
•Balloon Tamponade can be considered for short term stabilization
•Ultimately Requires urgent Endoscopy for active variceal bleeding.
Primary method of treatment is rubber banding of the varices, causing
thrombosis and obliteration.
Will generally need repeat EGD in 2-4 weeks to eradicate any remaining
varices.
Should also be started on non-selective beta blocker (nadolol,
propranolol) when clinically able to reduce risk of progression.
Gastric Varices
• Gastric varices which connect with
esophageal varices
(gastro(o)esophogeal varices or GOV)
are managed similar to esophageal
varices
• Isolated gastric varices are less
prevalent and less well studied than
esophageal varices.
• Do not respond as well to routine
banding – better outcomes with
cyanoacrolate injections (“glue
injections”) to obliterate varices,
which is a procedure only done by
select endoscopists.
• If unable to glue, next step is TIPS.
Rebleeding after treatment
• Can be due to ulceration at site of prior banding, or
recurrence of prior varices.
• May usually attempt repeat endoscopy to try to eradicate any
remaining varices – however the next step is often an
emergent transjugular intrahepatic portosystemic shunt (TIPS)
TIPS
• Shunt placed by
interventional radiology to
reduce portal hypertension
by redirecting blood from the
portal vein to the hepatic
vein (and thus the IVC).
• Goal is to reduce the portal
pressure gradient between
portal and hepatic veins to <
12 mmg Hg.
Portal Hypertensive Gastropathy
(PHG)
• Tends to cause slow mucosal oozing (as opposed to quicker variceal
hemorrhage).
• Due to increased portal pressures causing friable mucosa.
• Generally treated with beta blockers to reduce portal pressure and
sometimes PPIs to prevent concurrent ulceration. Consider argon
plasma coagulation (APC) for focal involement. TIPS, surgical shunting,
and liver transplant are other options.
Gastric Antral Vascular Ectasia
(GAVE)
• Aka “watermelon stomach”.
• Unusual vascular overgrowth
that is associated with
systemic sclerosis and portal
HTN.
• Tends to also cause slow
oozing as opposed to acute
hemorrhage.
• Can be treated with
electrocautery or APC as well.
Does NOT seem to respond to
methods of reducing portal
pressure (ie TIPS).
Case #3: Confusion
• 45 yo M with history of PSC cirrhosis presents with worsening
confusion for the last 3-4 days. Her husband says she has
been much more sleepy and isn’t recognizing normal things.
She is on the transplant list.
• V/S unremarkable
• Exam: Generally unremarkable. Oriented to self but not to
place. + asterixis.
• Further questions in history? What labs or other tests do you
want?
Hepatic or Portosystemic Encephalopathy
• Likely due to a combination of factors – poor clearance of
ammonia, impairment of GABA and other neurotransmitters
leading to enhanced neural inhibitions
• HE can be graded as follows:
Grade
Manifestations of HE
I
Mild confusion, sleep disturbances, altered mood
II
Moderate confusion, lethargy
III
Stuporous, incoherent, sleeping but arousable
IV
Comatose +/- posturing
Comments on Ammonia levels
• Ammonia level is checked in the ED and is 40 (ULN < 32).
• Ammonia levels are frequently checked in hepatic
encephalopathy but are generally not helpful (Ge and Runyon,
JAMA 2014). High levels are found in many patients with
cirrhosis without encephalopathy, and a low level does not
exclude hepatic encephalopathy. Hepatic encephalopathy is
a clinical diagnosis in the setting of liver disease – no lab
value is diagnostic.
• Ammonia does have some prognostic value in acute liver failure
in predicting mortality and development of cerebral edema.
Evaluation of Suspected HE
• As before, patients with cirrhosis are not immune to UTIs or
other common causes of AMS. Think about the typical causes
of AMS in any patient – infection, drugs, electrolytes,
hypercarbia, etc.
• Cirrhotics are particularly prone to renal failure and
subsequent uremia, hyponatremia, uncontrolled DM, sepsis,
thiamine deficiency, and intracranial hemorrhage.
• Always consider the full breadth of possibilities including the
need for ABG or head imaging. Pay attention to the
electrolytes.
• Key factors to investigate in your history/physical:
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Medication non-compliance or other medications.
Dehydration (often iatrogenic from diuretics)
GI bleed, sometimes occult (do a rectal exam!)
SBP (consider diagnostic para)
Decompensation of existing liver disease (development of
HCC, new portal/splenic thrombosis, spontaneous
development of extrahepatic shunt – consider getting an
US with dopplers).
Treatment of Hepatic Encephalopathy
• As with all causes of AMS, if an underlying cause is identified,
it should be treated.
• Treatment specific for cirrhosis include:
• Lactulose – generally 30 mL (20 grams), anywhere from q2h to
once a day. Instruction should be to titrate to 3-5 soft BM/day.
Avoid underdosing or frank watery diarrhea. If patient has an
ostomy or rectal tube, can instead aim for 500-750 cc stool
output/day.
• Some patients cannot tolerate lactulose due to taste – can offer
Kristalose (powdered lactulose) which is more expensive but tastes
better
• Rifaximin – non-absorbable antibiotic, given as 550 mg BID,
usually in addition to lactulose. Useful to prevent recurrance
Case #4: AKI
• 70 yo M with PMH of NAFLD cirrhosis who presented to the
hospital with worsening abdominal distension and pain. He
underwent paracentesis on day 1 with 7 L of ascites removed.
Ascites studies are consistent with SBP. His Cr on admission
was 1.1 – now on day 3 it has increased to 2.6.
Albumin replacement with
paracentesis
• For therapeutic paracentesis, the massive fluid shifts involved
can lead to decreased renal blood flow. AASLD recommends
(IIa recommendation) that for paracentesis with > 5 L fluid
removal, giving 6-8 g albumin/L removed.
• Don’t forget, for any patient with SBP, 1.5 g/kg of albumin on
day 1 and 1 g/kg of albumin on day 3 with any patient with
SBP.
AKI in Cirrhosis
• Hepatorenal syndrome (HRS) – one of many causes of renal
failure in cirrhosis and often a diagnosis of exclusion. Don’t
forget obstruction, ATN, contrast exposure, medications,
dehydration.
• Thought to be due to splanchnic vasodilation and decreased
renal perfusion. Unlikely to be the diagnosis without
significant sequelae of portal HTN (ascites, varices, etc).
• Type 1 HRS: > 2x increase in Cr from baseline, with Cr > 2.5
over 2 weeks
• Type 2 HRS: more indolent course, often characterized by
diuretic-refractory ascites
• Precipitants of type 1 HRS: infection, GI bleed, paracentesis
Diagnosis/Management of
HRS
• Underlying liver disease with portal hypertension + AKI +
bland sediment + failure to respond to volume challenge +
other causes excluded = HRS
• UA tends to lack RBCs or proteinuria. Urine electrolytes are
consistent with a sodium-avid state (FENa < 1%).
• Note that this looks very similar to a dehydration/prerenal
picture – thus, the initial management of suspected HRS is to
remove any potential contribution from dehydration.
• First step is to stop nephrotoxic medications, diuretics, and
give a volume challenge (often 25 g of 25% albumin q6h for a
day).
Management of HRS
• If kidney function does not improve with fluid resuscitation,
start the “HRS cocktail”:
• Midodrine 10 mg TID (alpha-1 agonist causing renal
vasoconstriction - can increase to 15 mg TID based on MAPs)
• Octreotide 100 mg SQ TID
• Albumin (50-100 g/day in divided doses)
• If they are in the ICU, can use norepinephrine with albumin
to also cause renal vasoconstriction – better outcomes than
with the HRS cocktail.Vasopressin analogs are used in europe.
• Last ditch efforts if renal function does not improve include
TIPS and dialysis – both are more temporizing measures while
awaiting liver transplantation.
Cirrhosis and Pulmonary Disease
• 3 unique complications of pulmonary disease in cirrhosis:
1. Hepatic hydrothorax – pleural effusion in setting of cirrhosis,
thought to be due to translocation of ascites through “holes in
diaphragm”
•
Treatment with salt restriction, diuretics, thoracentesis, and
consider TIPS – avoid chest tubes
2. Hepatopulmonary syndrome – hypoxia and dyspnea in setting of
cirrhosis, due to intrapulmonary shunting from small pulmonary AV
fistulas
•
•
Dx is generally with TTE with bubble study and CT angio
Tx is with supplemental O2 – can also obtain MELD exception
points
3. Portopulmonary HTN – combination of portal HTN and pulmonary
HTN in setting of cirrhosis
•
Treatment is similar to that for idiopathic pulm HTN
Cirrhosis and HCC
-Patients With Cirrhosis get hepatocellular carcinoma and are
usually asymptomatic
- Should be screened every 6 months with ultrasound
- Treatment options include
1.Surgical Resection
2.Liver transplant
3.RFAblation
4.TACE
5.Sorafenib
Pre-Transplant
• MELD > 15 or Complications of Cirrhosis such as ascites,
hemorrhage, or encephalopathy warrents evaluation for
transplant
• “Transplant workup”
- Quantiferon Gold
- UA and culture
- ABO blood type and Screen x2
- PSA (if male >50)
- ABG
- HCG (if female >12)
- Complete Metabolic Panel, Magnesium, Phosphorus
- CXR
- GGT
- EKG
- Ammonia
- ECHO
- Alpha Fetoprotein
- Dobutamine Stress Test
- Lipid Panel
- Ultrasound of the Abdomen with Doppler flow
- TSH, T4
- Obtain records of last colonoscopy
- CBC
- PFTs
- PT/INR
- Mammogram and pap smear for females
- Iron Studies (Iron level, TIBC, Transferrin, % sat, ferritin)
- Ceruloplasmin
- Hep A Ab,
- HBsAg (if HBsAg +, then check Hep B DNA quant and HBeAg)
- HBsAb
- HBcAb
- Hep C Ab (HCV genotype and viral load if HCV +)
- TPA EIA (RPR)
- EBV IgG
- CMV IgG
- HIV
Post-Transplant
• “Mercedes” or “Chevron” scar – telltale sign of prior liver
transplant, as it allows surgeons access to the liver as well as
all the surrounding vascular and luminal structures
Post-Transplant
• Know the date of transplant and indication for transplant.
• Any post-op complications.
• Review most recent liver biopsy – need to know if these
patients have cirrhosis or not.
• Know immunosuppressives and any prophylactic medications
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Prednisone
Tacrolimus (Prograf) – check a level on admission
Mycophenolate Mofetil (Cellcept)
Cyclosporine (Neoral or Sandimmune) – check a level on
admission
• Sirolimus (Rapamycin)
• TMP/SMX, valacyclovir, fluconazole for prophylaxis
• Don’t be afraid to call the GI fellow on call with questions.
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Objectives
Pathophysiology
Child Pugh
MELD
Diagnostic/therapeutic paras
Ascites
TIPS
SBP
GI bleed - EV, GV, PHG, GAVE
HCC
PSE
Hepatorenal
Pulm/cirrhosis - hepatic hydrothorax, portopulmonary HTN, portopulmonary
syndrome
• PVT
• Transplant meds
• Post transplant care