Transcript Cirrhosis Boot Camp

Cirrhosis Boot Camp
Brandon Szeto
3/29/2016
Objectives
• Brief introduction to the pathophysiology of cirrhosis
• Evaluation of the patient with cirrhosis
• Evaluation and management of common complaints 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 (aka Laennec’s cirrhosis to the surgeons, 60-70%)
Viral hepatitis (10%) – primarily HCV
Non-alcoholic fatty liver disease or NAFLD (10-15%)
Autoimmune hepatitis (~5%)
Metabolic (~5%): Hemochromatosis, A1AT deficiency, Wilson’s
disease
• Biliary (~5%): primary/secondary biliary cirrhosis, primary
sclerosing cholangitis
• Vascular: cardiac cirrhosis, Budd-Chiari, SOS
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.
Non-transplant patient
Pre/post transplant patient
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
Asterixis
Thought to be a limited form of myoclonus caused by abnormal balance
between agonist/antagonist muscles in the diencephalon.
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.
Case #1: abdominal pain
• Patient is a 55 yo M with PMH of ETOH cirrhosis who presents
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 #1 cont:
• 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.
• 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).
Diagnostic paracentesis
• Should be strongly considered in all patients with ascites who present to the
hospital, regardless or presenting complaint.
• Retrospective study looking at patients with presenting complaint of ascites or
encephalopathy showed a significant decrease in in-hospital mortality for all
patients who received paracentesis on admission (Orman et al, Clin Gastro Hep,
2014).
• Tools required:
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Sterile gloves
18 or 20 g needle
60 cc syringe with syringe cap
Alcohol/chlorhexidine swabs
Signed consent
+/- ultrasound to locate a suitable pocket for aspiration and avoid major vascular
structures
7. +/- lidocaine and a small needle/syringe for local anesthesia
8. +/- senior resident for supervision
• A diagnostic paracentesis takes 2 minutes to perform – gathering the materials
takes longer than the actual procedure. Do not hesitate to do diagnostic
paracentesis, even in the middle of the night - a therapeutic paracentesis can
always wait until the morning.
Ascites on ultrasound
Labs to send with paracentesis
• ALWAYS
• Cell count
• Bacterial culture
• SOMETIMES
• Albumin
• Total protein
• Cytology (esp if “bloody tap”)
• RARELY
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Glucose
Bilirubin (if brown)
Amylase
Triglycerides (esp if “milky” fluid)
Adenosine deaminase and mycobacterial culture
Cell count of ascitic fluid
• Cell count results are generally reported in WBC, RBC, and
WBC differential.
• Most important part of diagnosing spontaneous bacterial
peritonitis (SBP) is a PMN count (ie WBC count * PMN
percentage) > 250 and + ascitic cultures for bacteria.
• Elevated RBC count in ascites (often from a “traumatic tap”) can
skew automated cell count for WBC – generally subtract 1 WBC
for every 750 RBC, or 1 PMN for every 250 RBC
Management of SBP
• Spontaneous bacterial peritonitis (SBP) – occurs in patients with
cirrhosis, and is generally due to translocation of gut bacteria into
ascitic fluid
• Most common organisms: E coli, Klebsiella, Streptococcus
• Should be distinguished from secondary bacterial peritonitis, which is
generally shorthand for gut perforation and requires vastly different
management (polymicrobial coverage, imaging, and surgical
evaluation being key)
• Antibiotics:
• Cefotaxime (2 g IV q8h) has been most well studied – ceftriaxone (2 g
24h) or other 3rd gen cephalosporins are probably as effective. Total
treatment course generally 5 days, longer if poor response.
• Other options include fluoroquinolones (avoid if already on FQ for
SBP prophylaxis), pip/taz, carbapenems.
• Albumin – giving 1.5 g/kg of albumin at time of diagnosis and 1 g/kg
of albumin on day 3 after diagnosis was shown to decrease
mortality, generally due to lower incidence of renal failure (Sort et
al, NEJM 1999).
After diagnosis of SBP
• Repeat paracentesis – commonly done in our institution at
48h after initial paracentesis to document resolution of
infection (decrease in PMN count by >25%), although no
evidence that it changes outcomes.
• SBP antibiotic prophylaxis
• For all patients with prior history of SBP (~70% 1 year recurrence
rate)
• For patients with ascites total protein < 1.5 and impaired renal
function (Cr > 1.2, Na < 130) or liver function (Child Pugh >= B,
Tbili > 3.0)
• Common regimens include norfloxacin 400 mg daily, TMP/SMX DS
1 tab daily, cipro 750 mg qweek
Case #2: GI bleeding
• Patient 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 (o)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:
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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
• 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 transhepatic 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
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.
Causes of 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. As with any patient with AMS, they should
get CBC and RFP/LFTs, infectious workup, drug screens, +/brain imaging, etc.
• Most benzodiazapenes are hepatically metabolized and can
cause severe disorientation in cirrhotic patients – preferable
to use haloperidol in setting of agitation.
Causes of HE related to cirrhosis
• Key factors to investigate in your
history/physical:
• 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
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. Don’t forget obstruction, ATN, etc!
• 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
• UA tends to be bland. 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 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 also start norepinephrine
monotherapy to also cause renal vasoconstriction – better
outcomes than with the HRS cocktail.
• 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”
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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
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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
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Treatment is similar to that for idiopathic pulm HTN
Pre-Transplant
• MELD > 25 should be going to transplant surgery service or
have a transplant surgery consult.
• “Transplant workup”
- ABO blood type and Screen x2
- CXR
- ABG
- EKG
- Complete Metabolic Panel, Magnesium, Phosphorus
- ECHO
- GGT
- Dobutamine Stress Test
- Ammonia
- Ultrasound of the Abdomen with Doppler flow
- Alpha Fetoprotein
- Obtain records of last colonoscopy
- Lipid Panel
- PFTs
- TSH, T4
- Mammogram and pap smear for females
- CBC
- PT/INR
- 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
- Quantiferon Gold
- UA and culture
- PSA (if male >50)
- HCG (if female >12)
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