Cirrhosis Boot Camp

1
Cirrhosis Boot Camp

• Brandon Szeto
• 11/15/2016

2
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

3
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.

4
Etiologies of cirrhosis (in the US)

• Alcohol (aka Laennecs 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, Wilsons disease
• Biliary (5) primary/secondary biliary
  cirrhosis, primary sclerosing cholangitis
• Vascular cardiac cirrhosis, Budd-Chiari, SOS

5
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 post-transplant) and their
   hepatologist.

6
Non-transplant patient
7
Pre/post transplant patient
8
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
• Asterixis
• Ascites and LE swelling
• Lung findings
• Arteriovenous fistulas
• Less pertinent (on rounds) but sometimes
  interesting exam findings scleral icterus,
  spider angiomas, Terrys nails, palmar erythema,
  gynecomastia, caput medusa

9
Asterixis
Thought to be a limited form of myoclonus caused
by abnormal balance between agonist/antagonist
muscles in the diencephalon.
10
Icterus
11
Ascites
12
Other exam findings in cirrhosis
Spider angioma
Terrys nails (proximal nail bed whitening)
Caput medusa
13
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

14
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

15
MELD calculator
MELD 3.78lnserum bilirubin (mg/dL)
11.2lnINR 9.57lnserum creatinine (mg/dL)
http//www.mayoclinic.org/medical-professionals/mo
del-end-stage-liver-disease/meld-model-unos-modifi
cation
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Child-Pugh-Turcotte Score

• More traditional method of predicting mortality
  in cirrhosis.

17
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 patients baseline.
  INR 1.4.
• Diagnosis? What is your next step?

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Case 1 cont

• Dont 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).

19
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
• 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
• /- lidocaine and a small needle/syringe for
  local anesthesia
• /- 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.

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Ascites on ultrasound
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Labs to send with paracentesis

• ALWAYS
• Cell count
• Bacterial culture
• SOMETIMES
• Albumin
• Total protein
• Cytology (esp if bloody tap)
• RARELY
• Glucose
• Bilirubin (if brown)
• Amylase
• Triglycerides (esp if milky fluid)
• Adenosine deaminase and mycobacterial culture

22
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) gt 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

23
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).

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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 gt25), 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 lt 1.5 and
  impaired renal function (Cr gt 1.2, Na lt 130) or
  liver function (Child Pugh gt B, Tbili gt 3.0)
• Common regimens include norfloxacin 400 mg daily,
  TMP/SMX DS 1 tab daily, cipro 750 mg qweek

25
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?

26
GI bleed in cirrhosis

• Causes of GI bleeding
• 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.

27
Medical Management of GI Bleed

• Until the patient undergoes EGD, it is difficult
  to know what is the cause.
• Treatment includes
• 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.

28
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.

29
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.

30
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)

31
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 lt 12 mmg Hg.

32
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.

33
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).

34
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 isnt 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?

35
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
36
Ammonia levels

• Ammonia level is checked in the ED and is 40 (ULN
  lt 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.

37
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.

38
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).

39
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

40
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.

41
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 gt 5 L fluid removal, giving
  6-8 g albumin/L removed.
• Dont 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.

42
AKI in Cirrhosis

• Hepatorenal syndrome (HRS) one of many causes
  of renal failure in cirrhosis. Dont 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 gt 2x increase in Cr from baseline,
  with Cr gt 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

43
Diagnosis/Management of HRS

• UA tends to be bland. Urine electrolytes are
  consistent with a sodium-avid state (FENa lt 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).

44
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.

45
Cirrhosis and Pulmonary Disease

• 3 unique complications of pulmonary disease in
  cirrhosis
• 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
• 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
• Portopulmonary HTN combination of portal HTN
  and pulmonary HTN in setting of cirrhosis
• Treatment is similar to that for idiopathic pulm
  HTN

46
Pre-Transplant

• MELD gt 25 should be going to transplant surgery
  service or have a transplant surgery consult.
• Transplant workup

- ABO blood type and Screen x2 - ABG - Complete
Metabolic Panel, Magnesium, Phosphorus - GGT -
Ammonia - Alpha Fetoprotein - Lipid Panel -
TSH, T4 - 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 gt50) - HCG (if female gt12)

• - CXR
• - EKG
• - ECHO
• - Dobutamine Stress Test
• - Ultrasound of the Abdomen with Doppler flow
• - Obtain records of last colonoscopy
• PFTs
• - Mammogram and pap smear for females

47
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

48
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
• 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
• Dont be afraid to call the GI fellow on call
  with questions.

49

• 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