Learner Version
Module #15
Written by Jens Langsjoen 4/2014
Objectives:
See facilitator version
References
See facilitator version
CASE 1
60 yo female presents with 2 week history of worsening abdominal discomfort, nausea, lethargy, yellowing of skin, dark urine, and pale stools.
What additional history would you like to obtain from this patient?
What will you look for on physical exam?
What is your differential based on the results of your history and physical exam?
What labs/studies would you like to order?
What is the suspected diagnosis, how will you confirm?
How will you treat the patient?
How can you better determine if this patient needs a liver transplant?
What other organ system complications is this patient at risk of developing in the setting of acute liver failure?
What is the prognosis for this patient assuming she progresses to require and receives a liver transplant? What is she most likely to die of?
MKSAP QUESTIONS
Gastroenterology and Hepatology
82,71,5,91
Appendix
EXTRA CASE
CASE 2
A 22 y/o female presents with 3 week history of worsening nausea, occasional non-bloody vomiting, exertional fatigue, decreased appetite, yellowing of her skin and abdominal pain.
What is on the differential?
This sounds like Acute liver failure (!!!) (refer confused residents to title of module). Differential diagnoses should include viral hepatitis, toxins (mushrooms, TYLENOL), alcoholic hepatitis, autoimmune hepatitis, Wilson’s disease.
What further history would you like to know?
She works as a waitress. She denies any alcohol or IVDA history, has no tattoos, doesn’t eat or pick wild mushrooms, and has never had a blood transfusion. She has no documented PMH and takes no medications. She doesn’t even take Tylenol, not even ever. She never travels (Hep a, b risk). She doesn’t know her family history, she was adopted (hmm.. suspicious). Her friends tell her she has been talking funny for about a year, that words are out of place and occasionally too loud. She has also noticed that she has felt increasingly paranoid over the past 6 months.
What will you look for on exam?
Patient’s exam highlights: She appears unwell, slight reproducible RUQ abd pain, dysarthria, jaundice, resting tremor, no asterixis. Kayser Fleischer rings are not obviously visible.
What is on the differential now that you have history and physical exam data?
Alcoholic, viral, tylenol, or mushroom hepatitis all seem less likely given the history. Autoimmune hepatitis is still a possibility. Wilson’s disease is a possibility especially given the neuro-psychiatric symptoms found in the history (dysarthria, paranoia).
What labs/studies do you want to sort out this new differential?
Only give those results that are directly asked for by the residents.
wbc: 6.5, Hgb: 9, plts: 160,000 MCV: 69, INR: 2.8, AST: 192, ALT: 89, Alk Phos: 22, TBili: 9 (Direct: 1.1), albumin: 3.5, Na: 137, Cr 0.8, BUN: 24, negative pregnancy test, NH3: 20, Hepatitis panel: negative.
copper level 207 (nl 70-140), ceruloplasmin level 9 (nl 25-63), LDH: 1001 (nl 115-221), direct/indirect coombs tests: negative. AMA, Anti-SM ab negative.
(note: the biliary pattern and LDH consistent with coombs negative hemolytic anemia, the AST/ALT ratio of 2:1, and the subnormal alkaline phosphotase, all concerning for Wilson’s disease!)
studies: abdominal US: normal portal vein flow, normal biliary system, normal sized liver.
If residents ask for a slit lamp exam, this can be done and will show Kayser Fleischer rings.
Why is she anemic?
The patient has evidence of hemolytic anemia on laboratory work up. While Total bilirubin elevation can occur from acute liver failure it would not be expected to be all indirect, which raises concerns for hemolysis. The elevated LDH of 1001 is also consistent with hemolysis.
Once the residents determine that the patient has hemolytic anemia, they should ask for a direct/indirect coombs test, which is negative. This makes an autoimmune hemolytic anemia unlikely and should raise concern for another cause for hemolysis, in this setting something such as Wilson’s disease.
What is the rough likelihood that she has Wilson’s disease?
The Germans came up with a scoring system!
●Kayser-Fleischer rings (2 points)
●Neuropsychiatric symptoms suggestive of Wilson disease (2 points)
●Coombs-negative hemolytic anemia with high serum copper (1 point)
●Urinary copper in the absence of acute hepatitis
•1 to 2 times the upper limit of normal (1 point)
•>2 times the upper limit of normal (2 points)
•Normal, but >5 times the upper limit of normal after challenge with two doses of 0.5 g D-penicillamine(2 points)
●Liver copper quantitative measurement
•Normal (-1 point)
•Up to 5 times the upper limit of normal (1 point)
•>5 times the upper limit of normal (2 points)
●Rhodanine positive hepatocytes (if unable to obtain quantitative copper measurement) (1 point)
●Serum ceruloplasmin (based on using a nephelometric assay with a normal value >20mg/dL)
•Normal (0 points)
•10 to 20mg/dL(1 point)
•<10mg/dL(2 points)
●Mutation analysis
•Disease causing mutations on both chromosomes (4 points)
•Disease causing mutations on one chromosome (1 point)
•No diseased causing mutation (0 points)
If the score is ≥4, Wilson disease is highly likely; if it is 2 to 3, the diagnosis is probable, but more investigation is warranted (eg, obtaining a liver biopsy if not already done); if it is <2, Wilson disease is unlikely.
This patient has a million points so she is very likely to have Wilson’s disease. She probably doesn’t need a liver biopsy to make the diagnosis but you should ask GI anyway.
How will you treat this patient?
This patient will most likely need a liver transplant. In the meantime you will need to carefully monitor and provide supportive care for her rapidly progressive liver failure and hemolytic anemia. Plasmaphoresis might be helpful (some studies) while awaiting transplantation.
For long term management , ask GI, but tell them you are quite interested in chelating her serum copper ASAP with D-Penicillamine at a starting dose of 250mg-500mg/day with a goal of increasing urine copper excretion from a baseline of around 100mcg/day to closer to 2000mcg/day.
What dietary recommendations will you give to this patient?
You will have to break the news that a few of the world’s most delicious and luxurious high copper foods will now be off limits. These, unfortunately, include the following: shellfish, nuts, chocolate, mushrooms, and organ meats. You can reassure her that if she doesn’t die and is real good and sticks with her chelation therapy she can try some foie gras next year.
MKSAP QUESTIONS:
King’s College Criteria
Can be used as criteria to consider referral to a transplant center
Differential for Acute Liver Failure
Viral: hepatitis A, B, C, D, E, HSV, CMV, EBV, HVZ, adenovirus, hemorrhagic fever virus
Drugs: Idiosyncratic: Halothane, most HIV meds, INH, rifampicin, valproate, NSAID’s,
disulfuram, et al.
Dose-related: Acetaminophen, sulfonamides, tetracycline, ecstasy, cocaine, meth,
statins
Toxins: Alcohol, Amanita phylloides, Bacillus cereus toxin, CCl4, yellow phosphorus.
Herbs: Chaparral, germander, kava kava, ginseng, comfrey,
Vascular: Right heart failure, Budd-Chiari syndrome, portal vein thrombosis, ischemic/hypoperfusion “shock liver”, septic shock, heat stroke.
Metabolic: Wilson’s Disease, acute fatty liver of pregnancy, HELLP, Reye’s, adult Stills.
Classic Acute Liver Failure Definition
· Acute liver injury
· Impaired synthetic function (INR>1.5)
· Hepatic encephalopathy (poor prognosis if present)
· Illness duration <26 weeks
Presenting Symptoms
· Fatigue/malaise
· Nausea/vomiting
· RUQ pain
· Pruritis
· Jaundice
Physical exam findings
· Hepatic encephalopathy
o Grade 1: behavior change, mild confusion, slurred speech
o Grade 2: lethargy, moderate confusion
o Grade 3: Stupor, incoherent, sleeping
o Grade 4: coma, unresponsive to pain
· Asterixis: (in grade 1-3 encephalopathy)
· Jaundice
· Vesicular skin lesions, fever (HSV)
· RUQ pain and hepatomegaly
· Ascites
· Orthostasis
Lab abnormalities
· Typical
o INR >1.5
o Transaminitis (often marked elevation)
o High bilirubin
o Low platelets <150,000
· Disease specific abnormalities
o Tylenol OD
§ Transaminitis >3500, low Tbili, high INR
o Ischemic
§ Transaminitis >1000, high LDH
o HBV
§ Transaminitis 1000-2000, ALT>AST
o Wilsons
§ Transaminitis <2000, Coombs neg hemolytic anemia, AST/ALT ratio >2, normal Alk phos, ARF.
o Alcoholic
§ AST/ALT ratio 2:1
Workup:
· History
o Toxins: medications, ETOH, mushrooms, occupational, chupacabra bite.
o Ischemia risk factors: hypotension, CHF, hypercoag state, OCP, CA, NMFDS (New Mexico Found Down Syndrome).
o Viral risk factors: immunosuppression, chronic HBV, IVDA, travel (A,E)
o Family history (wilsons)
· Labs
o Initial workup to consider
§ INR, CBC, chem7, LFTs, Tylenol lvl, tox screen, viral serologies (A, B, C, HSV, VZV, E (if pregnant), pregnancy test, autoimmune (ANA, AMA, ASMA), NH3, lipase, ceruloplasmin.
· Imaging
o Abd US with Doppler (Budd Chiari, Portal HTN, cirrhosis, steatosis)
o Consider TTE if concern for ischemic hepatitis
o Consider CT or MRI if concern for malignancy
· Consider Liver biopsy for
o Unclear dx, malignant infiltration, autoimmune, wilsons, HSV
Management
· Monitoring
o Daily LFTs, INR, CBC, Chem7, Mg, Ph
o Beware hypoglycemia, development of HRS, hyponatremia, bleeding, infection
o
· Nutrition
o Early nutritional support is vital
o Don’t restrict protien
o Use oralàenteralàparenteral as necessary
· Primum Nocure
o Avoid sedating medications, especially narcotics and long acting benzos
· Disease specific management
o Tylenol OD
§ NAC (low threshold for use if suspected OD, especially if transaminitis or elevated Tylenol levels).
o Mushroom poisoning: early activated charcoal
o HBV: nucleoside analogue antiviral therapy
o Acute Budd Chiari: TIPS vs surgical decompression vs thrombolysis
o Alcoholic hepatitis: prednisone vs pentoxifyllin if DF>32.
o Autoimmune hepatitis: consider prednisone with caution for sepsis
· Hepatic encephalopathy
o Lactulose for 3 BMs/day. Consider Rifaxamin if not tolerating lactulose.
· Coagulopathy
o FFP only if bleeding or prior to procedure.
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111) or return to Dr. Patrick Rendon, Division of Hospital Medicine, UNM Hospital.
1) Topic of module:______
2) On a scale of 1-5, how effective was this module for learning this topic? ______
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:
______
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient curriculum in general:
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Attending Resident (R2/R3) Intern Medical student