chemist157

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HPI:
21 yo caucasian female presented to her primary care physician with jaundice and pruritis of two months duration. She has no fever, no malaise, and only slight lethargy.

Meds: Oral contraceptive.

PMH/PSH:
Significant for cholecystectomy at 19 yo.

ROS:
No abdominal pain. She has dark urine. No sore throat. She had a rash on her thigh that lasted for three days. No change in BM.

Exam:
There is no abdominal tendernes, no hepatomegaly and no splenomegaly. No erythema of the pharynx and no exudates, TM's are gray and glossy. There is scleral icterus and general jaundice.

Labs:
Total and conjugated bilirubin are elevated.
ALT and AST are about 10 times above normal. ALT>AST.
Alkaline phosphatase is elevated.
U/A shows 1+protein, urobilinogen and bilirubin.
Monospot test is negative
EBV test is pending.

Imaging:
U/S shows diffuse fatty liver, no calculi noted and no ductal dilitation.

What do you think?
 

Mental Gymnast

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Oooh, I wanna play :)

Here is my thought process.

Automatically, we know that her conjugated bilirubin is elevated. So the problem is either hepatic or post-hepatic. Now, we know she has her gallbladder out and has no ductal dilatation on imaging, so this rules out a post-hepatic obstruction like pancreatic cancer. Therefore, this is a hepatic problem as is further evidenced by her LFT's, alk phos, and conjugated bilirubin.

Of the diseases that cause bile ductule damage and hepatic destruction, we must consider hepatitis, cholangitis (including primary sclerosing), PBC, etc.

Now, we know from the exam that the liver looks great with no hepatomegaly or fever (signs of hepatitis). We also know from ultrasound that there is no ductal dilatation, which puts primary sclerosing cholangitis lower on the list (usually presents with ductule dilatation and narrowing on imaging, fever, and usually in fourth decade of life at least).

That leaves us with PBC. In 50% of these patients you can have an enlarged liver as was seen on imaging. This disease involves direct damage to the biliary tract, resulting in the lab abnormalities mentioned as well as jaundice.

I say Primary Biliary Cirrhosis. :thumbup:
 

analgold09

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How long has she been on OCPs?

I would add hormone induced cholestasis to the differential.

But I like PBC, too. Strong work.
 
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I'd like to know the actual value of alk phos to get more of a sense of whether this is more or less impressive than the AST/ALT elevation. AST/ALT 10x normal would be pretty unusual for PBC, wouldn't it?


HPI:
21 yo caucasian female presented to her primary care physician with jaundice and pruritis of two months duration. She has no fever, no malaise, and only slight lethargy.

Meds: Oral contraceptive.

PMH/PSH:
Significant for cholecystectomy at 19 yo.

ROS:
No abdominal pain. She has dark urine. No sore throat. She had a rash on her thigh that lasted for three days. No change in BM.

Exam:
There is no abdominal tendernes, no hepatomegaly and no splenomegaly. No erythema of the pharynx and no exudates, TM's are gray and glossy. There is scleral icterus and general jaundice.

Labs:
Total and conjugated bilirubin are elevated.
ALT and AST are about 10 times above normal. ALT>AST.
Alkaline phosphatase is elevated.
U/A shows 1+protein, urobilinogen and bilirubin.
Monospot test is negative
EBV test is pending.

Imaging:
U/S shows diffuse fatty liver, no calculi noted and no ductal dilitation.

What do you think?
 

Strength&Speed

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I'd like to know the actual value of alk phos to get more of a sense of whether this is more or less impressive than the AST/ALT elevation. AST/ALT 10x normal would be pretty unusual for PBC, wouldn't it?
Agreed. A very high alk phos and GGT would point more towards cholestasis (OCP or otherwise) rather than intrinsic liver injury. I would go with some sort of cholestasis probably--due to OCP's or PBC. sounds less likely to be autoimmune hep, or a hep b. hep c and a arent' likely based on history. nafld would be unusual with the high bili and ast's. unless it was endstage, i guess.

is she obese?

without knowing any more, i say cholestasis due to OCP's/Pregnancy or PBC
 

Mental Gymnast

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good catch on the OCP's guys, yes hormone induced cholestasis is DEF on that differental. Actual lab values would help too, regarding AST/ALT ratios, etc...
 
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chemist157

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HAV HBV and HCV all came back neg.

Alk phos is only mildly elevated.
Alt ~ 2100 AST ~ 1500
 

souljah1

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There are a finite amount of things that cause a transminitis over 1000.

Infection: HAV, HBV, HCV (less common), EBV, HSV, CMV, VZV. I'd make sure the other viral studies are negative

Autoimmune: Autoimmune Hepatitis (PSC and PBC rarely if ever cause ALT and AST to be this high), Autoimmune Cholangiapathy (mix of AH and PBC). This actually can fit pretty well. I'd get the necessary serologies.

Metabolic: Wilson's (perfect age) Is on the ddx for fulminant liver disease. I don't have enough data to really get at it, but I'd order a ceruloplasmin and 24hr urinary copper. Any depression, psych stuff as a teenager?

Toxins: a wide variety, but most commonly tylenol. The OCP is a great thought. It can also raise risks for clot, which if in the wrong place, can be devastating -> hepatic veins, ivc, etc

Stones: sometimes choledocholiths can cause massive transaminitis and the alk phos and bili can lag. Given the chronicity, I highly doubt this.

Vascular: Budd Chiari, VOD - usually would see on u/s (was there doppler). VOD is rare and usually with allo-BMT

Shock: not in this case, but I did see a case with adrenal insufficiency -> hypotension -> shock liver -- but there were other end organs damaged as well

Make sure she aint preggo

My money is on autoimmune hepatitis > drug > wilsons > vascular >>> stones, psc, pbc. Get all the labs and consider a liver bx. I'd also watch for synthetic function pretty closely.
 

Mental Gymnast

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Souljah1,

I agree with you that the lab results definitely add a lot more info and alter the differential as you mentioned. Autoimmune hepatitis/cholangiopathy fits with the jaundice, pruritis, lethargy, diffusely enlarged liver, transaminitis >1000, and skin rashes (common autoimmune association).

I would get a thorough ROS, since there is a very high association with other autoimmune diseases such as diabetes, UC, celiac sprue, etc. I know Chemist mentioned no BM changes.... the 1+ proteinuria is weird though...
 

Strength&Speed

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Souljah1,

I agree with you that the lab results definitely add a lot more info and alter the differential as you mentioned. Autoimmune hepatitis/cholangiopathy fits with the jaundice, pruritis, lethargy, diffusely enlarged liver, transaminitis >1000, and skin rashes (common autoimmune association).

I would get a thorough ROS, since there is a very high association with other autoimmune diseases such as diabetes, UC, celiac sprue, etc. I know Chemist mentioned no BM changes.... the 1+ proteinuria is weird though...
I wouldnt make much of the proteinuria--that can happen with a lot of things. as souljah said, knowing the transaminases being over 1000 is important, as there aren't too many things. he/she knows better than me what those are though.
 

souljah1

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For the sake of the discussion, do you know if she's anemic? If so, was hemolysis worked up? She has proteinuria as well. Was this quantified? New?

Wilson's disease is very rare - but she is the right age, it can have hemolytic anemia, can be associated with proteinuria, and classically has a relatively low alk phos (you said it is mildly elevated) relative to the bilirubin. It can also present as fulminant/subfulminant liver failure.

Regardless of what the cause is, I would keep a close eye on mental status, coags, renal function, etc - until the diagnosis is made and the correct treatment is initiated.
 

Soundwave

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I would guess budd chiari. oral contraceptives can make you hypercoagulable. the u/s makes no mention of a doppler which should be performed in this case as well.
 

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Wouldn't she have ascites with budd-chiari? "

I'm thinking autoimmune hepatitis or cholangiopathy. Possible post-op bile duct stricture?
 
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Alpha-1 Antitrypsin Deficiency

(sorry. back to anesthesia world I go)
 
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chemist157

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I would guess budd chiari. oral contraceptives can make you hypercoagulable. the u/s makes no mention of a doppler which should be performed in this case as well.
THe U/S did have doppler, no stasis from what they could see.
alpha-1 antitrypsin is neg.
budd-chiari would have more of a cholestatic pattern (ALP would be elevated out of proportion to ALT and AST) this is a hepatocellular pattern. also, again, no blockage or stasis seen on U/S.
Ceruloplamin was normal. Urinary copper was only slightly elevated over 24 h.
Ferritin and TIBC were high but transferrin sat only 19 (usu. > 45-50 in hemochromotosis).
neg ANA, antimitochondrial Ab (PBC), smooth muscle and microsomal Ab neg (autoimmune hepatitis), TTG (celiac) neg
no other pert pos in ROS. uncle had rheumatoid arthritis is only sig fam hx of autoimmune dz.
 

Gastrapathy

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souljah's list is excellent. If you want another zebra, you could ask about eating mushrooms. Your patient needs an MRCP/Liver MR and a Liver Bx. With that pattern and a "slightly elevated" urinary copper, you need to r/o Wilson's with bx (although classically, AST>ALT). This will also help with autoimmune and DILI.
 
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chemist157

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souljah's list is excellent. If you want another zebra, you could ask about eating mushrooms. Your patient needs an MRCP/Liver MR and a Liver Bx. With that pattern and a "slightly elevated" urinary copper, you need to r/o Wilson's with bx (although classically, AST>ALT). This will also help with autoimmune and DILI.
But wouldn't Wilson's have a lower Ceruloplasmin?

ALso, all the bili is conjugated, haptoglobin is normal so no hemolysis.

Seems like everyone's opinion here is that since she is asymptomatic a liver Bx would be too risky. Also, the enzymes have started to come down a little bit so everyone is taking a watch-and-wait approach.
 

Gastrapathy

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But wouldn't Wilson's have a lower Ceruloplasmin?

ALso, all the bili is conjugated, haptoglobin is normal so no hemolysis.

Seems like everyone's opinion here is that since she is asymptomatic a liver Bx would be too risky. Also, the enzymes have started to come down a little bit so everyone is taking a watch-and-wait approach.

Wilson's does not always cause a low ceruloplasmin, particularly in setting of FHF. Ceruloplasmin, urinary copper and serum copper are screening tests. If any are abnl, the next step is bx typically.

If she is rapidly improving, that makes a viral etiology more likely. HSV is a potential culprit. If your GI doesn't want to bx, she must be doing ok. Bx is quite safe. Bleeding is the most frequent complication and significant bleeding occurs in about 1% of perc bx's and less frequently with trans-jugular bx's by IR.
 

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AIH is not completely rule out. What is the immunoglobulin level?

what about AMA negative PBC or also known as autoimmune cholangiopathy? (the AST/ALT is a little too high for PBC or autoimmune cholangiopathy)

U/S does NOT completly rule out vascular obstruction as U/S is very operation dependent. The gold standard is venogram.

If everything is negative, then I would biopsy her for sure.

BTW what are the viral serology?


THe U/S did have doppler, no stasis from what they could see.
alpha-1 antitrypsin is neg.
budd-chiari would have more of a cholestatic pattern (ALP would be elevated out of proportion to ALT and AST) this is a hepatocellular pattern. also, again, no blockage or stasis seen on U/S.
Ceruloplamin was normal. Urinary copper was only slightly elevated over 24 h.
Ferritin and TIBC were high but transferrin sat only 19 (usu. > 45-50 in hemochromotosis).
neg ANA, antimitochondrial Ab (PBC), smooth muscle and microsomal Ab neg (autoimmune hepatitis), TTG (celiac) neg
no other pert pos in ROS. uncle had rheumatoid arthritis is only sig fam hx of autoimmune dz.
 

Vision

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You can also check un-bounded serum copper level which can be helpful. If it is fulminant, then the biopsy would just show necrosis and the hepatic copper level can be falsely abnormal. Wilson is a tricky one to diagnose. How 'bout a slit lamp?
 

Vision

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Liver biopsy is not as risky as people think.. so many ways of getting tissue.

Transjugular if you are worry, but she should be fine with percutaneous.


But wouldn't Wilson's have a lower Ceruloplasmin?

ALso, all the bili is conjugated, haptoglobin is normal so no hemolysis.

Seems like everyone's opinion here is that since she is asymptomatic a liver Bx would be too risky. Also, the enzymes have started to come down a little bit so everyone is taking a watch-and-wait approach.
 
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chemist157

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AIH is not completely rule out. What is the immunoglobulin level?

what about AMA negative PBC or also known as autoimmune cholangiopathy? (the AST/ALT is a little too high for PBC or autoimmune cholangiopathy)

U/S does NOT completly rule out vascular obstruction as U/S is very operation dependent. The gold standard is venogram.

If everything is negative, then I would biopsy her for sure.

BTW what are the viral serology?
All the viral serology tests came back negative. Her enzymes have significantly decreased and she was started on acyclovir for a probable viral hepatitis of unknown etiology. I guess we may never know. I'll be interested to see if it ever happens again.

Btw, interestingly our Hepatologist wanted to do a Bx but she opted to travel to a regional hospital with a big (huge) name/reputation where they told her the wanted to watch it for a while before doing the Bx d/t the risks. I suppose since she was asymptomatic and there wasn't evidence of acute liver failure.
 

Strength&Speed

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All the viral serology tests came back negative. Her enzymes have significantly decreased and she was started on acyclovir for a probable viral hepatitis of unknown etiology. I guess we may never know. I'll be interested to see if it ever happens again.

Btw, interestingly our Hepatologist wanted to do a Bx but she opted to travel to a regional hospital with a big (huge) name/reputation where they told her the wanted to watch it for a while before doing the Bx d/t the risks. I suppose since she was asymptomatic and there wasn't evidence of acute liver failure.
I think she should get the biopsy because we really, really want to know. That's pretty selfish.
 

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Did y'all ever run quanititative immunoglobulins on this lady? and what was her ANA?
 

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Did you run a tox screen on her (21 y/o female) and I have seen Tylenol spike up LFTs quickly before with those values. Just curious the resolution of this one.

If it's viral we'll never know... :( Adenovirus for the lose! :hardy:
 
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