Dr. krishnan final protected

Approach to Abnormal Liver Profiles

Prashant Krishnan, M.D.Gastroenterologist!

Peak Gastroenterology Associates!

!GI Section Chair!

Memorial Gastroenterology Department

Medical Director!Front Range Endoscopy Centers!

!Clinical Associate Professor!

Rocky Vista University

Copyright (c) 2014 Prashant V. Krishnan, MD | Peak Gastroenterology Associates, P.C.

Overview

Initial Testing!

Interpretation!

Hepatocellular Diseases

Cholestatic Diseases!

Fulminant Hepatic Failure!

Other Considerations


Initial Testing


Important Initial Tests

Liver profile!

Coagulation profile!

CBC!

Possibly imaging studies!

PATTERN RECOGNITION!!!


The Liver Profile

AST & ALT!

Alkaline phosphatase!

Total and direct bilirubin!

Total protein and albumin


The Aminotransferases

Where are they located?!

Markers of liver cell injury (Hepatocellular disease)!

AST is located in various extrahepatic tissue!

• Skeletal and cardiac muscle and more!

• Not as specific to liver


Alkaline Phosphatase

Where is this located?!

Membrane bordering hepatocytes and bile canaliculi!

Also found in bone and placenta!

How can you tell if elevation in alkaline phosphatase is from liver vs. other?!

GGT or fractionated alkaline phosphatase


Bilirubin

Unconjugated = Indirect (Water insoluble)!

Conjugated = Direct (Water soluble)!

Unconjugated becomes conjugated!

Indirect bilirubin flows to liver!

Hepatocytes conjugate bilirubin with glucuronic acid!

Bile becomes water soluble and excreted in bilirubin


Albumin

Abnormality typically indicates severe liver disease!

Short half life!

If no overt liver disease, think about:!

Urinary losses!

GI losses


Coagulation Profile

Prothrombin Time (PT) and INR!

Abnormality indicates severe liver disease!

PT is dependent on vitamin K and vitamin K dependent factors!

Vitamin K dependent factors synthesized in liver


CBC

Why should you look at this?!

Thrombocytopenia!

• What does this tell you?


Interpretation


Synthetic Function

Liver profile is different from liver function tests (LFTs)!

Function is determined by:!

Bilirubin!

Albumin!

PT/INR

Is the liver working?

Is the liver dying?Aminotransferases


Understanding Time Frames

You order the labs and get the results...now what?!

Look to the past!

Is this new or chronic?!

Does the person have chronic liver disease with something new superimposed?!

Patterns give you hints as to what could be going on


Primary Process

Is this primarily a hepatocellular process?!

Aminotransferases (AST & ALT)!

Is this primarily a cholestatic process?!

Alkaline phosphatase and bilirubin!

Is this a mixed picture?


Hepatocellular Diseases


Case # 1

75 y/o female in MVA found unconscious!

Has subdural hematoma!

Intubated for airway protection!

Sent to ICU where you pick up patient!

No documented hypotension!

Labs are checked - Mild troponin elevation and renal failure


Case # 1 ContinuedLiver profile!

AST = 4528!

ALT = 2350!

Alkaline phosphatase = 145!

Total bilirubin = 3.2!

Direct bilirubin = 1.2!

Total protein = 7.4!

Albumin = 3.5!

Hepatocellular, cholestatic, or mixed?


Case # 1 Continued

What do you think is going on with her liver?!

Why do you think so?!

What information supports your suspicion?!

What information would offer you further support?


Case # 1 Continued

ANSWER = Ischemic liver injury!

Ischemia not only refers to hypovolemia, but also decrease oxygen delivery to tissues!

S0 could be euvolemic with hypoxemia leading to liver injury!

Evidence for ischemia!

Elevation in troponin and ARF - Ischemia to other organs


Case # 1 Continued

With ischemia, rapid rise in aminotransferases and a rapid decline!

Treatment is IV fluids and improve oxygenation, if hypoxemic


Aminotransferases > 1000Viral hepatitis!

Hepatitis A, B, and C!

EBV, CMV, and HSV!

Drugs - Acetaminophen (Tylenol)!

Ischemic hepatopathy!

Trauma!

Autoimmune hepatitis!

Choledocholithiasis (Rare)


Aminotransferases > 1000Viral hepatitis - Social and sexual history is important!

HSV, Tylenol, and ischemia can elevate aminotransferases extremely high!

Drugs - Check acetaminophen level!

Ischemia - Hypovolemia or hypoxemia!

Trauma - History!

Autoimmune - ANA, ASMA, ALKM, quantitative immunoglobulins!

Choledocholithiasis (Rare) - Imaging


Case # 252 y/o Caucasian female with h/o HTN, hypercholesterolemia, and DM!

New to your clinic from another state!

Has 2 tattoos and is a “love machine”!

No h/o blood transfusions!

Physical exam - Obesity!

You draw some labs and find elevations in her liver profile



AST = 75!

ALT = 135!





Albumin = 4.1!

Coags and CBC normal!



Case # 2 ContinuedHow do you want to proceed?!

Check viral hepatitis screen - If negative, recheck in 3-6 months!

Still elevated...now what? - Exclude causes!

Inquire about EtOH history!

Hepatitis B and C screen, if not done!

Hemochromatosis (Caucasians) - Iron studies and ferritin!

Wilson’s disease - Probably too old but can check ceruloplasmin!

Autoimmune hepatitis - ANA, ASMA, ALKM, quantitative immunoglobulins!

Alpha 1 Anti-trypsin deficiency - Check level and phenotype!

DILI - Check medication list!

NASH - Can check fasting lipid profile and recommend weight loss


Case # 2 ContinuedDrinks 1-2 beers only on weekends!

Hepatitis B and C screen negative!

Autoimmune workup negative!

Iron studies, ferritin, and ceruloplasmin negative!

A1AT is normal!

LDL = 178


Case # 2 ContinuedWhy is her liver profile abnormal?!

NASH - Diagnosis of exclusion!

What is the difference between NAFLD and NASH?!

Can image liver to evaluate for fatty deposition!

Treatment:!

Weight loss!

Treat DM and hypercholesterolemia!

• Okay to use statins as long as aminotransferases < 3x upper limit of normal


Chronic HepatitisSo what are the causes of chronic hepatitis?!

EtOH!

Hepatitis B and C!

Hemochromatosis!

Wilson’s disease!

Autoimmune hepatitis!

A1AT deficiency!

DILI!

NASH


Case # 335 y/o male comes to your clinic - Physical exam shows scleral icterus and jaundice!

Liver profile!

AST = 250!

ALT = 110!




Total protein = 7!

Albumin = 3.1!



Case # 3 Continued

What further information would you want from him?!

What do you suspect and why?!

How do you treat him?


Alcoholic HepatitisSocial history is extremely important!

Patients underestimate consumption level!

Classic 2:1 ratio and aminotransferases < 400!

Bilirubin increased out of proportion to aminotransferases!

Treatment:!

Counseling and chemical dependency!

Many improve off EtOH!

Hydration and monitoring liver profile/coags periodically!

Consider pentoxifylline or steroids


Cholestatic Diseases


Case # 4

45 y/o new female patient with no medical problems!

Complains of fatigue!

Has some itching from time to time!

Physical exam is normal!

Labs checked



AST = 45!

ALT = 40!





Albumin = 4.1!

Ultrasound is done - No biliary dilation or cholelithiasis


Case # 4 Continued

Hepatocellular, cholestatic, or mixed!

What do you suspect and why?!

How would you confirm this?!

What else would be in your differential?!

How do you treat this?


Primary Biliary Cirrhosis

Middle aged females are predominantly affected!

Complaints include fatigue and pruritus!

Smaller intrahepatic bile ducts are mainly affected!

Diagnosis confirmed by AMA, although 5-10% could be negative for AMA and still have PBC!

Treat with Ursodiol (Actigall)!

May eventually need a liver transplant


Other ConsiderationsGallstones - U/S not suggestive & no biliary colic!

Difference between cholelithiasis and choledocholithiasis!PSC - Affects large extrahepatic ducts!

More common in men!Associated with ulcerative colitis (Board Question)!Diagnose with ERCP or MRCP!

DILI - Withdraw medication and should improve!SEPSIS - See many ICU patients with this!Infiltrative disorders - CT or MRI to image the liver!

Lymphoma, other malignancies, amyloidosis, and sarcoidosis


Case # 538 y/o male presents with RUQ and epigastric pain x 2 days!

RUQ pain began first, intermittently for 30 min to 3 hours!

Some nausea and clear emesis!

Had chills at home but did not check temperature!

Stools are slightly lighter in color


Case # 5 ContinuedTemp = 38.5oC!

Physical exam!

Tenderness in epigastrium and RUQ!

Jaundice!

U/S - 9 mm CBD and cholelithiasis!

No pericholecystic fluid or GB wall thickening



AST = 55!

ALT = 52!





Albumin = 3.6!

Lipase = 527


Case # 5 Continued

What do you suppose is the problem?!

How should you work up this patient?!

Is an ERCP necessary?!

How would you treat this patient?


Gallstone Pancreatitis and Cholangitis

Most likely sequence of events!Cholelithiasis leads to choledocholithasis!Pancreatitis, biliary stasis, and bacterial growth!Patient develops cholangitis!

• Charcot’s triad and Raynaud’s pentad!Cholangitis is a SERIOUS problem!

Act fast and act early!Aggressive IV hydration and antibiotics


Gallstone Pancreatitis and Cholangitis

If still obstructed, needs ERCP for intervention!

Persistent pain, dilated ducts, persistent fevers!

If not obstructed, would postpone ERCP!

One of the complications is pancreatitis!

Pain control!

Call surgery for cholecystectomy


Fulminant Hepatic Failure


Case # 656 y/o female brought in by boyfriend for confusion!

Had a fight 2 weeks ago - Extremely depressed!

Thinks she may have taken a “medicine” with EtOH!

Does not drink regularly!

1.5 weeks ago - Slightly yellow and become progressively worse!

Last night - Very confused!

She is not able to provide any history


Case # 6 Continued

Physical exam:!

Jaundice and asterixis!

Patient is very lethargic and drowsy!

No spider angiomata or caput medusae!

No known varices or prior liver disease


Case # 6 Continued

Liver profile!

AST = 163!

ALT = 137!





Albumin = 2.8

Ammonia = 120!

PT = 18.3!

INR = 2.34!

Platelets = 428


Case # 6 Continued

What do you think the “medicine” was she ingested?!

What is happening to her now?!

Her aminotransferases decrease - Is she getting better?!

What do you need to do?


Case # 6 Continued

She probably overdosed on Acetaminophen!

Check acetaminophen level!

Start N-acetylcysteine immediately!

She is in fulminant hepatic failure!

Decreased synthetic function!

Hepatic encephalopathy!

Hepatic burnout


Case # 6 ContinuedManagement needs to be deliberate and fast!

Address code status!

Move patient to ICU IMMEDIATELY - Intubation may be necessary for airway protection!

Call the transplant center IMMEDIATELY!

CT head and rule out infection (BCx, UA, UCx, CXR) - Minimize narcotics and sedation!

• If elevated intracranial pressure, move to SICU and a bolt should be placed IMMEDIATELY - Can also try Mannitol!

Lactulose and Rifaximin - Goal of 3-4 bowel movements per day!

Supportive care


Fulminant Hepatic Failure

Acute liver failure with encephalopathy within 8 weeks of onset of jaundice in a patient with no prior liver disease!

Encephalopathy - Cerebral edema!

Hypoglycemia!

Renal and electrolyte disturbances!

Lactic acidosis!

Infections


Other Considerations


Case # 7

85 y/o cirrhotic female from NASH falls at home and fractures her femur!

Seen by Ortho who wants to manage her non-surgically with brace since she is cirrhotic!

Bone displacement occurs even with brace so patient taken to the OR


Case # 7 Continued

On physical exam, she has multiple ares of ecchymosis


Case # 7 ContinuedWhat’s going on with her?!

What information supports your conclusion?!

Indirect hyperbilirubinemia!

Ecchymosis!

Elevated BUN!

How do you treat her?


Indirect Hyperbilirubinemia

Breakdown or resorption of heme from RBCs!

Look at the BUN - Can give you a clue!

Think of hemolysis!

Bilirubin, LDH, haptoglobin, retic count, peripheral smear - Possibly Coomb’s test!

Think of resorption of hematomas!

Gilbert’s syndrome - Everything else is normal!

Normal variant


Thank You


Any Questions?


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