Abnormal Liver Enzymes

Transcription

1 Abnormal Liver Enzymes Patrick Northup, MD, MHS Medical Director, Liver Transplantation Program Director, GI and Hepatology Fellowship University of Virginia

2 Case presentation 43 year old man Needs to start statin AST 64, ALT 72, ALP 88, TB 1.0 No new meds/herbs One drink EtOH per day No high risk practices or h/o transfusion

3 Question one 10 What would your next step be? A. Viral hepatitis serologies, ferritin, iron studies, ANA, AMA B. above plus RUQ ultrasound C. Advise patient to stop EtOH and recheck LFTs in 3 months D. Refer to hepatology E. Schedule f/u visit with your partner next week when you are on vacation Northup: Abnormal LFTS

4 Results A B C D E F Northup: Abnormal LFTS

5 Overview Definition of abnormal LFTs Abnormal AST and ALT Less than 5x upper limits of normal Greater than 15x upper limits of normal Elevations of ALP and total bilirubin Initial approach to workup When to refer?

6 What are the LFTs? ALT / AST TBili / ALP PT-INR / ALB GGT / 5 -NT LDH Hepatocellular damage Cholestasis, impaired conjugation, or biliary obstruction Synthetic function Cholestasis or biliary obstruction Hepatocellular damage, not specific for hepatic disease

7 What is abnormal? You think you are here You may be here

8 What is abnormal? 19,877 US Air Force recruits, 99 (0.5%) had confirmed ALT elevations Only 12 had identifiable liver disease Most people with abnormal LFTs have no identifiable liver disease Kundratos Dig Dis Sci 1993

9 What is abnormal? 1033 blood donors, 186 with HCV, 40 patients treated for HCV Piton Hepatology 1998 All tested once for level of ALT Percent with NORMAL LFTs 96% 42% Normal ALT does not guarantee normal liver Blood Donors 27% Active HCV Cured HCV

10 What is normal? Normal ranges at UVAHS: Test Lower limit normal Upper limit normal T. Bili (mg/dl) ALP (U/L) AST (U/L) 0 35 ALT (U/L) 0 55

11 Hepatocellular injury Primarily elevations of AST and or ALT 1. Mild: less than 5x ULN 2. Moderate: 5-15x ULN 3. Severe: greater than 15x ULN Could be due to causes from either group

12 AST/ALT less than 5x ULN Most common clinical scenario Widest differential diagnosis Consider non-hepatic causes Hemolysis Myopathy Thyroid disease Acute muscle injury due to strenuous exercise

13 AST/ALT less than 5x ULN Chronic viral (B and C) Acute viral (CMV, EBV) Steatohepatitis / NAFLD Hemochromatosis Medications / toxins Autoimmune hepatitis Alpha-1 antitrypsin Wilson s disease Celiac disease Cirrhosis

14 There is more alcohol than you think

15 AST/ALT less than 5x ULN - Meds Augmentin Amiodarone Anticonvulsants Glyburide Niacin Nitrofurantoin NSAIDS Sulfonamides Glitazones Herbs Anabolic steroids Cocaine Ecstasy PCP Carbon tetrachloride Hydrazine Toluene Chloroform

16 livertox.nih.gov

17 Suspected NAFLD/NASH

18 Suspected NAFLD/NASH Rule out other liver diseases (? specialist referral) In young you must think about Wilson s dz and AIH In polypharmacy, look at meds (amiodarone, corticosteroids) If all negative, manage metabolic syndrome aggressively, recheck in 4-6 months

19 Case presentation 21 yo male student RUQ pain, nausea, hungover beers per day for the past week Returned from spring break in Cancun TB 7.9, ALT 1089, AST 2036, ALP 199

20 Question two 10 Which is least likely to be the source of these findings? 1. Acute hepatitis A 2. Acetaminophen toxicity 3. Amanita toxicity 4. Acute alcoholic hepatitis 5. Acute hepatitis B Northup: Abnormal LFTS

21 Results Northup: Abnormal LFTS

22 AST/ALT more than 15x ULN Much smaller differential diagnosis More likely to have an acute symptomatic presentation History and physical exam are key When associated with encephalopathy and coagulopathy termed liver failure *Alcohol alone is rarely (if ever) solely responsible for this degree of elevation

23 AST/ALT more than 15x ULN Acute viral infection (A- E, HSV) Medication or toxin Acetaminophen Rx meds Amanita Ischemia Hypotension Budd-Chiari Autoimmune hepatitis Acute bile duct obstruction Wilson s disease (rare) Acute hepatic artery ligation or clot

24 Enzymes > 15x ULN Can be life threatening Can progress rapidly, sometimes in as little as 48 hours Limited differential diagnosis Need to assess for synthetic dysfunction INR Bilirubin Altered mentation

25 Isolated increased bilirubin Unconjugated (indirect) Gilbert s syndrome (rarely >4) Hemolysis (heart valve, vascular prosthesis) Ineffective erythropoiesis Hematoma resorption TIPS shunt Neonatal / Crigler-Najjar

26 Isolated increased ALP Hepatobiliary causes Biliary obstruction PBC / PSC Medications Infiltrating disease TB Sarcoid Fungal Metastases Nonhepatic Bone disease / trauma Pregnancy Chronic renal disease Non-liver malignancy CHF Normal childhood growth Chronic inflammation

27 Increased ALP and TBili Biliary obstruction Medications Chronic viral hepatitis PBC / PSC Sepsis TPN Pregnancy diseases Cirrhosis

28 Meds causing cholestasis Anabolic steroids Allopurinol Augmentin ACE-inhibitors Anticonvulsants Erythromycin Estrogens HIV meds NSAIDS TMP-sulfa Doxy / tetracycline

29 Question three 10 What is your initial lab/radiology workup of abnormal liver chemistries? A. Referral to hepatologist B. Stop meds / EtOH repeat chemistry in 3 months C. Repeat chemistries, HBs-Ag, HCV-Ab, Iron, TIBC, ferritin D. above plus RUQ ultrasound E. above plus abdominal CT Northup: Abnormal LFTS

30 Results Referral to hepatologist Stop meds / EtOH repeat chemistry in 3 months Repeat chemistries, HBs-Ag, HCV- Ab, Iron, TIBC, ferritin above plus RUQ ultrasound above plus abdominal CT Northup: Abnormal LFTS

31 Costs of labs / radiology Based on 2001 USD. Green Gastroenterol 2002: Abd U/S 80 HCV VL and geno Hepatitis ABC Hepatic Panel Charge Medicare Reimb

32 Initial workup of abnormal enzymes History and physical exam can help narrow the workup Marked abnormalities in chemistries, signs of chronic liver disease or cirrhosis should prompt expedited workup Extensive workup can be exhaustive and expensive and may be unnecessary in some cases

33 Initial workup of abnormal enzymes An isolated minor abnormality (<1.5 times upper limit of normal) in an asymptomatic individual should prompt retesting in 1 to 3 months, particularly after addressing potential causes or modifiable risk factors. Screen for HCV if in the right age group Disease specific tests including auto-antibodies, copper and iron studies, alpha-fetoprotein (AFP), and other specific viral markers should only be obtained in appropriate circumstances and usually in consultation with a specialist.

34 Initial more detailed workup Probably the most cost-effective and efficient initial workup for <5x normal: Stop EtOH/meds, recheck chem panel in 6-8 weeks If normal, recheck again in 6-8 weeks If abnormal: HBsAg, HCV-Ab, ferritin, TIBC, +/- ultrasound If no findings and persistent increase, then refer

35 Last Case 43 yo female with many years of MS. Multiple medications used for therapy Avonex, Copaxone distant past: poor tolerance Betaseron stopped 2008 Gilenya 2011: fatigue Tysabri in past, restarted April 2013

36 Labs ALP 468, ALT 1039, AST 682 Significant abdominal pain, N/V, poor po intake

37 Other workup HBV studies negative Hepatitis C positive Anti-nuclear ab positive 1:80 RUQ U/S showed no abnormalities No recent acetaminophen use What to do now?

38 Liver Biopsy

39 Summary Abnormal liver enzymes can be caused by many things Less than 5x upper limits of normal is rarely an emergency and requires a lot of detective work Greater than 15x upper limits of normal can be immediately life threatening Think about the common things, especially medications and don t panic about a single value If things don t get better or clarify themselves, call me

40 Questions?