asymptomatic elevation of transaminases

ASYMPTOMATIC ELEVATION OF TRANSAMINASES : 

ASYMPTOMATIC ELEVATION OF TRANSAMINASES Malay Misra PGT,Deptt. Of Medicine R G Kar Medical College,Kolkata

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INTRODUCTION: Up to 4% of asymptomatic population One airforce study(n=19877)-.5% But physicians with varied pts. likely to have to address such a problem more frequently. so an informed approach needed

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MARKERS OF HEPATIC INJURY AND NECROSIS: AST and ALT- two of the most reliable markers Levels elevated in a variety of disorders ALT more specific as low conc. elsewhere ALT/AST >2000 U/L- hepatitis,ischemia,drugs,toxins <250 U/L(<5 times upper level of normal)- commoner in primary care

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ETIOLOGY WHEN <5TIMES NORMAL: Hepatic causes-common 1.Alcohol excess 2.Hep B(chronic) 3.Hep C(chronic) 4.Cirrhosis 5.Steatosis/Steatohepatitis 6.Medications/Toxins 7.Acute viral hepatitis Hepatic causes-less common 1.AIH 2.Hemochromatosis 3.alppha-1 AT deficiency 4.Wilson’s disease Non-hepatic causes:1.Celiac disease 2.Hemolysis 3.Myopathy 4.Hyperthyroidism 5.Strenuous exercise 6.Macro-AST

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DRUGS CAUSUING ELEVATED TRANSAMINASES: Medications: 1.Acetaminophen.2.Amiodarone 3.Statins.4.Co-amoxyclav.5.Sulphonamides 6.Nitrofurantoin.7.Fluconazole. 8Ketoconazole.9.Carbamazepine. 10.Phenytoin.11.Labetelol.12.Heparin 13.Trazodone.14.NSAIDS. 15.INH.16.Glyburide Vitamins/herbs 1.Vit A 2.Senna 3.Ephedra and numerous others used in indigenous systems

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Important note Normal AST/ALT does not preclude significant liver disease in the setting of chronic hepatocyte injury(cirrhosis,Hep C)

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Interpretation of elevated transaminases: AST:ALT-some utility >2-alcoholic hepatitis <1-many acute and chronic diseases with liver injury steatosis particularly true in Hep C A recent study-n=140,with NASH proven by Bx. or alcoholic hepatitis AST:ALT=.9(mean) with NASH 2.6(mean) with alcohol 87% with AST:ALT >1.3 had NASH Increasing severity of NASH with increasing fibrosis with increased AST:ALT Mean AST:ALT=1.4 with cirrhosis related to NASH

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Interpretation contd. Wison’s disease-rare may cause AST:ALT>4 ELEVATION NOT LIVER EXCLUSIVE: 1.Hyperthyroidism 2.Genetic influences(ref. a recent Danish study) 3.Diurnal variation in ALT level 4.Black men>White men(by 15%) 5.Muscle injury 6.Strenuous exercise 7.Myopathy Usually AST elevation in last three

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SCREENING: Healthy asymtomatic patients using AST,ALT level-not useful A Japanese study:assessment of accuracy of AST/ALT to detect Hep C,fatty liver and alcohol excess in bank employees- Positive predictive value-low 3.9 with abnormal test-Hep C 8% with abnormal test-alcohol excess 35.7 with abnormal test-fatty liver

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MANAGEMENT: Thorough history and PE-cornerstone Risk factor identification with special attention to 1.family history 2.medications 3.illicit drug use 4.herbal remedies 5.vitamins 6.alcohol 7.blood or blood product transfusion 8.symptoms of liver disease

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Management contd. Clues to diagnosis- 1.Long-standing alcohol use 2.IV drug user,h/o blood transfusion.AST:ALT<1 3.Obesity,DM,Dyslipidemia,AST:ALT<1 4.AST:ALT>2 5.Increased Fe level 6.Polypharmacy,illicit drug,herbs 7.Frequent strenuous exercise 8.Bloating,oily,bulky stools 9.Hypergammaglobulinemia 10.Decreased ceruloplasmin,K-F ring 11.Decreased TSH Suggestion 1.Cirrhosis 2.Hep B,Hep C 3.Steatosis,Steatohepatitis 4.Alcoholic hepatitis, Wilson’s disease 5.Hemochromatosis 6.Substance induced 7.Exercise induced 8.Celiac disease 9.AIH 10.Wilsopn’ disease 11.Hyperthyroidism

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Management contd. Initial lab evaluation: Once history and PE yields no suggestion 1.Hep A, B and C serologies 2.PT and synthetic function 3.CBC and platelet 4.MCV(alcohol) 5.Ferritin,TIBC,serun iron for hemochromatosis 6.ALP and bilirubin as part of initial evaluation often normal despite hepatic injury

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Management contd. Life-style modification:asymptomatic and initial serum tests –ve 1.complete abstinence 2.control of diabetes 3.control of body weight 4.control of dyslipidemia 5.stopping suspected medications May be all needed

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Management contd. Follow-up and imaging: Transaminase level repeated after 6 months Shorter interval if deemed necessary Persistent elevation-USG CT offers no extra advantage Steatohepatitis often discovered May be the commonest cause of asymptoma- tic elevation One hospital-based study(referred patients to gastroenterology deptt.)- 83% with elevated AST,ALT but otherwise –ve --steatosis or steatohepatitis

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Management contd. Dx. still not apparent: Tests for alpha-1 AT deficiency for Wilson’s disease(serum ceruloplasmin) for Celiac disease for AIH for non-hepatic causes

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BIOPSY: On individual basis To be taken into account-Age Lifestyle Liver chemistry abnormality Desire for prognostic information Associated comorbidities

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ALGORITHM: Elevated AST,ALT <5 times normal | History and PE | Discontinue hepatotoxic agents | Confirm abnormality if error suspected | Liver chemistry-PT,albumin,CBC with platelets,Hep A,B,C serologies,serum Fe, TIBC,ferritin | --------------------------------------- | | Negative serology Positive serology | ----------------------------- | | Evidence of Asymto- Hepatic deompen. matic without decompens. CONTD.

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Algorithm contd. -ve serology +ve serology | | ---------------------------------------------------------- proceed with | | directed evalu- Evidence of CLD or hepatic asymtoma- ation and Rx. decompensation tic without decompen- | sation Expedited evaluation | | Life-style modi- fication | Follow-up at 6 months | Rpt. liver chem- istry |-----------Normal-observe Abnormal USG/CT,ANA,ASMA,Alpha-AT,Ceruloplasmin,Antigliadi Ab--------Biopsy

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