- Liver function tests (LFTs) are used to screen for and investigate liver disease, though they can be abnormal even in a healthy liver. - The most important part of evaluating abnormal LFTs is obtaining a thorough medical history regarding medications, chemical exposures, and symptoms. - Physical examination and additional lab tests can help determine if the abnormal LFT pattern is predominantly hepatocellular or cholestatic and suggest possible etiologies like viral hepatitis, alcohol use, or drug toxicity. - A liver biopsy may be necessary when the cause of abnormal LFTs remains unexplained after history, exams and other testing to identify the underlying liver disease.

1. Abnormal LFT’s Dr E M Said

2. why do we check LFT’s? Well person screening To investigate unexplained symptoms For pre-operative or base line assessment For investigation of suspected liver disease

3. What are LFT’s? The term “LFTs” is imprecise… Many of the tests reflecting the health of the liver are not direct measure if its function . Normal test values are arbitrarily defined as those occurring within two standard deviation of the the mean i.e 5% of of healthy individuals will have abnormal LFTs

4. According to the American Gastroenterological Association (AGA), 1 to 4 percent of the asymptomatic population may have elevated serum liver chemistries. This is consistent with the usual definition .

5. Remember…. abnormal LFTs often,but not always,indicate something wrong with the liver. The commonly used LFTs may be abnormal even in a healthy liver. Normal LFTs do not always mean that the liver is normal.

6. approach History: The most important part in evaluation of a patient with abnormal LFTs

7. approach History: The most important part in evaluation of a patient with abnormal LFTs Exposure to any chemicals Use of any medications The duration of abnormal LFTs The presence of accompanying symptoms e.g jaundice ,artheralgia,Wt loss fever,pruritus

8. approach History: The most important part in evaluation of a patient with abnormal LFTs Physical examination: ?finding suggestive CLD

9. approach History: The most important part in evaluation of a patient with abnormal LFTs Physical examination: ?finding suggestive CLD

10. approach History: The most important part in evaluation of a patient with abnormal LFTs Physical examination: ?finding suggestive CLD Lap testing: evaluate the overall pattern

11. LFT profile : Bilirubin Total protein ALT ALP Gamma GT Albumin Prothrombin time

12. Patterns of abnormal LFT’s Sole or combined elevation acute or chronic Predominantly Hepatocellular Predominantly cholestatic

13. Bilirubin Produced by haemoglobin catabolism Isolated hyper bilirubinaemia occurs in tow settings: Over production Impaired uptake,conjugation or excretion

15. ALT cytoplasmic enzyme that is predominantly hepatic in origin Lesser quantities are found in the kidneys, heart, and skeletal muscle Injury or disease of the liver parenchyma cause a release of the enzyme into the bloodstream Generally, most ALT elevations are caused by liver dysfunction

16. Typical ALT Values in Disease

18. ALP Largely originate from the liver,mainly cells lining biliary ducts or membranes adjoining the bile canaliculi,and bones Marked increase is typical of cholestasis (often with raised GGT) Variety of bone disorders (usually without raised GGT) Isoenzymes may be useful for distinguishing these sources

21. Gamma GT Found in the hepatocytes and biliary epithelial cells. Sensitive in detecting hepatobiliary disease but limited by lack of specificity Best used to evaluate elevation of other enzymes High GGT with otherwise normal liver should not lead to exhaustive work up for liver disease

22. Gamma GT Found in the hepatocytes and biliary epithelial cells. Sensitive in detecting hepatobiliary disease but limited by lack of specificity Best used to evaluate elevation of other enzymes High GGT with otherwise normal liver should not lead to exhaustive work up for liver disease Twofold elevation with AST:ALT ratio2:1suggest alcohol abuse

24. Albumin Albumin is synthesised in the liver Albumin has a plasma half-life of three weeks; therefore, serum albumin concentrations change slowly in response to alterations in synthesis. In practice, patients with low serum albumin concentrations and no other LFT abnormalities are likely to have a nonhepatic cause for low albumin, such as proteinuria or an acute or chronic inflammatory state.

25. Prothrombin time Not usually included in the LFTs panel abnormal PT prolongation may be a sign of serious liver dysfunction. An elevated PT can result from a vitamin K deficiency ,a trial of vitamin K injections is the most practical way to exclude vitamin K deficiency in such patients.

26. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis

27. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis Typically AST:ALT is 2:1 AST rarely exceed300

28. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis Viral hepatitis

29. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis Viral hepatitis Aminotransferase>500 ALT greater or equal AST

30. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis Viral hepatitis Toxic hepatitis Shock liver(ischemic hepatitis)

31. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis Viral hepatitis Toxic hepatitis Shock liver(ischemic hepatitis) exceeding1000IU/L Or 50x upper limit of normal

32. Predominantly Hepatocellular Usually ALT>ALP Alcoholic hepatitis Viral hepatitis Toxic hepatitis Shock liver(ischemic hepatitis) Wilson disease Autoimmune hepatitis

33. Copyright ©2003 BMJ Publishing Group Ltd. Limdi, J K et al. Postgrad Med J 2003;79:307-312 Suggested algorithm for evaluating raised transaminases

34. Predominantly cholestatic Usually ALP>ALT 1 st determine intra or extrahepatic Distinction may not be straightforward 1 st step is Ultrasound biliary dilatation extrahepatic cholestasis no dilatation intrahepatic cholestasis False negative in partial obstruction,cirrhosis or PSC

35. extrahepatic cholestasis Choledocholithiasis Malignant causes: Pancreatic,gall bladder,ampullary and cholangiocarcinoma Hilar lymphadenopathy Chronic pancreatitis AIDS cholangiopathy

36. intrahepatic cholestasis Drug induced Primary biliary cirrhosis Primary sclerosing cholangitis Other causes include: Sepsis,postoperative,paraneoplastic, thyroid cancer,Hypernephroma & prostate cancer

37. Copyright ©2003 BMJ Publishing Group Ltd. Limdi, J K et al. Postgrad Med J 2003;79:307-312 Suggested algorithm for evaluating a raised ALP

38. The role of liver biopsy Most patients with abnormal LFTs with suspected etiologic factors for liver disease are identified by history taking, physical examination, further blood tests, and imaging In patients with unexplained LFTs elevations, a liver biopsy may be helpful to identify the cause of liver disease The decision to perform a liver biopsy must balance the possible risks of the procedure (eg, discomfort, bleeding, peritonitis, pneumothorax) with the potential benefits