1. Evaluation of Abnormal Liver Function Tests Dr Deb Datta Consultant Gastroenterolgist

2. Overview Background Elevated Transaminases Isolated Hyperbilirubinaemia Elevated Alkaline phosphatase Mixed Picture Case History

3. Background Liver function tests ordered routinely 1-4% of asymptomatic patients have abnormal values Population based survey-8.9% raised ALT OBESITY Serious underlying disease uncommon Diagnosis often reached non invasively No consensus on cost effective approach

4. HISTORY Duration of abnormaL LFT Symptoms- Jaundice, arthralgia, pain, pruritus, weight loss Medication (Herbal) Travel History Transfusion IV drug abuse ALCOHOL

5. EXAMINATION Stigmata of chronic liver disease Lympadenopathy Periumbilical nodule Palpable mass

6. Transaminases May not be elevated in chronic liver disease –HCV –Cirrhosis Minimal ALT elevations (<1.5 X normal) –Race/Gender –Obesity –Muscle injury

7. Elevation in Serum Transaminases STEP 1 Medications, herbal treatment, drugs Screen for alcohol abuse (AST/ALT>2:1) Obtain serology for Hepatitis B & C Screen for Haemochromatosis (TIBC>45%) USG (?Fatty Liver)

8. Elevation in Serum Transaminases STEP 2 Consider Autoimmune liver disease Wilson’s Disease (<40) Alpha 1 antitrypsin Deficiency (Emphysema)

9. Elevation in Serum Transaminases STEP 3 Exclude muscle disorder (CK) Check TFT ?Coeliac (Fe def) Adrenal insufficiency STEP 4 Liver Biopsy ? When

10. Elevated AST & ALT, <4X normal Hx & physical; stop hepatotoxic medsmeds LFTs, PT, albumin, CBC, Hep A/B/C, Fe, TIBC, Ferritin Positive serologyyNegative serologyy Negative serology, asymptomaticc Serologies: HAV IgM HBsAg HBcIgM HCV Ab or RNA

11. Stop EtOH & meds; wt loss; glucose control Repeat LFTs Observation Ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin, gliadin & endomysial Ab Negative Serology- Asymptomatic Liver biopsy AbnormalNormal 6 months ☺

12. Consider ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin Liver biopsy Negative Serology- Clinical Signs/Symptoms of Liver Disease Abnormal ☺

13. Isolated Hyperbilirubinemia Product of hemoglobin breakdown Unconjugated (indirect)- insoluble Haemolysis (Reticulocyte count) Gilbert’s syndrome (3-7% population)

14. Alkaline Phosphatase Produced by biliary epithelial cells –Non-specific to liver: bone, intestine, placenta Elevations –Biliary duct obstruction –Primary biliary cirrhosis –Primary sclerosing cholangitis –Infiltrative liver disease- ie sarcoid, lymphoma –Hepatitis/cirrhosis –Medications

15. Elevated Serum alkaline phoaphatase Rule out physiological cause Pregnancy, post pandrial DETERMINE THE SOURCE GGT Normal Bone origin Increased Hepatobiliary origin

16. ALP Hepatobiliary origin Check AMA USG AMA Positive USG abnormal parenchyma LIVER BIOPSY Dilated bile ducts ERCP MRCP AMA negative USG -Normal Assess degree of ALP elevation LIVER BIOPSY MRCP

17. MIXED PICTURE Hepatocellular pattern with Jaundice Alcoholic hepatitis Viral Hepatitis (A &E) Toxic hepatitis (Paracetamol, Wild mushroom) Autoimmune Wilson’s

18. MIXED PICTURE CHOLESTATIC PICTURE USG Extrahepatic Choledocholithiasis Pancreatic cancer Cholangiocarcinoma PSC Intrahepatic (Drug induced,PBC,PSC,Pregnancy)

19. Other Liver Labs Albumin – decreased by trauma, inflammatory conditions, malnutrition Prothrombin time (PT) -no change until liver loses 80% capacity Ammonia –No correlation between brain & serum values –Related to encephalopathy

20. Summary Algorithms based on poor quality or absence of evidence Most asymptomatic patients can safely be followed for a period of time to see if abnormalities resolve If lab abnormalities persist be thoughtful with ordering

21. 48 yr male lawyer Dyspepsia HP – negative PPI -4 weeks No better – Right hypochondrial ‘discomfort’ DM Type 2 (Diet), Simvastatin (CH -5.8) Weight – 93.5 Kg Alcohol - rare

22. 48 yr male lawyer USG and new PPI ‘Increased echogenicity- fatty liver’ ALT-78 Asymptomatic but very anxious Hepatitis serology – negative – f/up 3 months ALT-92 Cholesterol -6.4 Glucose-8 WHAT NOW?

23. Stop statin and repeat blood in 3 months Continue statin and repeat blood in 3 months Strict diet, exercise programme and monitor Liver biopsy Do nothing – ‘go away !!!’

24. Nonalcoholic steatohepatitis No significant alcohol but liver biopsy similar to alcoholic steatohepatitis No hepatitis B or C Central obesity, type 2 DM, Dyslipidemia- Metabolic syndrome Men – 20-40% of population ?Insulin resistance /?oxidative injury

25. Nonalcoholic steatohepatitis Stable condition- compared to ALD Asymptomatic- ?fatigue Role of liver biopsy - prognosis 8-26% – histological progression- linked with obesity, liver biopsy –balloon degeneration, Mallory hyaline Cirrhosis – 3-15%( >45,0besity,DM)

26. Treatment Weight reduction- gradual Diabetic and Lipid control Vitamin E & Vitamin C Metformin Rosiglitazone Pentoxifylline

27. Mallory bodies

28. NASH

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