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Evaluation of Abnormal Liver Function Tests. Dr Deb Datta Consultant Gastroenterolgist. Overview. Background Elevated Transaminases Isolated Hyperbilirubinaemia Elevated Alkaline phosphatase Mixed Picture Case History. Background. Liver function tests ordered routinely
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Evaluation of Abnormal Liver Function Tests Dr Deb Datta Consultant Gastroenterolgist
Overview • Background • Elevated Transaminases • Isolated Hyperbilirubinaemia • Elevated Alkaline phosphatase • Mixed Picture • Case History
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
HISTORY • Duration of abnormaL LFT • Symptoms- Jaundice, arthralgia, pain, pruritus, weight loss • Medication (Herbal) • Travel History • Transfusion • IV drug abuse • ALCOHOL
EXAMINATION • Stigmata of chronic liver disease • Lympadenopathy • Periumbilical nodule • Palpable mass
Transaminases • May not be elevated in chronic liver disease • HCV • Cirrhosis • Minimal ALT elevations (<1.5 X normal) • Race/Gender • Obesity • Muscle injury
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)
Elevation in Serum Transaminases STEP 2 • Consider Autoimmune liver disease • Wilson’s Disease (<40) • Alpha 1 antitrypsin Deficiency (Emphysema)
Elevation in Serum Transaminases STEP 3 • Exclude muscle disorder (CK) • Check TFT • ?Coeliac (Fe def) • Adrenal insufficiency STEP 4 • Liver Biopsy ? When
Elevated AST & ALT, <4X normal Hx & physical; stop hepatotoxic meds Serologies: HAV IgM HBsAg HBcIgM HCV Ab or RNA LFTs, PT, albumin, CBC, Hep A/B/C, Fe, TIBC, Ferritin Negative serology, asymptomatic Negative serology Positive serology
Negative Serology- Asymptomatic Stop EtOH & meds; wt loss; glucose control 6 months Repeat LFTs Abnormal Normal Ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin, gliadin & endomysial Ab Observation Liver biopsy ☺
Negative Serology- Clinical Signs/Symptoms of Liver Disease Consider ultrasound, ANA, smooth muscle Ab, ceruloplasmin, antitrypsin Abnormal Liver biopsy ☺
Isolated Hyperbilirubinemia • Product of hemoglobin breakdown Unconjugated (indirect)- insoluble • Haemolysis (Reticulocyte count) • Gilbert’s syndrome (3-7% population)
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
MIXED PICTURE Hepatocellular pattern with Jaundice • Alcoholic hepatitis • Viral Hepatitis (A &E) • Toxic hepatitis (Paracetamol, Wild mushroom) • Autoimmune • Wilson’s
MIXED PICTURE CHOLESTATIC PICTURE • USG Extrahepatic • Choledocholithiasis • Pancreatic cancer • Cholangiocarcinoma • PSC Intrahepatic (Drug induced,PBC,PSC,Pregnancy)
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
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
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
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?
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 !!!’
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
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)
Treatment • Weight reduction- gradual • Diabetic and Lipid control • Vitamin E & Vitamin C • Metformin • Rosiglitazone • Pentoxifylline