Understanding liver test abnormalities. Emmanuel Tsochatzis Royal Free Hospital and UCL London, UK

Transcription

1 Understanding liver test abnormalities Emmanuel Tsochatzis Royal Free Hospital and UCL London, UK

2 Do not interpret on their own History Clinical examination Laboratory findings Imaging

3 Liver function tests Interpretation must be performed within the context of the patient s risk factors, symptoms, concomitant conditions, medications, and physical findings Rarely provide specific Dx, but rather suggest a general category of liver disease Differing laboratories differing normal values

4 Normal Laboratory Values Normal Abnormal 2 SD normal values = mean ± 2SD of normal population

5 LFT abnormalities classification Hepatocellular injury (AST, ALT) Cholestatic injury (ALP, γgt, bilirubin) Infiltration (ALP, γgt, occasionally bilirubin) Synthetic function (albumin, INR) Albumin, INR, bilirubin also used as prognostic factors (Child-Pugh, MELD, UKELD)

6 Aminotransferases AST ALT catalyze transfer amino groups to form pyruvic acid cytosol (20%) and mitochondria (80%), predominantly periportal hepatocytes T1/ hr catalyze transfer amino groups to form oxaloacetate cytosol T1/ hr. liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and RBC low concentration in other tissues more specific for liver disease than AST

7 Aminotranferases Level of transaminase elevation Predominant AST elevation Rate of transaminase decline

8 Level of elevation >15 times : acute hepatic injury 5-15 times : less useful <5 times : chronic hepatic injury

9 ALT and AST > 15 times Acute viral hepatitis (A- E, herpes) Medications/toxins Ischaemic hepatitis Acute bile duct obstruction Autoimmune hepatitis Wilson s disease Acute Budd-Chiari syndrome Hepatic artery ligation Heat stroke AST predominate : medication/toxin, ischemic >75 times : ischemic, toxic, viral (less common)

10 AST/ALT ratio <1 : majority of liver disease (usually 0.8) >2 : extrahepatic source alcoholic hepatitis ischemic and toxin acute Wilson s disease : haemolysis lymphoma cirrhosis >4 : fulminant Wilson s disease

11 Rate of transaminase decline rapid ischaemic short half life drug acute biliary tract obstruction fulminant hepatitis slow acute viral hepatitis long half life drug AIH metabolic disease (decline is ominous if INR)

12 Unexpected ALT elevation Muscle disease/injury (CPK, aldolase) Thyroid dysfunction (TSH) Coeliac sprue (anti-endomysial antibody)

13 Alkaline phosphatase Of cytosolic origin in the liver Present in placenta, ileal mucosa, kidney, bone Half life = 3 days Elevated in 3d trimester of pregnancy Blood types O and B: can have elevated ALP after fatty meal due to influx of intestinal ALP Liver origin: elevated GGT Bone origin: normal GGT

14 Alkaline phosphatase Physiologic >60 yr. child and adolescent pregnancy blood group O post meal (fatty meal) Pathologic intrahepatic extrahepatic

15 Infiltrative diseases modest (up to 3x) rise in aminotransferases, and up to 20x rise in ALP, bilirubin N-5x TB Fungal infection HCC Lymphoma Metastatic malignancy Amyloidosis Sarcoidosis Other granulomatous diseases

16 Infiltrative diseases Cancer, granulomatous disease, amyloidosis, Hodgkin s Disproportionate of ALP, ggt compared to bilirubin Sarcoidosis, tuberculosis Two most common that produce jaundice

17 γ-glutamyltransferase (GGT) catalyzed transfer of γ-glutamyl groups of peptides to other amino acid abundant in liver, kidney, pancreas, intestine, and prostate, spleen, heart, brain but not in bone T1/ days 28 days in alcohol-associated liver injury

18 γ-glutamyltransferase (GGT) Increase alcohol (even without liver disease) drug anticonvulsant (CBZ, phenytoin, and barbiturate), warfarin almost all type of liver diseases COPD, renal failure, DM, hyperthyroidism, RA, AMI, pancreatic disease

19 Isolated unconjugated hyperbilirubinemia IDB fraction > 85% of total bilirubin 1. increased production : hemolysis chronic hemolysis-not sustained increase of bilirubin >5 mg/dl in normal hepatic function ineffective erythropoiesis : folate, IDA drug : rifampicin, ribavirin, probenecid resolution of hematoma 2. defects in hepatic uptake/conjugation Gilbert s syndrome Crigler-Najjar syndrome

20 Gilbert s syndrome benign, unconjugated hyperbilirubinemia with otherwise normal liver chemistries up to 5% of normal population polymorphism in TATA box of gene encoding bilirubin UDP-GT impaired ability to conjugate bilirubin prominent in fasting state, systemic illnesses, haemolysis, some medications

21 Gilbert s syndrome Dx : asymptomatic, healthy mild unconjugated hyperbilirubinemia (<4 mg/dl) with otherwise normal liver chemistries test exclusion medications and hemolysis

22 Conjugated hyperbilirubinemia DB > 50% of total bilirubin Can t differentiate obstruction and parenchymal disease Delta fraction CB tightly bound to albumin tendency of hyperbilirubinemia to resolve more slowly than other biochemical tests

23 Diagnostic approach in elevated serum bilirubin

24 Common pitfalls

25 Ischaemic hepatitis low-flow hemodynamic state hypotension, sepsis, cardiac arrhythmia, MI, HF, hemorrhage, extensive burns, severe trauma, heat stroke hypotension often not documented usually subclinical

26 Ischaemic hepatitis sudden and massive (>2000) elevation of liver enzymes, tend to decrease rapidly and return normal within 1 wk. mild and transient elevation of bilirubin (80% < 2 mg/dl) and ALP extreme elevation LDH (>5000), ALT/LDH < 1.5 rare acute liver failure Rx and prognosis - underlying disease

27 Acute biliary obstruction aminotransferase peak early and decline rapidly over hr. with Abx despite unresolved obstruction after aminotransferase decrease, bilirubin and ALP increase ALP de novo synthesis, initial levels normal 25% of patients with AST > 10X

28 Alcoholic hepatitis History of alcohol consumption Systemic symptoms / SIRS Transaminases DO NOT exceed 300 IU/dl AST/ALT >1 in 92%, >2 in 70% - pyridoxine deficiency - mitochondrial injury GGT/ALP > 2.5

29 NAFLD Fatty liver present in 20-30% of general population Usually associated with features of metabolic syndrome Rarely ALT > 4 ULN ALT>AST (DDx from ALD) ALP and GGT raised less often than transaminases ferritin in 40% Liver biopsy and alcohol exclusion essential for diagnosis

30 Case 43 y old male, asymptomatic Referred for abnormal liver tests BMI 28 kg/m 2, glucose intolerance ALT 192, AST 110, ALP 420, GGT 1265 Liver screen negative US mild steatosis

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32 Acute hepatitis subfulminant Hepatocellular or cholestatic pattern Gallbladder wall thickening due to inflamed liver

33 Biliary complications post-lt 6-32% of all transplants 1/3 in 1 st month Strictures - Anastomotic - Non-anastomotic ischaemic type (ITBL) DDx from acute/chronic rejection Check hepatic artery Jaundice a late feature non specific LFT

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35 Liver chemistry tests Interpret within specific context normal may have abnormal tests normal value not ensure that patient is free of liver disease level of abnormality does not reflect severity but may help in DDx decrease in the value does not mean improvement limitation in sensitivity and specificity

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