Dr Mere Kende. MBBS,Mmed(Path), MAACB, MACTM, MACRRM Lecturer -SMHS

Transcription

1 Dr Mere Kende MBBS,Mmed(Path), MAACB, MACTM, MACRRM Lecturer -SMHS

2 Reasons for LFT Classification of Liver Diseases Signs and Symptoms of Liver Disease Routine Liver Tests Jaundice Examples of Liver Diseases and results Specialised liver Tests and diseases Other Liver tests for liver References

3 Investigating symptoms Baseline Test for drug administration or procedure Monitoring Treatment Overall Health Screen

4 Acquired Hepatitis (viruses, toxins, paracetamol) Inflammations (autoimmune) Obstructive Liver Diseases (hepatoma/gall stones/strictures) Chronic Liver disease (cirrhosis, ETOH) Hereditary Haemochromatosis A1 antitrypsin deficiency Wilsons Disease Dubin Johnson/rotor syndromes

5 HBV & HAV Glandular Fever (EBV) Typhoid Fever Dengue Chikungunya Sepsis Trauma

6 Alcoholic hepatitis Autoimmune hepatitis HCV hepatitis Non-alcoholic steatohepatitis (NASH) Fatty Liver

7 Asymptomatic (HCV infection/fatty hepatitis) RUQ pain Weight loss, anorexia, nausea/vomiting Fever & RUQ Jaundice +/- Pruritis Oedema & ascites hepatomegaly Incidentally deranged LFT (AST, ALT, ALP, GGT)

8 Not a true function test Basic /Routine Tests Eg; Enzymes (AST, AST, ALP, GGT) Specialised test (antibodies/copper/iron studies) Other Tests (uss/ct/biopsy)

9 Enzymes: ALT, AST, ALP, GGT Bilirubin (total, conj, unconj) Albumin Total protein PT (vitamin K-dependent factors) Urinary urobilinogen & bilirubin

10 Acute hepatitis Cholestasis Increased ALP/GGT Hyperbilirubinaemia & Jaundice Increased AST/ALT Hepatomegaly hypoalbuminaemia

11 Reflects cell Damage (Hepatocellular disease) ALT more specific

12 Acute HBV/HAV infection Liver toxicity (paracetamol OD, mushroom poison) Ischemic/Shocked Liver (AMI) Budd-chiari syndrome RHF

13 Increased in chronic process Increased in severe disease >2 occurs in alcoholic liver disease (?pyridoxal def)

14 Raised AST,ALT & bilirubin Normal GGT or ALP except if liver also damaged Normal PT & albumin

15 Bile canalicular/duct enzymes Very high levels (ALP>300) = cholestasis/obstruction Only slightly increased in hepatitis GGT is very sensitive for Liver disease /Alcoholic intake GGT synthesis increased by certain drugs (phenytoin, DM, obesity) Sources of ALP includes; bone, placenta & intestine

16 Features of hepatocellular damage & obstruction

17 Normal albumin in early stages (30-55g/L) Reflection of nutritional status Low in CLD/alcoholism Total protein may be normal-increased globulin High globulin Fraction (CLD/alcoholism/cirrhosis) May be low in acute illness/albumin t1/2~ 21 days High albumin only occurs in dehydration

18 Normal level<20micromol/l Unconjugated- hemolysis, no bilirubinuria, Conjugated- Hepatocellular Disease: mildly elevated bilirubin Cholestasis: Grossly elevated conjugated bili,

19 Urobilinogen present if no obstruction to bile duct Bilirubin present if increased conjugated (water soluble form) No bilirubin if jaundice due to unconjugated Bil (haemolysis)

20 Reflects high bilirubin (usu >50-80 umol/l) Unconjugate/Conjugated bilirubin Unconjugated bilirubin is dangerous to neonates (lipid soluble and diffuses into brain -kernicturus)

21 Hepatic Acquired Hepatitis/Obstructive jaundice Inherited Gilbert s/rotor s/crigler Najjar/DJ Extrahepatic (Haemolysis) RBC defects (enzymes/membranes/hb) Infections Drugs & toxins

22 Estimation of Neonatal bilirubin

23 Reflects synthesis of factors II, VII, IX, X and vitamin K Lowered plasma levels (PT) Acute severe liver injury Late stage of chronic liver disease, Malabsorption or Cholestasis Corrected by giving vitamin K

24 ALT & AST > often 1000s Ratio of ALT/AST ~ 1 ALP- normal or slight elevation <300u/L Albumin low in severe cases Prodromal stage- bilirubin may be normal, bilirubinuria

25 Icterus stage: after 5-10 days- high bilirubin, falling enzymes Convalescent phase- jaundice eases and symptoms disappear Similar changes in toxic injuries/paracetamol/ischaemic shock (AMI)

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27 Features HAV HBV HCV HDV HEV Viral Properties Incubation (days) Transmission Clinical Features RNA Picorna virus DNA Hepadnavi rus RNA Flavirus RNA - RNA calicivirus Percutaneous/Blood Products - Perinatal Perinatal + - mild moderate mild Mildsevere carrier No Yes Yes Yes No Chronic No 1-10% 80-90% common No Cancer No Yes Yes? No Prophylaxis Ig Vaccine HB Ig None HBV vaccine Faecaloral Faecaloral mild None

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29 Hx of? Paracetamol /other (>200mg/kg)/10grams Always suspect paracetamol even with other drug overdoses Take blood at least after 4hrs of hx of OD Damage more if pre-existing liver ds/alcoholic LFT deranged in 2-3 days Prophylaxis NAC may be required (Use Guidelines)

30 Paracetamol P450 system NAPQI N-acetylcysteine NAPQI=N-acetyl-p-benzo-quinone imine

31 90% of Gall stones assoc with cholecystitis Elevated liver enzymes <300 U/L Mild hyperbili <80umol/L Suspect cholangitis: fever, chills, RUQ pain, jaundice with obstructive picture

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33 Markedly elevated ALP & GGT >10x (>350) Only mild-moderate elevated transaminases <10x or <400 Often associated cell damage-mixed picture Bilirubin: mild elevation (100micromol ) to grossly elevated (1000micromol/L) Conjugated bili (majority) Dark urine/pale stool Impaired PT require vitamin K

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35 Enzyme induction /Liver damage Isolated GGT No liver damage/early marker Associated AST/ALP elevation =? liver damage Bouts of acute ETOH hepatitis can occur

36 5-10% chronic users > cirrhosis Biochemistry variable depending on stage GGT elevation proportionally >ALP AST>ALT Features similar to CAH/cirrhosis/fatty Liver

37 Atypical lymphocytes, lymphadenopathy, mild ALT, AST elevation (<400u/L), 30% have LFT abnormalities. bilirubin <100micromol/L

38 Associated with alcohol use or obesity/diabetes (NASH) Variable biochemistry abnormalities Bilirubin: usu normal or <100micromol/L Transaminases: mild elevation <200u/L ALP: normal slight elevation <200u/L GGT: isolated GGT elevation Albumin: normal

39 Variable biochemistry ALP: increased >300 u/l Transaminases: normal/mild elev n Albumin- low in late stage Bilirubin: Normal or slight elev n Bleeding tendency (PT) Alb α1 Α2 β2 Β2 gamma Elevated polyclonal IgA (beta-gamma fusion )

40 Secondaries/abscess/leukaemias/cysts Transaminases: normal/slightly increased AST Bilirubin: normal ALP: moderate gross elevation GGT: elevated Albumin: normal

41 Viral/drugs/autoimmune (CAH/CPH) Bilirubin may be normal Elevated Transaminases (x5-10) and globulin ALP/GGT normal/only slight elevation Occasionally isolated ALT elevation <10x (HCV)

42 Iron studies (hemochromatosis) AFP (marker of hepoma) HBV serology Auto-antibodies A1AT (genotyping, phenotyping) Liver biopsy/uss/ct scan

43 Biopsy Iron overload (70-80% saturation) Copper/caeruloplasmin (wilson disease) Cirrhosis/cancer

44 Causes of Iron Overload Repeated Transfusions (thalassaemia)

45 Elevated Transferrin saturation use>80% Elevated ferritin >600 mcg/l Genetic Studies HFE genes (homozygous c282y, or compound heterozygous c282y/h63d Liver biopsy if ferritin >1000mcg/L Iron deposition in parenchymal cells, kuffer cells spared

46 Pathophysiology: Inherited disorder of copper metabolism (1912) Mutation in Wilson's disease gene ATP7B (1993) P-type ATPase is involved in copper transport Transports copper out of hepatocyte. Copper overload -accumulates in the liver Liver damage- ultimately liver disease

47 Liver disease: chronic hepatitis/steatosis or cirrhosis in adolescents and young adults. CNS: basal ganglia degeneration-speech disorders and various movement disorders. Kidneys: Fanconi syndrome (proximal tubular damage)/hematuria Eyes: Kayser-Fleischer rings in the cornea (Cu++ deposits)

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49 reduced ceruloplasmin level, increased urinary excretion of copper, Elevated hepatic copper level (>250mcg/g dry weight decreased total plasma Cu+2 Free plasma Cu+2 is markedly increased Genetic: difficult > 200 mutations in ATP7B

50 Protease inhibitor MW 50,000DA 90% of A1 band in electrophoresis Acute phase reactants Associated with liver disease; cirrhosis & hepatitis in neonates Emphysema in young and adults Suspect if individual has co-existing liver and lung disease

51 Antibody studies ant-i-sm antibodies (ASMA) Anti-mitochondrial antibodies (AMA) Anti-nuclear antibodies (ANA) Viral studies: HBsAg Anti-HBc/HCV antibodies

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53 HBsAg HBs-IgG HBe-IgG HBc-IgM/-IgG HCV IgG AFP

54 normal HAV/HCV/HBV Hepatosplenomegaly/ascites/jaundice Young females Positive ANA & ASMA (80% of cases) Anti-mitochondrial antibodies (70%) Associated with HLA-A1/B8

55 Ultrasound -detects Cirrhosis Cancer Gall stones Fatty Liver Bile duct obstruction (cancer/stricture) Abscess/cysts Thrombus (hepatic vein thrombosis) Biopsy Iron overload & copper overload Cancer/cirrhosis Autoimmune hepatitis/fatty liver

56 Interpret LFT in context of clinical history ALT and AST reflects hepatocellular damage GGT is sensitive indicator of Liver disease but affected by drugs ALP & GGT reflex cholestatsis

57 ALP affected by bone/placenta/git source Low albumin is late sign in Liver disease PT indicates severity if acute liver disease Metabolic or inherited conditions are rare but should be included as a differential Consider Ultrasound as required

58 Harrison s Text Book of Medicine 17 th Edition IJ Beckingham. ABC of liver, Pancreas, Gall Bladder. BMJ 2001 ESC Koay, N Wamlsey; A Primer of Chemical Pathology, 2001 LG Gomella, SA Haist. Clinicians Pocket References 2007

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