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MGH                Claudio Puoti S.C. di Medicina Epato-Gastroenterologica,Emodinamica Epatica ed Endoscopia Digestiva    ...
Three diagnostic scenarios1.   A patient who has been referred because of clinical     symptoms (asthenia, fatigue, itchin...
Virus      Alcohol                                    Autoimmunity           The galaxy       of liver diseases           ...
Genetic testing                                            Fibroscan                       C282Y  Hemodynamic             ...
Liver function tests and their site of origin
De Ritis F, Coltorti M, Giusti G.Clin Chim Acta 1957; 2:70-4
Where do they come from?AST                            ALT• Cytosol and  mitochondria              • Cytosol• Liver       ...
Interpretation of Abnormal         Liver Biochemistry Values2.5% below       Normal people         2.5% above   2 SD      ...
“Historical”    “Updated” upper limits upper limits    (population at low risk                    for liver disease) 40 U/...
19.877 healthy       99 ALT elevation                         (0.5%)Air Force recruits                             12% 4 H...
95.977                                  Abnormal ALTasymptomatic subjects                           5107 (5%)             ...
4.072                             Abnormal ALTasymptomatic subjects                      714 (17%)                        ...
High chanceLow chance
354 patients with abnormal ALT and negative         serological/virological markers              AIH    PBC       OTHER   ...
OTHER ABNORMALITIESMAGNITUDE                       (GGT, bilirubin, ALP, PLT,                            cholesterol…)    ...
RISK                       EXTRA-HEPATICFACTORS                        DISEASES               ELEVATED           AMINOTRAN...
Diagnosis of symptomless ALT elevation :               role of clinical parameters       History                     Signs...
Male      Female   Middle-aged                 GGT ALT < 2-5 ULN  ALT > 5-10 ULN ALP, GGT, Glucose, lipidsHigh GGT        ...
Exclude:ALT > 10 ULN                                      drugsno history or physical evidence of CLD           alcohol   ...
Exclude:ALT > 10 ULN                                      drugsno history or physical evidence of CLD           alcohol   ...
Exclude:ALT > 10 ULN                                   drugs (DILI)no history or physical evidence of CLD           alcoho...
GGT ?               HCVAlcohol                     PLT?                +++ abuse             other liver chemistry ?   ++ ...
Other liver enzyme abnormalities                          Gamma GT   Liver cells and biliary enzyme activity   Cholestas...
Other liver enzyme abnormalities                  Alkaline phosphatase Biliary cells enzyme activity It means cholestasi...
Messaggio conclusivo I• Lievi alterazioni di laboratorio della funzionalità epatica  non sono rare in soggetti apparenteme...
Messaggio conclusivo II• Nel nostro Paese, le cause più frequenti di modeste  elevazioni degli enzimi epatici sono rappres...
Messaggio conclusivo III• Una corretta anamnesi personale, patologica e farmacologica  consente la diagnosi clinica nella ...
Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012
Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012
Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012
Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012
Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012
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Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012

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Puoti Claudio. FAD HT 2012. Come interpretare alterazioni lievi di laboratorio della Funzionalità Epatica. ASMaD 2012

  1. 1. MGH Claudio Puoti S.C. di Medicina Epato-Gastroenterologica,Emodinamica Epatica ed Endoscopia Digestiva Marino, Roma
  2. 2. Three diagnostic scenarios1. A patient who has been referred because of clinical symptoms (asthenia, fatigue, itching, vomiting…)2. A patient who has been referred because of signs (hepatomegaly, jaundice, bruises, bleeding, ascites)3. A patient who has just been found by chance to have slight liver enzymes abnormalities (sporadic determinations).
  3. 3. Virus Alcohol Autoimmunity The galaxy of liver diseases Other HCC SteatosisMetastases Vascular Haemochromatosis
  4. 4. Genetic testing Fibroscan C282Y Hemodynamic Liver Biopsy Virological testsAntibody detection BiochemistryEIA, RIBA Liver biochemistryGenome detection PLT countPCR, TMA History, Prothrombin timeGenotyping Clinical A/G ratio examination Fibrosis serum markers Imaging US Endoscopy CT, NMR
  5. 5. Liver function tests and their site of origin
  6. 6. De Ritis F, Coltorti M, Giusti G.Clin Chim Acta 1957; 2:70-4
  7. 7. Where do they come from?AST ALT• Cytosol and mitochondria • Cytosol• Liver • Liver• Kidney • Skeletal muscle• Heart • Kidney• Skeletal muscle• Spleen• Lung• Erythrocytes
  8. 8. Interpretation of Abnormal Liver Biochemistry Values2.5% below Normal people 2.5% above 2 SD 2 SD Age Age Gender Gender Blood group Blood group Post-prandial state Post-prandial state BMI BMI Alcohol Alcohol Lipid metabolism Lipid metabolism Carbohydrate metabolism Carbohydrate metabolism Smoke Smoke AGA technical Review, Gastro 2002 Ruhl et al, Gastro 2003
  9. 9. “Historical” “Updated” upper limits upper limits (population at low risk for liver disease) 40 U/L males 30 U/L males30 U/L females 19 U/L females
  10. 10. 19.877 healthy 99 ALT elevation (0.5%)Air Force recruits 12% 4 HBV IDENTIFIABLE 4 HCV CAUSES 2 autoimmune CH 1 cholelithiasis 1 GI infection
  11. 11. 95.977 Abnormal ALTasymptomatic subjects 5107 (5%) Mildly elevated ALT Severely elevated ALT 4440 (87%) 667 (13%)
  12. 12. 4.072 Abnormal ALTasymptomatic subjects 714 (17%) NAFLD UNKNOWN MET. SYNDR BOTH ALCOHOL HCV HBV
  13. 13. High chanceLow chance
  14. 14. 354 patients with abnormal ALT and negative serological/virological markers AIH PBC OTHER ALCOHOL NORMAL DRUGS NASHCRYPTOGENIC HEPATITIS STEATOSIS Skelly MM, J Hepatol 2001
  15. 15. OTHER ABNORMALITIESMAGNITUDE (GGT, bilirubin, ALP, PLT, cholesterol…) ELEVATED AMINOTRANSFERASE AST/ALT RATIO LEVELS SYMPTOMS SIGNS DURATION AGA technical Review, Gastro 2002
  16. 16. RISK EXTRA-HEPATICFACTORS DISEASES ELEVATED AMINOTRANSFERASE LEVELS HISTORY AGE AGA technical Review, Gastro 2002
  17. 17. Diagnosis of symptomless ALT elevation : role of clinical parameters History Signs Blood tests• Alcohol abuse • Abdominal wall veins • Albumin• Blood exposure • Ascites • AST/ALT ratio• Drugs • Jaundice • Bilirubin• Family history • Liver failure signs • GGT, ALP• • Obesity • IVDA Lipids • Spider naevi• Occupational exposure • PLT count • Splenomegaly• Previous diseases • PT • WBC
  18. 18. Male Female Middle-aged GGT ALT < 2-5 ULN ALT > 5-10 ULN ALP, GGT, Glucose, lipidsHigh GGT NASH/ Obesity gallstonesabnormal GGT, ALPBILIRUBIN ASH Diabetes Jaundice ? Alcohol abuse RUQ pain IVDA Young Chronic ALT 2-10 ULN HBsAg, WBC count ALT x 5-10 EBV serologyleukocytosis HCV/ Normal ALP a-HCV IMN Normal bilirubin fever, chills HBV Asymptomatic limphadenopathy sore throat
  19. 19. Exclude:ALT > 10 ULN drugsno history or physical evidence of CLD alcohol CBD disease Vascular disease HAV-IgM HBsAg identify > 90% of cases anti-HCV positive:acute viral hepatitis AGA Gastro 2002
  20. 20. Exclude:ALT > 10 ULN drugsno history or physical evidence of CLD alcohol CBD disease Vascular disease HAV-IgM HBsAg identify > 90% of cases anti-HCV negative: Autoimmunity positive: HCV RNAacute viral hepatitis HBcAb IgM each cause anti-HEV has a very ceruloplasmin low frequency others (<1%) AGA Gastro 2002
  21. 21. Exclude:ALT > 10 ULN drugs (DILI)no history or physical evidence of CLD alcohol CBD disease Vascular disease HAV-IgM HBsAg identify > 90% of cases anti-HCV re-evaluate negative: negative Autoimmunity positive: HCV RNAacute viral hepatitis HBcAb IgM each cause anti-HEV has a very ceruloplasmin low frequency others (<1%) AGA Gastro 2002
  22. 22. GGT ? HCVAlcohol PLT? +++ abuse other liver chemistry ? ++ HBV + Chronically raised ALT HBV/HDV Drug < 10 ULN +/- toxicity +/- Wilson disease NASH Haemochromatosis +++ α-1-AT deficiency others +/- vs +AGA Gastro 2002
  23. 23. Other liver enzyme abnormalities Gamma GT Liver cells and biliary enzyme activity Cholestasis Steatosis Drugs injury Heavy alcohol abuse GGT levels migth increase also during the course of:uraemia, renal tumours, myocardial infartion, COPD ,diabetes, intestinal infacrtion or ischemia High sensitivity, low specificity
  24. 24. Other liver enzyme abnormalities Alkaline phosphatase Biliary cells enzyme activity It means cholestasis Intra-hepatic : PBC, PSC Extra-hepatic: CBD obstruction (gallstones, malignancy) Several isoenzymes (bone, kidney, gut, leucocytes…) High specificity, low sensitiviy
  25. 25. Messaggio conclusivo I• Lievi alterazioni di laboratorio della funzionalità epatica non sono rare in soggetti apparentemente sani.• Quasi sempre queste alterazioni vengono rilevate a seguito di controlli biochimici casuali ed in assenza di qualunque sintomo o segno obiettivo.• Le alterazioni più frequenti riguardano le transaminasi e sono in genere inferiori a 2 volte i valori normali.
  26. 26. Messaggio conclusivo II• Nel nostro Paese, le cause più frequenti di modeste elevazioni degli enzimi epatici sono rappresentate dalla steatosi non alcolica, dalla epatite cronica da HCV, da cause iatrogene (farmaci, erbe) e dall’ abuso di alcol.• Molto più raramente sono riscontrabili altre cause (HBV, emocromatosi, autoimmunità, celiachia, ecc).• La corretta interpretazione del dato di laboratorio non può prescindere dalla valutazione integrata di tutti i parametri di funzione epatica, dell’ emocromo, dell’assetto metabolico (glicemia, lipidi) e dal dato ecografico.
  27. 27. Messaggio conclusivo III• Una corretta anamnesi personale, patologica e farmacologica consente la diagnosi clinica nella maggior parte dei casi.• L’assunzione di sostanze medicamentose “alternative” (“herbal medicine”) deve essere sempre indagata perché sovente il paziente tende a tacerne l’ uso, considerandole del tutto innocue.• Non si deve infine dimenticare che diverse patologie extra- epatiche sia gastroenteriche (celiachia, MICI) che sistemiche (neoplasie, patologie scheletriche, ecc) possono determinare alterazioni enzimatiche.

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