1. Evaluation of Liver Injury Mark J. Czaja Liver Research Center Albert Einstein College of Medicine Bronx, N.Y. Albert Einstein College of Medicine Bronx, N.Y. Mark J. Czaja Liver Research Center Albert Einstein College of Medicine Bronx, N.Y. Albert Einstein College of Medicine Bronx, N.Y.

2. Liver Function Tests Alanine aminotransferase (ALT)Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)Aspartate aminotransferase (AST) Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH) Alkaline phosphataseAlkaline phosphatase BilirubinBilirubin AlbuminAlbumin Alanine aminotransferase (ALT)Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)Aspartate aminotransferase (AST) Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH) Alkaline phosphataseAlkaline phosphatase BilirubinBilirubin AlbuminAlbumin

3. Mechanisms of Liver Dysfunction Direct cellular injuryDirect cellular injury Blockage in bile flowBlockage in bile flow Impaired blood flowImpaired blood flow Direct cellular injuryDirect cellular injury Blockage in bile flowBlockage in bile flow Impaired blood flowImpaired blood flow

4. Direct Cellular Injury - HCV Infection

5. Blockage in Bile Flow - Biliary Atresia

6. Impaired Blood Flow - CHF

7. Consequences of Liver Injury liver cell injury liver cell death proliferation matrix deposition sufficient inadequate altered architecture recovery liver failure cirrhosis

8. Types of Liver Tests True tests of liver functionTrue tests of liver function Biochemical markers of liver injuryBiochemical markers of liver injury Biochemical markers of specific liver diseasesBiochemical markers of specific liver diseases True tests of liver functionTrue tests of liver function Biochemical markers of liver injuryBiochemical markers of liver injury Biochemical markers of specific liver diseasesBiochemical markers of specific liver diseases

9. Testable Biochemical Liver Function Ability to transport organic anionsAbility to transport organic anions Capacity to metabolize certain substancesCapacity to metabolize certain substances Capability to synthesize various proteinsCapability to synthesize various proteins Ability to transport organic anionsAbility to transport organic anions Capacity to metabolize certain substancesCapacity to metabolize certain substances Capability to synthesize various proteinsCapability to synthesize various proteins

10. Steps in Organic Anion Transport Delivery and uptakeDelivery and uptake Metabolic alterationMetabolic alteration Secretion and excretionSecretion and excretion Delivery and uptakeDelivery and uptake Metabolic alterationMetabolic alteration Secretion and excretionSecretion and excretion

11. BilirubinBilirubin TetrapyroleTetrapyrole Toxic in neonates - kernicterusToxic in neonates - kernicterus Derived from:Derived from: l Senescent RBC (70-80%) l Hemoproteins (20-30%) l Ineffective erythropoiesis TetrapyroleTetrapyrole Toxic in neonates - kernicterusToxic in neonates - kernicterus Derived from:Derived from: l Senescent RBC (70-80%) l Hemoproteins (20-30%) l Ineffective erythropoiesis

12. Bilirubin Formation hemehemebiliverdinbiliverdinbilirubinbilirubin hemeheme oxygenaseoxygenase biliverdinbiliverdin reductasereductase Transport: hydrophobic due to internal H-bonding circulates bound to albumin circulates bound to albumin Transport: hydrophobic due to internal H-bonding circulates bound to albumin circulates bound to albumin

13. Bilirubin Metabolism UCB UCBligandin ligandin glucurony l transferasetransferase BMGBDGBMGBDG Alb AlbUCB UCB BMGBDGBMGBDG PlasmaPlasmaHepatocyteHepatocyte BileBile BMGBDGBMGBDG

14. Bilirubin Elimination Intestine Intestine BMG (20%) + BDG (80%) +UCB (trace)BMG (20%) + BDG (80%) +UCB (trace) Deconjugated to urobilinogenDeconjugated to urobilinogen Excreted or reab- sorbed (20%)Excreted or reab- sorbed (20%) Intestine Intestine BMG (20%) + BDG (80%) +UCB (trace)BMG (20%) + BDG (80%) +UCB (trace) Deconjugated to urobilinogenDeconjugated to urobilinogen Excreted or reab- sorbed (20%)Excreted or reab- sorbed (20%) Urine Urine BMG and BDGBMG and BDG No UCBNo UCB Urine Urine BMG and BDGBMG and BDG No UCBNo UCB

15. Measurement of Serum Bilirubin Normal concentration < 1 mg/dlNormal concentration < 1 mg/dl Conjugated < 5%Conjugated < 5% Jaundice if > 3 mg/dlJaundice if > 3 mg/dl Detected by diazo reaction - cleaved to colored azo-dipyroleDetected by diazo reaction - cleaved to colored azo-dipyrole l Conjugated reacts rapidly (direct) l Unconjugated reacts slowly (indirect) Normal concentration < 1 mg/dlNormal concentration < 1 mg/dl Conjugated < 5%Conjugated < 5% Jaundice if > 3 mg/dlJaundice if > 3 mg/dl Detected by diazo reaction - cleaved to colored azo-dipyroleDetected by diazo reaction - cleaved to colored azo-dipyrole l Conjugated reacts rapidly (direct) l Unconjugated reacts slowly (indirect)

16. Differential Diagnosis I PrehepaticPrehepatic IntrahepaticIntrahepatic l Congenital l Acquired PosthepaticPosthepatic PrehepaticPrehepatic IntrahepaticIntrahepatic l Congenital l Acquired PosthepaticPosthepatic

17. Differential Diagnosis II Unconjugated hyperbilirubinemiaUnconjugated hyperbilirubinemia l Increased bilirubin production (hematological) l Decreased uptake (drug) l Decreased conjugation (congenital) Conjugated hyperbilirubinemiaConjugated hyperbilirubinemia l Congenital l Drug l Liver disease l Biliary obstruction Unconjugated hyperbilirubinemiaUnconjugated hyperbilirubinemia l Increased bilirubin production (hematological) l Decreased uptake (drug) l Decreased conjugation (congenital) Conjugated hyperbilirubinemiaConjugated hyperbilirubinemia l Congenital l Drug l Liver disease l Biliary obstruction

18. Inherited Disorders Causing Unconjugated Hyperbilirubinemia Crigler-Najjar syndromeCrigler-Najjar syndrome l Type 1 – absent GT l Type 2 – reduced GT activity Gilbert’s syndrome – reduced GT activity due to genetic defect in TATAA element of GT promoterGilbert’s syndrome – reduced GT activity due to genetic defect in TATAA element of GT promoter Crigler-Najjar syndromeCrigler-Najjar syndrome l Type 1 – absent GT l Type 2 – reduced GT activity Gilbert’s syndrome – reduced GT activity due to genetic defect in TATAA element of GT promoterGilbert’s syndrome – reduced GT activity due to genetic defect in TATAA element of GT promoter

19. Inherited Disorders Causing Conjugated Hyperbilirubinemia Dubin-Johnson syndrome – mutations in multidrug resistance associated protein 2 (MRP2)Dubin-Johnson syndrome – mutations in multidrug resistance associated protein 2 (MRP2) Rotor’s syndrome – genetic defectRotor’s syndrome – genetic defect Dubin-Johnson syndrome – mutations in multidrug resistance associated protein 2 (MRP2)Dubin-Johnson syndrome – mutations in multidrug resistance associated protein 2 (MRP2) Rotor’s syndrome – genetic defectRotor’s syndrome – genetic defect

20. Hepatic Metabolic Capacity Clearance must depend on total functional mass or metabolic activityClearance must depend on total functional mass or metabolic activity Hepatic drug metabolism - [ 14 C]amino-pyrine breath testHepatic drug metabolism - [ 14 C]amino-pyrine breath test Galactose eliminationGalactose elimination Not used clinicallyNot used clinically Clearance must depend on total functional mass or metabolic activityClearance must depend on total functional mass or metabolic activity Hepatic drug metabolism - [ 14 C]amino-pyrine breath testHepatic drug metabolism - [ 14 C]amino-pyrine breath test Galactose eliminationGalactose elimination Not used clinicallyNot used clinically

21. Hepatic Synthetic Capacity Most major plasma proteins are made in the liverMost major plasma proteins are made in the liver Decreased hepatocytes = decreased protein synthesis and releaseDecreased hepatocytes = decreased protein synthesis and release Albumin and coagulation factors are clinically importantAlbumin and coagulation factors are clinically important Most major plasma proteins are made in the liverMost major plasma proteins are made in the liver Decreased hepatocytes = decreased protein synthesis and releaseDecreased hepatocytes = decreased protein synthesis and release Albumin and coagulation factors are clinically importantAlbumin and coagulation factors are clinically important

22. AlbuminAlbumin 50% of all synthesized hepatic protein50% of all synthesized hepatic protein Determinant of plasma oncotic pressureDeterminant of plasma oncotic pressure Important transport proteinImportant transport protein 50% of all synthesized hepatic protein50% of all synthesized hepatic protein Determinant of plasma oncotic pressureDeterminant of plasma oncotic pressure Important transport proteinImportant transport protein

23. Serum Albumin Levels Long half-life of 20 daysLong half-life of 20 days Large hepatic synthetic reserveLarge hepatic synthetic reserve Decreased with persistent, large injuryDecreased with persistent, large injury Decreased in chronic liver diseaseDecreased in chronic liver disease Poor prognostic signPoor prognostic sign Long half-life of 20 daysLong half-life of 20 days Large hepatic synthetic reserveLarge hepatic synthetic reserve Decreased with persistent, large injuryDecreased with persistent, large injury Decreased in chronic liver diseaseDecreased in chronic liver disease Poor prognostic signPoor prognostic sign

24. Non-hepatic Causes of Hypoalbuminemia Severe malnutritionSevere malnutrition Renal or GI lossRenal or GI loss l Glomerulopathy, HIV enteropathy High catabolismHigh catabolism l Infections, burns Severe malnutritionSevere malnutrition Renal or GI lossRenal or GI loss l Glomerulopathy, HIV enteropathy High catabolismHigh catabolism l Infections, burns

25. Coagulation Factors Half-lives of hours to daysHalf-lives of hours to days Liver synthesizes I, II, V, VII, IX, and XLiver synthesizes I, II, V, VII, IX, and X Large synthetic reserveLarge synthetic reserve Half-lives of hours to daysHalf-lives of hours to days Liver synthesizes I, II, V, VII, IX, and XLiver synthesizes I, II, V, VII, IX, and X Large synthetic reserveLarge synthetic reserve

26. Prothrombin Time (PT) PT detects abnormalities in I, II, V, VII and X (extrinsic pathway)PT detects abnormalities in I, II, V, VII and X (extrinsic pathway) PT is increased in liver diseasePT is increased in liver disease Best prognostic indicatorBest prognostic indicator l Acute liver disease l Chronic liver disease PT detects abnormalities in I, II, V, VII and X (extrinsic pathway)PT detects abnormalities in I, II, V, VII and X (extrinsic pathway) PT is increased in liver diseasePT is increased in liver disease Best prognostic indicatorBest prognostic indicator l Acute liver disease l Chronic liver disease

27. Non-hepatic Causes of Elevated PT Congenital coagulation factor deficienciesCongenital coagulation factor deficiencies Consumptive coagulopathiesConsumptive coagulopathies Vitamin K deficiency (II, VII, IX, X)Vitamin K deficiency (II, VII, IX, X) Congenital coagulation factor deficienciesCongenital coagulation factor deficiencies Consumptive coagulopathiesConsumptive coagulopathies Vitamin K deficiency (II, VII, IX, X)Vitamin K deficiency (II, VII, IX, X)

28. To Rule Out Vitamin K Deficiency Any patient with an elevated PTAny patient with an elevated PT Parental vitamin K for 3 daysParental vitamin K for 3 days Normalization of PT - vitamin K deficiencyNormalization of PT - vitamin K deficiency Failure to normalize - hepatocellular diseaseFailure to normalize - hepatocellular disease Any patient with an elevated PTAny patient with an elevated PT Parental vitamin K for 3 daysParental vitamin K for 3 days Normalization of PT - vitamin K deficiencyNormalization of PT - vitamin K deficiency Failure to normalize - hepatocellular diseaseFailure to normalize - hepatocellular disease

29. Serum Immunoglobulins Not produced by hepatocytesNot produced by hepatocytes Frequently elevated in liver diseaseFrequently elevated in liver disease Secondary to inflammatory processSecondary to inflammatory process ? produced by antigen shunting? produced by antigen shunting Not produced by hepatocytesNot produced by hepatocytes Frequently elevated in liver diseaseFrequently elevated in liver disease Secondary to inflammatory processSecondary to inflammatory process ? produced by antigen shunting? produced by antigen shunting

30. Biochemical Markers of Liver Injury

31. Liver Enzymes Low levels always present in serumLow levels always present in serum Leak out from cell after injuryLeak out from cell after injury Very sensitiveVery sensitive Magnitude of abnormality does not correlate well with degree of injuryMagnitude of abnormality does not correlate well with degree of injury Low levels always present in serumLow levels always present in serum Leak out from cell after injuryLeak out from cell after injury Very sensitiveVery sensitive Magnitude of abnormality does not correlate well with degree of injuryMagnitude of abnormality does not correlate well with degree of injury

32. Aspartate Aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT)Serum glutamic-oxaloacetic transaminase (SGOT) Transfers an  -amino group of aspartate to  -keto group of ketoglutaric acidTransfers an  -amino group of aspartate to  -keto group of ketoglutaric acid Present in skeletal muscle, kidney, brainPresent in skeletal muscle, kidney, brain Serum glutamic-oxaloacetic transaminase (SGOT)Serum glutamic-oxaloacetic transaminase (SGOT) Transfers an  -amino group of aspartate to  -keto group of ketoglutaric acidTransfers an  -amino group of aspartate to  -keto group of ketoglutaric acid Present in skeletal muscle, kidney, brainPresent in skeletal muscle, kidney, brain

33. Alanine Aminotransferase (ALT) Serum glutamic-pyruvic transaminase (SGPT)Serum glutamic-pyruvic transaminase (SGPT) Transfers an  -amino group of alanine to  -keto group of ketoglutaric acidTransfers an  -amino group of alanine to  -keto group of ketoglutaric acid Present principally in liverPresent principally in liver Serum glutamic-pyruvic transaminase (SGPT)Serum glutamic-pyruvic transaminase (SGPT) Transfers an  -amino group of alanine to  -keto group of ketoglutaric acidTransfers an  -amino group of alanine to  -keto group of ketoglutaric acid Present principally in liverPresent principally in liver

34. AST and ALT Elevated in most liver diseasesElevated in most liver diseases Highest levels are in acute liver diseasesHighest levels are in acute liver diseases Only slight elevations in chronic liver diseasesOnly slight elevations in chronic liver diseases Usually increase in parallelUsually increase in parallel Elevated in most liver diseasesElevated in most liver diseases Highest levels are in acute liver diseasesHighest levels are in acute liver diseases Only slight elevations in chronic liver diseasesOnly slight elevations in chronic liver diseases Usually increase in parallelUsually increase in parallel

35. AST/ALT in Alcoholic Hepatitis Transaminases rarely exceed 300Transaminases rarely exceed 300 AST:ALT >2AST:ALT >2 Transaminases rarely exceed 300Transaminases rarely exceed 300 AST:ALT >2AST:ALT >2

36. Factors Affecting AST/ALT Depressed by pyridoxine (vit. B 6 ) deficiencyDepressed by pyridoxine (vit. B 6 ) deficiency Decreased by uremia and renal dialysisDecreased by uremia and renal dialysis Depressed by pyridoxine (vit. B 6 ) deficiencyDepressed by pyridoxine (vit. B 6 ) deficiency Decreased by uremia and renal dialysisDecreased by uremia and renal dialysis

37. AST/ALT Controversies Should lower normal limits be used in females?Should lower normal limits be used in females? l Females < 30 vs. males < 40 Are the normal limits too high?Are the normal limits too high? l Females < 20 and males < 30 Should lower normal limits be used in females?Should lower normal limits be used in females? l Females < 30 vs. males < 40 Are the normal limits too high?Are the normal limits too high? l Females < 20 and males < 30

38. Lactate Dehydrogenase (LDH) Component of classic LFT’sComponent of classic LFT’s Highly non-specificHighly non-specific Component of classic LFT’sComponent of classic LFT’s Highly non-specificHighly non-specific

39. Tests of Impaired Hepatic Excretion Increased In CholestasisCholestasis Intra-hepatic biliary tract obstructionIntra-hepatic biliary tract obstruction Extra-hepatic biliary obstructionExtra-hepatic biliary obstruction CholestasisCholestasis Intra-hepatic biliary tract obstructionIntra-hepatic biliary tract obstruction Extra-hepatic biliary obstructionExtra-hepatic biliary obstruction

40. Alkaline Phosphatase Hydrolyzes phosphate esters at alkaline pHHydrolyzes phosphate esters at alkaline pH Also present in bone, kidney, placenta, intestineAlso present in bone, kidney, placenta, intestine Mainly liver and bone in adultsMainly liver and bone in adults Increased in children from bone growthIncreased in children from bone growth Placental form during pregnancyPlacental form during pregnancy Hydrolyzes phosphate esters at alkaline pHHydrolyzes phosphate esters at alkaline pH Also present in bone, kidney, placenta, intestineAlso present in bone, kidney, placenta, intestine Mainly liver and bone in adultsMainly liver and bone in adults Increased in children from bone growthIncreased in children from bone growth Placental form during pregnancyPlacental form during pregnancy

41. Elevated Alkaline Phosphatase Can occur in any liver diseaseCan occur in any liver disease Highest with cholestasis or biliary tract obstructionHighest with cholestasis or biliary tract obstruction Elevated in infiltrative diseasesElevated in infiltrative diseases Due to increase synthesis and secretionDue to increase synthesis and secretion Can occur in any liver diseaseCan occur in any liver disease Highest with cholestasis or biliary tract obstructionHighest with cholestasis or biliary tract obstruction Elevated in infiltrative diseasesElevated in infiltrative diseases Due to increase synthesis and secretionDue to increase synthesis and secretion

42. Alkaline Phosphatase Isoenzymes Source Heat Inactivation 5' NT GGTP LiverModerate++ BoneRapid-- PlacentaSlow-- IntestineSlow--

43. 5'-Nucleotidase Hydrolyzes 5'- adenosine monophosphateHydrolyzes 5'- adenosine monophosphate Mainly present in liverMainly present in liver Increases along with alkaline phosphataseIncreases along with alkaline phosphatase Hydrolyzes 5'- adenosine monophosphateHydrolyzes 5'- adenosine monophosphate Mainly present in liverMainly present in liver Increases along with alkaline phosphataseIncreases along with alkaline phosphatase

44.  -Glutamyl Transpeptidase (GGTP) Transfers  -glutamyl groupsTransfers  -glutamyl groups Widely distributedWidely distributed Sensitive correlate to alkaline phosphataseSensitive correlate to alkaline phosphatase Non-specific (alcoholism, MI, DM, pancreatic disease, renal failure)Non-specific (alcoholism, MI, DM, pancreatic disease, renal failure) Transfers  -glutamyl groupsTransfers  -glutamyl groups Widely distributedWidely distributed Sensitive correlate to alkaline phosphataseSensitive correlate to alkaline phosphatase Non-specific (alcoholism, MI, DM, pancreatic disease, renal failure)Non-specific (alcoholism, MI, DM, pancreatic disease, renal failure)

45. Biochemical Markers of Specific Liver Diseases

46. Etiology-specific Liver Tests Viral hepatitis serologiesViral hepatitis serologies Serum ferritin levelSerum ferritin level Ceruloplasmin levelCeruloplasmin level Alpha 1 -antitrypsin levelAlpha 1 -antitrypsin level Antimitochondrial antibody titerAntimitochondrial antibody titer Viral hepatitis serologiesViral hepatitis serologies Serum ferritin levelSerum ferritin level Ceruloplasmin levelCeruloplasmin level Alpha 1 -antitrypsin levelAlpha 1 -antitrypsin level Antimitochondrial antibody titerAntimitochondrial antibody titer

47. Viral Hepatitis Serology HAV – anti-HAV IgM and IgGHAV – anti-HAV IgM and IgG HBV – HBsAg, anti-HBsAg, and anti-HBcAgHBV – HBsAg, anti-HBsAg, and anti-HBcAg HCV – anti-HCV, HCV RNAHCV – anti-HCV, HCV RNA HAV – anti-HAV IgM and IgGHAV – anti-HAV IgM and IgG HBV – HBsAg, anti-HBsAg, and anti-HBcAgHBV – HBsAg, anti-HBsAg, and anti-HBcAg HCV – anti-HCV, HCV RNAHCV – anti-HCV, HCV RNA

48. Serum Ferritin Widely distributed storage proteinWidely distributed storage protein Levels reflect body iron storesLevels reflect body iron stores Elevated in primary hemochromatosisElevated in primary hemochromatosis Elevated in acute inflammation and cirrhosisElevated in acute inflammation and cirrhosis Widely distributed storage proteinWidely distributed storage protein Levels reflect body iron storesLevels reflect body iron stores Elevated in primary hemochromatosisElevated in primary hemochromatosis Elevated in acute inflammation and cirrhosisElevated in acute inflammation and cirrhosis

49. Serum Ceruloplasmin Copper-binding proteinCopper-binding protein Decreased in 95% of patients with Wilson’s diseaseDecreased in 95% of patients with Wilson’s disease 20% of heterozygotes have decreased levels20% of heterozygotes have decreased levels Copper-binding proteinCopper-binding protein Decreased in 95% of patients with Wilson’s diseaseDecreased in 95% of patients with Wilson’s disease 20% of heterozygotes have decreased levels20% of heterozygotes have decreased levels

50.  1 -Antitrypsin Inhibits serum trypsinInhibits serum trypsin Major component of  1 -globulinMajor component of  1 -globulin Deficiency cause of neonatal hepatitisDeficiency cause of neonatal hepatitis Inhibits serum trypsinInhibits serum trypsin Major component of  1 -globulinMajor component of  1 -globulin Deficiency cause of neonatal hepatitisDeficiency cause of neonatal hepatitis

51. Antimitochondrial Antibody (AMA) Directed against mitochondrial enzyme pyruvate dehydrogenase complexDirected against mitochondrial enzyme pyruvate dehydrogenase complex Positive in 90% of patients with primary biliary cirrhosisPositive in 90% of patients with primary biliary cirrhosis Directed against mitochondrial enzyme pyruvate dehydrogenase complexDirected against mitochondrial enzyme pyruvate dehydrogenase complex Positive in 90% of patients with primary biliary cirrhosisPositive in 90% of patients with primary biliary cirrhosis

52. Interpretation of Abnormal LFT’s Examine multiple testsExamine multiple tests Consider non-hepatic causesConsider non-hepatic causes Determine the most abnormal testsDetermine the most abnormal tests Examine multiple testsExamine multiple tests Consider non-hepatic causesConsider non-hepatic causes Determine the most abnormal testsDetermine the most abnormal tests

53. Hepatocellular vs. Cholestatic TestHepatocellularCholestatic ALT/AST2-3NL-1 Alk Phos NL-12-3 BilirubinNL-3NL-3 AlbuminNL-3NL PTNL-3NL

54. Case 1 ALT 2045 (15-45)ALT 2045 (15-45) AST 2300 (15-45)AST 2300 (15-45) Alk Phos 273 (50-150)Alk Phos 273 (50-150) ALT 2045 (15-45)ALT 2045 (15-45) AST 2300 (15-45)AST 2300 (15-45) Alk Phos 273 (50-150)Alk Phos 273 (50-150) Bili 3.9 (0.1-1.0)Bili 3.9 (0.1-1.0) Alb 4.2 (3.5-5.5)Alb 4.2 (3.5-5.5) PT 11.5 (10-12)PT 11.5 (10-12) Bili 3.9 (0.1-1.0)Bili 3.9 (0.1-1.0) Alb 4.2 (3.5-5.5)Alb 4.2 (3.5-5.5) PT 11.5 (10-12)PT 11.5 (10-12) 25 yo IVDA c/o 1 week of nausea, vomiting, and myalgias. Physical exam revealed jaundice.

55. Hepatocellular W/U H & P EtOH, medications, transfusions H & P EtOH, medications, transfusions Risk for viral hepatitis Risk factors for NASH Risk factors for NASH Autoimmune features Etiology-specific LFT’s USG and liver biopsy

56. HBV Infection - HBcAg Staining

57. Case 2 ALT 75 (15-45)ALT 75 (15-45) AST 115 (15-45)AST 115 (15-45) Alk Phos 650 (50-150)Alk Phos 650 (50-150) ALT 75 (15-45)ALT 75 (15-45) AST 115 (15-45)AST 115 (15-45) Alk Phos 650 (50-150)Alk Phos 650 (50-150) Bili 10.2 (0.1-1.0)Bili 10.2 (0.1-1.0) Alb 4.2 (3.5-5.5)Alb 4.2 (3.5-5.5) PT 11.0 (10-12)PT 11.0 (10-12) Bili 10.2 (0.1-1.0)Bili 10.2 (0.1-1.0) Alb 4.2 (3.5-5.5)Alb 4.2 (3.5-5.5) PT 11.0 (10-12)PT 11.0 (10-12) 67 yo c/o several months of weight loss, and 1 week of nausea, vomiting, and myalgias. Physical exam revealed cachexia and jaundice.

58. Cholestatic W/U H & P medications, gallstones, weight loss H & P medications, gallstones, weight loss AMA USG ERCP liver biopsy dilated ducts normal

59. Pancreatic Carcinoma - ERCP