An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

104
An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013

Transcript of An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Page 1: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

An Approach to Abnormal LFTs

Robert C. Lowe, M.D.

Boston Medical Center

July 17, 2013

Page 2: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST

ALT

ALP

T. BIL

ALB

INR

GGT

Page 3: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Chessboard

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ALTASTT. BILALPALBGGT

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Case 1

30 year old woman

4 days of malaise, fevers to 101, nausea

1 day of RUQ pain and jaundice

Exam - T 100.5

Icteric sclerae and jaundice

Tender hepatomegaly, no spleen tip

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Case 1

AST 1535 WBC 8.1

ALT 1602 HCT 41

ALP 128 PLT 353

T. Bil 7.3

Albumin 3.9

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Transaminases

AST - aspartate aminotransferase

ALT - alanine aminotransferase

Released when hepatocytes are injured - a sign of necrosis.

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AST - less specific for liver disease Muscle (skeletal and cardiac) Kidney Erythrocytes

ALT - very little outside of liver. A better marker of liver disease.

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Differential Diagnosis

Sky high transaminases > 15x normal

Page 10: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Differential Diagnosis

Sky high transaminases > 15x normal

Virus

Drug

Ischemia

} >80% of cases

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AST/ALT>1000

Virus

Toxin

Ischemia

History and Exam Points

Page 12: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Virus

Toxin

Ischemia

History and Exam Points

IVDU ArthralgiasSexual partners UrticariaTravel Herpetic lesionsFood exposures Stigmata of liver dz

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Page 14: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Virus

Toxin

Ischemia

History and Exam Points

IVDU ArthralgiasSexual partners UrticariaTravel Herpetic lesionsFood exposures Stigmata of liver dz

Page 15: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Virus

Toxin

Ischemia

History and Exam Points

IVDU ArthralgiasSexual partners UrticariaTravel Herpetic lesionsFood exposures Stigmata of liver dz

MedsOTC medsHerbs and supplements

Page 16: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Virus

Toxin

Ischemia

History and Exam Points

IVDU ArthralgiasSexual partners UrticariaTravel Herpetic lesionsFood exposures Stigmata of liver dz

MedsOTC medsHerbs and supplements

Recent surgeryHypotensionCardiac arrestCMP

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AST/ALT>1000

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AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

Page 19: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

Clinical Clues

Female gender

Personal or Family Hx of autoimmune dz

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AST/ALT>1000

Autoimmune

Wilson’s Disease

Bile DuctObstruction

Budd-Chiari

Clinical Clues

Female gender

Personal or Family Hx of autoimmune dz

ANAASMAIg levels

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AST/ALT>1000

Autoimmune

Wilson’s Disease

Bile DuctObstruction

Budd-Chiari

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AST/ALT>1000

Autoimmune

Wilson’s Disease

Bile DuctObstruction

Budd-Chiari

Clinical Clues

Male gender

< age 40

Neuropsychiatric syndromePsychosisMovement disorder

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AST/ALT>1000

Autoimmune

Wilson’s Disease

Bile DuctObstruction

Budd-Chiari

Clinical Clues

Male gender

< age 40

Neuropsychiatric syndromePsychosisMovement disorder

Low ALPHemolysisCeruloplasmin less useful in acute disease

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KF Rings

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Head CT

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AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

Page 27: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

Clinical Clues

H/O biliary colic or GS diseaseFH of gallstones

RUQ painN/V

Transaminases fall rapidly - over 1-3 days

U/S often diagnostic, but may need further imaging with MRCP/ERCP

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Page 29: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

Page 30: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

Clinical Clues

OCP usePrior venous thrombosisMyeloproliferative disorderMalignancy

Abdominal PainAscites

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Laboratory Testing

• Hepatitis A - IgM and IgG• Hepatitis B - sAg, cAb, eAg, HBV DNA• Hepatitis C - RNA level• ANA, ASMA, Ig levels• RUQ U/S with Doppler Study

• Consider other viral serologies, ceruloplasmin, MRCP

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Prognostic Features

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Prognostic Features

• Coagulopathy– INR elevation

• Encephalopathy– Mental Status– Asterixis– Apraxia

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Case 2

• Asymptomatic 45 year-old woman

• Cholesterol 245, Trig 266

• No significant FH

• No meds

• Works as an accountant

Page 39: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 2

AST 84 WBC 6.6

ALT 46 HCT 37

ALP 121 PLT 165

T. Bil 0.8

ALB 3.7

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Alcoholic LFT Pattern

• AST/ALT > 2:1

• Absolute AST and ALT < 300

• GGT elevation is helpful, but nonspecific.

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Alcoholic LFT Pattern

WHY?

ALT synthesis is decreased in EtOH hepatitis.

Partially due to pyridoxine deficiency - may correct with B6 therapy.

Page 42: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 2

AST 84 WBC 6.6

ALT 46 HCT 37

ALP 121 PLT 165

T. Bil 0.8

ALB 3.7

Page 43: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 2

AST 84 WBC 6.6

ALT 89 HCT 37

ALP 121 PLT 165

T. Bil 0.8

ALB 3.7

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Mildly Elevated Transaminases

ABCDE

FGH

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Mildly Elevated Transaminases

Alcohol / AutoimmuneB HepatitisC HepatitisDrugExotic

Wilson DiseaseAlpha-1-antitrypsin deficiency

Fatty liverGluten sensitive enteropathyHemochromatosis

Page 46: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Mildly Elevated Transaminases

Alcohol / AutoimmuneB Hepatitis C HepatitisDrugExotic

Wilson DiseaseAlpha-1-antitrypsin deficiency

Fatty liverGluten sensitive enteropathyHemochromatosis

Thyroid disease, myopathies

Page 47: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Mildly Elevated Transaminases

Alcohol / Autoimmune Alcohol HxB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrug Drug HxExotic

Wilson DiseaseAlpha-1-antitrypsin deficiency

Fatty liver RUQ U/S, TGGluten sensitive enteropathyHemochromatosis

Thyroid disease, myopathies

Page 48: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Mildly Elevated Transaminases

Alcohol / Autoimmune ANA, ASMA, Ig levelsB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrug Drug HxExotic

Wilson DiseaseAlpha-1-antitrypsin deficiency

Fatty liver RUQ U/S, TGGluten sensitive enteropathyHemochromatosis Fe, TIBC, Ferritin

Thyroid disease, myopathies

Page 49: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Mildly Elevated Transaminases

Alcohol / Autoimmune ANA, ASMA, Ig levelsB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrug Drug HxExotic

Wilson Disease CeruloplasminAlpha-1-antitrypsin deficiency A-1-AT level

Fatty liver RUQ U/S, TGGluten sensitive enteropathyHemochromatosis Fe, TIBC, Ferritin

Thyroid disease, myopathies

Page 50: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Mildly Elevated Transaminases

Alcohol / Autoimmune ANA, ASMA, Ig levelsB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrug Drug HxExotic

Wilson Disease CeruloplasminAlpha-1-antitrypsin deficiency A-1-AT level

Fatty liver RUQ U/S, TGGluten sensitive enteropathy Anti-TTGHemochromatosis Fe, TIBC, Ferritin

Thyroid disease, myopathies TSH, CK, Aldolase

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Liver Biopsy

1124 pts referred for elevated ALT ---81 cases with negative serologic workup

Page 52: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Liver Biopsy

1124 pts referred for elevated ALT ---81 cases with negative serologic workup

Biopsies -- 41 pts with steatosis 26 pts with NASH

8% normal biopsies

Daniel, et al. Am J Gastro, 1999

Page 53: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Liver Biopsy

354 patients with elevated ALT and negative workup

Biopsies -- 32% with steatosis 34% with NASH 9% cryptogenic 7.6% Drug-induced 5.9% normal histology 2.8% ETOH

Granulomatous dz, PBC, PSC, hemochromatosis,amyloidosis, glycogen storage disease = 6.3%

In 18%, management was changed based on the pathology.

Skelly, et al. J Hepatol, 2001

66% with NAFLD

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PAS with Diastase digestion

Page 57: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

An Approach to Abnormal LFTs

Robert C. Lowe, M.D.

Boston Medical Center

July 17, 2013

Page 58: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.
Page 59: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

An Approach to Abnormal LFTsPart 2

Robert C. Lowe, M.D.

Boston Medical Center

July 25, 2013

Page 60: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Virus

Toxin

Ischemia

Page 61: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST/ALT>1000

Virus

Toxin

Ischemia

Autoimmune

Wilson’s Disease

Bile DuctObstruction

Budd-Chiari

Page 62: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Alcohol / AutoimmuneB Hepatitis C HepatitisDrugExotic

Wilson’s DiseaseAlpha-1-antitrypsin deficiency

Fatty liverGluten sensitive enteropathyHemochromatosis

Thyroid disease, myopathies

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Page 64: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 3

35 year old womanMild fatigueNo significant PMHNo meds

Exam - cervical LAN 0.5 cm, nontender Liver 3 cm below RCM

Page 65: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 3

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Page 66: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 3

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

GGT = 650

Page 67: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Alkaline Phosphatase

Produced in liver, bone, placenta, intestine.

Blood group O and B may release intestinal ALP after a fatty meal.

Elevations up to 2x normal are very nonspecific. Up to 1/3 have no disease.

Page 68: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Elevated ALP

Bone disease -- Paget’s

Metastases

Myeloma

Use GGT or 5’NT to distinguish bone from liver.

Page 69: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

GGT and 5’ NT

GGT - not found in bone, present in biliary epithelium.

Problems - induced by EtOH, anticonvulsants, warfarin, so specificity is a problem.

GGT/ALP > 2.5 suggests EtOH, but only 33% sensitive!

Page 70: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

5’ Nucleotidase

More specific than GGT

Rises over several days after bile duct obstruction, slower than GGT.

Page 71: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Elevated ALP

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Elevated ALP

Biliary obstruction

Tumor masses - primary or metastatic

Drug Effect

Page 73: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Elevated ALP

Special circumstances -

Malignancy without liver involvement -- tumors produce Regan isoenzyme of ALP (gonadal and urologic)

Hodgkin’s Disease and RCC - can cause nonspecific hepatitis with elevated ALP

Page 74: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Workup of ALP Elevation

1) Confirm liver origin with 5’-NT or GGT

Page 75: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Workup of ALP Elevation

1) Confirm liver origin with 5’-NT or GGT

2) U/S or CT to R/O mass and dilated ducts

Mass -- biopsy

Dilated ducts -- MRCP/ERCP

Page 76: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Page 77: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Pruritus for 4 months with no rash

Page 78: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Pruritus for 4 months with no rash

AMA = 1:2500

Page 79: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Primary Biliary Cirrhosis

• F:M = 8-9:1

• Classic = fatigue, itching, elevated ALP

• Common = asyx elevated ALP

• NO jaundice until end-stage

• AMA is diagnostic (95% positive)

• Treat with ursodiol

Page 80: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.
Page 81: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.
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AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Page 83: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.
Page 84: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Page 85: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Patient reveals a 12 year history of ulcerative colitis

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Primary Sclerosing Cholangitis

• IBD in > 70% (typically UC)

• MRCP makes diagnosis

• pANCA (+) in the majority

• Progression to cirrhosis – median survival 10-12 yrs after Dx

• Risk of cholangiocarcioma is 10-15%

Page 89: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Page 90: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Patient with Cr. 2.0 and significant proteinuria

Page 91: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Liver biopsyLiver biopsy

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Liver biopsyLiver biopsy

Page 93: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

Page 94: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

41 M with advanced HIV – CD4 27

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Page 96: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

HIV Cholangiopathy

• Seen in advanced AIDS – CD4 <50

• High ALP, mildly elevated bilirubin

• Significant RUQ pain

• Survival is 6-9 months – due to other infections, wasting…

Page 97: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Case 3

35 year old womanMild fatigueNo significant PMHNo meds

Exam - cervical LAN 0.5 cm, nontender Liver 3 cm below RCM

Page 98: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.
Page 99: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Elevated ALP

Biliary obstruction

Tumor masses - primary or metastatic

Drug Effect

Page 100: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Elevated ALP

Biliary obstruction

Tumor masses - primary or metastatic

Drug Effect

PBC, PSC

Infiltrative disease - amyloid

Granulomatous diseases – sarcoid, TB, fungi

Autoimmune variants

Page 101: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Workup of ALP Elevation

1) Confirm liver origin with 5’-NT or GGT

2) Take a thorough drug history

3) U/S or CT to R/O mass and dilated ductsMass -- biopsyDilated ducts -- MRCP/ERCP

4) Neither -- check AMA, then biopsy liver.

Page 102: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.
Page 103: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

Final Case

AST 175

ALT 112

ALP 163

T. Bili 12.3

INR 1.9

ALB 3.0

Page 104: An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013.

An Approach to Abnormal LFTsPart 2

Robert C. Lowe, M.D.

Boston Medical Center

July 25, 2013