Download - An Approach to Abnormal LFTs

An Approach to Abnormal LFTs

Robert C. Lowe, M.D.Boston Medical Center

July 17, 2013

AST

ALT

ALP

T. BIL

ALB

INR

GGT

Chessboard

ALTASTT. BILALPALBGGT

Case 1

30 year old woman4 days of malaise, fevers to 101, nausea1 day of RUQ pain and jaundice

Exam - T 100.5Icteric sclerae and jaundiceTender hepatomegaly, no spleen tip

Case 1

AST 1535 WBC 8.1ALT 1602 HCT 41ALP 128 PLT 353T. Bil 7.3Albumin 3.9

Transaminases

AST - aspartate aminotransferase

ALT - alanine aminotransferase

Released when hepatocytes are injured - a sign of necrosis.

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

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

Differential Diagnosis

Sky high transaminases > 15x normal

Differential Diagnosis

Sky high transaminases > 15x normal

Virus

Drug

Ischemia

} >80% of cases

AST/ALT>1000

Virus

Toxin

Ischemia

History and Exam Points

AST/ALT>1000

Virus

Toxin

Ischemia


IVDU ArthralgiasSexual partners UrticariaTravel Herpetic lesionsFood exposures Stigmata of liver dz

AST/ALT>1000

Virus

Toxin

Ischemia



MedsOTC medsHerbs and supplements

AST/ALT>1000

Virus

Toxin

Ischemia



MedsOTC medsHerbs and supplements

Recent surgeryHypotensionCardiac arrestCMP

AST/ALT>1000

AST/ALT>1000

Autoimmune

Wilson Disease

Bile DuctObstruction

Budd-Chiari

AST/ALT>1000

Autoimmune

Wilson Disease


Budd-Chiari

Clinical Clues

Female gender

Personal or Family Hx of autoimmune dz

AST/ALT>1000

Autoimmune

Wilson’s Disease


Budd-Chiari

Clinical Clues

Female gender

Personal or Family Hx of autoimmune dz

ANAASMAIg levels

AST/ALT>1000

Autoimmune

Wilson’s Disease


Budd-Chiari

AST/ALT>1000

Autoimmune

Wilson’s Disease


Budd-Chiari

Clinical Clues

Male gender

< age 40

Neuropsychiatric syndromePsychosisMovement disorder

AST/ALT>1000

Autoimmune

Wilson’s Disease


Budd-Chiari

Clinical Clues

Male gender

< age 40

Neuropsychiatric syndromePsychosisMovement disorder

Low ALPHemolysisCeruloplasmin less useful in acute disease

KF Rings

Head CT

AST/ALT>1000

Autoimmune

Wilson Disease


Budd-Chiari

AST/ALT>1000

Autoimmune

Wilson Disease


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

AST/ALT>1000

Autoimmune

Wilson Disease


Budd-Chiari

AST/ALT>1000

Autoimmune

Wilson Disease


Budd-Chiari

Clinical Clues

OCP usePrior venous thrombosisMyeloproliferative disorderMalignancy

Abdominal PainAscites

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

Prognostic Features

Prognostic Features

• Coagulopathy– INR elevation

• Encephalopathy– Mental Status– Asterixis– Apraxia

Case 2

• Asymptomatic 45 year-old woman• Cholesterol 245, Trig 266• No significant FH• No meds• Works as an accountant

Case 2

AST 84 WBC 6.6ALT 46 HCT 37ALP 121 PLT 165T. Bil 0.8ALB 3.7

Alcoholic LFT Pattern

• AST/ALT > 2:1

• Absolute AST and ALT < 300

• GGT elevation is helpful, but nonspecific.

Alcoholic LFT Pattern

WHY?

ALT synthesis is decreased in EtOH hepatitis.

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

Case 2


Mildly Elevated Transaminases

ABCDE

FGH


Alcohol / AutoimmuneB HepatitisC HepatitisDrugExotic

Wilson DiseaseAlpha-1-antitrypsin deficiency

Fatty liverGluten sensitive enteropathyHemochromatosis


Alcohol / AutoimmuneB Hepatitis C HepatitisDrugExotic



Thyroid disease, myopathies


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


Fatty liver RUQ U/S, TGGluten sensitive enteropathyHemochromatosis



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


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




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

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




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

Liver Biopsy

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

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

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

PAS with Diastase digestion

An Approach to Abnormal LFTs


July 17, 2013

An Approach to Abnormal LFTsPart 2


July 25, 2013

AST/ALT>1000

Virus

Toxin

Ischemia

AST/ALT>1000

Virus

Toxin

Ischemia

Autoimmune

Wilson’s Disease


Budd-Chiari

Alcohol / AutoimmuneB Hepatitis C HepatitisDrugExotic

Wilson’s DiseaseAlpha-1-antitrypsin deficiency



Case 3

35 year old womanMild fatigueNo significant PMHNo meds

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

Case 3

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

Case 3


GGT = 650

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.

Elevated ALP

Bone disease -- Paget’s Metastases

Myeloma

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

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!

5’ Nucleotidase

More specific than GGT

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

Elevated ALP

Elevated ALP

Biliary obstruction Tumor masses - primary or metastaticDrug Effect

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

Workup of ALP Elevation

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

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 -- biopsyDilated ducts -- MRCP/ERCP


Pruritus for 4 months with no rash


Pruritus for 4 months with no rash

AMA = 1:2500

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


Patient reveals a 12 year history of ulcerative colitis

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%


Patient with Cr. 2.0 and significant proteinuria

Liver biopsyLiver biopsy


41 M with advanced HIV – CD4 27

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…

Case 3

35 year old womanMild fatigueNo significant PMHNo meds

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

Elevated ALP


Elevated ALP


PBC, PSCInfiltrative disease - amyloidGranulomatous diseases – sarcoid, TB, fungiAutoimmune variants

Workup of ALP Elevation1) 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.

Final Case

AST 175ALT 112ALP 163T. Bili 12.3INR 1.9ALB 3.0

An Approach to Abnormal LFTsPart 2


July 25, 2013