A Pratical Approach to Abnormal LFTs:
Acute vs Chronic
Brenda Appolo PAC, MHS
University of Pennsylvania, Perelman School of Medicine
Objectives
• Discuss history, physical and diagnostic work up of
patients with acute and chronic liver test
abnormalities
• Discussion of patient cases and practical ddx
Approach to the Liver Patient
Acute vs Chronic
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Acute Liver Failiure (ALF)
- Accepted definition: INR > 1.5 and any degree of mental alteration (HE)
in a patient without pre existing cirrhosis
- illness up to 26 weeks duration
-Most common: Viral, Drug
-Patients w/ Wilson Disease, vertically acquired HBV or AIH may be
included in spite of possibility of cirrhosis if their disease has only been
recognized for 26 weeks or less
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“Acute on Chronic” Liver Failure
-Acute-on-chronic liver failure (ACLF) is an increasingly recognized
entity encompassing an acute deterioration of liver function in
patients with cirrhosis, which is usually associated with a precipitating
event leading to liver or multi organ failure
Approach to the Liver Patient
Acute vs Chronic
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Acute Hepatitis
-Time limited injury to the liver
-Often does not lead to hepatic fibrosis
-Not a diagnosis rendered on liver biopsy alone
-Viral most common
HAV, HBV, EBV, HSV
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Chronic Hepatitis
-Inflammatory state with propensity to cause liver fibrosis
-Histological hallmark includes influx of chronic inflammatory cells,
lymphocytes and plasma cells
-“LFT elevations for > 6 months”
-Chronic hepatitis does NOT denote a specific etiology
Chronic hepatitis does not always signify chronic liver / intrinsic disease!
(i.e.: celiac disease is a reactive hepatopathy)
Approach to the Patient
History is paramount
• Sx onset; many patients asx though
• Sx – anorexia, weight change, fever, malaise, GI sx,
rash, pruritus, lymphadenopathy
• Family History
• Medications / Herbal therapies
• Social History
blood transfusions; IVDU; intranasal drugs; anabolic steroids; tattoos;
incarceration, EtOH, travel, occupational exposures
Approach to the patient
Physical Examination
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Nutritional Status
Proximal muscle wasting
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Neuro – Psych
Asterixis; Mini mental exam (serial 7s)
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Scleral icterus
Detectable typically if t bili > 3.0 mg/dL
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Skin
Ecchymosis; Petechia; Spider angiomata; Jaundice
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Abdominal Exam
Abdominal bruits; Caput Medusa
Hepatomegaly; Hepatic mass
Pulsatile Liver (tricuspid regurgitation)
Ascites (fluid wave; shifting dullness; tense abdomen)
RUQ pain
Splenomegaly
Approach to the patient
Laboratory Testing
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Liver Function Tests
(cholestasis / transaminitis / mix)
AST; AST; Alkaline Phosphatase
Total bilirubin – direct / indirect
GGT
Albumin
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CBC
Platelets; H/H; MCV; WBC
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PT / INR
Basic Metabolic Panel
Serum Sodium
Potassium
Creatinine / BUN
Approach to the patient
Laboratory Testing
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Viral serologies
HAV; HBV; HCV; EBV
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Iron panel
Total iron, Ferriten, T Sat, Transferriten
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Autoimmune panel
Anti-LKM Ab, ASMA
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Ceruloplasmin
Serum Copper
A1 Antitrypsin
AMA
ANA
Quantitative Immunoglobulins
IgM, IgG, IgA
Approach to Liver Patient
ALF – Initial Laboratory Assessment
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Prothrombin time/INR
Chemistries
sodium, potassium, chloride,
bicarbonate, calcium, magnesium,
phosphate
glucose
AST, ALT, alkaline phosphatase, GGT, total
bilirubin, albumin
creatinine, blood urea nitrogen
Acetaminophen level
Toxicology screen
Viral hepatitis serologies
anti-HAV IgM, HBSAg, anti-HBc IgM, antiHEV§, anti-HCV*
Ceruloplasmin Level / Copper *
Autoimmune markers
ANA, ASMA, Immunoglobulin levels
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Arterial blood gas
Arterial lactate
Complete blood count
Blood type and screen
Pregnancy test (females)
Ammonia (arterial if possible)
HIV status (if txp potential)
Amylase and lipase
*Done only if Wilson disease is a
consideration
e.g., in patients less than 40years
without another obvious
explanation for ALF); in this case
uric acid level and bilirubin to
alkaline phosphatase ratio may be
helpful as well.
Approach to patient: staging injury
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Percutaneous Needle Liver Biopsy
Transjugular Liver Biopsy (TJLB /
portal pressures)
Noninvansive Markers
Fibroscan
MR Elastography
Liver Diseases: Overview - DDx
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Viral
HAV
HBV
HCV
Other – EBV, CMV, HSV
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Steatohepatitis (Fatty Liver)
Alcohol
Non alcohol (metabolic syndrome)
Pregnancy (microvesicular fatty droplet formation)
Drug
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Autoimmune Hepatitis
Liver Diseases: Overview - DDx
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Metabolic
Wilson’s Disease – copper overload
Alpha 1 Antitrypsin Disease
Hereditary Hemochromatosis – iron overload
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Drug Toxicity
Antibiotics
Statins
Herbal / Other
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Vascular injury
Veno-occlusive Disease
Budd Chiari Syndrome
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Congenital
Congenital Hepatic Fibrosis
Polycystic Liver Disease
Caroli’s Disease
Alagille’s Syndrome
Case #1
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18 male presents with general malaise x 2 m, 10lb weight loss
to his primary care office
Student health records 6 m prior with normal LFTs
AST 901; ALT 848; AlkPhos 343; T bil 5.4;
WBC 8.6; Hg 14.7; MCV 92; Plt 201; INR 1.2
U/s Abd: borderline hepato-splenomegaly; otherwise normal
appearing liver; normal gb
Does this patient have acute liver failure or acute hepatitis?
What is your differential diagnosis?
What other information is helpful to you at this point?
Should we do a liver biopsy?
Does this patient have portal hypertension?
Case #2
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59 black male presents for yearly check up to primary care
Primary care opts to start a statin for hyperlipidemia; obtains pre
treatment labs
No other sig PMHx
FHx – CAD, DM, Hyperlipidemia
SHx – alcohol rare; never smoker; no illicit drug hx ; no transfusions
AST 64; ALT 84 ; AlkPhos 200; T bil 1.3; Albumin 3.2
WBC 6.2; Hg 16.7; MCV 98; Plt 117K
RUQ (limited) U/s Abd: Increased echogenicity of liver, no obvious
cirrhosis; no liver mass; no ascites; top normal spleen
What is your differential diagnosis?
What other information is helpful to you at this point?
Do you want a liver biopsy?
Is a statin contradindicated?
Case #3
• 67 yr old female presents with malaise, jaundice to
primary care
• PMHx – hypothyroidism
• T bil 6.5; AST 590; ALT 463; Alb 3.4; AlkPhos 300
• WBC 6.5; Hg 12.3; MCV 91; Plt 215k
• Cr 1.2; INR 1.3; AFP 3
What is your differential diagnosis?
What other information are helpful to you at this point?
Case #4
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53 F presents to GI office post hospitalization for jaundice, ascites and
abdominal pain
Discharge labs: Cr 1.4; Na 131; K 3.3; T bil 8.5; AST 75; ALT 32; AP 212;
Alb 2.6; Hg 9.4; WBC 13; Plt 90k; MCV 103; Fluid analysis 314 PMN;
culture negative; high SAAG
U/s Abd: hepatomegaly; mass can not be rule out based on limited exam;
distended gallbladder; no acute cholecystitis; moderate ascites; enlarged
spleen; PV patent
What is your differential diagnosis?
What other information are helpful to you at this point?
Surgery consult?