Document 6425104

Mild diffuse LFT
abnormalities
History and physical examination
(especially drugs, alcohol)
Obesity, diabetes, hyperlipidemia
Autoimmune features
Serum globulins, ANA, SMA
Miscellaneous considerations
Consider USG, CT, MRCP, ERCP
Liver biopsy as dictated by findings
and subsequent course
Lab Test Report
14 year old female with purpura, no liver,
spleen or lymphadenopathy. Her CBC
report is as follows:
CBC by prick
WBC
6400
Neutrophils
30 %
Lymphocytes 65 %
Eosinophils
03 %
RBC count
4.93 million
Hb
13.4 g/dl
HCT
40 %
MCV
81.1 Fl
MCH
27.2 pg
MCHC
33.5 %
Platelet
0.15 lakhs
Exciting
Prizes
Test for hemochromatosis
Wilson’s disease
Alpha-1 antitrypsin deficiency
Celiac disease
KNOWLEDGE TERMINUS
“I don't wish to confess that I learnt a lot from the issue
on lymphadenopathy. The tabular format and the simplicity
with which you have condensed such a vast topic in 4 pages
is highly commendable. Also how doctors will definitely
think twice before treating”.
Telephonic conversation
with a senior teacher
who did not wish
to be named.
SMS your diagnosis with your name
to 9820559573 or call on 24173232
3 winners will be chosen by lucky draw
from the correct entries
To discuss the above report call
Dr. Swati Kanakia on 9820229302
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Published by Dr. Raju R. Kanakia for Kanakia Health Care, 2, Neelkanth Niwas, Purandare Park, Dr. B. Ambedkar Road, Dadar Circle, Mumbai 400 014 and
printed by Medivision Infomedia Pvt. Ltd., Mumbai - 400 037. Tel.: 2410 3737 / 2410 3838 Fax:2410 3939 E-mail: [email protected]
Rs. 1
4
MH/MR/EAST/18/2004-05
Consider nonalcoholic fatty
liver disease (NASH)
Serologic tests for viral hepatitis
Risk factors for viral hepatitis
Train or Strain your Brain
Vol: 2 No: 2
OCTOBER 2005
RNI. MAHENG 09523/13/1/2004-TC
Dear Friends,
Dr. Raju Kanakia
MD, DNB (Gastroenterology)
l
Gastroenterologist l
Hepatologist
I am sure all of you must have enjoyed Navratri, thanks to the Supreme Court
relaxation of the deadline from 10 p.m. to midnight. But did you give a thought
to the harmful effects of noise pollution? Festivals have now become a
legitimate reason to indulge in noise pollution.
Now Diwali is just round the corner and it too will lead to noise pollution by
enthusiasts bursting crackers past midnight. We seem to have forgotten that
Diwali or Deepawali is a festival of lights and not noise. At KHC, we remember
and strive to light the “deep” of knowledge by providing you with practical
information useful in day today practice. “Interpretation of Liver Function
Tests” is yet another effort in that direction.
Drs Swati and Raju Kanakia
EDITOR’S PLATFORM
l
Interventional
G.I. Endoscopist
Mobile: 9820229301
l
Digestive Health Centre, Dadar
l
Lilavati Hospital, Bandra
l
S L Raheja Hospital, Mahim
l
Lion Tarachand Bapa Hospital, Sion
l
Rushabh Nursing Home, Chembur
Dr. Swati Kanakia
MD, DCH, PhD
l
Pediatric
Hematologist Oncologist
Mobile: 9820229302
l
Advanced
Blood & Cancer
Disorders Centre, Dadar
l
Lilavati Hospital, Bandra
l
Asian Institute of Oncology,
S L Raheja Hospital, Mahim.
l
Sir H N Hospital, Prarthna Samaj
l
Lion Tarachand Bapa Hospital, Sion
Liver Function Tests:
Liver function tests represent a broad range of normal functions performed by the liver.
The diagnosis of liver disease depends upon a complete history, complete physical
examination, and evaluation of liver function tests and further invasive and noninvasive
Abnormal LFTs often, but not always,
indicate that something is wrong with the
liver, and they can provide clues to the
nature of the problem. However, normal
LFTs do not always mean that the liver is
normal. Patients with cirrhosis and
bleeding esophageal varices can have
normal LFTs. Of the routine LFTs, only
serum albumin, bilirubin and prothrombin
time (PT) provide useful information on
how well the liver is functioning. The
commonly used liver function tests (LFTs)
primarily assess liver injury rather than
hepatic function. Indeed, these blood tests
may reflect problems arising outside the
liver, such as hemolysis (elevated bilirubin
level) or bone disease (elevated alkaline
phosphatase [ALP] level).
An isolated elevation of just one test result
should raise suspicion that a source other
than the liver is the cause. When several
liver tests are simultaneously out of the
normal range, consideration of nonhepatic sources becomes irrelevant.
Most clinical laboratories offer bundled blood tests, which often contain all or
most of the following:
TABLE 1- Basic Blood Tests in Hepatobiliary Disease
Test
Alanine transaminase
(ALT/SGPT)
Aspartate transaminase
(AST/SGOT)
Normal Range (adults)
Significance
5-40 U/L
Liver cell damage
Monitor disease progress
Liver cell damage
Confirm hepatic cause of AST elevation
5-40 U/L
Monitor disease progress
Alkaline phosphatase (ALP)
45-130 U/L
Hepatic infiltrative disease, cholestasis
Total bilirubin
1-1.5 mg/dL
Elevated in jaundice, hemolysis
Biliary obstruction, hepatitis, drugs
Conjugated (direct)
0.3 mg/dL
Unconjugated (indirect)
1.0 mg/dL
Gilbert’s disease, pernicious anemia,
hemolysis
3.5-5.0 g/dL
Lower with decreased liver function
Albumin
Gamma glutamyl
transpeptidase (GGT)
4-40 U/L
Prothrombin time (PT)
10-16 seconds
Screening for alcohol abuse
Monitor liver disease
Cholestasis
Monitor hepatic carcinoma progression
Increases with decreased liver function
KNOWLEDGE TERMINUS
1
Elevated alkaline
phosphatase
Bilirubin:
Table 2. Nonhepatic causes of abnormal liver function test results
Bilirubin, an endogenous
organic anion, binds reversibly
to albumin and is transported to
the liver, where it is conjugated
to glucuronic acid and excreted
in the bile. It is derived primarily
from catabolism of red blood cell
heme and to a lesser extent from
degradation of myoglobin,
cytochromes, catalase, and
peroxidase. Healthy people
have a small amount of
unconjugated (indirect) bilirubin
but no conjugated (direct)
bilirubin in their blood. However,
commonly used laboratory tests
often incorrectly identify some
serum bilirubin as being
conjugated in healthy people, so
most testing centers report a
range of normal for conjugated
bilirubin.
Test result
Nonhepatic causes
Decreased serum
albumin level
Protein-losing enteropathy
Serum globulins, alpha1-antitrypsin clearance
Nephrotic syndrome
Urinalysis, 24-hr urinary collection for protein
Congestive heart failure
Cardiac examination, two-dimensional
echocardiogram
Myocardial infarction
CK-MB, troponin, ECG
Muscle disorders
CK, ESR
Bone disease
GGT, serum leucine aminopeptidase,
59-nucleotidase
Pregnancy
GGT, 59-nucleotidase, hCG in serum and urine
Hepatobiliary disease is
indicated when the conjugated
fraction of total bilirubin exceeds
Elevated ALP level
Elevated bilirubin level
Elevated PT
Alkaline phosphatase electrophoresis
Hemolysis
Reticulocyte count, peripheral smear, LDH,
haptoglobin
Sepsis
Clinical setting, blood cultures
Ineffective erythropoiesis
Peripheral smear, urine bilirubin, hemoglobin
electrophoresis, bone marrow aspiration and
biopsy
Shunt hyperbilirubinemia
Clinical setting
Antibiotic use, anticoagulant use,
steatorrhea, dietary deficiency
Response to vitamin K
Extrahepatic source
FIGURE 1. Typical serum aspartate aminotransferase (AST) or
alanine aminotransferase (ALT) values for various diseases.
Toxic or ischemic
injury
Acute viral hepatitis
Alcoholic hepatitis
Chronic hepatitis
Cirrhosis
Normal
10
30
100
300
Normal
AMA, ACE level,
serologic tests for hepatitis,
alpha fetoprotein
Gallstones
Cholecystectomy and bile
duct exploration, if indicated
Focal lesion(s)
CT/MRI, biopsy
Billiary tract abnormalities
Cholangiography
(MRCP, ERCP, THC)
Primary
sclerosing
cholangitis
Above negative; elevation persists
Liver biopsy (including electron microscopy)
ALP, alkaline phosphatase; AST, aspartate aminotransferase; CK, creatine kinase; ECG, electrocardiogram; ESR,
erythrocyte sedimentation rate; GGT, gamma-glutamyltranspeptidase; hCG, human chorionic gonadotropin; LDH,
lactate dehydrogenase; PT, prothrombin time.
ALT is the enzyme produced within the cells of the liver. The
level of ALT abnormality is increased in conditions where
cells of the liver have been inflamed or undergone cell
death. As the cells are damaged, the ALT leaks into the
bloodstream leading to a rise in the serum levels. Any form
of hepatic cell damage can result in an elevation in the ALT.
The ALT level may or may not correlate with the degree of
cell death or inflammation. ALT is the most sensitive marker
for liver cell damage.
1,000
3,000
10,000
U per L
Colonoscopy
GGT elevations of about twice normal. A mildly elevated
GGT level is a typical finding in patients taking
anticonvulsants and by itself does not necessarily indicate
liver disease.
Alkaline Phosphatase (ALP):
Alkaline phosphatase is an enzyme, which is associated
with the biliary tract. It is not specific to the biliary tract. It is
also found in bone and the placenta. Renal or intestinal
damage can also cause the alkaline phosphatase to rise. If
the alkaline phosphatase is elevated, biliary tract damage
and inflammation should be considered. However,
considering the above, other etiologies must also be
entertained. One way to assess the etiology of the alkaline
phosphatase is to perform a serologic evaluation called
isoenzymes. Another more common method to asses the
etiology of the elevated alkaline phosphatase is to
determine whether the GGT is elevated or whether other
liver function tests are abnormal (such as bilirubin)
Serum proteins - Albumin / Globulin:
Most circulating proteins in plasma are synthesized in the
liver, and levels indicate synthetic capability of the liver.
Hypoalbuminemia is often associated with ascites and
expansion of the extravascular albumin pool at the expense
of intravascular albumin levels. In general, albumin is a good
marker of severity of chronic liver disease, but levels may be
affected by chronic renal insufficiency, urinary protein
losses, or gastrointestinal losses.
Markedly elevated levels of ALP suggest the possibility of
such disorders as extrahepatic biliary obstruction, primary
biliary cirrhosis, drug-induced cholestasis, primary
sclerosing cholangitis, and infiltrative processes (e.g.
tuberculosis, amyloid, granulomatous hepatitis, neoplasm).
Increases in serum globulin levels are common in chronic
liver disease but are nonspecific. However, the pattern of
elevation may give a clue to the underlying cause. For
example, in autoimmune hepatitis, the serum IgG level is
elevated, whereas in primary biliary cirrhosis, the serum IgM
level is elevated.
Gamma Glutamic Transpeptidase (GGT):
This enzyme is also produced by the bile ducts. However, it
is not very specific to the liver or bile ducts. It is used often to
confirm that the alkaline phosphatase is of the hepatic
etiology. The GGT level is often elevated in persons who
take three or more alcoholic drinks (45 g of ethanol or more)
per day. Thus, GGT is a useful marker for alcohol intake.
Phenobarbital, phenytoin and other drugs typically cause
Prothrombin time (PT):
Severity and prognosis of liver disease can be assessed
using PT, which reflects deficiency of one or more of the
liver-synthesized factors. In cholestatic liver disease, PT
prolongation can result from vitamin K deficiency, but
differential diagnosis includes malabsorption, disseminated
intravascular coagulation, inherited deficiencies of
coagulation factors, and medications that antagonize the
prothrombin complex. To correct PT, vitamin K is often given
at a dosage of 10 mg/day for 3 days. Correction by at least
30% within 24 hours suggests that hepatic function is intact
and that vitamin K deficiency may be the source of the
problem
Aspartate Aminotransferase (AST/SGOT):
This enzyme also reflects damage to the hepatic cell. It is
less specific for liver disease. It may be elevated in other
conditions such as a myocardial infarct (heart attack).
Although AST is not a specific for liver as the ALT, ratios
between ALT and AST are useful to physicians in assessing
the etiology of liver enzyme abnormalities.
Elevated ALT
History and physical examination
(especially drugs, alcohol, obesity,
diabetes)
IgM anti-HBc + Acute hepatitis
HBsAg
IgM anti-HBc + Chronic hepatitis
+
Normal
GGTP or 5' nucleotidase
Abdominal USG
Malignant tumor
Alanine Aminotransferase (ALT/SGPT):
Anti-HCV
History and physical examination
(especially pruritus, cholestasis, drugs,
pregnancy, renal disease, bone symptoms)
Elevated: hepatobilliary disease
Elevated AST level
the upper limit of normal, even if the total serum bilirubin
concentration is normal or near normal. The presence of
conjugated, water-soluble bilirubin in the urine (bilirubinuria)
always indicates hepatobiliary disease. Hemolysis and
Gilbert syndrome are common conditions that cause benign
elevation of unconjugated bilirubin.
+
Discriminating tests
Hepatitis C
Serum levels of AST and ALT are elevated to some extent in
almost all liver diseases. Mild elevation is typically found in
patients with fatty liver, nonalcoholic steatohepatitis, and
chronic viral hepatitis. Highest elevation occurs in acute viral
hepatitis, hepatic necrosis induced by drugs (e.g.
acetaminophen) or toxins, and ischemic hepatitis related to
circulatory shock.
Although elevated aminotransferase levels may be the first
clue to liver disease and screening has proved useful for
detecting subclinical disease in asymptomatic persons,
patients with normal levels may have significant liver
damage. For instance, recent studies have demonstrated
that patients with chronic HCV infection may have histologic
evidence of chronic hepatitis despite repeatedly normal
results on liver tests.
Above negative:
Consider
Wilson’s disease (<age 40): Cu, ceruloplasmin
Hemochromatosis: Fe, TIBC, ferritin
Autoimmune hepatitis: ANA, SMA serum globulins
Alpha-1 antitrypsin deticiency: AAT level
Celiac disease: transglutaminase antibody
AST:ALT ratio of more than 2:1 is characteristic in patients
with alcoholic liver disease.
Above negative:
?USG or CT for fatty liver
Consider liver biopsy
Elevated GGTP
History and physical examination
(especially alcohol, obesity, diabetes, drugs,
myocardial infarction, COPD, renal disease,
pancreatic disease)
Abdominal USG
Focal Lesion (s)
Biliary tract disease
Abnormal liver echotexture
CT/MRI, biopsy
Cholangiography
(MRCP, ERCP, THC)
Consider liver biopsy
Above negative; persistent elevation after
abstinence from alcohol for 2-3 months
Consider liver biopsy
2
3
Summary
Evaluating abnormal liver test results requires careful
attention to the corresponding clinical data obtained during
history taking and physical examination. Generally, it is
helpful to separate liver tests into three categories: tests that
assess synthetic function, tests that assess hepatocellular
necrosis (hepatocellular enzymes), and tests that assess
cholestasis. The clinical setting together with the specific
pattern of liver function abnormalities can narrow differential
diagnosis and provide a cost-effective approach to
assessing patients and identifying those who need liver
biopsy.