chronic liver disease due to hepatitis B infection is a common problem in our country' The sole method of accurate diagnosis is liver biopsy, which is an invasive technique associated with complications, and is expensive

2. Original Article
Efficacy of Asr/ALT Ratio for Assessment of Liver
Fibrosis in chronic Hepatitis B lnfection
Eram Mustafizl, Ruksana Kariml, Tasmina Parveen2, Matia Ahmed2' Md Shahadat Hossain3
Abstract
chronic liver disease due to hepatitis B infection is a common problem in our country' The
sole method of accurate diagnosis is liver biopsy, which is an invasive technique associated
with complications, and is ixpensive. The main aim of the current study is to evaluate the
efficacy of indirect serum markers for diagnosis of severity and extent of fibrosis in patients
with chronic hepatitis B. This is a cross-sectional study on sertlm aspartate aminotransferase
- serum alanine aminotransferase ratio (AST/ALT ratio) in patients with liver fibrosis following
chronic Hepatitis B infection. The study was done on a total of 50 biopsy-diagnosed'
treatment-naive Hepatitis B patients. serum AST and ALT were estimated by Kinetic UV
method. Fibrosis was scoied according to the scheuer scheme. Data were analyzed
statisticalty by spearman's rank correlation usrng sPSS softvvare version 12' Mean AST/
ALT ratio was found to be 0.92 x 0.28. AST/ALT ratio shows almost no correlation with mild
or significant fibrosis by spearman's rank correlation coefficient (r = 0'118; p >0'1)' lt can
thus be concluded from'this study that AST/ALT ratio has low diagnostic accuracy for
predicting significant fibrosis and cirrhosis in individuals with chronic hepatitis B infection'
Keywords: AST/ALT ratio, Liver fibrosis, Chronic hepatitis
(J tJttara Adhunik Med Colt' 2011; 1(2) : 52-55)'
lntroduction
Liver fibrosis is not an independent disease but
rather a scarring response that results f rom chronic
injury of any cause, including hepatitis B and C'
excessive alcohol ingestion, nonalcoholic
steatohepatitis (NASH), and iron overload' Chronic
viral hepatitis B and C are the most common causes
of liverfibrosisl.
Liver biopsy is the gold standard method to assess
liver fibrosis in patients with chronic liver disease' lt
plays a prominent role in the management of chronic
hepatitis B (CHB), which is helpful in confirming
diagnosis, identifying other causes of liver disease'
as well as assessing grade of inflammation and stage
of fibrosis. Results of liver biopsy also assist in guiding
1 . Department of Biochemistry, Uttara Adhunik Medical College'
Dhaka 1 230, Bangladesh,
2. Department of Physiology' Uttara Adhunik Medical College'
Dhaka 1 230, Bangladesh,
3. Department of Biochemistry, MAG Osmani Medical College'
Sylhet 3100, Bangladesh.
aOdress of Correspondence: Dr' Eram Mustafiz' Assistant
Professor, Department of Biochemistry, Uttara Adhunik Medical
College, Sonargaon Jonopath, Plot # 34, Road # 4' Sector # 9'
Uttara Model Town, Dhaka 1230, Bangladesh'
treatment strategy in patients with chronic hepatitis
B2-3.
However, liver biopsy is an invasive procedure
associated with major complications and expensive
as well. As a result, simple and reliable non-invasive
markers such as blood tests and/or liver imaging
modalities that accurately correlate with disease
activity and stage are urgently needed to assist in
the management of chronic hepatitis B patients
worldwideind so reduce the need for repeated liver
biopsiesa-6.
Many models involving routine lab^oi3to-rylests'
e'g''
,.prrtrt" aminotraniferase (AST), ALT (alanine
aminotransferase), platelet count, gamma-
glutamyltransferase (GGT), cholesterol' AST/ALT
iatio, APRI etc. are being evaluated for predicting the
different stages of liver fibrosis' The present study
involves the assessment of liver fibrosis using a model
involving a combination of routine laboratory tests'
namely serum aspadate aminotransferase-alanine
aminotransferase ratio (AST/ALTratio)' The main aim
of the current study is to assess the eff icacy of serum
AST/ALT ratio for diagnosis of severity and extent of
fibrosis in patients with chronic hepatitis B'

3. Efficacy of AST/ALT Ratio for Assessment of Liver Fibrosis in Chronic Hepatitis B lnfection Eram Mustafiz et al
significance. Data were analyzed statistically by
Spearman's rank correlation coefficient using SPSS
software version 12.
Results
The age range of the 50 patients was 15-47 years and
the mean age was 27.4 + 8.03. Males and females
were 37 (74'/") and 13 (26%) respectively. The mean
AST/ALT ratio was 0.92 t 0.28, the values ranging
f rom 0.41 lo 2.02. The values of AST/ALT ratio did not
show a linear relationship with increasing fibrosis stage
(Table 1 and Figure 1).
Table-l
AST/ALT ratio in relation to different stages
of fibrosis
Fibrosis stage No. (%) of patients AST/ALT
ratio (Mean + SD)
2 (4)
22 (44)
4 (8)
13 (26)
e (18)
50 (1oo) 0.92 x. O.28
01234
Stages of fibrosis
Fig.-l: Bar diagram of mean AST/ALT ratio in relation
to the stages of fibrosis.
Materials and Methods
A cross sectional study was designed in the
Department of Biochemistry, Dhaka Medical College,
Dhaka from July 2006 to June 2007. The study was
done on a total of 50 patients with chronic hepatitis B
who were admitted in the Depaftment of Hepatology,
Bangabandhu Sheikh Mujib Medical University
(BSMMU), and Department of Gastroenterology,
Dhaka MedicalCollege and Hospital (DMCH), Dhaka.
All patients were treatment-naive, had hepatitis B virus
surface antigen (HBsAg) positive for more than 6
months and hepatitis B virus (HBV) DNA level
>105copies/ml prior to entry into the trials with no
evidence of decom pensation, metabol ic abnorm alities,
associated co-infection, pregnancy or any other
disease that may alter the serum AST and ALT levels.
Only pre-treatment biopsies were used forthe current
study. Every patient was diagnosed clinically and
histopathologically. Fibrosis was scored according to
the Scheuer Scheme. According to the Scheuer
scheme, the stage F0 indicates no fibrosis, F1
indicates fibrous podal expansion, F2 indicates portal-
pofial septa, F3 indicates bridging with distotlion, and
F4 indicates cirrhosisT-8.
The study protocol was approved, permission was
taken from the concerned departments and authorities,
and ethical clearance was given by the Ethical
Committee, Dhaka Medical College and Hospital
(DMCH), Dhaka. Allthe patients gave informed written
consent on entry to the trials for use of these data for
research purposes. A preset data form was filled for
every subject.
Five millilitre of venous blood was drawn from each
subject under aseptic condition and centrifuged for
obtaining serum. Serum ALT and AST concentrations
were estimated by Kinetic UV method, and ASTiALT
ratio was calculated as follows:
AST/ALT ratio = Serum AST level (U/l)/Serum ALT
level(U/l)
Upper limit of normal range was taken as 45 U/ lor
AST and 40 UA for ALT. Values were expressed as
mean l SD (standard deviation) unless otherwise
stated. Relationships among different variables were
established by linear correlation (correlation coefficient
or 'r'). p value of <0.05 was taken as the level of
0
1
2
3
4
0.69 t 0.36
0.90 t 0.23
0.84 t Q.22
.1.03
t 0.35
0.90 t 0 25
1.20
1.00
0.00
53

4. J Uttara Adhunik Med. College Vol.01 , No.02, July 2011
Table-ll
AST/ALT ratio in retation to severity of fibrosis and Spearman's rank correlation between them
Fibrosis No. (%) of subjects AST/ALT rvalue pvalue
< Stage 2(mild to moderate fibrosis)
>Stage 2(signif icant fibrosis and cirrhosis)
28(56"/")
12(44%)
0.87 10.24
0.97 r0.32
0.034 0.865(>0.05)
0.17s 0.436(>0.05)
Table-lll shows fibrosis to have a weak positive correlation with AST/ALT ratio by Spearman's rank (rio) conelation
coefficient (r).
Table-lll
Spearman's rank correlation of serum AST/ALT ratio with stage of fibrosis
Parameter (Mean t SD) r value pvalue
Stages of Fibrosis AST/ALT ratio 0.92 t 0.28 0.118 0.414 (>0.05)"
.Correlation is not significant
Receiver operating characteristics (HOC) curves were
plotted and the area underthe ROC (AUROC) curyes
were determined to detect the ability of AST/ALT ratio
to predict the different stages of hepatic fibrosis. An
AUC of 1.0 is characteristic o{ an idealtest, whereas
an AUC of 0.5 or less indicates a test of no diagnostic
value.
The AUROC for AST/ALT ratio was al0.47 in mild
fibrosis, 0.41 in moderate fibrosis, 0.63 in significant
fibrosis, and 0.49 in cirrhosis. The AUROC curves of
AST/ALI- ratio were not significant and so were not
evaluated fudher.
Discussion
The ideal non-invasive diagnostic test for hepatic fibrosis
is one that is simple, readily available, inexpensive,
and accurate. Many models based on non-invasive
determinations have been developed for liverfibrosis in
chronic hepatitis C infection and some of them have
been tested in chronic hepatitis B as well, but their
clinical usefulness is still controversial. Liver biopsy is
still the gold standard for assessment of fibrosis.
The present study involves the assessment of liver
fibrosis using a model involving a combination of
routine laboratory tests like AST/ALT ratio. lt has been
previously applied in similar studies but the results
concerning its diagnostic powers were often
conflicting. The results of the current study showed
that the AST/ALT ratio is not significantly associated
with the extent of liver fibrosis in chronic hepatitis B.
The mean AST/ALT ratio in the current study was 0.92
t 0.28. AST/ALT ratio did not show linear relationship
with fibrosis stages. lt was more than 0.8 in all stages
of f ibrosis and no def inite differentiating level of AST/
ALT ratio could be identified in predicting advanced
fibrosis. lt showed almost no correlation with mild or
significant f ibrosis (r = 0.'118; p >0.1). The area under
the ROC curves of AST/ALTratiofor predicting different
stages of fibrosis were insignifrcant and so was not
evaluated further. The AUROC ranging f rom 0.41 to
0.63 was consistent with the findings repofted by Wai
et at.e where AUROC was at 0.58-0.63, and by
Lackner et a/.4 that AST/ALT ratio has low diagnostic
accuracy for predicting advanced fibrosis. According
to Fontana and Lok10, available serum iibrosis marker
panels cannot reliably distinguish between individual
stages of fibrosis but rather provide a binary
categorization of disease severity.
Serum ALT levels ref lect liver injury, but the correlation
between ALT levels and necroinflammatory and {ibrosis
scores is poor10. Despite the poor quantitative
correlation, most patients with persistently normalALT
levels (at least 3 normal values over a 6 to 12 month
period)have less inflammation and fibrosis, and slower
rate of fibrosis progression compared with patients
with elevated AST levels. One study found that AST
had a slronger correlation with liver histology, in
particular hepatic f ibrosis 11
.
Reversal of AST/ALT ratio was observed when patients'
progress from chronic hepatitis to cirrhosis and AST/
ALT ratio of more than t had been reported to have
very high specificity (82%to 100%)for cirrhosisl2-14.
Further studies should be done to evaluate the efficacy
of ALT/AST ratio as a marker of lrver fibrosis.
a

5. F
=1 cacy of AST/ALT Ratio for Assessment of Liver Fibrosis in Chronic Hepatitis B lnfection
-^e f inding of increased AST level with progression of
. er fibrosis has been reported in many studies. While
:ST had been persistenily found to be useful in
c'edicting significant fibrosis in patients with chronic
:epatitis B (CHB), it is not an independent factor in
credicting either significant fibrosis or cirrhosis in
catients with CHBe,15-17. El"rrtion of AST with
progression of liver fibrosis was believed to be due to
reduction in the clearance of AST18 and mitochondrial
injury with more marked release of AST relative to
ALT in CHCIe-20.
There are limitations to the study. The study included
patients from a university hepatology ward and allthe
patients were treatment-naTve. All the patients had
HBV DNA >105 copies/ml and so these models are
not applicable for those with inactive virological disease
(HBV DNA <10s copies/ml). Due to f und constraints,
other models with higher degrees of accuracy could
not be compared with the models in this study.
Conclusion
It can thus be concluded from this study that AST/
ALT ratio which was unable to differentiate between
the individual stages of fibrosis, has low diagnostic
accuracy for predicting significant fibrosis and cirrhosis
in individuals with chronic hepatitis B infection.
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