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Liv.52 Update
P R O B E
• V o l . L I I I • N o . 3 • A p r – J u n 2 0 1 4
were HBsAg positive at baseline and
received at least 1 dose of the study
medication. Data were expressed as
mean ± SD. One way ANOVA with
Bonferroni multiple comparison test
or Dunnett multiple comparison test
was performed wherever appropriate
using GraphPad version 4.00 for
Windows (GraphPad Software, San
Diego, CA, USA). A
P
value < .05 was
taken as statistically significant.
Results
Fourteen patients (12 males and 2
females) aged between 18 and 48
years with a mean age of 32.4 years
participated in this open study. All the
14 patients completed the 6-month
study as planned and no patient
was lost to follow up. The mode of
transmission of HBV was unknown
in most (78%) with blood transfusion
history being present in 14.3%.
Clinical response
The effect of HD-03/ES therapy on
weight loss and jaundice is shown
in Table 1. Although there was
progressive weight gain in patients
treated with HD-03/ES capsules, the
levels did not reach levels of statistical
significance. Clinical manifestations
of hepatitis improved significantly
in HD-03/ES-treated patients and
jaundice had disappeared in all the
patients after 24 weeks of therapy.
Table 1. Effect of HD-03/ES Therapy on
Weight and Jaundice
Time
(week)
Weight (kg)
Mean ± SD
Jaundice
Yes
No
0
57.89 ± 9.52 12
2
4
58.72 ± 8.08 11
3
8
58.92 ± 8.06
4
10
12
59.35 ± 7.93
2
12
16
59.03 ± 9.44
1
13
24
59.56 ± 7.97
0
14
Liver function tests and
alanine aminotransferase
normalization
Elevated ALT was present in all the
patients (Table 2). The median ALT
level was 153 U/L. As shown in the
table there was a progressive and
statistically significant reduction in the
level of ALT and this got normalized
in 9 of the 14 patients enrolled for the
study (Table 3). Only 5 patients who
completed therapy did not achieve the
set goal; but even in these people the
elevations ranged between 41 and 88
IU/L only.
Table 2. Effect of HD-03/ES Therapy on
Liver Function Tests
Liver
Function
Tests
Time (weeks)
Baseline 16
24
ALT (U/L)
195.3 ±
44.3
70.0 ±
10.8
a
62.4 ±
11.8
a
AST (U/L)
141.2 ±
37.7
78.7 ±
26.1
71.3 ±
11.6
b
Total
Protein
(g/dL)
6.4 ±
0.2
6.7 ±
0.2
7.0 ±
0.1
b
Protein
Fraction
Globulin
(g/dL)
2.7 ±
0.1
3.1 ±
0.1b
3.2 ±
0.2
b
Bilirubin
(total)
(mg/dL)
4.4 ±
1.3
1.9 ±
0.3
1.2 ±
0.2
b
ALT, alanine aminotransferase; AST,
aspartate aminotransferase.
a
P
< .01 as compared to control values.
b
P
< .05 as compared to control values.
Virological response
Before the treatment, HBsAg was
detected in all the patients (Table
3). In 10 of the 14 patients, HBsAg
became negative and this occurred
within 3 to 6 months after initiation
of HD‑03/ES therapy. Five of the 10
samples (50%) at the end of treatment,
who were treated with HD-03/ES,
had undetectable HBeAg. This
difference was statistically significant
(
P
< .05). HBV DNA loss also
occurred more frequently during
treatment with HD-03/ES in those 4
patients who were positive for HBV
DNA initially; they were negative for
the same at the end of therapy
(Table 3).
Table 3. Biochemical and Serological
Response to 24 Weeks of HD-03/ES Therapy
Variable
HD-03/ES
ALT
Normalization
(%)
16
Weeks
50
24
Weeks
64.3
Positive Negative
HBsAg Loss
0 Week 14
0
16
Weeks
7
7
24
Weeks
4
10
a
HBeAg Loss
0 Week 10
4
16
Weeks
6
8
24
Weeks
5
9
a
HBV DNA
Loss
0 week 9
5
16
Weeks
6
8
24
Weeks
5
9
a
ALT, alanine aminotransferase.
a
P
< .05 as compared to control values.
Safety
No serious or life-threatening side
effects were observed. Tiredness was
the only adverse effect reported by
2 patients during various periods of
therapy and was not severe enough
to warrant withdrawal of therapy.
Renal function tests showed normal
level of blood urea nitrogen and
blood creatinine during HD-03/ES
treatment.
Discussion
The results of this preliminary study
indicate that short-term therapy
with HD-03/ES is effective in the
management of CHB. Although
the initial results of this study are
promising, it remains to be seen
whether virological response will
be sustained during chronic dosing
and whether relapse rates after
cessation of therapy would be low
