Received: 6.1.2011 Accepted: 27.2.2011
a Associate Professor of Gastroenterology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
b Associate Professor of Gynecology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
c Academic Member of Medical Informatics Deptartment, School of Health Management and Information Sciences, Isfahan University of
Medical Sciences, Isfahan, Iran.
d Professor of Pharmacology, Isfahan University of Medical Sciences, Isfahan, Iran.
e Department of Gastroenterology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
* Corresponding Author
JRMS/ March 2011; Vol 16, No 3. 287
Effects of silybum marianum on patients with chronic hepatitis C
Hamid Kalantaria, Zahra Shahshahan*b, Sayed Mehdi Hejazic,
Taghi Ghafghazid, Vahid Sebghatolahie
BACKGROUND: Silymarin derived from silybum marianum (milk thistle), a flowering member of the daisy family, may
benefit liver function in people infected with the hepatitis C virus. The aims of this pilot study were to assess the effica-
cy and safety of silymarin on serum hepatitis C virus (HCV) RNA, serum aminotransferases (ALT, AST) levels, liver
fibrosis and well-being in patients with chronic hepatitis C (CHC).
METHODS: This prospective self-controlled trial study was conducted from March to September 2006 at Department of
Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran. 55 patients with HCV (10 female and 45 male)
with a mean age of 31.8 ± 6.4 years (10-67 years) were participated in the study. Patients received 24 weeks of silymarin
(630 mg/day). Baseline virological biochemical, liver fibrosis (by a serum fibrosis markers, including YKL–40 and Hyalu-
ronic acid), and SF-36 questionnaire were performed with biochemical tests repeated at the end of the treatment period.
RESULTS: There was statistically difference in mean of ALT (108.7 ± 86.6 vs 70.3 ± 57.7) before and after the treatment
(p < 0.001). The means of AST were 99.4 ± 139.7 and 59.7 ± 64.32 before and after the treatment with statistically dif-
ferences (p = 0.004). After the treatment, nine patients were found with negative HCV-RNA (p = 0.004) and statistical-
ly significant improvement in results of liver fibrosis markers were found only in fibrosis group (p = 0.015). Quality of
life was improved significantly (p < 0.001).
CONCLUSIONS: This study indicated that in patients with CHC performing silymarin (650 mg/day) for 6 months, im-
proved serum HCV-RNA titer, serum aminotransferases (ALT, AST), hepatic fibrosis and patient’s quality of life. More
future studies are warranted.
KEYWORDS: Hepatitis C Virus (HCV), Quality of life, Serum Aminotransferases.
JRMS 2011; 16(3): 287-290
epatitis C is a major cause of liver -
related morbidity and mortality.1,2 Ri-
bavirin plus interferon combination
therapy, is presently considered the optimal
treatment for patients with chronic hepatitis C,
but the recommended treatment regimen is
associated with considerable expense, adverse
effects and poor efficacy in some patients with
hepatitis C. Therefore, many hepatitis C pa-
tients use the herb silymarin (milk thistle), an
alternative therapy for hepatitis C, in addition
to or instead of standard treatment for chronic
hepatitis C virus infection.3
Although the popularity of silymarin has
been increased in people with liver disease4,5
but a little evidences with controversial results
exist in effect of silaymarin on chronic hepatitis
C. In one study in Egypt,6 a dose of 420
mg/day of silymarin has been used for one
year. The quality of life of the patients im-
proved very well, but the level of liver enzyme
did not change. An exhaustive search strategy
Effects of silybum marianum on chronic hepatitis C
Kalantari et al
288 JRMS/ March 2011; Vol 16, No 3.
identified 148 papers that studied silymarin
compounds in liver disease. Of these, four tri-
als included patients with hepatitis C which
only two trials reported a decrease in serum
According to existence of little evidences
with controversial results and increasing popu-
larity of using silymarin in chronic hepatitis C,
this study was conducted to evaluate the effect
of higher doses of silymarin (630 mg/day) for
6 months, on patients with hepatitis C along
with liver biopsy.
This prospective self-controlled trial study was
conducted from March 2006 to September 2006
at Department of Gastroenterology, Isfahan
University of Medical Sciences, Isfahan, Iran.
Inclusion criteria contained confirmed
chronic hepatitis C (HCV Ab (+), HCV-RNA
[with PCR] (+)), normal or increased liver en-
zymes (ALT and AST) and not using interfe-
ron or ribavirin due to patient sensitivity or
not consenting. The pregnant patients and pa-
tients with side effect which confirmed with
rechallenge test were excluded. The ethics
committee of Isfahan University of Medical
Sciences approved the study and all of partic-
ipants signed an inform consent after explain-
ing the aims and protocol of the study to
them. The study was registered at Clinical-
Trials.gov (Identifier: NCT01292161).
After measuring the baseline outcomes, we
performed 630 mg/day silymarin a product of
Goldaru pharmaceutical Co. Isfahan, Iran for
six months. Following serum components
were measured before and after the treatment:
liver enzymes (ALT and AST), HCV-RNA
(with PCR) and markers for liver fibrosis such
as YKL 40 and Hyaluronic Acid (HA). YKL 40
was measured with YKL 40–EIA Kit, Quaildel
comp. San Diego. CA. with cut off value of
284.8 ng/ml (sensitivity 80% and specificity
71%) 9 and HA was assessed by enzyme linked
binding protein assay (corgenix inc Denver)
with the cut-off value of 110 mg/l (sensitivity
79.2% and specificity 89.4%).10
According to liver fibrosis markers (YKL 40
and HA) results before treatment, patients
were divided into three stages:
Fibrosis group: YKL 40 > 150 ng/ml and HA >
60 ng/ml or YKL 40 > 150 ng/ml or HA > 100
ng/ml; Non-fibrosis group: YKL 40 < 100
ng/ml and HA < 20 ng/ml; Intermediate
group: the results with no agree with above
After the treatment patients were divided to
three groups according to their liver fibrosis
markers results. Fibrosis activity progress
group: YKL 40 > 100 ng/ml or HA > 50 ng/ml
more than the level before treatment. Fibrosis
activity regression group: YKL 40 decreased
more than 75 mg/ml or HA decreased ≥ 30
ng/ml compared with before treatment levels.
Fibrosis stable group: the level of liver fibrosis
markers were not agreed with above level after
treatment. For the determination of quality of
life, we used the Iranian version of short form
healthy survey (SF-36) questionnaire 11 before
and after treatment which it’s validity and re-
liability was established.
questionnaire is a generic measure of health
that is used to measure quality of life. It
consists of 36 questions (items) which alto-
gether score from 0 to 100.
Data were analyzed with the paired t-test,
McNemar, and chi–square statistical methods.
All analysis were done with SPSS v.16.
Seventy seven patients were enrolled in the
study. One patient died and 21 patients did not
participate in follow-up process. Finally, 55
patients (10 female and 45 male) with the
means age of 31.8 ± 6.4 years (10-67 years)
completed the study.
The mean of ALT before and after the treat-
ment were 108.7 ± 86.6 and 70.3 ± 57.7. Accord-
ing to paired t-test analysis there was a statistic-
al difference before and after the treatment with
silymarin (p < 0.001). The mean of AST were
99.4 ± 139.7 and 59.7 ± 64.32 before and after the
treatment. According to paired t-test analysis
there was statistically different from before the
treatment with silymarin (p = 0.004).
After the treatment, nine patients were found
Effects of silybum marianum on chronic hepatitis C Kalantari et al
JRMS/ March 2011; Vol 16, No 3. 289
Table 1. Liver fibrosis markers (YKL 40 and HA) results before and after the treatment
treatment after treatment
Fibrosis n (%) 42 (76%) 11 (26%)
Non-fibrosis n (%) 4 (7%)
Intermediate n (%) 9 (16%) 2 (22%)
Progression Stable after
with negative HCV-RNA which in regard to
McNemar test, it was significantly difference be-
fore and after the treatment (p = 0.004).
The results of liver fibrosis markers are
showed in table 1. According to hi-square me-
thod, there was a statistical improvement only
in fibrosis group (p = 0.015).
The means of SF-36 score were 51.06 ± 21.8
and 61.49 ± 22.8 before and after the treatment
respectively. According to paired t-test analy-
sis, there was a statistical improvement in
quality of life of patients (p < 0.001).
Silymarin has been claimed to have a beneficial
effect on various types of liver injury, includ-
ing alcoholic liver disease, drug and toxin in-
duced hepatotoxicity, and acute and chronic
viral hepatitis.8 Our results showed that per-
forming silymarin was significantly improved
the serum liver enzymes, HCV-RNA titer, he-
patic fibrosis and patient’s quality of life.
The mechanism of silymarin might be by
protecting liver cell injury with free radical
scavenging, stabilization of liver cell mem-
branes, stimulation of hepatocyte protein syn-
thesis, and modulation of the immune re-
sponse.12 Also recently determined silymarin
had antiviral effects against hepatitis C virus
cell culture infection that included inhibition of
virus entry, RNA and protein expression, and
infectious virus production.13
There is a little evidence for using this drug
for hepatitis C. Previous studies8,14 have re-
ported an improvement in a number of liver
chemistries, including ALT, following treat-
ment with S. marianum and our results sup-
ported their findings. Tanamly et al in a
double-blinded trial evaluated silymarin in
preventing complications of chronic hepatitis
C. Although they showed an improvement in
patient’s symptoms and quality of life, but no
significantly improvement in their liver en-
zymes, liver fibrosis markers and HCV-RNA
was achieved. Our results were not agreed
with their findings respectively. The difference
might be because of the performed dose of si-
lymarin, the study design and the genotypes of
Gordon et al in a randomized, double-blind,
placebo-controlled, crossover study examined
the effects of silybum marianum on patients
with chronic hepatitis C and showed no signifi-
cant effect on serum HCV-RNA, alanine amino-
transferase levels, quality of life or psychologi-
cal well-being.7 Our findings did not support
their findings respectively. It may be due to
their low sample size or study design which
may influence the results.
Adverse drug effects related to silymarin
have been published in studies and case reports
involving a total of over 7000 patients and
those confirmed that it is safe, with only three
reports of significant adverse reactions.5-12,14-18
Thus, it seems from the current data that pa-
tients with chronic hepatitis C are to benefit
from taking salymarin.
This study indicated that in patients with
chronic hepatitis C performing silymarin (650
mg/day) for 6 months, improved serum HCV-
RNA titer, serum aminotransferases (ALT,
AST), hepatic fibrosis and patient’s quality of
life. More future studies are warranted.
This research was supported by a grant (Grant
No. 83451) from the research council of Isfahan
University of Medical Sciences. The authors ac-
knowledge the kind assistance and financial
support provided by the Vice Chancellor for
Research at the Isfahan University of Medical
Effects of silybum marianum on chronic hepatitis C Kalantari et al Download full-text
JRMS/ March 2011; Vol 16, No 3.
Conflict of Interests
Authors have no conflict of interests.
HK carried out the design and coordinated the study, participated in most of the experiments and
prepared the manuscript. ZSH and TGH provide assistance in the design of the study, coordinated
and carried out all the experiments and participated in manuscript preparation. MH and VS pro-
vided assistance for all experiments. All authors have read and approved the content of the manu-
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