Chinese Medicine May Perform Better than Interferon or Lamivudine
for Chronic Hepatitis B
Various traditional Chinese medicine (TCM) formulations
were found to work as well as or better than the pharmaceutical
drugs interferon and lamivudine for people with chronic
hepatitis B, according to a joint U.S./Chinese review
of clinical trials published in the February
2010 issue of Hepatology. While many of
these studies were considered to be of poor quality
according to Western drug testing standards, the review
authors concluded that some TCM remedies appear effective
and warrant further study.
hepatitis B is major global health problem, but its impact
is especially great in Asia. In China, it is estimated that
approximately 120,000,000 people have chronic HBV infection.
For centuries, the disease has been treated with traditional
Lingyi Zhang, Herbert Bonkovsky, and colleagues performed a
meta-analysis of clinical trials of TCM formulations for treatment
of chronic hepatitis B reported in China from 1998 through 2008.
An ancient book called the Yellow Emperor's Internal Classic
indicates that TCM remedies have been used to treat chronic
liver disease in China at least since 475 BCE, the authors noted
as background. Today, TCM is still used extensively for the
treatment of chronic hepatitis B in China, with some 80% of
patients relying on Chinese remedies. While interferon
alpha and lamivudine (Epivir-HBV)
are often available, newer nucleoside/nucleotide analog drugs
such as adefovir (Hepsera), entecavir
(Baraclude), and tenofovir (Viread)
are "prohibitively expensive" and not widely used,
Thousands of different herbs have been used in TCM formulations
for liver disease, including astragalus (Huang Qi), bupleurum
(Chai Hu), licorice root (Gan Cao), red sage (Dan Shen), rhubarb
(Da Huang), and schisandra (Wu Wei Zi). "These TCM formulations
are based on the collective wisdom of Chinese clinicians and
practitioners, coupled with centuries of accumulated experience
working with these herbs," the researchers wrote.
The review authors searched electronic databases (China National
Knowledge Infrastructure and PubMed) to identify studies
that either compared TCM formulations versus interferon (alpha-1b,
alpha-2a, or alpha-2b, at least 3 million units administered
3 times per week for at least 3 months) or lamivudine (at least
100 mg administered once-daily for at least 30 consecutive days),
or that added Chinese remedies to interferon or lamivudine to
see if the combination worked better than the Western drugs
alone. They also looked at which specific Chinese herbs are
used most often.
The initial search included both randomized controlled trials
(RCTs) -- the "gold standard" for Western drug testing
-- and other types of studies that reported objective outcome
measures such as serum alanine aminotransferase (ALT) normalization,
HBV DNA viral load clearance, or hepatitis B "e" antigen
A total of 643 reports were selected for inclusion (596 in Chinese,
47 in English). Of these, 487 were clinical trials (356 RCT
and 131 non-RCT), 80 were pre-clinical experimental studies,
and 76 were summaries of non-randomized clinical experience.
Out of these studies, the researchers identified 53 RCTs that
reported random allocation of patients with chronic hepatitis
B to treatment with TCM formulations; these trials met the inclusion
criteria and were used in the meta-analysis. The studies used
a variety of TCM formulations, with an average of 9 ingredients,
but approximately 50%-60% of the herbs overlapped across different
Overall, the quality of studies was judged to be "poor";
16 (27%) of the 53 RCTs had Jadad scores (a standard algorithm
for assessing trials) of 3, while the rest (73%) had scores
of 2. None of the reports described methods used for randomization
or whether they were double-blind, single-blind, or unblinded.
Among the 53 selected RCTs, 16 (1918 total participants) compared
responses in patients receiving TCM formulations alone versus
interferon, 6 RCTs (723 total participants) compared TCM alone
versus lamivudine,18 trials (1738 total participants) compared
TCM plus interferon versus interferon alone, and another 14
trials (1548 total participants) compared TCM plus lamivudine
versus lamivudine alone
total of 203 different herbs were included in 230 TCM formulations
for the treatment of chronic hepatitis B.
formulations alone had a significantly greater beneficial
effect than interferon for ALT normalization (odds ratio
[OR] 2.42, or 2.4-fold greater; P = 0.0003).
formulations and interferon had a statistically similar
likelihood of reducing HBeAg (OR 1.60; P = 0.07).
and interferon also performed similarly with regard to HBV
viral load clearance (OR 1.31; P = 0.20).
formulations were significantly more effective than lamivudine
for normalizing ALT (OR 1.96, or nearly twice as effective;
P = 0.01).
and lamivudine showed no significant difference in likelihood
of reducing HBeAg (OR 1.57; P = 0.36).
TCM and lamivudine were about equally likely to produce
HBV DNA clearance (OR 1.20; P = 0.59).
used in combination, TCM plus interferon enhanced antiviral
activity and liver function improvement compared with interferon
normalization: OR 3.07, or about 3-fold greater benefit
(P < 0.00001);
reduction: OR 2.17, or about twice the benefit (P
DNA clearance: OR 2.05, again about twice the benefit
(P < 0.00001).
formulations plus lamivudine were also significantly more
effective than lamivudine alone:
normalization: OR 3.40 (P < 0.00001).
reduction: OR 2.54 (P < 0.00001);
DNA clearance: OR 3.20 (P < 0.00001);
a similar analysis of the 16 RCTs of higher technical quality
(Jadad scores of 3), the pattern of the results were similar.
20 RCTs that included information about adverse events,
no serious adverse side effects of TCM formulations were
Based on these findings, the review authors concluded, "Some
TCMs seem effective as alternative remedies for patients with
chronic hepatitis B, suggesting that further study of TCMs in
the treatment of chronic hepatitis B is warranted, both in preclinical
models of HBV infection and in higher quality RCTs worldwide."
"Our meta-analysis suggests that in patients with chronic
hepatitis B, (1) TCMs have a similar curative effect as interferon/lamivudine
on antiviral activity as evidenced by the loss of serum HBeAg
and HBV DNA; (2) TCMs have a better effect on normalization
of serum ALT; and (3) TCMs enhance interferon and lamivudine
antiviral activity and improvement of liver function,"
they elaborated in their discussion.
"It is noteworthy that there were no reported serious adverse
events associated with the combinations of TCM studied,"
they added. "As used in China, these formulations seem
to be very well tolerated, although many reports did not include
data on adverse effects of therapy."
Liver-Biliary-Pancreatic Center and the Liver, Digestive
Diseases, and Metabolism Laboratory, NC; McColl-Lockwood Laboratory,
Carolinas Medical Center, Charlotte, NC; Institute of Clinical
Medical Science, China-Japan Friendship Hospital, Beijing, China;
Department of Biology, University of North Carolina at Charlotte,
Charlotte, NC; Department of Medicine, University of North Carolina
at Chapel Hill, Chapel Hill, NC; Departments of Medicine and
Molecular, Microbial & Structural Biology, University of
Connecticut Health Center, Farmington, CT.
Zhang, G Wang, W Hou, and others. Contemporary clinical research
of traditional Chinese medicines for chronic hepatitis B in
China: An analytical review. Hepatology 51(2): 690-698
full text). February 2010.