Researchers analyzed 27 clinical trials in which chronic hepatitis B patients using Chinese herbal medicine alone, or with interferon alfa, were compared with a control group of patients that were taking only interferon alfa. The protein interferon alfa is a standard treatment for hepatitis B infection. Some of its side effects include strong flu-like symptoms, fatigue and depression.
The meta-analysis, to be published Oct. 1 in the American Journal of Public Health, found that the most encouraging results came from patients who used a combination of Chinese herbal treatments and interferon alfa.
"The results are encouraging enough that, if I had chronic hepatitis B and had previously failed interferon alfa treatment, I would talk to my doctor about combining interferon alfa with Chinese herbal medicine," said Michael McCulloch, a doctoral student in epidemiology at UC Berkeley's School of Public Health and lead author of the study.
According to the World Health Organization, 2 billion people worldwide are infected with hepatitis B, 350 million of whom have the chronic form of the disease. About three-fourths of those with chronic hepatitis B live in Asia.
"There is a wealth of data about hepatitis B from researchers in Asia because the disease is endemic in that part of the world, but accessing that information has been - and still is - difficult because few of those studies are published in English-language journals," said McCulloch, who is also a research fellow at the Chinese Academy of Sciences in Beijing.
McCulloch, who earned his bachelor's degree in Chinese studies at UC Berkeley, searched through six databases of medical literature, including clinical trials data published in Chinese-language journals.
The ingredients in the herbal treatments included mixtures of plant and root extracts, and they varied from study to study. Two of the 27 studies specifically looked at bufotoxin, an extract from the skin of the toad Bufo gargarizans. Another two studied kurorinone, an extract from the root of the plant Sophorae flavescentis.
The authors only included trials in which patients used Chinese herbal medicine alone or with interferon alfa and were then compared with a control group using only interferon alfa at least three times per week. The studies were required to include data on at least one of three markers of infection: levels of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA. All three measures indicate an active infection.
Overall, Chinese herbal medicine combined with interferon alfa was 1.5 to 2 times as effective as interferon alfa alone in reducing the hepatitis B viral load to undetectable levels for all three measures of infection. In particular, bufotoxin combined with interferon alfa was significantly more effective than interferon alfa alone in measures of HBeAg and HBV DNA, but not for measures of the surface antigen. Kurorinone was nearly as effective as interferon alfa in the two studies that tested it.
For measures of the surface antigen, patients receiving herbal treatment alone performed twice as well as those receiving only interferon alfa. The results did not differ significantly between the two groups for measures of HBeAg or HBV DNA.
"Bufotoxin and kurorinone have been singled out as having the best potential for being investigated for drugs," said McCulloch, a licensed acupuncturist for 16 years. "However, it may be that the key to the way these herbal therapies work is by acting together as a group. That's one of the great challenges in studying herbal treatments, yet it is one of the most fascinating aspects of Chinese medicines. These particular mixtures are a distillation of centuries of clinical use."
The investigators also showed that the quality of the studies left much room for improvement. Many of the studies had incomplete information on how patients were randomized, and "blinding" of patients and doctors to the type of treatment administered did not occur in most of the studies.
"We cannot make firm conclusions about the use of Chinese herbal medicines based upon the results from these clinical trials," said Dr. Jack Colford, associate professor of epidemiology at UC Berkeley's School of Public Health and senior researcher for the study. "But the findings revealed by this analysis certainly justify additional investigation of these herbal therapies in more rigorous trials."
Other co-authors of the study are Michael Broffman, co-founder with McCulloch of the Pine Street Clinic in San Anselmo; and Dr. Jin Gao, senior researcher and director of the Institute of Biophysics at the Chinese Academy of Sciences.