Some benefit was shown for particular Chinese herbal medicines, or compounds, in trials of poor methodological quality which reported antiviral and biochemical response rather than clinically relevant outcomes like prolonged survival, mortality, and development of liver cirrhosis or hepatocellular carcinoma. Few trials confirmed the diagnosis of chronic hepatitis B by liver biopsy. At present there is no evidence from high quality studies and the use of Chinese herbal medicines cannot be recommended in this context.

Hepatitis B is an infectious disease of the liver. It is a serious health problem with more than two billion sufferers worldwide, around 350 million of which are chronic carriers of the disease. Associated risks include cirrhosis of the liver and liver cancer from which more than one million people die annually. The virus is spread by contact with infected body fluids or from mother to child. The standard treatment for hepatitis B is alpha-2b-interferon which is expensive, has serious adverse effects and does not always prevent recurrence of the disease. Historically, Chinese herbal medicines have been used to treat liver disease, including chronic hepatitis B.

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Systematic review

Liu JP, McIntosh H, lin H. Chinese medicinal herbs for chronic hepatitis B (Cochrane review). In: The Cochrane Library, Issue 1, 2001. Oxford: Update Software.

Date review completed : Last update June 2000

Number of trials included : Nine

Number of patients : 936 in total

Control group : placebo, alpha-2b-interferon, non-specific treatment (e.g. vitamins, adenosine triphosphate).

Main outcomes : Viral response, biochemical response, adverse effects.

Inclusion criteria were randomised or quasi-randomised controlled trial which assessed Chinese herbal medicine in the treatment of chronic hepatitis B with a minimum follow-up period of three months. Chronic hepatitis B was defined as serum HBsAg positive persisting for at least six months, with elevated aminotransferase (ALT) and/or aspartate aminotransferase (AST) or with recurrent fluctuation, with or without liver biopsy findings compatible with chronic hepatitis. Chinese herbal medicines could consist of a single herb or a combination of herbs, or be used in combination with alpha-2b-interferon.

Medline, EMBASE, BIOSIS, the Cochrane Hepato-Biliary group register and the Cochrane Collaboration trials register were searched. In addition several, mainly Chinese, journals were hand searched. No language restrictions were made. Methodological quality was assessed using a validated scale. Relative risk and weighted mean difference, with 95% confidence intervals, were calculated using pooled data.

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Findings

Nine studies had adequate follow-up and were included in the analyses; these assessed 10 different Chinese herbal medicines. All, except one, of the studies were of poor methodological quality, with a mean sample size of 106 patients (range 25 to 252). The mean age of patients was 32 years. The constituents and dose of the herbs varied. Median duration of treatment was three months (range one to six). Non-specific treatments used as control included vitamins, alcamin, hypoxanthosine, potassium magnesium aspartate, coenzyme A pantothenic acid, and adenosine triphosphate. There was no significant effect of Potenlini, Kangdu Wan, Anisodamine plus salviae miltorrhizae or kuorinone compared with control for any of the assessed outcomes.

Antiviral activity

Fuzheng Jiedu Tang (a compound of herbs) produced significant antiviral activity compared with vitamin plus hypoxanthosine. The relative risks were 5.19 (95% confidence interval 1.24 to 21.79) for clearance of serum HBsAg, 10.85 (3.56 to 33.06) for clearance of serum HBeAg, and 8.50 (1.23 to 58.85) for clearance of serum HBV DNA.

Phyllanthus amarus (a single herb) produced significantly better clearance of serum HBeAg than vitamin plus hypoxanthosine plus alcamin over three months, relative risk 3.35 (1.49 to 7.56). There was no significant difference between Phyllanthus amarus and interferon (5 mega units every two days for three months) on clearance of serum HBeAg and HBV DNA.

Polyporus umbellatus polysaccharide was significantly better than vitamin C plus hypoxanthosine at improving serum HBeAg in two trials; relative risks 3.06 (95% confidence interval 1.13 to 8.29). There was no significant effect of Polyporus umbellatus polysaccharide on clearance of serum HBeAg and HBV DNA.

Eight trials (628 patients) compared Chinese herbs plus interferon with interferon alone. The average dose of interferon was 1.84 mega units per day, and the median duration of treatment was four months. Follow-up was shorter than three months in all studies. Chinese herbal medicine plus interferon was significantly better than interferon alone for clearance of serum HBeAg (relative risk 2.02 (1.63 to 2.51)), HBsAg (relative risk 2.61 (1.10 to 6.21)), and HBV DNA (relative risk (1.90 (1.50 to 2.41)).

Biochemical response

In four trials (189 patients), Chinese herbal medicines were significantly more effective than placebo or non-specific treatment at normalisation of serum ALT, relative risk 1.41 (1.14 to 1.75).

Combinations of Chinese herbal medicine with interferon were significantly more effective than interferon alone at normalisation of serum ALT (204 patients), relative risk 1.66 (1.30 to 2.13). Significant superiority of the combination was also shown in two trials (122 patients) for AST normalisation, relative risk 1.83 (1.31 to 2.55).

Adverse effects

Eight trials mentioned adverse effects. Ascites and lower limb oedema were reported in one patient with early-stage cirrhosis of the liver who took Potenlini. Enlarged lymph nodes which persisted for more than one week were reported with Polyporus umbellatus polysaccharide (8/60 patients). Dry throat was associated with Kang Du Wan. Anisodamine and Salviae miltiorrhizae were associated with thirst and rapid heart rate. None of the reported adverse effects were serious. The reviewers mentioned that Chinese herbal medicines have been reported to cause serious adverse effects, including liver toxicity.

Comment

The included studies were of poor methodological quality. Only two were double blind; the others made no attempt at blinding. In addition, only three trials confirmed the presence of chronic hepatitis B by liver biopsy. Clinically relevant end-points which were not assessed in the trials were mortality, development of liver cirrhosis and hepatocellular carcinoma, and survival. Instead, antiviral and biochemical response were assessed. These showed that Fuzheng Jiedu, Polyporus umbellatus polysaccharide and Phyllanthus amarus were more effective than non-specific treatment or placebo. The evidence for Fuzheng Jiedu was stronger since significant improvement was shown for several antiviral markers. It is not known, though, how effective these non-specific treatments are in chronic hepatitis B. The superiority of combinations of Chinese herbal medicines with interferon over interferon alone relied on an analysis of several different herbal medicines; there was insufficient information to determine the benefit of particular Chinese herbal medicines. At present high quality studies are not available and the results of these trials should be interpreted with caution.

Identifier CHINESE HERBAL MEDICINE FOR CHRONIC HEPATITIS B: Apr-2001

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