Review question
To assess the benefits and harms of Radix Sophorae flavescentis versus other medicines or herbs in people with chronic hepatitis B.
Background
Chronic hepatitis B virus (HBV) infection is a common liver disease, associated with high morbidity (illness) and death. It causes psychological stress and is a burden to people with chronic hepatitis B and their families. Radix Sophorae flavescentis is for treating people with chronic hepatitis B as it is believed that it decreases discomfort and prevents the replication of the virus in people with chronic hepatitis B. However, the benefits and harms are still unclear.
Search date
We searched scientific databases in December 2018.
Study characteristics
We included 10 randomised clinical trials (clinical studies where people are randomly put into one of two or more treatment groups) with 898 participants. All the trials were at high risk of bias. The trials covered oral capsules, intravenous (into a vein) infusion, intramuscular (into a muscle) injection, and acupoint (a specifically chosen site of acupuncture) injection of Radix Sophorae flavescentis with treatment duration from 1 month to 12 months. Radix Sophorae flavescentis was compared with lamivudine, adefovir, interferon, tiopronin, thymosin, and other Chinese herbs. Two trials included children up to 14 years old. Participants in one trial had cirrhosis (late stage of scarring of the liver) in chronic hepatitis B.
Study funding sources
Two of the 10 trials were not funded, and one received governmental funding. The remaining seven trials provided no information on funding. Undisclosed funding may have influence on trial results and lead to poor design of the trial.
Key results
None of the trials reported health-related quality of life (a measure of a person's satisfaction with their life and health), or followed people who have died from any reason or died from hepatitis B, or who were at risk of dying because of hepatitis B. Side effects considered 'not to be serious' was an outcome in two trials. We could not say if Radix Sophorae flavescentis versus other medicines or herbs was better or worse regarding the occurrence of side effects considered 'not to be serious'. We were uncertain whether Radix Sophorae flavescentis had a positive, neutral, or negative effect on the proportion of participants with detectable HBV-DNA (the genetic blueprint of the virus). Radix Sophorae flavescentis may have reduced the proportion of participants with detectable hepatitis B virus e-antigen (HBeAg; produced by the immune system). However, caution is needed with these findings as the trials providing data on them were small, at high risk of bias, and these outcomes have not yet been proven relevant to people with HBV infection. We identified 109 trials that not be included because of lack of information required for the conduct of this review. Accordingly, more information from properly designed randomised clinical trials is needed before one can determine the benefits or harms of Radix Sophorae flavescentis for people with chronic hepatitis B.
Certainty of the evidence
Certainty of evidence means 'the extent of one's confidence that review results are correct in supporting or rejecting a finding.' The certainty of the evidence on the use of Radix Sophorae flavescentis in people with chronic HBV in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to HBV infection, and serious side effects cannot be determined as none of the trials reported patient-relevant outcomes. Our certainty in the evidence that Radix Sophorae flavescentis, when compared with other medicines or herbs, would decrease or increase side effects considered 'not to be serious' and number of people with detectable HBV-DNA is very low. Our certainty in the evidence that Radix Sophorae flavescentis decreases the number of people with detectable HBeAg is also very low. These assessments of certainty of evidence are due to the poor design and reporting of the included trials.
The included trials lacked data on all-cause mortality, health-related quality of life, serious adverse events, hepatitis-B related mortality, and hepatitis-B related morbidity. The evidence on the effect of Radix Sophorae flavescentis on the proportion of participants with adverse events considered 'not to be serious' and on the proportion of participants with detectable HBV-DNA is still unclear. We advise caution regarding the results of Radix Sophorae flavescentis showing a reduction in the proportion of people with detectable HBeAg because the trials were at high risk of bias, because it is a non-validated surrogate outcome, and because of the very low certainty in the evidence. As we were unable to obtain information on a large number of studies regarding their trial design, we were deterred from including them in our review. Undisclosed funding may have influence on trial results and lead to poor design of the trial. In view of the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials assessing patient-centred outcomes.
Hepatitis B virus (HBV) infection is a liver disease caused by hepatitis B virus, which may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may also have coinfections including HIV and other hepatitis viruses (hepatitis C or D), and coinfections may increase the risk of all-cause mortality. Chronic HBV infection increases morbidity, psychological stress, and it is an economic burden on people with chronic hepatitis B and their families. Radix Sophorae flavescentis, a herbal medicine, is administered mostly in combination with other drugs or herbs. It is believed that it decreases discomfort and prevents the replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Radix Sophorae flavescentis on patient-centred outcomes are unknown, and its wide usage has never been established with rigorous review methodology.
To assess the benefits and harms of Radix Sophorae flavescentis versus other drugs or herbs in people with chronic hepatitis B.
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and seven other databases to December 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to December 2018.
We included randomised clinical trials, irrespective of publication status, language, or blinding, comparing Radix Sophorae flavescentis versus other drugs or herbs for people with chronic hepatitis B. In addition to chronic hepatitis B, participants could also have had cirrhosis, hepatocellular carcinoma, or any other concomitant disease. We excluded polyherbal blends containing Radix Sophorae flavescentis. We allowed cointerventions when the cointerventions were administered equally to all intervention groups.
Review authors in pairs individually retrieved data from published reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risk of bias using domains with predefined definitions. We conducted Trial Sequential Analyses to control the risks of random errors. We used GRADE methodology to evaluate our certainty in the evidence (i.e. "the extent of our confidence that the estimates of the effect are correct or are adequate to support a particular decision or recommendation").
We included 10 randomised clinical trials with 898 participants. We judged all trials at high risk of bias. The trials covered oral capsules, intravenous infusion, intramuscular injection, and acupoint (a specifically chosen site of acupuncture) injection of Radix Sophorae flavescentis with a follow-up period from 1 to 12 months. The drugs being used as a comparator were lamivudine, adefovir, interferon, tiopronin, thymosin, or other Chinese herbs. Two trials included children up to 14 years old. Participants in one trial had cirrhosis in chronic hepatitis B. None of the trials reported all-cause mortality, health-related quality of life, serious adverse events, hepatitis B-related mortality, or morbidity. We are uncertain as to whether Radix Sophorae flavescentis has a beneficial or harmful effect on adverse events considered 'not to be serious' (RR 0.86, 95% CI 0.42 to 1.75; I2 = 0%; 2 trials, 163 participants; very low-certainty evidence), as well as if it decreases or increases the proportion of participants with detectable HBV-DNA (RR 1.14, 95% CI 0.81 to 1.63; I2 = 92%; 8 trials, 719 participants; very low-certainty evidence). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable hepatitis B virus e-antigen (HBeAg) (RR 0.86, 95% CI 0.75 to 0.98; I2 = 43%; 7 trials, 588 participants; very low-certainty evidence).
Two of the 10 trials were not funded, and one received academic funding. The remaining seven trials provided no information on funding.
The randomisation process in another 109 trials was insufficiently reported to ensure the inclusion of any of these studies in our review.