Abstract: We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two of the trials included children up to 14 years old. Participants in two trials had cirrhosis in addition to chronic hepatitis B. All trials were assessed at high risk of bias, and certainty of the evidence for all outcomes was very low. Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials reported health-related quality of life, hepatitis B-related mortality, or morbidity. Adverse events considered 'not to be serious' was an outcome in 19 trials; nine of these trials had zero events in both groups. Radix Sophorae flavescentis versus placebo or no intervention showed no difference in effects on adverse events considered 'not to be serious' (RR 1.10, 95% CI 0.76 to 1.59; I² = 49%; 10 trials, 1050 participants). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable HBV-DNA (RR 0.61, 95% CI 0.55 to 0.68; I² = 56%; 29 trials, 2914 participants) and in the proportion of participants with detectable HBeAg (hepatitis B e-antigen) (RR 0.71, 95% CI 0.66 to 0.76; I² = 19%; 20 trials, 2129 participants). Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding. Additionally, 432 trials lacked the methodological information needed to ensure inclusion of these trials in our review. The included trials lacked data on health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The effects of Radix Sophorae flavescentis on all-cause mortality and on the proportion of participants with serious adverse events and adverse events considered 'not to be serious' remain unclear. We advise caution in interpreting results showing that Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and detectable HBeAg because the trials reporting on these outcomes are at high risk of bias and both outcomes are non-validated surrogate outcomes. We were unable to obtain information on the design and conduct of a large number of trials; therefore, we were deterred from including them in our review. Undisclosed funding may influence trial results and may lead to poor trial design. Given the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials in which patient-centred outcomes are assessed.

Plain-language summary: We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two trials assessed children under 14 years of age. Participants in two trials had cirrhosis in chronic hepatitis B (late-stage scarring of the liver). Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding. Undisclosed funding may influence trial results and may lead to poor trial design. Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials assessed health-related quality of life, and no trials followed people who died from hepatitis B or were at risk of dying because of hepatitis B. Adverse events considered 'not to be serious' was an outcome in 19 trials. We cannot say if Radix Sophorae flavescentis versus placebo or no intervention is better or worse regarding the occurrence of adverse events considered 'not to be serious'. Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and also the proportion of people with detectable HBeAg. However, caution is needed to understand these beneficial findings, as these trials were at high risk of bias, and these outcomes have not yet been proven relevant to patients. The 432 trials identified could not be included in the review 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 evidence' means "the extent of one's confidence that review results are correct in supporting or rejecting a finding". The certainty of evidence on the use of Radix Sophorae flavescentis for 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 adverse events cannot be determined, as only a few trials aimed to explore patient-relevant outcomes. Our certainty in the evidence that Radix Sophorae flavescentis, when compared with no intervention or placebo, decreases or increases adverse events considered not to be serious in people with chronic hepatitis B is very low. Our certainty in the evidence that Radix Sophoae flavescentis decreases the proportion of people with detectable HBV-DNA and the proportion 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.