Review question
To assess the benefits and harms of acupuncture versus no intervention or sham acupuncture (not real acupuncture) in people with chronic hepatitis B.
Background
Chronic hepatitis B infection has a substantial economic, psychological, and life impact on people with chronic hepatitis B and their families. Acupuncture has been used in treating people with chronic hepatitis B, as it is believed that it decreases discomfort and improves immune function in people with this disease. However, the benefits and harms of acupuncture have never been established in systematic reviews in a rigorous way.
Search date
The review includes trials published by 1 March 2019.
Study characteristics
We included eight randomised clinical trials with 555 participants. All trials compared acupuncture versus no intervention. Seven trials included participants with chronic hepatitis B. One trial included chronic hepatitis B participants with tuberculosis and ascites. These trials assessed heterogeneous acupuncture interventions (i.e. manual needle acupuncture, acupoint herbal patching, acupoint injection, and moxibustion). Acupoint is a specifically chosen site for acupuncture manipulation. All trials used heterogeneous co-interventions applied equally in the compared groups.
Study funding sources
Three of the eight included randomised clinical trials received academic funding. None of the remaining five trials reported information on support or funding.
Key results
None of the eight included trials reported data on clinically important outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. We are uncertain whether acupuncture compared with no intervention has a beneficial or harmful effect regarding adverse events considered not to be serious. Acupuncture compared with no intervention seems to reduce the proportion of people with detectable hepatitis B virus (HBV) DNA (a non-validated surrogate outcome; only one trial). We are uncertain whether acupuncture compared with no intervention has an effect on the proportion of people with detectable HBeAg (a non-validated surrogate outcome; only two trials). Caution is needed in interpreting these findings as data are provided by only one or a few trials at high risk of bias, and these surrogate outcomes have not yet been proven relevant for people with chronic hepatitis B. We are uncertain whether acupuncture compared with no intervention has an effect on the remaining separately reported adverse events considered not to be serious. We could not use data from 79 other studies, of possible interest to our review, because study authors provided highly insufficient information on their study design and methods. Accordingly, we need more information from randomised clinical trials before benefits or harms of acupuncture for chronic hepatitis B can be determined.
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 evidence on the use of acupuncture in people with chronic hepatitis B virus infection 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 data on these outcomes were lacking. The certainty of evidence on acupuncture, when compared with no intervention, in terms of adverse events considered not to be serious, the proportion of people with detectable HBV DNA, and the proportion of people with detectable HBeAg, is very low. Whether the last two outcomes are relevant to the well-being of people with chronic hepatitis B is still not scientifically proven. The very low certainty of the evidence is due to insufficient data ensuing from one, two, or very few trials with insufficient reporting.
The clinical effects of acupuncture for chronic hepatitis B remain unknown. 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 vast number of excluded trials lacked clear descriptions of their design and conduct. Whether acupuncture influences adverse events considered not to be serious is uncertain. It remains unclear if acupuncture affects HBeAg, and if it is associated with reduction in detectable HBV DNA. Based on available data from only one or two small trials on adverse events considered not to be serious and on the surrogate outcomes HBeAg and HBV DNA, the certainty of evidence is very low. In view of the wide usage of acupuncture, any conclusion that one might try to draw in the future should be based on data on patient and clinically relevant outcomes, assessed in large, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding.
Chronic hepatitis B is a liver disease associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming to reduce the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, as well as to improve health-related quality of life. Acupuncture is being used to decrease discomfort and improve immune function in people with chronic hepatitis B. However, the benefits and harms of acupuncture still need to be established in a rigorous way.
To assess the benefits and harms of acupuncture versus no intervention or sham acupuncture in people with chronic hepatitis B.
We undertook electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and SinoMed to 1 March 2019. 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 (ChiCTR) for ongoing or unpublished trials until 1 March 2019.
We included randomised clinical trials, irrespective of publication status, language, and blinding, comparing acupuncture versus no intervention or sham acupuncture in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B as defined by the trialists or according to guidelines. We allowed co-interventions when the co-interventions were administered equally to all intervention groups.
Review authors in pairs individually retrieved data from reports and through correspondence with investigators. Primary outcomes were all-cause mortality, proportion of participants with one or more serious adverse events, and health-related quality of life. Secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered not to be serious. We presented the pooled results as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed the risks of bias using risk of bias domains with predefined definitions. We put more weight on the estimate closest to zero effect when results with fixed-effect and random-effects models differed. We evaluated the certainty of evidence using GRADE.
We included eight randomised clinical trials with 555 randomised participants. All included trials compared acupuncture versus no intervention. These trials assessed heterogeneous acupuncture interventions. All trials used heterogeneous co-interventions applied equally in the compared groups. Seven trials included participants with chronic hepatitis B, and one trial included participants with chronic hepatitis B with comorbid tuberculosis. All trials were assessed at overall high risk of bias, and the certainty of evidence for all outcomes was very low due to high risk of bias for each outcome, imprecision of results (the confidence intervals were wide), and publication bias (small sample size of the trials, and all trials were conducted in China). Additionally, 79 trials lacked the necessary methodological information to ensure their inclusion in our review.
None of the included trials aim to assess all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. We are uncertain whether acupuncture, compared with no intervention, has an effect regarding adverse events considered not to be serious (RR 0.67, 95% CI 0.43 to 1.06; I² = 0%; 3 trials; 203 participants; very low-certainty evidence) or detectable hepatitis B e-antigen (HBeAg) (RR 0.64, 95% CI 0.11 to 3.68; I² = 98%; 2 trials; 158 participants; very low-certainty evidence). Acupuncture showed a reduction in detectable hepatitis B virus (HBV) DNA (a non-validated surrogate outcome; RR 0.45, 95% CI 0.27 to 0.74; 1 trial, 58 participants; very low-certainty evidence). We are uncertain whether acupuncture has an effect regarding the remaining separately reported adverse events considered not to be serious.
Three of the eight included trials received academic funding from government or hospital. None of the remaining five trials reported information on funding.