A Systematic Review Of Randomized Controlled Trials Of Herbal Medicines For The Treatment Of Hepatitis

Hepatitis c is a global infectious disease,affecting an estimated 115 million people worldwide and posing a serious threat to human health.At present,there are many problems that need to be solved,such as many adverse reactions,high cost and potential drug resistance risk.As with many other disease conditions,patients with hepatitis C often seek for the help of complementary and alternative medicine when they are dissatisfied with or develop resistance to conventional western medicine.In recent years,medicinal herbs have been proved to have certain efficacy in the treatment of hepatitis C in clinical practice and research,and are still widely used in clinical practice today.A large number of randomized controlled clinical trials have been published.However,due to the low application rate of its research results,it fails to provide high-level evidence for the formulation of clinical practice guidelines,and many treatment methods and formulas are difficult to summarize and popularize.It is of great significance to further improve the quality of clinical research on the treatment of hepatitis c with medicinal herbs and to form high-level evidence for promotion.The first part of our research is the literature review on the treatment of hepatitis C.The second part is the study on the quality evaluation of medicinal herbs in the treatment of hepatitis C.The third part is the systematic review of the efficacy and safety of medicinal herbs in randomized controlled trial of hepatitis C.Methods:the randomized controlled trials of 10 domestic and foreign databases and 3 clinical trial registries were searched systematically.The intervention is medicinal herbs,while the treatment group included traditional Chinese medicine decoction,traditional Chinese medicine preparations(tablet,pill,powder,capsule,injection,etc.)and herbal medicines,and the active ingredient extracts of medicinal materials and plant parts all belonged to the category of medicinal herbs.Control measures were no treatment,placebo,specific antiviral treatment and non-specific symptomatic support.In quality assessment research,data were extracted before the methodological quality and reporting quality of randomized controlled trials were evaluated using the Cochrane "risk of bias assessment" tool and the CONSORT(2010 edition)entry,and the outcomes of existing clinical studies were summarized.The outcome measures in the systematic review includes all-cause mortality,serious adverse events,health-related quality of life,HCV liver related mortality,HCV related complications,sustained virological response,non-serious adverse events,biochemical responses,and separate reports of adverse events.Literature screening,data extraction and methodological quality evaluation were conducted according to Cochrane systematic review Hand Book.We use Revman5.3 for data synthesis and sequential analysis of experiments.Results:114 clinical studies meeting the inclusion criteria were included for quality evaluation.The implementation report rates of randomized method,allocation concealment,blind method,dropouts and scheme registration were 17.5%,4.4%,14%,20.2%and 5.3%,respectively.Among the 37 items of CONSORT(2010 edition),the ones with good reporting quality were structural summary,inclusion criteria,intervention measures and statistical methods.The general quality of the report is the location and location of data collection,the recruitment period and follow-up time,hazards;The remaining items report poor quality or range(item reporting rate≤10%).English studies reported more entries(P<0.001).Of these 114 studies,27 outcomes were reported,with alanine aminotransferase levels most frequently reported(64 RCT,56.1%),adverse events(58 RCT,50.9%),and early virological response(50 RCT,43.9%).The systematic review included 24 randomized controlled trials involving 1946 subjects.All studies were rated as having a high risk of bias.Three studies reported all-cause mortality,involving 3 subjects:suicide,liver cancer death,and unexplained death;5 studies reported no significant differences in the incidence of serious adverse events.Five studies reported quality of life(SF-36,Chronic Liver Disease Questionnaire,WHO Self-administered Quality of Life Questionnaire,Arizona Sexual Experience Scale and Quality of Life Questionnaire),and there was no difference between groups.Meta-analysis:1.All-cause mortality:two studies showed no significant difference between medicinal herbs and placebo(FE,RD=0.01,95%CI[-0.03,0.06],I2=0,168 subjects);2.Serious adverse events:4 studies showed no significant difference between medicinal herbs and placebo(FE,RD=0.03,95%CI[-0.01,0.08],I2=0,270 subjects);3.Sustained virology response:9 studies showed that medicinal herbs combined with antiviral therapy were superior to antiviral drugs alone(FE,RR=0.75,95%CI[0.62,0.91],I2=54%,620 subjects).Subgroup analysis showed that TCM compound combined with antiviral therapy was superior to antiviral drugs alone(FE,RR=0.66,95%CI[0.51,0.85],I2=0%,548 subjects).4.Non-serious adverse events:nine studies have shown that the incidence of serious adverse events of medicinal herbs was obviously higher than that of placebo(FE,RR=1.28,95%CI(1.07,1.54],I2=37%,877 participants),6 study medicinal herbs combined with antiviral treatment significantly lower incidence of serious adverse events,with antiviral drugs(FE,RR=0.89,95%Cl(0.82,0.98],I2=70%,442 subjects);5.Biochemical response:four studies showed that combination antiviral therapy with medicinal herbs was superior to antiviral drugs alone(FE,RR=0.66,95%CI[0.45,0.93],I2=0,219 subjects).Conclusion:in patients with hepatitis C,current studies suggest that medicinal herbs combined with antiviral therapy may be more effective in achieving durable virology response and negative transformation of alanine aminotransferase,and that the incidence of non-serious adverse events associated with medicinal herbs combined with antiviral therapy is lower than that associated with antiviral therapy alone.However,sequential analysis of the trials shows that the sample size required for meta-analysis has not been reached yet,and more studies should be included in the future to verify the efficacy and safety of medicinal herbs combined with antiviral drugs in the treatment of hepatitis C.The number of serious adverse event reports included in the study is limited and safety outcomes should be treated with caution.Due to the limitations of methodological quality,research quantity and sample size,the evidence level is relatively low.Medicinal herbs may be tried as complementary treatments for the disease.It is recommended that the three core outcomes,all-cause mortality,severe adverse events and quality of life,be observed and reported in future clinical studies.At the same time,the follow-up time was extended as long as possible to evaluate the long-term efficacy of herbal preparations or end-point outcome events,such as the incidence of complications and hepatitis C-related mortality.