Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis:Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.

Chinese medicine formulas for nonalcoholic fatty liver disease: Overview of systematic reviews

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)affects more than one-quarter of the global population.Due to the lack of approved chemical agents,many patients seek treatment from traditional Chinese medicine(TCM)formulas.A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD.AIM To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD.METHODS Seven databases were systematically searched from their inception to 28 February 2020.The search terms included“non-alcoholic fatty liver disease,”“Chinese medicines,”“systematic review,”and their synonyms.Systematic reviews involving TCM formulas alone or in combination with conventional medications were included.The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2)and Risk of Bias in Systematic Review(ROBIS).The quality of outcomes was assessed by the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system.RESULTS Seven systematic reviews were ultimately included.All systematic reviews were conducted based on randomized controlled trials and published in the last decade.According to the AMSTAR 2 tool,one systematic review was judged as having a moderate confidence level,whereas the other studies were rated as having a low or extremely low level of confidence.The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns.According to the GRADE system,only two outcomes were determined as high quality;namely,TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement,and TCM formulas were superior to antioxidants in alanine aminotransferase normalization.Other outcomes were downgraded to lower levels,mainly because of heterogeneity among studies,not meeting optimal information sample size,and inclusion of excessive numbers of small sample studies.Nevertheless,the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness.CONCLUSION The quality of available systematic reviews was not satisfactory.Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.

A Protocol for Developing a Clinical Practice Guideline for Therapeutic Drug Monitoring of Vancomycin

This study aimed to develop a guideline for therapeutic drug monitoring（TDM） of vancomycin. We adopted the new guideline definition from the Institute of Medicine（IOM）, adhered closely to the six domains of the Appraisal of Guidelines for Research ＆ Evaluation Ⅱ（AGREE Ⅱ）, and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome（PICO） and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation（GRADE）.