Clinical Assessment of Common Medications for Nonalcoholic Fatty Liver Disease: A Systematic Review and Bayesian Network Meta-Analysis.

With a steadily rising prevalence, nonalcoholic fatty liver disease (NAFLD) was a leading global cause of liver-related health problems. In the clinical management of NAFLD, various western pharmaceuticals were widely utilized. This network meta-analysis aimed to evaluate the effectiveness of common western medications for NAFLD patients. We systematically reviewed and screened articles based on predesigned criterion about western medications for NAFLD, which were from Embase, Cochrane Library, PubMed, CNKI, WanFang, and China Science and Technology Journal Database until August 1, 2024. Eligible studies included randomized controlled trials of patients aged 18 or older with NAFLD, comparing Western medicines to placebos or other Western medicine treatments. The risk of bias assessment tool 2.0 from the Cochrane system was used to assess the quality of the included articles. A Bayesian network meta-analysis was conducted using WinBUGS 1.4.3 with a random-effects model and Markov Chain Monte Carlo methods. Treatment rankings were based on Surface Under the Cumulative Ranking Curve (SUCRA) values, and heterogeneity was assessed with I2 and Q statistics. The outcomes were analyzed in WinBUGS and visualized using Stata 14.0, generating network plots and cumulative probability rankings to compare treatment effects. The systematic review was registered in PROSPERO (CRD42024509176). Based on 37 included articles involving 7673 patients, pioglitazone demonstrated the most significant effects in resolving nonalcoholic steatohepatitis without worsening fibrosis, increasing high-density lipoprotein cholesterol levels, and achieving a ≥ 2-point reduction in NAFLD activity scores (odds ratio [OR] = 0.09, 95% confidence interval [CI]: 0.01 to 0.81), with a SUCRA probability of 91.4%. Aldafermin showed remarkable effects in improving liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase, with cumulative probabilities of 90% for ALT and 69.8% for AST. Cluster analysis revealed that Resmetirom and Aldafermin were superior options for enhancing liver function, while pioglitazone emerged as the best treatment for the comprehensive improvement of NAFLD. Pioglitazone outperformed other western medicines in terms of overall efficacy when treating NAFLD, but Aldafermin and Resmetirom showed superior improvement in liver function. This study provided a certain level of support for the use of specific clinical medications.

Shi R ，Chai K ，Wang H ，Zhou J ，Yang S ，Li J ，Qiao C ，Sheng X ，Zhang X ，Wu J ... -  《-》

Comparative effectiveness of five Chinese patent medicines for non-alcoholic fatty liver disease: A systematic review and Bayesian network meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is a metabolically stressed liver injury closely related to insulin resistance and genetic susceptibility and has become the leading chronic liver disease in China. To analyze the effectiveness of five Chinese patent medicines used alone or in combination with western medications (WM) for NAFLD using Bayesian network meta-analysis. Searches were conducted in Embase, Cochrane Library, PubMed, CNKI, Wanfang Database, VIP, and SinoMed for randomized controlled trials (RCTs) on Danning tablets, Huazhi Rougan granules, Dangfei Liganning capsules, Kezhi capsules, and Qianggan capsules, either alone or in combination with WM for NAFLD, up to January 10, 2024. This study was screened based on pre-designed inclusion and exclusion criteria, and the risk of bias was evaluated using the Cochrane ROB2 tool. The primary outcome was clinical efficacy rate, while secondary outcomes included levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglycerides (TG), and Low-density lipoprotein cholesterol (LDL-C). These data will be analyzed using WinBUGS 1.4.3 and then visualized using Stata 14.0 software. A total of 77 RCTs involving 7770 patients were included. The results indicated that Huazhi Rougan granules combined with WM (OR = 0.13, 95 % CI 0.05 ∼ 0.26) had a SUCRA probability value of 81.7 %, ranked first in clinical efficacy and significantly improved blood lipids levels including TG, High-density Lipoprotein Cholesterol (HDL-C), and LDL-C, Total cholesterol (TC). For the Chinese patent medicines alone, Danning tablets led with a 75.3 % clinical efficacy rate. Huazhi Rougan granules significantly increased levels of ALT (96.2 %) and AST (MD = -14.48, 95 % CI -23.38 ∼ -5.32). Dangfei Liganning capsules demonstrated significant efficacy in improving TG (73.1 %) and TC (83 %) levels. In the treatment of NAFLD, the combination of Huazhi Rougan granules and WM demonstrated significant clinical effectiveness and improvement in blood lipid profiles. For different outcome indicators, Danning tablets used alone showed the highest clinical efficacy, while significant improvement in liver function indicators was best achieved with Huazhi Rugan granules used alone.

Shi R ，Chai K ，Wang H ，Guo S ，Zhai Y ，Huang J ，Yang S ，Li J ，Zhou J ，Qiao C ，Sheng X ，Zhang X ，Wu J ... -  《-》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: A systematic review and Bayesian network meta-analysis of randomized controlled trials.

Sepsis or septic shock is a life-threatening medical emergency with a poor prognosis and a high economic burden for both individuals and healthcare resources. Evidence suggests that Chinese tonic medicines (CTMs), as adjuvant treatments, are effective in treating this disease. Nevertheless, the ongoing discourse regarding the optimal CTMs persists. This study was conducted to further explore the comparative effectiveness of CTMs for patients with sepsis or septic shock. We systematically searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP database from inception to November 15, 2023. Primary outcomes encompassed the delta Sequential Organ Failure Assessment (ΔSOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes included delta serum lactate (ΔLac) and delta mean arterial pressure (ΔMAP) levels at day 7 after interventions, as well as the duration of vasoactive drug administration. The safety outcome was adverse drug reactions or adverse drug events (ADRs/ADEs). The risk ratio (RR) and mean difference (MD) with a 95 % confidence interval (95 %CI) were selected as effect measures. The Bayesian network meta-analysis was conducted by R version 4.2.2 software. The surface under the cumulative ranking curve (SUCRA) values were used to rank each treatment. The Cochrane Risk of Bias V.2.0 tool was employed to assess the within-study risk of bias. The CINeMA (Confidence in Network Meta-Analysis) web application was utilized to assess the quality of evidence. This protocol was prospectively registered in PROSPERO (CRD4202348572). A total of 45 randomized controlled trials (RCTs) involving 3433 patients were identified in this study. Seven CTMs including Shenfu injection (SF), Shenmai injection (SM), Sini decoction (SN), Shenfu and Shengmai granules (SF+SGM), Shengmai injection (SGM), Yiqifumai injection (YQFM), and Shenqifuzheng injection (SQFZ) were involved. Regarding the ΔSOFA score, interventions combining SM with Western medicine (WM) (MD, -2.77; 95 %CI, -3.28 to -2.27), YQFM+WM (MD, -1.76; 95 %CI, -2.73 to -0.79), SGM+WM (MD, -1.11; 95 %CI, -1.88 to -0.34), and SF+WM (MD, -0.98; 95 %CI, -1.17 to -0.78) demonstrated superiority over WM alone. According to the SUCRA values, SM+WM (99.28 %) achieved the highest ranking for the ΔSOFA score. Concerning 28-day mortality, SM+WM (RR, 0.51; 95 %CI, 0.35 to 0.72) and SF+WM (RR, 0.73; 95 %CI, 0.65 to 0.83) exhibited a superior effect in reducing 28-day mortality. Based on the SUCRA values, SM+WM (82.49 %) secured the top ranking for 28-day mortality. Among the secondary outcomes, SM+WM (MD, -2.50; 95 %CI, -4.15 to -0.83; SUCRA, 94.27 %) emerged as the most favorable in reducing serum lactate levels. SF+WM (MD, 10.78; 95 %CI, 3.11 to 18.71; SCURA, 78.3 %) exhibited superior effectiveness compared to other treatments in improving mean arterial pressure (MAP). The certainty of evidence for these outcomes was assessed as low. CTMs combined with WM led to a significant improvement in ΔSOFA score and MAP, as well as a reduction in 28-day mortality and serum lactate levels. SM+WM emerged as the optimal treatment regimen for enhancing ΔSOFA, reducing 28-day mortality, and lowering serum lactate levels. Additionally, SF+WM exhibited superiority in improving MAP. Nevertheless, there is a need for large-scale, multicenter, and direct comparative RCTs to generate higher-quality evidence.

Yang R ，Hu C ，Zhuo Y ，Tan Q ，Shen Y ，Jiang K ，Xia Q ，Deng L ... -  《-》

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms. For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation). We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety). This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Sbidian E ，Chaimani A ，Guelimi R ，Garcia-Doval I ，Hua C ，Hughes C ，Naldi L ，Kinberger M ，Afach S ，Le Cleach L ... -  《Cochrane Database of Systematic Reviews》