In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2.

Cochlear inner hair cells (IHCs) are primary sound receptors, and are therefore a target for developing treatments for hearing impairment. IHC regeneration in vivo has been widely attempted, although not yet in the IHC-damaged cochlea. Moreover, the extent to which new IHCs resemble wild-type IHCs remains unclear, as is the ability of new IHCs to improve hearing. Here, we have developed an in vivo mouse model wherein wild-type IHCs were pre-damaged and nonsensory supporting cells were transformed into IHCs by ectopically expressing Atoh1 transiently and Tbx2 permanently. Notably, the new IHCs expressed the functional marker vGlut3 and presented similar transcriptomic and electrophysiological properties to wild-type IHCs. Furthermore, the formation efficiency and maturity of new IHCs were higher than those previously reported, although marked hearing improvement was not achieved, at least partly due to defective mechanoelectrical transduction (MET) in new IHCs. Thus, we have successfully regenerated new IHCs resembling wild-type IHCs in many respects in the damaged cochlea. Our findings suggest that the defective MET is a critical barrier that prevents the restoration of hearing capacity and should thus facilitate future IHC regeneration studies.

Aesthetic Improvement of Body Proportion Through Trunk Liposculpture: A Waistline-based Strategy.

BACKGROUND: Abdominal contouring through liposuction has been practiced for decades. However, few studies have focused on describing the definition and enhancement of the waistline in torso contouring procedures. OBJECTIVES: In the present study, the authors proposed a waistline-based strategy for abdominal liposculpture to achieve a better aesthetic outcome and emphasize high overall patient satisfaction. METHODS: The data of patients who underwent the waistline-based liposculpture procedure from 2020 to 2023 were retrospectively reviewed. Aesthetic improvement of the central trunk contour was evaluated and analyzed by comparing preoperative and postoperative photogrammetric measurements. Satisfaction with the outcome was assessed with a patient satisfaction questionnaire. RESULTS: A total of 70 patients were enrolled in this study. During 6 months of postoperative evaluation, the shape of the central trunk contour improved significantly (both waist concavity and hip convexity increased quantitatively, P < .05), while the position of the waist did not differ significantly postoperatively (P > .05). All patients were satisfied with their postoperative outcomes, including their overall aesthetic appearance, waistline position, and waist-to-hip ratio. There were no intraoperative complications or rare postoperative complications. CONCLUSIONS: Waistline-based liposculpture is a simple and effective procedure to improve the aesthetic outcomes of trunk contouring and has highly satisfactory results after long-term follow-up.

Lower Gluteal Liposuction Combined With Upper Gluteal and Infragluteal Region Fat Grafting: A Novel Concept to Improve Gluteal Ptosis.

BACKGROUND: Gluteal ptosis results in a severe disturbance of gluteal aesthetics. Currently, satisfactory procedures for improving gluteal ptosis are lacking. OBJECTIVES: To improve gluteal ptosis, the authors propose a novel concept of combined liposuction of the lower gluteal region and fat grafting to the upper gluteal and infragluteal regions, and verify its efficacy and safety. METHODS: Patients who underwent liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions between January 2020 and July 2023 were retrospectively reviewed. Postoperative changes in the gluteal ptosis grade, complications, and patient satisfaction were evaluated. RESULTS: A total of 28 patients were enrolled in this study; 21 (75.0%) patients had gluteal ptosis grade 4 and 7 (25.0%) patients had gluteal ptosis grade 5. The median fat removal volume was 210 mL, and the median fat graft injected volume was 355 mL in the gluteal region and 180 mL in the infragluteal region. All patients showed improvement in gluteal ptosis; 16 (57.1%) patients improved by 1 grade and 12 (42.9%) patients showed a 2-grade improvement. All patients were satisfied with their posttreatment outcomes. Only 1 patient showed lateral translocation of the fat graft. No other complications were observed. CONCLUSIONS: Liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions is effective in improving gluteal ptosis, with a low risk of complications and high patient satisfaction.

Clinical impact of hepatic steatosis on chronic hepatitis B patients in Asia: A systematic review and meta-analysis.

Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.

Association of nonalcoholic fatty liver disease and growth hormone deficiency: a systematic review and meta-analysis.

An association exists between nonalcoholic fatty liver disease (NAFLD) and growth hormone (GH). Patients with growth hormone deficiency (GHD) may be more susceptible to NAFLD. The prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) in GHD patients is currently unknown. Multiple databases were searched for experiments related to NAFLD (or NASH) and GHD. Screening, quality evaluation and data extraction were carried out independently by two authors. Analyses used random or fixed effects models, including NAFLD prevalence, NASH prevalence, odds ratio (OR) and 95% confidence interval (CI). We included 10 studies with a total of 782 participants. The results showed that the prevalence of NAFLD in GHD patients was 51% (95% CI: 39-63). The risk of NAFLD in GHD patients was significantly higher than that in controls (age-, sex- or body mass index-matched, without GHD) (pooled OR = 4.27, 95% CI: 1.33-13.68%, p = 0.015). The prevalence of NASH in GHD patients was 18% (95% CI: 5-31). The prevalence of NAFLD in GHD patients is significantly higher than that in the general population, especially NASH. There is a need to develop targeted strategies for the early identification, prevention, or control of NAFLD/NASH in patients with GHD.

Barriers and enabling factors in weight management of patients with nonalcoholic fatty liver disease: A qualitative study using the COM-B model of behaviour.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first-line treatments for NAFLD. OBJECTIVE: We aim to identify barriers and enabling factors in weight management among patients with NAFLD using the capability, opportunity, motivation, behaviour (COM-B) model of behaviour. DESIGN: This study adopted a qualitative design using semistructured interviews analysed with content analysis and the COM-B framework. SETTING AND PARTICIPANTS: Interviews were conducted with 27 patients with NAFLD who experienced successful or unsuccessful weight reduction. RESULTS: Our study included 27 participants: 15 participants with successful weight loss (successful weight loss refers to a decrease in body weight ≥7% of the initial body weight for patients with NAFLD) and 12 participants with unsuccessful weight loss. Thirty-five themes (19 barriers and 16 facilitators) were mapped onto the COM-B model as barriers and facilitators to weight management among patients with NAFLD. The key barriers were lack of time and energy, lack of awareness of weight, lack of attention to NAFLD, treating food as a reward or compensation and social entertainment. The key facilitators were having basic weight loss knowledge and skills, strong motivation, attention to NAFLD, unsuccessful weight loss experiences and positive feedback from phased success. CONCLUSION: In addition to identifying factors consistent with existing studies, this study identified factors that influence weight management in NAFLD patients, such as basic weight loss skills and rational thinking before weight loss, which were not previously reported. This has clinical implications for clinical healthcare providers and health management services for the improvement of education and support regarding lifestyle improvement and weight management in patients with NAFLD. PATIENT OR PUBLIC CONTRIBUTION: We recruited potential participants from the Bariatric Clinic, Hepatology Clinic and Physical Examination Center of hospitals between March 2021 and October 2021. Twenty-seven patients with NAFLD who had successful or unsuccessful weight loss experiences participated in the study and responded to questions on weight management.

The Clinical Efficacy Evaluation of Thigh Liposuction Based on 3-Dimensional Digital Technology: A Quantitative Study.

BACKGROUND: There is a lack of convenient and accurate objective methods to evaluate the clinical efficacy of thigh liposuction. METHODS: This retrospective study involved the 3-dimensional images of 19 patients who underwent bilateral thigh liposuction. Data such as volume change and volume change rate before and after surgery, circumference change, and circumference change rate of 3 planes (upper, middle, and lower) were analyzed. The correlation between body mass index and volume change rate and between preoperative circumference and circumference change rate of different planes were determined. RESULTS: There were significant differences between the preoperative and postoperative volume and circumference of 3 planes of 19 patients (38 thighs). The rate of change in total volume (16.90 ± 5.55%) correlated with the circumference change rate at the top of the thigh. There was also a linear relationship between body mass index and volume change rate, but not between preoperative circumference and circumference change rate. CONCLUSIONS: Three-dimensional imaging technology can accurately quantify the volume and circumference change of the thigh to objectively evaluate the clinical efficacy of thigh liposuction.

Efficacy and Safety of Perioral Mound Region Liposuction-A Novel Concept to Improve Perioral Mound Fullness.

BACKGROUND: Fullness of the perioral mound is considered a dissatisfying aspect of premature aging and has become a common complaint of patients seeking facial rejuvenation. OBJECTIVES: The authors propose a novel concept of improving perioral mound fullness by liposuction and verify its safety and efficacy through cadaver and clinical studies. METHODS: A cadaver study was conducted to discover the soft tissue structure of the perioral mound region and identify a vital use for liposuction. For clinical evaluation, 37 patients with perioral mound fullness who underwent liposuction were retrospectively reviewed. RESULTS: The cadaver study results showed moderate fatty tissue in the subcutaneous layer of the perioral mound region. The liposuction manipulation was limited to the subcutaneous fat layer. Among the 37 patients (including 74 perioral mound regions), the median fat removal volume per perioral mound region was 2.0 (1.2, 2.3) mL. After liposuction, the subcutaneous fat thickness significantly decreased (median 5.0 [3.9, 6.6] mm vs 0.7 [0.4, 1.0] mm per perioral mound region, P < .001). All patients were satisfied with their posttreatment outcomes. Two patients (5.4%) had slight skin hyperpigmentation in the liposuction area after treatment and recovered naturally in 3 months without any intervention. No other complications were noted. CONCLUSIONS: Liposuction is effective in improving perioral mound fullness with a low risk of complications.

Liposuction of the Zygomatic Arch Area: A Novel Concept to Improve the Midface Contour.

BACKGROUND: An ovoid, slender face with a smooth contour is preferred in oriental esthetics. We developed a novel concept to achieve a slimmer and harmonious midface contour by liposuction of the projection area of the zygomatic arch. METHODS: A cadaver study including anatomical dissection and histologic examination were conducted to better understand the soft tissue structure of the projection area of the zygomatic arch and the vital technique for liposuction. For the clinical evaluation, 49 patients with midface hypertrophy who underwent liposuction of the zygomatic arch area from January 2016 to June 2021 were retrospectively reviewed. RESULTS: Cadaver study showed that abundant fatty tissue existed in the subcutaneous layer of the zygomatic arch area. The liposuction manipulation was precisely limited to the subcutaneous fat layer, and nerve branches were observed in the deeper loose areolar tissue plane. Of the 49 patients enrolled in this study (including 98 zygomatic arch areas), the median fat removal volume per zygomatic arch area was 3.0 (2.0, 5.0) mL. The subcutaneous fat thickness was significantly decreased postoperatively [median 9 (6, 10) mm vs. 1 (1, 2) mm per zygomatic arch area, P < 0.001]. All patients were satisfied with their postoperative outcomes. Only three patients underwent slight depression of the liposuction area during making facial expression after surgery and subsequently recovered. CONCLUSIONS: Liposuction of the zygomatic arch area is effective in improving midface hypertrophy and achieving a harmonious facial contour with a low risk of complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Volume Retention After Facial Fat Grafting and Relevant Factors: A Systematic Review and Meta-analysis.

BACKGROUND: Autologous fat grafting is common in facial reconstructive and cosmetic surgeries; the most important drawbacks are the high absorption rate and unpredictable volume retention rate. Surgeons usually make clinical judgements based on their own experience. Therefore, this study aimed to systematically and quantitatively review the volume retention rate of facial autologous fat grafting and analyse the relevant influencing factors. METHODS: A systematic literature review was performed using the Medline, EMBASE, Cochrane Library, and Web of Science databases in October 2019 for articles that reported objectively measured volume retention rates of facial fat grafting. Patient characteristics, fat graft volumetric data, and complications were collected. A meta-analysis using a random-effects model was conducted to pool the estimated fat retention rate. Relevant factors were analysed and reviewed on the basis of subgroups. RESULTS: We included 27 studies involving 1011 patients with facial fat grafting. The volume retention rate varied from 26 to 83%, with a mean follow-up of 3-24 months. The overall pooled retention rate was 47% (95% CI 41-53%). The volume measurement method significantly influenced the reported retention rate. A trend towards better retention was found for secondary fat grafting procedures and patients with congenital deformities. Only 2.8% of all patients had complications. CONCLUSION: The exact percentage of facial fat grafts retained is currently unpredictable; the reported rate varies with different estimation methods. This review analysed studies that provided objectively measured volume retention rates, the pooled average percentage of facial fat graft retention (47%, 95% CI 41-53%), and relevant factors. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Application of a Proposed Multi-Positional Circumferential Arm Liposuction Method and Quantification of its Clinical Efficacy Evaluation.

BACKGROUND: Upper arm liposuction mainly focuses on the posterolateral region, which may lead to a lack of harmony between the aspirated and unaspirated areas. In addition, the treatment effect of arm liposuction is often evaluated only by preoperative and postoperative photograph comparison and simple measurement; quantitative research on this topic is still lacking. METHODS: The multi-positional circumferential arm liposuction (MCAL) technique was proposed and applied to a total of 34 females in our hospital from 2017 to 2019. Three-dimensional data of 12 patients before the operation and after 2-3 months were collected and processed by 3D imaging, and the volume reduction rate was evaluated quantitatively. RESULTS: The MCAL method was successfully applied in the clinic, and its surgical effect was quantitatively studied. The mean follow-up time of 12 patients was (75.2 ±13.1) days, and the postoperative volume was significantly reduced. The postoperative volume of patients with type I, type II and type III decreased by (10.79 ±2.55)%, (17.25 ±3.02)% and (22.76 ±3.51)%, respectively. CONCLUSION: Our new MCAL technique was successful, maximizing the esthetic results in upper limb contour refinements in the superficial fascial layer. The clinical efficacy of this proposed MCAL method was evaluated by CT and 3D digital technology, which provided further accuracy in demonstrating its effect on the shape of the arm. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com .

Transbrow Excision Blepharoplasty for Upper Eyelid Dermatochalasis: A Modified Approach.

BACKGROUNDS: Many aging women with upper lid dermatochalasis pluck their lower lateral eyebrows to combat lateral drooping. The authors present and evaluate outcomes of a modified excision blepharoplasty method performed using a transbrow excision approach instead of infra/suprabrow access to more efficiently correct upper eyelid dermatochalasis. METHODS: The authors conducted a retrospective review of 192 patients who underwent transbrow excision blepharoplasty (TBEB) between 2014 and 2019 at the Plastic Surgery Hospital of Beijing in China. The clinical features, complications, and outcomes of patients were reviewed. The Strasser grading system was used to evaluate surgical results postoperatively. Aesthetic improvement was subjectively judged by the patients. RESULTS: All 192 patients (aged 25-72 years old, mean 46 years old) were reviewed and followed up for 6 months to 2 years. Patients were evaluated after 1 week and after at least 6 months. All patients reported an improved aesthetic appearance of the lateral periorbital area, and 174 patients (90.6%) rated their results as satisfactory. No serious complications were related to the procedure. CONCLUSIONS: TBEB is used to correct problems that are not adequately managed by conventional excision blepharoplasty. Among 192 patients evaluated over 5 years, excision of the transbrow skin pad sufficiently reduced the redundancy of the upper eyelid and achieved an acceptable appearance of the periorbital area, where the postoperative location of a subtle scar defined a desired youthful brow position. In selected patients, this is an effective and safe method that uses patient-observed features to provide an alternate cosmetic approach.

Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival.

Mammals harbor a limited number of sound-receptor hair cells (HCs) that cannot be regenerated after damage. Thus, investigating the underlying molecular mechanisms that maintain HC survival is crucial for preventing hearing impairment. Intriguingly, Pou4f3-/- or Gfi1-/- HCs form initially but then rapidly degenerate, whereas Rbm24-/- HCs degenerate considerably later. However, the transcriptional cascades involving Pou4f3, Gfi1, and Rbm24 remain undescribed. Here, we demonstrate that Rbm24 expression is completely repressed in Pou4f3-/- HCs but unaltered in Gfi1-/- HCs, and further that the expression of both POU4F3 and GFI1 is intact in Rbm24-/- HCs. Moreover, by using in vivo mouse transgenic reporter assays, we identify three Rbm24 enhancers to which POU4F3 binds. Lastly, through in vivo genetic testing of whether Rbm24 restoration alleviates the degeneration of Pou4f3-/- HCs, we show that ectopic Rbm24 alone cannot prevent Pou4f3-/- HCs from degenerating. Collectively, our findings provide new molecular and genetic insights into how HC survival is regulated.

Prevalence and risk factors of postoperative delirium in tumor patients after free flap reconstruction: A systematic review and meta-analysis of case-control studies.

BACKGROUND: Postoperative delirium is a severe complication of flap transplantation surgery, adversely affecting surgical prognoses. The intricate pathophysiology of postoperative delirium renders the elucidation of its risk factors challenging. This research aims to delineate the prevalence and the specific risk factors of postoperative delirium in patients with cancer undergoing free flap reconstruction through a systematic review and meta-analysis to enlighten proactive prevention measures. METHODS: The researchers systematically queried both the international and Chinese databases. Searches were performed for publications from inception until September 14, 2023, using the terms "free tissue flaps," "delirium," "neoplasms," and "risk factors." Data synthesis and statistical analysis were conducted using Stata SE (version 15.0) to calculate the combined effect size for identified risk factors. Reported outcomes included weighted mean differences or odds ratios with their respective 95% confidence intervals. RESULTS: Twelve case-control studies were included (ntotal = 3,256). Among them, 515 patients developed postoperative delirium after free flap surgery, compared with 2,741 patients who did not. The outcomes suggest that the risk factors include but are not limited to age, male, late neoplasm staging, use of hypnotic or antipsychotic, history of background diseases, psychiatric review, tracheotomy, and impaired wound healing. In contrast, early neoplasm staging and others are the protective factors with statistical significance. Multivariate analysis further identified significant correlations between preoperative albumin, perioperative blood transfusion, sleep disturbance, postoperative visual analog scale, postoperative albumin, smoking, and the appearance of postoperative delirium. CONCLUSION: The determined risk factors were grouped into preoperative, intraoperative, and postoperative categories substantiated by current data to present instructions for postoperative delirium prevention.

Small-Scale High-Pressure Hydrogen Storage Vessels: A Review.

Nowadays, high-pressure hydrogen storage is the most commercially used technology owing to its high hydrogen purity, rapid charging/discharging of hydrogen, and low-cost manufacturing. Despite numerous reviews on hydrogen storage technologies, there is a relative scarcity of comprehensive examinations specifically focused on high-pressure gaseous hydrogen storage and its associated materials. This article systematically presents the manufacturing processes and materials used for a variety of high-pressure hydrogen storage containers, including metal cylinders, carbon fiber composite cylinders, and emerging glass material-based hydrogen storage containers. Furthermore, it introduces the relevant principles and theoretical studies, showcasing their advantages and disadvantages compared to conventional high-pressure hydrogen storage containers. Finally, this article provides an outlook on the future development of high-pressure hydrogen storage containers.

Reconstruction of total upper eyelid with prefabricated capsule-lined advancement flaps.

BACKGROUND: A total upper eyelid defect is a rare problem that may result from tumor excision, trauma, or burns. Reconstruction of a total upper eyelid defect involves the reconstruction of 2 fundamental elements: anterior and posterior lamellae. Because an expander capsule looks like the palpebral conjunctiva with a moist, smooth, white glistening appearance, its use was investigated in the repair of total upper eyelid defects in rabbits. METHODS: Sixty-six tissue expanders with the autogeneic conchal chondro-grafts were implanted into the foreheads of 66 rabbits. After 6 to 8 weeks, the sandwich-prefabricated advancement flaps were designed to reconstruct rectangular excisions of the upper eyelid. The cartilage was preliminarily inserted in a flap, formed by tissue expansion, and then transferred to an upper eyelid defect in the rabbit. Histopathology was evaluated at 3 days, 1 week, 2 weeks, 1 month, 2 months, and 4 months after reconstruction. The upper palpebral length was measured after 4 months of reconstruction as a 1-dimension reference point of flap contracture. RESULTS: No edema, congestion, infection, corneal damage, or necrosis were observed during the reconstructions. Histopathologic studies revealed that the long-term capsule had a normal conjunctiva-like appearance with a stratified columnar epithelium. The average shortening, measured as the length between inner to outer canthal folds, was inconspicuous. CONCLUSIONS: The expander capsule has the potential to act as an effective posterior lamellar substitute of eyelid in a rabbit model. Further studies should be undertaken to see if this represents a good model for a potential human clinical application.

Digital Therapeutics: Emerging New Therapy for Nonalcoholic Fatty Liver Disease.

The increased prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide is particularly worrisome, as no medication has been approved to treat the disease. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first-line treatment for NAFLD. However, due to the lack of standard and scientific guidance and out-of-hospital supervision, long-term outcomes of lifestyle interventions for patients with NAFLD are often unsatisfactory. In addition, the COVID-19 pandemic aggravated this dilemma. At the same time, digital therapeutics (DTx) are expected to be a new method for the convenient management and treatment of patients with NAFLD and are attracting a great deal of attention. DTx, which provide evidence-based medicine through software programs for remote intervention in preventing, treating, or managing diseases, overcome the drawbacks of traditional treatment. The efficacy of the approach has already been demonstrated for some chronic diseases, but DTx have not been fully developed for NAFLD. This study reviews the concepts, clinical value, and practical applications related to DTx, with an emphasis on recommendations based on unmet needs for NAFLD. A better understanding of the current state will help clinicians and researchers develop high-quality, standardized, and efficient DTx products, with the aim of optimizing the prognosis of patients with NAFLD.

Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials.

INTRODUCTION: There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included. RESULTS: Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)]. CONCLUSIONS: GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].

Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials.

Background: The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty liver disease (NAFLD) therapy has not been sufficiently investigated. Methods: Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included. Primary outcomes were improvements in liver enzymes and liver fat parameters, while secondary outcomes included anthropometric measures, blood lipids and glycemic parameters. The frequentist method was used to perform a network meta-analysis. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). Results: The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists). Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin. Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment. Conclusion: Semaglutide, liraglutide, and dapagliflozin all have a certain effect on NAFLD (or comorbid with type 2 diabetes) based on high confidence evidence from indirect comparisons, and semaglutide appears to have a therapeutic advantage over the other included medicines. Head-to-head studies are needed to provide more confidence in clinical decision-making.