scholarly journals Analysis of Mechanistic Pathways in the Treatment of Non-Alcoholic Steatohepatitis. Evidence from a Bayesian Network Meta-Analysis

2021 ◽  
Author(s):  
Mark Muthiah ◽  
Cheng Han Ng ◽  
Jieling Xiao ◽  
Yip Han Chin ◽  
Grace Lim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bayesian Network ◽  
Bile Acids ◽  
Meta Analysis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Point Reduction ◽  
Drug Classes ◽  
Credible Intervals ◽  
Significant Disease

Background and Aims: Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease contributing to significant disease burden worldwide. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs. Approach & Results: Medline, EMBASE and CENTRAL were searched for articles evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid, and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. From the 48 trials included, treatments modulating energy (Risk ratio (RR): 1.84, Credible intervals (Crl): 1.29 - 2.65) were the most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.68, Crl: 0.55 - 5.28), bile acids (RR: 1.34, Crl: 0.78 - 2.26) and inflammation (RR: 0.94, Crl: 0.59 - 1.46). Energy and bile acids modulation were effective in 2-point NAS reduction without worsening of fibrosis (RR: 1.60, Crl 1.13 - 2.30 and RR: 1.79, Crl 1.14 - 2.86) and 1-point fibrosis (RR: 1.27, Crl:1.05 - 1.52 and RR: 1.54, Crl: 1.20 - 1.97). Conclusions: This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.

Prevalence, diagnosis and treatment with 3 different statins of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in military personnel. Do genetics play a role?

2020 ◽  
Vol 18 ◽  
Author(s):  
Georgios Sfikas ◽  
Michael Psallas ◽  
Charalambos Koumaras ◽  
Konstantinos Imprialos ◽  
Evangelos Perdikakis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Military Personnel ◽  
Fatty Liver Disease ◽  
Exercise Group ◽  
Severe Form ◽  
Laboratory Evaluation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. Aim: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. Methods: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomised to 4 groups (n=151 each): dietexercise, atorvastatin, rosuvastatin or pitavastatin for 1 year (i.e. until the next routine evaluation). Results: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001); 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs 5.62, p=0.07; FIB-4 3.42 vs 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). Conclusions : Atorvastatin, rosuvastatin and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

scholarly journals Non‐alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta‐analysis

JGH Open ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 434-445
Author(s):  
Mohamed Shengir ◽  
Tianyan Chen ◽  
Elena Guadagno ◽  
Agnihotram V Ramanakumar ◽  
Peter Ghali ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Disease ◽  
Polycystic Ovary Syndrome ◽  
Fatty Liver Disease ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Ovary Syndrome ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Paraoxonase 1 and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2323
Author(s):  
Kazuhiko Kotani ◽  
Jun Watanabe ◽  
Kouichi Miura ◽  
Alejandro Gugliucci
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Laboratory Data ◽  
Paraoxonase 1 ◽  
Mixed Data ◽  
Alcoholic Fatty Liver ◽  
Paraoxonase Activity

Oxidative stress is involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, reliable biomarkers of NAFLD in relation to oxidative stress are not available. While paraoxonase 1 (PON1) is an antioxidant biomarker, there appears to be mixed data on PON-1 in patients with NAFLD. The aim of this meta-analysis was to assess the current data on PON1 activity (i.e., paraoxonase and arylesterase) in patients with NAFLD. A PubMed, CENTRAL, and Embase search identified 12 eligible articles. In the meta-analysis, the paraoxonase activity was low in patients with NAFLD (mean difference (MD) −27.17 U/L; 95% confidence interval (CI) −37.31 to −17.03). No difference was noted in the arylesterase activity (MD 2.45 U/L; 95% CI −39.83 to 44.74). In a subgroup analysis, the paraoxonase activity was low in biopsy-proven nonalcoholic steatohepatitis (MD −92.11 U/L; 95% CI −115.11 to −69.11), while the activity in NAFLD as diagnosed by ultrasonography or laboratory data was similar (MD −2.91 U/L; 95% CI −11.63 to 5.80) to that of non-NAFLD. In summary, the PON1, especially paraoxonase, activity could be a useful biomarker of NAFLD. Further studies are warranted to ascertain the relevance of PON1 measurements in patients with NAFLD.

scholarly journals FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (11) ◽  
pp. 2415
Author(s):  
Yasaman Vali ◽  
Jenny Lee ◽  
Jérôme Boursier ◽  
René Spijker ◽  
Joanne Verheij ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Multiple Thresholds ◽  
Meta Analyses ◽  
Alcoholic Fatty Liver Disease

(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.

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