Background: Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety. Methods: Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy. Results: Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years’ follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials. Conclusions: Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs—future real-world data should be focused on SOAE.

ObjectiveThe concept of using naturally occurring compounds such as polyenylphosphatidylcholine (PPC) as an adjunctive therapy to treat non-alcoholic fatty liver disease (NAFLD) and alleviate or reverse hepatic steatosis appears a very attractive option for liver protection. We aim to evaluate if PPC adjunctive therapy can effectively improve the ultrasonographic features of NAFLD in routine clinical practice in Russian patients with cardiometabolic comorbidities.DesignThis 24-week, observational, prospective study was carried out in 174 medical sites across 6 federal districts of Russia. A total of 2843 adult patients with newly diagnosed NAFLD, who had a least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus and hypercholesterolaemia, and who received PPC as an adjunctive treatment to standard care, were enrolled. The assessment of liver ultrasonography was qualitative.ResultsOverall, 2263 (79.6%) patients had at least two metabolic comorbidities associated with NAFLD, and overweight/obesity was the most common comorbidity reported in 2298 (80.8%) patients. Almost all study participants (2837/2843; 99.8%) were prescribed 1.8 g of PPC administered three times daily. At baseline, the most frequently identified abnormalities on ultrasound were liver hyperechogenicity (84.0% of patients) and heterogeneous liver structure (62.9%). At 24 weeks, a significant (p<0.05) improvement in liver echogenicity and in liver structure was observed in 1932/2827 (68.3%) patients (95% CI 66.6% to 70.1%) and in 1207/2827 (42.7%) patients (95% CI 40.9% to 44.5%), respectively. The analysis of ultrasonographic signs by number of comorbidities revealed similar findings—liver echogenicity improved in 67.2%–69.3% and liver structure in 35.6%–45.3% of patients depending on the number of comorbidities.ConclusionThis study showed that PPC adjunctive therapy may be useful in improving the ultrasonographic features of NAFLD in patients with associated cardiometabolic comorbidities. It also supports evidence regarding the role of PPC in the complex management of NAFLD.

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal results of liver function tests. Earlier research showed that polyenylphosphatidylcholine (PPC) has hepatoprotective effects and thus can be used for the treatment of NAFLD and the prevention of its progression. Accordingly, the aim of this observational study was to evaluate if PPC administered as adjunctive therapy in routine clinical practice can effectively improve liver function tests of NAFLD in Russian patients with associated metabolic comorbidities.DesignA total of 2843 adult patients with newly diagnosed NAFLD, who had a least one of four comorbidities, namely, overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who were prescribed 1.8 g/day of PPC as an adjunctive treatment to standard care, were enrolled during 2015–2016. Laboratory data were collected at baseline and 12 and 24 weeks of the study, and included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)), fasting plasma glucose, and lipid profile.ResultsOverall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD, and overweight/obesity was the most common comorbidity reported in 2298 (80.8%) patients. At 24 weeks, there was a significant decrease in liver enzyme levels (all p<0.001 compared with baseline). Across the four comorbidity subgroups, there was a mean drop of ALT levels ranging from 19.7 to 22.0 U/L, AST from 16.9 to 18.4 U/L, and GGT from 17.2 to 18.7 U/L. Similar findings were reported in subgroups with either one, two, three, or four comorbidities, with a significant decrease in liver enzyme levels ranging from 18.4 to 22.4 U/L for ALT, 14.8 to 18.7 U/L for AST, and 15.5 to 19.5 U/L for GGT.ConclusionsAdjuvant treatment with PPC resulted in consistent improvements in liver enzymes in patients with newly diagnosed NAFLD and associated metabolic comorbidities.Trial registration numberNCT00063622.

Background While no "gold-standard" pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) is yet established, essential phospholipids (EPLs) are reported to decrease steatosis and improve laboratory parameters. Objective This analysis evaluated adherence and satisfaction with EPL treatment as patient-reported outcomes and their relationship with changes in laboratory and ultrasound parameters among Russian patients with NAFLD. Methods Data were pooled from three observational Russian studies- MANPOWER (2015MANPOWER ( -2016, LIDER 1 (2012-2013), and LIDER 2 (2013)-in which EPLs were used for at least 12 weeks in the treatment of liver diseases and which measured both subjective and objective endpoints. Only patients who had NAFLD were included in this analysis. The main endpoints were to determine treatment adherence and satisfaction with 12 weeks of EPL therapy, relationship between adherence/satisfaction and changes in the laboratory and ultrasound parameters. A secondary subgroup analysis was performed to identify patients with NAFLD who responded better (or worse) to 24 weeks of adjunctive EPL treatment. Results Overall, 3384 patients were included. A total of 82.2% of patients were adherent to 12 weeks of EPL treatment; high/very high satisfaction was reported by 15.3%/65.9% of clinicians and 15.9%/64.4% of patients. There was positive correlation between patients' adherence and satisfaction and significant improvement in laboratory (transaminases, lipid profile; p < 0.001) and ultrasound (steatosis, p < 0.001) parameters, and improvement in symptoms (p < 0.001) after 24 weeks of EPL. Male patients, patients with unhealthy lifestyles, and those with more comorbidities showed a better response in laboratory and ultrasound parameters. Conclusions Patients with NAFLD treated with adjunctive EPL therapy in real-world clinical practice in Russia showed good treatment adherence and treatment satisfaction. Improvements in laboratory and ultrasound parameters, as well as dynamics of patient symptoms, were positively correlated with adherence and satisfaction.

ObjectivePrevious research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia.DesignA total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015–2016.ResultsOverall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD; overweight/obesity was the most common comorbidity reported in 2298 patients (80.8%). Simple steatosis was the most frequently identified clinical form of NAFLD, diagnosed in 2128 patients (74.9%). Among hypertensive patients, ACE inhibitors, statins, and sartans were most commonly prescribed. Biguanides were administered in more than half of diabetic patients. In patients with overweight/obesity and hypercholesterolaemia, statins were the most frequently prescribed medications. Almost all patients (2837/2843; 99.8%) were treated with 1.8 g of PPC three times per day. PPC therapy was associated with a 90.5% 6-month compliance rate, high treatment satisfaction, and a favourable safety profile. However, almost 15% of diabetic patients and 40% of overweight/obese patients received no further treatment.ConclusionsIn Russia, patients with newly diagnosed NAFLD represent a population heavily burdened by comorbidities, mainly overweight/obesity and hypercholesterolaemia. A significant part of these patients did not receive a comprehensive pharmacotherapy, highlighting the existing unmet need in the current management of NAFLD patients with metabolic syndrome in Russia.

Introduction: The current non-invasive tools for the diagnosis of non-alcoholic fatty liver disease (NAFLD) have methodological limitations. We aimed to develop a non-invasive scale to assist in the diagnosis of NAFLD. To achieve our aim, we conducted a secondary analysis of data from a large observational study conducted in Russia. Methods: This retrospective analysis assessed the frequency of NAFLD in the population of patients in the DIREG_L_06725 study, an epidemiological, observational, cross-sectional, multicenter study performed in 50,145 outpatients from 16 Russian cities. Among the cohort of patients diagnosed with NAFLD, we identified factors associated with the risk of NAFLD. To develop a non-invasive tool for diagnosing NAFLD, we also determined the frequency of steatohepatitis. Results: Our analysis included 48,297 patients; NAFLD was present in 20,281 patients (42.0%). The majority (64.1%) were women (80.3% postmenopause), and 87% had a body mass index (BMI) [ 27.0 kg/m 2. We developed a fully noninvasive scale (St-index) that showed a specificity of 91.4% for ruling in steatosis, and a sensitivity of 93.8% for ruling out steatosis. Multivariate regression analyses conducted in the subgroups of patients aged C 12 and \ 18 years and those with BMI \ 25.0 kg/m 2 produced area under the receiver operating characteristic (AUROC) curve values of 0.8243 and 0.7054, respectively. The factors most strongly associated with the development of NAFLD were age [ 35 years, presence of type 2 diabetes mellitus, and a waist circumference/ height ratio [ 0.54. Conclusion: Our non-invasive steatosis scale, St-index, can help physicians diagnose NAFLD in high-risk patients in the absence of ultrasound data.

Liver steatosis is a key pathology in non-alcoholic or metabolic associated fatty liver disease. Though largely ignored for decades it is currently becoming the focus of research in hepatology. It is important to consider its origin and current opportunities in terms of pharmacotherapy. Essential phospholipids (EPLs) rich in phosphatidylcholine (PCH) is a widely used treatment option for fatty liver disease, and there is a solid amount of consistent clinical evidence for the regression of steatosis after treatment with EPLs. As knowledge of PCH (a key component of EPLs) pharmacodynamics and mode of action driving this widely observed clinical effect is currently insufficient, we aimed to explore the potential molecular and metabolic pathways involved in the positive effects of PCH on steatosis regression.

Due to the high estimated prevalence of magnesium deficiency, there is a need for a rapid, non-invasive assessment tool that could be used by patients and clinicians to confirm suspected hypomagnesemia and substantiate laboratory testing. This study analyzed data from four large observational studies of hypomagnesemia in pregnant women and women with hormone-related conditions across Russia. Hypomagnesemia was assessed using a 62-item magnesium deficiency questionnaire (MDQ-62) and a serum test. The diagnostic utility (sensitivity/specificity) of MDQ-62 was analyzed using area under the receiver operating characteristic curve (AUROC). A logistic regression model was applied to develop a shorter, optimized version of MDQ-62. A total of 765 pregnant women and 8836 women with hormone-related conditions were included in the analysis. The diagnostic performance of MDQ-62 was “fair” (AUROC = 0.7−0.8) for women with hormone-related conditions and “poor” for pregnant women (AUROC = 0.6−0.7). The optimized MDQ-23 (23 questions) and MDQ-10 (10 questions) had similar AUROC values; for all versions of the questionnaire, there was a significant negative correlation between score and changes in total serum magnesium levels (p < 0.0001 for all comparisons; correlation coefficients ranged from −0.1667 to −0.2716). This analysis confirmed the value of MDQ in identifying women at risk of hypomagnesemia.