Publications by authors named "Vladimir Ivashkin"

34 Publications

Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial.

Probiotics Antimicrob Proteins 2021 Oct 13. Epub 2021 Oct 13.

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation.

The treatment of coronavirus disease (COVID-19) and COVID-19-associated diarrhea remains challenging. This study aimed to evaluate the efficacy of a multi-strain probiotic in the treatment of COVID-19. This was a randomized, controlled, single-center, open-label trial (NCT04854941). Inpatients with confirmed COVID-19 and pneumonia were randomly assigned to a group that received a multi-strain probiotic (PRO group) or to the control group (CON group). There were 99 and 101 patients in the PRO and CON groups, respectively. No significant differences in mortality, total duration of disease and hospital stay, incidence of intensive care unit admission, need for mechanical ventilation or oxygen support, liver injury development, and changes in inflammatory biomarker levels were observed between the PRO and CON groups among all included patients as well as among subgroups delineated based on age younger or older than 65 years, and subgroups with chronic cardiovascular diseases and diabetes. Diarrhea on admission was observed in 11.5% of patients; it resolved earlier in the PRO group than in the CON group (2 [1-4] vs. 4 [3-6] days; p = 0.049). Hospital-acquired diarrhea developed less frequently in the PRO group than in the CON group among patients who received a single antibiotic (0% vs. 12.5%; p = 0.023) unlike among those who received > 1 antibiotic (10.5% vs. 13.3%; p = 0.696). The studied probiotic had no significant effect on mortality and changes in most biomarkers in COVID-19. However, it was effective in treating diarrhea associated with COVID-19 and in preventing hospital-acquired diarrhea in patients who received a single antibiotic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12602-021-09858-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512595PMC
October 2021

Probiotics in hepatology: An update.

World J Hepatol 2021 Sep;13(9):1154-1166

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia.

The gut-liver axis plays an important role in the pathogenesis of various liver diseases. Probiotics are living bacteria that may be used to correct disorders of this axis. Notable progress has been made in the study of probiotic drugs for the treatment of various liver diseases in the last decade. It has been proven that probiotics are useful for hepatic encephalopathy, but their effects on other symptoms and syndromes of cirrhosis are poorly studied. Their effectiveness in the treatment of metabolic associated fatty liver disease has been shown both in experimental models and in clinical trials, but their effect on the prognosis of this disease has not been described. The beneficial effects of probiotics in alcoholic liver disease have been shown in many experimental studies, but there are very few clinical trials to support these findings. The effects of probiotics on the course of other liver diseases are either poorly studied (such as primary sclerosing cholangitis, chronic hepatitis B and C, and autoimmune hepatitis) or not studied at all (such as primary biliary cholangitis, hepatitis A and E, Wilson's disease, hemochromatosis, storage diseases, and vascular liver diseases). Thus, despite the progress in the study of probiotics in hepatology over the past decade, there are many unexplored and unclear questions surrounding this topic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4254/wjh.v13.i9.1154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473492PMC
September 2021

Safety and Effectiveness of Essential Phospholipids Paste in Patients with Non-alcoholic Fatty Liver Disease or Viral Hepatitis.

Turk J Gastroenterol 2021 09;32(9):750-757

Sanofi-Aventis, Moscow, Russia.

Background: Essential phospholipids (EPL) are used as adjuvant treatment in people with fatty liver disease and other chronic liver diseases. A new formulation of EPL paste was developed to improve patient compliance. The study was aimed to assess the safety, patient-reported outcomes, and impact on compliance of the new EPL paste formulation in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatitis.

Methods: The study enrolled 147 patients (48.3% male; mean ± standard deviation (SD) age 44.8 ± 10.5 years) in the intention-to-treat population; 72.8% had NAFLD and 27.9% had viral hepatitis B (HBV) or hepatitis C (HCV). Patients received EPL paste (one 600 mg sachet 3 times daily) for 12 weeks, with 4-, 8-, and 12-week scheduled visits and a 13-week follow-up visit. Patient-reported outcomes were evaluated at 4, 8, and 12 weeks compared with baseline using dedicated Likert scales. Compliance was assessed by comparing actual versus prescribed dosing of the EPL.

Results: After 12-week treatment with EPL paste, statistically significant improvements were observed in mean ± SD Global Overall Symptom scores (from 4.21 ± 1.09 to 1.87 ± 0.91; P < .01) and overall Gastrointestinal Symptom scores (from 19.91 ± 5.74 to 11.17 ± 3.57; P < .01), compared to baseline scores. Compliance with prescribed essential phospholipid treatment was 99% throughout the 12-week treatment period.

Conclusion: Essential phospholipids paste had a favorable safety profile associated with improved gastrointestinal symptoms and with high levels of compliance in patients with NAFLD and viral hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5152/tjg.2021.20294DOI Listing
September 2021

Food Intolerance: The Role of Histamine.

Nutrients 2021 Sep 15;13(9). Epub 2021 Sep 15.

Department of Internal Diseases Propedeutics, Sechenov University, 119121 Moscow, Russia.

Histamine is a natural amine derived from L-histidine. Although it seems that our knowledge about this molecule is wide and diverse, the importance of histamine in many regulatory processes is still enigmatic. The interplay between different types of histamine receptors and the compound may cause ample effects, including histamine intoxication and so-called histamine intolerance or non-allergic food intolerance, leading to disturbances in immune regulation, manifestation of gastroenterological symptoms, and neurological diseases. Most cases of clinical manifestations of histamine intolerance are non-specific due to tissue-specific distribution of different histamine receptors and the lack of reproducible and reliable diagnostic markers. The diagnosis of histamine intolerance is fraught with difficulties, in addition to challenges related to the selection of a proper treatment strategy, the regular course of recovery, and reduced amelioration of chronic symptoms due to inappropriate treatment prescription. Here, we reviewed a history of histamine uptake starting from the current knowledge about its degradation and the prevalence of histamine precursors in daily food, and continuing with the receptor interactions after entering and the impacts on the immune, central nervous, and gastrointestinal systems. The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13093207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469513PMC
September 2021

Interleukin 17 antagonist netakimab is effective and safe in the new coronavirus infection (COVID-19).

Eur Cytokine Netw 2021 Mar;32(1):8-14

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation.

Cytokine release syndrome is a serious complication of the new coronavirus infection (COVID-19). The aim of the study was to assess effectiveness and safety of the IL-17 antagonist nekatimab for its treatment. The retrospective study included COVID-19 patients with C-reactive protein levels >60 mg/L. Patients received either netakimab (group NET), IL-6 antagonist tocilizumab (group TOC) or no anti-cytokine treatment (group CON). Forty-four patients were enrolled in the NET group, 27 patients in the TOC group, and 47 patients in the CON group. Mortality was lower in the NET group than in TOC and CON groups (2.3% vs. 14.8% and 31.9%; p = 0.018 and p < 0.001). NET group patients required intensive care unit admission (6.8% vs. 25.9% and 46.3%; p = 0.025 and p < 0.001) and mechanical ventilation (4.6% vs. 22.2% and 31.9%; p = 0.022 and p = 0.002) less frequently than patients of the TOC and CON groups. After 7-10 days of anti-cytokine drug administration, a reduction in lung lesion volume (p = 0.016) and an increase in the proportion of patients who did not need oxygen support (p = 0.005) or stayed in prone position (p = 0.044) was observed in the NET group only group; C-reactive protein levels were the same in the TOC and NET groups (p = 0.136) and lower in the CON group (p < 0.001 and p = 0.005). IL-6 levels decreased in the NET group (p = 0.005) and did not change in the TOC group (p = 0.953). There was no difference in the incidence of side effects between groups. The IL-17 antagonist netakimab is effective and safe in the treatment of cytokine release syndrome in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ecn.2021.0463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491178PMC
March 2021

The Concept of Folic Acid in Health and Disease.

Molecules 2021 Jun 18;26(12). Epub 2021 Jun 18.

Department of Internal Diseases Propedeutics, Sechenov University, 119121 Moscow, Russia.

Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26123731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235569PMC
June 2021

Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis.

World J Hepatol 2021 May;13(5):557-570

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia.

Background: Gut dysbiosis is common in cirrhosis.

Aim: To study the influence of gut dysbiosis on prognosis in cirrhosis.

Methods: The case-control study included 48 in-patients with cirrhosis and 21 healthy controls. Stool microbiome was assessed using 16S ribosomal ribonucleic acid gene sequencing. We used modified dysbiosis ratio (MDR): [ (%) + (%)]/[ (%) + (%)]. Patients with MDR more the median made up the group with severe dysbiosis, others did the group with non-severe dysbiosis. The follow-up period was 4 years.

Results: The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis (54.2% 12.5%; = 0.001). The presence of severe dysbiosis was independent risk factors for death [hazard ratio = 8.6 × (1.9-38.0); = 0.005]. The abundance of ( = 0.002), ( = 0.002), and ( = 0.025) was increased and the abundance of ( = 0.025) and ( = 0.045) was decreased in the deceased patients compared with the survivors. The deceased patients had a higher MDR value than the survivors [0.131 × (0.069-0.234) 0.034 × (0.009-0.096); = 0.004]. If we applied an MDR value of 0.14 as the cutoff point, then it predicted patient death within the next year with a sensitivity of 71.4% and a specificity of 82.9% [area under the curve = 0.767 × (0.559-0.974)]. MDR was higher in patients with cirrhosis than in health controls [0.064 × (0.017-0.131) 0.005 × (0.002-0.007); < 0.001], and in patients with decompensated cirrhosis than in patients with compensated cirrhosis [0.106 × (0.023-0.211) 0.033 × (0.012-0.074); = 0.031]. MDR correlated negatively with prothrombin ( = -0.295; = 0.042), cholinesterase ( = -0.466; = 0.014) and serum albumin ( = -0.449; = 0.001) level and positively with Child-Turcotte-Pugh scale value ( = 0.360; = 0.012).

Conclusion: Gut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4254/wjh.v13.i5.557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173342PMC
May 2021

Immune disorders and rheumatologic manifestations of viral hepatitis.

World J Gastroenterol 2021 May;27(18):2073-2089

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia.

Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v27.i18.2073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117740PMC
May 2021

Tofacitinib reduces mortality in coronavirus disease 2019 Tofacitinib in COVID-19.

Pulm Pharmacol Ther 2021 08 21;69:102039. Epub 2021 May 21.

Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation.

Background And Aim: Cytokine release syndrome is a dangerous complication of the coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy and safety of tofacitinib in the management of this complication.

Methods: The retrospective study included COVID-19 patients with C-reactive protein (CRP) levels of 60-150 mg/L.

Results: Thirty-two patients who received tofacitinib (TOF group) and 30 patients who did not receive any anti-cytokine drugs (control [CON] group) were enrolled. Mortality and the incidence of admission to the intensive care unit were lower in the TOF group than in the CON group (16.6% vs. 40.0%, p = 0.009; and 15.6% vs. 50.0%, p = 0.004). There was a significant decrease in the volume of the affected part of the lungs (p = 0.022) and a significant increase in oxygen saturation (p = 0.012) in the TOF group than in the CON group 7-10 days after the beginning tofacitinib administration. CRP level was lower in the TOF group than in the CON group (7 [3-22] vs. 20 [5-52] mg/L; p = 0.048) 7-10 days after the start of the administration of tofacitinib. During this period, the number of patients requiring mechanical ventilation or those in the prone position increased in the CON group compared to those in the TOF group (26.7% vs. 0.0%, p = 0.002; 33.3% vs. 6.7%, p = 0.020). There was no significant difference in the development of secondary infections, liver or kidney injury, and cytopenia between the two groups.

Conclusion: Tofacitinib was effective and safe for managing the cytokine release syndrome in COVID-19. Randomized controlled double-blind trials with tofacitinib with and without the simultaneous use of glucocorticoids are required to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pupt.2021.102039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137353PMC
August 2021

Correlation of Objective Endpoints and Subjective Patient-Reported Outcomes in NAFLD Treatment with Essential Phospholipids: Real-World Data Based on Pooled Analysis of Observational Studies.

Drugs Real World Outcomes 2021 Sep 15;8(3):369-382. Epub 2021 May 15.

Department of Medical Affairs, Sanofi, 125009 Business Center "Summit", Tverskaya 22, Moscow, Russia.

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 (2015-2016), 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40801-021-00250-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123926PMC
September 2021

A clinical variant of coronavirus disease 2019 with diarrhoea as the initial symptom compared with other variants.

Minerva Gastroenterol (Torino) 2021 Apr 15. Epub 2021 Apr 15.

Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S2724-5985.21.02827-0DOI Listing
April 2021

Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease.

World J Gastroenterol 2021 Mar;27(10):959-975

Department of Therapy № 1 with Training General Practitioners, Tashkent Medical Academy, Tashkent 100109, Uzbekistan.

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Weight loss is a key factor for successful NAFLD and CVD therapy. Ursodeoxycholic acid (UDCA), which is one of the first-line therapeutic agents for treatment of NAFLD, is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.

Aim: To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests, lipid profile, hepatic steatosis and fibrosis, atherogenesis, and ASCVD risk in men and women with NAFLD, as well as to assess the impact of > 5% weight reduction on these parameters.

Methods: An open-label, multicenter, international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise. The efficacy criteria were liver enzymes, lipid profile, fatty liver index (FLI), noninvasive liver fibrosis tests (nonalcoholic fatty liver disease fibrosis score and liver fibrosis index), carotid intima-media thickness (CIMT), and ASCVD risk score. To test statistical hypotheses, the Wilcoxon test, paired -test, Fisher's exact test, and Pearson's chi-squared test were used.

Results: The alanine aminotransferase (ALT) level changed by -14.1 U/L (-31.0; -5.3) from baseline to 3 mo and by -6.5 U/L (-14.0; 0.1) from 3 to 6 mo. The magnitude of ALT, aspartate transaminase, and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo ( < 0.001, < 0.01, < 0.001, respectively). At 6 mo, in the total sample, we observed a statistically significant decrease in body weight and levels of FLI: 84.9 ± 10.4 72.3 ± 17.6, < 0.001, total cholesterol: 6.03 ± 1.36 5.76 ± 1.21, < 0.001, low-density lipoprotein: 3.86 ± 1.01 3.66 ± 0.91, < 0.001, and triglyceride: 3.18 (2.00; 4.29) 2.04 (1.40; 3.16), < 0.001. No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found. The CIMT decreased significantly in the total sample (0.985 ± 0.243 0.968 ± 0.237, = 0.013), whereas the high-density lipoprotein ( = 0.036) and 10-year ASCVD risk ( = 0.003) improved significantly only in women. Fifty-four patients (31%) achieved > 5% weight loss. At the end of the study, the FLI decreased significantly in patients with (88.3 ± 10.2 71.4 ± 19.6, < 0.001) and without > 5% weight loss (83.5 ± 10.3 72.8 ± 16.7, < 0.001). The changes in ALT, aspartate transaminase, glutamyltransferase, total cholesterol, and low-density lipoprotein levels were similar between the subgroups.

Conclusion: UDCA normalizes liver enzymes greatly within the first 3 mo of treatment, improves lipid profile and hepatic steatosis independent of weight loss, and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v27.i10.959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968130PMC
March 2021

Diarrhoea in adults with coronavirus disease-beyond incidence and mortality: a systematic review and meta-analysis.

Infect Dis (Lond) 2021 05 15;53(5):348-360. Epub 2021 Feb 15.

Department of Introduction to Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation.

Aim: Diarrhoea is a relatively common manifestation of coronavirus disease (COVID-19), but there is no systematic review which comprehensively describes it beyond its incidence and impact on prognosis. This study aims to provide a detailed systematic review of diarrhoea in adults with COVID-19.

Methods: A PUBMED and Scopus search (until 7 September 2020) was performed. Studies that were limited to describing incidence of diarrhoea and its effect on prognosis were excluded.

Results: Twenty-six papers including 7860 patients with COVID-19 were subjected to synthesis. Mean duration of diarrhoea was 4.2 (3.6-4.9) days (range 1-16 days), whereas mean bowel movement count was 4.6 (3.8-5.3) and maximum was 20 per day. Diarrhoea started on an average 5.1 (3.8-6.5) days after disease onset but was the first manifestation in 4.3% patients. Stool occult blood was detected in 6.8% of patients with diarrhoea, while 53.3% cases had watery diarrhoea. Patients with diarrhoea also had elevated faecal calprotectin. Viral genome in faeces was detected more often in patients with diarrhoea and most often in patients without respiratory symptoms. Fever, myalgia and respiratory symptoms were observed with the same incidence in patients with and without diarrhoea. Similarly, there were no differences noted in complete blood count and most inflammation biomarkers between patients with and without diarrhoea. However, nausea, vomiting abdominal pain, sneezing and headache were more common in patients with diarrhoea. Diarrhoea was the main manifestation of COVID-19 in 6.1% of cases and this form of the disease had specific features.

Conclusions: Diarrhoea in COVID-19 needs further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23744235.2021.1885733DOI Listing
May 2021

Fatty Liver and Systemic Atherosclerosis in a Young, Lean Patient: Rule Out Lysosomal Acid Lipase Deficiency.

Case Rep Gastroenterol 2019 Sep-Dec;13(3):498-507. Epub 2019 Dec 4.

Federal Research Center for Nutrition and Biotechnology, Moscow, Russian Federation.

Lysosomal acid lipase deficiency (LALD) is a rare genetic disease characterized by the accumulation of cholesteryl esters and triglycerides in many organs, including the liver, spleen, lymph nodes, bone marrow, and vascular endothelium. Patients with LALD can appear asymptomatic until liver failure or premature sudden death from coronary artery disease, stroke, and aneurysm, which lead to the diagnosis. Herein, we present a diagnostic workup in a young 17-year-old female patient who manifested hepatosplenomegaly, elevated liver enzymes, severe dyslipidemia, and systemic atherosclerosis. Liver biopsy demonstrated over 90% diffuse microvesicular steatosis, lipid accumulation in Kupffer cells, and birefringent cholesteryl ester crystals. The diagnosis of LALD was proven by the decrease of lysosomal acid lipase activity in dried blood spots and by the detection of two compound heterozygous mutations in the gene: nonsense mutation G796T (Gly266Term) and splicing site mutation G894A (E8SJM). The patient started enzyme replacement therapy with sebelipase alfa. Following the 1-year treatment, the patient remained asymptomatic, her serum aminotransferase levels were normal, liver density increased due to lipid resorption, and plaque-associated stenosis of carotid artery regressed. Moreover, liver biopsy showed a decrease of cholesteryl ester crystals in Kupffer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000504646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940451PMC
December 2019

The Evolution of Human Probiotics: Challenges and Prospects.

Probiotics Antimicrob Proteins 2020 12;12(4):1291-1299

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov, First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

In recent years, the intestinal microbiota has been found to greatly influence a number of biological processes important for human health and longevity. Microbial composition changes easily in response to external factors, such as an unbalanced diet, lack of physical activity, and smoking. Probiotics are a key factor in maintaining the optimal composition of the intestinal microbiota. However, a number of important questions related to probiotics, such as indication for prescription, comparative efficacy of monostrain and multistrain probiotics, methods of delivery, and shelf life, remain unresolved. The aim of this review is to highlight existing issues regarding probiotic production and their prescription. The review presents the most recent findings regarding advantages and efficacy of monostrain and multistrain probiotics, preservation of probiotic strains in capsules and microcapsules, production of probiotics in the form of biofilms for improved efficacy and survival, and results of clinical studies evaluating the benefits of probiotics against different pathologies. We believe that this work will be of interest to physicians and researchers alike and will promote the development of new probiotics and ensuing regimens aimed at the treatment of various diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12602-019-09628-4DOI Listing
December 2020

Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT.

BMC Gastroenterol 2019 Dec 31;20(1). Epub 2019 Dec 31.

The Institute of General Pathology and Pathophysiology, 8, Baltiyskaya St, Moscow, Russian Federation, 125315.

Background: The aim of this study was to investigate the efficacy and safety of the novel complex drug, consisting of released-active form of antibodies to S-100 protein, tumor necrosis factor-α and histamine, (Kolofort) under outpatient conditions in patients with functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap.

Methods: The subjects of the observational noninterventional retrospective program were the data of 14,362 outpatient records of patients with diagnosed FD, IBS, and/or overlap, who were observed by gastroenterologists from November 01, 2017, through March 30, 2018, who received the drug Kolofort in monotherapy for 12 weeks, 2 tablets twice a day. To assess the presence and severity of symptoms of functional gastrointestinal disorders (FGID), the "7*7" questionnaire developed by a working group from the Russian Gastroenterological Association was used. The evaluated parameters included the proportion of patients: who had a 50% or more reduction in the total score; who have switched to the less severe category of the condition; who have switched to the "healthy" or "borderline ill" severity categories; and the change in the score in domains 1-7.

Results: The final efficacy analysis included data from 9254 patients. A decrease in the total score by 50% or more was observed in 80.45% of patients with FD, 79.02% of patients with IBS, and in 83% of patients with both IBS and FD. Switch to a lower severity category of the condition at the end of therapy was noted in 93.35% of patients with FD, in 93.80% of cases in patients with IBS, and in 96.17% of cases in patients with a combination of IBS and FD. A total of 94 adverse events (AEs) were reported in 80 patients (0.65%).

Conclusion: The COMFORT program has demonstrated the positive effect of treatment in the majority of patients with IBS and FD and their combination in real clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-019-1143-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938622PMC
December 2019

Is small intestinal bacterial overgrowth a cause of hyperdynamic circulation in cirrhosis?

Turk J Gastroenterol 2019 Nov;30(11):964-975

Department of Gastroenterology and Hepatology, Sechenov University, Moscow, Russia.

Background/aims: Small intestinal bacterial overgrowth (SIBO) and hemodynamic changes are common in cirrhosis. We wanted to examine our hypothesis whether SIBO leads to hemodynamic changes in cirrhosis.

Materials And Methods: A total of 50 patients with cirrhosis and 15 healthy controls were enrolled in a pilot prospective study. All participants underwent the lactulose hydrogen breath test for SIBO and echocardiography with a simultaneous assessment of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated.

Results: Study participants with SIBO had a lower systolic blood pressure and systemic vascular resistance compared to those without SIBO and to healthy controls (110.2±12.3 mmHg vs. 126.2±21.0 mmHg and 121.2±9.8 mmHg; p=0.005 and p=0.011, respectively; 1312±352 dyn•s•cm-5 vs. 1704±424 dyn•s•cm-5 and 1648±272 dyn•s•cm-5; p=0.001 and p=0.006, respectively), but a higher cardiac output (5.38±1.41 l/min vs. 4.52±1.03 l/min and 4.40±0.68 l/min; p=0.034 and p=0.041, respectively) and C-reactive protein (10.5[1.2-16.5] mg/l vs. 2.8[0.6-9.1] mg/l; p=0.028; no comparison with healthy controls). There were no significant differences between patients without SIBO and healthy controls with regard to systolic blood pressure (p=0.554), systemic vascular resistance (p=0.874), and cardiac output (p=0.795). SIBO was associated with vasodilation and hyperdynamic circulation in decompensated cirrhosis (p=0.002; p=0.012), but not in compensated cirrhosis (p=1.000; p=0.474).

Conclusions: SIBO is associated with hyperdynamic circulation and other hemodynamic changes in cirrhosis and may be a principal factor causing these through systemic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5152/tjg.2019.18551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883995PMC
November 2019

Metabolic activity of intestinal microflora in patients with bronchial asthma.

Clin Pract 2019 Jan 28;9(1):1126. Epub 2019 Feb 28.

Chair of Internal Diseases Propedeutics.

The gut microbiota plays the important role to support the immunological tolerance. To study a metabolic activity of the intestinal microflora the 44 patients suffering from bronchial asthma and 17 healthy volunteers were tested. The short-chain fatty acids (SCFA) spectrum was determined using the method of gas-liquid chromatographic analysis. We have detected a significant decrease the total content of the fatty acids in the feces (P<0.001), the absolute concentrations of the individual acids (acetate, propionate, butyrate; P<0.001) and the total content of isoacids (P<0.001) for all of the patients with bronchial asthma in the study, regardless of the phenotype. The anaerobic type of the SCFA spectrum was detected for the majority (83%) of the patients tested. The aerobic type of the SCFA metabolic profile was detected for another part (17%) of the patients tested. Being detected the parameters change could play the principal role as for the bronchial asthma course as to support the organism sensibilisation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/cp.2019.1126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401556PMC
January 2019

Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden.

Infect Dis (Lond) 2019 Feb 30;51(2):131-139. Epub 2018 Nov 30.

o 15 Department of Internaö Medicine Division of Infectious Diseases , Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm , Sweden.

Background: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden.

Methods: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12).

Results: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events.

Conclusion: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23744235.2018.1535186DOI Listing
February 2019

Clinical validation of the "7 × 7" questionnaire for patients with functional gastrointestinal disorders.

J Gastroenterol Hepatol 2019 Jun 25;34(6):1042-1048. Epub 2018 Dec 25.

V.H. Vasilenko Clinic of Internal Diseases, Propedeutics, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia.

Background And Aim: Physicians use different scales and questionnaires to assess the severity of clinical symptoms in patients with functional gastrointestinal disorders. The current study aimed to validate the "7 × 7" questionnaire for assessment of severity of the symptoms as a tool for the efficacy of treatment of functional gastrointestinal disorders, using the Clinical Global Impressions scale as the reference standard.

Methods: Fifty inpatients aged from 18 to 64 with a confirmed diagnosis of irritable bowel syndrome (26 patients, 52%), functional dyspepsia (15 patients, 30%), or both (9 patients, 18%) were prospectively enrolled in the study. We used both the 7 × 7 questionnaire and the Clinical Global Impressions scale before and after 28 days of stable treatment.

Results: Our study revealed a significant correlation between the 7 × 7 questionnaire and the Clinical Global Impressions scale results in assessment of severity of the clinical symptoms and their dynamics during treatment. The 7 × 7 questionnaire showed sensitivity of 74.5% and specificity of 54.1% for evaluating patients with mild to severe disease and 66.6% and 76%, respectively, for evaluating patients with moderate to severe disease. The Cronbach's alpha coefficient was 0.719. The intraclass correlation coefficient among participants in whom the condition remained the same was 0.973 (12 participants [24.5%]).

Conclusions: The 7 × 7 questionnaire is a convenient, sensitive, and reliable tool for assessing the severity of symptoms and treatment efficacy in people with functional gastrointestinal disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.14546DOI Listing
June 2019

NT-proBNP as a biomarker for hyperdynamic circulation in decompensated cirrhosis.

Gastroenterol Hepatol Bed Bench 2018 ;11(4):325-332

Sechenov First Moscow State Medical University (Sechenov University), Clinic for Internal Diseases, Gastroenterology and Hepatology Pogodinskaya str., 1, bld. 1, 119435, Moscow , Russian Federation.

Aim: To assess NT-proBNP as a biomarker for hyperdynamic circulation in decompensated cirrhosis.

Background: Hyperdynamic circulation is common in decompensated cirrhosis. The previous studies reveal that N-terminal-proBNP (NT-proBNP) is elevated in cirrhosis.

Methods: A prospective study involved 47 patients with decompensated cirrhosis. All of them underwent echocardiography with simultaneous measurement of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated. The concentration of NT-proBNP in blood was measured with enzyme-linked immunosorbent assay.

Results: In patients with decompensated cirrhosis, the concentration of NT-proBNP in blood directly correlated with end-diastolic volume (r=0.482; p<0.001), stroke volume (r= 0.566; p<0.001), cardiac output (r=0.556; p<0.001), volume of the left atrium (r=0.292; p=0.047), and inversely correlated with systemic vascular resistance (r=-0.538; p<0.001). There was no significant correlation between NT-proBNP and ejection fraction (p=0.083). Patients with hyperdynamic circulation have higher concentration of NT-proBNP (152÷476 pg/ml vs. 31÷133 pg/ml, p<0.001) regardless of the presence of diastolic dysfunction (p=0.222). According to ROC analysis, the best cut-off values for detection of hyperdynamic circulation in decompensated cirrhosis are considered to be 170.0 pg/ml of blood NT-proBNP, showing sensitivity and specificity of 72.0 and 86.4%, respectively. The positive and negative predictive value are 86.4% and 73.1%, AUC = 0.829 (0.709-0.949).

Conclusion: NT-proBNP may serve as a non-invasive biomarker for hyperdynamic circulation in decompensated cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204251PMC
January 2018

Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta-analysis.

Hepatol Int 2018 Nov 4;12(6):567-576. Epub 2018 Oct 4.

Sechenov University, Pogodinskaya Str., 1, bld. 1, 119435, Moscow, Russian Federation.

Background: Small intestinal bacterial overgrowth (SIBO) was detected in cirrhosis in many studies. The aim is to perform a systematic review and meta-analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO with features of cirrhosis.

Methods: PUBMED search (until 14 January 2018) was performed. Specific search terms were: '(cirrhosis) AND (SIBO OR bacterial overgrowth)'. Studies not relating to cirrhosis or SIBO, animal studies, and non-original articles were excluded. A meta-analysis of all studies was performed using a random-effects model.

Results: 117 references were identified by the PUBMED search. 3 references were added after handsearching the reference lists of all the articles. 99 references were excluded. 21 studies (included in total 1264 cirrhotics and 306 controls) remained for qualitative analysis and quantitative synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8-47.1), while the prevalence of SIBO for controls was 10.7% (95% CI 5.7-19.0). OR 6.83 (95% CI 4.16-11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001). SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001), and was not associated with hypocoagulation. Further studies are required to clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt hepatic encephalopathy in past, esophageal varices and systemic inflammation.

Conclusion: Small intestinal bacterial overgrowth is more often detected in cirrhosis than in healthy persons and is associated with some features of cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-018-9898-2DOI Listing
November 2018

Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE).

J Antimicrob Chemother 2018 12;73(12):3430-3441

Medical University of Vienna, Vienna, Austria.

Objectives: Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD.

Methods: The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591.

Results: Median Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. Cmax ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 μg/g for fidaxomicin and 0-1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death.

Conclusions: Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dky368DOI Listing
December 2018

Prevalence of Clostridium Difficile-Associated Diarrhoea in Hospitalised Patients (Results of a Russian Prospective Multicentre Study).

Infect Dis Ther 2018 Dec 10;7(4):523-534. Epub 2018 Sep 10.

JSC "Astellas Pharma", Moscow, Russia.

Introduction: The objective of the study was to evaluate the prevalence of Clostridium difficile-associated diarrhoea (CDAD) among hospitalised patients with antibiotic-associated diarrhoea (AAD) in general and by specific types of medical care and hospital units.

Methods: A prospective, cross-sectional, non-interventional, multicentre study. The main inclusion criteria were: patient age ≥ 18 years, hospital stay of at least 48 h, current antibiotic therapy or antibiotic therapy within the previous 30 days, loose stools (Bristol stool types 5-7 and stool frequency ≥ 3 within ≤ 24 consecutive hours or exceeding normal for the patient) and signed informed consent form. The stool sample was taken to the local (study site) microbiology laboratory for detection of glutamate dehydrogenase (GDH) and toxins A/B using enzyme immunoassay (EIA) stool test.

Results: From April 2016 to April 2017, a total of 1245 patients from 12 large hospitals were enrolled in the study. Data on 81 patients were excluded from the analysis for different reasons. Data on 1164 patients (45.2% males and 54.8% females) with a mean age of 54.9 years (range 18-95 years) were analysed. Length of hospitalisation was 2-188 days (median, 8 days). The EIA stool test showed CDAD-positive results in 21.7% (253/1164) patients. The patients were from surgery units (546/1164), internal medicine units (510/1164) and intensive care units (108/1164). The prevalence of CDAD among patients from surgery, internal medicine and intensive care units was 26.2, 17.8 and 17.6%, respectively. Oncology, gastroenterology, septic surgery, oncohaematology and general medical hospital units accounted for more than 75% of all patients included; the prevalence of CDAD by those hospital units was 11.3, 15.0, 39.2, 17.6, and 27.2%, respectively. The proportion of GDH-positive and toxin A/B-negative patients by the rapid stool test result was 16.8% (196/1164). The prevalence of CDAD varied widely between the hospitals (from 0 to 44.3%).

Conclusions: The prevalence of CDAD among hospitalised patients with AAD in this study was 21.7% (95% confidence interval: 14.8 and 28.7%). The percentage of CDAD varied widely between hospitals and by specific types of medical care and hospital units.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-018-0209-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249186PMC
December 2018

Dose-Response Effect of Antibodies to S100 Protein and Cannabinoid Receptor Type 1 in Released-Active Form in the Light-Dark Test in Mice.

Dose Response 2018 Apr-Jun;16(2):1559325818779752. Epub 2018 Jun 26.

Research Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.

Earlier studies have shown that combination of antibodies to S100 protein and to cannabinoid receptor type 1 in released-active form (Brizantin) may possess anxiolytic properties and decrease nicotine dependence. Released-active form of antibodies is a novel approach that permits to modify natural functions of the target molecule (antigen) under investigation. The aim of the present study was to evaluate the anxiolytic-like effect of Brizantin in the light-dark test in mice, according to its ability to influence the number of entries into the lit compartment and the total time spent there. Three doses of Brizantin (2.5, 5, and 10 mL/kg) were compared with diazepam (1 mg/kg), placebo, and vehicle control. Anxiolytic-like effect of the tested drug was shown to be dose dependent, with an increasing trend from 2.5 to 10 mL/kg. Brizantin in its highest dose significantly increased studied behavioral parameters, although its effect was less pronounced than that of the reference drug diazepam (1 mg/kg).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1559325818779752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043939PMC
June 2018

Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease.

Minerva Gastroenterol Dietol 2018 Sep 8;64(3):208-219. Epub 2018 Feb 8.

Abbott Laboratories, LLC, Chicago, IL, USA.

Background: The effect of oral and/or parenteral ademetionine (500 mg intravenous [IV] and tablet formulation) on clinical symptoms and biochemical markers of intrahepatic cholestasis (IHC) was investigated in subjects with alcoholic liver disease (ALD) and compensated liver function.

Methods: Prospective, multicenter, open-label study consisting of a screening period and an 8-week treatment period and performed in subjects (18-75 years) with compensated ALD and confirmed IHC. Subjects with a baseline serum conjugated bilirubin value above normal range were initially treated with IV ademetionine for two weeks (500-800 mg daily) and continued with oral ademetionine 1500 mg daily for a further six weeks. Subjects with a baseline serum conjugated bilirubin value within normal range were treated with oral ademetionine for eight weeks.

Results: A total of 72 subjects were treated; 41 initially with IV ademetionine and 31 with oral ademetionine. Clinical symptoms status improved from baseline to end of treatment with an increase in the proportion of subjects with no symptoms. Ademetionine showed significant improvements in primary efficacy parameters alkaline phosphatase (ALP) and γ-glutamyltransferase (γGT) (P<0.0001). Although decreases of ALP were higher for subjects initially treated with IV ademetionine, these subjects also had higher baseline values. No safety concerns with ademetionine arose with respect to the severity or frequency of adverse events (AEs) during the treatment period, laboratory parameters, and vital signs.

Conclusions: Administration of oral or IV/oral ademetionine step-therapy for 8 weeks to subjects with IHC due to ALD was safe and provided a significant improvement of disease burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S1121-421X.18.02461-3DOI Listing
September 2018

Cholesteryl Ester Crystals in Lysosomal Acid Lipase Deficiency.

N Engl J Med 2017 Mar;376(9):e14

First Moscow State Medical University, Moscow, Russia

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMicm1610060DOI Listing
March 2017

Prednisolone plus S-adenosil-L-methionine in severe alcoholic hepatitis.

Hepatol Int 2016 Nov 23;10(6):983-987. Epub 2016 Jun 23.

I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.

Purpose/background: Severe alcoholic hepatitis (AH) is a life-threatening liver disease with a potential of 30-40 % mortality at 1 month. While steroids remain to be a first line therapy, they provide only about 50 % survival benefit. The aim of the study was to evaluate the efficacy of glucocorticoids plus S-adenosylmethionine (SAMe), as compared to glucocorticoids alone, in patients with severe alcoholic hepatitis.

Methods: Forty patients with severe AH were randomized in two groups and enrolled in the prospective trial. Group 1 (n = 20) patients received prednisolone 40 mg/daily per os, and group 2 (n = 20) patients were managed with prednisolone 40 mg/daily per os plus SAMe 800 mg i.v.

Treatment: Duration was 28 days.

Results: The response rate assessed by Lille model was significantly higher in the prednisolone plus SAMe group (19 of 20; 95 %) than in the prednisolone group (13 of 20; 65 %), p = 0.044. Two (10 %) patients died, both from the prednisolone group. There were no lethal outcomes in the prednisolone plus SAMe group. The Kaplan-Meier method showed no significant differences between the two groups (p = 0.151, log-rank). Hepatorenal syndrome (HRS) occurred in 20 % in the prednisolone group (4 of 20 patients) while no HRS cases were registered in the prednisolone plus SAMe group (p = 0.035).

Conclusions: Management of severe alcoholic hepatitis with prednisolone plus SAMe was associated with better therapy response (p = 0.044) and less frequent HRS occurrence (p = 0.035). Mortality was not significantly lower in the prednisolone-SAMe group than in the prednisolone-only group at 28 days (10 vs. 0 %, p = 0.151).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-016-9751-4DOI Listing
November 2016

Platelet count to spleen diameter ratio non-invasively identifies severe fibrosis and cirrhosis in patients with autoimmune hepatitis.

J Gastroenterol Hepatol 2016 Dec;31(12):1956-1962

Department of Hepatology, V.H. Vasilenko Clinic of Internal Diseases, Gastroenterology and Hepatology, First Moscow State Medical University n.a. I.M. Sechenov, Moscow, Russian Federation.

Background And Aim: Non-invasive markers are essential to assess the progression of chronic liver diseases to fibrosis/ cirrhosis and the effectiveness of therapeutic strategies. The aim of this study was to evaluate the ability of non-invasive markers to identify significant fibrosis, severe fibrosis, and cirrhosis in patients with autoimmune hepatitis (AIH).

Methods: Seventy-six patients with AIH were enrolled in the study and analyzed for the following parameters of liver fibrosis: Fibrosis 4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet count ratio (APRI), and platelet count to spleen diameter (PC/SD) ratio. All patients underwent liver biopsy. The diagnostic accuracy of tests was evaluated by the area under the receiver operating characteristic curve (AUROC).

Results: Among the 76 AIH patients, 55 (72.3%) had significant fibrosis (≥ F2), 37 (48.7%) had severe fibrosis (≥ F3), and 29 (38.2%) had cirrhosis (F4). PC/SD ratio (AUROC = 0.840) was superior to AAR (AUROC = 0.756), FIB-4 (AUROC = 0.702), and APRI (AUROC = 0.626) in discriminating between mild and significant fibrosis (≥ F2). The AUROCs of PC/SD ratio, FIB-4, AAR, and APRI were 0.884, 0.742, 0.731, and 0.707, respectively, for severe fibrosis (≥ F3); 0.968, 0.795, 0.744, and 0.723, respectively, for cirrhosis (F4). PC/SD ratio correctly identified 85.1% of patients with severe fibrosis, and 89.6% of patients with cirrhosis.

Conclusions: PC/SD ratio proved to be a simple non-invasive tool to correctly identify AIH patients with severe fibrosis and cirrhosis, thereby reducing the need for a liver biopsy in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.13407DOI Listing
December 2016

Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease.

Cochrane Database Syst Rev 2016 Mar 2;3:CD011602. Epub 2016 Mar 2.

The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.

Background: Heavy alcohol consumption causes alcoholic liver disease and is a causal factor of many types of liver injuries and concomitant diseases. It is a true systemic disease that may damage the digestive tract, the nervous system, the heart and vascular system, the bone and skeletal muscle system, and the endocrine and immune system, and can lead to cancer. Liver damage in turn, can present as multiple alcoholic liver diseases, including fatty liver, steatohepatitis, fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma, with presence or absence of hepatitis B or C virus infection. There are three scarring types (fibrosis) that are most commonly found in alcoholic liver disease: centrilobular scarring, pericellular fibrosis, and periportal fibrosis. When liver fibrosis progresses, alcoholic cirrhosis occurs. Hepatocellular carcinoma occurs in 5% to 15% of people with alcoholic cirrhosis, but people in whom hepatocellular carcinoma has developed are often co-infected with hepatitis B or C virus.Abstinence from alcohol may help people with alcoholic disease in improving their prognosis of survival at any stage of their disease; however, the more advanced the stage, the higher the risk of complications, co-morbidities, and mortality, and lesser the effect of abstinence. Being abstinent one month after diagnosis of early cirrhosis will improve the chance of a seven-year life expectancy by 1.6 times. Liver transplantation is the only radical method that may change the prognosis of a person with alcoholic liver disease; however, besides the difficulties of finding a suitable liver transplant organ, there are many other factors that may influence a person's survival.Ultrasound is an inexpensive method that has been used for years in clinical practice to diagnose alcoholic cirrhosis. Ultrasound parameters for assessing cirrhosis in people with alcoholic liver disease encompass among others liver size, bluntness of the liver edge, coarseness of the liver parenchyma, nodularity of the liver surface, size of the lymph nodes around the hepatic artery, irregularity and narrowness of the inferior vena cava, portal vein velocity, and spleen size.Diagnosis of cirrhosis by ultrasound, especially in people who are asymptomatic, may have its advantages for the prognosis, motivation, and treatment of these people to decrease their alcohol consumption or become abstinent.Timely diagnosis of alcoholic cirrhosis in people with alcoholic liver disease is the cornerstone for evaluation of prognosis or choosing treatment strategies.

Objectives: To determine the diagnostic accuracy of ultrasonography for detecting the presence or absence of cirrhosis in people with alcoholic liver disease compared with liver biopsy as reference standard.To determine the diagnostic accuracy of any of the ultrasonography tests, B-mode or echo-colour Doppler ultrasonography, used singly or combined, or plus ultrasonography signs, or a combination of these, for detecting hepatic cirrhosis in people with alcoholic liver disease compared with liver biopsy as a reference standard, irrespective of sequence.

Search Methods: We performed searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, The Cochrane Library (Wiley), MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation Index Expanded to 8 January 2015. We applied no language limitations.We screened study references of the retrieved studies to identify other potentially relevant studies for inclusion in the review and read abstract and poster publications.

Selection Criteria: Three review authors independently identified studies for possible inclusion in the review. We excluded references not fulfilling the inclusion criteria of the review protocol. We sent e-mails to study authors.The included studies had to evaluate ultrasound in the diagnosis of hepatic cirrhosis using only liver biopsy as the reference standard.The maximum time interval of investigation with liver biopsy and ultrasonography should not have exceeded six months. In addition, ultrasonography could have been performed before or after liver biopsy.

Data Collection And Analysis: We followed the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy.

Main Results: The review included two studies that provided numerical data regarding alcoholic cirrhosis in 205 men and women with alcoholic liver disease. Although there were no applicability concerns in terms of participant selection, index text, and reference standard, we judged the two studies at high risk of bias. Participants in both studies had undergone both liver biopsy and ultrasonography investigations. The studies shared only a few comparable clinical signs and symptoms (index tests).We decided to not perform a meta-analysis due to the high risk of bias and the high degree of heterogeneity of the included studies.

Authors' Conclusions: As the accuracy of ultrasonography in the two included studies was not informative enough, we could not recommend the use of ultrasonography as a diagnostic tool for liver cirrhosis in people with alcoholic liver disease. In order to be able to answer the review questions, we need diagnostic ultrasonography prospective studies of adequate sample size, enrolling only participants with alcoholic liver disease.The design and report of the studies should follow the Standards for Reporting of Diagnostic Accuracy. The sonographic features, with validated cut-offs, which may help identify clinical signs used for diagnosis of fibrosis in alcoholic liver disease, should be carefully selected to achieve maximum diagnostic accuracy on ultrasonography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD011602.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464787PMC
March 2016
-->