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Effect of probiotics on hemodynamic changes and complications associated with cirrhosis:A pilot randomized controlled trial

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World Journal of Hepatology 2022年第8期14卷 1667-1677页

作者： Roman Maslennikov Irina Efremova Vladimir Ivashkin Maria Zharkova elena Poluektova elena shirokova Konstantin Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Scientific Community for Human Microbiome Research Moscow 119435Russia Consultative and Diagnostic Center No.2 of Moscow Health Department Moscow 107764Russia

BACKGROUND Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease *** may reduce bacterial translocation and may therefore be useful to redress the circulatory *** To investigate the effect of probiotics on hemodynamic parameters,systemic inflammation,and complications of cirrhosis in this randomized placebocontrolled *** This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis;24 patients received probiotics(Saccharomyces boulardii)for 3 mo,and 16 patients received a placebo over the same *** function and the systemic hemodynamic status were evaluated pre-and *** and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic *** output and systemic vascular resistance were *** Following a 3-mo course of probiotics in comparison to the control group,we observed amelioration of hyperdynamic circulation[a decrease in cardiac output(P=0.026)and an increase in systemic vascular resistance(P=0.026)]and systemic inflammation[a decrease in serum C-reactive protein levels(P=0.044)],with improved liver function[an increase in serum albumin(P=0.001)and a decrease in the value of Child-Pugh score(P=0.001)]as well as a reduction in the severity of ascites(P=0.022),hepatic encephalopathy(P=0.048),and cholestasis[a decrease in serum alkaline phosphatase(P=0.016)and serum gamma-glutamyl transpeptidase(P=0.039)activity]and an increase in platelet counts(P<0.001)and serum sodium level(P=0.048).CONCLUSION Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.

关键词： Gut Gut-liver axis Microbiota Hemodynamics Heart Gut-heart axis Saccharomyces boulardii Portal hypertension

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Gut-liver axis in cirrhosis:Are hemodynamic changes a missing link?

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World Journal of Clinical Cases 2021年第31期9卷 9320-9332页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova elena Poluektova elena shirokova Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Interregional Public Organization"Scientific Community for the Promotion of the Clinical Study of the Human Microbiome" Moscow 119435Russia Department of Internal Medicine Consultative and Diagnostic Center of the Moscow City Health DepartmentMoscow 107564Russia

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially *** introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several *** dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic *** inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer *** majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with ***,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly *** remain a missing link in the gut-liver axis and a challenge for future research.

关键词： Gut microbiota Gut dysbiosis Small intestinal bacterial overgrowth Intestinal barrier Bacterial translocation Vasodilation Hyperdynamic circulation Gut microbiome Cardiac output Systemic vascular resistance

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Immune disorders and rheumatologic manifestations of viral hepatitis

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World Journal of Gastroenterology 2021年第18期27卷 2073-2089页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova elena shirokova Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Interregional Public Organization“Scientific Community for the Promotion of the Clinical Study of the Human Microbiome” Moscow 119435Russia Department of Internal Medicine 1 Сonsultative and Diagnostic Center 2 of the Moscow City Health DepartmentMoscow 107564Russia

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 *** relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and *** isolated cases of these associations are described for hepatitis *** links are least studied,and are often controversial for hepatitis E,possibly due to their relatively rare *** 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.

关键词： Hepatitis A Hepatitis B Hepatitis C Hepatitis E Vasculitis Rheumatoid factor

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Probiotics in hepatology:An update

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World Journal of Hepatology 2021年第9期13卷 1154-1166页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova elena Poluektova elena shirokova Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Internal Medicine Consultative and Diagnostic Center of the Moscow City Health DepartmentMoscow 107564Russia

The gut-liver axis plays an important role in the pathogenesis of various liver *** are living bacteria that may be used to correct disorders of this *** progress has been made in the study of probiotic drugs for the treatment of various liver diseases in the last *** has been proven that probiotics are useful for hepatic encephalopathy,but their effects on other symptoms and syndromes of cirrhosis are poorly *** 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 *** 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 *** 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.

关键词： Gut-liver axis Pathogenesis Gut dysbiosis Gut microbiota Gut microbiome Liver disease Probiotics Hepatic encephalopathy Cirrhosis Metabolic associated fatty liver disease Alcoholic liver disease Primary sclerosing cholangitis

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

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World Journal of Hepatology 2021年第5期13卷 557-570页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova Aliya Alieva Ekaterina Kashuh Ekaterina Tsvetaeva elena Poluektova elena shirokova Konstantin Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Interregional Public Organization“Scientific Community for the Promotion of the Clinical Study of the Human Microbiome” Moscow 119435Russia

BACKGROUND Gut dysbiosis is common in *** To study the influence of gut dysbiosis on prognosis in *** The case-control study included 48 in-patients with cirrhosis and 21 healthy *** microbiome was assessed using 16S ribosomal ribonucleic acid gene *** used modified dysbiosis ratio(MDR):[Bacilli(%)+Proteobacteria(%)]/[Clostridia(%)+Bacteroidetes(%)].Patients with MDR more the median made up the group with severe dysbiosis,others did the group with nonsevere *** follow-up period was 4 *** The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis(54.2%vs 12.5%;P=0.001).The presence of severe dysbiosis was independent risk factors for death[hazard ratio=8.6×(1.9-38.0);P=0.005].The abundance of Enterobacteriaceae(P=0.002),Proteobacteria(P=0.002),and Lactobacillaceae(P=0.025)was increased and the abundance of Firmicutes(P=0.025)and Clostridia(P=0.045)was decreased in the deceased patients compared with the *** deceased patients had a higher MDR value than the survivors[0.131×(0.069-0.234)vs 0.034×(0.009-0.096);P=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)vs 0.005×(0.002-0.007);P<0.001],and in patients with decompensated cirrhosis than in patients with compensated cirrhosis[0.106×(0.023-0.211)vs 0.033×(0.012-0.074);P=0.031].MDR correlated negatively with prothrombin(r=-0.295;P=0.042),cholinesterase(r=-0.466;P=0.014)and serum albumin(r=-0.449;P=0.001)level and positively with Child–Turcotte–Pugh scale value(r=0.360;P=0.012).CONCLUSION Gut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.

关键词： Cirrhosis Dysbiosis Gut ROC-analysis Microbiota Microbiome Gut-liver axis

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