Clostridioides difficile infection in patients with nonalcoholic fatty liver disease-current status

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathogenesis of NAFLD is not fully understood,although NAFLD is thought to be a hepatic form of metabolic syndrome.There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis,and as with many other conditions affecting the microbiota,NAFLD may be a novel risk factor for Clostridioides difficile(C.difficile)colonization(CDC)and C.difficile infection(CDI).CDI is an emerging nosocomial disease,and community-acquired cases of infection are growing,probably due to an increase in CDC rates.The association of NAFLD with CDI has been shown in only 4 studies to date,three of which included less than 1000 patients,although the frequency of NAFLD in these studies was observed in almost 20%of the total patient cohort.These data revealed that NAFLD is a risk factor for CDI development and,moreover,is a risk factor for intestinal complications of CDI.More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.

Patients with functional bowel disorder have disaccharidase deficiency:A single-center study from Russia

BACKGROUND Functional bowel disorder(FBD)may be caused by a decrease in disaccharidase activity.Thus,the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.AIM To determine the potential value of intestinal disaccharidases glucoamylase,maltase,sucrase,and lactase in understanding the etiology and pathogenesis of FBD.METHODS A total of 82 FBD patients were examined.According to the Rome IV criteria(2016),23 patients had diarrhea-predominant irritable bowel syndrome(IBS),33 had functional diarrhea,10 had constipation-predominant IBS,4 had functional constipation,and 12 had mixed IBS.The Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine,in duodenal biopsies obtained during esophagogastroduodenoscopy.RESULTS Lactase deficiency was detected in 86.5%of patients,maltase deficiency in 48.7%,sucrase deficiency in 50%,and glucoamylase deficiency in 84.1%.The activities of all enzymes were reduced in 31.7%of patients,and carbohydrase deficiency was detected in 63.5%of patients.The low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2%of patients.CONCLUSION In 78 of the 82 patients with FBD,gastrointestinal symptoms were associated with disaccharidase deficiency.

Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis

BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with cirrhosis.Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis,dysbiosis and SIBO were always studied separately.AIM To study the relationship of gut dysbiosis and SIBO in cirrhosis.METHODS This observational study included 47 in-patients with cirrhosis.Stool microbiome was assessed using 16 S r RNA gene sequencing.SIBO was assessed using the lactulose hydrogen breath test.RESULTS SIBO was found in 24/47(51.1%)patients.Patients with SIBO had a higher abundance of Firmicutes(P=0.017)and Fusobacteria(P=0.011),and a lower abundance of Bacteroidetes(P=0.013)than patients without SIBO.This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia(P=0.020)of the Lachnospiraceae family(P=0.047),while the abundance of other major families of this phylum[Ruminococcaceae(P=0.856),Peptostreptococcaceae(P=0.066),Clostridiaceae(P=0.463),Eubacteriaceae(P=0.463),Lactobacillaceae(P=0.413),and Veillonellaceae(P=0.632)]did not differ significantly between the patients with and without SIBO.Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum[Bacteroidaceae(P=0.014),Porphyromonadaceae(P=0.002),and Rikenellaceae(P=0.047)],with the exception of Prevotellaceae(P=0.941).There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis[Proteobacteria(P=0.790),Bacilli(P=0.573),Enterobacteriaceae(P=0.632),Streptococcaceae(P=0.170),Staphylococcaceae(P=0.450),and Enterococcaceae(P=0.873)]between patients with and without SIBO.CONCLUSION Despite the differences observed in the gut microbiome between patients with and without SIBO,gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.

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

BACKGROUND Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course.Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.AIM To investigate the effect of probiotics on hemodynamic parameters,systemic inflammation,and complications of cirrhosis in this randomized placebocontrolled trial.METHODS 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 period.Liver function and the systemic hemodynamic status were evaluated pre-and postintervention.Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators.Cardiac output and systemic vascular resistance were calculated.RESULTS 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.

Probiotics in hepatology:An update

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.

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

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.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 prognosis.The 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 cirrhosis.However,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 studied.They remain a missing link in the gut-liver axis and a challenge for future research.

Gut dysbiosis and body composition in cirrhosis

BACKGROUND Gut dysbiosis and changes in body composition(i.e.,a decrease in the proportion of muscle mass and an increase in extracellular fluid)are common in cirrhosis.AIM To study the relationship between the gut microbiota and body composition in cirrhosis.METHODS This observational study included 46 patients with cirrhosis.Stool microbiome was assessed using 16S rRNA gene sequencing.Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.RESULTS An increase in fat mass and a decrease in body cell mass were noted in 23/46(50.0%)and 15/46(32.6%)patients,respectively.Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis.The abundance of Bacteroidaceae(P=0.041)and Eggerthella(P=0.001)increased,whereas that of Erysipelatoclostridiaceae(P=0.006),Catenibacterium(P=0.021),Coprococcus(P=0.033),Desulfovibrio(P=0.043),Intestinimonas(P=0.028),and Senegalimassilia(P=0.015)decreased in the gut microbiome of patients with body cell mass deficiency.The amount of extracellular fluid increased in 22/46(47.6%)patients.Proteobacteria abundance(P<0.001)increased,whereas Firmicutes(P=0.023),Actinobacteria(P=0.026),Bacilli(P=0.008),Anaerovoraceceae(P=0.027),Christensenellaceae(P=0.038),Eggerthellaceae(P=0.047),Erysipelatoclostridiaceae(P=0.015),Erysipelotrichaceae(P=0.003),Oscillospiraceae(P=0.024),Rikenellaceae(P=0.002),Collinsella(P=0.030),Hungatella(P=0.040),Peptococcaceae(P=0.023),Slackia(P=0.008),and Senegalimassilia(P=0.024)abundance decreased in these patients.Patients with clinically significant ascites(n=9)had a higher abundance of Proteobacteria(P=0.031)and a lower abundance of Actinobacteria(P=0.019)and Bacteroidetes(P=0.046)than patients without clinically significant ascites(n=37).CONCLUSION Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.

Immune disorders and rheumatologic manifestations of viral hepatitis

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.