Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with liver disease receiving broad-spectrum antibiotic therapy

BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy.Due to overlapping spectrums of activity,combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary.A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease.It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.AIM To determine the clinical,safety,and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.METHODS This was a single-center,quasi-experimental,pre-post study based on a pilot pharmacist-driven protocol.Patients in the protocol group were prospectively identified via the medical intensive care unit(ICU)(MICU)protocol to have rifaximin withheld during broad-spectrum antibiotic treatment.These were compared to a historical cohort who received combination therapy with broadspectrum antibiotics and rifaximin.All data were collected retrospectively.The primary outcome was days alive and free of delirium and coma(DAFD)to 14 d.Safety outcomes included MICU length of stay,48-h change in vasopressor dose,and ICU mortality.Secondary outcomes characterized rifaximin cost savings and protocol adherence.Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.RESULTS Each group included 32 patients.The median number of delirium-and coma-free days was similar in the control and protocol groups[3 interquartile range(IQR 0,8)vs 2(IQR 0,9.5),P=0.93].In multivariable analysis,group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d.The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy[6 d control(IQR 3,9.5)vs 1 d protocol(IQR 0,1);P<0.001].Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements.Overall adherence to the protocol was 91.4%.The median estimated total cost of rifaximin therapy per patient was reduced from$758.40(IQR$379.20,$1200.80)to$126.40(IQR$0,$126.40),P<0.01.CONCLUSION The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.

Evolution of care in cirrhosis: Preventing hepatic decompensation through pharmacotherapy

Cirrhosis is a leading cause of morbidity and mortality,impacting more than 120 million people worldwide.Although geographic differences exist,etiologic factors such as alcohol use disorder,chronic viral hepatitis infections,and non-alcoholic fatty liver disease are prevalent in nearly every region.Historically,significant effort has been devoted to modifying these risks to prevent disease progression.Nevertheless,more than 11%of patients with compensated cirrhosis experience hepatic decompensation each year.This transition signifies the most important prognostic factor in the natural history of the disease,corresponding to a decline in median survival to below 2 years.Over the past decade,the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized,and non-selective beta-blockers have emerged as the most effective option to date.However,a critical therapeutic gap still exists,and additional therapies have been proposed,including statins,rifaximin,and sodium-glucose cotransporter-2 inhibitors.Based on the results of innovative retrospective analyses and small-scale prospective trials,these pharmacotherapies represent promising options,but further studies,including randomized controlled trials,are necessary before they can be incorporated into clinical use.This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.

Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice

Objective Rifaximin is an effective component of treatment strategies for liver and intestinal diseases.However,the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome(HSOS)has not been explored.The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS.Methods An HSOS model was established in mice through the administration of monocrotaline(MCT,800 mg/kg),and part of the HSOS mice were intragastrically administered with rifaximin.Then,the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings,liver proinflammatory cytokines,and alanine aminotransferase and aspartate aminotransferase levels.The Ussing chamber was used to evaluate the intestinal permeability,and tight junction(TJ)proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity.Then,the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay.Afterwards,an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins.Results Rifaximin effectively alleviated the MCT-induced HSOS liver injury,suppressed the expression of liver proinflammatory cytokines,and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6.Furthermore,rifaximin reduced the intestinal permeability,improved the intestinal barrier integrity,and promoted the expression of TJ proteins.Conclusion The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS.The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.

Rifaximin in the Treatment of Gastroesophageal Reflux Disease: A New Idea Based on the Relationship between Intestinal Microecology and Gastroesophageal Reflux Disease

Rifaximin in the Treatment of Gastroesophageal Reflux Disease (GERD) is a common clinical disorder, the most common symptom of which is a burning sensation behind the breastbone (heartburn) or reflux of stomach contents into the upper pharynx (acid reflux). The prevalence in China is increasing year by year, which can affect the quality of life of patients and also increase the economic burden on families and society. The pathogenesis of GERD is still unclear, and some studies suggest that intestinal microecology may be closely related to the development of GERD. Rifaximin is not readily absorbed orally and acts locally in the intestine, so it has mild adverse effects and good safety, and can be used to treat gastrointestinal diseases such as irritable bowel syndrome, traveler’s diarrhea, small intestinal bacterial overgrowth, diverticulosis, inflammatory bowel disease and hepatic encephalopathy. Therefore, this paper focuses on intestinal microecology as a possible pathogenesis of GERD and further explores the feasibility of rifaximin for the treatment of GERD.

Microbiota and the gut-liver axis:Bacterial translocation,inflammation and infection in cirrhosis

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called &#x0201c;gut-liver axis&#x0201d;, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

Current and future pharmacological therapies for managing cirrhosis and its complications

Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis,and may impede hepatic fibrogenesis and decompensation.Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management,nutritional optimisation and patient education.

Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint",characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined,and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover,in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis(SBP),hepatic encephalopathy(HE),and,portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic,immune-modulating and anti-inflammatory activity,a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE,and also to prevent the development of SBP,to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality,triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.

Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.

Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms:Experience with Rifaximin

AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.

Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.

Rifaximin vs conventional oral therapy for hepatic encephalopathy:A meta-analysis

AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identifi ed through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics[odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profi le (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical signifi cance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any signifi cant difference in the above fi ndings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profi le.

Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease:An observation on non-absorbable antibiotics

AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.

Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study

BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics.The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics.CONCLUSION Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites.A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria,thus improving the systemic inflammatory state.

Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver

Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.

Second and third line treatment options for Helicobacter pylori eradication

Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and thirdline treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis

Minimal hepatic encephalopathy(MHE)corresponds to the earliest stage of hepatic encephalopathy(HE).MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests.MHE may affect daily activities and reduce job performance and quality of life.MHE can increase the risk of accidents and may develop into overt encephalopathy,worsening the prognosis of patients with liver cirrhosis.Despite a lack of consensus on the therapeutic indication,interest in finding novel strategies for prevention or reversion has led to numerous clinical trials;their results are the main objective of this review.Many studies address the treatment of MHE,which is mainly based on the strategies and previous management of overt HE.Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia,and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose,antibiotics such as rifaximin,and administration of different probiotics.This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.

Irritable bowel syndrome: A concise review of current treatment concepts

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders causing patients to seek medical treatment. It is relatively resource intensive and the source of significant morbidity. Recent insights into the pathophysiology and treatment of IBS has given clinicians more options than ever to contend with this disorder. The purpose of our paper is to review older, &#x0201c;classic&#x0201d; treatments for IBS as well as newer agents and &#x0201c;alternative&#x0201d; therapies. We discuss the evidence base of these drugs and provide context to help develop appropriate treatment plans for IBS patients.

Chronic bacterial prostatitis and irritable bowel syndrome： effectiveness of treatment with rifaximin followed by the probiotic VSL#3

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis （PV） or prostate-vesiculo-epididymitis （PVE）. A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis （CBP） and irritable bowel syndrome （IBS） were randomly prescribed rifaximin （200 mg, 2 tablets bid, for 7 days monthly for 12 months） and probiotic containing multiple strains VSL#3 （450 × 10^9 CFU per day） or no treatment. Ninety-five of them （89.6%） complied with the therapeutic plan and were included in this study. Group A = ＂6Tx/6-＂： treatment for the initial 6 and no treatment for the following 6 months （n = 26）; Group B = ＂12Tx＂： 12 months of treatment （n = 22）; Group C = ＂6-/6Tx＂： no treatment for the initial 6 months and treatment in the last 6 months （n = 23）; Group D = ＂12-＂： no treatment （n = 24）. The patients of Groups A = ＂6Tx/6-＂ and B = ＂12Tx＂ had the highest frequency of chronic prostatitis （88.5% and 86.4%, respectively）. In contrast, group ＂12-＂： patients had the lowest frequency of prostatitis （33.4%）. The progression of prostatitis into PV in groups ＂6Tx/6-＂ （15.5%） and ＂6-/6Tx＂ （13.6%） was lower than that found in the patients of group ＂12-＂ （45.8%）. Finally, no patient of groups ＂6Tx/6-＂ and ＂6-/6Tx＂ had PVE, whereas it was diagnosed in 20.8% of group ＂12-＂ patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.