Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.     

Rifaximin therapy and hepatic encephalopathy: Pros and cons

Hepatic encephalopathy(HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life.Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy.Non-absorbable antibiotics,such as neomycin and paramomycin,are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects.To overcome these limitations,rifaximin use has been proposed.Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention,with a similar incidence of side-effects.Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern.Following long-term rifaximin therapy,Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients.In addition,selection of resistant mutants of both Gram-negative and-positive bacteria in the gastrointestinal tract cannot be definitely ruled out.Electrolyte alterations(sodium and potassium) have been reported during rifaximin therapy,a warning for its long-term use in cirrhotics.Moreover,a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients.The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides.While waiting for further safety data,caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to nonabsorbable disaccharides.     

Efficacy and safety of rifaximin associated with standard triple therapy (omeprazole,clarithromycin and amoxicillin) for H. pylori eradication: A phase IV pilot clinical trial

Background

A progressive decrease in Helicobacter pylori eradication rates has been described over the years, driving the need for new antibiotic treatments.

Clinical update for the diagnosis and treatment of Clostridium difficile infection

Clostridium difficile infection(CDI)presents a rapidly evolving challenge in the battle against hospitalacquired infections.Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests,such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production,which will soon revolutionize the diagnostic approach to CDI.New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents,while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI.Through a comprehensive review of current medical literature,this article aims to offer an intensive review of the current state of CDI diagnosis,discuss the strengths and limitations of available laboratory tests,compare both current and future treatments options and offer recommendations for best practice strategies.     

Rifaximin and Crohn’s disease

In a recent article,Longman and Swaminath analyzed our paper on the use of rifaximin in patients with moderately active Crohn’s disease(CD).Here we report some considerations concerning their article.The exploratory post-hoc subgroup analysis showed that early-stage disease and,differently from that written by Longman and Swaminath,also colonic involvement seemed to be associated with a significant higher efficacy of rifaximin-EIR 800 mg twice daily.Early-stage disease is generally considered as the more easily treatable phase of CD,and the better response to rifaximin in Crohn’s colitis is in accordance with the high concentration of bacteria in the colon.In addition,patients with C reactive protein level>5 mg/L achieved remission more significantly than patients with normal values,thus suggesting that the symptoms were probably caused by inflammation instead of by non-inflammatory causes.We also analyze the role of rifaximin against gut bacteria and the clinical situations that could obtain the best results from antibiotics.     

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.     

Eficacia de la rifaximina en los diferentes escenarios clínicos de la encefalopatía hepática

Hepatic encephalopathy is a frequent complication in patients with cirrhosis of the liver and is associated with a high mortality rate. Costs attributed to the management of patients with cirrhosis are especially high due to complications, such as hepatic encephalopathy, given that they increase the number of days of hospital stay. Different drugs are currently used to treat hepatic encephalopathy, and the main ones are lactulose, L-ornithine L-aspartate (LOLA), and certain antibiotics, especially rifaximin-α (RFX). Even though many of them have been shown to be effective to greater or lesser degrees, it is important to understand the differences between them, so that every patient receives individualized treatment and the best option is chosen, in accordance with the different clinical scenarios. Thus, the aim of the present study was to analyze the evidence on the advantages and disadvantages of the individual or combined use of the 3 main treatments for hepatic encephalopathy, specifically taking into consideration their different degrees of efficacy, their impact on quality of life, prophylaxis, and cost reduction.