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.     

利福昔明治疗急性细菌性肠道感染107例

目的　评价利福昔明治疗急性细菌性肠道感染疾病的疗效和安全性。方法　采用多中心随机双盲双模拟平行对照试验。急性细菌性肠道感染患者 211例,随机分为两组,治疗组 107例,每次给予利福昔明 0. 2g,po,q6h,同时给予环丙沙星模拟安慰药片 1片,bid,疗程 5d;对照组 104例每次给予环丙沙星 0 .25g,po,bid,同时给予利福昔明模拟安慰药片 2片,po,q6h,疗程 5d。评价两药的疗效及不良反应。结果　治疗组肠道感染的治愈率和显效率分别是 75 7%和 18 .7%,总有效率为 94 .4%;对照组分别是 84 .6%和 13 .5%,总有效率为 98 .1%。利福昔明和环丙沙星的细菌清除率分别是 96. 2%和 96 3%,不良反应发生率为 2. 8%和 2. 9%。各项结果的差异均无显著性 (P>0 .05)。结论　利福昔明治疗急性细菌性肠道感染具有较好的疗效,不良反应发生率低,与环丙沙星的疗效相仿。     

利福昔明治疗急性感染性腹泻的疗效观察

目的：利福昔明治疗急性感染性腹泻的疗效及安全性。方法：将50例急性感染性腹泻患者随机分成两组，每组各25例。治疗组给予口服利福昔明200mg3次／日，对照组给予环丙沙星200mg3／日口服，用药3天。观察药物的止泻天数，大便常规复常率及临床症状缓解，进行疗效评价。结果：利福昔明的止泻率、大便常规复常率及临床症状缓解与环丙沙星相比无显著性差异（P〉0．05）。结论：利福昔明治疗急性感染性腹泻具有明显疗效。未见不良反应。     

Structural elucidation of the Rifaximin Ph. Eur. Impurity H

Rifaximin, a semisynthetic, rifamycin-based non-systemic antibiotic is used in the treatment of acute and chronic gastrointestinal disorders. The aim of this study was the elucidation of the molecular structure of the 802 Dalton impurity which was found in Rifaximin industrial batches and reported with an erroneous structure in European Pharmacopoeia 6.5 (2009) [7] monograph as Rifaximin Impurity H. This impurity was isolated from Rifaximin by preparative HPLC and purified by column chromatography. The molecular structure was evidenced by means of ¹H and ¹³C NMR spectroscopy, mass spectrometry and FT-IR.     

Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test

Summary

To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10?g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400?mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p<0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r=0.49, p<0.01) and after rifaximin (r=0.58, p<0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin. The results indicate that, while an increase in pulmonary hydrogen excretion is evident in diverticular disease, the therapeutic effect of rifaximin does not seem to be due to a persistent correction of this alteration. In addition, this drug appears to cause no significant imbalance in the intestinal ecosystem.     

An open-label evaluation of rifaximin in the treatment of active Crohn's disease

ABSTRACT

Objective: This open-label study was conducted as a preliminary assessment of rifaximin (200?mg TID for 16 weeks) for the treatment of active Crohn's disease in patients (n = 29) with symptoms for at least 3 months before screening and a Crohn's Disease Activity Index (CDAI) score > 220 and < 400.

Results: At the end of month 4, mean ± SD CDAI score was reduced by 43% compared with baseline in the intent-to-treat population (n = 29; baseline = 278 ± 51; month 4 = 159 ± 102; p < 0.0001 month 4 versus baseline). A similar pattern of results was observed in the per-protocol population (i.e., patients at least 70% compliant with the treatment regimen and having no protocol violations thought to affect efficacy results; n = 16), in which mean CDAI scores at month 4 were reduced by 41% from a baseline of 262.9 ± 38.2 to 155.6 ± 104.5 (?p = 0.0009 month 4 versus baseline). Fifty-nine percent of patients (59%) had a ≥ 70‐point improvement in CDAI score beginning with the first assessment at the end of month 1. By the end of the treatment period, 78% of patients had a ≥ 70‐point improvement in CDAI score. Clinical remission, defined as CDAI score < 150, was observed at the end of treatment months 1, 2, 3, and 4 in 41%, 56%, 56%, and 59% of patients, respectively. Twenty-three (23) patients completed the 4-month course of rifaximin therapy, and 6 prematurely withdrew. The most common adverse events were abdominal pain, fatigue, and headache.

Conclusion: These data, which are consistent with the possibility that rifaximin may be useful for active Crohn's disease, warrant confirmation in a randomized, double-blind, placebo-controlled trial.     

Rifaximin,a non-absorbable rifamycin,for the treatment of hepatic encephalopathy. A double-blind,randomised trial

Summary

The aim of this study was to evaluate the efficacy and tolerability of rifaximin, a non-absorbable intestinal antibiotic, in comparison to neomycin in the short- and long-term treatment of hepatic encephalopathy (HE). Forty-nine patients with a definite diagnosis of cirrhosis were included in this double-blind, randomised, controlled trial. Patients were randomly assigned to one of the following treatments: (1) rifaximin 400?mg three times daily: (2) neomycin 1?g three times daily. Both drugs were administrated orally as tablets during 14 consecutive days each month, for a period of six months.

The neuropsychiatric signs and blood ammonia levels were examined before starting the treatment, and every 30 days, until the final assessment.

In all patients a progressive and important reduction in HE grade was observed, and no statistically significant difference between the two treatments was detected.

In both groups the disturbances in speech, memory, behaviour and mood, gait, asterixis, writing, and serial subtraction of 7s and five-pointed star tests all showed the highest proportion of improvement.

During the study blood ammonia levels decreased in both the rifaximin and in the neomycin groups, and again no statistically significant difference was found between groups.

Our findings confirm, therefore, the usefulness of rifaximin in the treatment of HE, supporting its use as a first-choice antibiotic, particularly in patients intolerant to neomycin or with impaired renal function.     

Faecal calprotectin levels after rifaximin treatment in patients with irritable bowel syndrome with diarrhoea: A single-center prospective study

Background and study aimsAlthough unclear, the pathophysiology of irritable bowel syndrome (IBS) is considered to be multifactorial. Recent studies have suggested that IBS is a low-grade inflammatory bowel disease (IBD) with high faecal calprotectin (FC) levels. Rifaximin is a potential therapeutic agent for IBS with diarrhoea (IBS-D) due to its ability to decrease FC levels. This study evaluated the role of FC as a follow-up marker of IBS-D after short-course rifaximin treatment.Patients and methodsNinety-six patients with chronic diarrhoea who fulfilled the Rome IV criteria for IBS-D were enrolled in this study from outpatient clinics. After excluding 18 patients who did not complete the study due to treatment noncompliance or missing follow-up visits, 78 patients (mean age, 39.2 ± 6.9 years) with IBS-D and elevated baseline FC levels were included. An FC level of <50 μg/g was considered normal. Abdominal symptoms were assessed using a Likert scale. All patients received oral rifaximin (550 mg three times daily) for 2 weeks, followed by assessment for abdominal symptoms and FC levels; the treatment was extended to 4 weeks if FC levels remained elevated after 2 weeks of treatment.ResultsFC levels normalised in 66 (84.6%) patients, including 60 and 6 patients treated for 2 and 4 weeks, respectively. The remaining 12 (15.4%) patients with persistently elevated FC levels despite 4 weeks of treatment also showed a significant decline in their final FC levels compared with the baseline, accompanied with a significant improvement in abdominal symptoms (p = 0.001). A cutoff baseline FC value of 148.5 μg/g could predict non-responders with 100% sensitivity and 50% specificity.ConclusionShort-course oral rifaximin treatment results in FC normalisation in IBS-D patients with high baseline FC values. Therefore, FC should be considered as a biomarker of follow-up after rifaximin treatment for IBS-D.     

Small Intestinal Bacterial Overgrowth in Patients with Interstitial Cystitis and Gastrointestinal Symptoms

Purpose Interstitial cystitis (IC) often coexists with irritable bowel syndrome (IBS). IBS may be explained by small-intestinal bacterial overgrowth (SIBO), which increases immune activation and visceral hypersensitivity. This prospective pilot study tested hypotheses that IC patients with gastrointestinal (GI) symptoms have SIBO, that nonabsorbable antibiotic use improves symptoms, and that improvement is sustained by prokinetic therapy. Methods Consecutive IC patients with GI symptoms had lactulose breath testing (LBT). Those with abnormal results received rifaximin 1,200–1,800 mg/day for 10 days then tegaserod 3 mg/nightly. Questionnaires addressed IC and GI global improvement. Results Of 21 patients, 17 (81%) had abnormal LBTs. Of 15 patients treated, GI global improvement was moderate to great in 11 (73%) and sustained in ten (67%). IC global improvement was moderate to great in six (40%) and sustained in seven (47%). Conclusions A majority of IC patients and GI symptoms had an abnormal LBT suggesting SIBO. Rifaximin improved symptoms, which was sustained by tegaserod.