Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized,double-blind,double-dummy,controlled clinical trial

BACKGROUND/AIMS: The efficacy and safety of rifaximin in comparison with lactitol in the treatment of acute hepatic encephalopathy was assessed in a prospective randomized, double-blind, double-dummy, controlled trial. METHODS: A total of 103 patients with grade I-III acute hepatic encephalopathy were randomized to receive rifaximin (50 patients, 1200 mg/day) or lactitol (53 patients, 60 g/day) for 5-10 days. Changes in the portal-systemic encephalopathy (PSE) index on entry and at the end of the study were used to evaluate the efficacy of the two therapies. RESULTS: Both groups were comparable before treatment with regard to demographic data and characteristics of the hepatic encephalopathy episode. The global efficacy of both therapies was similar: 81.6% in the rifaximin group and 80.4% in the lactitol group showed improvement or total regression of the episode. A significantly better evolution of the PSE index was observed in the rifaximin group, due to a greater effect of rifaximin in two components of the index: EEG abnormalities and ammonia levels. No serious adverse events related to either treatment were found during the study. CONCLUSIONS: Rifaximin may be considered a useful and safe alternative therapy to lactitol in the treatment of acute hepatic encephalopathy in cirrhosis.     

Treatment of chronic portal systemic encephalopathy with bromocriptine: a double-blind controlled trial.

A randomized double-blind clinical comparison of bromocriptine, a new dopamine agonist, and placebo was performed on 7 cirrhotic patients with chronic portal systemic encephalopathy (PSE). Before given either medication, patients were stabilized with a standard treatment (neomycin and cathartics). Serial semiquantitative assessments were done, including mental state, asterixis, number connection test, electroencephalogram, and ammonia blood levels. Three patients developed signs of precoma while ingesting both placebo and bromocriptine. Two patients experienced precoma only with placebo, and another patient only while taking bromocriptine. One patient remained awake throughout the study. All patients responded initially to neomycin and cathartics. Bromocriptine proved not to be significantly superior to placebo and was always inferior to standard treatment. During treatment with bromocriptine, 3 patients experienced constipation. This may be partially responsible for the ineffectiveness in the treatment of PSE.     

Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study

OBJECTIVE: To determine the efficacy, tolerability and safety of oral rifaximin given at three dose levels in patients with cirrhosis and mild to moderate hepatic encephalopathy (HE). DESIGN: Prospective, double-blind, randomized, parallel-group study. SETTING: Multi-centre trial in four university teaching hospitals. PARTICIPANTS: Fifty-four patients with cirrhosis and mild to moderate HE. INTERVENTION: Seven days treatment with rifaximin, 600, 1200 or 2400 mg/day in three divided doses. MAIN OUTCOME MEASURE: Change in the portal-systemic encephalopathy (PSE) index between baseline and day 7, calculated on the basis of mental state, asterixis, number connection test time, EEG mean cycle frequency and blood ammonia concentrations. RESULTS: Treatment with rifaximin was associated with an improvement in the PSE index. There was a trend towards a greater treatment effect of rifaximin with the highest dose of 2400 mg/day. Rifaximin was well tolerated; the few treatment-related adverse events showed no consistent pattern or dose relationship. CONCLUSION: Rifaximin may be useful as alternative or adjuvant therapy for grade I-III hepatic encephalopathy in patients with cirrhosis at a dose of 1200 mg/day.     

Lactitol,a second-generation disaccharide for treatment of chronic portal-systemic encephalopathy

A double-blind crossover trial was performed to test the therapeutic usefulness and safety of lactitol, a beta-galactoside sorbitol, against lactose in 18 patients with chronic portal-systemic encephalopathy (PSE). The study included four periods: two for washout and two for lactitol and lactose administration. During washout periods, which lasted two weeks each, patients were stabilized with neomycin plus milk of magnesia. Lactitol and lactose were administered during four weeks each. Ten patients were randomly assigned to receive lactose (group A) and eight patients to receive lactitol (group B) first. PSE parameters, ie, mental state, number connection test performance, asterixis and blood ammonia levels were assessed fortnightly. Electroencephalographic tracings and stool pHs were evaluated at the end of each study period. After the first administration of lactose and lactitol, no statistically significant differences in PSE parameters were found. At the same stage, a significant stool acidification (P<0.05) was detected. It is concluded that lactitol seems to be safe and efficacious in treating patients with chronic PSE.     

Porcine intestinal ammonia liberation. Influence of food intake, lactulose and neomycin treatment

Lactulose and neomycin have, besides influencing ammonia production of the intestinal flora, been proposed to reduce glutamine-dependent ammonia formation. To test this hypothesis we determined the effects of lactulose and neomycin on the release or uptake of ammonia, urea, and amino acids across the intestine of freely moving healthy pigs. Blood was sampled from catheterized piglets (20 +/- 0.8 kg; n = 6) before and 1, 2, 3, and 6 h after a standard pig meal (750 g, 12% protein). After a week of lactulose (Legendal; 2 x 60 g/day) or neomycin (8 g/day) treatment this procedure was repeated. Electromagnetic portal and small bowel flow measurements were carried out in separate groups of pigs. Flow measurements were independent of the kind of food ingested. No significant alterations in flow could be detected during the 6 h study period. Portal and porto-arterial ammonia differences were significantly decreased after lactulose (-20%) and neomycin (-35%) treatment. alpha-Amino-nitrogen absorption decreased in both groups as compared to controls, but this decrease did not reach significance. Systemic and portal glutamine levels as well as intestinal glutamine utilization were significantly lower in the treatment groups. Citrulline and glutamate levels and intestinal production decreased after treatment. In this in vivo model, ammonia liberation after protein meals decreased in animals pretreated with lactulose or neomycin. The decreased systemic and consequently intestinal glutamine utilization may contribute to a reduction of endogenous ammonia formation in the gut wall. Diminished absorption from the gut of alpha-amino-nitrogen may, however, also contribute to a decrease in ammonia production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety

The nonabsorbed (< 0.4%) oral antibiotic rifaximin, which has been available for enteric bacterial conditions for more than a decade in several countries outside the United States, was recently introduced in the United States for the treatment of travelers' diarrhea, and is being evaluated in clinical trials for possible introduction for hepatic encephalopathy and other conditions involving enteric bacteria. This article discusses the antimicrobial activity, efficacy, and safety of rifaximin in hepatic encephalopathy. Rifaximin is a nonsystemic antibiotic with antibacterial activity against enteric pathogens for gastrointestinal infections. In 15 studies, several of which were adequately powered to assess efficacy, rifaximin was at least as effective as lactulose/lactitol (the current mainstay of pharmacologic treatment for hepatic encephalopathy) and neomycin and paromomycin (the antibiotics most commonly prescribed for hepatic encephalopathy) in improving neurologic signs and symptoms and reducing blood ammonia levels. The results of studies employing small samples are similar to those of the larger studies. Finally, rifaximin has a good tolerability profile in patients with hepatic encephalopathy, and thus appears to constitute a promising new option for this disorder. The current database on rifaximin would be strengthened by results of placebo-controlled studies to quantify more precisely the benefits of therapy.     

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS: Rats with CCl₄-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy.     

Long-term results of partial splenic artery embolization as supplemental treatment for portal-systemic encephalopathy

OBJECTIVES: To present long-term results of angiographic partial splenic artery embolization (PSE) as a supplemental treatment of portal-systemic encephalopathy. METHODS: Twenty-five patients with portal-systemic encephalopathy were divided into two groups: 14 patients underwent transportal obliteration and/or balloon-occluded retrograde transvenous obliteration (BRTO) of portal-systemic shunts (PSS), followed by PSE (PSE(+) group), and 11 patients underwent only transportal obliteration and/or BRTO of PSS (PSE(-) group). RESULTS: Portal venous pressures pretreatment was similar to posttreatment in the PSE(+) group, but lower than posttreatment in the PSE(-) group. Serum ammonia levels were higher at pretreatment than at 1 wk posttreatment in both groups, but the levels in the two groups were similar at pretreatment, 1 wk, 3 months, 3 yr, 4 yr, and 5 yr posttreatment. However, serum ammonia levels were lower in the PSE(+) group than in the PSE(-) group 6 months, 9 months, 1 yr, and 2 yr posttreatment. Grades of encephalopathy were higher at pretreatment than at 1 wk posttreatment in both groups, but the levels in the two groups were similar at pretreatment, 1 wk, 2 yr, 3 yr, 4 yr, and 5 yr posttreatment. However, grades of encephalopathy were lower in the PSE(+) group than in the PSE(-) group 3 months, 6 months, 9 months, and 1 yr posttreatment. CONCLUSIONS: Obliteration of PSS followed by PSE benefit patients with portal-systemic encephalopathy.     

Lactitol vs. lactulose in the treatment of chronic recurrent portal-systemic encephalopathy

To compare the efficacy and patient acceptability of lactitol vs. lactulose in chronic recurrent portal-systemic encephalopathy (PSE), 25 cirrhotic patients with a history of repeated episodes of hepatic encephalopathy who required chronic administration of lactulose were included in a controlled cross-over clinical trial in which patients received, at random, lactitol (at an initial dosage of 10 g/6 h) or lactulose (15 ml/6 h, 66% w/v, containing 10 g of lactulose) during a 3 month period and then crossed-over to the alternative treatment for the following 3 months. Doses were adjusted to obtain two bowel movements per day. During the study period the daily protein intake was 40-60 g. Clinical and analytical data (including ammonia levels) were obtained, an EEG and the number connection test were performed and the PSE index was determined before treatment and monthly until the end of the treatment. No significant differences were found between the effects of lactitol and lactulose on the neurological and biological parameters, suggesting that the two treatments could be considered as equally effective. Lactitol was significantly better tolerated than lactulose (P = 0.02), the taste of which was assessed as being too sweet and provoking nausea. In conclusion, lactitol is a good alternative to lactulose for patients with chronic recurrent PSE, especially in those who do not tolerate the excessive sweetness of lactulose.     

Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE): A controlled trial

Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 ml/6 h) and group B (20 patients) lactitol (12 g/6 h). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.     

Antibiotic Treatment of Constipation-Predominant Irritable Bowel Syndrome

Background

The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects.

Aims

To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects.

Methods

A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up.

Results

Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) (P = 0.0042), with greater improvement in constipation (P = 0.007), straining (P = 0.017) and bloating (P = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) (P = 0.020).

Conclusions

Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.     

Efficacy of Switching from Kanamycin Sulfate to Rifaximin in Patients with Hepatic Cirrhosis

Objective This study evaluated the efficacy associated with switching to rifaximin in patients with hepatic cirrhosis receiving kanamycin sulfate for the treatment of hepatic encephalopathy and hyperammonemia. Methods We included 37 patients who switched from kanamycin sulfate to rifaximin at our institution from January 2017 to December 2018. The onset of hepatic encephalopathy and changes in blood ammonia values during a six-month period were retrospectively evaluated. Results There were 4 (11%) patients with hepatic encephalopathy at the time of switching from kanamycin sulfate to rifaximin. The cumulative incidence of hepatic encephalopathy was 3% and 16% at 3 and 6 months later, respectively. The blood ammonia levels at the time of switching to rifaximin and at 3 and 6 months later were 94 (range, 20-243) μg/dL, 95 (range, 33-176) μg/dL, and 81 (range, 32-209) μg/dL, respectively, and no significant changes were observed. However, in the 11 patients receiving an oral dose of <1,500 mg/day of kanamycin sulfate, the blood ammonia levels at the time of switching and at 3 and 6 months later were 136 (range, 35-243) μg/dL, 95 (range, 33-150) μg/dL, and 63 (range, 43-124) μg/dL, respectively. Furthermore, the blood ammonia levels significantly decreased at the time of the switching to rifaximin and at three and six months later (p=0.043 and p=0.011, respectively). Conclusion Switching to rifaximin in hepatic cirrhosis patients receiving kanamycin sulfate to treat hepatic encephalopathy and hyperammonemia showed effects that were equivalent to or greater than the original therapy, thereby demonstrating the clinical efficacy.     

脾栓塞对肝硬化患者外周血T淋巴细胞亚群的影响

目的 :研究部分脾栓塞治疗脾功能亢进对肝硬化患者T淋巴细胞亚群的影响。方法 :57例肝硬化并脾功能亢进患者 ,32例采用部分脾栓塞治疗 ,2 5例采用脾全切治疗 ,1 5例正常人作为对照 ,比较两组治疗前后外周血T淋巴细胞亚群的变化。结果 :肝硬化患者外周血T淋巴细胞 (CD3+ )、T辅助 /诱导淋巴细胞亚群 (CD4+ )、T辅助淋巴细胞 /T抑制淋巴细胞亚群 (CD4+ /CD8+ )明显低于正常人 (P <0 .0 1 ) ;脾栓塞组治疗前后CD3+ 、CD4+ 、CD8+ 、CD4+ /CD8+ 无明显差异 (P >0 .0 5) ;脾全切组治疗后CD3+ 、CD4+ 、CD4+ /CD8+ 均较治疗前及部分脾栓塞组治疗后明显降低 (P <0 .0 1 )。结论 :肝硬化患者外周血CD3+ 、CD4+ 、CD4+ /CD8+ 降低 ,部分脾栓塞治疗脾功能亢进 ,对肝硬化患者外周血T淋巴细胞亚群无明显影响 ,显著优于脾全切治疗     

A double‐blind,randomized, placebo‐controlled trial of intravenous l‐ornithine–l‐aspartate on postural control in patients with cirrhosis

Introduction: Hepatic encephalopathy (HE) is a complication of liver disease. Several treatments have been introduced but only l ‐ornithine–l ‐aspartate (LOLA) shows proven efficacy. This double‐blind, randomized, placebo‐controlled trial evaluated the effect of LOLA on postural control in cirrhotics. Methods: Forty patients were randomized to either LOLA or a placebo. HE was evaluated by psychometric testing (PSE Syndrome Test) and critical flicker frequency (CFF). Posturography [equilibrium score (ES)] provided information regarding postural control. Peripheral blood was analysed for ammonia concentration (NH₃) and the partial pressure of ammonia (pNH₃). Results: Both groups were comparable regarding baseline variables. Posturography and PSE Syndrome Test improved in both groups; improvement was greater in the LOLA group (ES: 5.3%; PSE: 1.9) compared with the placebo (ES: 3.9%; PSE: 1.3) but did not reach significance (ES: P=0.3; PSE: P=0.5). CFF remained unchanged during treatment and between groups (P=NS). NH₃ decreased in the LOLA group (Δ: ?15 μmol/L) and slightly increased in the placebo group (Δ: 11.1 μmol/L), but the differences did not reach statistical significance (P=0.07). pNH₃ remained largely unchanged (LOLA Δ: ?1.2 × 10^?5 mmHg vs. placebo Δ: ?0.3 × 10^?5 mmHg; P=0.21). Conclusion: In the LOLA group, an improvement of posturographic control and PSE Syndrome Test was observed, but a similar improvement was also achieved by the placebo. In LOLA, ammonia levels tended to decrease while they tended to increase in the placebo group. LOLA might augment the improvement achieved by intravenous fluids alone but a larger cohort will be needed to show this effect with statistical significance.     

Effects of Simulated Upper Gastrointestinal Hemorrhage on Ammonia and Related Amino Acids in Blood and Brain of Chronic Portacaval-shunted Rats

Gastrointestinal (GI) hemorrhage during compromised liver function is known to precipitate portal-systemic encephalopathy (PSE). Hypothetically, the induced hyperammonemia depletes cerebral glutamate pools. To investigate this hypothesis, rats were studied 14 days after portacaval shunt (PCS) or sham surgery (SHAM). Rats received 3 mL bovine erythrocytes or saline at t=0, 1, 2, and 3h via a previously placed gastrostomy catheter. At t=0, 2, 4, 6 and 8h arterial blood and at t=8h cerebral cortex were sampled for determination of ammonia and amino acids. Control rats (NORM) were sampled without previous surgery. Repeated intragastric blood administration increased the already elevated arterial ammonia levels in PCS rats further. This resulted in higher cerebral cortex ammonia and glutamine,levels after blood administration. Despite the accumulation of ammonia and glutamine, cerebral cortex glutamate concentrations remained unaltered. Yet, PCS rats became more encephalopathic after blood gavages, suggesting that there is not a clear-cut relation between cerebral cortex glutamate concentrations and degree of PSE. Interestingly, cerebral cortex concentrations of GABA, tyrosine and phenylalanine were markedly increased. Whether these observations are pathogenetically related to PSE remains to be established. The present model of simulated GI hemorrhage in PCS rats seems to be a suitable, clinically valid model for future research regarding hepatic encaphalopathy.     

缬沙坦联合氟伐他汀治疗肾性高血压的临床观察

目的:观察缬沙坦与氟伐他汀联合应用对慢性肾病继发性高血压的治疗作用。方法:58例肾性高血压患者被随机分成两组,每组29例:在慢性肾病常规治疗基础上,缬沙坦对照组给予缬沙坦80mg1次/d口服,联合用药组在缬沙坦对照组的基础上加用氟伐他汀40mg1次/d口服,疗程8周。观察治疗前后血压、血肌酐(Scr)、尿素氮(BUN)、24h尿蛋白定量以及血脂的变化。结果:治疗后两组血压、Scr、BUN、24h尿蛋白均显著下降(P0.01),肾功能明显改善,联合用药组Scr[(286.37±84.72):(327.52±92.63)μmol/L]、BUN[(8.35±5.24):(9.46±6.14)mmol/L]、24h尿蛋白[(0.89±0.71):(1.52±0.84)g/L]、血脂均较缬沙坦对照组显著下降(P均0.05)结论:缬沙坦与氟伐他汀联合应用能有效减轻肾病高血压患者的肾脏损害,其疗效优于单用缬沙坦治疗。     

Rifaximin has minor effects on bacterial composition,inflammation, and bacterial translocation in cirrhosis: A randomized trial

Background and Aim

Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo‐controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis.

Methods

Fifty‐four out‐patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end‐stage liver disease score 12 (± 3.9). Patients received rifaximin 550‐mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real‐time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing.

Results

Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell‐derived factor 1‐α, transforming growth factor β‐1, and high sensitivity C‐reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin.

Conclusion

Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).     

Partial splenic embolization prior to combination therapy of interferon and ribavirin in chronic hepatitis C patients with thrombocytopenia

Aim: A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism. Methods: We compared the clinical features of 10 patients receiving PSE prior to the combination therapy of IFN and ribavirin (RBV) (PSE group) with those of 10 non‐receiving PSE patients (non‐PSE group). Results: In all 10 patients, PSE was successfully performed without serious adverse events. After PSE, leukocyte, neutrophil, and platelet counts significantly increased. The period from PSE to the initiation of the combination therapy was 15 (7–21) days. In the PSE group, two of six patients (33%) infected with genotype 1, and all four patients infected with genotype 2, achieved SVR. In the non‐PSE group, only three patients infected with genotype 2 achieved SVR. Two patients in the PSE group and one in the non‐PSE group discontinued the combination therapy. Three patients of the PSE group and five of the non‐PSE group reduced the dose of pegylated IFN‐α‐2b because of thrombocytopenia. In the PSE group, platelet counts during the combination therapy fell to baseline levels; however, they did not fall to lower levels than baseline levels. In the non‐PSE group, platelet counts 1 month after the initiation of the therapy were lower than baseline levels. Conclusion: The increase of platelet counts after PSE may allow the safe use of IFN and RBV and improve the SVR rate in chronic hepatitis C patients with thrombocytopenia.     

Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.

BACKGROUND: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE. AIMS: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease. PATIENTS: 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study. METHODS: Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement). RESULTS: The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated. CONCLUSIONS: A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.     

Changes in Fecal Calprotectin After Rifaximin Treatment in Patients With Nonconstipated Irritable Bowel Syndrome

Background

Fecal calprotectin, an indicator of colonic inflammation, is associated with nonconstipated irritable bowel syndrome. Rifaximin is an antibiotic used to treat nonconstipated irritable bowel syndrome. We performed a retrospective review of patient charts to investigate the changes in fecal calprotectin levels and intestinal symptoms following treatment with rifaximin in patients with nonconstipated irritable bowel syndrome with elevated fecal calprotectin.