It has been suggested that the minimal absorption associated with rifaximin may make the agent more conducive for long-term use than other antibiotics, which are more readily absorbed and associated with significant side effects. Grande and colleagues conducted a double-blind crossover trial evaluating the use of rifaximin in patients with liver cirrhosis and minimal HE. A total of 17 patients were randomly assigned to rifaximin administered at 1,200 mg/day (2 200-mg tablets given every 8 hours), or placebo, for 4 weeks. After a 4-week washout period, patients received the alternative treatment (rifaximin or placebo) for the next 4 weeks. In this interim analysis, rifaximin was associated with a significant improvement in the area under the curve of glutamine oral challenge compared to placebo (-52.3±53 mg/mL/hr vs -5.62±10.56 mg/mL/hr; P=.045) in the first phase of the study but not the second phase of the study. However, rifaximin was associated with an improvement over placebo in the Psychometric Hepatic Encephalo-pathy Score in the second phase of the study (2±1.75 vs -1±1.15; P=.05).

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Long-term entecavir (Baraclude, Bristol-Myers Squibb) therapy induces durable virologic suppression and his-tologic benefit, including reversal of fibrosis or cirrhosis, in both HBeAg-positive and -negative chronic hepatitis B. Tong and colleagues evaluated long-term histologic outcomes following entecavir therapy in a nucleoside-naive Asian patient population. The investigators analyzed patients who completed the clinical trials ETV-022 or -027 and subsequently received entecavir 1.0 mg daily in the rollover study ETV-901. The group included 31 patients with baseline and follow-up biopsies, including 24 patients with HBeAg-positive disease. At baseline, the mean HBV DNA level was 9.5 log10 copies/mL; mean ALT was 127 U/L; mean Knodell necroinflammatory score was 7.5, and mean Ishak fibrosis score was 2.2. After a median entecavir treatment duration of 283 weeks, histologic improvement was observed in 100% of patients, representing an increase from the 71% histologic improvement rate observed at Week 48. The mean reductions from baseline in Knodell necroinflammatory score at Week 48 and at long-term follow-up were 3.4 and 6.2, respectively. The proportion of patients with improvements in Ishak fibrosis score was 29% and 87%, respectively, and the mean change in Ishak fibrosis score from baseline was -0.2 and -1.5, respectively. The proportion of patients with HBV DNA levels less than 300 copies/mL was 68% at Week 48 and 100% at long-term follow-up; ALT of no more than 1 times the upper limit of normal was observed in 61% and 77% of patients, respectively. No new safety issues were reported.

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In another analysis of RFHE3001, Sanyal and colleagues investigated the relationship between venous ammonia concentrations, breakthrough HE, and rifaximin treatment. Blood ammonia has been proposed as a useful marker of the severity of overt HE, as elevated ammonia levels are associated with the pathogenesis of overt HE and the development of central nervous system effects. In the current study, the investigators measured venous ammonia concentrations at baseline and on Days 24, 84, and 168 of treatment with rifaximin or placebo. Rifaximin was associated with significant reductions in venous ammonia concentrations versus placebo (5.7 vs 0.3 mg/dL; P=.0391). Breakthrough HE, defined as an increase in Conn score to at least 2, or an increase in Conn score to 1 and asterixis grade increase by 1 unit in patients with a baseline Conn score of 0.2, occurred in 35% of patients. Venous ammonia concentrations were significantly higher in patients with breakthrough HE versus those remaining in remission (mean TWA, 102.4 vs 85.4 mmol/L; P=.0079). A significant positive correlation was found between mean venous ammonia TWA and breakthrough HE (Spearman correlation coefficient, 0.22; P=.0005). Moreover, venous ammonia concentrations appeared to be a good predictor of breakthrough HE, as determined by a receiver operating characteristics curve analysis (0.64; 95% confidence interval [CI], 0.57-0.72). Given the significant independent association between venous ammonia concentrations and breakthrough HE, the investigators suggested that the Conn score is a reliable clinical indicator of breakthrough HE.

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Muir and colleagues reported results from Study 107, an open-label rollover study evaluating the addition of telaprevir to peginterferon alfa-2a and ribavirin in patients with genotype 1 chronic hepatitis C virus (HCV) who did not attain sustained virologic response (SVR) with peginterferon/ribavirin during a phase II trial of telaprevir. The study included null responders (patients with HCV RNA reductions <1 log₁₀ at Week 4 or <2 log₁₀ at Week 12), partial responders (patients with >2 log₁₀ decrease in HCV RNA at Week 12 but with detectable HCV RNA at Week 24), patients with viral breakthrough, and patients with HCV relapse. The analysis included 117 patients from the PROVE1/2/3 studies. Patients initially received telaprevir 750 mg every 8 hours plus standard-dose peginterferon/ribavirin for 12 weeks, followed by 12 weeks of standard-dose peginterferon/ribavirin. The study design was amended to allow an additional 24 weeks of peginterferon/ribavirin in patients with detectable HCV RNA at Week 4 and/or Week 12 and in null responders. Read the rest of this entry »

Rifaximin (Xifaxan, Salix) is a broad-spectrum oral antibiotic that is gut-selective and minimally absorbed. The agent has demonstrated efficacy in acute hepatic encephalopathy (HE). The randomized, double-blind, multinational, phase III trial RFHE3001, conducted in 299 patients with cirrhosis and a history of recurrent overt episodic HE, showed that rifaximin reduces the risk of breakthrough overt HE by 58% compared to placebo. In the current analysis, Sanyal and colleagues evaluated the effects of rifaximin and breakthrough HE on patient-reported health-related quality of life in patients enrolled in RFHE3001. Quality of life was assessed using the validated and disease-specific Chronic Liver Disease Questionnaire (CLDQ), in which 6 domains are ranked on a 7-point scale, with higher scores indicating a better quality of life. The investigators found that rifaximin was associated with a significant improvement in the mean time-weighted average (TWA) score for the overall CLDQ (3.7 vs 2.9; P=.0093) and for all individual domains, including fatigue (3.2 vs 2.5; P=.0087). Read the rest of this entry »

Manns and colleagues presented results of a pooled analysis evaluating the efficacy of tenofovir disoproxil fumarate (TDF; Viread, Gilead) in patients with suboptimal response to adefovir dipivoxil (ADV; Hepsera, Gilead). The analysis included patients enrolled across 3 clinical trials: Study 102 (in hepatitis B e antigen [HBeAg]-neg-ative patients), Study 103 (in HBeAg-positive patients), and Study 106 (in ADV-refractory chronic hepatitis B patients). The current analysis focused on patients with a suboptimal response to ADV, defined as 48 weeks of ADV exposure prior to enrolling in Studies 102 and 103 with a hepatitis B virus (HBV) DNA level of at least 69 IU/mL (>400 copies/mL) or with 24-96 weeks of

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