Rifaximin has the potential to prevent complications of cirrhosis

Background: Cirrhosis-related complications are associated with poor prognosis. With our analyses, we examined the potential benefit of rifaximin in reducing the risk of developing cirrhosis-related complications. Methods: Adults with cirrhosis and hepatic encephalopathy (HE) in remission were randomly assigned to receive rifaximin 550 mg twice daily or placebo for 6 months with concomitant lactulose permitted. Post hoc analyses examined time to cirrhosis-related complications (HE, spontaneous bacterial peritonitis (SBP), variceal bleeding, acute kidney injury/hepatorenal syndrome). Subgroup analyses evaluated efficacy for select baseline disease characteristics. Results: Of patients receiving rifaximin (n = 140) and placebo (n = 159), 53.6% and 49.1%, respectively, had baseline Model for End-Stage Liver Disease (MELD) score ⩾ 12 and international normalized ratio (INR) ⩾ 1.2. Baseline ascites was observed in 36.4% (rifaximin) and 34.6% (placebo) of patients. In patients with MELD score ⩾ 12 and INR ⩾ 1.2, rifaximin reduced the relative risk (RR) of any first complication experienced during trial by 59% [hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.25–0.67; p \u3c 0.001] versus placebo. For patients with baseline ascites, rifaximin reduced the RR of any first complication experienced during trial by 42% versus placebo (HR = 0.58, 95% CI: 0.34–1.0; p = 0.045). For some subgroups, there was a decrease in RR of complications of SBP, variceal bleeding, and acute kidney injury/hepatorenal syndrome with rifaximin versus placebo, although there were few events reported in the study. Conclusion: Rifaximin may reduce the incidence of cirrhosis-related complications and the recurrence of overt HE. [ClinicalTrials.gov identifier: NCT00298038.

Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment: Poordad et al.

Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA‐containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open‐label study (MAGELLAN‐1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent‐to‐treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61‐100), 95% (21/22, 95% confidence interval 78‐99), and 86% (19/22, 95% confidence interval 67‐95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow‐up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed. Conclusion: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389–397)

Rifaximin has the potential to prevent complications of cirrhosis

Background: Cirrhosis-related complications are associated with poor prognosis. With our analyses, we examined the potential benefit of rifaximin in reducing the risk of developing cirrhosis-related complications. Methods: Adults with cirrhosis and hepatic encephalopathy (HE) in remission were randomly assigned to receive rifaximin 550 mg twice daily or placebo for 6 months with concomitant lactulose permitted. Post hoc analyses examined time to cirrhosis-related complications (HE, spontaneous bacterial peritonitis (SBP), variceal bleeding, acute kidney injury/hepatorenal syndrome). Subgroup analyses evaluated efficacy for select baseline disease characteristics. Results: Of patients receiving rifaximin ( n = 140) and placebo ( n = 159), 53.6% and 49.1%, respectively, had baseline Model for End-Stage Liver Disease (MELD) score ⩾ 12 and international normalized ratio (INR) ⩾ 1.2. Baseline ascites was observed in 36.4% (rifaximin) and 34.6% (placebo) of patients. In patients with MELD score ⩾ 12 and INR ⩾ 1.2, rifaximin reduced the relative risk (RR) of any first complication experienced during trial by 59% [hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.25–0.67; p < 0.001] versus placebo. For patients with baseline ascites, rifaximin reduced the RR of any first complication experienced during trial by 42% versus placebo (HR = 0.58, 95% CI: 0.34–1.0; p = 0.045). For some subgroups, there was a decrease in RR of complications of SBP, variceal bleeding, and acute kidney injury/hepatorenal syndrome with rifaximin versus placebo, although there were few events reported in the study. Conclusion: Rifaximin may reduce the incidence of cirrhosis-related complications and the recurrence of overt HE. [ ClinicalTrials.gov identifier: NCT00298038.

Overt Hepatic Encephalopathy: Current Pharmacologic Treatments and Improving Clinical Outcomes

Overt hepatic encephalopathy is a generally reversible neurologic complication of cirrhosis. Overt hepatic encephalopathy has been associated with poor hospitalization- and mortality-related outcomes, important given increasing hepatic encephalopathy-related hospitalizations over time. The aim of this narrative review is to provide an overview of hospital- and mortality-related outcomes in patients with overt hepatic encephalopathy and the pharmacologic therapies that may improve these outcomes. Guideline-recommended prophylaxis with lactulose (first-line therapy) or secondary prophylaxis with rifaximin plus lactulose decreases hospital admissions and mortality rates. Rifaximin or lactulose treatment was beneficial for reducing the hospitalization rate in patients with hepatic encephalopathy compared with no treatment. Further, retrospective studies have shown that rifaximin with or without lactulose was effective for decreasing the number of hepatic encephalopathy episodes, hepatic encephalopathy-related hospitalizations, and duration of hospitalization. Ornithine phenylacetate, an ammonia-reducing agent currently in development, is also being investigated in hospitalized patients with hepatic encephalopathy. Overall, data support that prophylaxis for the prevention of hepatic encephalopathy recurrence improves outcomes in patients with cirrhosis and a history of hepatic encephalopathy