Bob Roehr

November 08, 2010

November 8, 2010 (Boston, Massachusetts) — In March of this year, the US Food and Drug Administration granted a label indication to the antibiotic rifaximin (Xifaxan 550 mg) for the treatment of hepatic encephalopathy. One consequence is a trickle of studies presented here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting that confirm the efficacy of the drug.

Rifaximin is a potent broad-spectrum antibiotic that has virtually no systemic absorption and is well suited to control intestinal bacterial overgrowth without systemic exposure. Cirrhotic patients are predisposed to intestinal bacterial overgrowth. Deterioration of the gut barrier function can result in the translocation of bacteria and increased abdominal inflammation, which in turn can result in increased portal venous pressure.

Jiannis Vlachogiannakos, MD, and colleagues from the Evangelismos General Hospital in Athens, Greece, conducted a retrospective matched study of patients with alcohol-related decompensated cirrhosis (Child-Pugh score above 7) and ascites. Patients took rifaximin for a short course (4 weeks) and, if they responded with improved liver hemodynamics on hepatic venous pressure gradient testing, were continued on a daily dose of 1200 mg.

The analysis consisted of 23 patients (20 male, 3 female) who took rifaximin, each of whom were sex and age matched (±5 years) to 2 control patients with decompensated cirrhosis of the same etiology who did not take rifaximin. All patients had abstained from alcohol consumption for at least 6 months prior to entering the registry. They were followed for 5 years, death, or liver transplantation, whichever came first.

Dr. Vlachogiannakos said the active group "had a significantly lower risk of developing variceal bleeding (35% vs 59.5%; P = .011), hepatic encephalopathy (31.5% vs 47%; P = .034), spontaneous bacterial peritonitis (5.5% vs 46%; = .027), and hepatorenal syndrome (4.5% vs 51%; P = .037) than controls."

Patients who did not take rifaximin died in disproportionate numbers (24/46 vs 7/23). He said that "the probability of 5-year survival was 61% in the rifaximin group and 13.5% in the control group (p = .012).

Michael D. Leise, MD, and colleagues from the Mayo Clinic in Rochester, Minnesota, examined medical records from the Mayo Clinic and identified 280 patients with hepatic encephalitis who were given rifaximin on a long-term open-label basis. They compared it with an algorithm of disease state and survival generated from data recorded in the Organ Procurement and Transplant Network.

They found that patients receiving rifaximin generally had better rates of survival, although the difference did not reach statistical significance except in the highest-risk patient group. The authors conclude that in addition to suggesting benefit, it provides assurance on the long-term safety of rifaximin.

Finally, a study from Virginia Commonwealth University in Richmond offered insights into improvement in brain function with rifaximin. Hepatic encephalopathy is associated with driving impairment.

Jasmohan Bajaj, MD, and colleagues used performance on a 15-minute driving-simulator test to evaluate driving and navigation skills (speeding tickets, collisions, and illegal turns) at baseline and 8 weeks after 42 hepatic encephalopathy patients were randomized in a 1:1 manner to receive rifaximin or placebo.

Comparing results from the 2 time points, he found that "76% of patients in the rifaximin group reduced their driving error, compared with only 33% in the placebo group, which is statistically significant." On the speeding ticket criteria, 81% and 33% of the respective groups reduced their errors. But there was no difference between them in terms of collisions, a fact that he attributed to the greater awareness of and learning from a simulated collision.

When asked what physicians might do if they believe a patient is suffering from hepatic-encephalopathy-related cognitive impairment, Dr. Bajaj said the findings are preliminary. More important, "if you have any questions about your patient's driving ability, you are not qualified as a doctor to make that decision. You should send those patients to your department of motor vehicles."

All of the studies were conducted as part of academic research. The researchers have disclosed no relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstracts 19, 24, and 22. Presented October 31, 2010.