Clinical

Antibiotics improve liver function in primary sclerosing cholangitis

Last Updated: 2013-02-18 16:30:06 -0400 (Reuters Health)

By Anne Harding

NEW YORK (Reuters Health) - Vancomycin may be an effective treatment for primary sclerosing cholangitis (PSC), a pilot study suggests.

There are currently no good medical treatments for PSC. The disease, which affects an estimated 25,000 people in the US, is the fifth-leading indication for liver transplant in this country -- but up to two-thirds of patients will develop recurrent disease after transplant, Dr. James Tabibian of the Mayo Clinic in Rochester, Minnesota told Reuters Health.

The new research, which targets the enteric microbiota, "thus far appears promising, and we may be one step closer to finding a safe and effective pharmacotherapy for patients with this illness," Dr. Tabibian and his colleagues wrote in a paper online February 5 in Alimentary Pharmacology and Therapeutics.

Small case series dating back to 1959 have suggested that antibiotics could ameliorate liver disease in PSC patients. More recently, investigators have theorized that "bacterially derived molecules" could be triggering the inflammation and fibrosis in PSC. To further investigate the potential of antibiotics as therapy, Dr. Tabibian and his team randomly assigned 35 PSC patients to vancomycin (125 mg or 250 mg four times daily) or metronidazole (250 mg or 500 mg three times daily) for four weeks.

"Vancomycin, particularly low-dose vancomycin, showed more promising therapeutic results," Dr. Tabibian said in an interview. "Patients in the low-dose vancomycin group were able to reach the primary end point of the study, which was a reduction in alkaline phosphatase. It seems that higher doses of either drug are not necessarily better."

In fact, all of the patients taking vancomycin had lower alkaline phosphatase (ALK) levels at 12 weeks, the authors report. ALK dropped by 43% in the low-dose group (p=0.03) and by 40% in the high dose group (p=0.02). ALK normalized in two low-dose patients.

Patients on low-dose metronidazole had a 20% reduction in bilirubin (p=0.03), while bilirubin fell 33% in the low-dose vancomycin group (p=0.06). Both low-dose groups showed significant reductions in Mayo PSC risk scores (0.55, p=0.02 for vancomycin; 0.16, p=0.03 for metronidazole). The high-dose metronidazole group also had a significant reduction in pruritis. Six patients discontinued the study drug due to adverse results, including four patients taking metronidazole.

Dr. Tabibian added that vancomycin is well-tolerated, especially when compared to other agents that have been tested for treating PSC, such as prednisone and other immunosuppressants.

"These findings suggest the need for longer term and larger studies to have a better sense of the safety and efficacy of low-dose antibiotics, be it oral vancomycin or other alternatives," he concluded.

SOURCE: http://bit.ly/YCc1rG

Aliment Pharmacol Ther 2013.