1. Oral Vancomycin Effect in Primary Sclerosing Cholangitis
Ruben Khan, MD1, Mohammed Albugeaey, MD2, Amol Rangnekar, MD3
MedStar Georgetown University Hospital, Department of Internal Medicine 2. MedStar Georgetown University Hospital, Division of Gastroenterology
3. MedStar Georgetown University Hospital, Transplant Institute
Georgetown University
Introduction
Results
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic disease of unknown etiology which can lead to recurrent episodes of cholangitis, increased risk for hepatobiliary and colon cancers, and ultimately cirrhosis and liver failure. The only treatment option know to improve survival is liver transplantation.1 Effective medical therapy has been lacking. Several drugs including ursodeoxycholic acid (UDCA) and various anti-inflammatory and immunomodulatory agents have been evaluated, but none of these therapies has shown substantial benefit with regards to improving survival or slowing progression of disease.1,2 Even UDCA, an agent used for many years in the treatment of PSC, may be associated with risk, particularly at higher doses.3,4,5 We report a case of a patient with PSC who was intermittently treated with oral vancomycin and had both symptomatic improvement and normalization of his liver associated enzymes (LAEs).
Case Report
Discussion
The patient is a 32 year old male with a history of PSC first diagnosed at 19 years old when he had elevated LAEs. Subsequent biopsies and magnetic retrograde cholangiopancreatography (MRCP) were consistent with PSC. He was treated with UDCA from 2001 to 2004, but eventually discontinued the agent due to the perceived risk of long term use. He remained generally asymptomatic until 2011 when he developed anorexia and episodes of cholangitis. In July 2013, he was hospitalized with an episode of cholangitis and was started on vancomycin 500mg orally twice per day with improvement of his symptoms. He later increased the vancomycin to 750mg orally three times per day with some improvement. Vancomycin was discontinued in October 2013, after which time he developed recurrent cholangitis in December The patient resumed vancomycin 1g by mouth once daily in January He changed to vancomycin 250mg orally four times per day and has been on this dose for over one year. Sequential MRCPs have demonstrated stable disease, and his liver enzymes have normalized. He has not experienced any recurrent episodes of cholangitis and remains asymptomatic (Figure 1).
Antibiotic therapy targeted against enteric bacteria has been associated with biochemical improvement in some patients with PSC. It has been hypothesized that enteric bacteria and bacterially derived molecules may enter the enterohepatic circulation in the setting of increased intestinal permeability, leading to chronic inflammation within the bile ducts. Oral metronidazole and vancomycin have been reported to lead to biochemical and symptomatic improvement in both pediatric and adult populations.6 Furthermore, oral vancomycin may have immunomodulatory functions including effects on levels of tumor necrosis factor-alpha and regulatory T cells.7
Recent prospective data demonstrate that vancomycin at low dose (125mg orally four times per day) for 12 weeks may significantly improve LAEs (including normalization of alkaline phosphatase) as well as symptoms.8 Prior studies have demonstrated improved outcomes and a reduced risk of cholangiocarcinoma in patients after normalization of alkaline phosphatase levels.9,10 Our patient achieved normal liver enzymes while on oral vancomycin and relapsed with discontinuation of the medication; this trend suggests that a more prolonged (if not indefinite) course of therapy may be required to affect the natural history of this disease. Long-term studies are needed to clarify whether sustained therapy with oral vancomycin is associated with more meaningful endpoints, such as a reduction in disease progression or an increase in transplant-free survival. Additionally, the ramifications of long-term oral vancomycin use remain unclear, particularly in regards to the risk of developing resistant bacterial species or adverse effects.
References
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7. Abarbanel D, Seki S, Davies Y, et al. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis.
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