Review article: the evidence that vancomycin is a therapeutic option for primary sclerosing cholangitis

Abstract

SummaryBackground and Aims: PSC is an autoimmune biliary inflammatory disorder that is often associated with inflammatory bowel disease (IBD), with 50%-75% of patients with PSC having coexisting IBD, most commonly ulcerative colitis. Currently, no medical therapies have been shown to improve the disease course or slow its progression. However, ongoing research has resulted in a growing interest in the use of antibiotics for treatment of PSC, of which vancomycin is the most studied. In this review, we summarise the current evidence on the use of vancomycin in PSC and comment on future research areas of interest.Methods: A comprehensive PUBMED and EMBASE literature search for articles on vancomycin, PSC, therapeutic options and microbiome was performed.Results: Two randomised clinical trials, three case series and two case reports were included in the study. These include uncontrolled data from at least 98 patients that include promising improvements in biochemistry and imaging. Optimal dosing regimens are unclear. Conclusion:Vancomycin is one of the most studied antibiotics used in the treatment of PSC with promising results. There is not currently sufficient evidence to support treatment recommendations. Further research is needed to establish if vancomycin is a PSC treatment.

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

“…Similar studies have not been performed in children, although short‐term biochemical improvement has been reported . Consequences of UDCA withdrawal in children with PSC are important for informing parents who may wish to discontinue the drug based on the adult study and to inform clinical trial design of UDCA studies with a control arm or any new PSC medications (e.g., vancomycin, farnesoid X receptor agonists) that would optimally be performed off UDCA …”

“…(7,16) Consequences of UDCA withdrawal in children with PSC are important for informing parents who may wish to discontinue the drug based on the adult study and to inform clinical trial design of UDCA studies with a control arm or any new PSC medications (e.g., vancomycin, farnesoid X receptor agonists) that would optimally be performed off UDCA. (13) During our study, we found that average liver biochemistries increased modestly overall with controlled UDCA withdrawal in children with quiescent PSC. Further analysis after stratification into treatment response groups showed that one third had normal ALT and GGT that remained normal in the absence of UDCA therapy (null group), one third increased above 100 IU/L (flare group), and the rest had intermediate responses (indeterminant group).…”

“…Ursodeoxycholic acid (UDCA) has been a mainstay of therapy in pediatrics, although quality of evidence supporting its long‐term use and benefits is lacking . Vancomycin has also been suggested to have therapeutic value in PSC in relatively small studies, and the overall experience with this drug is significantly less than with UDCA . Because of the paucity of data, clinicians, patients, and families are eager to employ any therapeutic regimen that may slow the progression of the disease.…”

“…(10,11) Vancomycin has also been suggested to have therapeutic value in PSC in relatively small studies, and the overall experience with this drug is significantly less than with UDCA. (12,13) Because of the paucity of data, clinicians, patients, and families are eager to employ any therapeutic regimen that may slow the progression of the disease. In this context, anecdotal approaches are often implemented to emphasize the critical need to avoid potential harm of unproven therapies.…”

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

“…lipopolysaccharides, LPS) also contributes by involving innate immune responses [32][33][34][35]. Furthermore, a series of studies now strongly indicate that the gut microbiota may be involved in PSC pathogenesis [17,[36][37][38][39][40] giving rise to clinical trials involving fecal transplantation, non-absorbable antibiotics, and other means of manipulating the gut microbiome in patients [17,[41][42][43]. In the bile ducts, bacterial, and fungal colonization may follow cholestasis and endothelial damage, through the establishing of a pathogenic biliary microbiota further propagating inflammation and intercurrent infections [44].…”