Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease of unknown cause characterized by patchy progressive inflammation of the biliary tree resulting in destruction and fibrosis. This liver disease can occur in children or adults. Disease progression, although variable, is almost universal in all patients, resulting in a loss of intrahepatic bile ducts leading to biliary cirrhosis and eventually liver failure. There is an increased risk of bile duct cancer, cholangiocarcinoma, in individuals with primary sclerosing cholangitis.
The rarity and complexity of PSC makes it a challenging disease to treat. There are no FDA approved treatments for PSC, and most patients are doomed to face disease progression with eventual worsening of symptoms, dramatically reduced quality of life and an eventual liver transplant. The disease often reoccurs after transplant, causing the cycle to begin again.
The diagnosis of primary sclerosing cholangitis has increased as a result of screening patients with inflammatory bowel disease (IBD) for abnormal liver function tests. The close association between primary sclerosing cholangitis and inflammatory bowel disease has been well established. 70% of patients with primary sclerosing cholangitis have inflammatory bowel disease, particularly ulcerative colitis. The course of the biliary disease is unrelated to the clinical course of the colitis.
There is increasing evidence that dysbiosis of the gut microbiota, leading to disruptions in the "liver/gut axis" as well as immune mechanisms play an essential role in the pathogenesis of primary sclerosing cholangitis. The cause and effect between dysbiosis in the gut microbiome, immunie mechanisms, liver/gut axis disruption, and bile duct injury has yet to be established. There are potential non-immune mechanisms that play a role in the pathogenesis of this liver disease. These include a toxic agent, possibly liberated by gut bacteria or ischemic injury. There have been many trials of pharmacological agents of which none have shown resolution in the effects of primary sclerosing cholangitis.
There is one promising therapy for PSC, oral vancomycin - that has shown efficacy for many patients in clinical settings and that has become the standard of care for patients in several health care institutions.
Since 1993, Dr. Kenneth Cox and a handful of other doctors have been successfully using the antibiotic vancomycin off-label to effectively treat and manage PSC. As word spreads of oral vancomycin's effectiveness, more and more PSC patients are able to pause their PSC progression and no longer require an eventual transplant.
Dr. Kenneth Cox and his team at Stanford have identified at least five factors that impact vancomycin’s efficacy, including the drug’s brand and dose and the patient’s age, phenotype, and stage of disease. You can read more about these nuances here.
Since many gastroenterologists and hepatologists aren’t familiar with these small Stanford studies and oral vancomycin’s nuances, they may prescribe vancomycin without the knowledge of the drug’s efficacy factors or following the proper guidelines. Then, if the patient doesn’t respond, the doctor simply believes that vancomycin is ineffective and they become unwilling to prescribe it to any other patients.
But when doctors account for these factors and prescribe vancomycin according to its best practices, it can stop, slow, or even reverse the progression of PSC.