Primary sclerosing cholangitis (PSC)

Overview of PSC

PSC is a chronic, generally progressive disease wherein bile ducts of various sizes, small and/or large, become inflamed and scarred for reasons which remain poorly understood.  It can affect males and females of essentially all ages, though it is most commonly diagnosed in men in their 30s.  Despite being considered a rare disease, there are an estimated 30,000 individuals with PSC in the United States (USA) alone, if not more.   Over the course of 10-20 years, PSC can lead to various major adverse events, including bile duct cancer (i.e. cholangiocarcinoma), cirrhosis (severe scarring of the liver due to longstanding inflammation related to impaired flow of bile through its normal course), and ultimately liver failure, though in some patients these may arise much sooner or not at all.  For these reasons and various others, PSC is considered a heterogeneous disorder.

An overview of PSC would be incomplete without also mentioning another related digestive disorder, namely inflammatory bowel disease (IBD).  Approximately 70% of individuals with PSC have or will develop concurrent IBD, which represents a remarkably strong clinical association.  Conversely, approximately 5% of individuals with IBD have or will develop concurrent PSC, thus while PSC in IBD is comparably not as frequent, one should remain cognizant of and watchful for this association.

Management of PSC

With regard to the management of PSC, there are several aspects to consider:

-First, and especially in individuals who've been newly diagnosed with PSC, the diagnosis itself should be examined to help ensure that it is a correct one, as there are several PSC mimics which, despite biochemical and/or radiographic similarities, are managed quite differently. 

-Second, it's important to monitor a number of associated aspects of overall health and take a proactive and preventative approach, recognizing that PSC isn't just a bile duct or liver problem but rather can secondarily impact numerous other aspects of health and wellness, no matter how early or mild one's PSC may be.  Included in this is the need to perform cancer surveillance, particularly for cholangiocarcinoma.

-Third, as 50% or so of patients will have symptoms at the time of PSC diagnosis or within a couple years thereafter, a watchful eye must be maintained and appropriate intervention taken.  For example if itching ("pruritus") has developed, it's vital to investigate this carefully so as to treat it most appropriately. 

-Fourth, we must learn to cope with the lamentable current reality that, despite decades of ongoing research, an effective pharmacologic treatment (i.e. a pill or other non-operative intervention) for PSC that can lead to a cure or complete healing of the bile ducts has yet to be found.  Thus, we are currently left only with medical interventions that might possibly delay progression of disease, some of which are only available through participation in clinical trials.  While this remains frustrating (to say the least) for patients, their families, other loved ones, and clinicians, we know more about PSC now than ever before, and the rate at which PSC research has been conducted over the last few years is, in the eyes of many, unprecedented.  Thus, the road ahead looks brighter than it has in the past, though there is still quite a ways to go.

-Fifth, though time is of the essence, to first do no harm ("primum non nocere"-- a principal precept of bioethics and a tenet of the Hippocratic oath), we should approach potential interventions (pharmacologic or other) with objectivity and clarity to whatever extent possible.  It's not difficult to become excited by hype and consequently develop false hope or worse (e.g. taking a medication which causes untoward severe liver or other organ injury).  

-Lastly (at least with respect to the short list of management considerations), some patients will go on to need surgical intervention, possibly liver transplantation (LT). PSC is the fifth most common indication for LT in the USA and a leading indication in some countries, e.g. in Scandinavia.  While potentially curative, some patients die while awaiting LT, and nearly 25% of patients who undergo LT will eventually develop recurrent PSC in the new liver.  For these and many other reasons, safe and effective pharmacotherapies that can veritably halt or at least significantly halt disease progression are desperately needed.  In the meantime though, there is much that can be done to make living with PSC more manageable and to promote living life amidst disease and distress.