Patients with Ulcerative Colitis and Primary sclerosing cholangitis who ultimately underwent a liver transplantation were found to have a significantly reduced need for a colectomy

Reference: Navaneethan, U., et al., Progressive primary sclerosing cholangitis requiring liver transplantation is associated with reduced need for colectomy in patients with ulcerative colitis. Clin Gastroenterol Hepatol, 2012. 10(5): p. 540-6.

A study out from Cleveland on the identification and comparison of clinical features for PSC-UC patients who 1) required liver transplantation vs. no-transplantation and 2) those who underwent a colectomy vs. no-colectomy.   

Brief Summary: Primary sclerosing cholangitis (PSC) is a chronic liver disease which causes inflammation of the bile ducts in the liver and often times, orthotopic liver transplantation (OLT) is required.  PSC is very common in patients with IBD – especially Ulcerative Colitis (UC) in particular.  The main objective of this investigation was to identify and compare the clinical and endoscopic features of those patients – with both PSC and UC - who ultimately required orthotpic liver transplantation (OLT) from those who did not undergo liver transplantation.  The authors analyzed data from 167 patients who had both PSC and UC and followed them from a period from 1985 until 2011.  The patients were followed until they either had OLT or their last clinical visit (in the case of no OLT).  A secondary objective was to investigate the risk factors for patients with PSC-UC who ultimately may require colectomy. 

Results: In general, UC-PSC patients who ultimately underwent an OLT had a much milder form of UC during the follow-up.  Particularly, the number of flares and needed medication use in the OLT group was significantly less than the non-OLT during follow-up.  Furthermore, the PSC-UC patient who ultimately underwent a OLT significantly reduced the need for a colectomy. 

Implications for Practice: If a patient has a severe form of UC along with PSC, a liver transplantation may lead to a milder form of UC post-liver transplantation.   

Discussion: Investigations like this are important, and I’m glad they are done.  The find that OLT transplantations lead to a milder form of UC (in many different respects) can definitely help the decision process of both patients and doctors when it comes down to doing a liver transplantation or not for UC patients.  For patients who have a more severe form of UC and PSC, it could definitely help. 

Some of the discussion points are really interesting.  Particularly, the authors noted in the discussion section that liver cirrhosis can actually be a preventive mechanism against more severe forms of UC.  This is due to the assumption that patients with liver cirrhosis have an impaired immune system.  As someone currently investigating the bio-pathogenesis of Ulcerative Colitis heavily, this really intrigues me. 

            Also, the authors noted in the discussion that UC may cause PSC through bacterial translocation and absorption of endotoxins into the liver.  This is also really interesting. I don’t know a whole lot on the background of PSC, and this makes me want to read up on it more.    

     

Commentary on Statistics  and Study Design: Overall, a good study design.  As the authors rightly noted, there are a number of limitations in this (really any) retrospective based study.  Most notably, there is a selection limitation (not bias).  This occurs since the observational units (the patients) recruited for the observational study may be un-like the general population of PSC-UC patients throughout the world according to several variables (both known and un-known).  However, there is little the investigator can do about this limitation other than just note it at the end of the discussion section.  It would obviously be better to perform a prospective rather than retrospective study (and follow the cohort into the future) in order to identify the risk factors of a given medical outcome, but sometimes this is also difficult to do.  Even with these limitations, useful information can still be gained – especially since a previous study in London concluded similar results.  This is important. 

            The only question I would have is why a multi-variate analysis was done for the secondary aim (colectomy vs. no-colectomy) but not the main aim (OLT vs. no-OLT).  This multi-variate analysis would be interesting to look it, because it would allow the doctor to narrow down the factors which are most associated with the outcome relative to all other factors.  It is usually best to report both uni-variate and multi-variate results.  The authors may have a reason that I don’t know for doing this.

            A big thanks for my buddies up in Cleveland for doing this.   Great job!