Published online Dec 7, 2017. doi: 10.3748/wjg.v23.i45.8008
Peer-review started: August 4, 2017
First decision: September 5, 2017
Revised: October 10, 2017
Accepted: October 17, 2017
Article in press: October 17, 2017
Published online: December 7, 2017
Ulcerative colitis (UC) has a variable clinical course ranging from disease remission to a severe exacerbation leading to colectomy. It is very difficult to predict the disease course at the time of UC diagnosis. There are several clinical and epidemiological factors available for Crohn’s disease to predict the disease course, but there are limited prognostic markers available at the time of UC diagnosis. We believe that identifying these predictive markers will help physicians identify a subset of patients likely to develop a more severe disease course in the future and subsequently manage them more effectively at disease onset. Inflammatory activity of UC can lower albumin level by various mechanisms, such as malnutrition, malabsorption, greater fractional catabolic rate of albumin and increase transfer of albumin out of the vascular system. In view of this, we hypothesized that hypoalbuminemia at the time of UC diagnosis can be predictive of a more severe disease course of UC. Previous studies have shown that lower serum albumin level “at the time of UC exacerbation” predicted treatment failure and colectomy but none of these studies have looked at the level of albumin at the time of UC diagnosis and its relationship with the clinical course of the disease.
It is very hard to predict the disease course at the time of UC diagnosis. There are limited numbers of prognostic factors available to determine the course of UC at the time of diagnosis. None of the studies have considered the role of albumin in predicting UC course which is easy to measure on routine blood work by general practitioner as well as gastroenterologist. We thought that by identifying this new prognostic factor that can predict the course of UC at the time of UC diagnosis, it would be helpful for the physicians to identify a subset of patients at high risk of developing severe course and manage them more effectively early on in the disease course. In future studies, the impact of more aggressive therapy at the time of UC diagnosis among patients with poor prognostic factors could be evaluated.
Our main objective was to identify a new prognostic marker which is cheap, reliable and readily available at the time of UC diagnosis that predicts the long-term clinical course of the disease. We hypothesized that hypoalbuminemia at the time of UC diagnosis is associated with a more severe disease course of UC. We were able to show that that low albumin at disease diagnosis was associated with a more severe subsequent disease course of UC. This in conjunction with other prognostic markers would help us identify a subset of UC patients who will eventually develop severe disease. This subset may benefit from closer follow up and early escalation therapy. The impact of early escalation of therapy can be evaluated in future studies.
We conducted a nationwide retrospective cohort study of newly diagnosed UC patients followed in the VA healthcare system. These patients were divided into 2 groups based on their albumin levels at the time of UC diagnosis, i.e., hypoalbuminemic (≤ 3.5 gm/dL) or normal albumin levels (> 3.5 gm/dL). Our outcomes of interest were 1) the use of 2 or more courses of oral corticosteroid, separated by a three month time interval between the courses; (2) use of thiopurines or anti-TNFs; and (3) colectomy for UC-related reasons during the clinical course of their UC. We also included other covariate data like patient demographics as well as the extent of UC at index colonoscopy based on the Montreal classification. We then subjected this data including all the covariates to statistical analysis and evaluation using the multivariate cox proportional hazard models to estimate the adjusted Hazard ratio (HR) along with 95%CI. The Kaplan Meier analysis was also conducted. The pH assumption was tested using Schoenfeld’s residuals. All this analysis was done using the STATA software, version 14 (STATA Corp., College Station, TX, United States).
Our cohort included 710 newly diagnosed UC patients who had their albumin levels checked at the time of diagnosis and amongst them, 174 patients, i.e., 24.5% had hypoalbuminemia. It was observed that there was a higher predilection to ≥ 2 courses of CS use as well as thiopurine or anti-TNF use during the clinical course of disease among hypoalbuminemic patients. The chances of requiring subsequent colectomy were also higher in this group, although it was not statistically significant. Thus, we identified a new factor that is readily available and measurable at the time of UC diagnosis which can prognosticate the disease course. The problem that needs to be resolved is the impact of more aggressive therapy at the time of UC diagnosis among patients with poor prognostic factors on the clinical course of the disease.
Low albumin at disease diagnosis was associated with a more severe subsequent disease course of UC. People with poor prognostic factors may benefit from aggressive therapy at onset of disease. We outlined the clinical and epidemiological factors in newly diagnosed UC patients which have been studied as prognostic indicators in UC at the time of diagnosis. This study identified a new prognostic factor which is readily available to predict the disease course of UC at the time of diagnosis. We hypothesized and confirmed that albumin level at the time of disease diagnosis can predict disease course of UC. Assessing albumin levels at UC diagnosis could help physicians identify patients who may require escalation of therapy and closer follow up.
By using a large nationwide cohort of patients, we were able to identify a new prognostic factor to determine the clinical course of UC. This was made possible by having complete medical records and long duration of follow up. Using other large nationwide cohorts future studies may be able to identify other predictive factors. The future research should address the impact of more aggressive therapy at the time of UC diagnosis among patients with poor prognostic factors on the clinical course of the disease. The methodology that was employed by us can be utilized in future research.