Primary Sclerosing Cholangitis With IBD Yields Worse Outcomes

Patients with primary sclerosing cholangitis plus comorbid inflammatory bowel disease present at a younger age, are more likely to develop cancer or undergo liver transplantation, and have higher mortality than do patients without IBD, reported Dr. Jing Hieng Ngu and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

"These observations imply that IBD is, at least, an important modifying factor in the pathogenesis and clinical course of PSC," the authors wrote. "It is also possible that PSC with and without IBD represent two different disease processes," added Dr. Ngu of the University of Otago in Christchurch, New Zealand.

In what they called the "first population-based study of the descriptive epidemiology of PSC performed in the Southern Hemisphere or Asia Pacific region," researchers affiliated with Christchurch Hospital analyzed all known cases of PSC in Canterbury, New Zealand, that were diagnosed between Jan. 1, 1980 and Dec. 31, 2006; thus, the study was both prospective and retrospective.

"The estimated population for this region in 2008 was 494,170, which [accounted for] 12% of the total New Zealand population," the authors wrote (Clin. Gastroenterol. Hepatol. 2011 Sept. 5 [doi:10.1016/j.cgh.2011.08.027]), and the region is "relatively geographically isolated," making it an ideal epidemiologic target.

First, they calculated the prospective crude incidence of PSC in Canterbury in 2008 to be 1.6 (95% confidence interval, 0.5-2.7) per 100,000 residents, with sex-adjusted incidences being 2.0 per 100,000 for males and 0.8 per 100,000 for females.

Annual incidence rates from 2001 to 2008 were slightly lower overall, with a mean of 1.2 (95% CI, 0.3-2.2) per 100,000. In comparison, the age-standardized world standard population incidence was 1.6 per 100,000.

The authors then compared PSC cases with and without concurrent IBD. Indeed, of the 79 cases identified in the study period, 60 were associated with IBD (76%), with the greatest percentage of patients having ulcerative colitis, followed by Crohn’s disease.

Among patients with PSC alone, the mean age at diagnosis was 59 years, compared with 47 years for patients with concurrent IBD (P = .003).

Moreover, the authors noted, although "none of the 19 PSC patients without concurrent IBD in our population-based cohort developed any of the known serious malignant complications associated with PSC," there were eight cases of cholangiocarcinoma, two cases of hepatocellular carcinoma, and four cases of colorectal carcinoma among patients with the dual diagnoses (P = .017 for all).

The group of patients with both IBD and PSC also underwent a total of seven liver transplants, compared with none in the PSC-only group, and 19 vs. 3 deaths, respectively (P = .03 for both comparisons).

In an attempt to explain their findings, the authors pointed to a recent genomewide association study in PSC that identified one gene: macrophage-stimulating 1 (MST1), which has also been implicated in IBD. "This observation does raise the possibility that PSC patients with IBD could have a different genotype than PSC patients without concurrent IBD," they wrote.

Another theory is that a higher bacterial load in the enterohepatic circulation, possibly due to greater intestinal permeability in IBD, might explain why PSC patients with IBD have worse outcomes. "However, to date, there has been no convincing evidence that intestinal permeability is abnormal in patients with IBD," the authors wrote. "These conflicting observations have reminded us that the etiopathogenesis of PSC is likely to be complex involving multiple genetic and environmental factors," they added.

The authors disclosed that Dr. Ngu is supported by grants from the Health Research Council of New Zealand, the Ferring/New Zealand Society of Gastroenterology, and the Canterbury Medical Research Foundation. The current study was supported by the Royal Australasia College of Physicians. The authors made no personal disclosures.

Patients with primary sclerosing cholangitis plus comorbid inflammatory bowel disease present at a younger age, are more likely to develop cancer or undergo liver transplantation, and have higher mortality than do patients without IBD, reported Dr. Jing Hieng Ngu and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

"These observations imply that IBD is, at least, an important modifying factor in the pathogenesis and clinical course of PSC," the authors wrote. "It is also possible that PSC with and without IBD represent two different disease processes," added Dr. Ngu of the University of Otago in Christchurch, New Zealand.

In what they called the "first population-based study of the descriptive epidemiology of PSC performed in the Southern Hemisphere or Asia Pacific region," researchers affiliated with Christchurch Hospital analyzed all known cases of PSC in Canterbury, New Zealand, that were diagnosed between Jan. 1, 1980 and Dec. 31, 2006; thus, the study was both prospective and retrospective.

"The estimated population for this region in 2008 was 494,170, which [accounted for] 12% of the total New Zealand population," the authors wrote (Clin. Gastroenterol. Hepatol. 2011 Sept. 5 [doi:10.1016/j.cgh.2011.08.027]), and the region is "relatively geographically isolated," making it an ideal epidemiologic target.

First, they calculated the prospective crude incidence of PSC in Canterbury in 2008 to be 1.6 (95% confidence interval, 0.5-2.7) per 100,000 residents, with sex-adjusted incidences being 2.0 per 100,000 for males and 0.8 per 100,000 for females.

Annual incidence rates from 2001 to 2008 were slightly lower overall, with a mean of 1.2 (95% CI, 0.3-2.2) per 100,000. In comparison, the age-standardized world standard population incidence was 1.6 per 100,000.

The authors then compared PSC cases with and without concurrent IBD. Indeed, of the 79 cases identified in the study period, 60 were associated with IBD (76%), with the greatest percentage of patients having ulcerative colitis, followed by Crohn’s disease.

Among patients with PSC alone, the mean age at diagnosis was 59 years, compared with 47 years for patients with concurrent IBD (P = .003).

Moreover, the authors noted, although "none of the 19 PSC patients without concurrent IBD in our population-based cohort developed any of the known serious malignant complications associated with PSC," there were eight cases of cholangiocarcinoma, two cases of hepatocellular carcinoma, and four cases of colorectal carcinoma among patients with the dual diagnoses (P = .017 for all).

The group of patients with both IBD and PSC also underwent a total of seven liver transplants, compared with none in the PSC-only group, and 19 vs. 3 deaths, respectively (P = .03 for both comparisons).

In an attempt to explain their findings, the authors pointed to a recent genomewide association study in PSC that identified one gene: macrophage-stimulating 1 (MST1), which has also been implicated in IBD. "This observation does raise the possibility that PSC patients with IBD could have a different genotype than PSC patients without concurrent IBD," they wrote.

Another theory is that a higher bacterial load in the enterohepatic circulation, possibly due to greater intestinal permeability in IBD, might explain why PSC patients with IBD have worse outcomes. "However, to date, there has been no convincing evidence that intestinal permeability is abnormal in patients with IBD," the authors wrote. "These conflicting observations have reminded us that the etiopathogenesis of PSC is likely to be complex involving multiple genetic and environmental factors," they added.

The authors disclosed that Dr. Ngu is supported by grants from the Health Research Council of New Zealand, the Ferring/New Zealand Society of Gastroenterology, and the Canterbury Medical Research Foundation. The current study was supported by the Royal Australasia College of Physicians. The authors made no personal disclosures.

Patients with primary sclerosing cholangitis plus comorbid inflammatory bowel disease present at a younger age, are more likely to develop cancer or undergo liver transplantation, and have higher mortality than do patients without IBD, reported Dr. Jing Hieng Ngu and colleagues in the December issue of Clinical Gastroenterology and Hepatology.

"These observations imply that IBD is, at least, an important modifying factor in the pathogenesis and clinical course of PSC," the authors wrote. "It is also possible that PSC with and without IBD represent two different disease processes," added Dr. Ngu of the University of Otago in Christchurch, New Zealand.

In what they called the "first population-based study of the descriptive epidemiology of PSC performed in the Southern Hemisphere or Asia Pacific region," researchers affiliated with Christchurch Hospital analyzed all known cases of PSC in Canterbury, New Zealand, that were diagnosed between Jan. 1, 1980 and Dec. 31, 2006; thus, the study was both prospective and retrospective.

"The estimated population for this region in 2008 was 494,170, which [accounted for] 12% of the total New Zealand population," the authors wrote (Clin. Gastroenterol. Hepatol. 2011 Sept. 5 [doi:10.1016/j.cgh.2011.08.027]), and the region is "relatively geographically isolated," making it an ideal epidemiologic target.

First, they calculated the prospective crude incidence of PSC in Canterbury in 2008 to be 1.6 (95% confidence interval, 0.5-2.7) per 100,000 residents, with sex-adjusted incidences being 2.0 per 100,000 for males and 0.8 per 100,000 for females.

Annual incidence rates from 2001 to 2008 were slightly lower overall, with a mean of 1.2 (95% CI, 0.3-2.2) per 100,000. In comparison, the age-standardized world standard population incidence was 1.6 per 100,000.

The authors then compared PSC cases with and without concurrent IBD. Indeed, of the 79 cases identified in the study period, 60 were associated with IBD (76%), with the greatest percentage of patients having ulcerative colitis, followed by Crohn’s disease.

Among patients with PSC alone, the mean age at diagnosis was 59 years, compared with 47 years for patients with concurrent IBD (P = .003).

Moreover, the authors noted, although "none of the 19 PSC patients without concurrent IBD in our population-based cohort developed any of the known serious malignant complications associated with PSC," there were eight cases of cholangiocarcinoma, two cases of hepatocellular carcinoma, and four cases of colorectal carcinoma among patients with the dual diagnoses (P = .017 for all).

The group of patients with both IBD and PSC also underwent a total of seven liver transplants, compared with none in the PSC-only group, and 19 vs. 3 deaths, respectively (P = .03 for both comparisons).

In an attempt to explain their findings, the authors pointed to a recent genomewide association study in PSC that identified one gene: macrophage-stimulating 1 (MST1), which has also been implicated in IBD. "This observation does raise the possibility that PSC patients with IBD could have a different genotype than PSC patients without concurrent IBD," they wrote.

Another theory is that a higher bacterial load in the enterohepatic circulation, possibly due to greater intestinal permeability in IBD, might explain why PSC patients with IBD have worse outcomes. "However, to date, there has been no convincing evidence that intestinal permeability is abnormal in patients with IBD," the authors wrote. "These conflicting observations have reminded us that the etiopathogenesis of PSC is likely to be complex involving multiple genetic and environmental factors," they added.

The authors disclosed that Dr. Ngu is supported by grants from the Health Research Council of New Zealand, the Ferring/New Zealand Society of Gastroenterology, and the Canterbury Medical Research Foundation. The current study was supported by the Royal Australasia College of Physicians. The authors made no personal disclosures.