Area Editoriale
Cinque lavori pubblicati a breve distanza hanno analizzato la casistica della Celveland Clinic consentendo di trarre le seguenti conclusioni:
- esiste una correlazione inversa fra la gravità della colangite sclerosante e quella della colite ulcerosa, in linea con quanto recentemente rilevato sulla casistica londinese del Royal Free Hospital (vedi riferimento in questa area tematica) Non vi è invece alcuna correlazione fra gravità di colangite sclerosante e gravità della malattia di Crohn.
- l'outcome dei pazienti con colangite sclerosante e colite ulcerosa è sovrapponibile a quello dei pazienti con colangite sclerosante non associata ad IBD. Recentemente un gruppo neozelandese aveva invece rilevato un decorso più aggressivo della colangite sclersante associata ad IBD rispetto alla colangite scleorsante isolata, (vedi riferimento in questa area tematica) mentre sulla casistica del John Radcliffe Hospital di Oxford stato rilevato un decorso più benigno nei pazienti con PSC associata a malattia di Crohn rispetto ai pazienti con PCS associata a colite ulcerosa
- non vi è alcuna correlazione fra la gravità della colangite sclerosante e il rischio di carcinoma colorettale
- dopo trapianto di fegato il numero di riacutizzazioni della colite ulcerosa si riduce nella maggior parte dei pazienti: tuttavia il 15 per cento dei pazienti trapiantati va incontro successivamente a colectomia. Una tendenza alla riduzione della attività infiammatoria intestinale dop trapianto di fegato è stata recentemente segnalata anche in una casistica norvegese (vedi riferimento su Pubmed)
The effects of liver transplantation on the clinical course of colitis in
ulcerative colitis patients with primary sclerosing cholangitis. Navaneethan U, Choudhary M, Venkatesh PG, Lashner BA, Remzi FH, Shen B, Kiran RP. Aliment Pharmacol Ther. 2012; 35: 1054-1063 .
BACKGROUND: The course of ulcerative colitis (UC) following orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear. AIM: To investigate the clinical course of UC, before and after OLT for PSC. METHODS: From a historical cohort of 86 patients with PSC-UC who underwent OLT, 77 patients who were followed up at our institution both before and after OLT from 1985 to 2011 were included. RESULTS: Ulcerative colitis was diagnosed in 77 (97.5%) patients before OLT. Nineteen of 77 (24.7%) patients underwent colectomy before OLT. In the other 58 patients, the course of UC after OLT when compared to
the last 5 years before OLT was quiescent in 48 patients (82.8%) while 9/58 (15.5%) of patients underwent colectomy post-OLT. There was a total of 97 colitis flares over a total of 621 years of follow-up from PSC/UC diagnosis to OLT (0.156 flares per patient year) whereas post-OLT, there were 31 flares over a total of 511 years of post-OLT follow-up (0.061 flares per patient year) (P < 0.001). On univariable analysis, the number of UC flares [Odds ratio (OR) 1.52; 95% Confidence interval (1.02-2.27), P = 0.04] and dysplasia [OR 47.00; 95% CI (6.48-340.66), P < 0.001] increased the risk of colectomy following OLT; the use of corticosteroids [OR 0.07; 95% CI (0.01-0.63), P = 0.008] and 5-aminosalicylate [OR 0.18; 95% CI (0.04-0.83), P = 0.04] was protective. CONCLUSIONS: Ulcerative colitis in the presence of primary sclerosing cholangitis remains quiescent, and
may improve in most patients after orthotopic liver transplantation.
The Impact of ulcerative colitis on the long-term outcome of patients with primary sclerosing cholangitis. Navaneethan U, Venkatesh PG, Lashner BA, Shen B, Kiran RP. Aliment Pharmacol Ther. 2012; 35:1045-1053
BACKGROUND: The impact of ulcerative colitis (UC) on the outcome of primary sclerosing cholangitis (PSC) outcome remains unclear. AIM: To investigate whether the presence of UC is associated with a worse clinical of associated PSC. METHODS: A total of 222 patients with PSC (167 with UC and 55 without UC) seen and followed at a single centre from 1985 to 2011 were included. Clinical and demographic variables were obtained and patients were followed until the date of their last clinic visit. RESULTS: The median age at presentation of PSC with associated UC was 38 vs. 47 years without UC (P < 0.001). At presentation, median serum bilirubin (2.1 vs. 4.5, P < 0.001) and the Mayo PSC Risk Score (0.95 vs 1.69, P < 0.001) were lower in those with UC vs. those without UC. A total of 55 of 167 (32.9%) patients with PSC-UC developed colon neoplasia in contrast to 1 of the 55 (1.8%) patients with PSC. (P < 0.001) On proportional hazards analysis, UC (hazard ratio (HR) = 0.90 [95% confidence interval (CI): 0.60-1.34, P = 0.60] was not associated with death or orthotopic liver transplantation (OLT), when adjusting for gender, Mayo risk score and year of PSC diagnosis; whereas the revised Mayo risk score [HR = 5.08, 95% CI: (2.62-9.86), P < 0.001] was associated with a greater risk of OLT or death. CONCLUSIONS: Primary sclerosing cholangitis often is recognised at an early stage in patients with concurrent ulcerative colitis; ulcerative colitis has no impact on long-term prognosis in terms of liver-related outcomes when adjusted for the severity of liver disease.
Duration and severity of primary sclerosing cholangitis is not associated with risk of neoplastic changes in the colon in patients with ulcerative colitis. Navaneethan U, Kochhar G, Venkatesh PG, Lewis B, Lashner BA, Remzi FH, Shen B, Kiran RP.Gastrointest Endosc. 2012;75:1045-1054.
BACKGROUND: Annual surveillance colonoscopy to detect colon cancer is recommended for patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). Limited data currently support these recommendations. OBJECTIVE: To study whether a relationship exists between the severity and duration of PSC and the risk of colon cancer and dysplasia (colon neoplasia). DESIGN: Retrospective, longitudinal study.
SETTING: Tertiary-care referral center. PATIENTS: Information pertaining to duration of PSC, UC, requirement for orthotopic liver transplantation, and time to diagnosis of colon neoplasia was obtained for patients with PSC and UC. Patients were evaluated and followed-up from 1985 to 2011 at a single institution. MAIN OUTCOME MEASUREMENTS: Association between the severity and duration of PSC-UC and the time of occurrence of colon neoplasia. RESULTS: Of 167 patients with a combined diagnosis of PSC-UC, 55 had colonic neoplasia on colonoscopy. Colonic neoplasia occurred more frequently within 2 years of a combined diagnosis of PSC-UC (6.6/100 patient-years of follow-up) than after 8 years from PSC-UC (2.7/100 patient-years of follow-up). On proportional hazards analysis, older age at PSC diagnosis (hazard ratio 1.23 for every 5 years; 95% confidence interval, 1.03-1.34; P = .014) increased the risk of colon
neoplasia. LIMITATIONS: Retrospective study. CONCLUSION: In this study, the severity of PSC was not significantly associated with the risk of colon neoplasia. Patients with PSC and UC have a high risk of colon neoplasia soon after the coexistence of the two diseases is discovered. Older age at PSC diagnosis increases this risk.
Severity of primary sclerosing cholangitis and its impact on the clinical outcome of Crohn's disease. Navaneethan U, G K Venkatesh P, Lashner BA, Lopez R, Kiran RP, Shen B. J Crohns Colitis. 2012;6:674-80.
BACKGROUND AND AIM: Crohn's disease (CD) is associated with primary sclerosing cholangitis (PSC). The aim of the study was to study the association between the severity of PSC and clinical outcome of CD, comparing the course of CD in patients with PSC not needing orthotopic liver transplantation (OLT) and those requiring OLT. METHODS: A total of 41 patients with PSC and CD seen at the Cleveland Clinic between 1985 and 2011 were included in this study. Clinical and demographic variables were obtained regarding the outcome of CD in patients with and without
OLT. RESULTS: Patients with PSC-CD were divided into two groups: 20 without OLT (non-OLT) and 21 with OLT. 18 (85.7%) of patients in the OLT group had pancolitis in contrast to 14 (70%) in the non-OLT group. (p=0.22). There were no significant differences regarding duration of CD, but the duration of PSC was longer in the OLT group [16.0±7.8 vs. 10.3±6.4, p=0.01]. The OLT and non-OLT groups did not differ in the number of CD flares [0 (0, 0) vs. 0 (0, 5), p=0.28) and need for surgery for CD [(6 (28.6%) vs. 9 (45%), p=0.27]. Colon carcinoma and dysplasia
were similar in the non-OLT and OLT groups [(4 (20%) vs. 3 (13.2%), p=0.52]. On Cox regression analysis, OLT for PSC [Hazards ratio (HR) 1.2 (95% confidence interval (C.I.): 0.38-3.7, p=0.79] did not impact the risk of colectomy. CONCLUSIONS: In contrast to UC, severe PSC requiring OLT does not appear to impact the clinical outcome of CD.
Progressive primary sclerosing cholangitis requiring liver transplantation is associated with reduced need for colectomy in patients with ulcerative colitis. Navaneethan U, Venkatesh PG, Mukewar S, Lashner BA, Remzi FH, McCullough AJ, Kiran RP, Shen B, Fung JJ. Clin Gastroenterol Hepatol. 2012;10:540-6.
BACKGROUND & AIMS: We investigated the association between the severity of primary sclerosing cholangitis (PSC) and clinical outcomes of patients with ulcerative colitis (UC) on the basis of need for colectomy.
METHODS: We analyzed data from 167 patients with PSC and UC who were followed from 1985 to 2011. Patients with PSC and UC were divided into groups that received orthotopic liver transplantation (OLT) (n = 86) or did not (non-OLT, n = 81). Clinical and demographic variables were obtained, and patients were followed until they received OLT or the date of their last clinical visit. RESULTS: The OLT group had significantly more subjects with less severe symptoms of UC (59, 68.6%) than the non-OLT group (12, 14.8%; P < .001). The subjects in the OLT group had a median of 0 UC flares compared with 3 in the non-OLT group (P < .001); fewer subjects in the OLT group required use of azathioprine or mercaptopurine (1, 1.2%), compared with the non-OLT group (14, 17.3%; P = .006). More subjects in the non-OLT group required colectomies (61, 75.3%) than in the OLT group (23, 26.7%; P < .001). On the basis of Cox regression analysis, OLT for PSC independently reduces the need for colectomy (hazard ratio
, 0.43; 95% confidence interval [CI], 0.25-0.75; P = .003), as does a high Mayo risk score at diagnosis (HR, 0.52; 95% CI, 0.37-0.72; P < .001). Development of colon neoplasia increased the risk for colectomy (HR, 2.47; 95% CI, 1.63-3.75; P < .001). CONCLUSIONS: Severe progressive PSC that requires liver transplantation appears to reduce the disease activity of UC and the need for colectomy.