| 31. |
- Lindstrom, L., et al.
(författare)
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High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia
- 2012
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Ingår i: Alimentary Pharmacology and Therapeutics. - Malden : Wiley. - 0269-2813 .- 1365-2036. ; 35:4, s. 451-457
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking. Aim To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD. Methods From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia. Results The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo-(n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. Conclusions Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.
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| 32. |
- Liu, Jimmy Z, et al.
(författare)
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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:6, s. 670-5
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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| 33. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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A Population-based Cohort Study of Pregnancy Outcomes Among Women With Primary Sclerosing Cholangitis
- 2014
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 12:1, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Studies of primary sclerosing cholangitis (PSC) and pregnancy outcomes have been limited in size and have been inadequate to rule out excess risks. We examined pregnancy outcomes among women with PSC.METHODS: Women with PSC were identified from inpatient and hospital-based outpatient data in the Swedish National Patient Register. Through linkage with the Medical Birth Register, we identified 229 singleton births, from 1987 through 2009, to women with PSC before delivery. These were compared with 2,304,863 births to women without a diagnosis of PSC. We used logistic regression, adjusted for maternal age, smoking, education, parity, and year of birth, to calculate adjusted prevalence odds ratios (aPORs) for adverse pregnancy outcomes.RESULTS: Maternal PSC was associated with a 3.63-fold increase in preterm birth (95% confidence interval [CI] for aPOR, 2.35-5.61) as well as an increased risk of cesarean section (aPOR, 2.18; 95% CI, 1.50-3.17). We found no increased risk based on analyses of the 5-minute Apgar score, small for gestational age, stillbirths, or neonatal deaths. Maternal PSC was not a risk factor for congenital abnormalities (aPOR, 1.12; 95% CI, 0.56-2.22). Stratification by inflammatory bowel disease status did not affect the risk estimates more than marginally.CONCLUSIONS: Maternal PSC is associated with both preterm birth and cesarean section but not with congenital malformation or other adverse outcomes of pregnancy. Pregnancy should not be discouraged in women with PSC.
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| 34. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Risk of diabetes and cardiovascular disease in patients with primary sclerosing cholangitis
- 2013
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 60:4, s. 802-808
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Primary sclerosing cholangitis (PSC) is associated with increased mortality. Cardiovascular disease is a leading cause of death in the Western world. We examined the risk of cardiovascular disease and diabetes (type 1 and type 2) in patients with PSC and their first-degree relatives. Methods: This prospective multicentre cohort study included 678 individuals with PSC diagnosed between 1970 and 2004, and 6347 non-PSC reference individuals matched for age, and sex. Through linkage of the Swedish Multigeneration Register we identified 3139 first-degree relatives to PSC patients and 30,953 first-degree relatives to the matched comparison cohort. We retrieved data on cardiovascular disease and type 1 and type 2 diabetes (T1D and T2D) from the National Patient Register, and then examined the association with PSC or having a family history of PSC using Poisson regression.Results: During 125,127 person-years of follow-up, 203 individuals with PSC had a diagnosis of cardiovascular disease. This corresponded to a 3.34-fold increased relative risk (RR) of cardiovascular disease in individuals with PSC (95% CI = 2.86-3.91). The highest risk estimates were seen for diseases of the arteries, veins, and lymphatic vessels while the RR was neutral for ischemic heart disease (0.90) or only slightly elevated for cerebrovascular disease (1.74). Meanwhile, PSC first-degree relatives were at no increased risk of cardiovascular disease (RR = 0.87; 95% CI = 0.80-0.95). Individuals with PSC (RR = 7.95; 95% CI = 4.82-13.12), and to some extent also their first-degree relatives (RR = 1.73; 95% CI = 1.19-2.52) were at increased risk of T1D. Also for T2D were the RR is higher in individuals with PSC (RR = 2.54; 95% CI = 1.56-4.13) than in PSC first-degree relatives (RR = 0.81; 95% CI = 0.65-1.02).Conclusions: PSC was associated with T1D, T2D, and non-ischemic cardiovascular disease. In contrast, first-degree relatives to PSC patients were only at a moderately increased risk of T1D, and at no increased risk of either cardiovascular disease or T2D.
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| 35. |
- Lundberg Båve, Aiva, et al.
(författare)
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Colectomy in patients with ulcerative colitis is not associated to future diagnosis of primary sclerosing cholangitis
- 2023
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Ingår i: United European Gastroenterology journal. - : John Wiley & Sons. - 2050-6406 .- 2050-6414. ; 11:5, s. 471-481
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary Sclerosing Cholangitis (PSC) is a hepatobiliary disease closely related to ulcerative colitis (UC). In PSC patients, colectomy has been linked to improved prognosis, especially following liver transplantation. This suggests an involvement of the gut-liver axis in PSC etiology.Objective: We aimed to investigate the association between colectomy and the risk of future PSC in an epidemiological setting.Method: Through nationwide registers, we identified all adults diagnosed with UC in Sweden 1990-2018 and retrieved information on PSC diagnosis and colectomy. Within the UC cohort (n = 61,993 patients), we matched 5577 patients with colectomy to 15,078 without colectomy. Matching criteria were sex, age at UC onset (±5 years), year of UC onset (±3 years), and proctitis at the time of colectomy. Incidence rates of PSC per 1000-person year were calculated, and the Cox proportional hazard regression model estimated hazard ratios (HRs) for PSC until 31 December 2019.Results: During the follow-up, 190 (3.4%) colectomized UC patients and 450 (3.0%) UC comparators developed PSC, yielding incidence rates of 2.6 and 2.4 per 1000 person-years (HR 1.07 [95% CI 0.90-1.28]). The cumulative incidence of colectomy decreased remarkably over calendar periods, but the cumulative incidence of PSC remained unchanged. The risk of developing PSC in colectomized versus comparators changed over time (HR 0.68 [95% CI; 0.48-0.96] in 1990-97 and HR 2.10 [95% CI; 1.37-3.24] in 2011-18).Conclusions: In UC patients, colectomy was not associated with a decreased risk of subsequent PSC. The observed differences in the risk of PSC development over calendar periods are likely due to changes in PSC-diagnosis and UC-treatment.
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| 36. |
- Lynch, Kate D, et al.
(författare)
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Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases.
- 2020
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Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n= 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P= .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P= .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
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| 37. |
- Magnusson, Maria, et al.
(författare)
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The international normalized ratio according to Owren in liver disease: Interlaboratory assessment and determination of international sensitivity index
- 2013
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Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 132:3, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The international normalized ratio (INR) is used to prioritize liver disease patients for transplantation. Previous studies have shown high interlaboratory variability in Quick-based INR determinations in samples of patients with liver disease. We assessed Owren-based INR reagents for analyzing INR in patients with liver disease. Further, we determined the difference between international sensitivity index (ISI) for patients on vitamin K antagonists (ISIVKA) and ISI for patients with liver disease (ISIliver). less thanbrgreater than less thanbrgreater thanPatients and Methods: Twenty patients with liver disease were included, 10 with INR 1.8-3.6 (group A1) and 10 with INR 1.2-1.5 (group C1). Plasma from these patients was analyzed for Owren-based INR in eight Swedish laboratories using either of following reagents: SPA+, Owrens PT or Nycotest PT. To determine ISI liver, the reference thromboplastin RBT/05 and additional 41 patients with liver disease and 20 normal controls were included. ISIVKA was determined according to the WHO procedure. The difference between the ISIVKA and ISIliver was calculated. less thanbrgreater than less thanbrgreater thanResults: The coefficients of variance for the Owren based INR methods were 6.2% in group A1, 3.9 % in group C1 and 5.3% for all patients. The difference between ISIVKA and ISIliver were -0.4%, -0.7% and -0.2% for SPA+, Owrens PT and Nycotest PT respectively. less thanbrgreater than less thanbrgreater thanConclusions: Interlaboratory variation in INR analyses according to Owren in patients with liver disease is low and the difference between ISIVKA and ISIliver is below 10% with this method. ISIVKA can therefore be used in the INR calibration, for the Owren reagents studied, when analyzing plasma from patients with liver disease.
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| 38. |
- Næss, Sigrid, et al.
(författare)
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Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
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| 39. |
- Nayagam, Jeremy S, et al.
(författare)
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Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis.
- 2023
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Ingår i: JHEP reports : innovation in hepatology. - 2589-5559. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes.We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used.There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p= 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p= 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p= 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p= 0.84).Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype.Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.
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| 40. |
- Nordenvall, Caroline, et al.
(författare)
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Restorative Surgery in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis Following a Colectomy
- 2018
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Ingår i: Inflammatory Bowel Diseases. - : LIPPINCOTT WILLIAMS & WILKINS. - 1078-0998 .- 1536-4844. ; 24:3, s. 624-632
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on surgical procedures in patients with concomitant primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have mainly been restricted to single centers. The aim was to compare surgical treatment of UC with or without PSC in a nationwide study. Methods: A cohort study including all patients diagnosed with UC between 1987 and 2014 in Sweden was undertaken. The impact of PSC on the risk of colectomy, the chance of restorative surgery, and risk of failure (presence of a stoma) following restorative surgery were estimated. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models. Results: Of 49 882 UC patients, 2079 had a PSC diagnosis at the end of follow-up. The risk of colectomy was unaffected by PSC diagnosis, whereas the chance of restorative surgery was elevated in PSC-UC patients (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.02-1.44). Ileorectal anastomosis (IRA) was performed in 63% of the PSC-UC patients and 43% of the non-PSC-UC-patients, and the corresponding numbers for ileal pouch anal anastomosis (IPAA) were 35% and 53%. There was no significantly increased risk of failure following restorative surgery in PSC patients (HR, 1.44; 95% CI, 0.93-2.22). In PSC-UC patients, the cumulative failure rates following an IRA at 3 and 5 years were 15% and 18%, and following an IPAA they were 11% and 18%, respectively. Conclusions: Presence of PSC is not associated with the risk of colectomy, whereas the chance of restorative surgery in PSC-UC patients is higher than in UC alone.
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