| 1. |
- Bergquist, Annika, et al.
(författare)
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Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis
- 2008
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Ingår i: Clinical Gastroenterology and Hepatology. - New York : Elsevier. - 1542-3565 .- 1542-7714. ; 6:8, s. 939-943
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.
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| 2. |
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| 3. |
- Vikingsson, Svante, et al.
(författare)
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Novel assay to improve therapeutic drug monitoring of thiopurines in inflammatory bowel disease
- 2014
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Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 8:12, s. 1702-1709
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The thiopurines are widely used in the treatment of inflammatory bowel disease, but are limited by poor dose effect relationship. The objective was to assess the ability of a novel assay, determining the mono-, di-, and triphosphates, of thioguanine as well as methylthioinosine as individual metabolites in erythrocytes, to predict clinical outcome compared to a routine assay, determining metabolites as sums. Methods: Samples from 79 patients with Crohns disease or ulcerative colitis treated with azathioprine or mercaptopurine were analysed by both assays. Clinical status was determined by the Harvey-Bradshaw and Walmsley indices. The genotypes of thiopurine methyltransferase (TPMT) and inosine triphosphatase were determined. Results: TPMT wild-type patients with thioguanine nucleotide (TGN) levels below the cut-off level were more likely to have active disease when TGN was measured by the novel assay (p = 0.02), and when thioguanosine triphosphate (TGTP) was measured separately (p = 0.01). When TGN was measured by the routine assay the correlation was not evident (p = 0.12). Neither TGN levels nor TGTP correlated to disease activity in TPMT deficient patients. Patients with methyl thioinosine nucleotide (meTIN) levels above 1500 pmol/8 x 10less than^greater than8 RBCs were more likely to have active disease (p = 0.07). We observed good correlations between the mono-, di-, and triphosphates and their respective sums (R-2 greater than 0.88). Conclusions: The novel TGN assay was better in predicting clinical outcome compared to the routine assay, while determination of TGTP had no clinical advantage and TGTP ratio was not correlated to disease activity. (C) 2014 European Crohns and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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| 4. |
- Wallerstedt, Sven, 1944, et al.
(författare)
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Moderate hyperkalemia in hospitalized patients with cirrhotic ascites indicates a poor prognosis
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 48:3, s. 358-365
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Development of ascites in patients with liver cirrhosis is an ominous sign with a poor outcome. A liver transplantation must be considered, and it then becomes important to know if there are any factors indicating a worsened prognosis. Material and methods. We used official registers for a follow-up study of at least 5 years considering the prognosis of 155 prospectively recruited in-patients with cirrhotic ascites from medical units at nine Swedish university hospitals. All patients had undergone at least one diagnostic ascites tap, and had initially been questioned about background factors and physically examined according to a standardized case record form, followed by sampling of blood, urine, and ascites. Results. Death occurred within 1 year after inclusion in 53% of the cases, and was primarily liver-related in 70%. In a multivariable analysis, the two ordinary variables that showed the strongest correlation with risk of death were serum potassium and abdominal tenderness. All 22 patients with a serum potassium concentration of at least 4.8 mmol/L (maximum 5.8 mmol/L) died within 1 year after inclusion. Potassium concentration was related to renal function and potassium-saving drugs. Conclusion. This follow-up study of a prospectively recruited cohort of in-patients with cirrhotic ascites confirms their poor prognosis. Awareness of an elevated serum potassium value, which would reflect a threatened renal function, seems essential, because it may offer a simple way to identify cases with the worst prognosis. An area for further research should be to explore the significance of including serum potassium in prognostic models.
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| 5. |
- Wallerstedt, Sven, 1944, et al.
(författare)
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Abdominal tenderness in ascites patients indicates spontaneous bacterial peritonitis
- 2007
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Ingår i: European journal of internal medicine. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 18:1, s. 44-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spontaneous bacterial peritonitis (SBP), which has been reported to be present in 10-30% of patients with cirrhotic ascites, may easily be overlooked. An important aim of our study was to determine whether there are any clinical signs which, in clinical practice, may predict or exclude SBP. Methods: We studied 133 patients with cirrhotic ascites from medical units at nine Swedish university hospitals where there had been at least one diagnostic ascites tap with analysis of polymorphonuclear leukocytes in the ascites fluid. The patients had initially been questioned about background factors and physically examined according to a standardized case record form. Samples of blood, urine, and ascites were then drawn for analysis according to a structured schedule. Results: SBP could be excluded in 80% of all the cases and was confirmed in 8% of the 133 patients in the final analysis. Abdominal pain and abdominal tenderness were more common in patients with SBP (p < 0.01), but no other physical sign or laboratory test could separate SBP cases from the others. Conclusions: SBP was present in about one-tenth of the hospitalized patients with cirrhotic ascites in this cohort. Performing repeated physical examinations and paying particular attention to abdominal tenderness may be the best way to become aware of the possible development of this complication.
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| 6. |
- Vikingsson, Svante, 1983-
(författare)
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Development of new methodology for therapeutic drug monitoring of thiopurine treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The three thiopurine drugs azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat several diseases, including inflammatory bowel disease (IBD). They are pro-drugs and are believed to act through the formation of thioguanine nucleotides (TGNs). Other important metabolites are the methylthioinosine nucleotides (meTINs). These metabolites are active in the white blood cells (WBCs).Most patients respond well to the thiopurine drugs but up to a third have to modify or discontinue their treatment due to adverse events or a lack of therapeutic effects. This could be caused by inter-patient variability in the metabolism of the drugs. Therapeutic drug monitoring (TDM) of thiopurine nucleotides in red blood cells (RBCs) is used to guide treatment. Current routine assays measure the nucleotides after hydrolysation to nucleic bases and are therefore unable to distinguish between mono-, di-, and triphosphates. Recently it was shown that these assays failed to predict the clinical outcome in about 40% of the patients. It has been suggested that measuring thioguanosine triphosphate (TGTP) (believed to be the most active of the TGNs) separately might increase the clinical value.An assay suitable for measuring thioguanosine mono- (TGMP) and diphosphate (TGDP) and TGTP, as well as methylthioinosine mono- (meTIMP), di- (meTIDP) and triphosphate (meTITP) separately in RBCs in clinical samples has been developed. In clinical studies of 82 IBD patients, we found no correlation between the thiopurine dose and metabolite levels in RBCs, thus illustrating the importance of metabolite measurements in the TDM of thiopurines.The TGN peak measured by the routine assay during TDM of patients treated with thiopurines consisted of TGTP and TGDP with a small contribution from TGMP. The meTIN also consisted of mono-, di- and triphosphates, but in different proportions, indicating differences in the formation. The inter-individual differences in nucleotide distribution were very small and a strong correlation between the different nucleotides and their respective sums was observed. As a consequence, measuring the mono-, di- and triphosphates separately was not beneficial in predicting remission, which was confirmed by the results from the clinical study.Further research into the metabolism and mode of action of thiopurine drugs is needed to understand the inter-patient variability in response and metabolite formation. An assay suitable for such studies, measuring TGNs and meTINs in cultured cells, has also been developed.
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| 7. |
- Danielsson Borssén, Åsa, 1977-, et al.
(författare)
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Pregnancy and childbirth in women with autoimmune hepatitis is safe, even in compensated cirrhosis
- 2016
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 51:4, s. 479-485
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Autoimmune hepatitis (AIH) is a liver disease that primarily affects women. Many become ill during childbearing age, and medication can be lifelong. Few studies exist on pregnancy outcome in women with AIH. Objectives: The aim was to assess the outcome of women with AIH and their children during pregnancy and postpartum.Materials and methods: Sixty-four women from a well-characterised cohort with AIH filled out a questionnaire with information about their disease, miscarriage/abortion, pregnancies and potential birth defects in 2012. In 2004, 106 women answered the same questionnaire and their results were analysed along with the new questionnaires. Results: One hundred and thirty-eight women have completed the questionnaire and 100 children have been born by 58 women. Fifty-seven women (41%) had cirrhosis. In 84% of the pregnancies, the AIH was stable or milder, 32% had an increase in activity postpartum. The proportion of preterm births (before week 38) was 22%, caesarean sections 17%, malformations 3%, and two children died. Twenty-three women with cirrhosis had children after diagnosis of cirrhosis but without more complications than for non-cirrhotic mothers. However, they did have a higher prevalence of caesarean sections. Conclusion: Pregnancy and childbirth in AIH appear to be safe for both child and mother, even in women with compensated liver cirrhosis.
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| 8. |
- Rajani, Rupesh, et al.
(författare)
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Budd-Chiari syndrome in Sweden : epidemiology, clinical characteristics and survival - an 18-year experience
- 2009
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Ingår i: Liver international (Print). - Oxford : Blackwell Munksgaard. - 1478-3223 .- 1478-3231. ; 29:2, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. AIMS: To investigate the epidemiology, clinical presentation and survival in patients with BCS. METHODS: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. RESULTS: Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. CONCLUSIONS: Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.
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| 9. |
- Aleman, Soo, et al.
(författare)
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Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 46:9, s. 1118-1126
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. Patients and methods. 373 patients with hemochromatosis detected through routine health checkups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 +/- 5.8 years. The degree of liver fibrosis and survival were analyzed. Results. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. Conclusion. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.
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| 10. |
- Almer, Sven, et al.
(författare)
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6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients
- 2009
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 41:3, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.
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