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Visuri, I., Eriksson, C., Mardberg, E., Grip, O., Gustavsson, A., Hjortswang, H., . . . Halfvarson, J. (2019). Anti-TNF agent drug survival in patients with IBD: real-world comparisons of individual anti-TNF agents based on the Swedish National Quality Registry for IBD (SWIBREG). Journal of Crohn's & Colitis, 13, S443-S444
Open this publication in new window or tab >>Anti-TNF agent drug survival in patients with IBD: real-world comparisons of individual anti-TNF agents based on the Swedish National Quality Registry for IBD (SWIBREG)
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2019 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, p. S443-S444Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Studies comparing drug survival in different anti-tumour necrosis factor (TNF) agents in IBD patients are scarce, especially for second-line anti-TNF agents. We aimed to (A) assess drug survival and predictors of response and adverse drug reactions to first-line anti-TNF treatment and (B) examine drug survival for individual anti-TNF agents when used as second-line anti-TNF. Methods: Well-characterised patients with IBD (n = 955)  starting their first anti-TNF treatment between 2006 and 2016 (Table  1), were identified from the Swedish National Quality Registry for IBD (SWIBREG). Drug survival was examined, stratified by reason for discontinuation, that is, lack/loss of clinical effectiveness or adverse drug reactions. Multi-variable Cox regression models were used to identify predictors of drug survival. Drug survival for the second anti-TNF was assessed by type of first anti-TNF agent. Results: Risk factors at baseline for shorter drug survival, in patients with Crohn’s disease, were use of infliximab as first-line anti-TNF (compared with adalimumab, adjusted HR  =  1.95, 95% CI: 1.19‒3.18) (Figure 1A) and colonic disease (L2) (compared with ileal disease (L1) and ileocolonic disease (L3), adjusted HR = 2.16, 95% CI: 1.25‒3.74). Consistently, Crohn’s disease patients who switched from adalimumab to infliximab had shorter drug survival, compared with those who switched from infliximab to adalimumab (Figure  1B). A  normalisation of CRP level at 3 months was associated with decreased risk of short drug survival in both Crohn’s disease (adjusted HR = 0.40, 95% CI: 0.19‒0.81) and ulcerative colitis (adjusted HR = 0.40, 95% CI: 0.19‒0.86). In Crohn’s disease, but not in ulcerative colitis, immunomodulators were associated with a lower risk of short drug survival due to adverse drug reactions (adjusted HR = 0.50, 95% CI: 0.31‒0.82). Conclusions: Drug survival duration was longer for adalimumab compared with infliximab both when used as first anti-TNF agent and when used as second-line treatment. The consistent pattern indicates that these differences are not only explained by channelling bias (differential prescribing behaviour).

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-157519 (URN)10.1093/ecco-jcc/jjy222.773 (DOI)000460544502205 ()
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved
Widbom, L., Schneede, J., Karling, P. & Hultdin, J. (2019). Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco. Journal of Crohn's & Colitis, 13, S508-S508
Open this publication in new window or tab >>Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco
2019 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, p. S508-S508Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-157520 (URN)10.1093/ecco-jcc/jjy222.898 (DOI)000460544503018 ()
Note

Supplement: 1

Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-11-19Bibliographically approved
Karling, P., Lundgren, D., Eklöf, V., Palmqvist, R. & Hultdin, J. (2019). Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin. Scandinavian Journal of Clinical and Laboratory Investigation
Open this publication in new window or tab >>Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin
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2019 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed) Epub ahead of print
Abstract [en]

Faecal calprotectin (FC) tests and faecal immunological tests (FIT) for haemoglobin have been used to monitor disease activity in patients with ulcerative colitis (UC) but used alone they have some limitation concerning the predictive ability. We aimed to test if an FC test used in combination with FIT could improve the predictive ability. Consecutive out-patients with UC (n = 93) who were admitted for colonoscopy completed a single faecal sample before the start of bowel preparation. A quantitative CALPRO (R) calprotectin ELISA test and a qualitative FIT (cut-off < 40 ng/mL) were analyzed. An estimated Mayo score and a score of histological inflammation was performed blinded to the result of the faecal tests. The sensitivity, specificity, negative predictive value and positive predictive value for endoscopic inflammation (Mayo score > 1) was for FIT 85%, 83%, 96%, 57% and for FC > 186 mu g/g 73%, 87%, 87%, 54%. Corresponding results for FIT*FC > 186 mu g/g (at least one test positive) were 92%, 69%, 97%, 43%. For detecting moderate/severe histological inflammation the results were for FIT 69%, 79%, 92%, 43%, for FC > 75 mu g/g 95%, 62%, 98%, 41%, and for FIT*FC > 75 mu g/g 100%, 60%, 100%, 36%. None of the markers alone or in combination were useful to predict deep remission (Mayo score = 0 and no histological inflammation). We conclude that using the combination of an FC test and FIT shows minor improvement in predictive ability for inflammatory activity and remission in patients with UC.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Faecal calprotectin, faecal immunochemical haemoglobin tests, inflammatory bowel disease, ulcerative colitis
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-161714 (URN)10.1080/00365513.2019.1622148 (DOI)000473803200001 ()31164011 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-05Bibliographically approved
Lundgren, D., Eklöf, V., Palmqvist, R., Hultdin, J. & Karling, P. (2019). Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy. Scandinavian Journal of Gastroenterology, 54(2), 152-157
Open this publication in new window or tab >>Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 2, p. 152-157Article in journal (Refereed) Published
Abstract [en]

Objectives: Faecal Calprotectin (FC) is a sensitive marker for gut inflammation. However, slightly elevated FC levels are also common in subjects without inflammation. We investigated the association between FC and clinical factors including concomitant use of medical therapy in patients with a normal colonoscopy.Material and methods: Out-patients (n=1263) referred for colonoscopy, performed FC test (CALPRO) the day before the start of bowel preparation. All subjects answered questionnaires that included questions on the present and past health history, concomitant medical treatment and gastrointestinal symptoms (GSRS). A medical record chart review was performed to check for concomitant disease, cause of referral and the result of the colonoscopy including biopsies. Inclusion criteria were a normal colonoscopy. Exclusion criteria were inflammatory bowel disease, colon cancer and high-grade dysplasia.Results: Five hundred ninety subjects fulfilled the inclusion criteria and completed the study. Thirty-six per cent of the subjects had a FC >50 mu g/g. In a logistic regression analysis, age (adjusted OR: 1.051; CI: 1.032-1.071), and the use of proton pump inhibitors (adjusted OR: 3.843; CI: 2.338-6.316), non-steroid anti-inflammatory drugs (adjusted OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (adjusted OR: 2.934; CI: 1.085-3.448) were significantly associated with an elevated FC (>50 mu g/g).Conclusions: More than one-third of the patients with a normal colonoscopy performed in clinical routine had a slightly elevated FC level. Our results emphasise the need for attention to age, the use of proton pump inhibitors, non-steroid anti-inflammatory drugs and acetylsalicylic acid in the interpretation of FC tests in clinical practice.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Faecal calprotectin, colonoscopy, non-steroidal inflammatory drugs, proton pump inhibitors
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-160629 (URN)10.1080/00365521.2019.1566493 (DOI)000468463000004 ()30676120 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Marberg, T., Karling, P., Söderberg, K., Anan, I. & Wixner, J. (2019). Self-reported gastrointestinal symptoms are more common in liver transplanted transthyretin amyloidosis patients than in healthy controls and in patients transplanted for end-stage liver disease. Paper presented at 16th International Symposium on Amyloidosis (ISA), Kumamoto, Japan, March 26-29, 2018. Amyloid: Journal of Protein Folding Disorders, 26, 47-48
Open this publication in new window or tab >>Self-reported gastrointestinal symptoms are more common in liver transplanted transthyretin amyloidosis patients than in healthy controls and in patients transplanted for end-stage liver disease
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2019 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, p. 47-48Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-162351 (URN)10.1080/13506129.2019.1582514 (DOI)000477775700026 ()31343318 (PubMedID)
Conference
16th International Symposium on Amyloidosis (ISA), Kumamoto, Japan, March 26-29, 2018
Note

Special issue, Supplement 1

Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-08-27Bibliographically approved
Ludvigsson, J. F., Andersson, M., Bengtsson, J., Eberhardson, M., Fagerberg, U. L., Grip, O., . . . Myrelid, P. (2019). Swedish Inflammatory Bowel Disease Register (SWIBREG): a nationwide quality register. Scandinavian Journal of Gastroenterology, 54(9), 1089-1101
Open this publication in new window or tab >>Swedish Inflammatory Bowel Disease Register (SWIBREG): a nationwide quality register
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 9, p. 1089-1101Article, review/survey (Refereed) Published
Abstract [en]

Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory relapsing disease with increasing incidence. IBD research and long-term follow-up of patients have, however, been hampered by lack of detailed data on disease phenotype, patient-reported outcome measures, Physician Global Assessment, disease activity, and hospital-administered drugs.

Aim: To review the Swedish IBD quality register (SWIBREG).

Methods: Review of SWIBREG including questionnaire data from users and patients.

Results: SWIBREG was launched in 2005, and as of April 2019, contains 46,400 patients with IBD (Crohn’s disease: n = 15,705, ulcerative colitis: n = 21,540, IBD unclassified and other colitis (including e.g., microscopic colitis): n = 9155). Of these IBD patients, 7778 had been diagnosed in childhood (16.8%). Earlier research has shown that combining SWIBREG and the Swedish National Patient Register (NPR) yields a positive predictive value of 100% (95%CI = 95–100%) for having a diagnosis of IBD. Moreover, out of all patients in the NPR with a diagnosis of IBD plus either IBD-related surgery or immunomodulatory/biological treatment during the past 18 months, SWIBREG covers 59.0%. SWIBREG records not only information on conventional therapies but also on biological treatment, surgery, smoking, disease activity, patient-reported outcome measures (PROMs), and patient-experienced measures (PREMs). Data are presented through a graphical decision support system.

Conclusion: SWIBREG benefits patients with IBD, and offers an ideal opportunity for healthcare personnel and researchers to examine disease phenotype and activity, PROMs/PREMs, and hospital-administered drugs in patients with IBD.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Inflammatory bowel disease, Crohn's disease, ulcerative colitis, patient reported outcome measure, tient reported experience measure, quality of life
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-164621 (URN)10.1080/00365521.2019.1660799 (DOI)000485641200001 ()31498717 (PubMedID)
Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-11-12Bibliographically approved
Wixner, J., Törnblom, H., Karling, P., Anan, I. & Lindberg, G. (2018). Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis. Neurogastroenterology and Motility, 30(9), Article ID e13354.
Open this publication in new window or tab >>Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis
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2018 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 30, no 9, article id e13354Article in journal (Refereed) Published
Abstract [en]

Background: Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients' small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non-amyloidosis patient controls.

Methods: ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24-hour duodenojejunal manometry (n=19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of 50years were defined as late-onset cases. For each patient, three age- and sex-matched patient controls (n=57) were selected from the total pool of investigated patients.

Key Results: Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P=.01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P<.01), and had a higher frequency of low-amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P=.10). Furthermore, late-onset patients showed a delay in octreotide response (5.4 vs 3.8minutes, P<.01), but this was not observed for early-onset patients or within the control group.

Conclusions and Inferences: Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non-amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late-onset patients warrants further investigation.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
Keywords
familial amyloid neuropathy, functional gastrointestinal disorders, intestinal motility, manometry, octreotide acetate, transthyretin amyloidosis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-152414 (URN)10.1111/nmo.13354 (DOI)000445193400010 ()29655299 (PubMedID)
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2019-05-16Bibliographically approved
Bonfiglio, F., Zheng, T., Garcia-Etxebarria, K., Hadizadeh, F., Bujanda, L., Bresso, F., . . . D'Amato, M. (2018). Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome. Gastroenterology, 155(1), 168-179
Open this publication in new window or tab >>Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome
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2018 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 155, no 1, p. 168-179Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also [GRAPHICS] associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
SNP, Biobank Research, Genetics, Bowel Symptoms
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-150480 (URN)10.1053/j.gastro.2018.03.064 (DOI)000439705600056 ()29626450 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Andersen, V., Chan, S., Luben, R., Khaw, K.-T., Olsen, A., Tjonneland, A., . . . Hart, A. (2018). Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD). Journal of Crohn's & Colitis, 12(2), 129-136
Open this publication in new window or tab >>Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD)
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no 2, p. 129-136Article in journal (Refereed) Published
Abstract [en]

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.

Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.

Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].

Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Dietary fibre, diet, epidemiology, fibre food, inflammatory bowel disease, prospective study
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-144945 (URN)10.1093/ecco-jcc/jjx136 (DOI)000423703000001 ()29373726 (PubMedID)
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2019-05-20Bibliographically approved
Henström, M., Diekmann, L., Bonfiglio, F., Hadizadeh, F., Kuech, E.-M., von Köckritz-Blickwede, M., . . . D'Amato, M. (2018). Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome. Gut, 67(2), 263-270
Open this publication in new window or tab >>Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 2, p. 263-270Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS.

DESIGN: We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population.

RESULTS: CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05).

CONCLUSIONS: SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-128591 (URN)10.1136/gutjnl-2016-312456 (DOI)000419604800011 ()27872184 (PubMedID)
Available from: 2016-12-07 Created: 2016-12-07 Last updated: 2018-06-09Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5607-0118

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