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  • 1.
    Alaish, Ram
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment2017In: International journal of clinical pharmacology and therapeutics, ISSN 0946-1965, Vol. 55, no 7, p. 594-600Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naive to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naive to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with.MCV = 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naive to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.

  • 2.
    Danielsson Borssen, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindgren, S
    Bergquist, A
    Almer, S
    Sangfelt, P
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Risk for hepatocellular carcinoma in autoimmune hepatitis: is there an indication for surveillance?2013In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 58, no Suppl. 1, p. S382-S383Article in journal (Refereed)
  • 3.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Departments of Medicine, Sections for Hepatology and Gastroenterology, Umeå University Hospital, Umeå, Sweden.
    Almer, Sven
    Prytz, Hanne
    Wallerstedt, Sven
    Friis-Liby, Inga-Lill
    Bergquist, Annika
    Nyhlin, Nils
    Hultcrantz, Rolf
    Sangfelt, Per
    Weiland, Ola
    Lindgren, Stefan
    Verbaan, Hans
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Departments of Medicine, Sections for Hepatology and Gastroenterology, Umeå University Hospital, Umeå, Sweden.
    Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis: a long-term follow-up study in 634 Swedish patients2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 2, p. 217-223Article in journal (Refereed)
    Abstract [en]

    Objectives. Cirrhosis is a well-known risk factor for hepatocellular cancer, but the true risk in autoimmune hepatitis (AIH) is scarcely studied. Other cancers may arise after prolonged use of immune-modulating drugs. The aim of this study was to investigate the cancer risk in a large cohort of AIH patients.

    Material and methods. Six hundred and thirty-four Swedish patients in a well-defined cohort were matched to the Cause of Death Registry and the Cancer Registry. Standard incidence ratios were calculated by relating the incidences in the cohort to an age-matched material from the Swedish background population.

    Results. A higher overall incidence of malignancies than the background population was found, counting from the date of diagnosis (standard incidence ratio (SIR) 2.08, 95% CI 1.68-2.55). The highest risk was found for hepatocellular carcinoma (HCC). We found 10 cases (4.0%) in 248 patients with cirrhosis, which gives an incidence rate of 0.3%. Standard incidence ratio for developing hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC only occurred in cirrhotic patients. There was also an increased risk for non-melanoma skin cancer (SIR 9.87, 95% CI 6.26-14.81).

    Conclusion. A slightly enhanced risk for malignancies in general compared to the background population was found. The risk of hepatobiliary cancer was increased, but the annual risk over the observational period was well under the postulated 1.5% when surveillance in cirrhotic patients is considered to be cost-effective.

  • 4.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marschall, Hanns-Ulrich
    Bergquist, Annika
    Rorsman, Fredrik
    Weiland, Ola
    Kechagias, Stergios
    Nyhlin, Nils
    Verbaan, Hans
    Nilsson, Emma
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.

    Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.

    Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.

    Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.

    Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

  • 5.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marschall, Hanns-Ulrich
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
    Bergquist, Annika
    Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet, Karolinska University Hospital Huddinge.
    Rorsman, Fredrik
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University.
    Weiland, Ola
    Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge.
    Kechagias, Stergios
    Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University.
    Nyhlin, Nils
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University.
    Verbaan, Hans
    Gastroenterology Division, Department of Clinical Sciences, Lund University, University Hospital Skane.
    Nilsson, Emma
    Gastroenterology Division, Department of Clinical Sciences, Lund University, University Hospital Skane.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitisManuscript (preprint) (Other academic)
    Abstract [en]

    Background Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.

    Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.

    Material and methods Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for University Hospitals with full coverage of cases and compared to the County of Västerbotten in Northern Sweden.

    Results AIH point prevalence was 17.3/100 000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100 000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<0.001) and died younger than women (p=0.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<0.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years. 

    Conclusions Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased. 

  • 6.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Kechagias, Stergios
    Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University.
    Marschall, Hanns-Ulrich
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
    Bergquist, Annika
    Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet.
    Rorsman, Fredrik
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University.
    Weiland, Ola
    Division of Infectious Diseases, Department of Medicine, Karolinska Institutet.
    Verbaan, Hans
    Gastroenterology Division, Department of Clinical Sciences, Lund University.
    Nyhlin, Nils
    Department of Medicine, Section of Hepatology and Gastroenterology, Örebro University Hospital and Faculty of Medicine and Health, Örebro University.
    Nilsson, Emma
    Gastroenterology Division, Department of Clinical Sciences, Lund University.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: a cohort study2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed)
    Abstract [en]

    Objectives Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis.

    Methods Two hundred fifty-eight liver biopsies from 101 patients (72 women, 29 men) were analysed by a single pathologist and classified accordingly to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased or stable), and groups were compared.

    Results Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only five patients at the last biopsy.

    Conclusions Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

  • 7.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wallerstedt, Sven
    Department of Medicine, Sections for Hepatology and Gastroenterology, Sahlgrenska University Hospital at Östra Sjukhuset, Gothenburg, Sweden .
    Nyhlin, Nils
    Department of Medicine, Sections for Hepatology and Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bergquist, Annika
    Department of Medicine, Sections for Hepatology and Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
    Lindgren, Stefan
    Department of Medicine, Sections for Hepatology and Gastroenterology, University Hospital of Skåne, Malmö, Sweden.
    Almer, Sven
    Department of Medicine, Sections for Hepatology and Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pregnancy and childbirth in women with autoimmune hepatitis is safe, even in compensated cirrhosis2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 4, p. 479-485Article in journal (Refereed)
    Abstract [en]

    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.

  • 8. Duarte-Salles, Talita
    et al.
    Misra, Sandeep
    Stepien, Magdalena
    Plymoth, Amelie
    Muller, David
    Overvad, Kim
    Olsen, Anja
    Tjonneland, Anne
    Baglietto, Laura
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Turzanski-Fortner, Renee
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Pala, Valeria
    Palli, Domenico
    Mattiello, Amalia
    Tumino, Rosario
    Naccarati, Alessio
    Bueno-de-Mesquita, H. B(as).
    Peeters, Petra H.
    Weiderpass, Elisabete
    Quiros, J. Ramon
    Agudo, Antonio
    Sanchez-Cantalejo, Emilio
    Ardanaz, Eva
    Gavrila, Diana
    Dorronsoro, Miren
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemmingsson, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ohlsson, Bodil
    Sjoberg, Klas
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Bradbury, Kathryn E.
    Gunter, Marc J.
    Cross, Amanda J.
    Riboli, Elio
    Jenab, Mazda
    Hainaut, Pierre
    Beretta, Laura
    Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population2016In: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 9, no 9, p. 758-765Article in journal (Refereed)
    Abstract [en]

    We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and a-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis.

  • 9. Efe, Cumali
    et al.
    Al Taii, Haider
    Ytting, Henriette
    Aehling, Niklas
    Bhanji, Rahima A.
    Hagstrom, Hannes
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Muratori, Paolo
    Klintman, Daniel
    Schiano, Thomas D.
    Montano-Loza, Aldo J.
    Berg, Thomas
    Larsen, Fin Stolze
    Alkhouri, Naim
    Ozaslan, Ersan
    Heneghan, Michael A.
    Yoshida, Eric M.
    Wahlin, Staffan
    Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis2018In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 63, no 5, p. 1348-1354Article in journal (Refereed)
    Abstract [en]

    We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.

  • 10. Efe, Cumali
    et al.
    Hagström, Hannes
    Ytting, Henriette
    Bhanji, Rahima A.
    Müller, Niklas F.
    Wang, Qixia
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marschall, Hanns-Ulrich
    Muratori, Paolo
    Gunşar, Fulya
    Klintman, Daniel
    Parés, Albert
    Heurgué-Berlot, Alexandra
    Schiano, Thomas D.
    Cengiz, Mustafa
    Tana, Michele May-Sien
    Ma, Xiong
    Montano-Loza, Aldo J.
    Berg, Thomas
    Verma, Sumita
    Larsen, Fin Stolze
    Ozaslan, Ersan
    Heneghan, Michael A.
    Yoshida, Eric M.
    Wahlin, Staffan
    Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 12, p. 1950-1956Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Predniso(lo) ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo) ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

  • 11. Fedirko, V.
    et al.
    Lukanova, A.
    Bamia, C.
    Trichopolou, A.
    Trepo, E.
    Noethlings, U.
    Schlesinger, S.
    Aleksandrova, K.
    Boffetta, P.
    Tjonneland, A.
    Johnsen, N. F.
    Overvad, K.
    Fagherazzi, G.
    Racine, A.
    Boutron-Ruault, M. C.
    Grote, V.
    Kaaks, R.
    Boeing, H.
    Naska, A.
    Adarakis, G.
    Valanou, E.
    Palli, D.
    Sieri, S.
    Tumino, R.
    Vineis, P.
    Panico, S.
    Bueno-de-Mesquita, H. B(as).
    Siersema, P. D.
    Peeters, P. H.
    Weiderpass, E.
    Skeie, G.
    Engeset, D.
    Quiros, J. R.
    Zamora-Ros, R.
    Sanchez, M. J.
    Amiano, P.
    Huerta, J. M.
    Barricarte, A.
    Johansen, D.
    Lindkvist, B.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Crowe, F.
    Khaw, K. T.
    Ferrari, P.
    Romieu, I.
    Chuang, S. C.
    Riboli, E.
    Jenab, M.
    Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 2, p. 543-553Article in journal (Refereed)
    Abstract [en]

    The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

  • 12. Fedirko, V
    et al.
    Trichopolou, A
    Bamia, C
    Duarte-Salles, T
    Trepo, E
    Aleksandrova, K
    Nöthlings, U
    Lukanova, A
    Lagiou, P
    Boffetta, P
    Trichopoulos, D
    Katzke, VA
    Overvad, K
    Tjønneland, A
    Hansen, L
    Boutron-Ruault, MC
    Fagherazzi, G
    Bastide, N
    Panico, S
    Grioni, S
    Vineis, P
    Palli, D
    Tumino, R
    Bueno-de-Mesquita, HB
    Peeters, PH
    Skeie, G
    Engeset, D
    Parr, CL
    Jakszyn, P
    Sánchez, MJ
    Barricarte, A
    Amiano, P
    Chirlaque, M
    Quirós, JR
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sonestedt, E
    Ericson, U
    Key, TJ
    Khaw, KT
    Ferrari, P
    Romieu, I
    Riboli, E
    Jenab, M
    Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC)2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 8, p. 2166-2173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations.

    METHODS: The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case-control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.

    RESULTS: HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74-0.95 and HR = 0.80, 95% CI 0.69-0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66-1.11 and RR = 0.74, 95% CI 0.50-1.09, respectively) in a nested case-control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.

    CONCLUSIONS: In this large European cohort, total fish intake is associated with lower HCC risk.

  • 13. Fedirko, Veronika
    et al.
    Duarte-Salles, Talita
    Bamia, Christina
    Trichopoulou, Antonia
    Aleksandrova, Krasimira
    Trichopoulos, Dimitrios
    Trepo, Elisabeth
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Kvaskoff, Marina
    Kühn, Tilman
    Lukanova, Annie
    Boeing, Heiner
    Buijsse, Brian
    Klinaki, Eleni
    Tsimakidi, Chrysanthi
    Naccarati, Alessio
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Peters, Petra H
    Lund, Eiliv
    Brustad, Magritt
    Standahl Olsen, Karina
    Weiderpass Vainio, Elisabete
    Zamora, Raul
    Sánchez, María-José
    Ardanaz, Eva
    Amiano, Pilar
    Navarro, Carmen
    Quirós, J Ramón
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Björn
    Malm, Johan
    Travis, Ruth C
    Khaw, Kay-Tee
    Stepien, Magdalena
    Scalbert, Augustin
    Romieu, Isabelle
    Lagiou, Pagona
    Riboli, Elio
    Jenab, Mazda
    Pre-diagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 4, p. 1222-1230Article in journal (Refereed)
    Abstract [en]

    The association between vitamin D status and hepatocellular carcinoma has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between pre-diagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and risk of hepatocellular carcinoma in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRR) of hepatocellular carcinoma associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of pre-diagnostic 25(OH)D. Higher 25(OH)D levels were associated with a 49% reduction in the risk of hepatocellular carcinoma (highest vs. lowest tertile: multivariable IRR = 0.51, 95% confidence interval, 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% confidence interval, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of pre-existing liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on Western European populations, serum levels of 25(OH)D were inversely associated with risk of hepatocellular carcinoma. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;).

  • 14. Hindorf, Ulf
    et al.
    Jahed, Khatoon
    Bergquist, Annika
    Verbaan, Hans
    Prytz, Hanne
    Wallerstedt, Sven
    Werner, Mårten
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Olsson, Rolf
    Björnsson, Einar
    Peterson, Curt
    Almer, Sven H C
    Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis.2010In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 52, no 1, p. 106-111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Corticosteroids alone or in conjunction with azathioprine (AZA) is the standard treatment in autoimmune hepatitis (AiH). Individual variations in thiopurine (TP) metabolism may affect both drug efficacy and toxicity. Our aim was to investigate the utility of thiopurine methyltransferase (TPMT) as well as thioguanine nucleotide (TGN) and methylthioinosine monophosphate (meTIMP) metabolite measurements with regard to clinical outcome. METHODS: Two hundred thirty-eight patients with AiH were included in this cross-sectional study. TPMT status was assessed in all patients, while TGN and meTIMP were measured in patients with ongoing TP medication. Clinical outcome was evaluated by liver tests and the ability to withdraw steroids. RESULTS: TPMT genotyping (n=229) revealed 207 (90.4%) wild-type and 22 heterozygous patients. One hundred forty-three patients had ongoing TP therapy with AZA (n=134) or mercaptopurine (MP; n=9); response was judged as complete response (CR) in 113 patients and partial response (PR) in 30 patients. Both TP dose (1.64 vs 1.19mg/kg; p=0.012) and TPMT activity (14.3 vs 13.5; p=0.05) were higher in PR, resulting in similar TGN levels (PR: 121pmol/8x10(8) red blood cells [RBC]; CR: 113pmol/8x10(8) RBC; p=0.33) but higher meTIMP levels in PR (1350 vs 400pmol/8x10(8) RBC; p=0.004). Patients able to withdraw steroids or who were using 5mg prednisolone daily were treated with lower TP doses than patients on higher steroid doses (1.15 vs 1.18 vs 1.82mg/kg; p<0.001). CONCLUSIONS: TP metabolite measurements are of clinical value in AiH patients who do not respond to standard TP treatment and for the identification of a shifted metabolism, which may demand an alternative treatment strategy.

  • 15.
    Ibrahim, Aghil
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The clinical course after glucocorticoid treatment in patients with inflammatory bowel disease is linked to suppression of the hypothalamic-pituitary-adrenal axis: a retrospective observational study2017In: Therapeutic Advances in Gastroenterology, ISSN 1756-283X, E-ISSN 1756-2848, Vol. 10, no 11, p. 829-836Article in journal (Refereed)
    Abstract [en]

    Background: Adrenal insufficiency (AI) secondary to treatment with glucocorticoids (GCs) is common in patients with inflammatory bowel disease (IBD), but little is known about the relationship between AI and the clinical course in IBD. The aim of the study was to compare the clinical course in IBD patients with normal adrenal function versus patients with subnormal adrenal function.

    Methods: A retrospective observational study on 63 patients with IBD who had performed a low-dose short Synacthen test (LDSST) (1 μg) immediately (1-7 days) after a standard course of GCs. A subnormal LDSST was defined as serum cortisol <550 nmol/L. Outcomes were time to next flare and fecal calprotectin levels.

    Results: Sixty-three percent (n = 40) of the IBD patients had a subnormal LDSST. Patients who were steroid-free (n = 41) after the LDSST were observed for 3 years. Patients with a peak serum cortisol <400 nmol/L immediately after GC treatment had significantly longer time until the next flare-up of their IBD and tended to use a lower cumulative prednisolone dose during the study period in comparison to the other subgroups. Fecal calprotectin levels were significantly lower in patients with a peak s-cortisol <550 nmol/L versus patients with peak s-cortisol ⩾550 nmol/L (median 336 µg/g (IQR 521) versus 955 µg/g (IQR 1867); p = 0.012).

    Conclusions: GC-induced AI is common in patients with IBD and is associated with lower disease activity. This suggests a link between responsiveness to GC treatment and suppression of the hypothalamic-pituitary-adrenal axis in IBD.

  • 16. Kong, So Yeon
    et al.
    Tran, Hao Quang
    Gewirtz, Andrew T.
    McKeown-Eyssen, Gail
    Fedirko, Veronika
    Romieu, Isabelle
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Bastide, Nadia
    Affret, Aurelie
    Kuehn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Kritikou, Maria
    Vasilopoulou, Effie
    Palli, Domenico
    Krogh, Vittorio
    Mattiello, Amalia
    Tumino, Rosario
    Naccarati, Alessio
    Bueno-de-Mesquita, H. B.
    Peeters, Petra H.
    Weiderpass, Elisabete
    Ramon Quiros, J.
    Sala, Nuria
    Sanchez, Maria-Jose
    Huerta Castano, Jose Maria
    Barricarte, Aurelio
    Dorronsoro, Miren
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Bradbury, Kathryn E.
    Freisling, Heinz
    Stavropoulou, Faidra
    Ferrari, Pietro
    Gunter, Marc J.
    Cross, Amanda J.
    Riboli, Elio
    Bruce, W. Robert
    Jenab, Mazda
    Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort2016In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 25, no 2, p. 291-301Article in journal (Refereed)
    Abstract [en]

    Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. Methods: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin-and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (P-interaction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10-2.51; P-trend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47-1.02; P-trend, 0.18). Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. Impact: Further studies are warranted to better clarify these preliminary observations. (C) 2016 AACR.

  • 17.
    Lorenz, Fryderyk
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Wahlin, Bjorn Engelbrekt
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, p. 7920-Article in journal (Refereed)
    Abstract [en]

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool.

  • 18.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
    Becker, Susen
    Hüsing, Anika
    Schock, Helena
    Fedirko, Veronika
    Trepo, Elisabeth
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Nöthlings, Ute
    Tjønneland, Anne
    Overvad, Kim
    Dossus, Laure
    Teucher, Birgit
    Boeing, Heiner
    Aleksandrova, Krasimira
    Palli, Domenico
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Peeters, Petra M
    Quiros, Jose Ramon
    Duell, Eric J
    Molina-Montes, Esther
    Chirlaque, Maria-Dolores
    Gurrea, Aurelio Barricarte
    Dorronsoro, Miren
    Lindkvist, Björn
    Johansen, Dorthe
    Werner, Mårten
    Sund, Malin
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Travis, Ruth C
    Rinaldi, Sabina
    Romieu, Isabelle
    Gunter, Marc J
    Riboli, Elio
    Jenab, Mazda
    Kaaks, Rudolf
    Pre-diagnostic plasma testosterone, sex hormone binding globulin, IGF-I and hepatocellular carcinoma: etiological factors or risk markers?2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 1, p. 164-173Article in journal (Refereed)
    Abstract [en]

    Elevated pre-diagnostic testosterone and insulin-like growth factor-I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk (OR for top versus bottom tertile of 3.86 (1.32-11.3), ptrend =0.009). As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p=0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with pre-diagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as pre-diagnostic risk marker for HCC.

  • 19. Schlesinger, Sabrina
    et al.
    Aleksandrova, Krasimira
    Pischon, Tobias
    Fedirko, Veronika
    Jenab, Mazda
    Trepo, Elisabeth
    Boffetta, Paolo
    Dahm, Christina C
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Palli, Domenico
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, HB
    van den Berg, Saskia
    Peeters, Petra HM
    Braaten, Tonje
    Weiderpass, Elisabete
    Quirós, J Ramón
    Travier, Noémie
    Sánchez, María-José
    Navarro, Carmen
    Barricarte, Aurelio
    Dorronsoro, Miren
    Lindkvist, Björn
    Regner, Sara
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Norat, Teresa
    Wark, Petra A
    Riboli, Elio
    Nöthlings, Ute
    Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 3, p. 645-657Article in journal (Refereed)
    Abstract [en]

    General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; p(trend) < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.

  • 20. Stepien, Magdalena
    et al.
    Duarte-Salles, Talita
    Fedirko, Veronika
    Floegel, Anne
    Barupal, Dinesh Kumar
    Rinaldi, Sabina
    Achaintre, David
    Assi, Nada
    Tjønneland, Anne
    Overvad, Kim
    Bastide, Nadia
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Kühn, Tilman
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Saieva, Calogero
    Agnoli, Claudia
    Panico, Salvatore
    Tumino, Rosario
    Naccarati, Alessio
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Dorronsoro, Miren
    Gavrila, Diana
    Barricarte, Aurelio
    Ohlsson, Bodil
    Sjöberg, Klas
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wareham, Nick
    Khaw, Kay-Tee
    Travis, Ruth C
    Schmidt, Julie A
    Gunter, Marc
    Cross, Amanda
    Vineis, Paolo
    Romieu, Isabelle
    Scalbert, Augustin
    Jenab, Mazda
    Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: findings from a prospective cohort study2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 2, p. 348-360Article in journal (Refereed)
    Abstract [en]

    Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.

  • 21. Stepien, Magdalena
    et al.
    Fedirko, Veronika
    Duarte-Salles, Talita
    Ferrari, Pietro
    Freisling, Heinz
    Trepo, Elisabeth
    Trichopoulou, Antonia
    Bamia, Christina
    Weiderpass, Elisabete
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Kuehn, Tilman
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Boeing, Heiner
    Lagiou, Pagona
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Bueno-de-Mesquita, H. Bas
    Peeters, Petra H.
    Lund, Eiliv
    Quiros, J. Ramon
    Napoles, Osmel Companioni
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Maria Huerta, Jose
    Ardanaz, Eva
    Ohlsson, Bodil
    Sjoberg, Klas
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Key, Timothy J.
    Gunter, Marc
    Cross, Amanda
    Riboli, Elio
    Romieu, Isabelle
    Jenab, Mazda
    Prospective association of liver function biomarkers with development of hepatobiliary cancers2016In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 40, p. 179-187Article in journal (Refereed)
    Abstract [en]

    Introduction: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. Methods: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95% CI). Results: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95% CI: 2.72-6.59; OR(ALP) = 3.43, 95% CI: 2.31-5.10; OR(AST) = 3.00, 95% CI: 2.04-4.42; OR(ALT) = 2.69, 95% CI: 1.89-3.84; OR(Bilirubin) = 2.25, 95% CI: 1.58-3.20). Each liver enzyme (OR(GGT) = 4.98; 95% CI: 1.75-14.17; OR(AST) = 3.10, 95% CI: 1.04-9.30; OR(ALT) = 2.86, 95% CI: 1.26-6.48, OR(ALP) = 2.31, 95% CI: 1.10-4.86) but not bilirubin (OR(Bilirubin) = 1.46,95% CI: 0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR (ALP) = 1.59, 95% CI: 1.20-2.09). Conclusion: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

  • 22. Stepien, Magdalena
    et al.
    Hughes, David J.
    Hybsier, Sandra
    Bamia, Christina
    Tjønneland, Anne
    Overvad, Kim
    Affret, Aurélie
    His, Mathilde
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Kuehn, Tilman
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Lagiou, Pagona
    Orfanos, Phlippos
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Ricceri, Fulvio
    Panico, Salvatore
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Weiderpass, Elisabete
    Lasheras, Cristina
    Bonet Bonet, Catalina
    Molina-Portillo, Elena
    Dorronsoro, Miren
    Maria Huerta, José
    Barricarte, Aurelio
    Ohlsson, Bodil
    Sjöberg, Klas
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wareham, Nick
    Khaw, Kay-Tee
    Travis, Ruth C.
    Freisling, Heinz
    Cross, Amanda J.
    Schomburg, Lutz
    Jenab, Mazda
    Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans2017In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, no 5, p. 688-696Article in journal (Refereed)
    Abstract [en]

    Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n = 106, IHDB n = 34, GBTC n = 96) and their matched controls (1: 1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. Results: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR = 0.36; 95% CI: 0.13-0.98, Ptrend = 0.0123), but no association for copper (OR = 1.06; 95% CI: 0.45-2.46, Ptrend = 0.8878) in multivariable models. The calculated Cu/ Zn ratio showed a positive association for HCC (OR = 4.63; 95% CI: 1.41-15.27, Ptrend = 0.0135). For IHBC and GBTC, no significant associations were observed. Conclusions: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

  • 23. Trichopoulos, Dimitrios
    et al.
    Bamia, Christina
    Lagiou, Pagona
    Fedirko, Veronika
    Trepo, Elisabeth
    Jenab, Mazda
    Pischon, Tobias
    Noethlings, Ute
    Overved, Kim
    Tjonneland, Anne
    Outzen, Malene
    Clavel-Chapelon, Francoise
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Boeing, Heiner
    Aleksandrova, Krasimira
    Benetou, Vassiliki
    Zylis, Dimosthenis
    Palli, Domenico
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-De-Mesquita, H. Bas
    Van Kranen, Henk J.
    Peeters, Petra H. M.
    Lund, Eiliv
    Ramon Quiros, J.
    Gonzalez, Carlos A.
    Sanchez Perez, Maria-Jose
    Navarro, Carmen
    Dorronsoro, Miren
    Barricarte, Aurelio
    Lindkvist, Bjorn
    Regner, Sara
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy
    Romieu, Isabelle
    Chuang, Shu-Chun
    Murphy, Neil
    Boffetta, Paolo
    Trichopoulou, Antonia
    Riboli, Elio
    Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study2011In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 103, no 22, p. 1686-1695Article in journal (Refereed)
    Abstract [en]

    Background: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.

    Methods: Using data collected from 1992 to 2006, which included 4 409 809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort.

    Results: Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors.

    Conclusions: Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.

  • 24. Trichopoulos, Dimitrios
    et al.
    Bamia, Christina
    Lagiou, Pagona
    Fedirko, Veronika
    Trepo, Elisabeth
    Jenab, Mazda
    Pischon, Tobias
    Nthlings, Ute
    Overvad, Kim
    Tjonneland, Anne
    Outzen, Malene
    Clavel-Chapelon, Francoise
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Boeing, Heiner
    Aleksandrova, Krasimira
    Benetou, Vassiliki
    Zylis, Dimosthenis
    Palli, Domenico
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-De-Mesquita, H. Bas
    Van Kranen, Henk J.
    Peeters, Petra H. M.
    Lund, Eiliv
    Ramon Quiros, J.
    Gonzalez, Carlos A.
    Sanchez Perez, Maria-Jose
    Navarro, Carmen
    Dorronsoro, Miren
    Barricarte, Aurelio
    Lindkvist, Bjoern
    Regner, Sara
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy
    Romieu, Isabelle
    Chuang, Shu-Chun
    Murphy, Neil
    Boffetta, Paolo
    Trichopoulou, Antonia
    Riboli, Elio
    Re: Hepatocellular Carcinoma Risk factors and Disease Burden in a European Cohort: A Nested Case-Control Study Response2012In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 104, no 21, p. 1683-1684Article in journal (Refereed)
  • 25.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Autoimmune hepatitis in Sweden2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Autoimmune hepatitis (AIH) was identified as an entity by the Swedish professor Jan Waldenström in the 1950s. It was then denoted lupoid hepatitis, characterized by liver inflammation and most often affecting young women. During the years the diagnosis has become more defined (as the non A non B hepatitis has been identified as Hepatitis C) and now can be safely separated from other diseases with liver inflammation. Studies of epidemiological data and long term prognosis have been scarce in the literature. Within a collaboration between the university hospitals in Sweden, we collected what we believe is the largest cohort in the world of patients with AIH. Data from the medical records of 473 individuals was, after AIH-score calculations where the diagnosis was confirmed, collected in a data base, in which most of the analysis was done. Data from the Swedish national registers of cancer, death cause, and birth register was searched for these patients as well as controls. The aim of the thesis was to explore epidemiological and clinical outcome of AIH.The onset of AIH may be at any age, but the incidence seems to increase after 50 years of age; 75% are females, the overall incidence (0.85/ 100,000 inhabitants and year) and prevalence (11/100,000 inhabitants) are figures that are within the range of another but smaller Scandinavian study. Approximately 30 % had cirrhosis already at diagnosis and 87% displayed at some time positive auto-antibodies indicating AIH (Smooth muscle ab and or antinuclear ab).  Indications of future risk for liver transplantation or death is an advanced AIH at diagnosis with liver cirrhosis, decompensated liver disease, elevated PK INR as well as age. Acute hepatitis-like onset seems to carry a lower risk for later liver transplantation or death. Current Swedish national therapy traditions with immune suppression seem to be well tolerated. Five and ten years overall life expectancy does not differ from controls. Thirty-five women gave birth to 63 children, for 3 after liver transplantation of the mother. Thirteen of the women had liver cirrhosis. Current pharmacological treatment seems to be safe both for the patient and the foetus. Thirty percent of the patients experienced flair after delivery. It has been supposed that there is an overrisk for hepatocellular cancer (HCC) associated with AIH. Our figures are the first in the world to be presented that confirms a twenty-three fold overrisk (95% Confidence Interval 7.5-54.3) for hepatobiliar cancer. We found as well an overrisk of non-Hodgkin lymphomas of 13.09 (95% CI 4.2-30.6).Conclusion:  Our epidemiological results confirm that AIH is a fairly uncommon disease, and that many already at time of diagnosis have an advanced disease with liver cirrhosis. There is a clear overrisk for HCC and lymphoma. For those women with AIH who become pregnant the prognosis for the child as well as for the mother is good, even for those women who already have compensated cirrhosis. There is a risk for relapse after delivery. The overall survival for AIH patients with current therapy is good.

  • 26.
    Werner, Mårten
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Almer, Sven
    Prytz, Hanne
    Lindgren, Stefan
    Wallerstedt, Sven
    Björnsson, Einar
    Bergquist, Annika
    Sandberg-Gertzén, Hanna
    Hultcrantz, Rolf
    Sangfelt, Per
    Weiland, Ola
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hepatic and extrahepatic malignancies in autoimmune hepatitis: A long-term follow-up in 473 Swedish patients2009In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 50, no 2, p. 388-393Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk. The aim was to investigate the risks of malignancies in a large cohort of AIH patients. METHODS: Four hundred and seventy-three patients with AIH were matched to the Swedish national cancer register as well as to the death cause register. RESULTS: We found an overall higher risk of malignancies in the cohort of AIH patients from the date of diagnosis with a SIR of 1.51 (95% CI 1.10-2.03). SIR in the subpopulation of well defined catchment areas and complete case finding was 23.28 (95% CI 7.5-54.34) for HCC. Lymphomas were found a SIR of 13.09 (95% CI 4.22-30.56). CONCLUSIONS: There was an overall increased risk of malignancies in a cohort of AIH patients, which manly was caused by hepatobiliary cancers. However, the true risk of HCC in an AIH cirrhotic cohort has yet to be investigated. A significantly higher risk of lymphomas was also found, but no clear cut association to the use of immune modulators.

  • 27.
    Werner, Mårten
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Björnsson, Einar
    Prytz, Hanne
    Lindgren, Stefan
    Almer, Sven
    Broomé, Ulrika
    Wallerstedt, Sven
    Sandberg-Gertzén, Hanna
    Hultcrantz, Rolf
    Sangfeldt, Per
    Nilsson, Jenny
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding?2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 8, p. 986-991Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In published studies there is a lack of data about the risks, management and how women with autoimmune hepatitis (AIH) decide on and are advised about pregnancy. The aim of this study was to investigate how women with AIH consider pregnancies, are advised and pharmacologically treated, as well as the outcome.

    MATERIAL AND METHODS: A questionnaire was mailed to 128 women with AIH diagnosed during their fertile period and data from the Swedish National Birth Register was also used for matched controls.

    RESULTS: There was an 83% response rate to the questionnaires. Sixty-three pregnancies were reported by 35 women. 48% did not consult their doctors before getting pregnant. More than half of the women reduced or stopped the immune suppression during pregnancy or breastfeeding. Some women were advised to abstain from pregnancy or even to have an abortion. Caesarean sections were performed more frequently in the AIH group (16% compared with 6.5% in the control group p<0.01).There were no significant differences in the number of stillborn infants or infants with malformations. However, 30% of the patients experienced flare-up after delivery.

    CONCLUSIONS: In general, the outcome of pregnancy in women with AIH seems to be good. Current pharmacological treatment appears to be safe, including azathioprine during pregnancy and lactation. After delivery an active preparedness to increase pharmacotherapy should be considered.

  • 28.
    Werner, Mårten
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    [Autoimmune hepatitis often requires lifelong treatment]2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 21, p. 1388-1391Article in journal (Refereed)
    Abstract [en]

    Autoimmune hepatitis (AIH) is a rare disease with an incidence of around 1 / 100,000 inhabitants, and a prevalence rate of 16 / 100,000. As many as 30 % of AIH-patients already have liver cirrhosis at diagnosis. The diagnosis is established with liver function tests of hepatocellular pattern, presence of autoimmune antibodies, increased polyclonal IgG, and a compatible liver biopsy. Mostly, immune suppressive treatment with corticosteroids alone or in combination with azathioprine brings the disease into remission. In cirrhotic patients there is an increased risk of hepatocellular cancer (HCC) with a SIR of 23.

  • 29.
    Werner, Mårten
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Prytz, Hanne
    Ohlsson, Bodil
    Almer, Sven
    Björnsson, Einar
    Bergquist, Annika
    Wallerstedt, Sven
    Sandberg-Gertzén, Hanna
    Hultcrantz, Rolf
    Sangfelt, Per
    Weiland, Ola
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 10, p. 1232-1240Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH.

    MATERIAL AND METHODS: Analyses were performed in 473 patients identified as having probable or definite AIH. RESULTS: The incidence of AIH was 0.85/100,000 (95% CI 0.69-1.01) inhabitants, which is somewhat lower than reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8-13.1), and 76% of the cases were females. The age-related incidence curve was bimodal but men were found to have only one incidence peak in the late teens, whereas women had a peak after menopause. AIH was presented as a spectrum of clinical settings from detected "en passant" to acute liver failure. Almost 30% of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases were frequently found (49%).

    CONCLUSIONS: The incidence and prevalence figures confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms at presentation were unspecific, but almost half of the patients were jaundiced, with around 30% having liver cirrhosis. The majority of Swedish AIH patients had AIH type 1.

1 - 29 of 29
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