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Autoimmune hepatitis in Sweden
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Gastroenterologi)
2009 (English)Doctoral 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.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2009. , 60 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1233
Keyword [en]
Autoimmune hepatitis, epidemiology, cirrhosis, prognosis, thiopurines, pregnancy, breast feeding, relapse, hepatocellular cancer, lymphoma
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:umu:diva-18545ISBN: 978-91-7264-701-5 (print)OAI: oai:DiVA.org:umu-18545DiVA: diva2:160445
Public defence
2009-03-20, Sal B, Byggnad 1D, Tandläkarhögskolan, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2009-03-04 Created: 2009-02-13 Last updated: 2015-09-07Bibliographically approved
List of papers
1. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study
Open this publication in new window or tab >>Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study
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2008 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 43, no 10, 1232-1240 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Informa Healthcare, 2008
Keyword
ANA, autoimmune hepatitis, cirrhosis, epidemiology, initial presentation, SMA
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-18535 (URN)10.1080/00365520802130183 (DOI)000259318200011 ()18609163 (PubMedID)
Available from: 2009-02-13 Created: 2009-02-13 Last updated: 2015-09-07Bibliographically approved
2. Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response.
Open this publication in new window or tab >>Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response.
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2010 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 45, no 4, 457-467 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Autoimmune hepatitis (AIH) is a liver disease which, if untreated, may lead to liver cirrhosis and hepatic failure. Limited data exist regarding factors predicting the long-term outcome. The aims of this study were to investigate symptoms at presentation, prognostic features, management and treatment in relation to long-term outcome of AIH. MATERIAL AND METHODS: A cohort of 473 Swedish patients with AIH was characterized regarding initial symptoms and signs, factors predicting death and future need for liver transplantation. Survival and causes of death were retrieved from Swedish national registers. RESULTS: At diagnosis, fatigue was a predominant symptom (69%), 47% of the patients were jaundiced and 30% had liver cirrhosis. Another 10% developed cirrhosis during follow-up. Markedly elevated alanine aminotransferase levels at presentation were correlated with a better outcome. A high international normalized ratio (INR) at diagnosis was the only risk factor predicting a need for later liver transplantation. Histological cirrhosis, decompensation and non-response to initial treatment were all factors that correlated with a worse outcome. Overall life expectancy was generally favourable. However, most deaths were liver-related, e.g. liver failure, shock and gastrointestinal bleeding. CONCLUSIONS: Cirrhosis at diagnosis, a non-response to initial immune-suppressive treatment or elevated INR values were associated with worse outcome and a need for later liver transplantation. In contrast, an acute hepatitis-like onset with intact synthetic capacity indicated a good response to treatment and favourable long-term prognosis. Lifetime maintenance therapy is most often required.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-32964 (URN)10.3109/00365520903555861 (DOI)20082594 (PubMedID)
Available from: 2010-03-31 Created: 2010-03-31 Last updated: 2010-04-01Bibliographically approved
3. Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding?
Open this publication in new window or tab >>Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding?
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2007 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 8, 986-991 p.Article in journal (Refereed) Published
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.

Keyword
Adult, Aged, Breast Feeding, Female, Fertility, Hepatitis; Autoimmune/*drug therapy, Humans, Middle Aged, Pregnancy, Questionnaires
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-17527 (URN)10.1080/00365520601155266 (DOI)000247778700013 ()17613929 (PubMedID)
Available from: 2008-06-26 Created: 2008-06-26 Last updated: 2017-12-08Bibliographically approved
4. Hepatic and extrahepatic malignancies in autoimmune hepatitis: A long-term follow-up in 473 Swedish patients
Open this publication in new window or tab >>Hepatic and extrahepatic malignancies in autoimmune hepatitis: A long-term follow-up in 473 Swedish patients
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2009 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 50, no 2, 388-393 p.Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-18533 (URN)10.1016/j.jhep.2008.08.022 (DOI)19070390 (PubMedID)
Available from: 2009-02-13 Created: 2009-02-13 Last updated: 2012-08-13Bibliographically approved

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