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Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet, Karolinska University Hospital Huddinge.
Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University.
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(English)Manuscript (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. 

National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:umu:diva-134618OAI: oai:DiVA.org:umu-134618DiVA: diva2:1094415
Available from: 2017-05-09 Created: 2017-05-09 Last updated: 2017-05-10
In thesis
1. Autoimmune hepatitis: life, death and in-between
Open this publication in new window or tab >>Autoimmune hepatitis: life, death and in-between
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that is overrepresented in women (75% of cases). Studies have described a 10-year survival after diagnosis near to that of the general population, but less is known about the long-term survival. The inflammation in AIH causes fibrotic tissue to form in the liver and about 1/3 of AIH patients have cirrhosis at diagnosis. Studies have shown that treatment of the underlying liver disease can reverse fibrosis, and sometimes even cirrhosis, but only a few studies have examined the response to treatment in AIH. AIH affects all ages and some women will have cirrhosis during pregnancy, which is a risk factor for an adverse outcome. Cirrhosis is also a risk factor for hepatocellular carcinoma (HCC), but the true risk for HCC in cirrhotic AIH patients is not known.

Aim To study the epidemiology of AIH in Sweden, the causes of death and the risk of cancer for AIH patients, the efficacy of medical treatment on fibrosis and cirrhosis, and outcomes for the mother and child in pregnancy.

Material and methods A cohort of 634 AIH patients was established at the Swedish University hospitals. Prevalence and incidence were calculated, and a relative survival analysis was performed in which survival after AIH diagnosis was compared to that of the general population. Causes of deaths were retrieved from the Cause of Death Registry.

The Cancer Registry was used to calculate standard incidence ratios (SIR) and compare cancer risk to that of the general population.

Two hundred fifty-eight liver biopsies from 101 patients were analyzed by a single pathologist and classified according to the Ishak grading and staging system. Liver histology was stratified according to the temporal changes of fibrosis stage, and groups were compared.

A questionnaire was answered by 138 women with AIH about medication, pregnancies, disease behavior during and after pregnancy, and pregnancy outcomes.

Results The incidence and prevalence of AIH were 1.2/100 000 and 17.3/100 000 respectively. The relative survival started to decline after 4 years compared to the reference population, and was even more pronounced after 10 years. Men were diagnosed (33.5 years versus 48.0 years, p<0.001) and died (59.7 versus 75.4 years, p=0.002) at a younger age than women. Patients with cirrhosis at diagnosis had an inferior survival (p<0.001). Liver-related death was the most common cause of death (32.7%). Among AIH patients a higher incidence of cancer was found compared with that of the general Swedish population, SIR of 2.08 (95% Confidence Interval (CI) 1.68-2.55). SIR for non-melanoma skin cancer was 9.87 (95% CI 6.26-14.81) and hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC was found in 4% of the cirrhotic patients and the incidence rate was 0.3% per year. A reduction of fibrosis stage from first to last biopsy was common (62.4% of patients) and patients on a continuous glucocorticoid medication more often had a decreased fibrosis stage than those with withdrawal attempts (p=0.002). One hundred children were born by 58 women with AIH, of which 23 women had 43 children after diagnosis of cirrhosis. Malformations were reported in 3%, and pre-term births (<week 38) in 22% of the pregnancies. Cirrhotic women gave birth without more complications than others, but with a higher frequency of caesarean sections than non-cirrhotic women (p=0.047).

Conclusion Contrary to previous reports, AIH patients’ life expectancy was significantly inferior to that of the control population already 4 years after onset of disease, and liver disease was the most common cause of death. AIH patients had an overall enhanced risk for cancer, mainly from an increased risk of non-melanoma skin cancer and HCC. However, the annual risk of HCC was only 0.3% in cirrhotic patients. Histological improvement of liver fibrosis was common in AIH. The proportion of pre-term births was high, but overall pregnancy and childbirth appear to be safe in AIH, even in compensated cirrhosis. 

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2017. 55 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1887
Keyword
autoimmune hepatitis, autoimmune liver disease, hepatocellular carcinoma, surveillance, pregnancy, pregnancy outcome, cirrhosis, fibrosis, epidemiology, cause of death
National Category
Clinical Medicine Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-134556 (URN)978-91-7601-679-4 (ISBN)
Public defence
2017-06-02, Hörsal B, byggnad 1D, 9tr, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Funder
Västerbotten County Council, VLL678171Swedish Society of Medicine, SLS-407311
Available from: 2017-05-12 Created: 2017-05-09 Last updated: 2017-05-11Bibliographically approved

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