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Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: a cohort study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University.
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
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2017 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2017. Vol. 96, no 34, article id e7708
Keywords [en]
autoimmune hepatitis, autoimmune liver disease, cirrhosis, fibrosis, inflammation
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:umu:diva-134616DOI: 10.1097/MD.0000000000007708ISI: 000408504800012OAI: oai:DiVA.org:umu-134616DiVA, id: diva2:1094362
Note

Originally included in thesis in manuscript form 

Available from: 2017-05-09 Created: 2017-05-09 Last updated: 2018-06-09Bibliographically approved
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. p. 55
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1887
Keywords
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: 2018-06-09Bibliographically approved

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