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Autoimmune hepatitis: life, death and in-between
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
2017 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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. 

sted, utgiver, år, opplag, sider
Umeå: Umeå universitet , 2017. , s. 55
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1887
Emneord [en]
autoimmune hepatitis, autoimmune liver disease, hepatocellular carcinoma, surveillance, pregnancy, pregnancy outcome, cirrhosis, fibrosis, epidemiology, cause of death
HSV kategori
Forskningsprogram
medicin
Identifikatorer
URN: urn:nbn:se:umu:diva-134556ISBN: 978-91-7601-679-4 (tryckt)OAI: oai:DiVA.org:umu-134556DiVA, id: diva2:1094417
Disputas
2017-06-02, Hörsal B, byggnad 1D, 9tr, Norrlands Universitetssjukhus, Umeå, 09:00 (svensk)
Opponent
Veileder
Forskningsfinansiär
Västerbotten County Council, VLL678171Swedish Society of Medicine, SLS-407311Tilgjengelig fra: 2017-05-12 Laget: 2017-05-09 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Delarbeid
1. Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis: a long-term follow-up study in 634 Swedish patients
Åpne denne publikasjonen i ny fane eller vindu >>Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis: a long-term follow-up study in 634 Swedish patients
Vise andre…
2015 (engelsk)Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, nr 2, s. 217-223Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
Informa Healthcare, 2015
Emneord
autoimmune hepatitis, autoimmune liver disease, cancer, extrahepatic cancer, hepatocellular rcinoma
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-100123 (URN)10.3109/00365521.2014.983154 (DOI)000347692700013 ()
Tilgjengelig fra: 2015-03-04 Laget: 2015-02-24 Sist oppdatert: 2018-06-07bibliografisk kontrollert
2. Pregnancy and childbirth in women with autoimmune hepatitis is safe, even in compensated cirrhosis
Åpne denne publikasjonen i ny fane eller vindu >>Pregnancy and childbirth in women with autoimmune hepatitis is safe, even in compensated cirrhosis
Vise andre…
2016 (engelsk)Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, nr 4, s. 479-485Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
Taylor & Francis, 2016
Emneord
Abortion, autoimmune, hepatitis, liver cirrhosis, pregnancy, pregnancy outcome, spontaneous
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-116729 (URN)10.3109/00365521.2015.1115893 (DOI)000368696900013 ()
Tilgjengelig fra: 2016-02-19 Laget: 2016-02-11 Sist oppdatert: 2018-06-07bibliografisk kontrollert
3. Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: a cohort study
Åpne denne publikasjonen i ny fane eller vindu >>Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: a cohort study
Vise andre…
2017 (engelsk)Inngår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, nr 34, artikkel-id e7708Artikkel i tidsskrift (Fagfellevurdert) 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.

Emneord
autoimmune hepatitis, autoimmune liver disease, cirrhosis, fibrosis, inflammation
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-134616 (URN)10.1097/MD.0000000000007708 (DOI)000408504800012 ()
Merknad

Originally included in thesis in manuscript form 

Tilgjengelig fra: 2017-05-09 Laget: 2017-05-09 Sist oppdatert: 2019-05-10bibliografisk kontrollert
4. Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis
Åpne denne publikasjonen i ny fane eller vindu >>Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
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. 

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-134618 (URN)
Tilgjengelig fra: 2017-05-09 Laget: 2017-05-09 Sist oppdatert: 2018-06-09

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