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Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis: a long-term follow-up study in 634 Swedish patients
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Departments of Medicine, Sections for Hepatology and Gastroenterology, Umeå University Hospital, Umeå, Sweden.
Vise andre og tillknytning
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. Vol. 50, nr 2, s. 217-223
Emneord [en]
autoimmune hepatitis, autoimmune liver disease, cancer, extrahepatic cancer, hepatocellular rcinoma
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-100123DOI: 10.3109/00365521.2014.983154ISI: 000347692700013OAI: oai:DiVA.org:umu-100123DiVA, id: diva2:792502
Tilgjengelig fra: 2015-03-04 Laget: 2015-02-24 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Inngår i avhandling
1. Autoimmune hepatitis: life, death and in-between
Åpne denne publikasjonen i ny fane eller vindu >>Autoimmune hepatitis: life, death and in-between
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
autoimmune hepatitis, autoimmune liver disease, hepatocellular carcinoma, surveillance, pregnancy, pregnancy outcome, cirrhosis, fibrosis, epidemiology, cause of death
HSV kategori
Forskningsprogram
medicin
Identifikatorer
urn:nbn:se:umu:diva-134556 (URN)978-91-7601-679-4 (ISBN)
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-407311
Tilgjengelig fra: 2017-05-12 Laget: 2017-05-09 Sist oppdatert: 2018-06-09bibliografisk kontrollert

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