| 1. |
- Bergquist, Annika
(författare)
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Cholangiocarcinoma in primary sclerosing cholangitis
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown causes closely associated with ulcerative colitis. PSC is a progressive disease leading to liver failure and need for liver transplantation. Cholangiocarcinoma (CC) occurs in 10-20% of patients with PSC. The prognosis for CC is poor, even after liver transplantation. It is of great importance to identify PSC patients at risk for malignant development and transplant them at an early stage. Tools for early diagnosis of CC and possibilities to detect pre-malignancy are lacking. The general purpose of this thesis was therefore to identify early diagnostic markers and risk factors for malignancy in PSC. The first study was a case-control study comparing 20 PSC patients with CC and 20 patients with end stage PSC without cancer, the aims were to assess and compare clinical features in these groups and identify risk factors for the development of cancer. No difference was found in clinical presentation, laboratory or radiological findings. The number of patients being either current or former smokers was significantly higher in the cancer group than among controls (p<0.0004). To analyse the concept of bile duct dysplasia and the possibility of agreement of this morphological feature and determine reproducibility of the diagnosis, livers from 26 PSC patients with and 60 without concomitant CC were studied. Criteria for bile duct dysplasia were defined with reasonable level of agreement among three hepatopathologists, the kappa level for dysplasia being 0.44. Comparison of the frequency of bile duct dysplasia in livers from patients with PSC with and without CC showed dysplasia in 19% (5/26) of the cancer patients and in 0% (0/60) of non-cancer patients (p<0.001). In CCs and in nontumourous liver tissue from 16 PSC patients with and 16 patients without CC, bile duct cell proliferation, apoptosis and expression of p53 and bcl-2 proteins were studied. Histological stage, presence of bile duct dysplasia and immunohistochemical staining for Ki-67, nuclear DNA fragmentation, p53 and bcl-2 in non-tumorous liver tissue from PSC patients with and without CC did not differ significantly. Patients with bile duct dysplasia (n=9) had a significantly higher frequency of moderate/marked bile duct proliferation than those without bile duct dysplasia (p< 0.01). In addition, evaluation of the ploidy of DNA in CCs from patients with and without PSC was made. CCs from patients with PSC displayed DNA aneuploidy significantly more often (8/10) than CCs from patients without PSC (7/18) (p<0.05). 12% (2/17) of large bile ducts from PSC patients without CC displayed aneuploidy of DNA. In a large cohort of Swedish PSC patients (n=604), we assessed the risk of malignancies in PSC compared to the general Swedish population. The frequency of hepatobiliary malignancies was 13.3%. The standardized incidence rate for hepatobiliary carcinoma was 16 1, and 14 for pancreatic carcinoma. In conclusion, it is difficult in clinical settings to distinguish PSC patients with end stage disease from those with liver malignancy. PSC patients being current or former smokers are at an increased risk of developing hepatobiliary carcinoma. Criteria for bile duct dysplasia can be agreed on and the entity recognised in liver biopsies. The strong association of biliary dysplasia with cholangiocarcinoma in PSC suggests that occurrence of dysplasia can be used as a marker for current or developing malignancy. Increased bile duct proliferation may be used as a surrogate marker for premalignancy in PSC. The majority of CCs in PSC display DNA- aneuploidy. PSC patients also run an increased risk of developing pancreatic carcinoma.
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| 2. |
- Bergquist, Annika M., et al.
(författare)
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Hepatobiliary malignancy surveillance strategies in primary sclerosing cholangitis associate with reduced mortality
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:Suppl. 2, s. S227-S228
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Patients with primary sclerosing cholangitis (PSC) are at increased risk for hepatobiliary malignancies, especially cholangiocarcinoma. Although many recommend surveillance for malignancy in PSC, different strategies are used by various centers and countries. We aimed to evaluate different surveillance strategies and their effectiveness in PSC with the hypothesis that surveillance imaging improves survival.Method: We queried centers about surveillance practices and retrospectively collected imaging surveillance data for hepatobiliary cancer in 2, 975 patients with PSC from 28 centers within the International PSC Study Group (IPSCSG). Surveillance strategies were grouped in (i) non-surveillance (no imaging in asymptomatic patients), (ii) magnetic resonance imaging (MRI) and/or ultrasound (US) surveillance (regular imaging regardless of symptoms/labs) and (iii) surveillance including endoscopic retrograde cholangiopancreatography (ERCP)-based (imaging and/or ERCP regardless of symptoms/labs). The primary end point was all-cause mortality. Cox-proportional hazard regression models were used to estimate hazard ratios (HRs).Results: 65.6% (1953/2975) of patients were male, mean age (SD) at diagnosis of PSC was 35.6 (14.2) years, with concomitant IBD in 71.5% (2127/2973). Hepatobiliary malignancy was found in 175 (5.9%) patients at 7.9 years of follow-up (Figure). Surveillance strategies differed significantly between centers. Of patients undergoing surveillance, 83% were subjected to MRI/MRCP, 49% to US and 28% to ERCP. Deaths were more frequent in the non-surveillance group 23.4% (82/350) than in the surveillance group 8.3% (218/2625). Mortality rate (95% CI) per 1000 person-years was 23.1 (18.1–28.1) inthe non-surveillance group (n = 350), 12.5 (10.6–14.5) in imaging surveillance with MRI and/or US (n = 1897) and 8.4 (6.3–10.5) in surveillance that included ERCP (n = 728). The risk of dying wasr educed in patients undergoing any type of surveillance (HR 0.53; 95% CI: 0.41–0.68) and the reduced risk remained after adjusting for sex, age and start year of follow-up (HR 0.61; 95% CI: 0.47–0.80).Conclusion: A broad variety of surveillance strategies across centers are used. Regular sur veillance for hepatobiliary malignancy in patients with PSC is associated with improved survival.
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| 4. |
- Björnsson, Einar, et al.
(författare)
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Akut leversvikt - viktigt med snabb multidisciplinär handläggning : [Acute liver failure--rapid multidisciplinary management]
- 2007
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:4, s. 210-213
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A recent study in Sweden on patients with acute liver failure (ALF) 1994-2003 demonstrated that the most common causes were paracetamol toxicity (42%) and idiosyncratic drug reactions (15%). In 11% of cases of ALF no definite etiology could be established. Among patients with paracetamol toxicity, the spontaneous survival without liver transplantation was 82% compared to 49% in patients with reactions to other drugs and 29% among the patients with indeterminate cause. Patients with ALF need a rapid and effective diagnostic work-up to detect the etiology as this often determines the outcome. In ALF it is of major importance to make an early contact with a transplant centre as the search for a suitable donor organ may take time in patients who are candidates for a liver transplantation. Patients with acute liver failure need a multidisciplinary care with co-operation between hepatologists, intensive care unit specialists and transplant surgeons.
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| 5. |
- Danielsson Borssén, Åsa, et al.
(författare)
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Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 7. |
- Rajani, Rupesh, et al.
(författare)
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High prevalence of the germline JAK2 46/1 haplotype and V617-mutationin Swedish patients with Budd-Chiari syndrome and Portal Vein Thrombosis
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background & Aims: To determine the prevalence of the somatic JAK2 V617F mutation and distribution of the germline JAK2 46/1 haplotype in Budd-Chiari Syndrome (BCS) and portal vein thrombosis (PVT). Methods: Real-time PCR was performed to genotype for the JAK2V 617F mutation and the 46/1 haplotype (tag-SNPs rs12343867, T>C and rs12340895, C>G) in blood samples of 19 BCS and 91 PVT patients (without intra-abdominal malignancy), and 283 controls from a background population. Results: The prevalence of JAK2 V617F-mutation was 63% in BCS and 14% in PVT patients. 10% in BCS and 2% in PVT had V617F negative MPD. Conversely, V617F positive subjects without known MPD was found in 5% of the BCS and in 1% of PVT patients. The frequency of the JAK2 46/1 haplotype was significantly higher in BCS (53%) and PVT (36%) patients compared to controls (27%) (p=0.02; OR=3.0; 95% CI 1.5-5.9 and OR=1.51; 95% CI 1.1-2.1, respectively). In PVT patients the JAK2 haplotype was highly enriched in non-cirrhotic patients (41%) (p <0.01 ; OR=1.8; 95% CI 1.2-2.6) but not in cirrhotic patients (23%) (p=0.53 ; OR= 0.8; 95% CI 0.4-1.7). An increased JAK2 46/1 haplotype frequency was evident only in V617F mutation positive patients. Conclusions: The prevalence of JAK2 V617F was high in BCS (63%) and non-cirrhotic PVT (14%), facilitating detection of latent MPD. A negative result dose not rule out MPD. The occurrence of the JAK2 46/1 haplotype was significantly higher in V617F mutation positive patients but not in mutation negative patients, suggesting that the haplotype may not have an independent role separated from the V617F mutation in BCS and PVT patients.
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