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- Hagstrom, Hannes, et al.
(författare)
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Cardiovascular risk factors in non-alcoholic fatty liver disease
- 2019
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Ingår i: Liver international (Print). - : WILEY. - 1478-3223 .- 1478-3231. ; 39:1, s. 197-204
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Tidskriftsartikel (refereegranskat)abstract
- Background amp; Aims Patients with non-alcoholic fatty liver disease (NAFLD) are at an increased risk for cardiovascular disease (CVD). It is unclear whether histological variables may help predict CVD risk. We evaluated histology and traditional CV risk factors as predictors of CVD outcomes in a large NAFLD cohort. Methods We included 603 biopsy-proven NAFLD patients free of baseline CVD and matched these (1:10, by age, sex and municipality) to 6269 population controls. All individuals were cross-linked to national registries to ascertain incident CVD events, defined as acute ischaemic heart disease or stroke. The presence of CV risk factors and liver histology were available in NAFLD patients only. Cox regression models were used to estimate hazard ratios (HR) for incident CVD. Results During a mean follow-up of 18.6 years, 168 (28%) of NAFLD patients and 1325 (21%) of controls experienced a CVD event (HR 1.54, 95%CI 1.30-1.83). Within the NAFLD cohort, age, male sex, type 2 diabetes, smoking and triglycerides were associated with risk of CVD. Taking these CV risk factors into account, no histological parameter, including presence of NASH and fibrosis stage, were associated with incident CVD. Conclusions Patients with NAFLD are at an increased risk for CVD compared to matched controls, but histological parameters do not seem to independently predict this risk.
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- Hagström, Hannes, et al.
(författare)
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Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up
- 2016
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Ingår i: Liver international (Print). - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 36:11, s. 1688-1695
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.METHODS: We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into "high" (n = 89) and "normal" (n = 133) ferritin values, using a cut-point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality was obtained from a national, population based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.RESULTS: The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (p < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high-ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01-1.21, p < 0.05). There was no difference in mortality between patients with different iron overload patterns.CONCLUSIONS: High levels of ferritin are associated with a long-term increased risk of death. This article is protected by copyright. All rights reserved.
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- Holmer, M., et al.
(författare)
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Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries
- 2018
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 38:11, s. 2082-2090
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims Nonalcoholic fatty liver disease(NAFLD) is the second most common cause of liver transplantation in the US. Data on NAFLD as a liver transplantation indication from countries with lower prevalences of obesity are lacking. We studied the temporal trends of NAFLD as an indication for liver transplantation in the Nordic countries, and compared outcomes for patients with NAFLD to patients with other indications for liver transplantation. MethodResultsPopulation-based cohort study using data from the Nordic Liver Transplant Registry on adults listed for liver transplantation between 1994 and 2015. NAFLD as the underlying indication for liver transplantation was defined as a listing diagnosis of NAFLD/nonalcoholic steatohepatitis, or cryptogenic cirrhosis with a body mass index 25kg/m(2) and absence of other liver diseases. Waiting time for liver transplantation, mortality and withdrawal from the transplant waiting list were registered. Survival after liver transplantation was calculated using multivariable Cox regression, adjusted for age, sex, body mass index and model for end-stage liver disease. A total of 4609 patients listed for liver transplantation were included. NAFLD as the underlying indication for liver transplantation increased from 2.0% in 1994-1995 to 6.2% in 2011-2015 (P=.01) and was the second most rapidly increasing indication. NAFLD patients had higher age, model for end-stage liver disease and body mass index when listed for liver transplantation, but overall survival after liver transplantation was comparable to non--NAFLD patients (aHR 1.03, 95% CI 0.70-1.53 P=.87). ConclusionNAFLD is an increasing indication for liver transplantation in the Nordic countries. Despite more advanced liver disease, NAFLD patients have a comparable survival to other patients listed for liver transplantation.
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- Mikus, Maria, et al.
(författare)
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Elevated levels of circulating CDH5 and FABP1 in association with human drug-induced liver injury
- 2016
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Ingår i: Liver international. - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 37:1, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The occurrence of drug-induced liver injury (DILI) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI cases and controls. Methods: An initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI biomarker candidates generated a DILI array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and/or tuberculosis receiving treatment, DILI cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins. Results: We observed elevated levels of cadherin 5, type 2 (CDH5) and fatty acid-binding protein 1 (FABP1) in DILI cases. In the two longitudinal cohorts, CDH5 was elevated already at baseline. FABP1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT). The elevations were verified in the DILI cases treated with various drugs. In the heparin cohort, CDH5 was stable over time whereas FABP1 was elevated. Conclusions: These results suggest that CDH5 may have value as a susceptibility marker for DILI. FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI. Further studies are needed to determine the clinical utility of the proposed markers.
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- Mueller, Michaela, et al.
(författare)
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Ursodeoxycholic acid: Effects on hepatic unfolded protein response, apoptosis and oxidative stress in morbidly obese patients.
- 2018
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Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - : Wiley. - 1478-3231. ; 38:3, s. 521-531
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Tidskriftsartikel (refereegranskat)abstract
- Ursodeoxycholic acid (UDCA) is a secondary hydrophilic bile acid (BA) used as therapy for a range of hepatobiliary diseases. Its efficacy in non-alcoholic fatty liver disease (NAFLD) is still under debate. Here, we aimed to decipher molecular mechanisms of UDCA in regulating endoplasmic reticulum (ER) homeostasis, apoptosis and oxidative stress in morbidly obese patients.In this randomized controlled pharmacodynamic study, liver and serum samples from 40 well-matched morbidly obese NAFLD-patients were analysed. Patients received UDCA (20mg/kg/d) or no treatment 3weeks before samples were obtained during bariatric surgery.Patients treated with UDCA displayed higher scoring of steatosis (S), activity (A) and fibrosis (F), the so called SAF-scoring. UDCA partially disrupted ER homeostasis by inducing the expression of the ER stress markers CHOP and GRP78. However, ERDJ4 and sXBP1 levels were unaffected. Enhanced CHOP expression, a suggested pro-apoptotic trigger, failed to induce apoptosis via BAK and BAX in the UDCA treated group. Potentially pro-apoptotic miR-34a was reduced in the vesicle-free fraction in serum but not in liver after UDCA treatment. Thiobarbituric acid reactive substances, 4-hydroxynonenal and mRNA levels of several oxidative stress indicators remained unchanged after UDCA treatment.Our data suggest that UDCA treatment has ambivalent effects in NAFLD patients. While increased SAF-scores and elevated CHOP levels may be disadvantageous in the UDCA treated cohort, UDCA's cytoprotective properties potentially changed the apoptotic threshold as reflected by absent induction of pro-apoptotic triggers. UDCA treatment failed to improve the oxidative stress status in NAFLD patients.
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- Romeo, Stefano, 1976
(författare)
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Don't forget to ask how mum and dad are doing.
- 2019
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Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - : Wiley. - 1478-3231. ; 39:4, s. 623-624
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Sternby Eilard, Malin, 1974, et al.
(författare)
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Quality of life as a prognostic factor for survival in hepatocellular carcinoma
- 2018
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 38:5, s. 885-894
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Prognostication in hepatocellular carcinoma (HCC) is demanding. Not only tumour extent and performance status are to be considered, but also liver function, which is often limiting for both survival itself and for treatment possibilities. This study was conducted to assess whether patient-reported questionnaires containing general and liver-specific questions could improve prognostication of survival. Methods: 185 patients with hepatocellular carcinoma in Norway and Sweden were prospectively included. Patients completed the quality-of-life questionnaires EORTC QLQ C30 and HCC18, and clinical, radiological and laboratory parameters were registered. Multivariate Cox regression and Harrell's C-statistics were used to identify the model that best predicted mortality. Results: Quality-of-life data were prognostic for overall survival. Fatigue and nutrition scales were prognostic in the multivariable analyses alone and in combination with clinical parameters. The prognostic value of established scoring systems was increased by the addition of QoL data. The best prognostic power was achieved by combining HCC18 nutrition scale with selected background parameters. Conclusion: Quality-of-life questionnaires can prognosticate mortality in HCC patients. When combined with established scoring systems, both the general cancer questionnaire EORTC QLQ C30, and the additional liver cancer-specific HCC18 increased the prognostic accuracy slightly.
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- Stokkeland, Knut, et al.
(författare)
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Increased risk of preterm birth in women with autoimmune hepatitis : a nationwide cohort study
- 2016
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Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 36:1, s. 76-83
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The aim of our study was to investigate the risks of pregnancy and childbirth complications in women with autoimmune hepatitis compared to the population controls. Methods: In a nationwide cohort study of all pregnancies between 2006 and 2011 we investigated the risks of adverse pregnancy outcome in 171 births in women with diagnosed autoimmune hepatitis using the data from the Swedish Medical Birth and Patient Registries. Births to women without autoimmune hepatitis served as population controls (n = 576 642). Relative risks (RR) with 95% confidence intervals (CI) were calculated using Poisson regression models adjusting for potential confounders. Results: Women with AIH had an increased risk of gestational diabetes (RR = 4.35, 95% CI 2.21-8.57), of preterm birth (RR = 3.21, 95% CI 1.97-4.92) and of low-birth-weight child (RR = 2.51, 95% CI 1.51-4.19). We found no statistically significant association between autoimmune hepatitis and pre-eclampsia, caesarean section, low 5-min Apgar score, small for gestational age birth, congenital malformation and neonatal mortality. Conclusions: Autoimmune hepatitis is a risk factor for adverse pregnancy outcomes. High quality prenatal and antenatal care is important for women with autoimmune hepatitis and their infants.
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- von Seth, Erik, et al.
(författare)
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Primary sclerosing cholangitis increases the risk for pancreatitis after endoscopic retrograde cholangiopancreatography
- 2015
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Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 35:1, s. 254-262
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Patients with primary sclerosing cholangitis (PSC) have an increased risk for adverse events following endoscopic retrograde cholangiopancreatography (ERCP), mainly caused by bacterial cholangitis. The risk of pancreatitis is less examined. Therefore, our aim was to study adverse events following ERCP and to evaluate if PSC is a risk factor for pancreatitis.METHODS: Data were collected through a Swedish nationwide quality registry comprising fifty-one Swedish ERCP centres. The final study cohort consisted of 8932 adults who had undergone ERCP from 1 January 2007 to 31 December 2009. A total of 141 patients had PSC. Variables of importance for adverse events were entered into a multivariate logistic regression model for risk factor analysis.RESULTS: The following adverse events were increased in PSC as compared with non-PSC patients: overall (18.4% vs. 7.3%), pancreatitis (7.8% vs. 3.2%, P = 0.002), cholangitis (7.1% vs. 2.1%, P < 0.001) and per-operative extravasation of contrast (5.7% vs. 0.7%, P < 0.001). PSC was shown to be an independent risk factor for all of these adverse events: pancreatitis, OR 2.02 (95% CI, 1.04-3.92), cholangitis, OR 2.88 (95% CI, 1.47-5.65), and extravasation of contrast, OR 5.84 (95% CI, 2.24-15.23).CONCLUSION: The rate of adverse events overall following ERCP in PSC is 18% and PEP occurs in 8%. PSC is an independent risk factor for PEP and the risk is doubled. These findings underline the importance of a careful selection of PSC patients eligible for ERCP as well as a need for high competence of the treating team.
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- Muche, M., et al.
(författare)
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Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients
- 2019
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 39:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Background Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg-negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). Methods HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg-positive non-CHD non-KTx patients (positive controls) and 40 HBsAg-negative healthy subjects (negative controls). Results Chronic haemodialysis group: two of 376 patients were HBsAg-positive. The 374 HBsAg-negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg-positive. One of 403 HBsAg-negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti-HBc-negative and HBV DNA-negative in both serum and PBMCs. In the long term, the only case of anti-HBc-negative OBI lost anti-HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re-seroconversion. Conclusions We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value.
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| 19. |
- Zheng, Yi Hu, et al.
(författare)
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BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin
- 2016
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 36:12, s. 1836-1847
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma (HCC). Methods: RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with shRNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. Results: BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2/M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2/M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. Conclusion: BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC.
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