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Sökning: WFRF:(Hagström Hannes)

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1.
  • Hegmar, Hannes, et al. (författare)
  • Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD
  • 2024
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 296:2, s. 177-186
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis-4 Index (FIB-4).METHODS: Serum from patients with MASLD (n = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used.RESULTS: An LSM >8 kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67-0.79) to detect patients >8 kPa, compared to FIB-4 (0.71, (95%CI = 0.64-0.77, p = 0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, p = 0.93.CONCLUSIONS: ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.
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2.
  • Akbari, Camilla, et al. (författare)
  • Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD
  • 2024
  • Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & AimsLong-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.MethodsWe conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.ResultsMALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2–8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years).ConclusionsThis study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.Impact and implicationsSeveral implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.
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3.
  • Andreasson, Anna, et al. (författare)
  • The prediction of colorectal cancer using anthropometric measures : A Swedish population-based cohort study with 22 years of follow-up
  • 2019
  • Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:9, s. 1250-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity is a risk factor for colorectal cancer (CRC).Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI).Methods: Data were analysed from the Malmo Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women.Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men.Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.
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4.
  • Andreasson, Anna, et al. (författare)
  • Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index : A Population-based Cohort Study
  • 2017
  • Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 15:8, s. 1294-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.
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5.
  • Bengtsson, Bonnie, et al. (författare)
  • Validity of administrative codes associated with cirrhosis in Sweden
  • 2020
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:10, s. 1205-1210
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Although cirrhosisis a major cause of liver-related mortality globally, validation studies of the administrative coding for diagnoses associated with cirrhosis are scarce. We aimed to determine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes corresponding to cirrhosis and its complications in the Swedish National Patient Register (NPR).Methods: We randomly selected 750 patients with ICD codes for either alcohol-related cirrhosis (K70.3), unspecified cirrhosis (K74.6) oesophageal varices (I85.0/I85.9), hepatocellular carcinoma (HCC, C22.0) or ascites (R18.9) registered in the NPR from 72 healthcare centres in 2000-2016. Hospitalisation events and outpatient visits in specialised care were included. Positive predictive values (PPVs) were calculated using the information in the patient charts as the gold standard.Results: Complete data were obtained for 630 (of 750) patients (84%). For alcohol-related cirrhosis, 126/136 cases were correctly coded, corresponding to a PPV of 93% (95% confidence interval, 95%CI: 87-96). The PPV for cirrhosis with unspecified aetiology was 91% (121/133, 95%CI: 85-95) and 96% for oesophageal varices (118/123, 95%CI: 91-99). The PPV was lower for HCC, 84% (91/109, 95%CI: 75-90). The PPV for liver-related ascites was low, 43% (56/129, 95%CI: 35-52), as this category often consisted of non-hepatic ascites. When combining the ascites code with a code for chronic liver disease, the PPV for liver-related ascites increased to 93% (50/54, 95%CI: 82-98).Conclusions: The validity of ICD-10 codes for cirrhosis, oesophageal varices and HCC is high. However, coding for ascites should be combined with a code of chronic liver disease to have an acceptable validity.
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6.
  • Bergman, David, et al. (författare)
  • Incidence of ICD-based diagnoses of alcohol-related disorders and diseases from swedish nationwide registers and suggestions for coding
  • 2020
  • Ingår i: Clinical Epidemiology. - Macclesfield, United Kingdom : Dove Medical Press Ltd.. - 1179-1349. ; 12, s. 1433-1442
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To improve consistency between register studies in Sweden and ensure valid comparisons of possible changes in alcohol-related disorders and diseases (ARDDs) over time, we propose a definition of ARDDs. Based on this definition, we examined Sweden’s incidence rates of ARDDs from 1970 to 2018 in non-primary healthcare settings (inpatient and outpatient). Methods: Swedish Society of Epidemiology members were invited to give feedback on the International Classification of Disease (ICD) codes with a potential link to alcohol use. We then calculated age-standardised and age-specific incidence of ARDDs over time according to the National Patient Register, and the lifetime prevalence of ARDDs diagnosed in adults alive in Sweden on Dec 31, 2018. Results: Sweden’s estimated incidence of ARDDs increased substantially after introducing the new ICD-9 codes in 1987. In the past 10 years (2009–2018), the incidence of ARDDs has been stable (males: 110/100,000 person-years, females: 49/100,000 person-years). Requiring at least two ICD records for diagnosed ARDDs led to a somewhat lower incidence of ARDDs (males: 71 per 100,000 person-years, females: 29 per 100,000 person-years). In Sweden, the lifetime prevalence of diagnosed ARDDs in adults on Dec 31, 2018, was 1.9% (95% CI=1.9–1.9). Conclusion: In this nationwide study, we found an incidence of ARDDs of 50–100/ 100,000 person-years. In 2018, 1 in 52 adults in Sweden had been diagnosed with ARDDs in the National Patient Register.
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7.
  • Ekstedt, Mattias, et al. (författare)
  • Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
  • 2015
  • Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 61:5, s. 1547-1554
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.
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9.
  • Hagström, Hannes, et al. (författare)
  • Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease
  • 2020
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:1, s. 200-214
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events. METHODS: We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline. RESULTS: A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83. CONCLUSIONS: Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.
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10.
  • Hagström, Hannes, et al. (författare)
  • Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life
  • 2018
  • Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 68:3, s. 505-510
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease.Methods: We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied.Results: During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day.Conclusion: Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised.Lay summary: We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969–1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more.
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11.
  • Hagström, Hannes, et al. (författare)
  • Body composition measurements and risk of hematological malignancies : A population-based cohort study during 20 years of follow-up
  • 2018
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
  • Tidskriftsartikel (refereegranskat)abstract
    • High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmo Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.
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12.
  • Hagström, Hannes, et al. (författare)
  • Body mass index in early pregnancy and future risk of severe liver disease : a population-based cohort study
  • 2019
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Science Ltd.. - 0269-2813 .- 1365-2036. ; 49:6, s. 789-796
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women.AIM: To study the association between BMI early in life and development of liver disease later in life in women.METHODS: We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education.RESULTS: (95% CI 1.02-1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI.CONCLUSION: A high BMI early in life in women is associated with a dose-dependent, increased risk for future severe liver disease.
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13.
  • Hagström, Hannes, et al. (författare)
  • Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:7, s. 1841-1853.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups.METHODS: We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019.RESULTS: At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis).CONCLUSIONS: Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.
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16.
  • Hagström, Hannes, et al. (författare)
  • Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up
  • 2016
  • Ingår i: Liver international (Print). - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 36:11, s. 1688-1695
  • 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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17.
  • Hagström, Hannes, et al. (författare)
  • Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD
  • 2017
  • Ingår i: Journal of Hepatology. - : ELSEVIER SCIENCE BV. - 0168-8278 .- 1600-0641. ; 67:6, s. 1265-1273
  • Tidskriftsartikel (refereegranskat)abstract
    • Background amp; Aims: Non-alcoholic fatty liver disease (NAFLD) is very common in the general population, but identifying patients with increased risk of mortality and liver-specific morbidity remains a challenge. Non-alcoholic steatohepatitis (NASH) is thought to enhance this risk; therefore, resolution of NASH is a major endpoint in current pharmacologic studies. Herein, we aim to investigate the long-term prognosis of a large cohort of NAFLD patients, and to study the specific effect of NASH and fibrosis stage on prognosis. Methods: We conducted a retrospective cohort study of 646 biopsy-proven NAFLD patients. Each case was matched for age, sex and municipality to ten controls. Outcomes on mortality and severe liver disease, defined as cirrhosis, liver decompensation/failure or hepatocellular carcinoma, were evaluated using population-based registers. Cox regression models adjusted for age, sex and type 2 diabetes were used to examine the long-term risk according to fibrosis stage. Likelihood ratio tests were used to assess whether adding NASH to these models increased the predictive capacity. Laplace regression was used to estimate the time to severe liver disease according to stage of fibrosis. Results: During a follow-up of mean 20 years (range 0-40) equivalent to 139,163 person-years, 12% of NAFLD patients and 2.2% of controls developed severe liver disease (p amp;lt; 0.001). Compared to controls, the risk of severe liver disease increased per stage of fibrosis (hazard ratio ranging from 1.9 in F0 to 104.9 in F4). Accounting for the presence of NASH did not change these estimates significantly (likelihood ratio test amp;gt; 0.05 for all stages of fibrosis). Similar results were seen for overall mortality. The lower end of the 95% confidence interval for the 10th percentile of time to development of severe liver disease was 22-26 years in F0-1, 9.3 years in F2, 2.3 years in F3, and 0.9 years to liver decompensation in F4. Conclusions: In this, the largest ever study of biopsy-proven NAFLD, the presence of NASH did not increase the risk of liver-specific morbidity or overall mortality. Knowledge of time to development of severe liver disease according to fibrosis stage can be used in individual patient counselling and for public health decisions. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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18.
  • Hagström, Hannes, et al. (författare)
  • Health Care Costs of Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease Are Nearly Twice Those of Matched Controls
  • 2020
  • Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 18:7, s. 1592-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Data on healthcare resource use and costs associated with nonalcoholic fatty liver disease (NAFLD) in clinical practice are lacking. We compared real-life healthcare costs of patients with NAFLD to matched controls. METHODS: We performed a retrospective study of 646 patients with biopsy-proven NAFLD in Sweden from 1971 through 2009. Each patient was matched for age, sex, and county of residence with 10 persons from the general population (controls). We retrieved all healthcare contacts through Dec 31, 2014 from national registers. Unit costs were assigned to arrive at a total healthcare cost (in USD [$]) per study subject. RESULTS: During a mean follow-up of 19.9 years, we recorded a mean of 0.27 hospitalizations per year for patients with NAFLD vs 0.16 for controls (P <.001). This corresponded to an incremental cost of $635 per year for patients with NAFLD. Patients with NAFLD had a higher mean use of outpatient care visits: 1.46 contacts per year compared with 0.86 per year in controls, corresponding to $255 in additional costs (P <.001). Total costs incurred by patients with stage 3-4 fibrosis were higher than by patients with fibrosis stage 0-2 (mean annual costs, $4397 vs $629). Cumulative costs were higher for all stages of fibrosis compared to controls. CONCLUSIONS: Healthcare costs are nearly twice as high in patients with NAFLD than in matched controls. This is mostly attributable to higher costs for hospitalizations, but also to more outpatient visits. Patients with advanced fibrosis had the highest costs.
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19.
  • Hagström, Hannes, et al. (författare)
  • Improved prediction of 10-year risk of severe liver disease in the general population using commonly available biomarkers
  • 2023
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 57:4, s. 418-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Estimating the risk for cirrhosis in the general population is complex. Existing prediction tools are in general unsatisfactory.Aims: To explore if using commonly available biomarkers can improve the commonly used FIB-4 score in the identification of subgroups at risk of cirrhosis.Methods: We used laboratory and clinical data on 126,925 individuals aged 35–79 years in Stockholm, Sweden, undergoing health examinations from 1985 to 1996. We used Swedish nationwide registries to ascertain 10-year cumulative incidence of severe liver disease, a composite of diagnoses corresponding to cirrhosis and its complications. We considered combinations of biomarkers associated with severe liver disease to identify subgroups with different risk profiles.Results: During an average follow-up of 9.3 years, we ascertained 630 incident cases of severe liver disease (0.5%). Age, the FIB-4 score, diabetes or impaired glucose and gamma-glutamyl transferase (gGT) were the most relevant characteristics for classifying risk profiles. Using these factors, we identified 24 groups with a cumulative incidence of severe liver disease at 10 years ranging from 0.2% (age 35–65, low FIB-4, no diabetes or impaired glucose and normal gGT) to 32.1% (age 35–65, high FIB-4, diabetes or impaired glucose and high gGT).Conclusions: Identification of subjects at increased risk of severe liver disease in the general population using the FIB-4 score can be substantially improved by adding age and specific biomarkers commonly available in the primary care setting. These parameters should be considered for inclusion in the development of future risk prediction models.
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20.
  • Hagström, Hannes, et al. (författare)
  • Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease
  • 2017
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:2, s. 159-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD. Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled. Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p = .017). The lowest risk for fibrosis was found with the lowest odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p = .006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth >= 0.3 mu mol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p = .047). Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.
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21.
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22.
  • Hagström, Hannes, et al. (författare)
  • Maternal obesity increases the risk and severity of NAFLD in offspring
  • 2021
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:5, s. 1042-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Maternal obesity has been linked to the development of cardiovascular disease and diabetes in offspring, but its relationship to non-alcoholic fatty liver disease (NAFLD) is unclear.Methods: Through the nationwide ESPRESSO cohort study we identified all individuals <= 25 years of age in Sweden with biopsy verified NAFLD diagnosed between 1992 and 2016 (n = 165). These were matched by age, sex, and calendar year with up to 5 controls (n = 717). Through linkage with the nationwide Swedish Medical Birth Register (MBR) we retrieved data on maternal early-pregnancy BMI, and possible confounders, in order to calculate adjusted odds ratios (aORs) for NAFLD in offspring.Results: Maternal BMI was associated with NAFLD in offspring: underweight (aOR 0.84; 95% CI 0.14-5.15), normal weight (reference, aOR 1), overweight (aOR 1.51; 0.95-2.40), and obese (aOR 3.26; 1.72-6.19) women. Severe NAFLD (biopsy-proven fibrosis or cirrhosis) was also more common in offspring of overweight (aOR 1.94; 95% CI 0.96-3.90) and obese (aOR 3.67; 95% CI 1.61-8.38) mothers. Associations were similar after adjusting for maternal pre-eclampsia and gestational diabetes. Socio-economic parameters (smoking, mother born outside the Nordic countries and less than 10 years of basic education) were also associated with NAFLD in offspring but did not materially alter the effect size of maternal BMI in a multivariable model.Conclusions: This nationwide study found a strong association between maternal overweight/obesity and future NAFLD in offspring. Adjusting for socio-economic and metabolic parameters in the mother did not affect this finding, suggesting that maternal obesity is an independent risk factor for NAFLD in offspring.Lay summary: In a study of all young persons in Sweden with a liver biopsy consistent with fatty liver, the authors found that compared to matched controls, the risk of fatty liver was much higher in those with obese mothers. This was independent of available confounders and suggests that the high prevalence of obesity in younger persons might lead to a higher risk of fatty liver in their offspring.
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23.
  • Hagström, Hannes, et al. (författare)
  • Mortality in biopsy-proven alcohol-related liver disease : a population-based nationwide cohort study of 3453 patients
  • 2021
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:1, s. 170-179
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with alcohol-related liver disease (ALD) are at increased risk of death, but studies have rarely investigated the significance of histological severity or estimated relative risks compared with a general population. We examined mortality in a nationwide cohort of biopsy-proven ALD.Design: Population-based cohort study in Sweden comparing 3453 individuals with an International Classification of Disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 16 535 matched general population individuals. Swedish national registers were used to ascertain overall and disease-specific mortality, starting follow-up at the latest of first ICD diagnosis or liver biopsy plus 3 months. Cox regression adjusted for relevant confounders was used to estimate HRs in ALD and histopathological subgroups.Results: Median age at diagnosis was 58 years, 65% were men and 52% had cirrhosis at baseline. Five-year cumulative mortality was 40.9% in patients with ALD compared with 5.8% in reference individuals. The risk for overall mortality was significantly increased (adjusted HR (aHR)=4.70, 95% CI 4.35 to 5.08). The risk of liver-related death was particularly high (43% of all deaths, aHR=167.6, 95% CI 101.7 to 276.3). Mortality was significantly increased also in patients with ALD without cirrhosis and was highest in the first year after baseline but persisted after >= 10 years of follow-up (aHR=2.74, 95% CI 2.37 to 3.16).Conclusion: Individuals with biopsy-proven ALD have a near fivefold increased risk of death compared with the general population. Individuals with ALD without cirrhosis were also at increased risk of death, reaffirming the need to increase vigilance in the management of these individuals.
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24.
  • Hagström, Hannes, et al. (författare)
  • Overweight in late adolescence predicts development of severe liver disease later in life : A 39 years follow-up study
  • 2016
  • Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 65:2, s. 363-368
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: The increased prevalence of overweight has been suggested to contribute to the worldwide increase in liver diseases. We investigated if body mass index (BMI) in late adolescence predicts development of severe liver disease later in life.METHODS: We performed a cohort study using data from 44,248 men (18-20years) conscribed to military service in Sweden between 1969 and 1970. Outcome data were collected from national registers to identify any diagnosis of severe liver disease (i.e., diagnosis of decompensated liver disease, cirrhosis or death in liver disease) until the end of 2009. A Cox regression model was applied using BMI as independent variable. The model was adjusted for use of alcohol, use of narcotics, smoking, high blood pressure and cognitive ability at time of conscription.RESULTS: During a follow-up period of a mean of 37.8years, 393 men were diagnosed with severe liver disease (mean time to diagnosis 24.7years). BMI (Hazard ratio [HR]=1.05 for each unit increase in BMI, 95% confidence interval [CI]: 1.01-1.09, p=0.008) and overweight (HR=1.64 for BMI 25-30 compared to BMI 18.5-22.5, 95% CI: 1.16-2.32, p=0.006) were associated with an increased risk of development of severe liver disease.CONCLUSIONS: Being overweight in late adolescence is a significant predictor of severe liver disease later in life in men.LAY SUMMARY: We investigated close to 45,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40years of follow-up, we found that being overweight was a risk factor for developing severe liver disease, independent of established risk factors such as alcohol consumption.
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25.
  • Hagström, Hannes, et al. (författare)
  • Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease
  • 2020
  • Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 73:5, s. 1023-1029
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: It is unclear whether the identification of individuals at risk of cirrhosis using non-invasive tests can be improved by repeated measurements. Herein, we tested whether repeated measurements of fibrosis-4 index (FIB-4) could improve the identification of individuals at risk of severe liver disease.Methods: Data were derived from the population-based Swedish AMORIS cohort with baseline examinations from 1985-1996. FIB4 was calculated at 2 time points within 5 years. Thereafter, we associated changes in FIB-4 with outcomes. Incident severe liver disease data was ascertained through linkage to Swedish national registers until 2011. Hazard ratios (HRs) and CIs for outcomes were calculated using Cox regression.Results: Of 126,942 individuals with available FIB-4 data, 40,729 (32.1%) underwent a second test within 5 years (mean interval 2.4 years). During 613,376 person-years of follow-up, 581 severe liver disease events were documented (0.95/1,000 person-years). An increase of 1 unit in FIB-4 was associated with an elevated risk of severe liver disease (adjusted hazard ratio [aHR] 1.81; 95% CI 1.67-1.96). Transitioning from a low-or intermediate-to a high-risk group was associated with an increased risk of severe liver disease compared with those consistently in the low-risk group (aHR 7.99 and 8.64, respectively). A particularly increased risk of severe liver disease was found in individuals defined as high risk at both tests (aHR 17.04; 95% CI 11.67-24.88). However, almost half of all events occurred in those consistently in the low-risk group.Conclusions: Repeated testing of FIB-4 within 5 years improves the identification of individuals at an increased risk of severe liver disease in the general population. However, the sensitivity is comparatively low and improved tests are needed for screening in a general population or primary care setting.Lay summary: The fibrosis-4 scoring system is often used to estimate the risk of advanced fibrosis in liver diseases. Herein, we found that changes in this score over time are associated with the risk of future severe liver disease in a population-based cohort. However, even if the prediction is improved by repeated testing, the overall ability of the score to predict future events is relatively low.
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26.
  • Hagström, Hannes, et al. (författare)
  • Reply.
  • 2019
  • Ingår i: Hepatology communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 3:6
  • Tidskriftsartikel (refereegranskat)
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27.
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28.
  • Hagström, Hannes, et al. (författare)
  • Risk Behaviors Associated with Alcohol Consumption Predict Future Severe Liver Disease
  • 2019
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 64:7, s. 2014-2023
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExcess consumption of alcohol can lead to cirrhosis, but it is unclear whether the type of alcohol and pattern of consumption affects this risk.AimsWe aimed to investigate whether type and pattern of alcohol consumption early in life could predict development of severe liver disease.MethodsWe examined 43,242 adolescent men conscribed to military service in Sweden in 1970. Self-reported data on total amount and type of alcohol (wine, beer, and spirits) and risk behaviors associated with heavy drinking were registered. Population-based registers were used to ascertain incident cases of severe liver disease (defined as cirrhosis, decompensated liver disease, liver failure, hepatocellular carcinoma, or liver-related mortality). Cox regression models were used to estimate hazard ratios for development of severe liver disease.ResultsDuring follow-up, 392 men developed severe liver disease. In multivariable analysis, after adjustment for BMI, smoking, use of narcotics, cardiovascular fitness, cognitive ability, and total amount of alcohol, an increased risk for severe liver disease was found in men who reported drinking alcohol to alleviate a hangover (“eye-opener”; aHR 1.47, 95% CI 1.02–2.11) and men who reported having been apprehended for being drunk (aHR 2.17, 95% CI 1.63–2.90), but not for any other risk behaviors. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.ConclusionsCertain risk behaviors can identify young men with a high risk of developing severe liver disease. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.
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29.
  • Hagström, Hannes, et al. (författare)
  • Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease : A long-term follow-up study.
  • 2018
  • Ingår i: Hepatology communications. - : John Wiley & Sons. - 2471-254X. ; 2:1, s. 48-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI < 25.0), overweight (BMI 25.0-29.9), or obese (BMI ≥ 30.0) at the time of biopsy. Each case was matched for age, sex, and municipality to 10 controls. Overall mortality and development of severe liver disease were evaluated using population-based registers. Cox regression models adjusted for age, sex, type 2 diabetes, and fibrosis stage were used to examine the long-term risk of mortality and liver-related events in lean and nonlean NAFLD. Lean NAFLD was seen in 19% of patients, while 52% were overweight and 29% were obese. Patients with lean NAFLD were older, had lower transaminases, lower stages of fibrosis, and lower prevalence of nonalcoholic steatohepatitis at baseline compared to patients with a higher BMI. During a mean follow-up of 19.9 years (range 0.4-40 years) representing 12,631 person years and compared to patients who were overweight, patients with lean NAFLD had no increased risk for overall mortality (hazard ratio 1.06; P =  0.73) while an increased risk for development of severe liver disease was found (hazard ratio 2.69; P =  0.007). Conclusion: Although patients with lean NAFLD have lower stages of fibrosis, they are at higher risk for development of severe liver disease compared to patients with NAFLD and a higher BMI, independent of available confounders. (Hepatology Communications 2018;2:48-57).
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30.
  • Hagström, Hannes, et al. (författare)
  • Risk of Cancer in Biopsy-Proven Alcohol-Related Liver Disease : A Population-Based Cohort Study of 3410 Persons
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:4, s. 918-929
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Persons with alcohol-related liver disease (ALD) are at an increased risk of death and liver-related endpoints, but the association with incident cancer is not well understood, and whether it differs across histopathological subgroups is undefined.METHODS: We investigated the risk of cancer in 3,410 persons with a diagnosis of ALD and an available liver biopsy in Sweden between 1969-2016, compared to a matched reference population. Administrative coding from national registers and liver biopsy data were used to define exposure and outcome status. Competing risk regression, adjusted for available confounders and using non-cancer mortality as the competing risk, was used to estimate subdistribution hazard ratios (sHRs) for incident cancer.RESULTS: At baseline, persons with ALD had a median age of 58.2 years, 67% were men, and 2,042 (60%) had cirrhosis. ALD was not associated with cancer in general (sHR = 1.01, 95%CI = 0.92-1.11), although the risk was increased in persons surviving >= 1 year (sHR = 1.19, 95% CI = 1.08-1.32). The risk of liver cancer was elevated sHR = 12.80, 95%CI = 9.38-17.45). HCC incidence among ALD persons with cirrhosis was 8.6 cases/1,000 person-years, corresponding to a cumulative incidence after 10 years of 5.0%.CONCLUSIONS: Persons with biopsy-proven ALD that survive the initial time after diagnosis are at an elevated risk for cancer, in particular HCC compared with the general population. Although the risk for HCC was elevated, data do not suggest that routine surveillance for HCC in ALD cirrhosis is cost-effective.
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31.
  • Hagström, Hannes, et al. (författare)
  • Risk of infections and their role on subsequent mortality in biopsy-proven alcohol-related liver disease
  • 2022
  • Ingår i: United European Gastroenterology journal. - : John Wiley & Sons. - 2050-6406 .- 2050-6414. ; 10:2, s. 198-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The risk for infection in alcohol-related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital-based infections in a nationwide cohort of biopsy-proven ALD, and the subsequent risk of death.Methods: Population-based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals.Results: Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person-years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85-3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36-3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89-4.78) were linked to subsequent death.Conclusions: Individuals with biopsy-proven ALD have a three-fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.
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32.
  • Hagström, Hannes, et al. (författare)
  • SAF score and mortality in NAFLD after up to 41 years of follow-up
  • 2017
  • Ingår i: Scandinavian Journal of Gastroenterology. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 52:1, s. 87-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: A new score for the histological severity of nonalcoholic fatty liver disease (NAFLD), called SAF (Steatosis, Activity and Fibrosis) has been developed. We aimed to evaluate the impact of this score on overall mortality. Methods: We used data from 139 patients with biopsy-proven NAFLD. All biopsies were graded according to the SAF scoring system and disease severity was classified as mild, moderate or severe. Causes of death were extracted from a national, population-based register. A Cox regression model, adjusted for sex, body mass index (BMI) and diabetes mellitus type 2, was applied. Results: At baseline 35 patients presented with mild or moderate disease respectively, and 69 patients with severe disease. During follow-up (median 25.3 years, range 1.7-40.8) 74 patients died, 11 in the mild group (31%), 18 in the moderate group (51%) and 45 in the severe group (65%), p=.002. Compared to patients with mild disease, patients with moderate disease did not have a significant increase in overall mortality (HR 1.83, 95% CI 0.89-3.77, p=.10). Patients with severe disease had a significant increase in mortality (HR 2.65, 95% CI 1.19-5.93, p=.017). However, when adjusting for fibrosis stage, significance was lost (HR 1.85, 95% CI 0.76-4.54, p=.18). NASH, defined as per the FLIP algorithm, was not associated with mortality compared to not having NASH (HR 1.46, 95% CI 0.74-2.90, p=.28). Conclusions: After adjustment for fibrosis, the SAF score was not associated with increased mortality in NAFLD. This finding should be corroborated in larger cohorts with similar follow-up time.
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33.
  • Hagström, Hannes (författare)
  • The importance of fat and alcohol for progression and prognosis in chronic liver disease
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chronic liver disease is an increasing cause of global morbidity and mortality. The popular belief is that liver disease is caused mainly by alcoholic liver disease or viral hepatitis. However, the most common cause of chronic liver disease today is non-alcoholic fatty liver disease (NAFLD), which is associated with obesity and insulin resistance rather than alcohol. NAFLD is considered to become the most common cause for need of liver transplantation in the coming years. Today, the most common cause of liver transplantation in Sweden is primary sclerosing cholangitis (PSC) - a rare but very serious disease of the bile ducts that become inflamed and obliterated, and is associated with a high risk of development of cholangiocarcinoma. The role of concurrent use of alcohol in NAFLD and PSC is controversial. Part of this thesis explores the effect of alcohol on the degree of liver damage in these two diseases. We found that a low consumption of alcohol, around one unit per day, is not associated with a higher stage of fibrosis in the liver in PSC and should be safe in these patients. For NAFLD, we found that a low to moderate consumption of alcohol was associated with a lower risk for a higher fibrosis stage, up to thirteen units of alcohol per week. However, patients who had biochemical evidence of high alcohol consumption had a higher risk of more severe liver damage. This is well in line with other studies and indicates a J-formed risk profile for alcohol consumption in NAFLD. In another part of the thesis we studied the long-term risk of having fat accumulation in the liver and if overweight per se can predict development of severe liver disease. We found that the strongest histological marker for disease-specific mortality in NAFLD after a follow-up of in mean 26 years was the stage of fibrosis, and found no excess mortality in patients with signs of inflammation in the liver after adjustment for the stage of fibrosis. The risk of being overweight was studied in close to 45.000 men in their late adolescence who were conscribed to military service in 1969-1970 after adjustment of potential confounders, such as alcohol consumption. Body mass index (BMI) was found to be an independent predictor of development of severe liver disease after a mean follow-up of 39 years. Taken together, this thesis indicates that a low to moderate consumption of alcohol is safe in PSC and possibly protective in NAFLD. Furthermore, we found that the strongest predictor of disease-specific mortality in NAFLD is the stage of fibrosis, which can have implications for the design of endpoints in future clinical studies. Also, the finding that overweight per se is a predictor for development of severe liver disease is important for public health decisionmaking.
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34.
  • Holmer, Magnus, et al. (författare)
  • Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up
  • 2022
  • Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 42:12, s. 2769-2780
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims Several genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD. Method DNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis (NASH) was histologically defined. Additionally, 5396 controls matched for age, sex and municipality were identified from population-based registers. Events of severe liver disease and all-cause mortality were collected from national registries. Hazard ratios (HRs) adjusted for age, sex, body mass index and type 2 diabetes were estimated with Cox regression. Results In NAFLD, the G/G genotype of PNPLA3 was associated with a higher prevalence of NASH at baseline (odds ratio [OR] 3.67, 95% CI = 1.66-8.08), but not with advanced fibrosis (OR 1.81, 95% CI = 0.79-4.14). After up to 40 years of follow-up, the PNPLA3 G/G genotype was associated with a higher rate of severe liver disease (adjusted hazard ratio [aHR] 2.27, 95% CI = 1.15-4.47) compared with the C/C variant. NAFLD patients developed cirrhosis at a higher rate than controls (aHR 9.00, 95% CI = 6.85-11.83). The PNPLA3 G/G genotype accentuated this rate (aHR 23.32, 95% = CI 9.14-59.47). Overall mortality was not affected by any genetic variant. Conclusion The PNPLA3 G/G genotype is associated with an increased rate of cirrhosis in NAFLD. Our results suggest that assessment of the PNPLA3 genotype is of clinical relevance in patients with NAFLD to individualize monitoring and therapeutic strategies.
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35.
  • Järbrink-Sehgal, M. Ellionore, et al. (författare)
  • Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization
  • 2018
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 16:9, s. 1474-1480
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. METHODS: We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. RESULTS: Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). CONCLUSIONS: In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later.
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36.
  • Larsson, Tobias E, et al. (författare)
  • Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community
  • 2010
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 30:2, s. 333-339
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Hyperphosphatemia is a cardiovascular risk factor in patients with chronic kidney disease. Relations of circulating calcium (Ca) and phosphorus (Pi) to long-term mortality risk in the community require further investigation. METHODS AND RESULTS: Associations of serum Ca and Pi to mortality were evaluated in a community-based cohort of 2176 men (mean age, 50.1 years). During follow-up (median, 29.8 years), 1009 men died, and 466 of these deaths resulted from cardiovascular causes. In Cox proportional hazards models, serum Pi and [CaxPi] were independent predictors of total mortality (hazard ratio per SD, 1.06; 95% CI, 1.01-1.12; P=0.03; 1.07; 95% CI, 1.01-1.12; P=0.01) and cardiovascular mortality (1.10; 95% CI, 1.02-1.18; P=0.01; 1.10; 95% CI, 1.03-1.19; P=0.008). Serum Ca was associated with risk of total mortality (1.08; 95% CI, 1.01-1.16; P=0.02) and noncardiovascular mortality (1.10; 95% CI, 1.01-1.21; P=0.04). Results were consistent after multivariate adjustments in subsamples of individuals with estimated glomerular filtration rate >90 mL/min and low-to-normal serum Ca and Pi. CONCLUSIONS: Circulating Ca and Pi levels are associated with risks of total, cardiovascular, and noncardiovascular mortality in the community, and their conjoint effects are additive. Additional studies are warranted to evaluate whether Ca and Pi are modifiable risk factors in the general population.
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37.
  • Ludvigsson, Jonas F., 1969-, et al. (författare)
  • Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden
  • 2021
  • Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 21-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting.Methods: Four versions of the CCI were compared and evaluated by disease-specific experts.Results: We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing.Conclusion: This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.
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38.
  • Ludvigsson, Jonas F., 1969-, et al. (författare)
  • Pregnancy Outcome in Women Undergoing Liver Biopsy During Pregnancy: A Nationwide Population-Based Cohort Study.
  • 2018
  • Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 68:2, s. 625-633
  • Tidskriftsartikel (refereegranskat)abstract
    • Liver biopsy is an important procedure in the investigation of liver disease. We examined pregnancy outcomes in women who underwent liver biopsy during pregnancy. In a nationwide population-based cohort study we linked data from the Swedish Medical Birth Registry (for births between 1992 and 2011) with those from the Swedish Patient Registry. We identified 23 pregnancies exposed to liver biopsy. We calculated relative risks (RRs) for adverse pregnancy outcomes according to liver biopsy status using 1,953,887 unexposed pregnancies with and without a record of liver disease as reference. Our main outcome measures were stillbirth and preterm birth. There were no stillbirths in pregnancies exposed to liver biopsies compared with 0.3% stillbirths in unexposed pregnancies. 3/23 (13%) exposed pregnancies were preterm (RR=2.6; 95%CI=0.9-7.5). Compared with women with a record of liver disease, preterm birth was not increased in those exposed to liver biopsy (RR=0.9; 95%CI=0.1-6.0). Except for an increased risk of small for gestational age birth in pregnancies exposed to liver biopsy (RR=5.2; 95%CI=1.8-14.8), other adverse pregnancy outcomes were independent of liver biopsy status when the analysis was restricted to women with a diagnosis of liver disease. Compared with unexposed sibling pregnancies, pregnancies with a liver biopsy were 7 days shorter, but birth weights did not differ between the siblings (-67g; p>0.05).Apart from a moderately increased risk of preterm birth and small for gestational age, there was no association between liver biopsy during pregnancy and adverse pregnancy outcome. Potential excess risks should be weighed against the advantages of having a liver biopsy that may influence clinical management of the patient indirectly influencing fetal health. This article is protected by copyright. All rights reserved.
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39.
  • Lykiardopoulos, Byron, et al. (författare)
  • Development of Serum Marker Models to Increase Diagnostic Accuracy of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: The New LINKI Algorithm Compared with Established Algorithms
  • 2016
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aim Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms. Methods We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, Kings score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC). Results Of established algorithms FIB-4 and Kings score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89. Conclusion The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.
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40.
  • Montagnese, Sara, et al. (författare)
  • A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy
  • 2021
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:1, s. 98-107
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis.Methods: Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks’ dosing with golexanolone (10, 40 or 80 mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days.Results: Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p = 0.047), MDF (p = 0.142) and DT/AB (p = 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well.Conclusion: Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone.Lay summary: Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug.Clinical trial registration number: EudraCT 2016-003651-30.
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41.
  • Nasr, Patrik, et al. (författare)
  • Incidence, prevalence and mortality of chronic liver diseases in Sweden between 2005 and 2019
  • 2022
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 77:Suppl. 1, s. S82-S82
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background and aims: Chronic liver diseases affects approximately 844 million individuals and causes an estimated two million deaths per year. The most common causes are chronic viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. With the availability of curative treatments and effective vaccines for viral hepatitis and increasing prevalence of metabolic syndrome-thel andscape of liver diseases is shifting. In this study, we aimed to describe the incidence and prevalence of a wide range of chronic liver diseases as well as their role in mortality in Sweden.Method: In this register-based, nationwide cohort study, aggregated statistics, stratified on categories of age, sex and geographic allocations, on all adult Swedish inhabitants with a diagnosis of liver disease during 2005 to 2019 were obtained from National registers.Results: During 2005 to 2019, there were substantial changes in the epidemiology of liver diseases in Sweden. The incidence of alcohol-related cirrhosis increased by 18% annually (incidence rate 13.1/100, 000 in 2019). The incidence rate of non-alcoholic fatty liver diseasea nd cirrhosis with unspecified etiology increased by 14% and 20% annually respectively (incidence rate 15.2 and 18.7/100, 000). Furthermore, incidence rates of chronic hepatitis C steeply declined, while autoimmune hepatitis increased (3.4/100, 000). In parallel with the increasing incidence of liver cirrhosis, liver malignancies have become more common.The most common causes of liver related mortality were alcohol-related disease without a code for cirrhosis, alcohol-related cirrhosis, and unspecified liver disease with mortality rates of 4.1, 2.9, and 2.8/100, 000. Most liver diseases were more frequent amongst men. Furthermore, varying differences was seen in the incidence ratebetween regions, with some etiologies (e.g. autoimmune liver diseases) being more common in rural areas.Conclusion: The incidence rates of non-alcoholic fatty liver disease, alcohol-related cirrhosis, unspecified liver cirrhosis has increased during the last 15 years, in parallel with a decreasing incidence of viral hepatitis. The incidence of AIH and hepatobiliary malignancies is also increasing. Worryingly, mortality in several liver diseases increased, likely reflecting the increasing incidence of cirrhosis. Significant disparities of liver diseases exist across sex and geographical regions, which needs to be considered when allocating healthcare resources.
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42.
  • Qadri, Sami, et al. (författare)
  • Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease
  • 2022
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:5, s. e2008-e2020
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. Objective: To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. Design: Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3). Setting: Tertiary referral center. Patients: We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m(2)]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS. Main Outcome Measures: Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage >= F3 fibrosis or nonalcoholic steatohepatitis with >= F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)]. Results: The scores with an AUROC >= 0.85 to identify >= F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out >= F3 fibrosis in groups with BM Is <30.0, 30.0 to 39.9, and >= 40.0 kg/m(2). This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose >= F3 fibrosis. Conclusions: In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.
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43.
  • Shang, Ying, et al. (författare)
  • Non-alcoholic fatty liver disease does not increase dementia risk although histology data might improve risk prediction
  • 2021
  • Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 3:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is common in the general population, but its association with dementia is unclear. We aimed to assess the risk of dementia related to NAFLD, and to determine whether histological parameters could improve the predictive capacity of a conventional risk model for dementia in patients with biopsy-proven NAFLD. Methods: A retrospective matched cohort study of 656 NAFLD patients underwent liver biopsy at 2 hospitals between 1971 and 2009. Up to 10 individuals (controls) from the general population (n = 6,436) were matched for age, sex, and municipality to each patient. Dementia was ascertained from National registers until 2014. Using Cox regression, we estimated hazard ratios for dementia with 95% confidence intervals. In the biopsy cohort, the discriminative power of adding histological markers to a conventional risk model was assessed by Harrells C-index and compared with a likelihood-ratio test. Results: During a mean follow-up of 19.7 +/- 8.7 years, 3.3% of the NAFLD patients and 4.9% of the controls developed dementia (p = 0.07). Overall, NAFLD was not significantly associated with incident dementia. In the biopsy cohort, the model of conventional risk factors (age, sex, hypertension, and cardiovascular diseases) had a C-index of 0.912 to predict incident dementia. Adding individual histological parameters significantly increased the prediction of dementia, with the most pronounced improvement for fibrosis stage (C-index = 0.938, p <0.05). Conclusions: Although NAFLD was not associated with the risk of dementia, we found that adding histological markers to a conventional risk model for dementia enhanced the predictive capacity, indicating a shared metabolic origin. Lay summary: Both non-alcoholic fatty liver disease (NAFLD) and dementia are increasing in prevalence because of a more sedentary lifestyle, increased prevalence of obesity and population ageing. However, the link between these 2 diseases is not well studied. We investigated the association between NAFLD and the risk of dementia and found no association. However, liver histology parameters, especially fibrosis, could significantly improve the prediction of dementia risk. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
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44.
  • Shang, Ying, et al. (författare)
  • Risk of cardiovascular disease and loss in life expectancy in NAFLD
  • 2022
  • Ingår i: Hepatology. - : Wiley. - 0270-9139 .- 1527-3350. ; 76:5, s. 1495-1505
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims Conflicting evidence exists on cardiovascular disease (CVD) risk in patients with NAFLD, and data are lacking on whether NAFLD increases mortality after a CVD event. Moreover, life expectancy in NAFLD has not been studied. We therefore examined CVD risk and life expectancy in patients with NAFLD compared with the general population. Approach and Results In this nationwide population-based cohort, all patients with NAFLD diagnosis and without baseline CVD (ascertaining from the Swedish National Patient Register from 1987 to 2016, n = 10,023) were matched 10:1 on age, sex, and municipality to individuals from the general population (controls, n = 96,313). CVD diagnosis and mortality were derived from national registers. Multistate models and flexible parametric survival models were used to estimate adjusted hazard ratios (aHRs) for CVD risk and loss in life expectancy due to NAFLD. We identified 1037 (10.3%) CVD events in patients with NAFLD and 4041 (4.2%) in controls. CVD risk was 2.6-fold higher in NAFLD compared with controls (aHR = 2.61, 95% CI = 2.36-2.88) and was strongest for nonfatal CVD (aHR = 3.71, 95% CI = 3.29-4.17). After a nonfatal CVD event, the risk for all-cause mortality was similar between patients with NAFLD and controls (aHR = 0.89, 95% CI = 0.64-1.25). Life expectancy in patients with NAFLD was, on average, 2.8 years lower than controls, with the highest loss of life-years when NAFLD was diagnosed in middle age (40-60 years). Conclusions NAFLD was associated with a higher risk of nonfatal CVD but did not affect post-CVD mortality risk. Patients diagnosed with NAFLD have a lower life expectancy than the general population.
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45.
  • Sharma, Rajani, et al. (författare)
  • Cancer Risk in Patients With Autoimmune Hepatitis : A Nationwide Population-Based Cohort Study With Histopathology
  • 2022
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 191:2, s. 298-319
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969-2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR) = 2.69) and lymphoma (HR = 1.89). Sibling analyses yielded similar risk estimates for any cancer (HR = 1.84) and HCC (HR = 23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.
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46.
  • Sharma, Rajani, et al. (författare)
  • Increased Mortality Risk in Autoimmune Hepatitis : A Nationwide Population-based Cohort Study With Histopathology
  • 2021
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:12, s. 2636-2647.e13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting.METHODS: This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death.RESULTS: During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI=31.1-33.6) for AIH individuals and 14.1% (95%CI=13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI=2.17-2.41), which remained elevated ≥20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR=4.55; 95%CI=3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR=1.27; 95%CI=1.15-1.40), liver disease (HR=66.24; 95%CI=48.19-91.03) and extrahepatic malignancy (HR=1.69; 95%CI=1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death.CONCLUSION: AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.
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47.
  • Simon, Tracey G., et al. (författare)
  • Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease : A Population-Based Cohort Study
  • 2021
  • Ingår i: Hepatology. - : Wiley-Interscience Publishers. - 0270-9139 .- 1527-3350. ; 74:5, s. 2410-2423
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Recent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity.Approach and Results: We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to <= 5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person-years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18-1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; P-trend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers.Conclusions: Compared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.
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48.
  • Simon, Tracey G., et al. (författare)
  • Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease
  • 2023
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:3, s. 573-580
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Longitudinal evidence is lacking regarding the long-term risk of major adverse cardiovascular events (MACE) in children and young adults with non-alcoholic fatty liver disease (NAFLD).DESIGN: This nationwide cohort study included all Swedish children and young adults ≤25 years old with histologically confirmed NAFLD and without underlying cardiovascular disease (CVD) at baseline (1966-2016; n=699). NAFLD was defined from prospectively recorded histopathology, and further categorised as simple steatosis or non-alcoholic steatohepatitis (NASH). NAFLD patients were matched to ≤5 population controls without NAFLD or CVD (n=3353). Using Cox proportional hazards modelling, we calculated multivariable-adjusted HRs (aHRs) and 95% CIs for incident MACE (ie, ischaemic heart disease, stroke, congestive heart failure or cardiovascular mortality). In secondary analyses, we also explored rates of incident cardiac arrhythmias.RESULTS: Over a median follow-up of 16.6 years, incident MACE was confirmed in 33 NAFLD patients and 52 controls. NAFLD patients had significantly higher rates of MACE than controls (3.1 vs 0.9/1000 person-years (PY); difference=2.1/1000 PY; aHR=2.33, 95% CI=1.43 to 3.78), including higher rates of ischaemic heart disease (difference=1.4/1000 PY; aHR=3.07, 95% CI 1.62 to 5.83) and congestive heart failure (difference=0.5/1000 PY; aHR=3.89, 95% CI=1.20 to 12.64). Rates of incident MACE outcomes appeared to be further augmented with NASH (aHR=5.27, 95% CI=1.96 to 14.19). In secondary analyses, NAFLD patients also had significantly higher rates of cardiac arrythmias (aHR=3.16, 95% CI=1.49 to 6.68).CONCLUSION: Compared with matched population controls, children and young adults with biopsy-proven NAFLD had significantly higher rates of incident MACE, including ischaemic heart disease and congestive heart failure. Research to better characterise cardiovascular risk in children and young adults with NAFLD should be prioritised.
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49.
  • Simon, Tracey G., et al. (författare)
  • Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease : a nationwide histology cohort study
  • 2023
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prior studies suggest a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and incident arrhythmias, including atrial fibrillation (AF). However, robust data are lacking from cohorts with liver histology, which remains the gold standard for staging MASLD severity.Methods: This population-based cohort included all Swedish adults with histologically-confirmed MASLD and without prior cardiac arrhythmias (1966-2016; n = 11,206). MASLD was defined from prospectively-recorded histopathology, and characterized as simple steatosis, non-fibrotic steatohepatitis (MASH), non-cirrhotic fibrosis, or cirrhosis. MASLD patients were matched to <= 5 controls without MASLD or arrhythmias, by age, sex, calendar year and county (n = 51,856). Using Cox proportional hazards modeling, we calculated multivariable-adjusted hazard ratios (aHRs) for incident arrhythmias (including AF, bradyarrhythmias, other supraventricular arrhythmias, ventricular arrhythmias/cardiac arrest).Results: Over a median follow-up of 10.8 years, incident arrhythmias were confirmed in 1351 MASLD patients (10.3/1000 person-years [PY]) and 6493 controls (8.7/1000PY; difference = 1.7/1000PY; aHR = 1.30, 95%CI 1.22-1.38), and MASLD patients had significantly higher rates of incident AF (difference = 0.9/1000PY; aHR = 1.26, 95%CI 1.18-1.35). Rates of both overall arrhythmias and AF were significantly elevated across all MASLD histological groups, particularly cirrhosis (differences, 8.5/1000PY and 5.3/1000PY, respectively). In secondary analyses, MASLD patients also had significantly higher rates of incident ventricular arrhythmias/cardiac arrest (aHR = 1.53, 95%CI 1.30-1.80), bradyarrhythmias (aHR = 1.26, 95%CI 1.06-1.48), and other supraventricular arrhythmias (aHR = 1.27, 95%CI 1.00-1.62), compared to controls.Conclusions: Compared to matched controls, patients with biopsy-confirmed MASLD had modest but significantly higher incidence of cardiac arrhythmias, including AF, bradyarrhythmias, other supraventricular arrhythmias and ventricular arrhythmias/cardiac arrest. Excess risk was observed across all stages of MASLD and was highest with cirrhosis.
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50.
  • Simon, Tracey G., et al. (författare)
  • Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis : Results From a Nationwide Swedish Population
  • 2019
  • Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 171:5, s. 318-327
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown.Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis.Design: Prospective propensity score (PS)-matched cohort.Setting: Swedish registers, 2005 to 2013.Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults.Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs).Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The in- verse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -62 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users.Limitation: Lack of lipid, fibrosis, or HCC surveillance data.Conclusion: In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.
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