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Nasr, Patrik
Publications (8 of 8) Show all publications
Dulai, P. S., Singh, S., Patel, J., Soni, M., Prokop, L. J., Younossi, Z., . . . Loomba, R. (2017). Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic Review and Meta-analysis.. Hepatology, 65(5), 1557-1565
Open this publication in new window or tab >>Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic Review and Meta-analysis.
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2017 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 65, no 5, p. 1557-1565Article, review/survey (Refereed) Published
Abstract [en]

BACKGROUND: Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD.

METHODS: Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement.

RESULTS: 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19-2.11); stage 2, MRR, 2.52 (95% CI 1.85-3.42); stage 3, MRR, 3.48 (95% CI 2.51-4.83), and stage 4, MRR, 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17-11.95); stage 2, MRR, 9.57 (95% CI 1.67-54.93); stage 3, MRR, 16.69 (95% CI 2.92-95.36); and stage 4, MRR, 42.30 (95% CI 3.51-510.34).

LIMITATIONS: Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group.

CONCLUSION: The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-134875 (URN)10.1002/hep.29085 (DOI)000399459800011 ()28130788 (PubMedID)
Note

Funding agencies: American Gastroenterological Association Foundation [K23-DK090303, R01-DK106419-01]; National Institute of Diabetes and Digestive and Kidney Diseases [5T32DK007202]; National Institute of Environmental Health Sciences of the National Institutes of Health 

Available from: 2017-02-28 Created: 2017-02-28 Last updated: 2018-04-18
Hagström, H., Nasr, P., Ekstedt, M., Kechagias, S., Onnerhag, K., Nilsson, E., . . . Stal, P. (2017). Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease. Scandinavian Journal of Gastroenterology, 52(2), 159-165
Open this publication in new window or tab >>Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 2, p. 159-165Article in journal (Refereed) Published
Abstract [en]

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 amp;gt;= 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.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2017
Keywords
NAFLD; NASH; alcohol; lifetime alcohol consumption; fibrosis stage
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-134618 (URN)10.1080/00365521.2016.1239759 (DOI)000392488000008 ()27650916 (PubMedID)
Note

Funding Agencies|Stockholm County Council (ALF) [20140329, 20150403]; Royal Swedish Academy of Sciences Foundations [ME2015-0011]; Swedish Society of Medicine (Gastroenterology Fund); Ruth and Richard Julins Fund; ALF [2015403]

Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-04-18
Hagström, H., Nasr, P., Ekstedt, M., Kechagias, S., Stal, P., Bedossa, P. & Hultcrantz, R. (2017). SAF score and mortality in NAFLD after up to 41 years of follow-up. Scandinavian Journal of Gastroenterology, 52(1), 87-91
Open this publication in new window or tab >>SAF score and mortality in NAFLD after up to 41 years of follow-up
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 1, p. 87-91Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2017
Keywords
NAFLD; NASH; SAF-score; NAS-score; fibrosis; mortality
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-134617 (URN)10.1080/00365521.2016.1230779 (DOI)000392486600016 ()27616339 (PubMedID)
Note

Funding Agencies|Stockholm County Council (ALF) [20140329, 20150403]; Royal Swedish Academy of Sciences Foundations [ME2015-0011]; Swedish Society of Medicine; Ruth and Richard Julins Fund; Stockholm City Council (ALF) [2015403]; Swedish Cancer Foundation; King Gustaf V:s and Queen Victorias Freemasons Foundation

Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-04-18
Nasr, P., Forsgren, M. F., Ignatova, S., Dahlström, N., Cedersund, G., Dahlqvist Leinhard, O., . . . Kechagias, S. (2017). Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis. Gastroenterology, 153(1), 53-+
Open this publication in new window or tab >>Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
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2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 1, p. 53-+Article in journal (Refereed) Published
Abstract [en]

It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-136544 (URN)10.1053/j.gastro.2017.03.005 (DOI)000403918300022 ()
Note

Funding agencies: Swedish Research Council/Medicine and Health [VR/M 2007-2884, VR/M 2012-3199]; Swedish Research Council/Natural and Engineering Sciences [VR/NT 2014-6157]; Swedish Innovation Agency VINNOVA [2013-01314]; Region Ostergotland (ALF)

Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2018-04-18Bibliographically approved
Nasr, P., Hilliges, A., Thorelius, L., Kechagias, S. & Ekstedt, M. (2016). Contrast-enhanced ultrasonography could be a non-invasive method for differentiating none or mild from severe fibrosis in patients with biopsy proven non-alcoholic fatty liver disease. Scandinavian Journal of Gastroenterology, 51(9), 1126-1132
Open this publication in new window or tab >>Contrast-enhanced ultrasonography could be a non-invasive method for differentiating none or mild from severe fibrosis in patients with biopsy proven non-alcoholic fatty liver disease
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2016 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 9, p. 1126-1132Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The gold standard for diagnosing fibrosis stage in non-alcoholic fatty liver disease (NAFLD) is liver biopsy. The aim of this study was to determine whether contrast-enhanced ultrasonography (CEUS) with transit time measurements could be a non-invasive alternative for differentiating none or mild from severe fibrosis in NAFLD patients. Various serum markers and clinical variables were also evaluated.

MATERIALS AND METHODS: Fifty-eight patients with NAFLD underwent CEUS prior to liver biopsy. All patients were also evaluated according to the Göteborg University Cirrhosis Index (GUCI), the AST-Platelet Ratio Index (APRI), the NAFLD fibrosis score, and the FIB-4 and BARD score.

RESULTS: The hepatic vein arrival time (HV) was shorter in patients with severe fibrosis (25.9 ± 4.8 vs 29.5 ± 4.7 s, p = 0.023), and the difference between the hepatic and portal vein (ΔHV-PV) was shorter (2.3 ± 2.8 vs 6.4 ± 2.8 s, p < 0.0001) while the difference in arrival time between the portal vein and hepatic artery (ΔPV-HA) arrival time was significantly longer (6.0 ± 2.2 vs 3.6 ± 1.6 s, p < 0.0001). The area under receiver operating characteristics curve values for HV, ΔHV-PV and ΔPV-HA to separate none or mild from severe fibrosis was 0.71, 0.83 and 0.84, respectively. The corresponding figures for GUCI, APRI, NAFLD fibrosis score, FIB-4 and BARD score were 0.93, 0.92, 0.86, 0.90 and 0.77, respectively.

CONCLUSIONS: CEUS and non-invasive scoring systems could exclude severe fibrosis in NAFLD patients.

Place, publisher, year, edition, pages
Taylor & Francis, 2016
Keywords
Contrast-enhanced ultrasonography, fibrosis, fibrosis scores, non-alcoholic fatty liver disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-129954 (URN)10.3109/00365521.2016.1172336 (DOI)000381406800018 ()27161854 (PubMedID)
Note

Funding agencies: Research Council of Southeast Sweden [F2004-303]; ALF Grants, Region Ostergotland

Available from: 2016-07-02 Created: 2016-07-02 Last updated: 2017-11-28Bibliographically approved
Hagström, H., Nasr, P., Bottai, M., Ekstedt, M., Kechagias, S., Hultcrantz, R. & Stål, P. (2016). Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up. Liver international (Print), 36(11), 1688-1695
Open this publication in new window or tab >>Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up
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2016 (English)In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 36, no 11, p. 1688-1695Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
Keywords
ferritin;fibrosis, long-term outcome, mortality, NAFLD activity score, non-alcoholic fatty liver disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-129955 (URN)10.1111/liv.13144 (DOI)000385863400016 ()27064133 (PubMedID)
Note

Funding agencies:Stockholm County Council (ALF projects from the Swedish Society of Medicine [20140329, 20150403]; Ruth and Richard Julins Foundation; Medical Research Council of Southeast Sweden [311151]; ALF grants, Region Ostergotland, Sweden

Available from: 2016-07-02 Created: 2016-07-02 Last updated: 2017-11-28Bibliographically approved
Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stal, P., Kechagias, S. & Hultcrantz, R. (2016). Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY [Letter to the editor]. Hepatology, 64(1), 310-311
Open this publication in new window or tab >>Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY
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2016 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 64, no 1, p. 310-311Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-124403 (URN)10.1002/hep.28314 (DOI)000379233400041 ()26517017 (PubMedID)
Available from: 2016-01-28 Created: 2016-01-28 Last updated: 2017-11-30
Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S. & Hultcrantz, R. (2015). Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology, 61(5), 1547-1554
Open this publication in new window or tab >>Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
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2015 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, no 5, p. 1547-1554Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015
Keywords
NAFLD activity score; cohort study; fatty liver; liver fibrosis; mortality
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-112707 (URN)10.1002/hep.27368 (DOI)000353233500015 ()25125077 (PubMedID)
Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2017-12-05
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