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Nasr, P., Fredrikson, M., Ekstedt, M. & Kechagias, S. (2020). The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.. Liver international (Print)
Open this publication in new window or tab >>The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.
2020 (English)In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.

METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC.

RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).

CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
Stereological point count (SPC), hepatic steatosis, quantitative steatosis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-163934 (URN)10.1111/liv.14414 (DOI)32087038 (PubMedID)
Available from: 2020-02-27 Created: 2020-02-27 Last updated: 2020-03-30Bibliographically approved
Hagstrom, H., Nasr, P., Ekstedt, M., Stål, P., Hultcrantz, R. & Kechagias, S. (2019). Accuracy of Noninvasive Scoring Systems in Assessing Risk of Death and Liver-Related Endpoints in Patients With Nonalcoholic Fatty Liver Disease. Clinical Gastroenterology and Hepatology, 17(6), 1148-1156.e4
Open this publication in new window or tab >>Accuracy of Noninvasive Scoring Systems in Assessing Risk of Death and Liver-Related Endpoints in Patients With Nonalcoholic Fatty Liver Disease
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2019 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 17, no 6, p. 1148-1156.e4Article in journal (Refereed) Published
Abstract [en]

Background and Aims

Several non-invasive scoring systems have been developed to determine risk of advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). We examined the association between 4 scoring systems and incident severe liver disease and overall mortality in a large cohort of patients with biopsy-proven NAFLD.

Methods

We performed a retrospective analysis of data from 646 patients with biopsy-proven NAFLD, recruited from 2 hospitals in Sweden, from 1971 through 2009. The NAFLD fibrosis score (NFS), FIB-4, APRI, and BARD scores were calculated at the time of the liver biopsy. Based on each score, patients were assigned to categories of low, intermediate, or high risk for advanced fibrosis. Overall mortality and severe liver disease (cirrhosis, decompensated liver disease, liver failure, or hepatocellular carcinoma) were ascertained through linkage with national registers until the end of 2014. Cox regression, area under the receiver operating characteristic (AUROC) curve, and C-statistic analyses were used to study the predictive capacity of each scoring system.

Results

During a mean follow-up time of 19.9±8.7 years, there were 214 deaths and 76 cases of severe liver disease. For overall mortality, AUROC curve values were: NFS, 0.72 (95% CI, 0.68–0.76); FIB-4, 0.72 (95% CI, 0.68–0.76); BARD, 0.62 (95% CI, 0.58–0.66); and APRI, 0.52 (95% CI, 0.47–0.57). For severe liver disease, AUROC curve values were: NFS, 0.72 (95% CI, 0.66–0.78); FIB-4, 0.72 (95% CI, 0.66–0.79); BARD, 0.62 (95% CI, 0.55–0.69); APRI, 0.69 (95% CI, 0.63–0.76). C-statistics for all scores were of moderate capacity to predict outcomes.

Conclusions

In a retrospective analysis of data from 646 patients with biopsy-proven NAFLD, we found the NFS and the FIB-4 scores to most accurately determine risk of overall death or severe liver disease. However, the AUROC values for these scoring systems are not high enough for use in the clinic; new systems are needed to determine prognoses of patients with NAFLD.

Place, publisher, year, edition, pages
Saunders Elsevier, 2019
Keywords
NASH; Fibrosis; Cirrhosis; Epidemiology
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-156920 (URN)10.1016/j.cgh.2018.11.030 (DOI)000464657100026 ()30471458 (PubMedID)2-s2.0-85064181289 (Scopus ID)
Note

Funding Agencies|Stockholm City Council - Clinical Postdoctoral Appointment; Bengt Ihre Fellowship

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-06-03Bibliographically approved
Nasr, P. (2019). Non-Alcoholic Fatty Liver Disease: Aspects on Diagnosis and Long-term Prognosis. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Non-Alcoholic Fatty Liver Disease: Aspects on Diagnosis and Long-term Prognosis
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population and is commonly recognized as the hepatic manifestation of the metabolic syndrome. The histological spectrum of NAFLD ranges from isolated steatosis to non-alcoholic steatohepatitis (NASH), with risk of developing fibrosis and subsequent cirrhosis and hepatocellular carcinoma. The gold standard for diagnosing NAFLD is liver biopsy. However, because of its invasive nature, several non-invasive methods have been developed and validated in evaluating fat and fibrosis in patients with NAFLD.

Liver fat content can be assessed using various methods. The conventional histopathological method consists of a visual semiquantitative approach in which the pathologist uses a four-point scale: grade 0 corresponds to fat deposition in <5% of hepatocytes and grade 1−3 (which is needed for the diagnosis of NAFLD) corresponds to ≥5%. An alternate approach is to quantitatively assess steatosis using stereological point counting (SPC) – which rely on liver biopsy. However, in vivo proton magnetic resonance spectroscopy (1H-MRS) is a reliable noninvasive method that can be used to quantitatively assess total hepatic lipid content, or proton density fat fraction (PDFF).

In Paper I we compared the conventional semiquantitative histological method (grade 0-3) with SPC and 1H-MRS. We found a strong positive correlation between 1H-MRS and SPC, whereas the correlations between 1H-MRS or SPC and histopathological grading were substantially weaker. Using the widely used cut-off value of PDFF ≥5%, all participants were found to have steatosis (specificity 100%, sensitivity 53%). Reducing the cut-off value to 3% maintained 100% specificity while increasing sensitivity to 79%.

In Paper IV we evaluated quantitative steatosis, by SPC, in 106 biopsy-proven NAFLD patients during a 20-year follow-up. SPC was independently associated with an increased risk of all-cause mortality and development of T2DM. Moreover, in the 59 patients with sequential biopsies (approximately 10 years apart), a reduction of quantitative hepatic steatosis decreased the all-time risk of developing T2DM.

NASH is commonly seen as a histological feature portending a worse prognosis in NAFLD. Interestingly, no dual biopsy study has ever shown that NASH predicts fibrosis progression. Yet, NASH is seen as a surrogate marker in pharmaceutical trials – were resolution in NASH is equivalent to future resolution of fibrosis.

In Paper II we conducted a long-term follow-up study (20 years) in a large cohort of biopsy-proven NAFLD patients (n=646), in a collaboration with Karolinska Institute. We could not ascertain that NASH had any effect on all-cause, or disease-specific mortality. However, higher stages of fibrosis predicted all-cause and disease specific mortality. In Paper III, we present 129 biopsy-proven NAFLD patients, in which we had prospective, longitudinal data. They were included between 1988 and 1993. All patients alive, were re-invited 2003-2005 and 2013-2015. Dual biopsies were present in 68 patients, and three consecutive biopsies were available in 33 patients. Results showed that NAFLD is a highly heterogeneous disease, with 9.3% developing end-stage liver disease and 16% progressing to advanced stages of fibrosis without any clinically significant baseline data predicting disease progression. In summary, when using 1H-MRS as a diagnostic method for NAFLD, the diagnostic cut-off should be reduced from 5% to 3%. Furthermore, quantitative amount of hepatic steatosis could be used to stratify patients with NAFLD related to future risk of developing T2DM. Moreover, we have shown that NASH does not predict future all-cause or disease-specific mortality nor end-stage liver disease, therefore a different surrogate marker should be used in clinical trials when assessing NAFLD improvement, so to not imbue false reliance in new therapies. Lastly, we have shown that NAFLD has a more dismal prognosis than previously reported, and that it is unexpectedly difficult to predict fibrosis progression in individual NAFLD patients, emphasizing the need for robust non-invasive biomarkers suitable to monitor large number of patients.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 98
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1690
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-160523 (URN)10.3384/diss.diva-160523 (DOI)9789176850381 (ISBN)
Public defence
2019-10-25, Berzeliussalen, Building 463, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2019-09-25 Created: 2019-09-25 Last updated: 2020-02-27Bibliographically approved
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: 2019-09-25Bibliographically 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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2928-4188

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