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- Hagstrom, Hannes, et al.
(författare)
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Serum levels of endotrophin are associated with nonalcoholic steatohepatitis
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:4, s. 437-442
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Tidskriftsartikel (refereegranskat)abstract
- Background and aimsThere are no currently available biomarkers that can accurately indicate the presence of non-alcoholic steatohepatitis (NASH). We investigated the association between endotrophin, a cleavage product of collagen type 6α3, and disease severity in patients with non-alcoholic fatty liver disease (NAFLD).MethodsWe measured serum endotrophin levels in 211 patients with NAFLD and nine healthy controls. Liver biopsy data was available for 141 (67%) of the patients. Associations between endotrophin and the presence of NASH and advanced fibrosis were investigated alone and in combination with standard clinical parameters using logistic regression.ResultsA total of 211 patients were enrolled in this study, consisting of 108 (51%) men and 103 (49%) women with a mean age of 55.6 years. 58 (27%) of the patients had advanced fibrosis. Of those with biopsy data, 87 (62%) had NASH. Serum levels of endotrophin were significantly higher in patients with NAFLD than those in healthy controls (37[±12] vs. 17[±7] ng/mL, p<.001). Serum levels of endotrophin were also significantly higher in patients with NASH than in those without NASH (40[±12] vs. 32[±13] ng/mL, p<.001). A model using age, sex, body mass index and levels of alanine aminotransferase (ALT), glucose and endotrophin effectively predicted the presence of NASH in a derivation (AUROC 0.83, 95%CI = 0.74–0.92) and validation cohort (AUROC 0.71, 95%CI = 0.54–0.88). There was no significant association between serum levels of endotrophin and advanced fibrosis.ConclusionsThese data suggest that serum endotrophin could be a valuable biomarker for diagnosing NASH, but not for detecting advanced fibrosis in NAFLD.
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| 2. |
- Hegmar, Hannes, et al.
(författare)
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Liver stiffness predicts progression to liver-related events in patients with chronic liver disease - A cohort study of 14 414 patients
- 2024
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Ingår i: Liver international. - : WILEY. - 1478-3223 .- 1478-3231.
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterogenous populations. Methods: This Swedish multi-centre cohort study included patients (n = 14 414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C-index was used to measure discrimination of VCTE. Results: Included patients had a median age of 46 (interquartile range 34-57), median LSM of 5.9 kPa (4.6-8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow-up of 5.9 (4.3-8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM >= 25 kPa, 28.7% developed cirrhosis with portal hypertension within 5 years of follow-up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval = 37.6-62.0). VCTE had a high discriminative ability, with C-indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC. Conclusions: Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow-up and treatment decisions.
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| 4. |
- Hegmar, Hannes, et al.
(författare)
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Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD
- 2024
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796.
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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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