A new detection system for serum fragmented cytokeratin 18 as a biomarker reflecting histologic activities of human nonalcoholic steatohepatitis

Iwasa, Motoh; Yamada, Minori; Tamai, Youichi; Shigefuku, Ryuta; Hasegawa, Hiroshi; Hirokawa, Yoshifumi; Hayashi, Akiko; Okuno, Koji; Nakatsuka, Takuma; Enooku, Kenichiro; Sakaguchi, Koji; Kobayashi, Yoshinao; Yamaguchi, Tetsuji; Watanabe, Masatoshi; Takei, Yoshiyuki; Nakagawa, Hayato

doi:10.1002/hep4.1971

Cited by 12 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For the MTX and non-MTX group, there was a significant relationship between the level of ALT and CK-18 levels. Many previous studies have published similar findings (31)(32)(33). Altaf et al reported that ALT levels correlated with CK-18 in a study comprising 148 NAFLD subjects in Pakistan (33).…”

Section: Discussionsupporting

confidence: 53%

Elucidating the Effects of Methotrexate Therapy on Serum Cytokeratin-18 Levels in Rheumatology

Balakrishnan¹,

Sakthiswary²,

Deborah³

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: CK-18 is a serological marker of apoptosis that has been widely associated with fibrosis and steatosis in NASH. Many studies have showed association CK-18 levels with NAFLD. To date, there is a profound lack of rheumatology studies on the effect of MTX therapy with regard to CK-18 levels. The relationship between CK-18 levels and cumulative MTX dose, MTX treatment duration, weekly MTX dose is not available in the literature. Objectives: The main purpose of this study was to determine the relationship between serum cytokeratin-18 (CK-18) and cumulative methotrexate dose in rheumatology patients on methotrexate (MTX) therapy. Besides, we studied the correlations between CK-18 and clinical parameters including age, disease duration , duration of MTX therapy, cumulative steroid dose and biochemical parameters such as alanine transaminase (ALT) and aspartate aminotransferase AST). Methods : We recruited 79 rheumatology patients on methotrexate (MTX) therapy as MTX group and 38 patients not on MTX therapy as non-MTX group . All subjects were tested for their serum CK-18 levels using an enzyme-linked immunosorbent assay (ELISA) test. We identified 20 patients with the highest CK-18 levels and 20 patients with the lowest CK-18 levels and had ultrasound liver performed on them. Results : The median serum CK-18 levels were marginally higher among the patients on MTX (1.20 ng/mL [0.19-37.15]) compared to the non-MTX group (1.17 ng/mL [0.37-34.32]). There was a significantly positive relationship between serum CK-18 levels and cumulative MTX dose (r = 0.329, p = 0.003) and total duration of MTX therapy (r = 0.284, p = 0.011). Apart from the above-mentioned variables, the CK-18 levels in MTX group significantly correlated with age (r = 0.265, p = 0.018), ALT (r = 0.440, p = <0.001) and AST (r = 0.478, p= 0.004). Ultrasound liver findings showed median CK-18 levels was higher among patients with abnormal liver findings although statistical significance was not reached. Conclusion : Among patients on MTX therapy, serum CK-18 levels correlated positively with cumulative MTX dose , total duration of MTX treatment , ALT and AST levels. These findings are preliminary and requires validation by future studies in the field of rheumatology.

show abstract

Section: Discussionsupporting

confidence: 53%

Elucidating the Effects of Methotrexate Therapy on Serum Cytokeratin-18 Levels in Rheumatology

Balakrishnan¹,

Sakthiswary²,

Deborah³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The search for alternative plasma biomarkers has increased due to the fact that serum ALT levels are not always predictive of MAFLD. Markers like caspase-generated fragmented cytokeratin 18 (fCK18), β-trophin, and adipokines like adiponectin and visfatin are currently being developed as alternatives to ALT and AST for the detection of MAFLD [35][36][37].…”

Section: Liver Disease Classificationmentioning

confidence: 99%

Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

et al. 2022

View full text Add to dashboard Cite

The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver in combination with metabolic dysfunction in the form of overweight or obesity and insulin resistance. It is also associated with an increased cardiovascular disease risk, including hypertension and atherosclerosis. Hepatic lipid metabolism is regulated by a combination of the uptake and export of fatty acids, de novo lipogenesis, and fat utilization by β-oxidation. When the balance between these pathways is altered, hepatic lipid accumulation commences, and long-term activation of inflammatory and fibrotic pathways can progress to worsen the liver disease. This review discusses the details of the molecular mechanisms regulating hepatic lipids and the emerging therapies targeting these pathways as potential future treatments for MAFLD.

show abstract

“…We conclude that these results do not suggest progressive liver injury over the course of the study. It should be noted that suggested thresholds vary quite markedly, 36 , 37 , 38 , 39 , 40 , 41 and in most studies and systematic reviews, researchers suggest that CK‐18 fragment results are viewed alongside a range of other measures (e.g. liver biopsy) to determine the degree of hepatocyte inflammation.…”

Section: Discussionmentioning

confidence: 99%

Long‐term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia

Larrey

D’Erasmo

O’Brien³

et al. 2022

Liver International

View full text Add to dashboard Cite

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor for patients with homozygous familial hypercholesterolaemia. Due to its mechanism of action, potential hepatic effects of lomitapide are of clinical interest. This study aimed to determine the long-term hepatic safety of lomitapide. Methods: Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1 years; serum total bilirubin, transaminases, cytokeratin-18 [CK-18] and enhanced liver fibrosis [ELF] score, fat-soluble vitamins and essential fatty acids), 8-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) and real-world evidence from a cohort of patients treated with lomitapide in Italy (hepatic elastography, and FIB-4 score for hepatic fibrosis).Results: In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy's law cases were detected in up to 8 years follow-up. There were no clinically relevant increases among hepatic biomarkers CK-18, CK-18 fragments or ELF score and fatsoluble vitamins and essential fatty acids remained above normal levels. In 34 patients treated in Italy with lomita pide for more than 9 years, elevations in hepatic fat were mild-to-moderate; hepatic stiffness remained normal, and the mean FIB-4 score remained below the fibrosis threshold value of 2.67. Conclusions:These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow-up.

show abstract

A new detection system for serum fragmented cytokeratin 18 as a biomarker reflecting histologic activities of human nonalcoholic steatohepatitis

Cited by 12 publications

References 31 publications

Elucidating the Effects of Methotrexate Therapy on Serum Cytokeratin-18 Levels in Rheumatology

Elucidating the Effects of Methotrexate Therapy on Serum Cytokeratin-18 Levels in Rheumatology

Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

Long‐term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia

Contact Info

Product

Resources

About