Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients

Maher, Mohamed; Ibrahim, Wesam A.; Saleh, Shereen A.; Shash, Lobna S; Gabal, Hoda Abou; Tarif, Mohammed; Gamal, Mohammed

doi:10.1016/j.ejmhg.2014.11.003

Cited by 12 publications

(6 citation statements)

References 21 publications

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“…Our findings are consistent with prior work showing that 7 days of treadmill walking at ∼85% of HR max caused a significant decrease in CK18 in obese adults with non-alcoholic fatty liver disease independent of weight loss (Fealy et al, 2012). Lower CK18 may improve with EX + SC through decreased oxidative stress, hepatic triglyceride stores, or Mallory bodies (Schweizer et al, 2006;Maher et al, 2015). Why SC in contrast had increased plasma CK18 is unclear given the metabolic control prior to testing.…”

Section: Discussionsupporting

confidence: 89%

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Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery

et al. 2020

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Section: Discussionsupporting

confidence: 89%

“…In contrast, CK18 had a robust lowering effect to our EX + SC treatment. CK18 is a biomarker of hepatocyte apoptosis that predicts and correlates to the development of hepatic inflammation, fibrosis, as well as nonalcoholic steatohepatitis (Maher et al, 2015). EX + SC decreased CK18 by 23.6% compared to an 11.6% increase with SC.…”

Section: Discussionmentioning

confidence: 99%

Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery

et al. 2020

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“… 33 Optimal cut‐off‐points of serum CK‐18 fragments suggested for NAFLD and definite NASH range from 230 to 270 U/L, respectively. 34 , 35 At no time point did the mean CK‐18 fragments levels exceed these thresholds in our analysis. Mean increases were noted in CK‐18, and CK‐18 fragments versus baseline but these increases did not continue to increase over time.…”

Section: Discussionmentioning

confidence: 62%

Long‐term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia

Larrey

D’Erasmo

O’Brien³

et al. 2022

Liver International

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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.

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“…Of note, only a small percentage (7.9%) of the non-MTX group were diabetics. Maher et al revealed significant positive correlation between CK-18 and HbA1c (35). Some authors consistently reported the same despite ethnic variations across the studies (36)(37)(38).…”

Section: Discussionmentioning

confidence: 84%

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

Balakrishnan¹,

Sakthiswary²,

Deborah³

et al. 2023

Preprint

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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.

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Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients

Cited by 12 publications

References 21 publications

Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery

Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery

Long‐term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia

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

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