Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study
Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsiste...
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2023
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my.um.eprints.386462024-11-11T04:51:24Z http://eprints.um.edu.my/38646/ Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study Zhang, Huai Rios, Rafael S. Boursier, Jerome Anty, Rodolphe Chan, Wah-Kheong George, Jacob Yilmaz, Yusuf Wong, Vincent Wai-Sun Fan, Jiangao Dufour, Jean-Francois Papatheodoridis, George Chen, Li Schattenberg, Joern M. Shi, Junping Xu, Liang Wong, Grace Lai-Hung Lange, Naomi F. Papatheodoridi, Margarita Mi, Yuqiang Zhou, Yujie Byrne, Christopher D. Targher, Giovanni Feng, Gong Zheng, Minghua R Medicine (General) Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) >= 5 with a score of >= 1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS <= 2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).Results:A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference SMD]: 0.87 0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension (P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% 52%-59%]) and positive predictive value (59%) were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH. Lippincott Williams & Wilkins 2023-02 Article PeerReviewed Zhang, Huai and Rios, Rafael S. and Boursier, Jerome and Anty, Rodolphe and Chan, Wah-Kheong and George, Jacob and Yilmaz, Yusuf and Wong, Vincent Wai-Sun and Fan, Jiangao and Dufour, Jean-Francois and Papatheodoridis, George and Chen, Li and Schattenberg, Joern M. and Shi, Junping and Xu, Liang and Wong, Grace Lai-Hung and Lange, Naomi F. and Papatheodoridi, Margarita and Mi, Yuqiang and Zhou, Yujie and Byrne, Christopher D. and Targher, Giovanni and Feng, Gong and Zheng, Minghua (2023) Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study. Chinese Medical Journal, 136 (3). pp. 341-350. ISSN 03666999, DOI https://doi.org/10.1097/CM9.0000000000002603 <https://doi.org/10.1097/CM9.0000000000002603>. 10.1097/CM9.0000000000002603 |
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R Medicine (General) Zhang, Huai Rios, Rafael S. Boursier, Jerome Anty, Rodolphe Chan, Wah-Kheong George, Jacob Yilmaz, Yusuf Wong, Vincent Wai-Sun Fan, Jiangao Dufour, Jean-Francois Papatheodoridis, George Chen, Li Schattenberg, Joern M. Shi, Junping Xu, Liang Wong, Grace Lai-Hung Lange, Naomi F. Papatheodoridi, Margarita Mi, Yuqiang Zhou, Yujie Byrne, Christopher D. Targher, Giovanni Feng, Gong Zheng, Minghua Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study |
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Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) >= 5 with a score of >= 1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS <= 2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).Results:A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference SMD]: 0.87 0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension (P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% 52%-59%]) and positive predictive value (59%) were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH. |
| format |
Article |
| author |
Zhang, Huai Rios, Rafael S. Boursier, Jerome Anty, Rodolphe Chan, Wah-Kheong George, Jacob Yilmaz, Yusuf Wong, Vincent Wai-Sun Fan, Jiangao Dufour, Jean-Francois Papatheodoridis, George Chen, Li Schattenberg, Joern M. Shi, Junping Xu, Liang Wong, Grace Lai-Hung Lange, Naomi F. Papatheodoridi, Margarita Mi, Yuqiang Zhou, Yujie Byrne, Christopher D. Targher, Giovanni Feng, Gong Zheng, Minghua |
| author_facet |
Zhang, Huai Rios, Rafael S. Boursier, Jerome Anty, Rodolphe Chan, Wah-Kheong George, Jacob Yilmaz, Yusuf Wong, Vincent Wai-Sun Fan, Jiangao Dufour, Jean-Francois Papatheodoridis, George Chen, Li Schattenberg, Joern M. Shi, Junping Xu, Liang Wong, Grace Lai-Hung Lange, Naomi F. Papatheodoridi, Margarita Mi, Yuqiang Zhou, Yujie Byrne, Christopher D. Targher, Giovanni Feng, Gong Zheng, Minghua |
| author_sort |
Zhang, Huai |
| title |
Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study |
| title_short |
Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study |
| title_full |
Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study |
| title_fullStr |
Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study |
| title_full_unstemmed |
Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: An international registry study |
| title_sort |
hepatocyte apoptosis fragment product cytokeratin-18 m30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study |
| publisher |
Lippincott Williams & Wilkins |
| publishDate |
2023 |
| url |
http://eprints.um.edu.my/38646/ |
| _version_ |
1816130403872800768 |
| score |
13.244413 |