IDDF2022-ABS-0120 Hepatocyte apoptosis fragment product cytokeratin-18 M30 and non-alcoholic steatohepatitis risk prediction: an international registry study
BackgroundLiver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in predicting NASH, but results across studies have been inconsistent. The ai...
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creator | Zhang, Huai Rios, Rafael S Boursier, Jerome Anty, Rodolphe Chan, Wah-Kheong George, Jacob Yilmaz, Yusuf Wong, Vincent Wai-Sun Sookoian, Silvia Fan, Jian-Gao Dufour, Jean-François Papatheodoridis, George Chen, Li Schattenberg, Jörn M Shi, Jun-Ping Xu, Liang Wong, Grace Lai-Hung Pirola, Carlos J Lange, Naomi F Papatheodoridi, Margarita Mi, Yu-Qiang Zhou, Yu-Jie Byrne, Christopher D Targher, Giovanni Feng, Gong Zheng, Ming-Hua |
description | BackgroundLiver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in predicting NASH, but results across studies have been inconsistent. The aim of this study was to identify the feasibility of CK-18 M30 concentrations as a non-invasive alternative to liver biopsy for diagnosing NASH.MethodsUsing an open online reporting form, individual data were collected from 15 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients circulating CK-18 M30 levels were measured. These data included sex, age, ethnic, hypertension, diabetes, and serum alanine aminotransferase, but not personal health identifier. Individuals with NAFLD activity score (NAS) ≥ 5 including a score of ≥ 1 for each of steatosis, ballooning and lobular inflammation were diagnosed as having definite NASH; individuals with NAS ≤ 2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL) (simple steatosis). (IDDF2022-ABS-0120 Table 1, IDDF2022-ABS-0120 Table 2).Abstract IDDF2022-ABS-0120 Table 1Main patient characteristics of the included cohorts Center Country Age range, (mean) years Number (%) Men, n (%) NASH, n (%) Ln CK-18 M30 (mean±SD) U/L Angers (France) France 21–79 (56.4) 199 (18.4) 104 (52.3) 175 (87.9) 5.75±0.752 Buenos Aires (Argentina) Argentina 18–78 (53.7) 75 (6.9) 23 (30.7) 56 (74.7) 5.66±0.408 Athens (Greece) Greece 19–72 (46.1) 42 (3.9) 22 (52.4) 17 (40.5) 5.48±0.608 Sydney (Australia) Australia 17–79 (47.8) 62 (5.7) 34 (54.8) 32 (51.6) 5.26±1.141 Mainz (Germany) Germany 25–61 (42.7) 7 (0.6) 5 (71.4) 7 (100.0) 6.64±1.088 Hanzhou (China) China 24–70 (41.2) 30 (2.8) 23 (76.7) 30 (100.0) 5.33±0.761 Hong Kong (China) China 26–70 (46.9) 58 (5.4) 36 (62.1) 33 (56.9) 5.97±0.862 Kuala Lumpur (Malaysia) Malaysia 26–68 (50.6) 90 (8.3) 41 (45.6) 82 (91.1) 6.26±0.764 Nice (France) France 21–62 (42.6) 48 (4.4) 10 (20.8) 43 (89.6) 5.88±0.589 Shanghai Ruijin (China) China 21–70 (49.7) 34 (3.1) 20 (58.8) 34 (100.0) 5.35±0.765 Shanghai Xinhua (China) China 18–66 (39.1) 31 (2.9) 22 (71.0) 24 (77.4) 5.90±0.589 Bern (Switzerland) Switzerland 28–75 (55.3) 31 (2.9) 12 (38.7) 28 (90.3) 5.63±0.558 Tianjin (China) China 18–62 (38.4) 17 (1.6) 9 (52.9) 17 (100.0) 5.25±0.977 Istanbul (Turkey) Turkey 29–70 (48.8) 110 (10.2) 58 (52.7) 101 (91.8) 4.80±1.015 Wenzhou (China) China 12–71 (38. |
doi_str_mv | 10.1136/gutjnl-2022-IDDF.99 |
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Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in predicting NASH, but results across studies have been inconsistent. The aim of this study was to identify the feasibility of CK-18 M30 concentrations as a non-invasive alternative to liver biopsy for diagnosing NASH.MethodsUsing an open online reporting form, individual data were collected from 15 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients circulating CK-18 M30 levels were measured. These data included sex, age, ethnic, hypertension, diabetes, and serum alanine aminotransferase, but not personal health identifier. Individuals with NAFLD activity score (NAS) ≥ 5 including a score of ≥ 1 for each of steatosis, ballooning and lobular inflammation were diagnosed as having definite NASH; individuals with NAS ≤ 2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL) (simple steatosis). (IDDF2022-ABS-0120 Table 1, IDDF2022-ABS-0120 Table 2).Abstract IDDF2022-ABS-0120 Table 1Main patient characteristics of the included cohorts Center Country Age range, (mean) years Number (%) Men, n (%) NASH, n (%) Ln CK-18 M30 (mean±SD) U/L Angers (France) France 21–79 (56.4) 199 (18.4) 104 (52.3) 175 (87.9) 5.75±0.752 Buenos Aires (Argentina) Argentina 18–78 (53.7) 75 (6.9) 23 (30.7) 56 (74.7) 5.66±0.408 Athens (Greece) Greece 19–72 (46.1) 42 (3.9) 22 (52.4) 17 (40.5) 5.48±0.608 Sydney (Australia) Australia 17–79 (47.8) 62 (5.7) 34 (54.8) 32 (51.6) 5.26±1.141 Mainz (Germany) Germany 25–61 (42.7) 7 (0.6) 5 (71.4) 7 (100.0) 6.64±1.088 Hanzhou (China) China 24–70 (41.2) 30 (2.8) 23 (76.7) 30 (100.0) 5.33±0.761 Hong Kong (China) China 26–70 (46.9) 58 (5.4) 36 (62.1) 33 (56.9) 5.97±0.862 Kuala Lumpur (Malaysia) Malaysia 26–68 (50.6) 90 (8.3) 41 (45.6) 82 (91.1) 6.26±0.764 Nice (France) France 21–62 (42.6) 48 (4.4) 10 (20.8) 43 (89.6) 5.88±0.589 Shanghai Ruijin (China) China 21–70 (49.7) 34 (3.1) 20 (58.8) 34 (100.0) 5.35±0.765 Shanghai Xinhua (China) China 18–66 (39.1) 31 (2.9) 22 (71.0) 24 (77.4) 5.90±0.589 Bern (Switzerland) Switzerland 28–75 (55.3) 31 (2.9) 12 (38.7) 28 (90.3) 5.63±0.558 Tianjin (China) China 18–62 (38.4) 17 (1.6) 9 (52.9) 17 (100.0) 5.25±0.977 Istanbul (Turkey) Turkey 29–70 (48.8) 110 (10.2) 58 (52.7) 101 (91.8) 4.80±1.015 Wenzhou (China) China 12–71 (38.4) 249 (23.0) 81 (32.5) 232 (93.2) 5.49±1.124 Total / 12–79 (47.3) 1083 (100) 500 (46.2) 911 (84.1) 5.58±0.958 Abstract IDDF2022-ABS-0120 Table 2Histological Characteristics of Patients Factor All patients (N=1083) NAFL (N=172) NASH (N=911) Steatosis, n (%) 1 (5–33%) 209 (19.3) 145 (84.3) 64 (7.0) 2 (33–66%) 336 (31.0) 27 (15.7) 309 (33.9) 3 (>66%) 538 (49.7) 0 538 (59.1) Lobular inflammation, n (%) 0 142 (13.1) 142 (82.6) 0 1 488 (45.1) 30 (17.4) 458 (50.3) 2 408 (37.7) 0 408 (44.8) 3 45 (4.2) 0 45 (4.9) Ballooning, n (%) 0 149 (13.8) 149 (86.6) 0 1 429 (39.6) 23 (13.4) 406 (44.6) 2 505 (46.6) 0 505 (55.4) Fibrosis, n (%) 0 291 (26.9) 172 (100.0) 119 (13.1) 1 356 (32.9) 0 356 (39.1) 2 213 (19.7) 0 213 (23.4) 3 168 (15.5) 0 168 (18.4) 4 55 (5.1) 0 55 (6.0) Results2716 participants were screened and 1083 participants (172 with NAFL and 911 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 150 U/L; standardized mean difference: 0.78 [0.62–0.95]), and there was interaction between CK-18 levels and serum alanine aminotransferase (P<0.001). CK-18 M30 levels were positively associated with histological NAS in most centers. The AUROC for NASH was 0.728 (95% CI: 0.691–0.764) and the Youden index was 275.7 U/L for CK-18 M30 (IDDF2022-ABS-0120 Figure 1. Diagnostic performances of CK-18 M30 level at the optimal cut-off value of 275.7 U/L. (A) Sensitivity in registry center. (B) Specificity in registry center. (C) Sensitivity in main characteristics subgroup. (D) Specificity in main characteristics subgroup). Sensitivity (54% [51–58%]) and positive predictive value (52%) were both not ideal.Abstract IDDF2022-ABS-0120 Figure 1ConclusionsThis large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for predicting NASH.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2022-IDDF.99</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Alanine ; Alanine transaminase ; Apoptosis ; Balloon treatment ; Biopsy ; Clinical Hepatology ; Cytokeratin ; Diabetes mellitus ; Fatty liver ; Fibrosis ; Inflammation ; Liver ; Liver diseases ; Sampling error ; Steatosis</subject><ispartof>Gut, 2022-09, Vol.71 (Suppl 2), p.A79-A80</ispartof><rights>Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2022 Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Zhang, Huai</creatorcontrib><creatorcontrib>Rios, Rafael S</creatorcontrib><creatorcontrib>Boursier, Jerome</creatorcontrib><creatorcontrib>Anty, Rodolphe</creatorcontrib><creatorcontrib>Chan, Wah-Kheong</creatorcontrib><creatorcontrib>George, Jacob</creatorcontrib><creatorcontrib>Yilmaz, Yusuf</creatorcontrib><creatorcontrib>Wong, Vincent Wai-Sun</creatorcontrib><creatorcontrib>Sookoian, Silvia</creatorcontrib><creatorcontrib>Fan, Jian-Gao</creatorcontrib><creatorcontrib>Dufour, Jean-François</creatorcontrib><creatorcontrib>Papatheodoridis, George</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Schattenberg, Jörn M</creatorcontrib><creatorcontrib>Shi, Jun-Ping</creatorcontrib><creatorcontrib>Xu, Liang</creatorcontrib><creatorcontrib>Wong, Grace Lai-Hung</creatorcontrib><creatorcontrib>Pirola, Carlos J</creatorcontrib><creatorcontrib>Lange, Naomi F</creatorcontrib><creatorcontrib>Papatheodoridi, Margarita</creatorcontrib><creatorcontrib>Mi, Yu-Qiang</creatorcontrib><creatorcontrib>Zhou, Yu-Jie</creatorcontrib><creatorcontrib>Byrne, Christopher D</creatorcontrib><creatorcontrib>Targher, Giovanni</creatorcontrib><creatorcontrib>Feng, Gong</creatorcontrib><creatorcontrib>Zheng, Ming-Hua</creatorcontrib><title>IDDF2022-ABS-0120 Hepatocyte apoptosis fragment product cytokeratin-18 M30 and non-alcoholic steatohepatitis risk prediction: an international registry study</title><title>Gut</title><addtitle>Gut</addtitle><description>BackgroundLiver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in predicting NASH, but results across studies have been inconsistent. The aim of this study was to identify the feasibility of CK-18 M30 concentrations as a non-invasive alternative to liver biopsy for diagnosing NASH.MethodsUsing an open online reporting form, individual data were collected from 15 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients circulating CK-18 M30 levels were measured. These data included sex, age, ethnic, hypertension, diabetes, and serum alanine aminotransferase, but not personal health identifier. Individuals with NAFLD activity score (NAS) ≥ 5 including a score of ≥ 1 for each of steatosis, ballooning and lobular inflammation were diagnosed as having definite NASH; individuals with NAS ≤ 2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL) (simple steatosis). (IDDF2022-ABS-0120 Table 1, IDDF2022-ABS-0120 Table 2).Abstract IDDF2022-ABS-0120 Table 1Main patient characteristics of the included cohorts Center Country Age range, (mean) years Number (%) Men, n (%) NASH, n (%) Ln CK-18 M30 (mean±SD) U/L Angers (France) France 21–79 (56.4) 199 (18.4) 104 (52.3) 175 (87.9) 5.75±0.752 Buenos Aires (Argentina) Argentina 18–78 (53.7) 75 (6.9) 23 (30.7) 56 (74.7) 5.66±0.408 Athens (Greece) Greece 19–72 (46.1) 42 (3.9) 22 (52.4) 17 (40.5) 5.48±0.608 Sydney (Australia) Australia 17–79 (47.8) 62 (5.7) 34 (54.8) 32 (51.6) 5.26±1.141 Mainz (Germany) Germany 25–61 (42.7) 7 (0.6) 5 (71.4) 7 (100.0) 6.64±1.088 Hanzhou (China) China 24–70 (41.2) 30 (2.8) 23 (76.7) 30 (100.0) 5.33±0.761 Hong Kong (China) China 26–70 (46.9) 58 (5.4) 36 (62.1) 33 (56.9) 5.97±0.862 Kuala Lumpur (Malaysia) Malaysia 26–68 (50.6) 90 (8.3) 41 (45.6) 82 (91.1) 6.26±0.764 Nice (France) France 21–62 (42.6) 48 (4.4) 10 (20.8) 43 (89.6) 5.88±0.589 Shanghai Ruijin (China) China 21–70 (49.7) 34 (3.1) 20 (58.8) 34 (100.0) 5.35±0.765 Shanghai Xinhua (China) China 18–66 (39.1) 31 (2.9) 22 (71.0) 24 (77.4) 5.90±0.589 Bern (Switzerland) Switzerland 28–75 (55.3) 31 (2.9) 12 (38.7) 28 (90.3) 5.63±0.558 Tianjin (China) China 18–62 (38.4) 17 (1.6) 9 (52.9) 17 (100.0) 5.25±0.977 Istanbul (Turkey) Turkey 29–70 (48.8) 110 (10.2) 58 (52.7) 101 (91.8) 4.80±1.015 Wenzhou (China) China 12–71 (38.4) 249 (23.0) 81 (32.5) 232 (93.2) 5.49±1.124 Total / 12–79 (47.3) 1083 (100) 500 (46.2) 911 (84.1) 5.58±0.958 Abstract IDDF2022-ABS-0120 Table 2Histological Characteristics of Patients Factor All patients (N=1083) NAFL (N=172) NASH (N=911) Steatosis, n (%) 1 (5–33%) 209 (19.3) 145 (84.3) 64 (7.0) 2 (33–66%) 336 (31.0) 27 (15.7) 309 (33.9) 3 (>66%) 538 (49.7) 0 538 (59.1) Lobular inflammation, n (%) 0 142 (13.1) 142 (82.6) 0 1 488 (45.1) 30 (17.4) 458 (50.3) 2 408 (37.7) 0 408 (44.8) 3 45 (4.2) 0 45 (4.9) Ballooning, n (%) 0 149 (13.8) 149 (86.6) 0 1 429 (39.6) 23 (13.4) 406 (44.6) 2 505 (46.6) 0 505 (55.4) Fibrosis, n (%) 0 291 (26.9) 172 (100.0) 119 (13.1) 1 356 (32.9) 0 356 (39.1) 2 213 (19.7) 0 213 (23.4) 3 168 (15.5) 0 168 (18.4) 4 55 (5.1) 0 55 (6.0) Results2716 participants were screened and 1083 participants (172 with NAFL and 911 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 150 U/L; standardized mean difference: 0.78 [0.62–0.95]), and there was interaction between CK-18 levels and serum alanine aminotransferase (P<0.001). CK-18 M30 levels were positively associated with histological NAS in most centers. The AUROC for NASH was 0.728 (95% CI: 0.691–0.764) and the Youden index was 275.7 U/L for CK-18 M30 (IDDF2022-ABS-0120 Figure 1. Diagnostic performances of CK-18 M30 level at the optimal cut-off value of 275.7 U/L. (A) Sensitivity in registry center. (B) Specificity in registry center. (C) Sensitivity in main characteristics subgroup. (D) Specificity in main characteristics subgroup). Sensitivity (54% [51–58%]) and positive predictive value (52%) were both not ideal.Abstract IDDF2022-ABS-0120 Figure 1ConclusionsThis large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for predicting NASH.</description><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Apoptosis</subject><subject>Balloon treatment</subject><subject>Biopsy</subject><subject>Clinical Hepatology</subject><subject>Cytokeratin</subject><subject>Diabetes mellitus</subject><subject>Fatty liver</subject><subject>Fibrosis</subject><subject>Inflammation</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Sampling error</subject><subject>Steatosis</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpFkUtOwzAQhi0EEqVwAjaWWJt64iS22fGmEogF3UdO7LQuwS6xs-iODefgbpwEhyKxGs3M_3-aB0KnQM8BWDlbDnHtOpLRLCPzm5u7cyn30ATyUhCWCbGPJpQCJwXP5SE6CmFNKRVCwgR9jfJf3-XVC6GQ0e-PzwezUdE322iw2vhN9MEG3PZq-WZcxJve66GJOPX9q-lVtI6AwE-MYuU0dt4R1TV-5Tvb4BBNQq1GoI2J0tvwmghG2yZa7y6SBVsXTe_UmKsO92ZpQ-y3yTro7TE6aFUXzMlfnKLF3e3i-oE8Pt_Pry8fSV0KTrjWAhQvS11wZlhtRJFDWVMQvClbbgqhJLSNhFQQmTYlg0ZpwWpgRc4FY1N0tsOm5d4HE2K19kOaqQtVxgFoxoTkSTXbqeq39b8AaDU-odo9oRqPWY1XraRkPw3kfmY</recordid><startdate>20220902</startdate><enddate>20220902</enddate><creator>Zhang, Huai</creator><creator>Rios, Rafael S</creator><creator>Boursier, Jerome</creator><creator>Anty, Rodolphe</creator><creator>Chan, Wah-Kheong</creator><creator>George, Jacob</creator><creator>Yilmaz, Yusuf</creator><creator>Wong, Vincent Wai-Sun</creator><creator>Sookoian, Silvia</creator><creator>Fan, Jian-Gao</creator><creator>Dufour, Jean-François</creator><creator>Papatheodoridis, George</creator><creator>Chen, Li</creator><creator>Schattenberg, Jörn M</creator><creator>Shi, Jun-Ping</creator><creator>Xu, Liang</creator><creator>Wong, Grace Lai-Hung</creator><creator>Pirola, Carlos J</creator><creator>Lange, Naomi F</creator><creator>Papatheodoridi, Margarita</creator><creator>Mi, Yu-Qiang</creator><creator>Zhou, Yu-Jie</creator><creator>Byrne, Christopher D</creator><creator>Targher, Giovanni</creator><creator>Feng, Gong</creator><creator>Zheng, Ming-Hua</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ Publishing Group LTD</general><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20220902</creationdate><title>IDDF2022-ABS-0120 Hepatocyte apoptosis fragment product cytokeratin-18 M30 and non-alcoholic steatohepatitis risk prediction: an international registry study</title><author>Zhang, Huai ; Rios, Rafael S ; Boursier, Jerome ; Anty, Rodolphe ; Chan, Wah-Kheong ; George, Jacob ; Yilmaz, Yusuf ; Wong, Vincent Wai-Sun ; Sookoian, Silvia ; Fan, Jian-Gao ; Dufour, Jean-François ; Papatheodoridis, George ; Chen, Li ; Schattenberg, Jörn M ; Shi, Jun-Ping ; Xu, Liang ; Wong, Grace Lai-Hung ; Pirola, Carlos J ; Lange, Naomi F ; Papatheodoridi, Margarita ; Mi, Yu-Qiang ; Zhou, Yu-Jie ; Byrne, Christopher D ; Targher, Giovanni ; Feng, Gong ; Zheng, Ming-Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b687-7dd81a766d573e3be85416b0187c6f7e58a91fc9118782de631cad83b13547833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alanine</topic><topic>Alanine transaminase</topic><topic>Apoptosis</topic><topic>Balloon treatment</topic><topic>Biopsy</topic><topic>Clinical Hepatology</topic><topic>Cytokeratin</topic><topic>Diabetes mellitus</topic><topic>Fatty liver</topic><topic>Fibrosis</topic><topic>Inflammation</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Sampling error</topic><topic>Steatosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Huai</creatorcontrib><creatorcontrib>Rios, Rafael S</creatorcontrib><creatorcontrib>Boursier, Jerome</creatorcontrib><creatorcontrib>Anty, Rodolphe</creatorcontrib><creatorcontrib>Chan, Wah-Kheong</creatorcontrib><creatorcontrib>George, Jacob</creatorcontrib><creatorcontrib>Yilmaz, Yusuf</creatorcontrib><creatorcontrib>Wong, Vincent Wai-Sun</creatorcontrib><creatorcontrib>Sookoian, Silvia</creatorcontrib><creatorcontrib>Fan, Jian-Gao</creatorcontrib><creatorcontrib>Dufour, Jean-François</creatorcontrib><creatorcontrib>Papatheodoridis, George</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Schattenberg, Jörn M</creatorcontrib><creatorcontrib>Shi, Jun-Ping</creatorcontrib><creatorcontrib>Xu, Liang</creatorcontrib><creatorcontrib>Wong, Grace Lai-Hung</creatorcontrib><creatorcontrib>Pirola, Carlos J</creatorcontrib><creatorcontrib>Lange, Naomi F</creatorcontrib><creatorcontrib>Papatheodoridi, Margarita</creatorcontrib><creatorcontrib>Mi, Yu-Qiang</creatorcontrib><creatorcontrib>Zhou, Yu-Jie</creatorcontrib><creatorcontrib>Byrne, Christopher D</creatorcontrib><creatorcontrib>Targher, Giovanni</creatorcontrib><creatorcontrib>Feng, Gong</creatorcontrib><creatorcontrib>Zheng, Ming-Hua</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Huai</au><au>Rios, Rafael S</au><au>Boursier, Jerome</au><au>Anty, Rodolphe</au><au>Chan, Wah-Kheong</au><au>George, Jacob</au><au>Yilmaz, Yusuf</au><au>Wong, Vincent Wai-Sun</au><au>Sookoian, Silvia</au><au>Fan, Jian-Gao</au><au>Dufour, Jean-François</au><au>Papatheodoridis, George</au><au>Chen, Li</au><au>Schattenberg, Jörn M</au><au>Shi, Jun-Ping</au><au>Xu, Liang</au><au>Wong, Grace Lai-Hung</au><au>Pirola, Carlos J</au><au>Lange, Naomi F</au><au>Papatheodoridi, Margarita</au><au>Mi, Yu-Qiang</au><au>Zhou, Yu-Jie</au><au>Byrne, Christopher D</au><au>Targher, Giovanni</au><au>Feng, Gong</au><au>Zheng, Ming-Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IDDF2022-ABS-0120 Hepatocyte apoptosis fragment product cytokeratin-18 M30 and non-alcoholic steatohepatitis risk prediction: an international registry study</atitle><jtitle>Gut</jtitle><stitle>Gut</stitle><date>2022-09-02</date><risdate>2022</risdate><volume>71</volume><issue>Suppl 2</issue><spage>A79</spage><epage>A80</epage><pages>A79-A80</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><abstract>BackgroundLiver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in predicting NASH, but results across studies have been inconsistent. The aim of this study was to identify the feasibility of CK-18 M30 concentrations as a non-invasive alternative to liver biopsy for diagnosing NASH.MethodsUsing an open online reporting form, individual data were collected from 15 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients circulating CK-18 M30 levels were measured. These data included sex, age, ethnic, hypertension, diabetes, and serum alanine aminotransferase, but not personal health identifier. Individuals with NAFLD activity score (NAS) ≥ 5 including a score of ≥ 1 for each of steatosis, ballooning and lobular inflammation were diagnosed as having definite NASH; individuals with NAS ≤ 2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL) (simple steatosis). (IDDF2022-ABS-0120 Table 1, IDDF2022-ABS-0120 Table 2).Abstract IDDF2022-ABS-0120 Table 1Main patient characteristics of the included cohorts Center Country Age range, (mean) years Number (%) Men, n (%) NASH, n (%) Ln CK-18 M30 (mean±SD) U/L Angers (France) France 21–79 (56.4) 199 (18.4) 104 (52.3) 175 (87.9) 5.75±0.752 Buenos Aires (Argentina) Argentina 18–78 (53.7) 75 (6.9) 23 (30.7) 56 (74.7) 5.66±0.408 Athens (Greece) Greece 19–72 (46.1) 42 (3.9) 22 (52.4) 17 (40.5) 5.48±0.608 Sydney (Australia) Australia 17–79 (47.8) 62 (5.7) 34 (54.8) 32 (51.6) 5.26±1.141 Mainz (Germany) Germany 25–61 (42.7) 7 (0.6) 5 (71.4) 7 (100.0) 6.64±1.088 Hanzhou (China) China 24–70 (41.2) 30 (2.8) 23 (76.7) 30 (100.0) 5.33±0.761 Hong Kong (China) China 26–70 (46.9) 58 (5.4) 36 (62.1) 33 (56.9) 5.97±0.862 Kuala Lumpur (Malaysia) Malaysia 26–68 (50.6) 90 (8.3) 41 (45.6) 82 (91.1) 6.26±0.764 Nice (France) France 21–62 (42.6) 48 (4.4) 10 (20.8) 43 (89.6) 5.88±0.589 Shanghai Ruijin (China) China 21–70 (49.7) 34 (3.1) 20 (58.8) 34 (100.0) 5.35±0.765 Shanghai Xinhua (China) China 18–66 (39.1) 31 (2.9) 22 (71.0) 24 (77.4) 5.90±0.589 Bern (Switzerland) Switzerland 28–75 (55.3) 31 (2.9) 12 (38.7) 28 (90.3) 5.63±0.558 Tianjin (China) China 18–62 (38.4) 17 (1.6) 9 (52.9) 17 (100.0) 5.25±0.977 Istanbul (Turkey) Turkey 29–70 (48.8) 110 (10.2) 58 (52.7) 101 (91.8) 4.80±1.015 Wenzhou (China) China 12–71 (38.4) 249 (23.0) 81 (32.5) 232 (93.2) 5.49±1.124 Total / 12–79 (47.3) 1083 (100) 500 (46.2) 911 (84.1) 5.58±0.958 Abstract IDDF2022-ABS-0120 Table 2Histological Characteristics of Patients Factor All patients (N=1083) NAFL (N=172) NASH (N=911) Steatosis, n (%) 1 (5–33%) 209 (19.3) 145 (84.3) 64 (7.0) 2 (33–66%) 336 (31.0) 27 (15.7) 309 (33.9) 3 (>66%) 538 (49.7) 0 538 (59.1) Lobular inflammation, n (%) 0 142 (13.1) 142 (82.6) 0 1 488 (45.1) 30 (17.4) 458 (50.3) 2 408 (37.7) 0 408 (44.8) 3 45 (4.2) 0 45 (4.9) Ballooning, n (%) 0 149 (13.8) 149 (86.6) 0 1 429 (39.6) 23 (13.4) 406 (44.6) 2 505 (46.6) 0 505 (55.4) Fibrosis, n (%) 0 291 (26.9) 172 (100.0) 119 (13.1) 1 356 (32.9) 0 356 (39.1) 2 213 (19.7) 0 213 (23.4) 3 168 (15.5) 0 168 (18.4) 4 55 (5.1) 0 55 (6.0) Results2716 participants were screened and 1083 participants (172 with NAFL and 911 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 150 U/L; standardized mean difference: 0.78 [0.62–0.95]), and there was interaction between CK-18 levels and serum alanine aminotransferase (P<0.001). CK-18 M30 levels were positively associated with histological NAS in most centers. The AUROC for NASH was 0.728 (95% CI: 0.691–0.764) and the Youden index was 275.7 U/L for CK-18 M30 (IDDF2022-ABS-0120 Figure 1. Diagnostic performances of CK-18 M30 level at the optimal cut-off value of 275.7 U/L. (A) Sensitivity in registry center. (B) Specificity in registry center. (C) Sensitivity in main characteristics subgroup. (D) Specificity in main characteristics subgroup). Sensitivity (54% [51–58%]) and positive predictive value (52%) were both not ideal.Abstract IDDF2022-ABS-0120 Figure 1ConclusionsThis large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for predicting NASH.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><doi>10.1136/gutjnl-2022-IDDF.99</doi></addata></record> |
fulltext | fulltext |
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ispartof | Gut, 2022-09, Vol.71 (Suppl 2), p.A79-A80 |
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language | eng |
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source | PubMed Central |
subjects | Alanine Alanine transaminase Apoptosis Balloon treatment Biopsy Clinical Hepatology Cytokeratin Diabetes mellitus Fatty liver Fibrosis Inflammation Liver Liver diseases Sampling error Steatosis |
title | IDDF2022-ABS-0120 Hepatocyte apoptosis fragment product cytokeratin-18 M30 and non-alcoholic steatohepatitis risk prediction: an international registry study |
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