1.Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study.
Huai ZHANG ; Rafael S RIOS ; Jerome BOURSIER ; Rodolphe ANTY ; Wah-Kheong CHAN ; Jacob GEORGE ; Yusuf YILMAZ ; Vincent Wai-Sun WONG ; Jiangao FAN ; Jean-François DUFOUR ; George PAPATHEODORIDIS ; Li CHEN ; Jörn M SCHATTENBERG ; Junping SHI ; Liang XU ; Grace Lai-Hung WONG ; Naomi F LANGE ; Margarita PAPATHEODORIDI ; Yuqiang MI ; Yujie ZHOU ; Christopher D BYRNE ; Giovanni TARGHER ; Gong FENG ; Minghua ZHENG
Chinese Medical Journal 2023;136(3):341-350
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.
Humans
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Non-alcoholic Fatty Liver Disease/diagnosis*
;
Keratin-18
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Biomarkers
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Biopsy
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Hepatocytes/pathology*
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Apoptosis
;
Liver/pathology*
Result Analysis
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