Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining
Autor: | Masayuki Mizuno, Tsuyoshi Iwasaki, Takeshi Okanoue, Kazuto Yamazaki, Junji Ichihara, Toshihide Shima, Hayao Ebise, Keito Yoshimura |
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Rok vydání: | 2015 |
Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Pathology Cirrhosis digestive system Gastroenterology 03 medical and health sciences 0302 clinical medicine Non-alcoholic Fatty Liver Disease Fibrosis Internal medicine Nonalcoholic fatty liver disease medicine Data Mining Humans Prospective Studies Hepatology medicine.diagnostic_test business.industry nutritional and metabolic diseases Middle Aged medicine.disease digestive system diseases 030220 oncology & carcinogenesis Liver biopsy Hepatocellular carcinoma Biomarker (medicine) Female 030211 gastroenterology & hepatology Steatosis business Biomarkers |
Zdroj: | Hepatology. 63:462-473 |
ISSN: | 1527-3350 0270-9139 |
DOI: | 10.1002/hep.28226 |
Popis: | It is important that patients with nonalcoholic steatohepatitis (NASH) are diagnosed and treated early to prevent serious complications, such as liver cirrhosis or hepatocellular carcinoma. However, current methods for NASH diagnosis are invasive given that they rely on liver biopsy, making early diagnosis difficult. In this study, we developed novel noninvasive markers for the diagnosis of NASH and NASH-related fibrosis. A total of 132 Japanese patients with nonalcoholic fatty liver disease were included in this study. Blood samples were collected, and 261 biomolecules were quantified in serum. Using cluster and pathway analyses, we identified biomolecule modules connected to biological events that occur with disease progression to NASH. The modules were used as variables for diagnosis, leading to a NASH diagnostic marker associated with two biological events, that is, protective response to hepatic steatosis and hepatitis-causing innate immune response. Regarding the NASH-related fibrosis marker, immunological responses to hepatocyte injury were identified as a biological event. To develop diagnostic markers for NASH and NASH-related fibrosis, specific biomolecules were selected from each biomolecule module. The former marker was obtained by averaging the levels of four biomolecules, whereas the latter was obtained by averaging the levels of two biomolecules. Both markers achieved a diagnostic accuracy of almost 0.9 of the area under the receiver operating characteristic curve, and the latter exhibited equivalent performance in an independent group of 62 prospectively recruited patients. Conclusion: We developed highly accurate markers for the diagnosis of both NASH and NASH-related fibrosis (i.e., FM-NASH index and FM-fibro index, respectively). These markers may be used as an alternative diagnostic tool to liver biopsy. (Hepatology 2016;63:462–473) |
Databáze: | OpenAIRE |
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