Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis in chronic hepatitis B

Abstract

Cell death markers, M65 and M30, have been suggested to be sensitive markers of liver inflammation and fibrosis in nonalcoholic fatty liver disease and chronic hepatitis C. Our aim was to investigate whether these markers were useful in diagnosing liver inflammation and fibrosis in chronic hepatitis B (CHB).We examined 186 patients with CHB; 18 sex- and age-matched healthy subjects were controls. The blood samples were collected from CHB patients within 1 week before or after liver biopsy. According to METAVIR score system, liver inflammation was graded from A0 to A3, and fibrosis from F0 to F4.Serum M65 and M30 levels were in parallel with the grades of liver inflammation. M65, not M30, increased significantly in patients with severe inflammation and normal alanine aminotransferase. M65 is one of the independent predictors of severe liver inflammation (≥A2). The levels of M65 and M30 levels significantly increased in parallel with the degree of inflammation in F1 patients, whereas they showed no statistical difference between different stages of fibrosis in A1 patients.Serum M65 is a useful indicator of liver inflammation in CHB patients. Serum M65, not M30, is valuable in the grading of liver fibrosis.

Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals

“…To date, non-invasive approaches by either laboratory or imaging modalities have become the mainstream in assessing histological liver fibrosis. However, there has been the lack of reliable laboratory biomarkers to detect “subclinical microscopic hepatic necro-inflammation” 33–36 . Therefore, according to the physicians’ discretion, liver biopsy should be considered seriously at least in selected cases with specific host and viral factors 34,37 .…”

Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives

“…However, in end stage of AALF, ccK18 levels decreased throughout the liver while it persisted in circulation at levels exceeding those in healthy controls, suggesting that ccK18 is not of hepatic origin (Possamai et al, 2013). Other diseases were also associated with elevated M30 and M65 levels, such as non-small-cell lung cancer, biliary tract cancer, chronic hepatitis B (CHB), hepatitis C virus (HCV), and nonalcoholic fatty liver disease (NAFLD) (Kronenberger et al, 2005;Joka et al, 2012;Chu et al, 2017;Wei et al, 2017;Sugimoto et al, 2018). Therefore, K18 may not be liver specific as it is expressed by all the single-epithelial cells.…”

“…• In various liver diseases, elevations in K18 and ccK18 may represent liver inflammation, and their ratio could assess the extent of hepatocyte necrosis and apoptosis. Thulin et al, 2014;Ku et al, 2016;Chu et al, 2017;Wei et al, 2017;Sugimoto et al, 2018 SDH • Early recognition of DILI could detect liver injury caused by special types of drugs.…”

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

“…For the different biochemical measurements, blood samples were collected and allowed to stand for 30 min at 37 °C, and then centrifuged at 3000g for 15 min at 4 °C to separate sera, and then were stored at -70 °C for the determination of hepatotoxicity parameters such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) as a prominent marker of hepatic injury (Jaeschke and McGill 2013) and caspase-cleaved cytokeratin-18 M30 (CK-18 M30) which is an epithelial cell-specific filament released into circulation during cell death, an outstanding marker of hepatic apoptosis (Wei et al 2017). Also, interleukin-10 (IL-10) was estimated in serum as an indicator for splenic function (Hassan et al 2014).…”