HATs add an acetyl group to the lysine residues (Lys or K), thus neutralizing the positive charge, weakening the interaction between histone and DNA, and increasing the accessibility of transcription factors to their target genes to prime transcription and elongation. Histone acetylation, which is a key modulator of chromatin structure and gene transcription, is regulated dynamically and reversibly by histone acetyltransferases (HATs) and by histone deacetylases (HDACs). This evidence suggests that the remnant liver function can be compensated in a regeneration-independent manner however, the underlying mechanism remains unknown. In addition, in animal studies, rodents could survive on the remnant liver after a 70% partial hepatectomy even when liver regeneration was severely deprived. Liver regeneration is commonly considered an adaptive process by which liver structure and function are recovered however, cirrhotic patients can maintain their liver function at a normal level for many years, although the remnant hepatocytes are continuously lost. Proliferative hepatocytes, bile ducts, pseudolobules, fibrous tissues and inflammatory cells constitute the major pathological and morphological characteristics of cirrhosis progression. In developing countries, chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major risk factors for cirrhosis, although dietary exposure to aflatoxin B1 also plays an important role in cirrhosis. Cirrhosis is also a consequence of an excessive healing response to various and continuous liver injuries. In the follow-up cases, patients with > 70% H2AK5ac +, H3K9/K14ac + or H3K27ac + hepatocytes had statistically lower survival rates ( P 70% H2AK5ac + or H3K27ac + hepatocytes were strong independent predictors of overall survival ( P < 0.05).ĬONCLUSION: The proportions of acetyl-histone-positive hepatocytes are closely associated with the liver function and prognosis of cirrhotic patients.Ĭirrhosis, which is the end stage of liver fibrosis, usually destroys the normal architecture and the synthetic and metabolic functions of the liver by increasing the fibrous tissues and regenerative nodules. RESULTS: The proportions of H2AK5ac +, H3K9/K14ac + and H3K27ac + hepatocytes gradually increased with deteriorating liver function and with increasing levels of serum markers of liver injury. The proportions of positive hepatocytes were recorded, and their correlations to clinical and laboratory indicators were analyzed statistically. Paraffin tissue microarray was prepared for immunohistochemistry to examine acetyl-histone expression. METHODS: In total, 611 cirrhotic cases from 3701 patients who were diagnosed during the past 15 years were screened, and 152 follow-up cases were selected. AIM: To investigate whether the proportions of acetyl-histone-positive hepatocytes could be used as markers of deteriorating liver function.
0 kommentar(er)
