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Unfolded protein response (UPR) plays an important role in the pathogenesis of many liver diseases. BMI1 has a liver protection effect, but whether it participates in the regulation of hepatocyte death through UPR is not well defined. Herein, the endoplasmic reticulum stress model was established by inducing hepatocyte line (MIHA) with tunicamycin (TM, 5 µg/ml). Cell counting kit-8 assay and flow cytometry were used to evaluate the viability and apoptosis of hepatocytes. The expression levels of BMI1, KAT2B, and proteins related to UPR (p-eIF2α, eIF2α, ATF4, and ATF6), NF-κB (p65 and p-p65), apoptosis (cleaved caspase-3, bcl-2, and bax) and necroptosis (p-MLKL and MLKL) were determined by Western blot. The relationship between KAT2B and BMI1 was determined by co-immunoprecipitation and ubiquitination assay. The results showed that TM not only promoted UPR, apoptosis, and necroptosis in hepatocytes but also upregulated the expression levels of BMI1 and KAT2B and activated NF-κB pathway. BAY-117082 reversed the effects of TM on viability, apoptosis, NF-κB pathway, and BMI1 but strengthened the effects of TM on KAT2B/MLKL-mediated necroptosis. BMI1 promoted the ubiquitination of KAT2B, and BMI1 overexpression reversed the effects of TM on viability, apoptosis, and KAT2B/MLKL-mediated necroptosis. In summary, overexpression of BMI1 promotes the ubiquitination of KAT2B to block the MLKL-mediated necroptosis of hepatocytes.

Objective: To explore the diagnostic value of liver biopsy in patients with acute/chronic liver diseases and to evaluate the application value of repeated liver biopsy in assessing the efficacy of antiviral therapy in patients with chronic hepatitis B., Methods: This retrospective study involved 146 patients with acute and chronic liver diseases who underwent liver biopsy at the Affiliated Hospital of Putian University from January 2018 to December 2023. Differential diagnoses were made for patients with liver diseases based on their pathological results from liver biopsy. Additionally, the effectiveness of antiviral treatment and changes in liver fibrosis in patients with hepatitis B infection before and after antiviral therapy were assessed using repeated liver biopsy., Results: The overall concordance rate between clinical and histopathological diagnoses was 79.45% (116/146). Specifically, the highest concordance rate was for chronic hepatitis B at 82.61% (76/92), followed by fatty liver disease at 77.78% (7/9), autoimmune liver disease at 75% (12/16), and drug-induced liver injury at 72.72% (16/22), and lastly, hepatitis B-related cirrhosis at 71.43% (5/7). After antiviral therapy, the number of cases with positive HBeAg and HBV-DNA significantly decreased compared to before treatment, while the number of cases with negative HBeAg increased, showing a statistically significant difference (P<0.001). The number of patients at fibrosis stages S3-S4 decreased after antiviral therapy compared to before treatment (P=0.040 and P=0.028), while the number of patients at stage S2 increased (P=0.040)., Conclusion: Liver biopsy aids in the diagnosis of liver diseases and can effectively evaluate the degree of liver fibrosis before and after antiviral therapy for chronic hepatitis B., Competing Interests: None., (AJTR Copyright © 2024.)