LIVE IMAGING BY TIME-LAPSE MICROSCOPY CAN MORE CLEARLY EVALUATE THE ANTI-APOPTOTIC STATE OF PRIMARY HEPATOCYTES ISOLATED FROM THE DRS KNOCKOUT MOUSE

To investigate the anti-apoptotic state of primary hepatocytes isolated from the drs knockout(KO)mice, Fas-mediated apoptosis was observed by flow cytometry and time-lapse microscopy. Treatment with anti-Fas antibody plus actinomycin D or cycloheximide induced over 50% apoptosis for primary hepatocytes based on annexin V staining. At 24 hr later under these apoptotic stimuli, the sub G1 fraction of hepatocytes isolated from the drs KO mice was significantly decreased in comparison to wild C57BL/ 6 mice. In contrast, sequential time-lapse microscopic analysis revealed clearer and larger differences in the apoptotic responses of primary hepatocytes from the drs KO and wild-type mice from 4 hr to 24 hr after apoptotic induction. The time-lapse microscopic analysis clearly indicated the hepatocytes isolated from the drs KO mouse to be more resistant to the apoptotic stimuli than other methods. The time-lapse microscopy is very useful for the sequential observation of viable primary hepatocytes

Mac‐2‐binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C

Abstract Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non‐HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non‐HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct‐acting antiviral (DAA) treatment were analyzed. The cumulative post‐SVR incidence of non‐HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non‐HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac‐2‐binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post‐SVR incidence of non‐HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post‐SVR incidence of non‐HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post‐SVR incidence of non‐HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival

Association of Serum Albumin Levels and Long-Term Prognosis in Patients with Biopsy-Confirmed Nonalcoholic Fatty Liver Disease

The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). 1383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5–4.0 g/dL), and low (p p < 0.001). Among biopsy-confirmed NAFLD patients, those with intermediate or low serum albumin had a significantly higher risk of death or OLT than those with high serum albumin