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Objectives: In this study we aimed to assess the impact of acetylation of hepatocyte nuclear factor 4α (HNF4α) on lysine 458 on the differentiation therapy of hepatocellular carcinoma (HCC). Methods: Periodic acid‐Schiff (PAS) staining, Dil‐acetylated low‐density lipoprotein (Dil‐Ac‐LDL) uptake, and senescence‐associated β‐galactosidase (SA‐β‐gal) activity analysis were performed to assess the differentiation of HCC cells. HNF4α protein was detected by western blot and immunohistochemistry (IHC). The effects of HNF4α‐K458 acetylation on HCC malignancy were evaluated in HCC cell lines, a Huh‐7 xenograft mouse model, and an orthotopic model. The differential expression genes in Huh‐7 xenograft tumors were screened by RNA‐sequencing analysis. Results: K458R significantly enhanced the inhibitory effect of HNF4α on the malignancy of HCC cells, whereas K458Q reduced the inhibitory effects of HNF4α. Moreover, K458R promoted, while K458Q decreased, HNF4α‐induced HCC cell differentiation. K458R stabilized HNF4α, while K458Q accelerated the degradation of HNF4α via the ubiquitin proteasome system. K458R also enhanced the ability of HNF4α to inhibit cell growth of HCC in the Huh‐7 xenograft mouse model and the orthotopic model. RNA‐sequencing analysis revealed that inhibiting K458 acetylation enhanced the transcriptional activity of HNF4α without altering the transcriptome induced by HNF4α in HCC. Conclusion: Our data revealed that inhibiting K458 acetylation of HNF4α might provide a more promising candidate for differential therapy of HCC. [ABSTRACT FROM AUTHOR]

Objectives: Covert hepatic encephalopathy (CHE) negatively affects the health‐related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long‐term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. Methods: This was a single‐center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow‐up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. Results: CHE was detected in 35.61% cirrhotic patients. During the follow‐up, patients with CHE had a higher risk of developing OHE (log‐rank 5.840, P = 0.016), exacerbation of ascites (log‐rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log‐rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log‐rank 4.462, P = 0.035). At the end of the follow‐up, patients with CHE had a lower survival rate compared to those without CHE (log‐rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child–Pugh score, were risk factors for impaired survival in cirrhotic patients. Conclusion: CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (WFA+‐M2BP) is a novel glycobiomarker for evaluating liver fibrosis, but less is known about its role in liver cirrhosis (LC). This study aimed to investigate the utility of WFA+‐M2BP in evaluating liver function and predicting prognosis of cirrhotic patients. METHODS: We retrospectively included 197 patients with LC between 2013 and 2016. Serum WFA+‐M2BP and various biochemical parameters were measured in all patients. With a median follow‐up of 23 months, liver‐related complications and deaths of 160 patients were recorded. The accuracy of WFA+‐M2BP in evaluating liver function, predicting decompensation and mortality were measured by the receiver operating characteristic (ROC) curve, logistic and Cox's regression analyses, respectively. RESULTS: WFA+‐M2BP levels increased with elevated Child–Pugh classification, especially in patients with hepatitis B virus (HBV) infection. ROC analysis confirmed the high reliability of WFA+‐M2BP for the assessment of liver function using Child–Pugh classification. WFA+‐M2BP was also significantly positively correlated with the model for end‐stage liver disease (MELD) score. Multivariate logistic regression analysis indicated WFA+‐M2BP as an independent predictor of clinical decompensation for compensated patients (odds ratio 11.958, 95% confidence interval [CI] 1.876–76.226, P = 0.009), and multivariate Cox's regression analysis verified WFA+‐M2BP as an independent risk factor for liver‐related death in patients with HBV infection (hazards ratio 10.596, 95% CI 1.356–82.820, P = 0.024). CONCLUSION: Serum WFA+‐M2BP is a reliable predictor of liver function and prognosis in LC and could be incorporated into clinical surveillance strategies for LC patients, especially those with HBV infection. [ABSTRACT FROM AUTHOR]