Hepatocytes, the major parenchymal cells in the liver, are responsible for a variety of cellular functions including carbohydrate, lipid and protein metabolism, detoxification and immune cell activation to maintain liver homeotasis. Recent studies show hepatocytes play a pivotal role in liver inflammation. After receiving liver insults and inflammatory signals, hepatocytes may undergo organelle damage, and further respond by releasing mediators and expressing molecules that can act in the microenvironment as well as initiate a robust inflammatory response. In this review, we summarize how the hepatic organelle damage link to liver inflammation and introduce numerous hepatocyte-derived pro-inflammatory factors in response to chronic liver injury.

The aim of this study was to investigate the performance and predictive value of hypocalcemia in severe COVID-19 patients. We retrospectively investigated the clinical and laboratory characteristics of severe COVID-19 patients. 107 patients were divided into hypocalcemia group and normal serum calcium group. The clinical and laboratory data were compared between two groups. The discriminative power of hypocalcemia regarding poor outcome were evaluated by receiver operating curves (ROC) analyses. Sixty seven patients (62.6%) had hypocalcemia. In hypocalcemia group, leukocytes, c-reactive protein (CRP), procalcitonin (PCT), Interleukin 6 (IL-6), and D-dimer levels was higher, while lymphocytes and albumin (ALB) levels was lower. No significant difference was identified in gender, age, signs and symptoms, comorbidities and other laboratory indicators. Serum calcium levels were negatively correlated with leukocytes, CRP, PCT, IL-6 and D-dimer, while positively correlated with lymphocytes and ALB. Patients with hypocalcemia more commonly presented poor outcome (47.8% (32/67) vs 25% (10/40), p=0.02). Median serum calcium levels were significantly lower in the patients with poor outcome (2.01(1.97-2.05) vs 2.10(2.03-2.20), p<0.001), and it could predict the prognosis with an area under the ROC curve (AUC) of 0.73(95% confidence interval (CI) 0.63-0.83, p<0.001). Hypocalcemia commonly occurred in severe COVID-19 patients and it was associated with poor outcome.

Colorectal cancer (CRC) liver metastasis is a significant clinical problem for which better therapies are urgently needed. Tumor-associated macrophage, a major cell population in the tumor microenvironment, is a known contributor to primary cancer progression and cancer metastasis. Here, we found TAM recruitment and M2 polarization were increased in the hepatic metastatic lesion compared with the primary site of human CRC tissues. Moreover, Pearson correlation analysis showed that TAM recruitment and polarization were closely correlated with the elevated TCF4 expression in the metastatic site. To investigate the role of TCF4 in CRC liver metastasis, we generated a syngeneic mouse model using MC38 cells splenic injection. Results from in vivo experiments and mouse models revealed that TCF4 deficiency in MC38 cells does not affect their proliferation and invasion; however, it reduces TAM infiltration and M2 polarization in the metastasis site. Further studies indicated that these effects are mediated by the TCF4 regulated CCL2 and CCR2 expression. TCF4 or CCL2 silencing in the tumor cells prevent CRC liver metastasis in the mouse model. Altogether, these findings suggest that the TCF4-CCL2-CCR2 axis plays an essential role in CRC liver metastasis by enhancing TAMs recruitment and M2 polarization.

Background and Aims: In December 2019, an outbreak of coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China. Although it has been reported that some patients with COVID‐19 showed elevated liver biochemistries, there are few studies regarding the clinical features and prognosis of these patients. Approach and Results: In this multicenter, retrospective study, we collected data on laboratory‐confirmed patients with COVID‐19 from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. Data on demographics, comorbidities, clinical symptoms, laboratory examinations on admission, complications, treatment, and outcome were collected. A total of 482 patients were enrolled in this study. Of those, 142 (29.5%) patients showed abnormal liver biochemistries on admission, and patients with elevated alanine aminotransferase, aspartate aminotransferase (AST), and total bilirubin (TBIL) accounted for 67.6%, 69.0%, and 16.2%, respectively. Those with abnormal liver biochemistries showed higher percentages of severe cases and comorbidities and were more likely to have dyspnea, chest distress or pain, and increased hemoglobin (Hb) on admission. Higher rates of complications and mortality and worse recovery when discharged were observed in patients with abnormal AST or TBIL. Multivariable regression analysis showed that chest distress or pain (odds ratio [OR], 1.765; P = 0.018), dyspnea (OR, 2.495; P = 0.001), elevated C‐reactive protein level (OR, 1.007; P = 0.008), elevated white blood count (OR, 1.139; P = 0.013), and elevated Hb concentration (OR, 1.024; P = 0.001) were independent factors associated with elevated liver biochemistries in patients with COVID‐19. Conclusions: Elevated liver biochemistries were common in patients with COVID‐19. Patients with hypoxia or severe inflammation are more likely to experience increased liver biochemistries on admission. Those with abnormal AST or TBIL on admission are more likely to suffer from severe complications and death.

Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.