Endoplasmic reticulum (ER) stress, a type of cellular stress, always occurs when unfolded or misfolded proteins accumulating in the ER exceed the protein folding capacity. Because of the demand for rapid viral protein synthesis after viral infection, viral infections become a risk factor for ER stress. The hepatocyte is a cell with large and well-developed ER, and hepatitis virus infection is widespread in the population, indicating the interaction between hepatitis viruses and ER stress may have significance for managing liver diseases. In this paper, we review the process that is initiated by the hepatocyte through ER stress against HBV and HCV infection and explain how this information can be helpful in the treatment of HBV/HCV-related diseases.

Liver X receptor α (LXRα), a member of the nuclear receptor superfamily, is identified as a protein activated by ligands that interacts with the promoters of specific genes. It regulates cholesterol, bile acid, and lipid metabolism in normal physiological processes, and it participates in the development of some related diseases. However, many studies have demonstrated that LXRα is also involved in regulating numerous human malignancies. Aberrant LXRα expression is emerging as a fundamental and pivotal factor in cancer cell proliferation, invasion, apoptosis, and metastasis. Herein, we outline the expression levels of LXRα between tumor tissues and normal tissues via the Oncomine and Tumor Immune Estimation Resource (TIMER) 2.0 databases; summarize emerging insights into the roles of LXRα in the development, progression, and treatment of different human cancers and their diversified mechanisms; and highlight that LXRα can be a biomarker and therapeutic target in diverse cancers.

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), one of the most prevalent malignant tumors worldwide that poses a significant threat to human health. The multifunctional regulator known as Hepatitis B virus X-protein (HBx) interacts with host factors, modulating gene transcription and signaling pathways and contributing to hepatocellular carcinogenesis. The p90 ribosomal S6 kinase 2 (RSK2) is a member of the 90 kDa ribosomal S6 kinase family involved in various intracellular processes and cancer pathogenesis. At present, the role and mechanism of RSK2 in the development of HBx-induced HCC are not yet clear. In this study, we found that HBx upregulates the expression of RSK2 in HBV-HCC tissues, HepG2, and SMMC-7721 cells. We further observed that reducing the expression of RSK2 inhibited HCC cell proliferation. In HCC cell lines with stable HBx expression, RSK2 knockdown impaired the ability of HBx to promote cell proliferation. The extracellularly regulated protein kinases (ERK) 1/2 signaling pathway, rather than the p38 signaling pathway, mediated HBx-induced upregulation of RSK2 expression. Additionally, RSK2 and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were highly expressed and positively correlated in HBV-HCC tissues and associated with tumor size. This study showed that HBx upregulates the expression of RSK2 and CREB by activating the ERK1/2 signaling pathway, promoting the proliferation of HCC cells. Furthermore, we identified RSK2 and CREB as potential prognostic markers for HCC patients.

Although gut microbiota plays a pivotal role in numerous biological functions (e.g., energy, nutrients, metabolism, and immunological processes), growing evidence demonstrates that the gut microbiota is involved in the progression of liver diseases. The liver can be greatly influenced by alterations in intestinal microbiota due to increased gut permeability, allowing for the entry of bacterial products into the liver through the gut–liver axis. Recently, clinical and experimental research findings have demonstrated that microbiota dysbiosis plays an important role in the pathogenesis and progression of HBV-related liver diseases. In this review, we provide an overview of the gut microbiota and the microbiota–gut–liver axis in health; review HBV infection interactions with microbiota; discuss the role of microbiota dysbiosis in the pathogenesis of HBV-related liver disease, such as chronic HBV infection, liver cirrhosis, and hepatocellular carcinoma; and, finally, assess the potential for microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation. This review will provide novel insights into individualized therapy for CHB patients based on gut microbiota alteration.