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.

Background: Hepatitis C virus (HCV) eradication with sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, hepato-cellular carcinoma (HCC), or HCV/hepatitis B (HBV), HCV/HIV, or HCV/HBV/HIV coinfection. Methods: In this real-world prospective observational study, we recruited patients from the West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults with with CHC and any genotype (GT), with or without cirrhosis, hepatocellular carcinoma (HCC), HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered SOF/VEL (400/100 mg) +/- ribavirin (RBV) once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). Adverse events (AEs) were evaluated during treatment. Results: The study included 483 patients with HCV genotypes 1, 2, 3, 6 and uncertain ones. Among them, 35.4 % (171/483, ITT) and 36.7 % (166/452, mITT) received SOF/VEL + RBV. At the end of treatment , 99.2 % (ITT, 479/483) and 99.1 % (mITT, 448/452) of patients had undetectable HCV RNA. SVR12 rates were 92.8 % [intention to treat (ITT), 448/483] and 99.1 % [modified ITT (mITT), 448/452]. In the mITT analysis, SVR12 for patients with HCV GT3b, those with cirrhosis or HCC, and those coinfected with HBV/HIV was 99.2 % (130/131), 99.4 % (168/169), and 97.6 % (40/41), respectively. The albumin-bilirubin (ALBI) (-3.01 vs. -3.18 P < 0.001), Fibrosis-4 (FIB4) Index (2.53 vs. 1.88, P = 0.004) and AST to Platelet Ratio Index (APRI) (0.99 vs. 0.44, P < 0.001) scores showed a significant decrease from baseline to SVR12. No patients experienced grade 3-5 AEs. Conclusions: Although a high proportion of patients included in this study had HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection, SOF/VEL +/- RBV was highly effective and well tolerated in Chinese patients with CHC.

Objectives: To develop new tools integrating host immune response and viral activity to predict Peg-IFNα therapy efficiency in nucleos(t)ide analogues (NUCs)-treated chronic hepatitis B (CHB) patients. Methods: This post-hoc study analyzed data from 758 CHB patients who completed 48 weeks of Peg-IFNα add-on therapy in a prospective study. Clinical and biochemical data were collected every 12 weeks and evaluated for their predictive value of HBsAg seroclearance and seroconversion. Results: Age, qHBsAg, and ALT levels at Week 12 were associated with both HBsAg seroclearance and seroconversion. The ASAP-12 score, defined as the ALT to qHBsAg and age proportion at Week 12, demonstrated strong discrimination for both endpoints (AUROCs: 0.802 [cut-off 0.07] and 0.787 [cut-off 0.12], respectively; p <0.05). Patients with scores above the respective cut-offs had significantly higher cumulative probabilities of HBsAg seroclearance (63.4% vs. 17.8%, Log-rank test p <0.001) and seroconversion (47.3% vs. 11.0%, Log-rank test p <0.001). Higher ASAP-12 scores ( β =0.206, p =0.006) also independently correlated with elevated Week 48 HBsAb levels. Conclusions: The ASAP-12 score is an effective tool for predicting both HBsAg seroclearance and seroconversion at Week 48 of Peg-IFNα add-on therapy in NUCs-experienced CHB patients, enabling personalized therapeutic decisions.