RESUMO
Objective To investigate HBV RNA level in patients with HBV-related hepatocellular carcinoma after long-term antiviral therapy and its clinical significance. Methods A total of 60 patients with HBV-related hepatocellular carcinoma who were admitted to Tianjin Second People's Hospital from June 2019 to August 2020 were enrolled in this study. These patients received antiviral therapy with nucleos(t)ide analogues (NAs) for at least two years, and high-sensitivity HBV DNA detection showed a HBV RNA level of < 20 IU/mL at least twice at an interval of 3 months. Liver function, HBV serum markers, and HBV RNA level were measured for all patients. The Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; a Pearson correlation analysis was used to investigate the influencing factors for HBV RNA. Results Among the 60 patients with HBV-related hepatocellualr carcinoma who received long-term antiviral treatment, 9 (15%) tested positive for HBV RNA. According to the level of alpha-fetoprotein (AFP), the patients were divided into AFP positive group and AFP negative group, and there was no significant difference in HBV RNA level between the two groups [0(0-3.57) vs 0(0-2.00), Z =-1.474, P =0.141). According to Barcelona Clinic Liver Cancer (BCLC) stage, they were divided into BCLC stage A group and BCLC stage B+C+D group, and there was no significant difference in HBV RNA level between the two groups [0(0-2.0) vs 0(0-2.0), Z =-0.607, P =0.544]. According to HBeAg level, the patients were divided into HBeAg positive group and HBeAg negative group, and there was a significant difference in HBV RNA level between the two groups [2.99(0-4.80) vs 0(0-0.50), Z =-3.400, P =0.001]. According to the titer of HBsAg, they were divided into HBsAg≤100 IU/mL group, 100 IU/mL < HBsAg < 1500 IU/mL group, and HBsAg ≥1500 IU/mL group, and there was a significant difference in HBV RNA level between the three groups [0(0-0.0) vs 0(0-0.20) vs 2.00(0.0-4.54), H =-7.899, P =0.019]. A Pearson correlation analysis was performed for age, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, alpha-fetoprotein, HBsAg, and HBeAg, and the results showed that HBsAg level was correlated with HBV RNA quantification ( r =0.292, P < 0.05). Conclusion In patients with HBV-related hepatocellualr carcinoma receiving long-term antiviral therapy with NAs, HBV RNA can still be detected after HBV DNA is lower than the lower limit of detection. HBsAg titer may be correlated with serum HBV RNA level.
RESUMO
Objective To investigate HBV RNA level in patients with HBV-related hepatocellular carcinoma after long-term antiviral therapy and its clinical significance. Methods A total of 60 patients with HBV-related hepatocellular carcinoma who were admitted to Tianjin Second People's Hospital from June 2019 to August 2020 were enrolled in this study. These patients received antiviral therapy with nucleos(t)ide analogues (NAs) for at least two years, and high-sensitivity HBV DNA detection showed a HBV RNA level of < 20 IU/mL at least twice at an interval of 3 months. Liver function, HBV serum markers, and HBV RNA level were measured for all patients. The Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; a Pearson correlation analysis was used to investigate the influencing factors for HBV RNA. Results Among the 60 patients with HBV-related hepatocellualr carcinoma who received long-term antiviral treatment, 9 (15%) tested positive for HBV RNA. According to the level of alpha-fetoprotein (AFP), the patients were divided into AFP positive group and AFP negative group, and there was no significant difference in HBV RNA level between the two groups [0(0-3.57) vs 0(0-2.00), Z =-1.474, P =0.141). According to Barcelona Clinic Liver Cancer (BCLC) stage, they were divided into BCLC stage A group and BCLC stage B+C+D group, and there was no significant difference in HBV RNA level between the two groups [0(0-2.0) vs 0(0-2.0), Z =-0.607, P =0.544]. According to HBeAg level, the patients were divided into HBeAg positive group and HBeAg negative group, and there was a significant difference in HBV RNA level between the two groups [2.99(0-4.80) vs 0(0-0.50), Z =-3.400, P =0.001]. According to the titer of HBsAg, they were divided into HBsAg≤100 IU/mL group, 100 IU/mL < HBsAg < 1500 IU/mL group, and HBsAg ≥1500 IU/mL group, and there was a significant difference in HBV RNA level between the three groups [0(0-0.0) vs 0(0-0.20) vs 2.00(0.0-4.54), H =-7.899, P =0.019]. A Pearson correlation analysis was performed for age, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, alpha-fetoprotein, HBsAg, and HBeAg, and the results showed that HBsAg level was correlated with HBV RNA quantification ( r =0.292, P < 0.05). Conclusion In patients with HBV-related hepatocellualr carcinoma receiving long-term antiviral therapy with NAs, HBV RNA can still be detected after HBV DNA is lower than the lower limit of detection. HBsAg titer may be correlated with serum HBV RNA level.
RESUMO
Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that the 73-amino-acid protein encoded by ORF9c of the viral genome contains a putative transmembrane domain, interacts with membrane proteins in multiple cellular compartments, and impairs antiviral processes in a lung epithelial cell line. Proteomic, interactome, and transcriptomic analyses, combined with bioinformatic analysis, revealed that expression of only this highly unstable small viral protein impaired interferon signaling, antigen presentation, and complement signaling, while inducing IL-6 signaling. Furthermore, we showed that interfering with ORF9c degradation by either proteasome inhibition or inhibition of the ATPase VCP blunted the effects of ORF9c. Our study indicated that ORF9c enables immune evasion and coordinates cellular changes essential for the SARS-CoV-2 life cycle. One-sentence summarySARS-CoV-2 ORF9c is the first human coronavirus protein localized to membrane, suppressing antiviral response, resembling full viral infection.
