Research on HBV DNA inhibition of plasmid acute infection mouse with betulinic acid

2020 ◽  
Author(s):  
YAYUN LIU ◽  
XueSong Liang ◽  
AiJing Xu ◽  
Hao Xu ◽  
Jiao Yu ◽  
...  

Abstract Background and Aims The efficacy and safety of long-term antiviral therapy with nucleoside analogues (NAs) for chronic hepatitis B (CHB) patients in immune tolerate (IT) phase is uncertain.We retrospectively evaluated the efficacy and safety of 61 CHB patients in IT phase receiving NAs therapy from 2013 through 2018. Methods We performed a retrospective study of CHB patients who had high HBV DNA, normal or minimum alanine aminotransferase (ALT), liver biopsy confirmed light necro-inflammation and received NAs therapy from 2012 through 2018.All patients received NAs at least 12 months. Patients on-treatment monitoring were in accordance with the roadmap concept and were followed after their treatment start date to the treatment end date (if any) or 6 years at least once every 6 months. The median follow-up time was 36(16; 52) months. We assessed the virological response (the proportions of patients with plasma HBV DNA loads less than the limit of quantification,100IU/ml) and serological endpoints (HBeAg loss and seroconcersion to anti-HBe, and HBsAg loss and seroconversion to anti-HBs). Safety and tolerability, including serious events, were regularly assessed. Results At 48 weeks on treatment, 55.6%(95%confidence interval(CI):37.0-70.0%) patients with CHB in IT phase achieved HBV DNA less than quantitative limit(<100IU/ml), and the accumulate proportion of patients who achieved HBV DNA less than quantitative limit was 76.7%(95%CI: 58-90.0%) and 95.8%(95%CI: 79-100%) at 96 weeks and ≥144weeks on treatment, respectively. The HBeAg loss or seroconversion rate in patients with CHB in IT phase on NAs treatment at 48, 96 and ≥144weeks was 2.7%(95%CI: 0-14.0%), 13.3% (95%CI: 4-31.0%) and 29.2%(95%CI: 13-51%), respectively. During the study only one patient achieved HBsAg seroconversion after 3years NAs therapy and only one patient experienced drug-related breakthrough during the study. Conclusion Patients with CHB in IT phase have relatively preferable safety and HBV DNA inhibition efficacy on long-term NAs treatment.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1352
Author(s):  
Lorenzo Piermatteo ◽  
Mohammad Alkhatib ◽  
Stefano D’Anna ◽  
Vincenzo Malagnino ◽  
Ada Bertoli ◽  
...  

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.


2021 ◽  
Vol 9 (8) ◽  
pp. 1787
Author(s):  
Maria Bousali ◽  
George Papatheodoridis ◽  
Dimitrios Paraskevis ◽  
Timokratis Karamitros

Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It targets human hepatocytes and can lead to chronic HBV infection either after acute infection via horizontal transmission usually during infancy or childhood or via maternal–fetal transmission. HBV has been found in ~85% of HBV-related Hepatocellular Carcinomas (HCC), and it can integrate the whole or part of its genome into the host genomic DNA. The molecular mechanisms involved in the HBV DNA integration is not yet clear; thus, multiple models have been described with respect to either the relaxed-circular DNA (rcDNA) or the double-stranded linear DNA (dslDNA) of HBV. Various genes have been found to be affected by HBV DNA integration, including cell-proliferation-related genes, oncogenes and long non-coding RNA genes (lincRNAs). The present review summarizes the advances in the research of HBV DNA integration, focusing on the evolutionary and molecular side of the integration events along with the arising clinical aspects in the light of WHO’s commitment to eliminate HBV and viral hepatitis by 2030.


Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
CA Dehelean ◽  
C Peev ◽  
C Soica ◽  
S Cinta-Pinzaru ◽  
Z Aigner
Keyword(s):  

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
E Kovac-Besovic ◽  
K Duric ◽  
Z Kaloðera ◽  
E Sofic
Keyword(s):  

2010 ◽  
Vol 223 (01) ◽  
Author(s):  
I Jeremias ◽  
H Ehrhardt ◽  
I Höfig ◽  
N Terziyska ◽  
P Obexer

2020 ◽  
Vol 4 (11) ◽  
pp. 676-681
Author(s):  
V.V. Sapozhnikova ◽  
◽  
A.L. Bondarenko ◽  

Aim: to determine the association between clinical laboratory parameters, the production of cytokines (IL-17A, -23, -33, -35), and specific IgM and IgG in the serum of patients with Lyme borreliosis without erythema migrans. Patients and Methods: complete blood count, the concentrations of IL-17A, -23, -33, -35, and the levels of specific IgM and IgG were measured during acute infection and convalescence (n=30). The control group included age- and sex-matched healthy individuals (n=30). Statistical analysis was performed using the StatSoft Statistica v 10.0 software (parametric and non-parametric methods and multifactorial analysis, i.e., principal component analysis). Results: most (80%) patients with Lyme borreliosis without erythema migrans are the people of working age. In most patients, the combination of the specific antibodies against Borrelia afzelii and Borrelia garinii (76.7%) and severe intoxication and inflammatory process (100%) were detected. Moderate and severe disease associated with meningism was diagnosed in 90% and 10%, respectively. The mean duration of hectic period was 8.3±1.27 days. Abnormal ECG was reported in 40% of patients, i.e., conduction abnormalities in 20%, sinus bradycardia in 16.7%,and sinus tachycardia in 3.3%. The clinical laboratory signs of hepatitis without jaundice were identified in 26.7%. During treatment, the significant reduction in band and segmented neutrophil counts as well as the significant increase in platelet count were revealed compared to these parameters at admission. Abnormal cytokine levels (i.e., the increase in IL-17A, -23, -33 and the deficiency of IL-35) were detected. Conclusions: multifactorial analysis has demonstrated that the severity of immunological abnormalities in patients with Lyme borreliosis without erythema migrans is associated with fever, cardiac and liver disorders, the high levels of IL-23 and IL-33, and the lack of IL-35 and specific IgM and IgG. KEYWORDS: tick-borne borreliosis, Lyme disease without erythema migrans, clinical laboratory signs, cytokines, specific antibodies, multifactorial analysis, principal component analysis. FOR CITATION: Sapozhnikova V.V., Bondarenko A.L. Multifactorial analysis of clinical laboratory signs, the levels of IL-17A, IL-23, IL-33, IL-35, and specific antibodies in the serum of patients with Lyme borreliosis without erythema migrans. Russian Medical Inquiry. 2020;4(11):676–681. DOI: 10.32364/2587-6821-2020-4-11-676-681.


Sign in / Sign up

Export Citation Format

Share Document