ABSTRACT
Abstract Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.
ABSTRACT
Human immunodeficiency virus (HIV) infection causes severe systemic immune system damage and ultimately leads to patient death. Despite the success of anti-retroviral therapy (ART), which can effectively supress viral replication, there is currently no cure for HIV infection, which requires lifelong treatment. Due to the presence of HIV latent reservoir, the virus persists during antiretroviral treatment. "Shock and Kill" is currently one of the most recognized strategies for removing HIV latent reservoir. The solution is mainly to reactivate viral transcription by using latency-reversing agents (LRAs), which triggers cell lysis or immune-mediated clearance to kill the reactivated HIV infected cells and achieve functional cure. This article gives an overview of current research progress on HIV LRAs and their mechanism of action.
ABSTRACT
The clinical outcome of hepatitis B virus (HBV) infection mostly depends on the interaction between HBV and host immune system. Although there are still no drugs for the radical treatment of hepatitis B at present, more and more studies have found that functional cure, characterized by persistent negative conversion of HBsAg and HBV DNA in serum, has become an achievable goal for the treatment of chronic hepatitis B. Meanwhile, immunoregulatory therapy based on a new understanding of the mechanism of immune control of HBV infection has been used as one of the important strategies for functional cure of chronic hepatitis B. This article elaborates on the immune control of HBV infection and the advances and challenges of its application in the research on the strategies for functional cure.
ABSTRACT
Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/ combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA)] or immunomodulators (such as pegylated interferon alpha (Peg-IFN)] for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.
ABSTRACT
Background@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*Methods@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*Results@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*Conclusion@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.
ABSTRACT
Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/ combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA)] or immunomodulators (such as pegylated interferon alpha (Peg-IFN)] for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.
Subject(s)
Humans , Antiviral Agents , Therapeutic Uses , Consensus , DNA, Viral , Blood , Hepatitis B Surface Antigens , Blood , Hepatitis B e Antigens , Blood , Hepatitis B virus , Hepatitis B, Chronic , Therapeutics , Practice Guidelines as Topic , Randomized Controlled Trials as TopicABSTRACT
Currently available antiviral treatment can not eradicate hepatitis B virus completely, and needs long-term or lifelong therapy for the majority of patients with chronic hepatitis B. New antiviral inhibitors and immune modulatory therapies are in development, and have opened new possibilities to cure chronic hepatitis B. This paper summarises status and progress in chronic hepatitis B cure.
ABSTRACT
Functional cure of chronic hepatitis B ( CHB) through antiviral therapy is the goal and main focus of research worldwide.The criteria of functional cure of CHB are undetectable serum HBV DNA, persistent loss of HBsAg, with or without anti-HBs seroconversion, persistence of cccDNA in a transcriptionally inactive status and the absence of spontaneous relapse after treatment cessation .Current antiviral therapy can effectively control viral replication , but is still quite far from achieving functional cure. From the virological point of view , HBV cccDNA reservoir and its transcription activity can hardly be inhibited by the existing antiviral therapy , and the integration of viral genomic DNA leads to the continuous expression of HBsAg, which are the two main causes of the low functional cure rate in CHB patients. Furthermore, the high frequency of viral mutation can also result in a reduction of HBsAg loss .This article reviews the new strategies and advances about functional cure of CHB based on the virology research .
ABSTRACT
Currently, clinical antiviral therapies for chronic hepatitis B virus (HBV) infection can efficiently control HBV replication.However, it remains difficult to achieve HBsAg clearance and sustains off-therapy, that is the functional cure of chronic hepatitis B ( CHB) in most of patients.Host immune responses play critical roles in HBV clearance and HBV infection control by activating innate and adaptive immune responses, resulting in improving the functional cure rate of patients with CHB.This article reviews the recent advances in immunology studies related to functional cure of CHB.
ABSTRACT
Chronic hepatitis B ( CHB), characterized by recurrent liver inflammation caused by hepatitis B virus(HBV), can further develop into decompensated liver cirrhosis ,liver cancer or liver failure. The currently used therapeutic drugs nucleos ( t) ide analogues and interferon can effectively inhibit virus replication, but it is difficult to achieve functional cure ( clinical cure) because of their inability to destroy covalently closed ring DNA ( cccDNA).So we are still facing problems of low HBsAg clearance rate and high recurrence rate after drug withdraw.In recent years, the emerging of new drugs and biological agents provide novel ideas and directions for the functional cure of CHB.This article briefly reviews the new therapeutic methods and strategies for functional cure of CHB.
ABSTRACT
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients. In recent studies, we and others have demonstrated that it is the serum HBV RNA that reflects the cccDNA activity in infected hepatocytes, particularly among the patients on NAs. Here we suggest that instead of measuring serum HBV DNA only, simultaneous measurement of both viral DNA and RNA would improve the accuracy to reflect the cccDNA activity; therefore, the virological response should be redefined as consistent loss (less than the lower limit of detection) of both serum HBV DNA and RNA, which indicates the safety of drug discontinuation. Accumulating evidence has suggested that for the CHB patients with lower serum HBsAg, switch-to or add-on pegylated interferon (Peg-IFN) treatment would result in loss of serum HBsAg in a relatively large proportion of CHB patients. Since serum HBV RNA is an ideal biomarker to reflect the intrahepatic cccDNA activity, for the patients with a serum HBsAg level lower than 1 500 IU/ml after long-term NAs treatment, the serum HBV RNA should be measured. If serum HBV RNA is detected, peg-IFN should be added on; if serum HBV RNA is not detected, NAs treatment should be switched to peg-IFN treatment. We believe the therapy based on serum HBV RNA would make the functional cure of CHB (serum HBsAg loss or even conversion to anti-HBs) more efficient.