Dual or Single Hepatitis B and C Virus Infections in Childhood Cancer Survivors: Long-Term Follow-Up and Effect of Interferon Treatment

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4046-4052
Author(s):  
Riccardo Utili ◽  
Rosa Zampino ◽  
Pasquale Bellopede ◽  
Marta Marracino ◽  
Enrico Ragone ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Seroconversion Rate ◽  
Childhood Cancer Survivors ◽  
Hbv Dna ◽  
Hcv Rna ◽  
Spontaneous Clearance ◽  
Virus Infections ◽  
Ifn Treatment

We conducted a long-term prospective study of 89 cancer survivor children who had acquired hepatitis B virus (HBV) and/or hepatitis C virus (HCV) during treatment for neoplasia, the aim being to evaluate the natural history of the diseases and the effect of interferon (IFN) treatment. Patients were followed up for a median period of 13 years (range, 8 to 20); 46 were infected by HBV, 11 by HCV, and 32 coinfected by HBV and HCV. A spontaneous clearance of hepatitis B surface antigen (HBsAg) occurred more frequently in coinfected patients (19%) than in the HBV-infected (2%; P = .004), with an annual seroconversion rate of 2.1% and 0.2%, respectively (P= .008). Loss of hepatitis Be antigen (HBeAg) occurred in 44% of coinfected and in 28% of HBV-infected patients. Clearance of serum HCV-RNA was observed in 34% and 9%, respectively, of coinfected and HCV-infected patients. Seventeen HBV-infected, 4 HCV-infected, and 16 coinfected patients received -IFN treatment. In the HBV group, 6 patients (35%) cleared serum HBV DNA and seroconverted to anti-HBe; in the HCV-group, none cleared HCV-RNA. In the coinfected group, 1 patient cleared both HBV DNA and HCV-RNA, 6 patients cleared serum HCV-RNA alone, and 1 only HBV DNA and HBeAg. Overall, the diseases showed a mild histological course with no evidence of liver cirrhosis. A reciprocal interference on viral replication between HBV and HCV may occur in coinfected patients. Treatment seems to be effective for selected cases and is justified in view of the uncertain prognosis of the disease in these patients.

Dual or Single Hepatitis B and C Virus Infections in Childhood Cancer Survivors: Long-Term Follow-Up and Effect of Interferon Treatment

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4046-4052 ◽  
Author(s):  
Riccardo Utili ◽  
Rosa Zampino ◽  
Pasquale Bellopede ◽  
Marta Marracino ◽  
Enrico Ragone ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Seroconversion Rate ◽  
Childhood Cancer Survivors ◽  
Hbv Dna ◽  
Hcv Rna ◽  
Spontaneous Clearance ◽  
Virus Infections ◽  
Ifn Treatment

Abstract We conducted a long-term prospective study of 89 cancer survivor children who had acquired hepatitis B virus (HBV) and/or hepatitis C virus (HCV) during treatment for neoplasia, the aim being to evaluate the natural history of the diseases and the effect of interferon (IFN) treatment. Patients were followed up for a median period of 13 years (range, 8 to 20); 46 were infected by HBV, 11 by HCV, and 32 coinfected by HBV and HCV. A spontaneous clearance of hepatitis B surface antigen (HBsAg) occurred more frequently in coinfected patients (19%) than in the HBV-infected (2%; P = .004), with an annual seroconversion rate of 2.1% and 0.2%, respectively (P= .008). Loss of hepatitis Be antigen (HBeAg) occurred in 44% of coinfected and in 28% of HBV-infected patients. Clearance of serum HCV-RNA was observed in 34% and 9%, respectively, of coinfected and HCV-infected patients. Seventeen HBV-infected, 4 HCV-infected, and 16 coinfected patients received -IFN treatment. In the HBV group, 6 patients (35%) cleared serum HBV DNA and seroconverted to anti-HBe; in the HCV-group, none cleared HCV-RNA. In the coinfected group, 1 patient cleared both HBV DNA and HCV-RNA, 6 patients cleared serum HCV-RNA alone, and 1 only HBV DNA and HBeAg. Overall, the diseases showed a mild histological course with no evidence of liver cirrhosis. A reciprocal interference on viral replication between HBV and HCV may occur in coinfected patients. Treatment seems to be effective for selected cases and is justified in view of the uncertain prognosis of the disease in these patients.

scholarly journals Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Takuro Uchida ◽  
Michio Imamura ◽  
C. Nelson Hayes ◽  
Nobuhiko Hiraga ◽  
Hiromi Kan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
High Dose ◽  
Chimeric Mice ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Ifn Treatment

ABSTRACT Nucleot(s)ide analogues and peginterferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long-term loss of HBsAg in human hepatocyte chimeric mice. Mice were treated with a high dose of entecavir and/or PEG-IFN for 6 weeks. High-dose combination therapy with both drugs resulted in persistently negative HBV DNA in serum. Although small amounts of HBV DNA and cccDNA (0.1 and 0.01 copy/cell, respectively) remained in the mouse livers, some of the mice remained persistently negative for serum HBV DNA at 13 weeks after cessation of the therapy. Serum HBsAg and hepatitis B core-related antigen (HBcrAg) continued to decrease and eventually became negative at 12 weeks after cessation of the therapy. Analysis of the HBV genome in treated mice showed accumulation of G-to-A hypermutation and CpG III island methylation. Persistent loss of serum HBV DNA and loss of HBV markers by high-dose entecavir and PEG-IFN combination treatment in chimeric mice suggests that control of HBV can be achieved even in the absence of a cellular immune response.

scholarly journals Efficacy of 104-week Telbivudine-based optimization strategy in patients with HBeAg-negative chronic hepatitis B virus infections

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Weiqiang Gan ◽  
Jianguo Li ◽  
Chunlan Zhang ◽  
Xuefu Chen ◽  
Chaoshuang Lin ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Chinese Patients ◽  
Optimization Strategy ◽  
Virus Infections ◽  
Open Label ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Hepatitis B Virus Infections

Abstract Background Evaluate the safety and efficacy of 104-week regimen of Telbivudine(LdT)-based optimization strategy for Chinese patients who have chronic hepatits B(CHB) with HBeAg-negative. Methods This multi-center, open-label, prospective study enrolled 108 HBeAg-negative CHB patients who received LdT (600 mg/day) for 24 weeks, Adefovir (ADV) was added if HBV DNA remained detectable at week 24, otherwise LdT was maintained to use until 104 weeks. HBV DNA, alanine amino transferase (ALT), hepatitis B surface antigen(HBsAg), creatinine kinase(CK), and estimated glomerular filtration rate (eGFR) were measured, safety was assessed. Results Eighty-eight patients (81%) had HBV-DNA undetectable at 24 weeks and maintained to receive LdT monotherapy until 104 weeks, whereas the other 20 patients had HBV-DNA detectable and ADV was used in combination. For all patients, 72% of patients reached ALT normalization at 24 weeks, which increased to 80% at 52 weeks and 104 weeks, respectively.. 81% of total patients had undetectable HBV-DNA at 24 weeks, 92% at 52 weeks, and 94% at 104 weeks. The HBsAg titre declined steadily from baseline to 104 weeks (3.62 vs. 2.98 log10 IU/mL, p < 0.05), and the eGFR increased steadily from baseline to 104 weeks (92.9 vs. 104.4 mL/min/1.73 m2, p < 0.05). Although 79 patients (73%) had at least one time of elevated CK, most of these patients had CK elevated in Grade 1/2. Conclusions LdT was well tolerated and effective, and 94% of patients achieved virological suppression after 104 weeks. Trial registration This study was registered in clinicaltrials.gov on January 31, 2012 and the ID No. was NCT01521975.

scholarly journals Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study

2021 ◽  
Vol 9 (11) ◽  
pp. e003195
Author(s):  
Kunyuan Wang ◽  
Ying Xia ◽  
Yun Zhu ◽  
Wenxuan Yu ◽  
Yabing Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Factor ◽  
Hepatitis B ◽  
Real World ◽  
Patient Survival ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbsag Level ◽  
Virological Breakthrough

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data demonstrating the impact of ICIs on HBV DNA level in HBV-HCC patients undergoing nucleos(t)ide analog (NA) therapy and of HBV DNA variation on patient survival. In this study, we aimed to investigate this issue in the real world.MethodsIn this single-center retrospective study, we reviewed 182 baseline hepatitis B surface antigen (HBsAg)-positive HBV-HCC patients who were treated with ICIs and pre-emptive NAs. The demographic characteristics, tumor status, treatments, HBV DNA, HBsAg, liver function, antitumor response, and patient survival were investigated. The primary endpoints were the virological breakthrough (VB) rate, HBV reactivation (HBVr) rate, and long-term HBV DNA control; the secondary endpoints were the overall survival (OS) and progression-free survival (PFS).Results(1) VB and HBVr occurred in 18.1% (33/182) and 4.4% (8/182) of patients with a median occurrence time of 3.9 months (range, 0.7–16.0) and 8.0 months (range, 3.0–16.0), respectively. The HBV DNA negative rates were 26.1% and 0 at 24 and 48 weeks in the VB group and 12.5% and 0 in the HBVr group, respectively. A baseline HBsAg level ≥200 IU/mL was the only risk factor for VB (OR 9.9, 95% CI 2.2 to 45.2, p=0.003); (2) patients with VB had much shorter median OS and median PFS than those without (12.3 months vs 18.1 months, p=0.035; 4.5 months vs 7.5 months, p=0.011).ConclusionsThere was a high risk of VB and a moderate risk of HBVr in HBsAg-positive HBV-HCC patients (with poor long-term HBV DNA control) undergoing ICI and pre-emptive NA therapies. The only risk factor for VB was the pretreatment HBsAg level. Further, VB might be considered as a clinical biomarker predicting inferior OS and PFS in the patients.

scholarly journals Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1654-1658 ◽  
Author(s):  
MG Rumi ◽  
M Colombo ◽  
R Romeo ◽  
G Colucci ◽  
A Gringeri ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hybridization Technique ◽  
Virus Infections ◽  
Hbsag Carriers ◽  
B Virus ◽  
Spot Hybridization ◽  
Hepatitis B Virus Infections

Abstract The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV- DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti- HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV- DNA may coexist with markers thought to reflect immunity against HBV.

scholarly journals Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1654-1658
Author(s):  
MG Rumi ◽  
M Colombo ◽  
R Romeo ◽  
G Colucci ◽  
A Gringeri ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hybridization Technique ◽  
Virus Infections ◽  
Hbsag Carriers ◽  
B Virus ◽  
Spot Hybridization ◽  
Hepatitis B Virus Infections

The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV- DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti- HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV- DNA may coexist with markers thought to reflect immunity against HBV.

scholarly journals Absence of HBV Reactivation in Patients With Resolved HBV Infection Following DAA Therapy for Hepatitis C: A 1-Year Follow-up Study

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Marcus M Mücke ◽  
Victoria T Mücke ◽  
Kai-Henrik Peiffer ◽  
Christoph Sarrazin ◽  
Stefan Zeuzem ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Hepatitis B ◽  
De Novo ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Direct Acting Antiviral ◽  
Long Term Follow Up

Abstract Background Patients with chronic hepatitis C virus (HCV) infection and active or previous hepatitis B virus (HBV) are at risk of HBV reactivation (HBV-R) during direct-acting antiviral (DAA) therapy. Recent reports suggest that HBV-R may even occur several months after completion of DAA therapy. The aim of this study was to assess the risk of HBV-R in patients with resolved HBV after successful DAA therapy during long-term follow-up (FU). Methods Among 848 patients treated for chronic HCV, all patients with resolved HBV and long-term FU data were eligible for inclusion. Patients were HBV DNA/hepatitis B surface antigen (HBsAg)–negative at the end of therapy (EOT) and were followed for up to 52 weeks thereafter. Patients underwent regular alanine transaminase (ALT) testing, and additional HBV DNA/HBsAg testing was performed at FU week 12, end of FU, and in case of an ALT increase above the upper limit of normal (&gt;ULN). Results A total of 108 patients were followed up for a mean (range) of 41.5 (24–52) weeks after EOT. None of the patients experienced reverse HBsAg seroconversion or reappearance of HBV DNA. One patient received a liver transplantation; 1 patient was diagnosed with de novo hepatocellular carcinoma, and 2 patients died. Eighteen patients (16.7%) had increased ALT levels (grade 0/1). Of those, the majority were male (72.2%) and significantly more patients had cirrhosis (66.7% vs 36.2%, P = .015) or received ribavirin as part of their treatment regimen (86.7% vs 46.8%, P = .041). None of these were associated with HBV-R. Conclusions Our results indicate that the risk of HBV-R in patients with resolved HBV treated with DAAs for HCV is low during long-term follow-up.

scholarly journals Prevalence of HCV and/or HBV coinfection in Iranian HIV-infected patients

2020 ◽  
Author(s):  
Farzaneh Dehghani-Dehej ◽  
Zinat Hosseini ◽  
Poupak Mortazkar ◽  
Khadijeh Khanaliha ◽  
Maryam Esghaei ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Cross Sectional Study ◽  
Hbv Dna ◽  
Hcv Rna ◽  
Hepatitis B E Antigen ◽  
Hbv Genotype ◽  
Cross Sectional ◽  
Hiv Rna ◽  
Hcv Coinfection

Aim: HIV-infected patients risk coinfection with HBV and HCV. This study aimed to investigate molecular epidemiology of HBV and HCV coinfection in Iranian HIV-infected individuals. Materials & methods: In this cross-sectional study, serological markers of HBV and HCV infection (hepatitis B surface antigen [HBsAg], hepatitis B e-antigen [HBeAg], hepatitis B e-antibody [HBeAb] and hepatitis B core antibody [HBcAb]) and anti-HCV antibodies [anti-HCV Abs] were tested in 198 Iranian HIV-infected patients. From plasma, HBV viral load was determined using COBAS TaqMan 48, and HCV-RNA was detected by reverse transcriptase-nested PCR. Results: 85 out of 198 (42.9%) patients were anti-HCV Ab positive and 42/198 (21.2%) had detectable HCV-RNA. Eight (4.0%) had traceable HBV-DNA. All these patients were infected by HBV genotype D. 55 (27.8%) were HBcAb positive. Nine (4.4%) were HBsAg and anti-HCV Ab positive. Conclusion: None were HIV-RNA/HCV-RNA/HBV-DNA positive, 21.2% were HIV-RNA/HCV-RNA positive and 4.0% were HIV-RNA/HBV-DNA positive. Therefore, studies on diagnosing these infections in HIV-infected individuals may be valuable.

scholarly journals Persistent HBV replication and serological response during up to fifteen years of tenofovir-based antiretroviral therapy in HIV-hepatitis B coinfected patients: a multicenter prospective cohort study

2021 ◽  
Author(s):  
Lorenza N C Dezanet ◽  
Patrick Miailhes ◽  
Caroline Lascoux-Combe ◽  
Julie Chas ◽  
Sarah Maylin ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hepatitis E ◽  
Hbv Dna ◽  
Serological Response ◽  
Viral Loads ◽  
Hbsag Seroclearance

Objectives To determine the extent of hepatitis B virus (HBV) suppression and its association with hepatitis "e" antigen (HBeAg) and hepatitis B surface antigen (HBsAg)-seroclearance in HIV-HBV-coinfected patients undergoing long-term tenofovir (TDF)-based antiretroviral therapy (ART). Methods We prospectively followed 165 HIV-HBV-coinfected patients undergoing TDF-based ART. Serum HBV-DNA viral loads, HBeAg and HBsAg were obtained at TDF-initiation and every 6-12 months. We calculated the proportion achieving virological response (VR, <60 IU/mL) during follow-up. We also calculated rates of HBeAg- and HBsAg-seroclearance, which were compared between those who achieved versus never achieved VR during follow-up using an exact binomial test. Results During a median 8.1 years (IQR=4.0-13.2) of TDF-treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up=608 IU/mL, range=67-52,400,000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during TDF-treatment: 15.1% (n=14/93) at 5-years, 3.2% (n=2/62) at 10-years and, 3.2% (n=1/31) at 15-years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, p=0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, p=0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (p<0.001). Conclusions During long-term TDF-based ART for HIV-HBV coinfection, persistent HBV viremia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression.

scholarly journals Combination of Entecavir or Tenofovir with Pegylated Interferon-α for Long-Term Reduction in Hepatitis B Surface Antigen Levels: Simultaneous, Sequential, or Add-on Combination Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1456
Author(s):  
Kanako Yoshida ◽  
Masaru Enomoto ◽  
Akihiro Tamori ◽  
Shuhei Nishiguchi ◽  
Norifumi Kawada
Keyword(s):  
Hepatitis B ◽  
Combination Therapy ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Interferon Α ◽  
Chronic Hepatitis B Virus ◽  
Hbsag Seroclearance

Seroclearance of hepatitis B surface antigen (HBsAg) (“functional cure”) is the optimal endpoint of antiviral therapy for chronic hepatitis B virus (HBV) infection. Currently available anti-HBV therapy includes nucleoside/nucleotide analogs (NAs) and peginterferon-α (Peg-IFNα). Combination of NAs and Peg-IFNα, each with different mechanisms of action, is an attractive approach for treating chronic HBV infection. In earlier studies, compared with monotherapy using IFNα, combination therapy showed greater on-treatment HBV DNA suppression but no difference in the sustained response. However, responses to the combination of non-pegylated IFNα with lamivudine or adefovir were not assessed based on HBsAg quantification but were defined by normal alanine aminotransferase levels, testing negative for hepatitis B e-antigen, and low HBV DNA load over a short term. Here, we reviewed previous reports regarding the effects of combination therapy of entecavir or tenofovir with Peg-IFNα, focusing on long-term reduction in HBsAg levels. Regimens of combination therapy were classified into “simultaneous” combination (“de novo” strategy); “sequential” combination, which involved starting with one therapy followed by the other (“switch-to” strategy); “add-on” combination, which involved adding Peg-IFNα to an ongoing NAs. Some studies have shown promising results, but there is no robust evidence that combination therapy is superior to monotherapy. Large studies are needed to assess the safety and efficacy of combination therapies to increase the rates of HBsAg seroclearance over the long term.

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