Low-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.
Antiviral Agents/therapeutic use* ; DNA, Viral ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Nucleosides/therapeutic use* ; Tenofovir/therapeutic use* ; Treatment Outcome ; Viremia/drug therapy*

Oral nucleos(t)ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB). Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. "An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues," is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.
Antiviral Agents/therapeutic use* ; Consensus ; Guidelines as Topic/standards* ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Humans ; Nucleosides/therapeutic use* ; Outcome Assessment, Health Care/methods* ; Practice Guidelines as Topic ; Treatment Outcome

A high maternal viral load is the most important factor affecting immunoprophylaxis against mother-infant transmission of HBV. The application of antiviral drugs in pregnant women with a high serum HBV DNA level (>10(6)~10(7) IU/ml) during the second and third trimesters can reduce the prenatal serum HBV DNA level and significantly increase the success rate of blocking mother-infant transmission in neonates. This article interprets the contents related to antiviral therapy for pregnant women carrying HBV with the purpose of blocking mother-infant transmission of HBV in the guidelines published by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, National Institute for Health and Care Excellence, Korean Association for the Study of the Liver, and World Health Organization.
Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B ; drug therapy ; prevention & control ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Practice Guidelines as Topic ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Viral Load

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the management of drug-resistant chronic hepatitis B. However, it remains unclear whether TDF-nucleoside analogue combination therapy provides better outcomes than TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B. METHODS: This retrospective cohort study included 76 patients receiving TDF-based rescue therapy for more than 12 months. Suboptimal response was defined as serum HBV-DNA level of >60 IU/mL during prior rescue therapy. Multi-drug resistance was defined as the presence of two or more drug resistance-related mutations confirmed by mutation detection assay. The relationship between baseline characteristics and virologic response (HBV DNA <20 IU/mL) at 12 months were evaluated using logistic regression analysis. RESULTS: Fifty-five patients (72.4%) were suboptimal responders to prior rescue therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%) received combination therapy with nucleoside analogues. Virologic response at 12 months was not significantly different between the TDF monotherapy group and TDF-nucleoside analogue combination therapy group (p=0.098). The serum HBV DNA level was reduced to -4.49+/-1.67 log10 IU/mL in the TDF monotherapy group and to -3.97+/-1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy group at 12 months (p=0.18). In multivariate analysis, female sex (p=0.032), low baseline HBV-DNA level (p=0.013), and TDF monotherapy (p=0.046) were predictive factors for virologic response at 12 months. CONCLUSIONS: TDF monotherapy showed similar efficacy to that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.
Adult ; Aged ; Antiviral Agents/pharmacology/*therapeutic use ; Cohort Studies ; DNA, Viral/blood ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Hepatitis B virus/drug effects/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Nucleosides/chemistry/therapeutic use ; Retrospective Studies ; Sex Factors ; Tenofovir/*therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the efficacy and related factors of pegylated-interferon alpha-2a (PEG-IFN-2a) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who achieved partial viral response with nucleoside analogue (NA) therapy.

METHODSPatients with HBeAg-positive CHB and partial viral response to NA treatment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personlized duration of time. The existing NA therapy was continued in combination with the new PEG-IFN-2a treatment for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg and hepatitis B e antibody (anti-HBe) were taken at baseline (prior to addition of the PEG-IFN-2a therapy) and every 3 months afterwards.For determining response to treatment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg less than 10 IU/mL and HBeAg seroconversion.Statistical analysis was carried out using SPSS statistical software.

RESULTSA total of 81 consecutive patients with an average of 12.0 months (range: 6.0-24.0 months) of NA therapy were included in the study and received an average of 19.6 months (range: 15.5-33.3 months) of PEG-IFN-2a treatment. At the end of PEG-IFN-2a therapy, 7 (8.6%) of the patients achieved undetectable HBsAg and seroconversion, and 14 (17.3%) showed HBsAg less than 10IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that (38.3%) seen in treatment-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at less than 1500 IU/mL may predict end of PEG-IFN-2a treatment response for HBsAg less than 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%.

CONCLUSIONPatients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic strategy.

Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Nucleosides ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Sensitivity and Specificity ; Treatment Outcome ; Viral Load

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Prognosis

Adenine ; analogs & derivatives ; therapeutic use ; Drug Combinations ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleic Acid Synthesis Inhibitors ; therapeutic use ; Nucleosides ; antagonists & inhibitors ; biosynthesis ; Organophosphonates ; therapeutic use ; Thymidine ; analogs & derivatives ; therapeutic use

Antiviral Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; administration & dosage ; therapeutic use ; Nucleosides ; administration & dosage ; therapeutic use ; Polyethylene Glycols ; administration & dosage ; therapeutic use

DNA, Circular ; blood ; Hepatitis B ; blood ; drug therapy ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Humans ; Nucleosides ; therapeutic use

Adult ; Aged ; Carcinoma, Hepatocellular ; epidemiology ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Neoplasms ; epidemiology ; Male ; Middle Aged ; Nucleosides ; administration & dosage ; therapeutic use