Tenofovir alafenamide (TAF) is recommended for chronic hepatitis B (CHB) treatment in international guidelines according to its efficacy and safety. However, in phase III study, an increased LDL-c was observed in those who were switched from Tenofovir disoproxil fumarate (TDF) to TAF. Limited data exists on whether lipid profiles change only in individuals who switched to TAF from TDF or from any nucleoside/nucleotide analogues (NUC). We investigated how switching to TAF affected lipid and cardiovascular outcomes in Thai CHB patients.

We conducted a prospective observational study including CHB patients who had to switch from their prior NUC to TAF according to the national reimbursement policy in late 2022. All enrolled patients had lipid tests and transient elastography (TE) done at 0 and 48-week post-switch to TAF. Demographic data, prior NUC, liver biochemistry, controlled attenuated parameter (CAP) and liver stiffness (elastic modulus; E) data measured by TE were collected. The changes in lipid, Thai cardiovascular (CV) risk score, and TE results between 0 and 48-week were compared.

A total of 110 patients who were switched to TAF and completed 48-week follow-up were analyzed. The prior NUCs were as follows: 47 Lamivudine (LAM), 22 Entecavir (ETV), and 41 TDF-based. Baseline characteristics were similar between the three groups except for underlying hypertension was more frequent and baseline total cholesterol was lower in the TDF-based group. At 48-week post-switch, the median LDL-c changes were -2.45, -5.9 and +8.8 mg/dL (p<0.001), and total cholesterol changes were -4.5, -4 and +17 mg/dL (p<0.001), in the ETV, LAM, and TDF-based group, respectively. Whereas the changes in hepatic steatosis (measured by CAP), and liver stiffness (measured by E) as well as Thai CV risk score were not significantly different. No cardiovascular events occurred during follow-up.

Significant increase in LDL-c and total cholesterol after switching to TAF were observed only in patients with prior TDF, but not in those with prior ETV or LAM. Careful monitoring of lipids after the switch may not be universally needed. Data regarding long-term cardiovascular outcomes are warrant.

The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

The risk of mother-to-child transmission for pregnant women with chronic hepatitis B (CHB) still exists, especially for those with high HBV DNA levels. The guidelines for initiating prophylaxis for pregnant women with CHB vary across countries. We aimed to explore the latest prophylaxis initiation time for these women.

We collected the real-world clinical data of 328 pregnant women aged 20-49 with CHB, who were treated with telbivudine or tenofovir disoproxil fumarate, from July 2010 to December 2020 in China. A mathematical model was developed to describe the viral kinetics of HBV after prophylaxis. We calculated the time required to reduce viral load below the threshold value of 5.3 log10 IU/ml. We derived the prophylaxis initiation time by subtracting the required time to threshold from the childbirth gestational week.

The median time for 328 women to reduce HBV DNA levels below the threshold of 5.3 log10 IU/ml was 4.2 (range: 0.2-12.8) weeks, corresponding to a prophylaxis initiation time of no later than 35.1 (25.2-41.4) weeks. Specifically, for women with viral loads >8.0 log10 IU/ml, prophylaxis should be initiated before 33.9 (25.2-39.5) weeks, and even before the lower bound of 25.2 weeks, to maximize clinical safety. For women with viral load >7.0 to ≤8.0 log10 IU/ml, prophylaxis should be initiated before 35.5 (28.6-39.8) weeks, and for women with viral load >5.3 to ≤7.0 log10 IU/ml, prophylaxis should be initiated before 36.2 (28.3-41.4) weeks.

Pregnant women with HBV DNA levels >5.3 to ≤8.0 log10 IU/ml can initiate prophylaxis before 28 gestational weeks. However, women with HBV DNA >8.0 log10 IU/ml could consider initiating prophylaxis before 25 weeks.

This study investigates how long it takes to decrease maternal viral load below a threshold (5.3 log10 IU/ml) after receiving antiviral prophylaxis in pregnant women with different HBV DNA levels based on real-world clinical data and mathematical modelling, which provides quantitative evidence on the initiation time of antiviral prophylaxis. The results show that pregnant women with CHB infection at high HBV DNA levels (>8 log10 IU/ml) should initiate antiviral prophylaxis earlier to decrease the risk of mother-to-child transmission of HBV. Physicians can determine when to begin antiviral prophylaxis for those women according to their maternal HBV DNA levels. Our findings justify the initiation time of antiviral prophylaxis recommended by the Chinese guidelines and will offer new insights for other international guidelines.

The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study.

In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log 10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected 8 week) or to 4 weeks postpartum (expected 12 week) were randomly enrolled at a 1:1 ratio and followed until 6 months postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary end point was the safety of mothers and infants. The secondary end point was the HBV-MTCT rate of infants at the age of 7 months.

Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in 2 groups completed the study. Overall, TAF was well tolerated, no one discontinued the therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n = 231) and at 7 months (n = 222) was normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log 10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at the age of 7 months. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) vs 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the 2 groups had mildly elevated alanine aminotransferase levels at 3 months and 6 months postpartum, respectively ( P = 0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] vs 0% [0/120, 0%-3.1%]).

Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected 8-week prenatal duration is feasible. ClinicalTrials.gov , NCT04850950.

In an aging population, patients with chronic hepatitis B (CHB) may face a higher risk of osteopenia, osteoporosis, or fractures. We investigated the epidemiology and risk factors associated with osteopenia or osteoporosis in patients with CHB.

This retrospective cohort study included patients ≥ 19 years who underwent bone mineral density (BMD) testing ≥ 2 times between 2005 and 2021 at Severance Hospital, Seoul, South Korea. Demographic factors and comorbidities for patients with or without CHB were matched based on a 1:4 ratio. Cox proportional hazard regression models were used to estimate hazard ratios to assess osteopenia or osteoporosis risk.

A total of 275 patients with CHB and 7868 patients without CHB who had normal BMD were analyzed. The incidence of osteopenia or osteoporosis in patients with and without CHB was 25.8% and 28.7%, respectively. After propensity score matching, in the second BMD test, 73.8%, 24.7%, and 1.5% of patients with CHB and 70.7%, 26.5%, and 2.8% of patients without CHB had normal BMD, osteopenia, and osteoporosis, respectively. Risk factors for osteopenia or osteoporosis in these patients were age, body mass index < 25, chronic kidney disease, and proton pump inhibitor use. There were no significant differences in cumulative hazard for patients with or without CHB.

Patients with or without CHB showed similar risks of osteopenia or osteoporosis. In addition to providing closer monitoring for patients with CHB with greater bone disease risk, further studies of bone disease in these patients may help to understand the factors that impact bone health.

Extrahepatic manifestations of chronic hepatitis B virus (HBV) infection include development of kidney disease (KD). While anti-HBV treatment reduces the risk of liver-related events, the impact of HBV treatment on KD remains unclear. Using a large US-based electronic medical record (EMR) database, we examined whether patients with HBV are at higher risk of developing KD, whether the development of KD is associated with HBV-related liver disease, and whether anti-HBV treatment mitigates these risks.

Data were queried from the IQVIA Ambulatory EMR database from 2006 to 2020. Propensity score matching was performed to better ensure balance across analyses. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs for onset of KD between groups.

Among patients with and without HBV (n = 11,772 each), those with HBV were more than twice as likely to develop KD vs. matched controls without HBV infection (HR, 2.18 [95% CI, 1.90-2.50]; p < 0.001); most events occurred after age 55 years. Patients with HBV and concomitant hypertension, diabetes, or obesity had a greater likelihood for development of KD by age 75 years (19% with HBV vs. 6% without HBV); the cumulative probability of developing KD among patients with HBV along with concomitant comorbidities surpassed the additive risk of developing KD among those who had the comorbidities without HBV or only had HBV. Among patients with HBV, advanced liver disease was not significantly associated with KD. Patients treated with antivirals had a lower risk for KD compared with untreated HBV patients (HR, 0.61 [95% CI, 0.42-0.87]; p < 0.01).

HBV infection contributes to the development of KD, and anti-HBV treatment can lower KD risk. As such, clinicians should consider screening patients for HBV infection or initiating treatment early, particularly in patients with risk factors for KD.

Clinical studies of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) treatment in patients with HBV-related decompensated cirrhosis (HBV-DC) are limited. This study evaluated the efficacy and safety of TMF versus TAF in naive-treated patients with first-time HBV-DC. Based on the antiviral drug used, patients were categorised into the TMF group and the TAF group. Virological and serological responses, hepatic and renal functions and blood lipid changes in both groups were evaluated during 48 weeks of treatment. A total of 98 patients were enrolled, 45 in the TMF group and 53 in the TAF group. At 48 weeks of treatment, the proportions of patients who achieved complete virological response (CVR) were 85.7% and 90.7%, respectively (p = 0.791). Improvement of at least 2 points in Child-Turcotte-Pugh scores was observed in 64.3% versus 79.1% (p = 0.169) of the patients. There were no significant changes in serum creatinine, estimated glomerular filtration rate or total cholesterol from baseline to week 48 between the two groups. Cystatin C remained stable in the TMF group but increased over time in the TAF group (p < 0.001). Low-density lipoprotein cholesterol remained stable in the TMF group but increased significantly in the TAF group at week 48 (p = 0.015). These results suggest that both TMF and TAF can rapidly suppress HBV replication, improve hepatic function and have no negative effects on renal function among patients with HBV-DC. Regarding lipid metabolism, both showed a better safety, while regular monitoring of blood lipid levels is recommended.

The Asia-Pacific (AP) region carries a substantial burden of HBV. Affordable HBV treatment is crucial to attain WHO's elimination goal. This study assesses the pricing and affordability of HBV treatment in AP.

A survey conducted among APASL members from 2 Aug to 30 Oct, 2023, gathered data on antiviral HBV drugs, treatment costs covering stages of chronic hepatitis B (CHB), compensated cirrhosis (CC), hepatocellular carcinoma (HCC), liver transplant, and monitoring expenses. Drug costs for TDF and ETV were compared to international reference price (TDF: $30, ETV: $36 per person per year), generating a median price ratio (MPR) where MPR < 1 indicated an acceptable local price. Affordability was evaluated by comparing yearly CHB treatment cost to yearly minimum wage in each country/area, all converted to 2023 US$.

ETV costs ranged from $42 per person per year in Pakistan to $2640 in Malaysia, while TDF costs varied from $12 in mainland China to $2446 in Hong Kong. Almost all MPR exceeded 1. Affordability of HBV treatment varied, with CHB patients in Australia paying 1.4% of minimum yearly wage to get 1 year CHB treatment, in contrast to Myanmar's 78.6%. Affordability disparities were also evident for patients with CC, HCC, and liver-transplant needs, though monitoring costs were generally affordable.

Despite patent expiration and availability of low-cost generics for TDF and ETV, HBV medication costs in Asia-Pacific region remain high. CHB treatment is generally unaffordable for patients, posing a significant barrier to HBV elimination in this endemic region.

Liver cancer is the third leading cause of death globally, with hepatitis B virus (HBV) infection being identified as the primary risk factor for its development. The occurrence of HBV-related hepatocellular carcinoma (HCC) is attributed to various mechanisms, such as chronic inflammation and liver cell regeneration induced by the cytotoxic immune response triggered by the virus, abnormal activation of oncogenes arising from HBV DNA insertion mutations, and epigenetic alterations mediated by viral oncoproteins. The envelope protein of the HBV virus, known as hepatitis B surface antigen (HBsAg), is a key indicator of increased risk for developing HCC in HBsAg-positive individuals. The HBsAg seroclearance status is found to be associated with recurrence in HCC patients undergoing hepatectomy. Additional evidence indicates that HBsAg is essential to the entire process of tumor development, from initiation to advancement, and acts as an oncoprotein involved in accelerating tumor progression. This review comprehensively analyzes the extensive effects and internal mechanisms of HBsAg during the various stages of the initiation and progression of HCC. Furthermore, it highlights the importance and potential applications of HBsAg in the realms of HCC early diagnosis and personalized therapeutic interventions. An in-depth understanding of the molecular mechanism of HBsAg in the occurrence and development of HCC is provided, which is expected to develop more precise and efficient strategies for the prevention and management of HCC in the future.

Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group (P < 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2400089257.

Hepatitis B virus (HBV) infection remains a significant global health challenge, often leading to severe liver complications such as cirrhosis and cancer. Current treatments rely heavily on nucleos(t)ide analogues like adefovir and tenofovir due to their potent antiviral effects. However, their clinical utility is limited by insufficient liver targeting, leading to off-target side effects, particularly nephrotoxicity. To improve liver-specific drug delivery and reduce adverse effects, we designed novel liver-targeted prodrugs by conjugating adefovir and tenofovir with N-acetylgalactosamine (GalNAc) and tris-GalNAc ligands, which have high affinity for the asialoglycoprotein receptor (ASGPR) predominantly expressed in hepatocytes. Four prodrugs (A1, A2, T1, and T2) were synthesized and evaluated for cytotoxicity, maximum tolerated dose, anti-HBV activity, metabolic stability, pharmacokinetics, and liver-targeting properties. The prodrugs exhibited low cytotoxicity, robust anti-HBV activity, and enhanced selectivity compared to their parent drugs. Notably, the tris-GalNAc conjugates A2 and T2 demonstrated superior liver targeting, showing a threefold higher concentration in the liver compared to the kidneys, thus minimizing renal exposure. These findings suggest that GalNAc and tris-GalNAc conjugation is a promising strategy for enhancing the therapeutic efficacy and safety of adefovir and tenofovir, with potential for further optimization as liver-targeted anti-HBV prodrugs.

The data on tenofovir alafenamide (TAF) in kidney transplant recipients (KTRs) with chronic hepatitis B virus (HBV) infection is limited.

Retrospective cohort study SETTING & STUDY POPULATIONS: HBsAg-positive KTRs who received TAF between 2019 and 2022 were included in the analysis, categorized into treatment-naïve and treatment-experienced groups. Additionally, a subgroup of patients receiving ETV was analyzed for comparison.

Four treatment-naïve (Group I) and 35 treatment-experienced (Group II) patients received TAF for 26.4±11.3 and 43.7±19.0 months, respectively. Both groups showed significant HBV DNA reduction, but Group I achieved higher rates of undetectable HBV DNA (50%, 75%, 75%, 100% at 6, 12, 24, 30 months, compared with 16.7%, 25.3%, 31.4%, 34.7% in Group II, p=0.018). Renal allograft function remained stable during follow-up, and bone toxicity was minimal. For ETV, 10 patients demonstrated excellent viral suppression (HBV DNA undetectable in 70% at 48 weeks and 100% at 96 weeks) with stable renal function over a median of 5.2 years.

Retrospective study with a lack of prospective comparison of TAF and ETV.

Our results suggest that TAF provides favorable efficacy, renal safety, and tolerability in KTRs. ETV also provided effective and sustainable viral suppression. TAF may offer additional advantages such as no concern of viral resistance and dose adjustment by eGFR levels for long-term management of HBsAg-positive KTRs.

RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression.

We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months.

Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or <100 IU/mL at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg <100 IU/mL and >100 IU/mL at nadir or ≤24 weeks from last dose could maintain or achieve HBsAg <100 IU/mL at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs 0.21 log IU/mL/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r=-0.427, p=0.001).

Short-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants.

Tenofovir disoproxil fumarate (TDF) is a third-generation nucleoside analogue commonly used as a first-line therapy for chronic hepatitis B virus (HBV) infection. However, it is associated with nephrotoxicity, which can occur through mechanisms such as mitochondrial deoxyribonucleic acid (DNA) depletion and damage to renal tubules. This nephrotoxic effect typically manifests as a mild increase in serum creatinine and a decrease in serum phosphate, usually within 4-12 months after starting treatment. Recent studies suggest that novel biomarkers, such as urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, may predict acute kidney injury (AKI) earlier and more accurately than traditional markers like serum creatinine. In line with this, we investigated NGAL and cystatin C levels in HBV patients receiving TDF therapy to assess their potential in monitoring kidney function.

The study included 350 cases in total. Each participant underwent a thorough assessment, including a detailed medical history, clinical examination, and routine blood tests, as outlined in the study's working proforma. Based on the above details, 226 cases fulfilling the inclusion criteria were enrolled for the second step of the study, where a 5 mL urine sample from each case was taken and sent to the pathology laboratory for estimation of cystatin C and NGAL by the ELISA method with the help of a kit.

The average age of the participants was 37.93 years, with 124 individuals falling within the 18-35-year age-group. After accounting for confounding factors, 87 cases were identified, predominantly young males, who exhibited elevated levels of both urinary NGAL and cystatin C.

In this cross-sectional study, after controlling for confounding factors, we observed that TDF treatment was linked to elevated levels of urinary NGAL and cystatin C in 87 (38.4%) of the cases. Notably, increased levels of these biomarkers were also found in the younger age-group (18-35 years). These findings suggest the need for further prospective studies with larger sample sizes to better understand the direct impact of TDF on kidney function in hepatitis B patients.

Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the immune response against HBV but are functionally impaired in patients with chronic hepatitis B. The underlying mechanisms involved in HBV-induced DC dysfunctions remain to be elucidated.

We explored DC modulations by HBV and HBsAg by exposing blood-derived cDC1s, cDC2s, and plasmacytoid DCs from healthy donors to HBV or HBsAg and stimulating them with toll-like receptor ligand. Their phenotypic and functional features, as well as their metabolic profile, were analyzed through multiparametric flow cytometry and multiplex assays and further explored on patients' samples.

We found that HBV deeply reshaped the DC secretome in response to toll-like receptor ligand. Strikingly, we observed that HBV-exposed DCs secrete high levels of CX3CL1 (fractalkine), a chemokine responsible for attracting antiviral effectors to the site of infection. HBsAg exposure favored DC activation while drastically altering TRAIL expression in response to toll-like receptor ligand and increasing the secretion of cytokines/chemokines involved in immune tolerance. HBsAg further dampened the metabolism of DC subsets while driving metabolic switches. Notably, the relevance of the CX3CL1/CX3CR1 axis, TGF-β, and metabolic disturbances was demonstrated within intrahepatic DC subsets in patients according to disease stage.

Our work brings new insights into the immunomodulation induced by HBV on DCs, which contribute to impaired antiviral responses and progression toward chronicity.

We aimed to analyze the relationships between single nucleotide polymorphisms in the ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2) genes and plasma concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC).

We recruited 10 people living with HIV receiving once-daily treatment with a single tablet containing TAF (25 mg), FTC (200 mg), and bictegravir (50 mg). Peripheral blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, and 24 h after administration. Plasma concentrations of TAF, TFV, and FTC were quantified using liquid chromatography-tandem mass spectrometry. Genotyping for allelic variants of ABCB1, including 1236C > T (rs1128503), 2677 G > T/A (rs2032582), 3435C > T (rs1045642), 4036 A > G (rs3842) and ABCG2 421C > A (rs2231142), was performed using TaqMan Drug Metabolism Assays.

None of the genotypes for ABCB1 1236C > T, 2677 G > T/A, 3435C > T, and ABCG2 421C > A exhibited correlations with plasma concentrations of TAF, TFV, and FTC. In contrast, individuals with the ABCB1 4036 AG genotype (188.7 ng/mL, n = 3) exhibited a significantly higher mean peak plasma concentration of TAF than those with the ABCB1 4036 AA genotype (67.7 ng/mL, n = 7) (p = 0.0167). However, these genotypes did not affect the elimination of terminal half-lives of TAF.

The allelic variant ABCB1 4036 A > G is associated with reduced protein expression and function of ABCB1. Individuals with this genetic variant exhibited significantly high peak plasma concentrations of TAF, potentially due to the reduced expression of efflux transporters in the intestines linked to this variant.

There is limited information comparing the off-therapy relapse rates of patients discontinued tenofovir alafenamide (TAF) to those stopping entecavir or tenofovir disoproxil fumarate (TDF).

A total of 805 hepatitis B e antigen-negative patients without cirrhosis receiving entecavir (n = 406), TDF (n = 260), or TAF (n = 139) were enrolled. Propensity score matching method was applied to eliminate the significant differences in clinical characteristics.

The cumulative incidences of virological relapse, clinical relapse, and retreatment at 96 weeks were higher in the off-TAF group (89.6%, 70.3%, and 59.2%, respectively) than that in the off-entecavir group (65.9%, 42.8%, and 28.8%, respectively) or the off-TDF group (73.7%, 49.8%, and 35.7%, respectively). The median time to clinical relapse was much earlier for off-TAF patients than for off-entecavir or off-TDF (median 14, 57, and 26 weeks, respectively), and these findings persisted even after propensity score matching. Multivariate analysis indicated that TAF therapy was an independent risk factor of virological relapse, clinical relapse, and retreatment when compared with entecavir or TDF. Hepatitis B surface antigen levels at end of treatment were predictive of virological, but not clinical, relapse in the off-TAF group, although this group had a lower rate of severe hepatitis on clinical relapse than the off-TDF group. Finally, there was no significant difference in the hepatic decompensation rate among the entecavir, TDF, and TAF groups.

There is an earlier and higher hepatitis B virus relapse rate in patients who discontinue TAF therapy than in comparable patients discontinuing entecavir or TDF therapy. Close monitoring is necessary after TAF withdrawal, particularly in the first 3 months.

In this editorial, we comment on the article by Meng et al. Chronic hepatitis B (CHB) is a significant global health problem, particularly in developing countries. Hepatitis B virus (HBV) infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma. Prevention and treatment of HBV are key measures to reduce complications. At present, drug therapy can effectively control virus replication and slow disease progression, but completely eliminating the virus remains a challenge. Anti-HBV treatment is a long-term process, and there are many kinds of antiviral drugs with different mechanisms of action, it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients' compliance. We will summarize the current status of CHB drug treatment, hoping to provide a reference for the selection of clinical antiviral drugs.

Chronic hepatitis B remains a substantial global health challenge, impacting approximately 254 million people worldwide. A cure for this condition is yet to be discovered. Early identification and effective treatments coupled with vigilant monitoring can help alleviate associated morbidity and mortality due to potential complications such as liver cirrhosis and hepatocellular carcinoma.

Background. Chronic hepatitis B (CHB) is a lifelong disease requiring long-term or indefinite therapy, resulting in substantial economic burden. Thus, careful consideration must be used in the selection of therapies. Aim. This analysis assessed the cost-effectiveness of tenofovir alafenamide (TAF) compared with tenofovir disoproxil fumarate (TDF) and entecavir (ETV) from the perspective of the Taiwan National Health Insurance Administration Healthcare payer for the management of CHB over a lifetime horizon. Methods. An individual patient simulation model assessed the impact of treatment on CHB infection for liver- and safety-related outcomes. Patients could achieve spontaneous or treatment-induced responses, experience a reactivation of the disease, develop long-term liver complications, or experience treatment-related renal or bone complications. Patient population profiles were based on clinical trial and real-world data. Data on clinical parameters (safety, mortality, resistance risk, and flare), health utilities, and costs were sourced from the published literature. Results. TAF was associated with fewer liver disease events and fewer cases of bone and renal complications per 100 person-years. TAF also had higher eAg and sAg seroconversion compared with TDF and ETV. As compared with both treatments, TAF was both more effective and more costly, resulting in incremental cost-effectiveness ratios of USD 3,348 and USD 3,940 per quality-adjusted life-year gained versus TDF and ETV, respectively. Conclusion. TAF leads to better health outcomes at acceptable incremental costs compared with the most commonly used therapies in the management of CHB, thus making it a cost-effective option for the treatment of CHB in Taiwan.

The cost-effectiveness of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) and entecavir (ETV) was assessed in patients with chronic hepatitis B in Taiwan.TAF was associated with fewer liver disease events, fewer cases of bone and renal complications, and higher eAG and sAG seroconversion compared with TDF and ETV; TAF was found to be cost-effective compared with both treatments.

Achieving HBsAg seroclearance is a key goal in treating chronic hepatitis B virus (HBV) infection but remains difficult with nucleos(t)ide analogues (NAs). Tenofovir alafenamide fumarate (TAF), a recommended NA for managing chronic HBV infection (CHB), has uncertain effects on HBsAg levels and potential adverse events when used long-term after switching from entecavir (ETV). We retrospectively evaluated 77 CHB patients, including 47 who switched from ETV to TAF with a median follow-up of 40 months post-switch and a median of 60 months of HBsAg monitoring pre-switch. No significant change in HBsAg levels was observed in the overall cohort post-switch, consistent with the ETV continuation group. However, a significant decrease in HBsAg was noted in patients with HBsAg < 100 IU/mL at the time of switching. HBsAg loss occurred in three patients who switched to TAF. No adverse effects were observed, and TAF was well tolerated. The most significant factor associated with achieving HBsAg < 100 IU/mL was the Fib-4 index, a marker of liver fibrosis, at the time of switching. Switching from ETV to TAF is an effective strategy in CHB management, with hepatic inflammation potentially playing an essential role in achieving HBsAg decrease. Patients with increased Fib-4 index were significantly more likely to show decreased HBsAg. This finding suggests patients with mild to moderate fibrosis may respond better to TAF in terms of HBsAg reduction.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain significant public health challenges in Asia, affecting millions and contributing to substantial morbidity and mortality. The prevalence of these infections varies across the region, with factors such as vaccination coverage, healthcare infrastructure, and sociocultural barriers influencing the epidemiology of both viruses. The persistent burden of chronic HBV, particularly in older populations, and the evolving HCV genotype landscape highlight the need for targeted, region-specific strategies. Universal screening programs have emerged as essential tools for detecting undiagnosed cases and optimizing healthcare resource allocation. Given the overlapping epidemiology of HBV and HCV, comprehensive public health interventions tailored to the unique contexts of different Asian countries are crucial for achieving global elimination goals. This review examines the epidemiological trends, challenges, and opportunities for addressing HBV and HCV in Asia, emphasizing the importance of overcoming sociocultural barriers to improve prevention, diagnosis, and treatment efforts across diverse populations.

Hepatitis B virus (HBV) affects hundreds of millions globally, with many cases stemming from perinatal transmission. Chronic hepatitis B (CHB) in children can progress to cirrhosis and hepatocellular carcinoma (HCC) in adulthood. Treatment options include interferons and nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs) such as tenofovir alafenamide (TAF).

This review covers the epidemiology of pediatric CHB and current treatments, with a focus on tenofovir-based therapies, particularly tenofovir disoproxil fumarate (TDF) and TAF. TDF has been used for years, but its risks of bone mineral density loss and renal impairment have raised concerns. TAF, with lower systemic exposure, appears to mitigate these risks. Ongoing trials are evaluating TAF's safety in younger children. There are knowledge gaps in long-term safety and the potential for combination therapies.

TAF offers a safer alternative to TDF for children with CHB, showing high antiviral efficacy and fewer side effects. However, more data are needed on its use in younger children and long-term safety. The future of CHB treatment in pediatrics may include combination therapies and personalized approaches, potentially improving outcomes and minimizing risks over a lifetime of treatment. As research progresses, TAF is likely to become a cornerstone in pediatric CHB management.

Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). No data are available on the long-term prognosis or safety of tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), or entecavir (ETV) in treating HBV-ACLF globally. This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.

In this prospective, real-world cohort study, patients with HBV-ACLF were assigned to the TAF, TDF, and ETV groups. A total of 199 patients completed the 144-week follow-up. After propensity score matching (PSM), 44 patients remained in each group for further analysis of survival status, incidence of hepatocellular carcinoma (HCC), virological response, and liver and renal function indicators.

In the original cohort, HCC developed in one patient in each group. No serious drug-related adverse events were observed. In the PSM cohort, the 144-week survival rates were 56.82%, 75.00%, and 59.09% in the TAF, TDF, and ETV groups, respectively (P = 0.118). When stratified into noncirrhosis and cirrhosis subgroups at baseline, the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients (P = 0.338), and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients (P = 0.052), but the differences were not statistically significant. The long-term overall survival rates in the TAF, TDF, and ETV groups were comparable. After 144 weeks, no significant difference in the virological response rate or liver or renal function indicators was found among the three groups, except for the level of aspartate aminotransferase, which was significantly higher in the TDF group than in the ETV group at week 144 (P = 0.001).

There were no significant differences in the survival rate, incidence of HCC, efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.

ClinicalTrials.gov NCT03920618.

This study aimed to compare the serum lipid profiles between tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in the long-term treatment of chronic hepatitis B (CHB). We analyzed data from treatment-naïve CHB patients administered with TDF or TAF, collected from electronic medical records between May 2017 and September 2022. Serum lipid indices, including total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL), and their ratios (TC/HDL, LDL/HDL), were assessed at baseline, and at 48 and 96 weeks. Propensity score matching (PSM) adjusted for baseline differences between groups. From 2344 patients initially screened, 418 were included for the 48-week analysis (265 on TDF, 153 on TAF) and 292 for the 96-week analysis (238 on TDF, 54 on TAF). At 48 weeks, comparing the serum lipid indicators between the pre- and post-treatment, TDF significantly reduced TC and TC/HDL, whereas TAF induced widespread dyslipidemia, characterized by elevated levels of TC, TG, LDL, LDL/HDL, and TC/HDL, and reduced HDL (P < 0.05). After PSM grouping, TAF remained significantly associated with higher TC, TG, LDL, LDL/HDL, and TC/HDL compared to TDF (P < 0.05). Over 48 weeks, TAF treatment was associated with significant increases in TC, TG, and LDL, whereas TDF treatment led to decreases (P < 0.05). TC/HDL and LDL/HDL increased in both groups, but more significant in TAF (P < 0.05). At 96 weeks, the TAF group continued to exhibit significantly higher levels of TC, LDL, and LDL/HDL compared to the TDF group (P < 0.05). Notably, LDL levels were 115.65 ± 28.07 mg/dL in TAF versus 96.07 ± 23.97 mg/dL in TDF. The increase in TC/HDL ratio in the TAF group was higher than in the TDF group, though not statistically significant. Furthermore, TAF treatment was associated with significant increases in LDL (18.58 ± 24.35 mg/dL) and LDL/HDL ratio (0.41 ± 0.95) over 96 weeks, while TDF treatment showed reductions in TC (-8.13 ± 30.86 mg/dL). Between 48 and 96 weeks, most lipid changes in the TDF group were not statistically significant, except for increases in LDL and LDL/HDL. In the TAF group, an increasing trend of LDL and TC/HDL was noted, although LDL showed a slight turnover after 48 weeks. This real-world study provides new evidence that TAF can induce dyslipidemia, while TDF exhibits a lipid-lowering effect in CHB. Patients at high risk for hepatic steatosis and cardiovascular diseases should consider these effects when choosing between TAF and TDF.

Over 300 million individuals worldwide are chronically infected with hepatitis B virus and at risk for progressive liver disease. Due to the lack of a therapy that reliably achieves viral elimination and the variability of liver disease progression, treatment decisions are guided by the degree of liver disease and viral biomarkers as the viral life-cycle is well characterized and largely conserved between individuals. In contrast, the immunological landscape is much more heterogeneous and diverse and the measurement of its components is less well standardized. Due to the lack of a universal and easily measurable set of biomarkers, clinical practice guidelines remain controversial, aiming for a balance between simplifying treatment decisions by reducing biomarker requirements and using all available biomarkers to avoid overtreatment of patients with low risk for disease progression. While approved therapies such as nucleos(t)ide analogs improve patient outcomes, the inability to achieve a complete cure highlights the need for novel therapies. Since no treatment candidate has demonstrated universal efficacy, biomarkers will remain important for treatment stratification. Here, we summarize the current knowledge on virological and immunological biomarkers with a specific focus on how they might be beneficial in guiding treatment decisions in chronic hepatitis B.

Hepatitis B virus (HBV) infection is a contagious condition posing a major public health risk in various nations, including Vietnam. In 2019, the Ministry of Health introduced tenofovir alafenamide (TAF) to treat patients with chronic HBV infection and reduce the long-term toxicity of tenofovir disoproxil fumarate (TDF). This study aimed to assess the effectiveness and safety of these 2 medications in individuals with hepatitis B e antigen (HBeAg)-positive chronic HBV.

This retrospective cohort study included data collected from the medical records of patients with chronic HBV who visited the Liver Clinic at University Medical Center Ho Chi Minh City between 2018 and 2020.

After 2 years of treatment, the proportion of HBeAg loss in the TAF group was twice that of the TDF group (22.4% vs 11.2%), indicating a statistically significant difference in the probability of HBeAg loss (adjusted hazard ratio = 2.22; 95% confidence interval [CI] 1.43-3.42; P < 0.01). In addition, there was a statistically significant difference in the rate and ability of antiviral response between patients treated with TAF and TDF (65% vs 54.5%, respectively; adjusted hazard ratio = 1.34; 95% CI 1.08-1.69; P < 0.01). A total of 93.9% of patients achieved the goal of restoring alanine aminotransferase to normal, a higher percentage compared with the 81.2% in the TDF group, and the likelihood of achieving normal alanine aminotransferase levels with TAF was greater compared with those on TDF (adjusted hazard ratio = 1.67; 95% CI 1.38-2.01; P < 0.01). Moreover, there was a statistically significant difference in the variation in renal function between the TAF and TDF groups. Serum creatinine levels in the TAF group increased less than those in the TDF group by 0.03 mg/dL every 6 months (95% CI -0.04 to -0.01, P < 0.01), and the estimated glomerular filtration rate in the TAF group was higher than that in the TDF group every 6 months by 2.78 mL/min/1.73 m 2 (95% CI 0.98-4.57, P < 0.01). However, there was no statistically significant difference in the likelihood of HBeAg seroconversion between patients with chronic hepatitis B treated with TAF or TDF (adjusted hazard ratio = 1.79; 95% CI 0.91-3.53; P = 0.09), nor in the risk of adverse events between the 2 groups (adjusted odds ratio = 1.34; 95% CI 0.88-2.05; P = 0.17). In addition, although the HBsAg concentration in the TAF group was lower than in the TDF group by an average of 0.05 log 10 IU/mL every 6 months (95% CI -0.15 to 0.05), this difference also did not reach statistical significance ( P = 0.35).

TAF has been demonstrated to achieve some therapeutic efficacy goals and reduce nephrotoxicity better than TDF. However, no differences were found in seroconversion or adverse events between the patient groups.

Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB).

We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed.

Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups.

TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB.

A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF).

In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P < 0.001). After TAF treatment, a significant elevation was observed in triglyceride (TG) levels (from 0.83 mmol/L to 1.02 mmol/L, P < 0.001) and total cholesterol (TC) levels (from 4.16 mmol/L to 4.32 mmol/L, P < 0.001). Similar changes in TG and TC levels were observed in the TAF group after propensity score matching (PSM). The TG levels (from 0.83 mmol/L to 1.04 mmol/L, P < 0.001) and TC levels (from 4.16 mmol/L to 4.38 mmol/L, P < 0.001) were both increased significantly compared to the baseline levels in the PSM cohort of patients treated with TAF. TAF treatment was independently associated with elevated TG levels (HR = 2.800, 95% CI: 1.334-5.876, P = 0.006) and TC levels (HR = 9.045, 95% CI: 3.836-21.328, P < 0.001).

Compared with TDF treatment, TAF treatment was associated with dyslipidemia in patients with CHB. Close monitoring of lipid profiles is needed in patients with CHB who received TAF treatment.

Background: Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir for the treatment of chronic hepatitis B (CHB) that has shown a favourable renal safety profile while offering suppression of HBV DNA similar to tenofovir disoproxil fumarate (TDF). We aimed to study changes in markers of HBV replication and renal function in a real-world setting in European patients. Methods: In our prospective single-arm, non-interventional observational study, HBeAg-positive and HBeAg-negative patients with chronic HBV mono-infection receiving TAF as their first or following line treatment were enrolled. HBV DNA, HBsAg, markers of bone metabolism, and renal function were determined at baseline and every consecutive 3 months. Results: A total of 50 patients (70% male) were included. The mean duration of TAF treatment was 18 (3-36) months. In 20 patients with detectable HBV DNA at baseline, median serum levels of HBV DNA log10 changed from 2.33 (0.766-6.47) to 1.04 IU/mL at the end of observation and became undetectable in 11 patients. Median HBsAg log10 decreased from 3.37 (0.88-5.10) to 2.39 (1.52-4.19) IU/mL. During the entire observation period, the renal function parameters remained stable in patients with normal renal function and even in those with renal dysfunction. Mild adverse events were reported by 14 patients (28%). Conclusions: TAF was a safe and effective treatment, also in patients with decreased renal function.

Evaluate the real-world effectiveness and safety of different treatment regimens for treatment-naïve high viral load chronic hepatitis B (CHB) patients. Between January 2021 and August 2022, CHB patients with HBV DNA ≥ 107 IU/mL were collected from four medical centers in Shenzhen. Patients treated with mono or combine antiviral therapy. The primary endpoint was the cumulative incidence of virological response at 48 weeks, and other endpoints included changes in HBsAg, HBeAg, ALT, and eGFR at 48 weeks. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the bias. Weighted logistics regression was used to estimate the factors affecting virological response. A total of 391 patients were included in the study, with 296 patients undergoing statistical analysis after IPTW. The patients were distributed into four groups: ETV (n = 62), TDF (n = 89), TAF (n = 36), TDF + LdT/ETV (n = 109). The 48-week cumulative incidence of virological response was significantly lower in ETV group (52.3%) compared to TDF (71.7%), TAF (74.2%), and TDF + LdT/ETV groups (77.9%) (P < 0.05). There were no significant differences in HBsAg loss among the four groups, but the HBeAg seroconversion rate was significantly higher in the TAF group. The ALT normalization rate was significantly higher in the TAF group (72.2%) compared to the others at 48 weeks (P < 0.05). In treatment-naïve CHB patients with high viral load, combination therapy was not superior to TDF or TAF monotherapy in virological response. Patients treated with TDF or TAF showed superior virological response compared to those treated with ETV. The TAF group demonstrated superiority in terms of ALT normalization and HBeAg seroconversion.

Criteria for antiviral treatment initiation in Thailand were complex and difficult to implement. This study determined the cost-effectiveness of 2 simplified antiviral treatment initiation criteria among patients with chronic hepatitis B in Thailand.

A hybrid model of the decision tree and Markov model was developed. Two simplified antiviral treatment initiation criteria were the expanded criteria, treating patients with hepatitis B surface antigen positive and viral load (hepatitis B virus deoxyribonucleic acid) >2000 IU/mL or cirrhosis by tenofovir alafenamide (TAF), and the test-and-treat criteria, treating patients with hepatitis B surface antigen positive and viral load >10 IU/mL or cirrhosis by TAF. PubMed was searched from its inception to July 2023 to identify input parameters. Best supportive care was chosen for patients who were ineligible for TAF. Incremental cost-effectiveness ratio per quality-adjusted life-year (QALY) was calculated.

The expanded criteria and the test-and-treat could reduce the occurrence of patients progressing to hepatocellular carcinoma. In particular, both criteria could reduce 4846 new cases of hepatocellular carcinoma per 100 000 patients. The incremental cost-effectiveness ratios for the expanded criteria and the test-and-treat criteria were 24 838 Thai baht (THB)/QALY and 163 060 THB/QALY, respectively.

At the current willingness to pay of 160 000 THB/QALY, the expanded criteria were cost-effective, but the test-and-treat criteria were not cost-effective to be the simplified antiviral treatment initiation criteria for patients with chronic hepatitis B in Thailand.

Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother- to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment.

Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α.

In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored.

As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment.

TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.