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Objective: Hepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis B (CHB) but this rarely occurs with currently approved therapies. We aimed to develop and validate a prognostic model for HBsAg loss on treatment using longitudinal data from a large, prospectively followed, nationwide cohort., Design: CHB patients receiving nucleos(t)ide analogues as antiviral treatment were enrolled from 50 centres in China. Quantitative HBsAg (qHBsAg) testing was prospectively performed biannually per protocol. Longitudinal discriminant analysis algorithm was used to estimate the incidence of HBsAg loss, by integrating clinical data of each patient collected during follow-up., Results: In total, 6792 CHB patients who had initiated antiviral treatment 41.3 (IQR 7.6-107.6) months before enrolment and had median qHBsAg 2.9 (IQR 2.3-3.3) log 10 IU/mL at entry were analysed. With a median follow-up of 65.6 (IQR 51.5-84.7) months, the 5-year cumulative incidence of HBsAg loss was 2.4%. A prediction model integrating all qHBsAg values of each patient during follow-up, designated GOLDEN model, was developed and validated. The AUCs of GOLDEN model were 0.981 (95% CI 0.974 to 0.987) and 0.979 (95% CI 0.974 to 0.983) in the training and external validation sets, respectively, and were significantly better than those of a single qHBsAg measurement. GOLDEN model identified 8.5%-10.4% of patients with a high probability of HBsAg loss (5-year cumulative incidence: 17.0%-29.1%) and was able to exclude 89.6%-91.5% of patients whose incidence of HBsAg loss is 0. Moreover, the GOLDEN model consistently showed excellent performance among various subgroups., Conclusion: The novel GOLDEN model, based on longitudinal qHBsAg data, accurately predicts HBsAg clearance, provides reliable estimates of functional hepatitis B virus (HBV) cure and may have the potential to stratify different subsets of patients for novel anti-HBV therapies., Competing Interests: Competing interests: JH received consulting fees from GlaxoSmithKline, Gilead Sciences and a Grant from Roche. NVN is an independent advisor to HistoIndex and a member of the scientific advisory board for InSphero. The other authors declare no conflicts of interest that pertain to this work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease's characteristics and antiviral treatment strategies, are discussed here.

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

Objective: To prospectively explore the treatment strategies for clinical difficulties in patients with hyperviremia HBeAg-positive chronic hepatitis B with incomplete response to first-line nucleos(t)ide analogues (NAs). Methods: Patients with hyperviremia HBeAg-positive chronic hepatitis B were treated with first-line NAs, including entecavir, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) for 48 weeks or more. Tenofovir amibufenamide (TMF) or TAF therapy was changed when HBV DNA remained positive and then divided into a TMF group and a TAF group. Clinical efficacy of treatment was evaluated at 24 and 48 weeks, including HBV DNA undetectable rates and virological and serological responses in both patient groups. Results: In the TMF group and the TAF groups, 30 and 26 cases completed 24-week follow-up, while 18 and 12 cases completed 48-week follow-up. There were no statistically significant differences in baseline HBV DNA, HBsAg, and HBeAg levels between the two groups before switching to TMF/TAF therapy ( P > 0.05). At 24 weeks of treatment, 19 (19/30, 63.33%) cases in the TMF group had HBV DNA negative conversion, while 14 (14/26, 53.85%) cases in the TAF group had HBV DNA negative conversion ( P > 0.05). Among the patients who completed 48 weeks of follow-up, 15 (15/18, 83.33%) cases in the TMF group and 7 (7/12, 58.33%) cases in the TAF group had negative HBV DNA tests ( P > 0.05). The changes in HBsAg and HBeAg levels between the two groups of patients at 24 and 48 weeks of treatment were not statistically significant compared to baseline ( P > 0.05). Conclusion: TMF is effective in treating patients with hyperviremia HBeAg-positive CHB with an incomplete response to first-line NAs treatment, but there is no significant difference compared to TAF.

Objective : The proportion of hepatitis e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients in China has increased rapidly. However, the response of these patients to peginterferon (peg-IFN) treatment is poor, and the antiviral treatment strategies are inconsistent. This study aimed to investigate the role of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) in early prediction of response in HBeAg-negative CHB patients receiving peg-IFN α-2a. Patients and Methods : Treatment-naïve HBeAg-negative patients were involved in this prospective study during 2014-2018. The HBV DNA and HBsAg were quantified at baseline and during treatment (weeks 12, 24 and 48) in sera. The factors associated with HBV DNA undetectable and HBsAg <100 IU/ml at treatment 48 weeks were assessed. Results : This study involved 45 patients. There was HBV DNA undetectable in 36 cases (80%), including 19 (52.8%) with HBsAg <100 IU/ml at week 48. The HBV DNA <2.0 log 10 IU/ml at week 24 (PPV = 96.9%, NPV = 66.7%, P = 0.018) was an independent predictor of HBV DNA undetectable at week 48. The HBsAg <800 IU/ml at baseline (PPV = 92.1%, NPV = 69.7%, P = 0.054) and HBsAg decline >5.00-fold at week 24 (PPV = 83.3%, NPV = 77.8%, P = 0.038) were independent predictors of HBsAg <100 IU/ml and HBV DNA undetectable at week 48. Conclusion : Early on-treatment quantification of HBV DNA and HBsAg in patients with HBeAg-negative CHB treated with peg-IFN α-2a may help identify those likely to be cured by this method and optimize therapy strategies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC) in China. The occurrence of HCC can significantly be reduced with effective long-term antiviral treatment. Since the widespread clinical use of nucleos(t)ide analogues, such as entecavir and tenofovir that has a strong potency and high genetic barrier to resistance; the detection rate of HBV DNA in serum of patients with chronic hepatitis B is no more than 85% ~ 95%, but HCC can still occur in a small number of patients. This article will review whether the timing and selection of NAs treatment differ to prevent and reduce the incidence of HCC.

Background: Switching from nucleos(t)ide analogues to interferon (IFN) improves hepatitis B surface antigen (HBsAg) loss. We aimed to evaluate whether combining immunomodulators such as interleukin-2 (IL-2) and therapeutic vaccine with IFN enhances HBsAg loss in entecavir (ETV)-suppressed patients., Methods: Ninety-four patients exhibiting virological suppression and hepatitis B e antigen (HBeAg) loss following ETV treatment were randomized 1:1:1 to receive ETV (group I) or IFN (group II) for 48 weeks, or IFN and vaccine for 48 weeks plus IL-2 for 12 weeks (group III). The primary endpoint was HBsAg loss at week 48. Peripheral natural killer (NK) cells and regulatory T cells (Treg) were measured as immune checkpoint indicators., Results: Mean HBsAg decline at week 48 was significantly greater in group III (0.85 log 10 IU/mL) and group II (0.74 log 10 IU/mL), than in group I (0.13 log 10 IU/mL). At week 48, 9.38%, 3.03%, and 3.70% of subjects in group III, II, and I, respectively, achieved HBsAg loss. Among patients with baseline HBsAg titers ranging from 100 to 1500 IU/mL, HBsAg loss rate was 27.3, 7.1, and 0% in group III, II, and I, respectively. Responders in group III showed a significantly higher increase in CD56 bright CD16 - NK cells from week 24 to 36, and a significant decline in Treg from week 12 to 24 than non-responders., Conclusion: For ETV-suppressed patients, particularly those with low baseline HBsAg levels, combination therapy with IFN and other immunomodulators may enhance HBsAg loss, while successful response correlates with partial restoration of NK cells and Tregs.

In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The main transmission route of chronic hepatitis B virus infection is mother-to-child transmission of hepatitis B virus and the main cause of combined immune prophylaxis failure in neonates at the end of pregnancy is high viral load. Moreover, oral administration of nucleos(t)ide analogues (NAs) during the second and third trimesters of pregnancy can significantly reduce or even completely block mother-to-child transmission of HBV. This article focuses on the necessity and feasibility of oral NAs antiviral therapy for HBV carrier pregnant woman with high viral load, and the issues commences at the time of medication and viral load thresholds.

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2-5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis ( t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log(10) IU/ml and (3.95 + 0.40) log(10) IU/ml; t = 8.465, P < 0.001). Conclusion: Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

Background: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes., Methods: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed., Findings: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment., Interpretation: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis., Funding: Gilead Sciences., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 ( n = 153) or 96 weeks ( n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Background and Aim: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6., Methods: Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12)., Results: Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment-unrelated adverse events., Conclusions: Sofosbuvir-based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype., (© 2018 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Liver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for noninvasive liver fibrosis assessment in pretreatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan ® every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen-positive treatment-naive patients receiving telbivudine-based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (-2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6-49.5) kPa at baseline to 6.1 (2.2-37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (-0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs 5.3 kPa, P < .001) while ALT levels remained stable within the normal range. More importantly, liver stiffness declined significantly irrespective of baseline ALT levels and liver necroinflammation grades. From baseline to week 104, the proportion of patients with no or mild fibrosis (Ishak, 0-2) increased from 74.4% (122/164) to 93.9% (154/164). Multivariate analysis revealed that percentage decline of 52-week liver stiffness from baseline was independently associated with 104-week liver fibrosis regression (odds ratio, 3.742; P = .016). Early decline of 52-week liver stiffness from baseline may reflect the remission of both liver inflammation and fibrosis and was predictive of 104-week fibrosis regression in treated patients with chronic hepatitis B., (© 2017 John Wiley & Sons Ltd.)

Background: In China, the clinical management of chronic hepatitis B (CHB) is complicated by the use of variousnucleoside/nucleotide analogue (NUC) regimens in treatment-naive patients, including NUCs with low genetic barriers to resistance, with/without add-on therapy and de novo NUC combinations. This longitudinal observational study therefore investigated the real-world clinical management and efficacy of NUC therapy in treatment-naive CHB patients in China., Methods: Treatment-naive CHB patients initiated on NUC therapy were enrolled from 63 hospitals in tier-2 Chinese cities. Demographic and treatment-specific data were collected, with the objective of reporting real-world treatment patterns and comparing the effectiveness of entecavir (ETV) treatment and lamivudine (LAM)-based treatment. We herein report the first-year data., Results: 3,408 NUC-naive patients were enrolled and treated with NUCs (53% ETV, 18% LAM-based, 29% other). Overall, 6.6% of patients modified their initial treatment, with ETV having lower rates of treatment modification than other major NUCs (P<0.05). At week 52, the virological response rate was higher with ETV than with LAM-based treatment (77.0% versus 61.4%; P<0.0001). LAM-based treatment was associated with a higher probability of virological breakthrough and genotypic resistance (21.4% and 19.6%, respectively) than ETV (1.6% and 0.1%, respectively; P<0.0001). Treatment-related adverse events or serious adverse events were uncommon., Conclusions: In this nationwide observational study, more than 50% of patients with CHB in tier-2 city hospitals in China initially received ETV therapy. Consistent with clinical trial results, ETV was more effective than LAM-based treatments in a real-world setting, with the rate of treatment modification being relatively low in ETV-treated patients. ClinicalTrials.gov Identifier: NCT01726439.

Chronic hepatitis B infection (CHB) causes up to 1.0 million deaths annually. Currently, more than 90% of CHB patients worldwide are receiving indefinite nucleos(t)ide analogue (NA) therapy. New strategies for optimizing hepatitis B surface antigen (HBsAg) loss are required for NA-treated patients as the majority are unable to achieve HBsAg loss and may require lifelong therapy. In hepatitis B e antigen (HBeAg)-positive patients, switching from NAs to finite peginterferon (PegIFN) therapy can double HBeAg seroconversion rates. One in five patients who switch to PegIFN can achieve HBsAg loss, whereas patients who continue NA therapy typically do not. In HBeAg-negative NA-treated patients, add-on PegIFN therapy achieves higher, albeit modest, HBsAg loss rates compared with continued NA monotherapy and offers the opportunity for NA-treated patients to achieve the inactive carrier state. In the absence of curative therapies, PegIFN represents a valuable, finite option for NA-treated patients who would otherwise require potentially lifelong therapy., (© 2017 John Wiley & Sons Ltd.)

Objective: To observe the success rate of telbivudine (LdT) for the prevention of perinatal transmission of hepatitis B virus (HBV) and the incidence of alanine aminotransferase (ALT) elevation during LdT treatment and after LdT withdrawal in HBV-infected pregnant woman with high viremia in immune-tolerant phase and receiving LdT treatment at the end of pregnancy, and to evaluate the efficacy of LdT in the prevention of perinatal transmission and the safety for pregnant women., Methods: Pregnant women infected with HBV in immune-tolerant phase who had normal ALT levels (≤40 U/L) and high viremia (HBV DNA ≥6 log10 IU/ml) with positive HBeAg were enrolled as subjects. All pregnant women received antiviral treatment with LdT at the end of pregnancy to prevent perinatal transmission of HBV. All infants received standard combined immunoprophylaxis. Failure for prevention of perinatal transmission of HBV was defined as positive HBsAg or HBV DNA in infants 7 months of age (or at one month after the third injection of hepatitis B vaccine). Liver function, HBV DNA, and HBV serological markers were evaluated at baseline, after 1 month of treatment, before childbirth, and 1, 3, and 6 months after drug withdrawal. SPSS 16.0 software was used to analyze the data. Between-group comparison of continuous data was made by t test, and comparison of categorical data was made by chi-square test., Results: One hundred and four pregnant women (treatment group) received oral administration of 600 mg LdT once a day, and 25 pregnant women (observation group) did not receive any antiviral therapy. The success rate for the prevention of perinatal transmission was significantly higher in the treatment group than in the observation group (100% vs 89.47%, χ (2) = 9.862, P = 0.028). There was no significant difference in the incidence of ALT elevation during treatment and within 6 months after drug withdrawal between the treatment group and the observation group (4.81% (5/104) vs 4.00% (1/25), χ (2) = 0.030, P = 1.000). In the treatment group, the mean HBV DNA at baseline was significantly higher than that before childbirth (8.20±0.78 vs 3.98±0.90 log10IU/ml, t = 6.979, P < 0.001). One hundred patients with drug withdrawal had HBV DNA increased to 8.11±0.80 log10 IU/ml at one month after childbirth., Conclusion: LdT treatment at the end of pregnancy can effectively reduce the incidence of perinatal transmission of HBV in pregnant women with high viremia in immune-tolerant phase. The immediate drug withdrawal after childbirth is safe for the mother. The incidence of hepatitis is low after drug withdrawal.

Objective: To study the efficacy and outcome predictors of combined re-treatment with pegylated interferon (Peg-IFN) α-2a and ribavirin in recurrent chronic hepatitis C (CHC) patients., Methods: A multicenter, prospective, randomized trial was designed. A total of 125 recurrent CHC patients were recruited in 16 clinical centers and randomly assigned into two groups: one was Peg-IFNα-2a combined with ribavirin for 48 weeks (group A) and the other the same combination for 72 weeks (group B). HCV RNA levels in patients' serum were detected at baseline, week 4, 12, 24, 48, 72 (group B) after treatment initiation, and 24 weeks after treatment., Results: Of all the 90 patients who completed treatment and 24 weeks follow-up, 80.0% achieved sustained virological response (SVR) yet 12.2% relapsed. There was no significant difference between two groups. The SVR rate in patients previously treated with interferon alone was higher than that in patients with interferon plus ribavirin (92.6% vs 74.6%), but the difference was of no statistical significance (P = 0.05). Moreover, patients previously treated with common interferon (c-IFN) showed a higher SVR rate than patients with Peg-IFN (84.7% vs 71.0%, P > 0.05). The positive predictive value (PV) of rapid virological response (RVR) and complete early virological response for SVR was 92.3% and 86.4% respectively, and the negative PV of RVR, early virological response and delayed virological response for SVR was 36.8%, 66.7% and 100.0% respectively. Overall, 62.1% patients reported adverse events (AEs) and 1.6% patients were severe AEs., Conclusions: A high SVR rate has been achieved in recurrent CHC patients who were retreated with Peg-IFNα-2a and ribavirin for 48 weeks. Better SVR cannot be achieved in spite of a prolonged course of 72 weeks. Early virological response at week 12 was the most important predictor for SVR.

Background and Aim: Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE)., Methods: Adult patients without antiviral therapy within 6 months before screening with hepatitis B virus (HBV)-DNA ≥ 10(5) copies/mL, alanine aminotransferase 1.3-10 times upper limit of normal and compensated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were randomized into three groups with 1:1:1 ratio. Patients in OPTIMIZE group started with lamivudine 100 mg q.d., and ADV 10 mg q.d. was added to suboptimal responders (HBV-DNA > 1000 copies/mL at week 24) from week 30 to week 104, whereas patients with early virological response (HBV-DNA ≤ 1000 copies/mL at week 24) continued MONO until week 104. For all the patients receiving MONO, ADV would be added if virological breakthrough was confirmed., Results: At week 104, more patients in COMBO and OPTIMIZE groups achieved HBV-DNA < 300 copies/mL (53.3% [64/120] and 48.3% [58/120]), with less lamivudine resistance (0.8% and 6.7%) compared with MONO group (HBV-DNA < 300 copies/mL 34.8% [41/118], lamivudine resistance 58.5%). Patients under MONO with early virological response showed superior efficacy at week 104 (HBV-DNA < 300 copies/mL 73.1% [38/52], HBeAg seroconversion 40.4% [21/52]). All regimens were well tolerated., Conclusion: Combination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HBeAg-positive CHB patients. In lamivudine-treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The aim of this study was to investigate the role of T-helper cell (Th)1/Th2 cytokines in the chronicity of hepatitis C virus (HCV) infection and the outcome of interferon (IFN) alpha therapy. A total of 30 patients with chronic hepatitis C were enrolled in the study. The levels of Th1/Th2 cytokines were determined. The differentiation of HCV genotypes was determined by direct sequencing. HCV RNA loads were detected by fluorescence quantitative polymerase chain reaction (qPCR). In chronic hepatitis C, the levels of interleukin (IL)-2 and transforming growth factor (TGF)-β significantly decreased, and IL-5 and IL-18 levels increased compared with normal controls. The IL-6 serum levels were directly proportional to the serum levels of alanine aminotransferase, and were inversely proportional to the HCV RNA loading levels. Patients with severe hepatitis C had higher levels of IL-4, IL-6, and IL-1β compared to milder cases. Patients with genotype 1 showed higher serum levels of IL-6 than those with genotype 2. The levels of IL-2 and IL-18 showed a decreasing tendency, whereas TGF-β, IL-6, and IL-1β showed an increasing tendency over time. There was no difference in any cytokines detected between the response and nonresponse groups before IFN therapy. However, the IFN-y level increased after IFN therapy in the response group. There was no correlation between the Th1/Th2 cytokine levels in the serum before IFN treatment and in the outcome of IFN therapy. Increasing IFN-y levels in the serum induced by IFN treatment is associated with systemic vascular resistance.

Unlabelled: An optimization strategy based on the Roadmap concept is supposed to improve the clinical outcomes of patients with suboptimal antiviral response. The aim of this study was to prove the concept with a multicenter, open-label, randomized, controlled study. In all, 606 hepatitis B e antigen (HBeAg)-positive, nucleos(t)ide-naive chronic hepatitis B patients were randomized to the Optimize or Mono group. Patients in the Optimize group were treated with telbivudine for 24 weeks, after which those suboptimal responders with HBV DNA ≥300 copies/mL at week 24 received telbivudine plus adefovir until week 104, while the early virological responders continued telbivudine monotherapy. Patients in the Mono group received telbivudine monotherapy. All patients with telbivudine monotherapy had adefovir added if viral breakthrough developed. Sixty-eight percent (204/300) of patients in the Optimize group had adefovir added due to suboptimal response. At week 104, compared to the Mono group, more patients in the Optimize group achieved HBV DNA <300 copies/ml (76.7% versus 61.2%, P < 0.001) with less genotypic resistance (2.7% versus 25.8%, P < 0.001). The rates of HBeAg seroconversion and alanine aminotransferase (ALT) normalization were comparable between the two groups (23.7% versus 22.1%; 80.7% versus 79.2%). For week 24 suboptimal responders, telbivudine plus adefovir showed an additive antiviral potency, with 71.1% achieving virological response at week 104 and only 0.5% developing genotypic resistance, compared with 46.6% who achieved virological response and 37.8% who developed genotypic resistance with telbivudine monotherapy. Both treatment regimens were well tolerated, with an observed persistent increase of the glomerular filtration rate., Conclusion: For suboptimal virological responders to telbivudine at week 24, adjusting the treatment strategy is recommended. Adding adefovir can benefit these patients with additive antiviral potency and low resistance without increased side effects., (© 2014 by the American Association for the Study of Liver Diseases.)