Baseline HBV DNA Level Research Articles

Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results: 593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores. Conclusion: After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B

ObjectiveThe association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association...

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Clinical efficacy analysis of TMF for the treatment of hyperviremia HBeAg-positive chronic hepatitis B patients with incomplete response to first-line oral antiviral nucleos(t)ide analogues

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.

Adverse Effect of Nonalcoholic Fatty Liver Disease on the Therapeutic Response in Patients with Chronic Hepatitis B.

The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation. Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR). We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004]; G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR. In CHB patients receiving initial antiviral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Effects of on-treatment ALT flares on serum HBsAg and HBV RNA in patients with chronic HBV infection.

As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5×ULN. The association between flares and HBsAg and HBV RNA changes were examined. On-treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4-12], 7.6×ULN [IQR 6.2-10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no-flare group. More flares were observed on PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) vs. PEG-IFN-α add-on (2%) or NA monotherapy (1%) (p<.001). On-treatment flares were significantly and independently associated with HBsAg and HBV RNA decline ≥1log10 at the final visit declines started shortly before the flare, progressing towards 24weeks thereafter. On-treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG-IFN-α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG-IFN-α add-on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising.

HBsAg Loss Due to Tenofovir Treatment for HBV Reactivation Following DAAs Therapy in One Patient with HBV-HCV Coinfection

Abstract Hepatitis B virus (HBV) reactivation induced by administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported in previous studies, the subsequent clinical outcomes varied from no symptom to liver failure or death, however, the timing of anti-HBV treatment is controversial. We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) therapy. Her baseline HCV RNA, HBV DNA, alanine aminotransferase (ALT), and liver stiffness measurement levels were 5,560,000 IU/mL, &lt;15 IU/mL, 48 U/L, and 11.8 kPa, respectively. At 8 weeks of PrOD treatment, her HCV RNA, HBV DNA, and ALT levels were &lt;15 IU/mL, 2,880,000 IU/mL, and 837 U/L, respectively, and clinical reactivation was diagnosed. Meanwhile, tenofovir was immediately used for anti-HBV treatment. Fortunately, HBV DNA and ALT were undetectable and normalized after 16 weeks of anti-HBV therapy, and unexpectedly, hepatitis B surface antigen loss occurred at 80 weeks of anti-HBV treatment. This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBV-HCV coinfected patients, and proper initiation timing may lead to functional cure of chronic HBV infection.

Clinical characteristics of chronic hepatitis B cured by peginterferon in combination with nucleotide analogs

ObjectivesThe purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy. MethodsForty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease. ResultsThe combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log10 IU/mL, and week 48 HBsAg levels were < 0.88 log10 IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks. ConclusionsIndividualized extension of combination therapy to more than 96 weeks depending on the patient’s response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations.

Effect of nucleos(t)ide analogue on serum HBsAg level in chronic hepatitis B patients: A 3-years study

AimWe aim to explore the effects of nucleos(t)ide analogues (NUCs) on the changes of HBsAg in chronic hepatitis B (CHB) patients. MethodsA total of 264 CHB patients were enrolled in our study. All of them were treated with NUCs for at least three years. Quantification of HBsAg levels were measured by Elecsys HBsAg II. ResultsAlthough HBsAg levels were significantly higher in HBeAg seropositive CHB patients at baseline than in HBeAg seronegative CHB patients (3.84 ± 0.82 vs 3.21 ± 0.59 IU/mL), HBsAg levels declined more rapidly in the HBeAg seropositive group (P < 0.001). In HBeAg-positive CHB patients, HBsAg level in the telbivudine (LDT)-treated group was 3.68 ± 0.56 IU/mL after 52-week of treatment, which was significantly higher than that in lamivudine (LAM)-treated group (P = 0.009). Multivariable analyses showed that baseline HBV DNA viral load (OR = 0.75, P = 0.018), baseline ALT level (OR = 0.99, P = 0.015), and baseline HBsAg level (OR = 0.188, P < 0.001) were independent factors that affected HBsAg decline in HBeAg seropositive CHB patients. For HBeAg seronegative CHB patients, the average of serum HBsAg levels in LAM-, LdT-, adefovir (ADV)-, and entecavir (ETV)-treated groups at baseline, 52 weeks, 104 weeks, and 156 weeks were similar. Multivariable analyses showed that only baseline HBV DNA level (OR = 0.56, P = 0.020) and baseline HBsAg level (OR = 0.57, P = 0.012) were independent factors that affected HBsAg decline in HBeAg seronegative patients with CHB. Baseline HBV DNA level (OR = 0.72, P = 0.010) and baseline HBsAg level (OR = 0.19, P < 0.001) were independent factors that affected all CHB patients. ConclusionsCHB Patients who had received NUCs antiviral treatment showed a slow but significant decrease in serum HBsAg level. Long-term monitoring and continuous antiviral treatment are necessary, especially for those patients with risk factors associated with HBsAg decline.

Long-term observation on hepatitis B surface antigen seroclearance in therapy experienced HIV/HBV co-infected Chinese.

The aim of this retrospective study was to observe hepatitis B surface antigen (HBsAg) seroclearance and explore predictors of HBsAg loss in HIV/HBV-co-infected patients receiving long-term lamivudine or both tenofovir and lamivudine containing therapies. Quantification of HBsAg, hepatitis B e antigen and HBV DNA before and after initiation of HBV-active antiretroviral therapy in a total of 268 HIV/HBV-co-infected patients started treatment between 2005 and 2017 were performed. Over a median of 65.63months of follow-up, 10 (3.7%) were observed HBsAg loss and the quantification of HBsAg in 7 (2.6%) patients were less than 50IU/mL. With the prolongation of antiretroviral therapy duration time, the rates of HBsAg seroclearance tended to increase gradually, rising from 1.8% (3/163) during 2-4years treatment to 29.4% (10/34) after antiretroviral therapy for up to 10years. Lower baseline qHBsAg and HBV DNA levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance. The event of HBsAg seroclearance is uncommon among Chinese individuals with HIV/HBV co-infection who have been treated with anti-HBV containing antiretroviral therapy, and lifelong therapy for HBV is needed for HIV/HBV co-infected patients. Baseline qHBsAg and HBV DNA levels and qHBsAg decline rate were predictors for HBsAg seroclearance.

Correlation Between Serum Entecavir Concentration and Virological Response in Patients with Chronic Type B Hepatitis.

BackgroundThis study was conducted to investigate the relationship between trough concentrations of serum entecavir and the virological response of patients with chronic type B hepatitis (CHB).Material/MethodsA total of 59 CHB patients who had been receiving antiviral therapy with entecavir for >3 months were included in this study. Serum entecavir concentrations, HBV DNA levels, and other biochemical indicators were determined after drug treatments.ResultsThe serum entecavir concentrations in the good response and poor response groups were 0.58±0.38 and 0.43±0.15 ng/mL, respectively. The antiviral efficacy was 52.38%, 65.63%, and 100% in low, middle, and high entecavir groups, respectively. The baseline HBV DNA level among the patients with poor response was significantly higher than in the group with good response. Among the 14 patients with a high viral load, 5 patients showed a good response and had a higher entecavir concentration than the other 9 patients with poor response. Entecavir in patients with cirrhosis was higher than in those without cirrhosis (0.63±0.45 ng/mL vs. 0.46±0.16 ng/mL), and the virological response rate in patients with cirrhosis was higher than in those without cirrhosis (83.33 vs. 51.43%). Cirrhosis progression was reversed in 3 patients with high serum entecavir concentration.ConclusionsSerum entecavir concentrations vary among individuals, and higher serum entecavir concentration is correlated with more efficient viral clearance. Therefore, for patients with poor response, high doses may be beneficial for viral clearance.

Antiviral therapy to reduce hepatocellular carcinoma recurrence in patients with low HBV-DNA levels: A randomized controlled trial.

1510 Background: Despite antiviral treatment has been shown to reduce hepato- cellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. Methods: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were ran- domly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. Results: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P 1/4 0.016, P 1/4 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409– 0.884; P 1/4 0.010] and 0.509 (95% CI, 0.333–0.778; P 1/4 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recur- rence (hazard ratio [HR] 1/4 0.316, 95% CI 0.157 – 0.637; P 1/4 0.001) but not of early tumor recurrence (HR 1/4 0.782, 95% CI, 0.493–1.240; P 1/4 0.296). Conclusions: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection. Clinical trial information: ChiCTR-IPR-15006587.

Impact of cessation of antiviral therapy at delivery on postpartum liver function in mothers with chronic hepatitis B virus infection

Objective: To investigate the impact of immediate cessation of antiviral therapy on postpartum liver function and the factors influencing postpartum abnormality in mothers with chronic hepatitis B virus infection. Methods: A retrospective cohort study was conducted. One hundred eighty-eight pregnant women with HBV DNA level > 2×106 IU/ml were enrolled from June 2014 to June 2018. Demographic information and clinical data of liver function and HBV DNA load during gravidity, intrapartum and postpartum period were collected. According to the antiviral treatment recommendations during pregnancy, the women were divided into three groups, namely, tenofovir (TDF), telbivudine (LdT) and control group. Liver function abnormalities among the three groups were compared within 6 months after delivery, and the factors influencing abnormal liver function were analyzed by unconditional logistic regression. Results: Of the 188 cases, 72 cases were in the TDF group, 80 cases in the LdT group, and 36 cases in the control group. Pregnant women in the TDF and LdT groups received oral TDF (300 mg/d) and LdT (600 mg/d) from 28 ± 4 weeks of gestation till delivery. Among the 188 patients, 30 (16.0%) had abnormal postpartum liver function abnormality. The incidence of postpartum liver function abnormality [alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN)] in the TDF, LdT, and control groups was 19.4%, 12.5%, and 16.7%, respectively. The postpartum peak levels of ALT (median, range) in the three groups were 34.5 (12.0-946.0) U/L, 37.5 (12.0-733.8) U/L, and 39.0 (7.0-513.0) U/L, respectively. There was no significant difference between the two indexes among the three groups (P > 0.05). There was no statistically significant difference in the degree of postpartum liver function abnormalities between the three groups (P = 0.944). Most of the liver function abnormalities were mild to moderate (2 × ULN≤ALT < 10 × ULN), and usually resolved spontaneously or by treatment. Univariate and multivariate analysis showed that baseline ALT level during pregnancy was an independent factor associated with postpartum liver function abnormality (OR = 1.031, CI 95%: 1.005-1.058; χ(2) = 5.340, P = 0.021), whereas age, antiviral therapy, HBeAg-positivity, baseline HBV DNA levels, gravidity, parity, preterm delivery and delivery mode were not significantly associated with postpartum liver function abnormality. Conclusion: Cessation of antiviral therapy after delivery did not significantly increase the risk of postpartum liver function abnormality in pregnant women with chronic HBV infection. The ALT level during pregnancy is a factor influencing postpartum liver function abnormality.

Antiviral Therapy Reduces Hepatocellular Carcinoma Recurrence in Patients With Low HBV-DNA Levels: A Randomized Controlled Trial.

Despite antiviral treatment has been shown to reduce hepatocellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were randomly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.016, P = 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409-0.884; P = 0.010] and 0.509 (95% CI, 0.333-0.778; P = 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recurrence (hazard ratio [HR] = 0.316, 95% CI 0.157-0.637; P = 0.001) but not of early tumor recurrence (HR = 0.782, 95% CI, 0.493-1.240; P = 0.296). In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection.

Suppression of hepatitis B surface antigen production by combination therapy with nucleotide analogues and interferon in children with genotype C hepatitis B virus infection.

Sustained suppression of hepatitis B surface antigen (HBsAg) production after interferon (IFN) treatment has not been reported for children with genotype C chronic hepatitis B virus (HBV) infection, which is prevalent in Asia. Among children with hepatitis B envelope antigen-positive genotype C chronic HBV infection, we compared the efficacy of combination therapy with nucleotide analogues and IFN-α in 11 children with 12 historical cases treated with IFN monotherapy. The combination of lamivudine and conventional IFN-α was introduced for the first three patients; the other eight patients were treated with entecavir and pegylated IFN. Demographic factors as well as baseline HBsAg titers and HBV-DNA levels were similar between the two groups. In the combination therapy group, viral loads were suppressed in 9/11 to below 4.0logcopies/mL both at the end of the therapy (EOT) and at 6months after EOT. In contrast, in the IFN monotherapy group, suppression of viral loads was observed in 2/12 and 3/12 at EOT and at 6months after EOT, respectively. In the combination therapy group, HBsAg titers dropped from 4.03 at pretreatment to 2.91logIU/mL at 6months after EOT with 4/11 showing a drop to below 1000IU/mL (one patient achieved HBsAg clearance). In contrast, the amount of HBsAg did not change during the corresponding periods in the IFN monotherapy group. Our preliminary results suggest that combination therapy might be effective in the suppression of HBsAg production as well as HBV-DNA production for children with genotype C chronic HBV infection.

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co-infected patients from Western Africa.

The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)-infected patients. Whether this mutation affects the therapeutic course of HIV-HBV co-infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)-naïve HIV-HBV co-infected patients from Côte d'Ivoire, initiating ARV-treatment containing lamivudine (n=53) or tenofovir (n=33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV-DNA, hepatitis B "e" antigen (HBeAg) seroclearance (in HBeAg-positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV-initiation, median HBV-DNA was 6.04 log10 copies/mL (IQR=3.70-7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (P<.001) and had basal core promotor A1762T/G1764A mutations (P<.001). Patients were followed for a median 36months (IQR=24-36). Cumulative proportion of undetectable HBV-DNA was significantly higher in patients with baseline mutation (pcG1896A=86.6% vs no pcG1896A=66.9%, P=.04), but not after adjusting for baseline HBV-DNA levels and anti-HBV agent (P=.2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A=57.1% vs no pcG1896A=54.3%, P=.7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A=0% vs no pcG1896A=36.9%, P<.001), even after adjusting for baseline HBsAg quantification and anti-HBV agent (P<.001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.

Role of hepatitis B surface antigen in hepatitis B virus relapse after entecavir or tenofovir prophylaxis in patients undergoing cancer chemotherapy.

This study investigated whether hepatitis B surface antigen (HBsAg) could predict hepatitis B virus (HBV) relapse after cessation of entecavir or tenofovir disoproxil fumarate (TDF) prophylaxis for chronic hepatitis B cancer patients who are undergoing chemotherapy. The study enrolled 122 hepatitis B e-antigen-negative cancer patients who underwent chemotherapy with entecavir or TDF for antiviral prophylaxis and posttreatment follow-up for at least 6months. Of the 122 patients, 52 and 18 experienced virological and clinical relapse, which had 3-year cumulative incidences of 46.6% and 18.6%, respectively. Multivariate analysis showed that end-of-treatment HBsAg levels and baseline HBV-DNA≥2000IU/mL were independent predictors of virological relapse. The best HBsAg cutoff value was 500IU/mL. An end-of-treatment HBsAg of 500IU/mL was useful for predicting virological relapse in patients with baseline HBV-DNA<2000IU/mL (3-year rate: 21.3% vs 46.4%, P=0.038, in patients with HBsAg <500 and ≥500IU/mL, respectively), but not in patients with baseline HBV-DNA≥2000IU/mL. Of the 52 patients who experienced virological relapse, 13 experienced transient virological relapse. Patients with baseline HBV-DNA level<2000IU/mL experienced a higher rate of transient virological relapse (42.1% vs 15.2%, P=0.031). Three patients experienced hepatic decompensation upon alanine aminotransferase flares, and no patient died after timely retreatment. Ten patients experienced posttreatment HBsAg loss, and the 3-year HBsAg loss rate was 30.7% in patients with end-of-treatment HBsAg<100IU/mL. The baseline HBV-DNA and end-of-treatment HBsAg levels could predict virological relapse after withdrawal of entecavir and TDF prophylaxis for chemotherapy.

EFFICACY AND SAFETY OF OZONE THERAPY FOR PATIENTS WITH CHRONIC HEPATITIS B: A MULTICENTER, RANDOMIZED CLINICAL TRIAL

Background: Ozone therapy has a long history. Some studies proved that ozone therapy was useful in treatment of virus hepatitis.Objective: To evaluate the efficacy and safety of new medical ozone therapy system for the treatment of chronic hepatitis B.Method One hundred eighty-nine patients with chronic hepatitis B were included in this open-label, phase 3 study, and randomly assigned to receive ozone autohemotherapy with experimental ozone generator TianYi (group 1) or with ozone generator Humares (group 2) or oral diammonium glycyrrhizinate capsules (group 3) in a 1:1:1 ratio for 12 weeks. The primary efficacy end point was sera HBV DNA level of less than 1×103 IU/ml or having a more than 2 log10 reduction in HBV DNA level at the end of 12 weeks treatment as compared to baseline HBV DNA level. Secondary end points included HBeAg seroconversion, biochemical response, and combined response.Results At the end of 12 weeks treatment, the proportion of patients reached the primary end point of virologic response in group 1, group 2, and group 3 were 22.4% (13/58, 95% CI, 12.5 to 35.3), 14.7 (9/61, 95% CI, 7.0 to 26.2) and 3.9% (2/51, 95% CI, 0.5 to 13.5), respectively (p=0.021) in the pre-protocol population. Virologic response occurred in more patients receiving ozone therapy with experimental device than patients receiving oral diammonium glycyrrhizinate capsules (mean difference 18.5%, 95% CI 6.3 to 31.5, p=0.005). However, there was no statistical difference in VR12 rates between the treatment of medical ozone therapy system with experimental device (group 1) and with Humares (group 2) (mean difference 7.7%, 95% CI -6.5 to 22.0, p=0.282). More HBeAg seroconversion in patients treated by Tianyi ozone therapy system than those treated by Humares ozone therapy device and oral diammonium glycyrrhizinate capsules (14.8%, 5.1% and 7.3%, respectively, P = 0.272). Higher biochemical response rate was observes in patients receiving ozone therapy than oral diammonium glycyrrhizinate capsules (31.6%, 36.7% and 24.0%, respectively, p = 0.359). The safety profile was similar for the three treatment groups and adverse events were .scare infrequent and mild.Conclusions: Ozone therapy had superior antiviral efficacy with a similar safety profile as compared with oral diammonium glycyrrhizinate capsules through week 12 treatment. Ozone therapy is also associated with normalized ALT and AST levels, demonstrating that ozone therapy could benefit the patients with chronic hepatitis B.

Comparison between tenofovir disoproxil fumarate and entecavir treatment in real‐world clinical practice

SummaryBackground and aimsEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are effective as two first‐line anti‐viral therapies for chronic hepatitis B (CHB); however, data are limited on directly comparing the safety and effectiveness of these two antivirals. Hence, we compared the efficacy and safety of TDF and ETV on treatment‐naïve patients with CHB.MethodsWe performed a hospital‐based, retrospective cohort study of 257 treatment‐naïve patients with CHB receiving TDF (n = 79) or ETV (n = 178). Virological and biochemical response as well as nephrotoxicity were assessed between TDF and ETV treatment groups.ResultsAt month 12, TDF group had faster on HBV DNA complete suppression than ETV group (p = 0.001). Multivariate analysis indicated that treatment with TDF was a significant predictor of HBV DNA suppression (HR = 1.33; 95% CI = 1.01 – 1.76; p = 0.045). In addition, HBeAg positivity (HR = 0.70; 95% CI = 0.52 – 0.96; p = 0.025) and higher baseline HBV DNA level (HR = 0.84; 95% CI = 0.76 – 0.92; p &lt; 0.001) were significant negative predictors for viral suppression. The ALT normalization rate between these two treatment groups were similar (p = 0.114). TDF group had more populations in ≧ 20% decrease of eGFR MDRD at month 24 than ETV group (31.5% vs. 17.2%, p = 0.044), but only the baseline eGFR was the independent factor by multivariate analysis (OR = 1.05; 95% CI = 1.03 – 1.07; p &lt; 0.001).ConclusionsTDF was significantly more effective in achieving complete viral suppression beyond month 12, and there was no significance in nephrotoxicity than ETV group.Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.