Efficacy of Nucleotide/Nucleoside Analogues and Hepatitis B Immunoglobulin Therapy in Blocking Mother-to-Child Transmission of Hepatitis B in an Eastern Chinese Group.

The objective of this study was to investigate the efficacy and potential side-effects of nucleotide/nucleoside analogues and hepatitis B immunoglobulin injection of newborns in blocking mother-to-child transmission of hepatitis B virus in the middle and late pregnancy period. 238 cases of enrolled pregnant women were divided into the Telbivudine group, the Tenofovir group, the Lamivudine group, and the hepatitis B immunoglobulin (HBIG) group. Enrolled patients received corresponding therapies. Clinical and laboratory data were collected. Results showed that the levels of HBV DNA of the enrolled pregnant women in the Telbivudine, Tenofovir, and Lamivudine groups decreased rapidly after 12 weeks of drug intervention compared with those in the control. HBsAg positive rate in newborns and in children 24 weeks after birth was 0/60, 0/60, 0/60, 3/30, and 11/28 in the Telbivudine, Tenofovir, Lamivudine, HBIG, and control groups, respectively. No significant side-effects were identified after following up to 12 months after birth. Our results show that routine HBV vaccine plus HBIG injections is insufficient in blocking mother-to-child HBV transmission. Administration of nucleotide/nucleoside analogues or HBIG at pregnancy is suggested to maximize the blocking of vertical HBV transmission.

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

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

Efficacy of telbivudine and entecavir against virus reactivation in HBeAg-patients undergoing chemotherapy.

The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg-) patients receiving chemotherapy (C/T).Records of 260 HBeAg-, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.Of the 126 HBeAg- patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ±â€Š23.1 to 87.3 ±â€Š21.3 ml/minute/1.73 m (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ±â€Š32.2 to 85.5 ±â€Š85.7 ml/minute/1.73 m (P = .0009).The absolute risk reduction ARR is 27.8% - 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% - 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg-status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.

Efficacy and Safety of Lamivudine or Telbivudine in Preventing Mother-to-Child Transmission of Hepatitis B Virus: A Real-World Study.

BACKGROUND: There are few large sample studies evaluating the safety and efficacy of lamivudine (LAM) or telbivudine (LdT) in preventing hepatitis B mother-to-child transmission (MTCT) in highly viremic mothers in the third trimester of pregnancy in real-world settings. The purpose of this study was to analyze a large sample size of HBV-infected mothers to better understand the safety and efficacy of LAM and LdT under the aforementioned criteria. METHODS: During the period of November 2008 to November 2017, we retrospectively enrolled mothers with HBV DNA > 1 × 106 IU/mL who received LAM or LdT during the third trimester of pregnancy and compared them to untreated mothers. All mothers were divided into the three following groups: the LAM group, the LdT group, and the control group. RESULTS: A total of 2624 HBV-infected mothers were enrolled in the study, with 363 in the LAM group, 1283 in the LdT group, and 978 in the control group. The MTCT rates were significantly lower in the LAM or LdT group than that in the control group (0.4% or 0.3% versus 9.0%, P < 0.001). Infants born to untreated mothers had a significantly higher risk of HBV infection (OR = 28.6, 95% CI: 10.4-78.7, P < 0.001). There were no significant differences in perinatal complications between the three groups (P > 0.05). There were also no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates. Postpartum discontinuation of antiviral therapy did not seem to increase the risk of postpartum alanine aminotransferase (ALT) flare. CONCLUSION: LAM or LdT treatment initiated in the third trimester for mothers with HBV DNA > 1 × 106 IU/mL was equally safe and effective in preventing MTCT.

Nucleos(t)ide analogues for the treatment of chronic hepatitis B: a systematic review with network meta-analysis.

OBJECTIVES: Chronic hepatitis B (CHB) is a major global health problem caused by hepatitis B virus (HBV) infection, and can put patients at high risk of death from cirrhosis and liver cancer. However, CHB can be treated with nucleos(t)ide analogues. We aimed to evaluate the effectiveness and safety of nucleos(t)ide analogues for the treatment of CHB patients. METHODS: A systematic literature search was performed. Direct comparison meta-analyses and network meta-analysis (NMA) were carried out. RESULTS: Thirty-six randomized controlled trials (RCTs) met inclusion criteria. Compared with placebo, the nucleos(t)ide analogues were all effective in HBeAg seroconversion, HBeAg loss, and achieving undetectable HBV DNA. Telbivudine was associated with higher HBeAg seroconversion compared with entecavir. For HBeAg loss rate and proportion of achieving undetectable HBV DNA, tenofovir ranked as the best. Entecavir might be the most potent in the normalization of alanine aminotransferase (ALT). The nucleos(t)ide analogues did not have higher serious adverse events rate as compared with placebo. CONCLUSION: The nucleos(t)ide analogues are all effective for HBeAg seroconversion, HBeAg loss, undetectable HBV DNA, and most are effective for ALT normalization in adults with CHB. RCTs of multi-center, low risk of bias, and long-term follow-up are still needed.

Potential Effects of Telbivudine Versus Entecavir on Renal Function in Patients With Chronic Hepatitis B Virus Receiving Glucocorticoids Therapy.

Data remains limited about the optimal nucleos(t)ide analogue therapy for patients infected with hepatitis B virus (HBV) while treated with glucocorticoids because of kidney diseases. We aim to evaluate the safety and efficacy of long-term antiviral therapy with telbivudine (LdT) and entecavir (ETV) in this specific population. In this prospective randomized controlled study, a total of 60 patients with both kidney diseases and chronic hepatitis B were randomly divided into LdT group and ETV group. We analyzed changes in estimated glomerular filtration rate (eGFR), variation in HBV DNA, seroconversion of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HBsAg). During the 18 month follow-up period, serum HBV DNA load was decreased significantly at 3, 6, 12, 18 months, compared to the pre-treatment value in both LdT and ETV cohorts. No patients achieved HBeAg loss-seroconversion or HBsAg loss-seroconversion with ETV therapy whilst one patient experienced HBeAg and HBsAg loss-seroconversion with LdT therapy. No significant changes in eGFR were seen in patients with ETV therapy compared to baseline. However, eGFR increased 7.43, 18.97 mL/min/1.73m2 , respectively at 12 and 18 months in LdT group and the changes were significant compared to baseline. Further analysis also demonstrated that eGFR significantly improved 11.8, 23.25 mL/min/1.73m2 at 12 and 18 months in LdT group for patients with impaired renal function. LdT is superior to ETV in patients with chronic hepatitis B and kidney diseases because of the renal protection it confers by increasing eGFR.

Effects of entecavir, tenofovir and telbivudine treatment on renal functions in chronic hepatitis B patients.

BACKGROUND AND STUDY AIMS: The aim of this study was to enlighten the controversy about the renal safety of entecavir, tenofovir, and telbivudine treatments in chronic hepatitis B (CHB) patients by comparing these treatments in real-world conditions. PATIENTS AND METHODS: We retrospectively enrolled 104 treatment-naive patients with CHB monoinfection into our study. Patients were treated with entecavir monotherapy (n=38), tenofovir monotherapy (n=35), or telbivudine monotherapy (n=31). We then compared and statistically analyzed the effects of these drugs on the estimated glomerular filtration rate (eGFR) over a 24-month follow-up period. RESULTS: In the entecavir group, time-dependent change in eGFR was not statistically significant (p = 0.357). There was a statistically significant increase in eGFR in the telbivudine group at 12 months (p<0.001) and at 24 months (p<0.001) and, in contrast, a statistically significant decrease in the tenofovir group at 12 months (p<0.001) and at 24 months (p<0.001). There was no significant relationship between entecavir and eGFR change (p = 0.763). We found that tenofovir and telbivudine were independent predictors of eGFR change (decrease in eGFR, p<0.001 and increase in eGFR, p = 0.001, respectively). CONCLUSIONS: We recommend close follow-up of renal functions, especially for patients treated with tenofovir. Telbivudine was superior to the other drugs in terms of renal function. We conclude that an individualized therapy program considering treatment efficacy and side effects is the best option for patients.

A randomized open label trial of tenofovir monotherapy versus tenofovir plus telbivudine in spontaneous reactivation of hepatitis B.

BACKGROUND/AIM: Acute-on-chronic liver failure (ACLF-B) in spontaneous reactivation of chronic hepatitis B (SR-CHB) has high mortality. Tenofovir disoproxil fumarate (TDF) improves survival by ~40% in ACLF-B but is potentially nephrotoxic. Combining telbivudine (LDT) with TDF may negate this risk and could boost rapid viral clearance and improve clinical outcomes. PATIENTS AND METHODS: Seventy consecutive patients with SR-CHB were randomized to TDF (300 mg/day, n = 35) or TDF plus LDT (600 mg/day; n = 35). In all, 25 had ACLF-B and none had option for liver transplantation. Primary endpoint was survival at 3 months. Secondary endpoints were survival at 3 months in ACLF-B, serial reduction in hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) loss and liver-related complications. RESULTS: Overall baseline clinical and laboratory parameters in the two groups were comparable. Reduction in HBV DNA at weeks 2, 4 and 12 was independent of treatment groups and presence of ACLF-B (P < 0.01). All six patients with HBsAg loss at 12 weeks had lower HBV DNA at baseline and none had ACLF-B. Patients with no ACLF-B had more rapid decline in bilirubin and alanine aminotraminase at week 2 compared with ACLF-B. Patients on TDF plus LDT showed significant improvement in AKI on follow-up (five of six patients) compared with TDF monotherapy (none of six patients) and had less reduction in estimated glomerular filtration rate at week 12. Eight of 10 patients with liver-related deaths received TDF monotherapy (P = 0.02). New-onset septic shock, TDF monotherapy, e-antibody positivity, and higher baseline model for end-stage liver disease score were predictors of mortality in ACLF-B. None had treatment-related severe adverse effects. CONCLUSION: Addition of LDT to tenofovir is safe and may be renoprotective in spontaneous reactivation of hepatitis B. Combination therapy improves survival in ACLF-B despite comparable HBV DNA suppression to tenofovir monotherapy.

Effectiveness of tenofovir or telbivudine in preventing HBV vertical transmission for pregnancy.

To evaluate the efficacy and safety of telbivudine (LdT) and tenofovir (TDF) for preventing hepatitis B virus (HBV) vertical transmission for HBV-positive pregnant women.Pregnant women (n = 145) from January 2013 to June 2017 were enrolled when they met inclusion criteria, which included HBV DNA ≥1.0 × 10 copies/mL and increased alanine aminotransferase (ALT) levels. Groups A (n = 58) and B (n = 51) were treated with LdT and TDF, respectively. Group C (n = 36) received no antiviral treatment. All infants were vaccinated with hepatitis B immunoglobulin and HBV vaccine. Vertical transmission of HBV was indicated by the presence of hepatitis B surface antigen (HBsAg) in infants 6 months and 12 months after birth.There is no difference of clinical characteristics of patients among the 3 groups. Serum HBV DNA levels of the 3 groups were similar at baseline (Group A vs. Group B vs. Group C, 7.88 ±â€Š0.65 vs. 7.91 ±â€Š0.75 vs. 7.69 ±â€Š0.53 P = .25). In addition, the after anti-HBV treatment in Groups A and B were significantly decreased. Also, the serum HBV DNA levels in both Groups A and B were lower than that of Group C (P < .01, both). The HBV infection rate in Group A treated with LdT was not different from Group B treated with TDF. The dynamic changes of serum ALT level were similar. ALT levels were similar among the 3 Groups (P = .171), while there is statistically significant difference between A and C, and between B and C before delivery (P < .01). For the infants, there were no significant differences among body weight, height, head circumference, or Apgar score. However, the HBsAg positivity rates of infants in Groups A, B, C at postpartum 24 weeks and 48 weeks was 0%, 0%, and 11.1%, respectively (P < .001).Administration of LdT or TDF to HBV-infected mothers are effective and safe to block mother-to-infant HBV transmission.

The different effects of adefovir dipivoxil and telbivudine on the prognosis of hepatitis b virus-related hepatocellular carcinoma patients after curative resection.

Numerous studies suggested that antiviral therapy could reduce the recurrence in hepatocellular carcinoma (HCC) patients after hepatectomy. The impact of nucleotide and nucleoside analogues on prognosis of chronic hepatitis B (CHB) related HCC remains to be explored. We aimed to investigate the role of the telbivudine and adefovir dipivoxil on the prognosis of CHB-related HCC patients after hepatectomy.One hundred eighty-eight CHB-related patients who received hepatectomy from February 2010 to February 2017 were divided into telbivudine (LdT) and adefovir dipivoxil (ADV) groups. The characteristics and survival information of both groups were retrospectively compared and analyzed.One hundred eleven and 77 patients received telbivudine and adefovir dipivoxil monotherapy, respectively. Alanine aminotransferase (ALT), total bilirubin level, status of hepatitis B e antigen (HBeAg), serum HBV-DNA level were compared between groups. OS and DFS in ADV-treatment group were significantly better than it in LdT-treatment group (P < .05). In the subgroups analysis, we found that ADV treatment was significantly associated with better DFS and OS among patients with cirrhosis, HBeAg-negative patients, or those with detectable HBV-DNA.CHB-related HCC patients receiving long-term ADV-treatment had a better OS and DFS than patients receiving LdT-treatment after hepatectomy.

Changes in Liver Tissue Trace Element Concentrations During Hepatitis B Viral Infection Treatment.

Approximately 350-400 million people in the world have Hbs Ag (hepatitis B virus surface antigen) positivity. In the international guidelines, the permanent suppression of replication in chronic hepatitis B virus (HBV) infection therapy is reported as the primary therapeutic goal. Trace elements play a key role in liver diseases. The aim of our study is to determine some trace element concentrations in the liver during HBV treatment periods. The measurement of 11 trace elements (manganese, lead, nickel, chromium, cadmium, iron, copper, zinc, silver, cobalt, and aluminum) was carried out by the method of inductively coupled plasma mass spectrometry in liver biopsy materials (before starting treatment and at the sixth month of the treatment period). There was an increase in zinc and copper concentrations in liver materials at the sixth month of treatment compared to the pre-treatment values (the median zinc value was 48.05 µg/g before treatment and 74.9 µg/g at 6 months after initial treatment, p = 0.035; median copper was 2.82 µg/g before treatment and 5.31 µg/g after 6 months, p = 0.002). General estimations indicated that zinc (p = 0.002), iron (p = 0.0244), copper (p = 0.0003), and aluminum (p = 0.0239) values may be effective in HAI (histological activity index) changes. Only iron levels could be at a very low level effective on the changes caused by fibrosis (p = 0.0002). Liver tissue zinc and copper levels increased in parallel with the improvement of inflammation in antiviral-treated HBV patients. In addition, the levels of zinc and copper in the liver tissue can be useful markers for liver tissue damage detection.

Telbivudine and adefovir dipivoxil combination therapy improves renal function in patients with chronic hepatitis B: A STROBE-compliant article.

Few studies have addressed the impact of adefovir dipivoxil (ADV)-based combination therapy on the renal function of patients with chronic hepatitis B (CHB). This study evaluated the effects of ADV combined with other antiviral nucleotide analogs (NAs) on renal function of patients with CHB, and analyzed the risk factors for more than 20% reduction of baseline estimated glomerular filtration rate (eGFR).The data of 164 patients with CHB were retrospectively analyzed in this study. Of the 164 patients, 42 received entecavir (ETV) combined with ADV (ETV + ADV group), 68 lamivudine (LAM) combined with ADV (LAM + ADV group), and 54 telbivudine (LDT) combined with ADV (LDT + ADV group). Serum creatinine (SCr) level, eGFR, and proportion of patients with eGFR ≥ 90 mL/min/1.73 m were observed. Also, the independent risk factors for more than 20% reduction of baseline eGFR were analyzed.After 104-week combination therapy, compared with the baseline level, SCr levels were significantly increased in the ETV + ADV group (67 µmol/L vs 73 µmol/L, P = .012) and LAM + ADV group (68 µmol/L vs 79 µmol/L, P = .008), but it was significantly decreased in the LDT + ADV group (69 µmol/L vs 64 µmol/L, P = .023). Compared with the baseline level, eGFR was significantly decreased in the ETV + ADV group (107.8 mL/min/1.73 m vs 96.1 mL/min 1.73/m, P = .004), and LAM + ADV group (105.4 mL/min/1.73 m vs 87.3 mL/min/1.73 m, P = .000), but it was significantly increased in the LDT + ADV group (104.1 mL/min 1.73/m vs 116.2 mL/min/1.73 m,P = .005). The proportion of patients with normal renal function (≥90 mL/min/1.73 m) was significantly higher in the LDT + ADV group than in the ETV + ADV group (P = .002) and LAM + ADV group (P = .001). Multivariate analysis showed that age (P = .035), male (P = .005), baseline eGFR (P < .001), LAM combined with ADV (P < .008), and ETV combined with ADV (P = .03) were independent risk factors for 20% reduction of baseline eGFR.As compared with ETV and ADV combination therapy as well as LAM and ADV combination therapy, LDT and ADV combination therapy can improve eGFR level, so LDT and ADV combination therapy is suitable for the patients with potential renal impairment.

[Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection].

Objective: To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients. Methods: A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ (2) test. Results: There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min(-1) ·(1.73 m(2))(-1)] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal. Conclusion: For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Rare clinically significant hepatic events and hepatitis B reactivation occur more frequently following rather than during direct-acting antiviral therapy for chronic hepatitis C: Data from a national US cohort.

Recently, cases of hepatitis B virus reactivation (HBVr) with direct-acting antiviral therapy (DAAs) for HCV have been reported. However, few data exist from large, Western cohorts. The study objectives were to evaluate the incidence of alanine aminotransferase (ALT) flares, clinically significant hepatic events, and HBVr among a national cohort of US veterans with prior exposure to HBV (anti-HBc+) treated with DAAs. We used a national administrative database to identify patients treated with DAAs from January 2014 through November 2016 and obtained clinical and demographic as well as HBV and HCV treatment data. HBVr was defined as an at least 1-log increase in HBV DNA titre. Among 17 779 anti-HBc+ patients, 17 400 were HIV- and 379 were HIV+. Among the HIV- patients, 17 266 (99%) were HBsAg- prior to DAA therapy and 134 were HBsAg+. Among HIV-, HBsAg- patients, ALT elevations greater than 10 times the upper limit of normal (ULN; ≥300 IU/mL) were rare and occurred more frequently after treatment completion: 31 cases (<0.1%) during vs 85 (0.6%) following treatment. Clinically significant hepatic events defined as ALT increases >100 IU/L with total bilirubin >2.5 mg/dL occurred in 39 cases (0.3%), most often following DAA completion (n = 35 cases, 3/35 in setting of HCV relapse). Among 31 patients with post-DAA hepatic events without HCV relapse, 10 (32%) were confirmed unrelated to HBVr by HBsAg and/or HBV DNA testing, 1 (3%) confirmed due to HBVr, and 20 (65%) did not have documented HBV-related testing. One additional case of HBsAg- to + seroreversion was identified. Among HBsAg+ DAA recipients, 2/97 (2%), both with cirrhosis, experienced ALT elevations ≥300 IU/mL in the setting of HBVr. In conclusion, clinically significant hepatic events and HBVr were rare and much more likely among HBsAg-positive individuals. Anti-HBc + patients should be monitored for ALT flares and HBVr during and possibly for up to 6 months post-DAA therapy.