Telbivudine-induced rhabdomyolysis in a patient undergoing haemodialysis: A case report and review of literature.

Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.

Efficacy and Long-term Safety of Telbivudine Usage During Second or Third Trimester in Hepatitis B Surface Antigen Positive Mothers With High Viral Load: A 10-year Prospective Study.

GOALS: The study is to evaluate the efficacy and long-term safety of telbivudine (LdT) usage for hepatitis B surface antigen (HBsAg) positive pregnant women with high viral load. BACKGROUND: The efficacy and safety of LdT during pregnancy were not assessed from a long-term perspective. STUDY: HBsAg-positive pregnant women were enrolled and grouped according to antiviral initiation time. Group A (n=100) and group B (n=100) were treated with LdT initiated in the second or third trimester. Group C (n=90) received no antiviral treatment. The efficacy and safety of LdT treatment were compared and infants were followed-up at 1, 5, and 10 years. Denver developmental screening test was conducted at 5 years. RESULTS: Viral loads before delivery in LdT-treated groups were lower than that in group C and group A was lower than that in group B ( P <0.001). No infants in LdT-treated groups were infected whereas 8.8% (8/90) infants in group C had positive HBsAg (χ 2 =23.20, P <0.001). All LdT-treated mothers were well tolerated and no LdT-related adverse events in infants were reported. Part of the physical growth index of infants was higher than Chinese standard values (SV) and showed significant differences. In groups A and B, the developmental screening test qualified rate of 100% (48/48) and 97.96% (48/49) showed no significant difference compared with 92% in normal Chinese children (χ 2 =5.72, P =0.06). CONCLUSIONS: Treatment initiated during the second trimester could strengthen the success of mother-to-child transmission blockage. LdT treatment during pregnancy is safe for both mothers and infants in the long term.

Renal mitochondrial toxicity: effects of thymidine analogues and tenofovir disoproxil fumarate in African people with HIV.

We investigated the contributions of thymidine analogue and tenofovir disoproxil fumarate (TDF) antiretroviral therapy on renal mitochondrial toxicity in Ghanaian people with HIV (PWH). Similar levels of renal biochemical and mitochondrial dysfunction were seen, and there was no increased risk in PWH who had sequenced from thymidine analogue to TDF. However, mild renal impairment was associated with mitochondrial DNA damage in TDF but not thymidine analogue-treated PWH. These data support the continued use of TDF in resource-limited settings.

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.

Glucagon Receptor Antagonist-Stimulated α-Cell Proliferation Is Severely Restricted With Advanced Age.

Glucagon-containing α-cells potently regulate glucose homeostasis, but the developmental biology of α-cells in adults remains poorly understood. Although glucagon receptor antagonists (GRAs) have great potential as antidiabetic therapies, murine and human studies have raised concerns that GRAs might cause uncontrolled α-cell growth. Surprisingly, previous rodent GRA studies were only performed in young mice, implying that the potential impact of GRAs to drive α-cell expansion in adult patients is unclear. We assessed adaptive α-cell turnover and adaptive proliferation, administering a novel GRA (JNJ-46207382) to both young and aged mice. Basal α-cell proliferation rapidly declined soon after birth and continued to drop to very low levels in aged mice. GRA drove a 2.4-fold increase in α-cell proliferation in young mice. In contrast, GRA-induced α-cell proliferation was severely reduced in aged mice, although still present at 3.2-fold the very low basal rate of aged controls. To interrogate the lineage of GRA-induced α-cells, we sequentially administered thymidine analogs and quantified their incorporation into α-cells. Similar to previous studies of ß-cells, α-cells only divided once in both basal and stimulated conditions. Lack of contribution from highly proliferative "transit-amplifying" cells supports a model whereby α-cells expand by self-renewal and not via specialized progenitors.

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors.

BACKGROUND: Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors. METHODS: In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses. RESULTS: Exposure to thymidine analogs and/or ddI was associated with 21.6 cm larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to thymidine analogs and/or ddI [3.7 cm per year (2.3-5.1)], but not time since discontinuation [-1.1 cm per year (-3.4 to 1.1)], was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension [adjusted odds ratio (aOR) 1.62 (1.13-2.31)], hypercholesterolemia [aOR 1.49 (1.06-2.11)], and low high-density lipoprotein [aOR 1.40 (0.99-1.99)]. CONCLUSIONS: This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.

Effectiveness of telbivudine antiviral treatment in patients with hepatitis B virus-associated glomerulonephritis: A 104-week pilot study.

The aim of this study was to evaluate clinical efficacy of telbivudine in treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN).A total of 43 HBV-GN patients combined with chronic hepatitis B were treated with telbivudine for 104 weeks. Serum levels of HBV DNA viral load, HBeAg, HBeAb, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), and 24-hour urinary protein were evaluated after telbivudine treatment of 12, 24, 52, 76, and 104 weeks. Estimated glomerular filtration rate (eGFR) was calculated at baseline, 24 weeks, 52 weeks, and 104 weeks of treatment, respectively. Complete remission (CR) was defined as urinary protein <0.3 g/day, with normal ALT, AST, Cr, and eGFR. Criteria for partial remission include: 24-hour urinary protein excretion decreased by >50% compared with baseline level, and ALT and AST decreased >50%.Proteinuria level gradually decreased in patients with HBV-GN after telbivudine treatment. The percentages of PR + CR were 90.7% and 95.3%, respectively, at 52 and 104 weeks. Compared to baseline, eGFR were significantly increased from 69.2 ±â€Š23.1 mL/min/1.73 m to 116.2 ±â€Š26.3 mL/min/1.73 m at 104 weeks of treatment. Multivariate analysis indicated that baseline HBV DNA viral load (odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.11-2.19, P = .02) and baseline urinary protein (OR = 1.08, 95% CI 1.04-2.44, P = .03) were independent risk factors associated with CR after telbivudine treatment among patients with HBV-GN.Our study demonstrates that telbivudine can be used to treat HBV-GN and effectively improve eGFR in these patients.

Increase of Serum Kallikrein-8 Level After Long-term Telbivudine Treatment.

BACKGROUND/AIM: Our previous cDNA microarray study revealed increased cellular mRNA levels of a panel of genes, including kallikrein-8 (KLK8), after long-term telbivudine treatment in chronic hepatitis B patients. The aim of this study was to verify whether serum protein levels of KLK8, a cancer-related enzyme, are indeed increased after telbivudine treatment. PATIENTS AND METHODS: A total of 83 chronic hepatitis B patients receiving telbivudine for >2 years were retrospectively analyzed. Serum KLK8 protein and estimated glomerular filtration rate (eGFR) changes were compared before and after treatment. RESULTS: Both serum KLK8 protein and eGFR increased significantly after long-term telbivudine treatment (paired t-test: KLK8, p<0.001; eGFR, p=0.001). No direct correlation was found between KLK8 increase and eGFR change. However, eGFR change was positively associated with post-treatment KLK8 levels following adjustment for body height (p<0.001). CONCLUSION: Telbivudine treatment resulted in increased levels of serum KLK8 protein. Furthermore, eGFR increase was associated with body height-adjusted, post-treatment KLK8 levels.

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B.

BACKGROUND: Current treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ. As mitochondria are the main sites of oxidative phosphorylation, there will be an increase of pyruvate reduction to lactic acid and insufficient adenosine triphosphate. The accumulation of lactic acid causes LA, while lack of energy leads to cell dysfunction and mitochondria-associated disease, including RM. All five NAs, except tenofovir, have been reported causing LA and RM. Here we report the first case of CHB patients developing fatal LA and RM during telbivudine and tenofovir treatment. CASE PRESENTATION: The patient is a 51-year-old man who was hospitalized in November 2015. He had taken telbivudine regularly because of CHB. Later, tenofovir was added to antiviral treatment because of HBV resistance. Then he had myalgia, chest tightness and anorexia. The blood lactate was 12.7 mmol/L. The arterial blood gas analysis showed pH 7.25, base excess 21.1 mmol/L. CPK was 991 U/L, myoglobin was 1745 ng/ml and creatine was 83 µmol/L. Abdomen magnetic resonance revealed cirrhosis. Muscle biopsy revealed myogenic lesion with abnormality of mitochondria and fat metabolism. The patient was diagnosed with Hepatitis B envelope Antigen positive CHB, cirrhosis, LA and RM characterized by myalgia and elevated myoglobin. He was given tenofovir alone as antiviral treatment instead. After hemodialysis and 4 weeks` treatment of corticosteroids, his symptoms recovered, and blood lactate gradually returned to a normal range. CONCLUSIONS: This case shows that tenofovir may trigger muscle damage and fatal RM in combination with telbivudine treatment in CHB patients. Thus, patients receiving tenofovir and telbivudine should be closely monitored for muscular abnormalities, blood lactate level and other mitochondrial toxicity associated side effects.

Motor development delay in offspring is associated with prenatal telbivudine exposure.

Telbivudine is an orally nucleoside analog with potent and specific antihepatitis B virus (HBV) activity, and it has been reported to block mother-to-infant transmission. However, few studies have focused on the safety of prenatal exposure for offspring development.This is a prospective noninterventional study. Participants were enrolled during delivery through the Women's Hospital of Zhejiang University School of Medicine between January 2012 and September 2013. Neonate's umbilical cord arterial blood (UCAB) was collected after delivery. Hepatitis B virus DNA copy, HBV serology, alanine aminotransferase (ALT), creatine kinase (CK), creatinine (CRE), and blood urea nitrogen (BUN) were measured. The development of the offspring was evaluated by the Chinese Revision of Bayley Scales of Child Development (BSCD-CR) at 12 to 24 months old.Around 30 and 31 chronic hepatitis B mothers were recruited in untreated group (non-LdT group) and telbivudine-treatment group (LdT group), respectively, and 2 children (one in non-LdT group and 1 in LdT group) were lost in follow-up. Sixty-one normal women and their children were recruited as a normal control (control group). Compared with non-LdT group, telbivudine treatment effectively blocks HBV transmission from mother to infant. However, CK in UCAB was significantly increased in the LdT group. Moreover, children with prenatal telbivudine exposure showed lower level of serum creatinine than non-LdT group, reduction of psychomotor developmental index and increased risk of motor development delay.Prenatal telbivudine exposure is correlated with motor development delay in offspring.

Safety and efficacy of telbivudine in late pregnancy to prevent mother-to-child transmission of hepatitis B virus: A multicenter prospective cohort study.

Infection of hepatitis B virus (HBV) occurs in ~10% of infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg) after immunoprophylaxis. We aimed to evaluate the safety and efficacy of telbivudine used during late pregnancy for preventing mother-to-child transmission of HBV. We conducted a multicenter prospective cohort study in 5 hospitals from 2012 to 2014, which enrolled HBV-infected singleton pregnant women with positive HBeAg. By their choice, women were divided into therapy (telbivudine 600 mg/day, from gestation 28-32 weeks to 3-4 weeks postpartum) and control (no antiviral agent) groups. Infants received passive-active immunoprophylaxis and follow-up at the age of 7-14 months. Totally, 328 pregnant women were included: 149 in the telbivudine group and 179 in the control group. Baseline HBV DNA levels were similar in the 2 groups (7.43 vs 7.37 log10 IU/mL, P = .711). At delivery, HBV DNA levels in the telbivudine and control groups were 3.80 and 7.26 log10 IU/mL, respectively (P < .0001). Of the infants, 128 (85.9%) in the telbivudine group and 156 (87.2%) in the control group were followed up. No infant in the telbivudine group had chronic infection, while 2 (1.28%) infants in the control group did (P = .503). Three (2.34%) infants in the telbivudine group, but none in the control group, had severe congenital or developmental abnormalities (P = .090). The data indicate that telbivudine may block perinatal HBV transmission. However, larger studies are required to clarify whether anti-HBV therapy in pregnancy is associated with severe adverse effects in the foetuses and infants.

Rhabdomyolysis, lactic acidosis, and multiple organ failure during telbivudine treatment for hepatitis B: a case report and review of the literature.

BACKGROUND: Telbivudine can cause severe side effects, including myositis, neuritis, rhabdomyolysis, and lactic acidosis. However, reported cases of telbivudine leading to multiple organ failure are rare. Here, we report a case of telbivudine-induced severe polymyositis, lactic acidosis, and multiple organ failure. CASE PRESENTATION: A 30-year-old Chinese man with hepatitis B virus infection received antiviral treatment with 600 mg of telbivudine daily for more than 11 months. He developed progressive weakness and myalgia, and subsequently experienced palpitations, chest tightness, lethargy, hypotension, and hypoxemia. Blood tests showed markedly elevated levels of alanine aminotransferase (955 U/L), aspartate aminotransferase (1375 U/L), blood urea nitrogen (14.9 mmol/L), creatine kinase (peak at 8050 U/L), and blood lactate (>20.0 mmol/L). His symptoms improved after continuous renal replacement therapy and short-term methylprednisolone treatment. Hyperbaric oxygen therapy, physical therapy, and rehabilitation for more than 2 months led to recovery of muscle strength to the normal range. CONCLUSIONS: We conclude that continuous renal replacement and steroid therapies play key roles in stabilizing telbivudine-induced severe rhabdomyolysis, lactic acidosis, and multiple organ failure. Hyperbaric oxygen, physical therapy, and rehabilitation may aid in functional recovery after the acute phase of lactic acidosis and organ failure.

Comparing Efficacy of Lamivudine, Adefovir Dipivoxil, Telbivudine, and Entecavir in Treating Nucleoside Analogues Naïve for HBeAg-Negative Hepatitis B with Medium Hepatitis B Virus (HBV) DNA Levels.

BACKGROUND The antiviral effect of HBV in different nucleos (t) ide analogues is still not well known. This study was conducted to compare the effectiveness of lamivudine (LMV), adefovir dipivoxil (ADV), telbivudine (LdT), and entecavir (ETV) monotherapy in chronic HBeAg-negative hepatitis B patients with medium load of HBV DNA. MATERIAL AND METHODS The effective data of 207 patients treated by LMV (n=43), ADV (n=57), LdT (n=54) or ETV (n=53) were collected and analyzed during 144-week follow-up by retrospective analysis. RESULTS Serum HBV DNA levels were significantly lower in the ETV group 1.91±0.45 log10 IU/ml) than in the LdT group (2.09±0.62 log10 IU/ml), ADV group (2.26±0.73 log10 IU/ml), and LMV group (2.08±0.75 log10 IU/ml) at 12 weeks (P=0.0464). HBV DNA levels were maintained at lower levels in the ETV group compared to other 3 groups during follow-up (48 weeks, P<0.001; 96 weeks, P<0.001). Multivariate Cox regression analysis showed that LMV (P=0.001), ADV, (P<0.001), and LdT (P<0.001) were all negative predictors of HBV DNA-negative time, but ETV was not. Viral breakthrough occurred in 34.8% (15/43) of patients in the LMV group; 5.26% (3/57) in the ADV group, 7.4.0% (4/54) in the LdT group, and 0% (0/53) in the ETV group at the end of follow-up. No significant differences were found in mean ALT levels (all P>0.05) or in cumulative normalization rates (P=0.473). CONCLUSIONS ETV was more potent and faster for viral response and lower viral breakthrough in medium load of HBV DNA when compared to LMV, ADV, or LdT monotherapy in HBeAg-negative CHB.

The Ca2+/CaMKK2 axis mediates the telbivudine induced upregulation of creatine kinase: Implications for mechanism of antiviral nucleoside analogs' side effect.

Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from creatine kinase (CK) elevation to myopathy. The purpose of this study was to explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on mitochondrial morphology and proteins (TK2 and ß-actin), oxidative stress, intracellular Ca2+ levels, Ca2+-related signaling pathway (CaMKK2/AMPK), and Ca2+-related biomarkers such as superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed in human skeletal muscle cells (HSKMCs). The results showed that LdT induced a dose-dependent increase in CK activity in HSKMCs, without affecting mitochondrial morphology, and TK2 and ß-actin protein levels, following 72 h of treatment. In addition, LdT increased Ca2+ production, ROS generation, MDA and lipid peroxide (LPO) levels, and activated the CaMKK2/AMPK signaling pathway. Moreover, these effects were attenuated by the BAPIA-AM (the calcium chelator). We also confirmed the presence of relevant markers (MDA, LPO, and SOD) in serum from CHB patients after LdT treatment, and found that CK was positively correlated with MDA and LPO, and negatively associated with SOD. These findings indicate that LdT induces CK elevation and oxidative stress associated with imbalance of intracellular Ca2+ in HSKMCs, suggesting that Ca2+/CaMKK2 axis imbalance may underlie human LdT-induced CK elevation. The present findings provide a solid basis for assessing the mechanism of drug-induced CK elevation, which can help develop new tools for the prevention and treatment of diseases associated with drug-induced CK elevation.

Safety and efficacy of telbivudine for chronic hepatitis B during the entire pregnancy: Long-term follow-up.

The management of hepatitis B virus (HBV) infection in pregnancy is a unique issue. Telbivudine (LdT) is recommended to block HBV mother-to-child transmission (MTCT) in the third trimester. However, the safety of LdT treatment during the entire pregnancy for the long-term growth of infants is unclear. The aim of this study was to evaluate the efficacy and long-term safety of LdT for the entire pregnancy period. This retrospective cohort study included 40 pregnant women and 43 children from 2011 to 2017. The antiviral effects and maternal abnormalities were evaluated. In addition, adverse events regarding infants at delivery and HBV vaccination outcomes were recorded. The status of physical development in the children during follow-up was also evaluated. Among pregnant women, the rates of HBV DNA flare were 5.00% during pregnancy and 7.50% postpartum, and the HBeAg seroconversion rates were 7.50% during pregnancy and 7.50% postpartum. No severe maternal abnormalities were observed. Regarding the infants, no one was positive for HBsAg, and only one infant was negative for anti-HBs in children over 7 months of age. Furthermore, no birth defects or severe adverse events were observed at delivery, and 97.67% normal height and 93.02% normal weight in children were observed on follow-up until 5 years of age. In conclusion, LdT use for the entire pregnancy is both effective for treating pregnant women and blocking HBV MTCT. Moreover, LdT is safe for women and infants. Most importantly, the long-term follow-up indicated that LdT is safe and does not affect the growth of children.

Improvement of telbivudine on renal function and massive proteinuria: A case report.

The quality of life and extended survival of patients with chronic hepatitis B (CHB), especially those with decompensated liver cirrhosis, has been improved markedly with nucleos(t)ide analogs treatment. In such conditions, the influence of hepatitis B virus (HBV) infection and antiviral agents on renal function becomes a consideration with long-term use and ageing. Membranous glomerulonephritis has been confirmed as the most common histological renal lesion. In this study, we reported a CHB patient with decompensated cirrhosis showing a significant improvement in massive proteinuria along with elevation of estimated glomerular filtration rate (eGFR) after 1 year treatment with telbivudine. However, a well-designed study should be performed to confirm the causal association, and the molecular mechanism needs further investigation.

Prospective cohort study on the efficacy and safety of telbivudine used throughout pregnancy in blocking mother-to-child transmission of hepatitis B virus.

Women with chronic hepatitis B should maintain nucleotide analogue treatment to prevent disease progression during pregnancy. The aim of this study was to prospectively evaluate the efficacy and safety of telbivudine used throughout pregnancy for preventing hepatitis B virus (HBV) mother-to-child transmission (MTCT). From January 2012 to June 2014, women who were receiving telbivudine therapy and became pregnant were enrolled in group A at 28 weeks of gestation. Pregnant women with an HBV DNA level >106  IU/mL were enrolled in either group B (telbivudine started at 28 weeks of gestation) or group C (control group without treatment). MTCT was defined as infants who were positive for serum hepatitis B surface antigen at 7 months after birth. There were 41, 179 and 177 pregnant women (397 infants) enrolled in groups A, B and C, respectively. The HBV DNA load at 28 weeks of gestation and delivery was 1.50 ± 0.62 vs 1.45 ± 0.61, 8.05 ± 0.37 vs 4.24 ± 0.89 and 7.94 ± 0.62 vs 7.86 ± 0.73 log10 IU/mL in groups A, B and C, respectively. The rate of MTCT in group C was 4.60%, which was significantly higher than the rates in groups A and B (0% and 0.6%, respectively) (P = .043). The difference between group A and group B was not significant. The rates of neonatal congenital abnormalities were 2.4%, 0.6% and 2.3% in groups A, B and C, respectively, and there were no significant differences (P = .140). Telbivudine used throughout pregnancy may be safe and effective for mothers and infants, but it may not enhance the efficacy of an HBV MTCT block compared with treatment starting at 28 weeks of gestation (NCT02253485).

Comparison of 208-week sequential therapy with telbivudine and entecavir in HBeAg-positive chronic hepatitis B patients with suboptimal responses to 24 weeks of Peg-IFNα-2a therapy: An open-labelled, randomized, controlled, "real-life" trial.

The purpose of the study was to compare the efficacy and safety of 208-week sequential therapy with telbivudine and entecavir in HBeAg-positive chronic hepatitis B (CHB) patients with suboptimal responses to 24 weeks of Peg-IFNα-2a therapy. This was an open-label, randomized, controlled, "real-life" trial. HBeAg-positive CHB patients with serum HBV DNA ≥5.0 lg IU/mL and a < 1 lg IU/mL decline of HBsAg level from baseline who underwent at least 24 weeks of Peg-IFNα-2a therapy were included. Enrolled patients were randomized to receive either telbivudine (600 mg/d, n = 95) or entecavir (0.5 mg/d, n = 95) for 208 consecutive weeks. Six patients were lost to follow-up (4 patients in the telbivudine group and 2 in the entecavir group). Treatment was combined with adefovir when week 24 HBV DNA levels declined to <2 lg IU/mL versus baseline, when viral breakthrough occurred during treatment,or when HBV DNA remained detectable at 52 weeks (HBV DNA ≥500 IU/mL). Responses and safety were assessed after 208 weeks of treatment. There were no significant differences among the baseline characteristics, including age, gender, and ALT, HBV DNA, HBsAg or HBeAg levels. After 208 weeks of treatment, there was no significant difference in the rates of undetectable HBV DNA (HBV DNA<500 IU/mL) between the telbivudine group and the entecavir group (84/91,92.31% vs 88/93,94.62%, respectively, P = .525). More patients in the telbivudine group than the entecavir group achieved HBeAg clearance (74.73% vs 46.24%, respectively, P < .001) and HBeAg seroconversion (64.84% vs 38.71%, respectively, P < .001). Univariate analysis (Enter, a = 0.05) of both groups showed that telbivudine, male gender and baseline HBeAg levels were significantly correlated with HBeAg seroconversion after 208 weeks of sequential therapy. Cox regression analysis (Enter, a = 0.05) of the telbivudine group showed that the HBeAg seroconversion rate at 208 weeks was significantly correlated with gender (male) (P = .006, HR=4.406), baseline HBeAg level (P = .005, HR=0.433) and 24 w-HBeAg level reduction of more than 0.5 lg IU/ml from baseline (P = .027, HR=0.487). All patients tolerated sequential telbivudine treatment; only slightly elevated creatine kinase levels were observed. Stratification analysis found that patients with baseline HBeAg levels less than 3 lg COI who switched to telbivudine may have had significantly improved HBeAg seroconversion rates. In conclusion, telbivudine promotes HBeAg seroconversion that merits investigation in HBeAg-positive CHB patients with suboptimal responses to 24 weeks of Peg-IFNα-2a therapy. We would suggest that patients with baseline HBeAg levels under 3 lg COI switch to telbivudine to achieve higher HBeAg seroconversion rates and use the early reductions in HBeAg levels (24 weeks) to guide treatment.

Long-term outcome of telbivudine versus entecavir in treating higher viral load chronic hepatitis B patients without cirrhosis.

Chronic hepatitis B (CHB) patients with higher hepatitis B virus (HBV) load (higher viral load [HVL], HBV DNA ≥1 × 107 copies/mL) require antiviral therapy, but data for evaluating the long-term outcome of this therapy with antiviral agents remain limited. We comparatively evaluated the efficacy and the safety of nucleoside analogues in 179 noncirrhotic CHB patients with HVL over 5 years. The HBeAg-positive (n = 104) or HBeAg-negative (n = 75) patients were treated consecutively with telbivudine (LdT, n = 88) or entecavir (ETV, n = 91) and evaluated for viral response, drug resistance and safety. HBV DNA, viral serology, biochemistries, HBV mutation and off-therapy relapse were determined. The cumulative rates of HBV DNA negativity were 86.4% and 94.5% for LdT and ETV at year 5, respectively. The rates of early viral response (EVR, HBV DNA <103 copies/mL at month 6) under LdT and ETV treatments were 58.0% and 34.1%, respectively (P < .05). Hepatitis B e antigen (HBeAg) and Hepatitis B surface antigen (HBsAg) loss-seroconversions were 47.7% and 18.2% on LdT and 16.5% and 2.2% on ETV (P < .01). Eighteen patients (age 28.2 ± 3.1) experienced HBsAg loss-seroconversion, followed by 33 ± 4.6 month off-therapy without a relapse. Viral mutations and serum creatine kinase elevation were 9.1% and 8.0% on LdT, but only 1.1% and 0% on ETV. Both LdT and ETV suppressed HBV replication in HVL CHB patients within 5 years. LdT therapy achieved a higher EVR, HBeAg and HBsAg seroconversion, especially in the younger patients, whereas ETV caused lower drug resistance and fewer adverse events. This finding might help to identify the optimal treatment for CHB patients with HVL.