Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleosides ; adverse effects ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; Pyrimidinones ; adverse effects ; therapeutic use ; Thymidine ; analogs & derivatives ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the occurrence and prognosis of telbivudine (LdT) therapy-associated elevations in creatine kinase (CK) in chronic hepatitis B (CHB) patients.

METHODSForty-nine patients treated with LdT from 2004 to 2010 were evaluated for development of CK elevation. In particular, the occurrences of grade 3/4 CK elevations (7-times the upper limit of normal (ULN)) and muscle damage were assessed over duration of the LdT treatment.

RESULTSThe rate of CK elevation increased with duration of LdT treatment (1 year: 61.2%; 5 years: 95.9%). In addition, the severity of CK elevation showed a trend for increasing with duration of LdT treatment, with grade 1/2 CK elevations increasing from 57.1% at year 1 to 81.6% at year 5 and grade 4 increasing from 4.1% at year 1 to 14.3% at year 5. Grade 3/4 CK elevations were observed in seven patients between LdT treatment weeks 36 and 168, but occurred most frequently between weeks 52 and 104, when the maximum peak value occurred (35.8-times the ULN). LdT treatment was stopped in two patients due to excessive CK elevation and one patient due to myositis. The majority of cases of LdT-associated grade 3/4 CK elevations were self-limiting, transient (decreasing to grades 0 or 2 within 2-3 weeks), and present without myalgia.

CONCLUSIONElevation of CK was not rare in CHB patients treated with LdT, but most cases resolved spontaneously. In general, the severity and persistence of CK elevation was not sufficient to warrant withdrawal of LdT.

Adolescent ; Adult ; Aged ; Antiviral Agents ; adverse effects ; therapeutic use ; Creatine Kinase ; metabolism ; Hepatitis B, Chronic ; drug therapy ; metabolism ; Humans ; Middle Aged ; Thymidine ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo investigate the efficacy of anti-hepatitis B virus (HBV) drugs for preventing vertical transmission of HBV and the safety of these drugs when given as treatment during pregnancy (to women) or insemination (to men).

METHODSCases of women and men who had taken anti-HBV drug therapy during pregnancy or insemination, respectively, were retrospectively selected for study from among 18 hospitals and 33 specialists in the Guangdong Province. Demographic, HBV infection and treatment data was collected for puerperal men or women and their newborns from the medical records.

RESULTSA total of 122 cases with detailed follow-up data were included in the study and including 74 women who were administered lamivudine (LAM) more than telbivudine (LdT) more than adefovir (ADV)more than entecavir (ETV) (hierarchy ranking by number of cases) and 48 men who were administered LAM more than ADV more than LdT more than ETV.None of the 122 newborns related to these cases showed HBV infection at 7 months of follow-up.None of the 74 puerperal women showed complications related to reproduction.There was one ease of a newborn being underweight at birth (2.1 kg), for which the mother had taken LdT during pregnancy. There was also one case of a newborn with a harelip and one case of a newborn with an inguinal hernia, for which both of the fathers had taken ADV during the time of insemination.

CONCLUSIONThis retrospective investigation carried out in Guangdong Province indicated that not only are anti-HBV drugs efficacious for blocking vertical transmission of HBV but also are safe for both mothers and infants when taken by fathers or mothers during the reproduction phases of insemination and pregnancy.

Adenine ; analogs & derivatives ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; Hepatitis B ; drug therapy ; Hepatitis B virus ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Lamivudine ; Male ; Mothers ; Organophosphonates ; Pregnancy ; Retrospective Studies ; Thymidine ; analogs & derivatives ; Time Factors

Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine has a more potent and sustained antiviral activity with a lower frequency of viral resistance than lamivudine. Although there are several reports concerning the safety profile of telbivudine, most adverse events are described as mild and transient in nature. Here we report two cases of telbivudine-induced myopathy in patients with chronic hepatitis B who were siblings.
Adult ; Antiviral Agents/adverse effects/*therapeutic use ; Creatine Kinase/blood ; Electromyography ; Hepatitis B, Chronic/*drug therapy/metabolism/pathology ; Humans ; Male ; Muscle, Skeletal/pathology ; Muscular Diseases/etiology ; Siblings ; Thymidine/adverse effects/*analogs & derivatives/therapeutic use

OBJECTIVETo observe the long-term efficacy and safety of telbivudine (LdT) for pregnant women with chronic hepatitis B (CHB) and their children born from the treatment period.

METHODSA total of 118 pregnant women with CHB were enrolled in the study and provided informed consent for participation. The women opted for participation in the treatment group (7 =73; LdT 600 mg once daily, starting in early pregnancy and continued until after delivery) or in the control group (n =45; no LdT treatment). All newborns were given active and passive immunization upon birth and tested for serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody (anti-HBs) and HBV DNA at 0, 1, 7 and 12 months of age. The Paediatrics Neuropsychological Development Scale for Children aged 0 - 6 (5 items) established by the Capital Institute was used to test the children; in addition, the children were evaluated by observation for action ability (fine and gross motor skills), adaptability, language ability and social behaviour. Total IQ was estimated as a developmental quotient (DQ) by using the equation: points from the 5 scale items actual age in months * 100.

RESULTSThe LdT group included 69 women with successful pregnancies, 1 case of miscarriage and 3 cases that were lost to follow-up. The control group included 34 women with successful pregnancies, 4 cases of miscarriage, 1 case with fatal outcome, and 6 cases of no pregnancy. Compared to the control group, the LdT group had a significantly higher successful pregnancy rate (x² =4.86 in the LdT group, P < 0.05). In addition, the LdT group had a significantly higher rate of term delivery (53 cases vs. 34 cases, x² = 6.38, P < 0.05). The neonates born to the women in the LdT group included 53 cases of weakly-negative HBsAg at birth and 1 case at 1 month old, as well as negativity for HBV DNA, and HBsAg remaining weakly positive at 6 months old; the intrauterine infection rate was 1.8% and no case of deformity occurred.Among the 34 neonates in the control group, 6 showed HBsAg positivity at 1 month old, and the HBsAg positivity remained for all 6 at 6 months old; the intrauterine infection rate was 16.6%, which was significantly higher than that of the LdT group (x² = 5.10, P < 0.05). The neonates in the LdT group had a significantly higher anti-HBs production rate at 1 year old than those in the control group (98.1% (52/53 vs. 82.4% (28/34). X² = 4.87, P < 0.05). The neonates in the LdT group showed normal growth and development for all 53 cases of young children, and IQ levels of excellent for 3 cases, smart for 8 cases, normal for 40 cases, and low for 2 cases. The neonates in the control group showed normal growth and development for all 34 cases of young children, and IQ levels of excellent for 2 cases, smart for 4 cases, normal for 27 cases, and low for 1 case.

CONCLUSIONChildbearing chronic HBV patients treated with LdT had higher rates of successful pregnancy, blocking of intrauterine infection and anti-HBs reduction compared to their untreated counterparts. The children bom to LdT-treated women showed no difference in long-term growth and development and total IQ from the children born to the untreated women with chronic HBV.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; Thymidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of telbivudine treatment in pregnant patients with chronic hepatitis B to block mother-to-child transmission of hepatitis B virus (HBV).

METHODSMedline and the Chinese Biomedical Literature Database were searched for studies of HBV, mother-to-child transmission, and telbivudine. Of the 68 potentially relevant publications, eight randomized controlled trials (RCTs) conformed to the inclusion and exclusion criteria. Following data extraction, a meta-analysis was carried out with RevMan5.1 software.

RESULTSSeven of the eight RCTs were in Chinese, and the remaining study was in English but carried out at a Chinese site. The RCTs comprised a total of 678 subjects, including 352 cases and 326 controls. Infants born to telbivudine-treated mothers had a significantly lower rate of HBsAg positivity and HBV DNA positivity at birth than the control group of infants (odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.17, 0.43, P less than 0.00001; OR = 0.14, 95% CI: 0.06, 0.32, P less than 0.00001). Infants born to telbivudine-treated mothers also had significantly lower rates of mother-to-child transmitted HBV at 6 months (OR = 0.06, 95% CI: 0.02, 0.22, P less than 0.00001; OR = 0.05, 95% CI: 0.01, 0.25, P = 0.0003) and 12 months (OR = 0.13, 95% CI: 0.03, 0.56, P = 0.007; OR = 0.08, 95% CI: 0.02, 0.37, P = 0.001) after birth. The pre-telbivudine treatment levels of HBV DNA were not significantly different between pregnant women in the telbivudine-treated group and the control group (OR = 0.12, 95% CI: 0.00, 0.24, P = 0.04), but the HBV DNA levels were significantly lower in the telbivudine-treated group of pregnant women prior to delivery (OR = -3.92, 95% CI: -4.90, -2.95, P less than 0.00001). There was no evidence of telbivudine treatment being associated with more adverse side effects or complications during pregnancy or in the infant (OR = 1.72, 95% CI: 0.68, 4.38, P = 0.25; OR=0.69, 95% CI: 0.04, 11.24, P = 0.80).

CONCLUSIONTelbivudine treatment effectively and safely prevents mother-to-child transmission of HBV from chronically infected mothers with a high degree of infectivity late in pregnancy.

Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; prevention & control ; transmission ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; prevention & control ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Randomized Controlled Trials as Topic ; Thymidine ; adverse effects ; analogs & derivatives ; therapeutic use

Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Hepatitis B ; prevention & control ; transmission ; Humans ; Infectious Disease Transmission, Vertical ; prevention & control ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; virology ; Thymidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of telbivudine use during the second and third trimester of pregnancy for reducing hepatitis B virus (HBV) transmission from highly viremic hepatitis B e antigen-positive (HBeAg+) mothers to their fetuses.

METHODSPregnant women, between weeks 20 to 32 of gestation, who were HBeAg+ and had HBV DNA more than 1.0*10(7) copies/mL were enrolled in our study. The women were offered inclusion into one of two treatment arms, based upon their personal preference: telbivudine or no telbivudine. The patients in the telbivudine treatment arm were administered 600 mg/d telbivudine at least until postpartum week 4. All delivered infants in both treatment arms were administered hepatitis B immune globulin (HBIG; 200 IU) within 12 hours of delivery and recombinant HBV vaccine (20 mug) at 0, 1 and 6 months. The HBV perinatal transmission rate was determined by measuring HBsAg and HBV DNA in infants at postpartum week 28.

RESULTSA total of 220 pregnant women were enrolled in our study, 120 chose the telbivudine arm and 100 chose the control arm. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Telbivudine treatment was associated with a marked reduction in the mothers' serum HBV DNA, HBeAg and ALT levels before delivery. A striking decline of HBV DNA levels in treated mothers was observed at week 2 of treatment, which was followed by a gradual and steady decrease that continued until delivery. Thirty-seven (31%) of the telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia at delivery. At week 28, 0% of the infants delivered from telbivudine-treated mothers were HBsAg+ or HBV DNA+, as compared to 8% HBsAg+ or HBV DNA+ in the untreated control arm (P = 0.002). No telbivudine discontinuations occurred from adverse events, and no congenital deformities were observed in the infants delivered to telbivudine-treated mothers. Eighty mothers discontinued telbivudine at week 4 postpartum, and there were no cases of severe hepatitis. There were no significant differences between the two treatment arms for postpartum hemorrhage, adverse events during pregnancy, cesarean section, gestational age, or infants' height/weight or Apgar scores.

CONCLUSIONSTelbivudine use during the second and third trimester of pregnancy in HBeAg+ highly viremic mothers can safely reduce perinatal HBV transmission rates. Telbivudine was well-tolerated by our patient group. Furthermore, no safety concerns were observed in either the telbivudine-treated mothers or their delivered infants in short term follow-up.

Adult ; DNA, Viral ; Female ; Hepatitis B ; transmission ; virology ; Hepatitis B virus ; Humans ; Infectious Disease Transmission, Vertical ; prevention & control ; Nucleosides ; adverse effects ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; prevention & control ; virology ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Pyrimidinones ; adverse effects ; therapeutic use ; Thymidine ; analogs & derivatives ; Viral Load ; Young Adult

OBJECTIVETo prospectively observe the long-term antiviral efficacy and safety of telbivudine (LDT) administered as a monotherapy and as a combination therapy with adefovir dipivoxil (ADV) in patients diagnosed with chronic hepatitis B (CHB) and positivity for hepatitis B e antigen (HBeAg).

METHODSA total of 140 patients with HBeAg-positive CHB were randomly divided into treatment groups for LDT monotherapy (n = 75; 600 mg orally, once daily) and LDT+ADV combination therapy (n = 65; LDT 600 mg plus ADV 10 mg orally, once daily). The shortest treatment course was 96 weeks and the longest was 240 weeks. At treatment weeks 12, 24, 48?, 96, 144, 192, and 240 patients were tested for hepatitis B virus (HBV) DNA, HBeAg seroconversion and ALT normalization time; in addition, the incidence and type of adverse drug reactions were recorded. Data were statistically analyzed to determine the significance of differences observed between groups.

RESULTSThe rate of patients experiencing more than or equal to 2 log HBV DNA reduction was higher in the LDT + ADV group (92.3%(60/65) vs. LDT: 86.7%(65/75), X2 = 1.58). The HBV DNA negative rates of the LDT and LDT + ADV groups were 62.7% and 61.5% (X2 = 0.01) at week 24, 76.0% and 81.5% (X2 = 0.63) at week 48, 80.0% and 89.2% (X2 = 2.2) at week 96, 78.3% and 93.3% (X2 = 3.24) at week 144, 83.7% and 91.7% (X2 = 0.47) at week 192, and 93.3% and 88.9% at week 240 (comparison between two groups for each point P more than 0.05); both groups showed higher early and rapid sustained HBV DNA negative rates. For the HBeAg seroconversion, the rates of the LDT and LDT + ADV groups were 17.3% and 23.1% (X2 = 0.71) at week 24, 29.3% and 30.8% (X2 = 0.03) at week 48, 42.7% and 40.0% (X2 = 0.10) at week 96, 55.0% and 43.3% (X2 = 1.08) at week 144, 55.8% and 66.7% (X2 = 0.45) at week 192, and 63.3% and 66.7% at week 240; however, pairwise comparison showed no statistically significant differences between the groups (P more than 0.05). Similarly, there was no significant difference between the two groups in incidence of resistance at week 48 (4.0% and 1.5%), week 96 (5.3% and 3.1%), week 144 (10.0% and 3.3%, X2 = 1.23), week 192 (11.6% and 8.3%), and week 240 (13.3% and 11.1%) (all P more than 0.05). Three patients experienced muscle soreness (LDT, n = 2; LDT + ADV, n = 1) and two patients experienced increased creatine phosphokinase (LDT, n = 1; LDT + ADV, n = 1); all side effects resolved spontaneously or with symptom-appropriate treatment.

CONCLUSIONThe long-term efficacy of LDT as a monotherapy or as a combination therapy with ADV was similar and the two different treatment approaches were associated with similar rates of resistance. The long-term safety was good for both treatment approaches.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; therapeutic use ; Retrospective Studies ; Thymidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo investigate the efficacy of nucleosides as a prophylactic agent against reactivation of hepatitis B virus (HBV) in HBsAg-positive patients with non-hepatic tumors after chemotherapy.

METHODSFifty-eight patients with non-hepatic tumors were divided into prevention group and control group. The patients of prevention group received nucleosides as a prophylactic agent before chemotherapy and were compared with the control ones about the clinical manifestation of HBV reactivation. Then, the patients of the control group were divided into three groups according to antiviral drugs, use or not and time of the use. The patients having HBV reactivation but never received nucleosides were included in the group A, the patients receiving nucleosides after having HBV reactivation were divided into the group B, and the patients receiving nucleosides before HBV reactivation were divided into the group C. The progression, prognosis and curative effect among the three groups were compared.

RESULTSThe rate of HBV reactivation, incidence of severe hepatitis, mortality rate of the control group (61.1%, 27.8%, 16.7%) were significantly higher than those of the prevention group (13.6%, 0, 0), and liver dysfunction was more serious than that in the prevention group. In the control group, all the 5 patients of group A died of liver failure. Of the 13 patients in the group B, 4 cases suffered from severe hepatitis and 1 of them died of the disease. Of the 18 patients in the group C, 4 cases suffered from HBV reactivation, but the clinical manifestation was milder than that of the group B.

CONCLUSIONNucleosides can be used as a prophylactic measure to prevent HBV reactivation. If chemotherapy had begun, the use of nucleosides may reduce the risk of HBV reactivation. Even if patients had suffered from HBV reactivation, the use of nucleosides may still help the recovery of liver function and improve prognosis.

Adult ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antiviral Agents ; therapeutic use ; Breast Neoplasms ; blood ; drug therapy ; Female ; Follow-Up Studies ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B ; drug therapy ; prevention & control ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; physiology ; Humans ; Lamivudine ; therapeutic use ; Lung Neoplasms ; blood ; drug therapy ; Lymphoma ; blood ; drug therapy ; Male ; Middle Aged ; Nucleosides ; therapeutic use ; Pyrimidinones ; therapeutic use ; Retrospective Studies ; Thymidine ; analogs & derivatives ; Virus Activation ; drug effects