Safety of lamivudine treatment for chronic hepatitis B in early pregnancy

AIM:To evaluate the safety of lamivudine(LAM) treatment for chronic hepatitis B in early pregnancy.METHODS:A total of 92 pregnant women who received LAM treatment either before pregnancy or in early pregnancy were enrolled in this study.All of the pregnant women volunteered to take lamivudine during pregnancy and were not co-infected with hepatitis C virus,human immunodeficiency virus,cytomegalovirus,or other viruses.All infants received passiveactive immunoprophylaxis with 200 IU hepatitis B immunoglobulin and three doses of 10 μg hepatitis B vaccines(0-1-6 mo) according to the guidelines for the prevention and treatment of chronic hepatitis B.Adverse events were observed throughout the entire pregnancy and perinatal period,and the effectiveness of lamivudine treatment for blocking mother-to-infant transmission of hepatitis B virus(HBV) was evaluated.All adverse events in mothers and infants during pregnancy and the perinatal period and the HBV motherto-infant transmission blocking rate were compared with the literature.RESULTS:Among the 92 pregnant women,spontaneous abortions occurred in 11 cases,while 3 mothers had a second pregnancy after the initial abortion;72 mothers delivered 73 live infants,of whom 68 infants were followed up for no less than 6 mo,and 12 mothers were still pregnant.During pregnancy,the main maternal adverse events were vaginitis(12/72,16.7%),spontaneous abortion(11/95,11.6%),and gestational diabetes(6/72,8.3%);only one case had 1-2 degree elevation of the creatine kinase level(195 U/L).During the perinatal period,the main maternal adverse events were premature rupture of the membranes(8/72,11.1%),preterm delivery(5/72,6.9%),and meconium staining of the amniotic fluid(4/72,5.6%).In addition,2 infants were found to have congenital abnormalities;1 had a scalp hemangioma that did not change in size until 7 mo,and the other had early cerebral palsy,but with rehabilitation training,the infant's motor functions became totally normal at 2 years of age.The incidence of adverse events among the mothers or abnormalities in the infants was not higher than that of normal mothers or HBV-infected mothers who did not receive lamivudine treatment.In only 2 cases,mother-to-infant transmission blocking failed;the blocking rate was 97.1%(66/68),which was higher than has been previously reported.CONCLUSION:Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 wk or throughout the entire pregnancy.

Tenofovir rescue therapy in pregnant females with chronic hepatitis B

AIM:To evaluate the safety and efficacy of tenofovir monotherapy in pregnant females resistant to lamivudine or telbivudine.The effect of tenofovir on the fetus was also assessed.METHODS:The clinical data of 17 females were reviewed in this study.Adverse events and pregnancy outcomes from January 1,2011 to June 30,2013 were evaluated in the Department of Gynecology and Obstetrics of BeijingDitan Hospital,Capital Medical University,Beijing,China.These pregnant females developed lamivudine(LAM)-or telbivudine(Ld T)-resistant chronic hepatitis B and received tenofovir(TDF)therapy(300 mg/d),and its curative effect,maternal and perinatal adverse events,fetal growth and development,and neonatal prognosis were evaluated.RESULTS:The median hepatitis B virus(HBV)DNA level in the pregnant females with LAM or Ld T resistance was 5.9(range,4.2-7.2)log10 copies/m L before the initiation of TDF.Ten of these females had abnormal alanine aminotransferase(ALT)levels.The patients were treated with TDF for a median of 24 wk(range,12-40 wk).Fourteen females(82.4%)had an HBV DNA level of<500 copies/m L at the time of delivery.This decrease was statistically significant(P<0.0001).Serum ALT levels were normalized in all subjects with an elevated serum ALT level at baseline(P=0.0003).There were no significant changes in serum creatinine and phosphorus levels during TDF treatment.In addition,no adverse events related to TDF treatment were observed.Seventeen females delivered 17 live infants,and all infants had good Apgar scores.The mean birth weight was 3226.5±331.7 g,and the mean length at birth was 50.4±1.1 cm.The growth and development of the infants was normal at birth,and no infants had birth defects related to TDF treatment.Eleven infants completed HBV vaccination and had no evidence of vertical transmission.CONCLUSION:The use of TDF in pregnant females with chronic HBV and LAM or Ld T resistance was safe and effective.

Inherited Genetic Susceptibility to Nonimmunosuppressed Epstein-Barr Virus-associated T/NK-cell Lymphoproliferative Diseases in Chinese Patients

Epstein-Barr virus(EBV)T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells,including chronic active EBV infection of T/NK-cell type(CAEBVT/NK),EBV-associated hemophagocytic lymphohistiocytosis(EBV HLH),extranodal NK/T-cell lymphoma of nasal type(ENKTL),and aggressive NK-cell leukemia(ANKL).However,the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown.A total of 171 nonimmunosuppressed patients with EBV T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed.The 94 gene variants,mostly located in UNCI 3D,LYST,ITK,and PRF1 genes were detected,and mutations covered 28/50(56.00%)of CAEBV-T/NK,31/51(60.78%)of EBV HLH,13/28(46.42%)of ENKTL,and 13/48(27.09%)of ANKL.Most mutations represented monoallelic and missense.Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations(P=0.0284,P=0.0137).Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV*T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.

Acute Onset Pancreatitis in the Third Trimester of Pregnancy in HBV Carrier Women Taking Telbivudine for Blocking Mother-to-Infant Transmission

Acute pancreatitis in pregnancy(APIP) is rare and the reasons for APIP are biliary disease and congenital or acquired hypertriglyceridemia, which could occur during any trimester but more than 50% cases happened during the third trimester. In this report, one case of a young pregnant woman, a HBV carrier in her 37 th week + 5 d of gestation, was admitted to Emergency Department due to acute abdominal pain, vomiting and diarrhea. The patient was in antiretroviral treatment with telbivudine from 28 weeks of gestation to prevent motherto-child transmission of HBV. Laboratory tests demonstrated hypertriglyceridemia, abdominal computed tomography scan revealed peripancreatic edema. Hyperlipidemic pancreatitits was primary diagnosed and the patient was admitted to the intensive care unit. Considering the possible role in the pathogenesis of pancreatitis, telbivudine was interrupted after birth giving. After supportive treatment, her condition gradually improved. Since it is the first description of APIP during treatment with telbivudine, the association between pregnancy, hyperlipidemia, telbivudine and acute pancreatitis has been well investigated.