Objective:To compare the efficacy and safety of telbivudine (LDT) and tenofovir disoproxil fumarate (TDF) treatment during the second and third trimester in pregnant women with high viral load of hepatitis B virus (HBV).Methods:Totally 506 pregnancy women with HBV infection who received antiviral therapy during the second and third trimester of pregnancy in the obstetrical clinic of The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 1, 2016 to December 31, 2018 were retrospectively enrolled, and the anti-viral efficacy and safety in mothers and neonates were evaluated. Pregnancy women were divided into TDF group and LDT group according the medications. The efficacies including decline and negative rate of HBV DNA, the vertical transmission (VT) rate, the normalization rate of liver function in mothers between the two groups were compared. The safeties including birth weight of neonates, congenital deformities and the rates of preterm between the two groups were also compared. Chi-square test, independent sample t test or rank sum test were used for statistical analysis. Results:There were 239 pregnant women in the LDT group and 267 in the TDF group. The maternal HBV DNA levels before treatment in the LDT and TDF groups were (7.83±0.75) lg IU/mL and (7.82±0.66) lg IU/mL, respectively, while the maternal HBV DNA levels prior to delivery were 2.91(1.20) lg IU/mL and 2.83(1.01) lg IU/mL, respectively. The normalization rates of alanine aminotransferase (ALT) of chronic hepatitis B (CHB) pregnant women prior to delivery in TDF group and LDT group were 95.00%(38/40) and 98.18%(54/55), respectively. There were all no significant differences between the two groups ( t=0.097, U=1.040 and χ2=0.767, respectively, all P>0.05). For CHB pregnant women, the HBV DNA negative rate at one month postpartum in TDF group was 85.45%(47/55) and that in LDT group was 82.50%(33/40). The normalization rate of ALT in TDF group was 94.55%(52/55), and that in LDT group was 92.50%(37/40). There were no significant differences between the two groups ( χ2=0.152 and 0.164, respectively, P=0.697 and 0.687, respectively). The VT rates were 0(0/262) in TDF group and 0.43%(1/231) in LDT group, which had no significant difference between the two groups ( χ2=1.127, P=0.288). Two patients in LDT group who continued taking LDT 11 months postpartum switched to TDF because of HBV rt204 mutation, and no one had virus mutation in TDF group. No significant increased in creatine kinase in LDT group, and no significant abnormal calcium and phosphorus metabolism in the TDF group. The preterm rate was 7.87%(21/267) in TDF group and 4.18%(10/239) in LDT group, but there was no significant difference between the two groups ( χ2=2.970, P=0.085). However, the birth weight of neonates in TDF group ((3 204.72±490.50) g) was lower than that in LDT group ((3 374.31±467.50) g), and the difference was statistically significant ( t=3.780, P<0.01). During the course of treatment, no pregnant women discontinued treatment due to drug intolerance, and no infants presented with drug-related birth defects. Safeties for mothers and neonates were both good. Conclusions:Both LDT and TDF treatment could reduce the VT rate in pregnant women with high HBV viral load. The safety is good for both mothers and neonates. However, for CHB pregnant women who continue antiviral therapy postpartum, TDF is superior to LDT because of lower virus mutation, thus to reduce the risk of drug resistance.

Objective To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9. Methods The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed. Results The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ²=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P > 0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABL^IS≤ 1% rate in the deletion group were lower than those in the non-deletion group (P < 0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ²=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ²=0.008, P=0.931). Conclusion The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression.

Recently， the European Association for the Study of the Liver organized the development of the clinical practice guidelines for the management of liver diseases in pregnancy， which include 105 recommendations for the clinical management of liver diseases in pregnancy. This article gives an excerpt of the main contents of the guidelines.

OBJECTIVETo analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia (CML).

METHODSNested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain. Then, the amplified product was purified and sequenced in both direction. The homologous analysis was performed in combination of clinical data.

RESULTSThe ABL domain point mutations were detected in 32 patients (45.7%) including 16 patients in chronic phase (CP), 6 patients in accelerated phase(AP)and 10 patients in blast phase (BP), which were detected as T315I, E255K, C475Y, Y253H, G321W, G250E, F317L, E258K, F359V, E459K and F311I, respectively. Sokal score with intermediate and high risk and Ph+ chromosome with complex karyotype were important risk factors for ABL domain point mutations. The 5-year overall survival (OS) was not significantly different between the patients with or without ABL domain point mutations (78.1% vs 84.2%, P=0.985), while the 5-year cumulative event-free survival (EFS) of two groups were 34.4% and 68.4% (P=0.034), respectively. The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation (allo-HSCT) compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics (P=0.001).

CONCLUSIONPatients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations. Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis. And allo-HSCT was a more effective therapy for patients with advanced phase.

Adolescent ; Adult ; Aged ; Benzamides ; therapeutic use ; Child ; Drug Resistance, Neoplasm ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Point Mutation ; Prognosis ; Proto-Oncogene Proteins c-abl ; genetics ; Pyrimidines ; therapeutic use ; Young Adult