[Efficacy of combination antiviral therapy following childbirth in pregnant HBV carriers receiving telbivudine for prevention of mother-to-child transmission].

OBJECTIVE: To observe the clinical efficacy of combination therapy with peg-IFNalpha and adefovir (CPIA) in women who were hepatfis B virus (HBV) carriers and had just given birth and received telbivudine (LdT) during pregnancy for prevention of mother-to-child transmission. METHODS: One-hundred-and-fifty third trimester-pregnant women who were HBV carriers with highly-viremic were treated with LdT until time of birth. After delivery, those women with alanine aminotransferase (ALT) level exceeding two times the upper limit of normal and HBV DNA level that had decreased more than 31 gIU/mL or hepatitis B e antigen (HBeAg) titer that had decreased more than 50% were switched to CPIA for 96 weeks. RESULTS: Following delivery, 45 of the women were switched to the CPIA treatment, of which 91.1% (41/45) achieved virological response, 55.6% (25/45) achieved HBeAg clearance or seroconversion, and 26.7% (12/45) achieved hepatitis B surface antigen (HBsAg) clearance or seroconversion.The immediate post-delivery (and pre-CPIA) levels of HBeAg and HBV DNA were negatively associated with HBeAg clearance. Ninety-eight of the total study participants stopped the LdT treatment and there were no cases of significant deterioration of liver function. CONCLUSION: Pregnant women who are HBV carriers and receive LdT for protection against mother-to-child transmission, and who show significant ALT elevation and decreased HBeAg titer and/or reduced HBV DNA after delivery, may be good candidates for the CPIA therapy following delivery.

Bone marrow suppression or active proliferation? An analysis of neutropenia after pegylated interferon treatment of patients with chronic hepatitis C.

BACKGROUND: Neutropenia is a common adverse effect of the treatment of chronic hepatitis C with pegylated interferon and ribavirin. However, the mechanism involved is unknown. The present study aimed to investigate the cause of treatment-induced neutropenia by determining cytokine levels in plasma and in bone marrow smears. METHODS: Fifteen patients with chronic hepatitis C were enrolled in this study. Plasma cytokine levels were determined using the Luminex assay before and during treatment. We simultaneously determined the levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and 7 other cytokines, and performed bone marrow cytology when blood cell counts indicated neutropenia. RESULTS: Only 1 bone marrow smear indicated a low cell proliferation level, whereas active proliferation was observed in the remaining 14 patients. The levels of G-CSF, GM-CSF, interleukin (IL)-2, IL-4, IL-6, and interferon (IFN)-γ decreased significantly in patients with neutropenia (p < 0.05). In contrast, the levels of IL-8, IL-10, and tumor necrosis factor (TNF)-α showed no significant change (p = 0.713, 0.930, 0.833, respectively) before or after treatment. CONCLUSIONS: The bone marrow of most patients with IFN-induced neutropenia showed active cell proliferation. Elevated G-CSF and GM-CSF but not bone marrow suppression was observed along with neutropenia after pegylated interferon treatment, suggesting a causative role of G-CSF and GM-CSF in neutropenia.

[Efficacy and safety of peginterferon alfa-2a (40 kd) plus adefovir for 96 weeks in HBeAg-negative chronic hepatitis B patients].

OBJECTIVE: To investigate the efficacy and safety of an extended course (96-week) of combination treatment with peginterferon alfa-2a (Peg-IFNa-2a; 40 kd] plus adefovir (ADV) for treating chronic hepatitis B (CHB) in Chinese patients with negativity for hepatitis B e antigen (HBeAg). METHODS: A total of 25 consecutive patients with HBeAg-negative CHB were administered Peg-IFNa-2a (135-180 mug/week) plus ADV (10 mg/day) for 96 weeks. All patients were followed-up for 24 weeks after treatment completion. Levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HbsAg) were measured by fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescent microparticle immunoassay, respectively, at 12-week intervals throughout the treatment course and at the end-of-follow-up (week 120). Patients underwent serological analysis at 3-6 month intervals during treatment and follow-up to evaluate occurrence of adverse events; serological parameters included blood count, markers of liver, kidney and thyroid function, and levels of autoantibodies and creatine kinase. RESULTS: For all patients, the 96-week course of Peg-IFNa-2a plus ADV reduced the level of HBV DNA below the detection threshold (less than 500 copies/ml by FQ-PCR). The overall rate of HBsAg seroconversion was 12% (3/25) at week 48, 28% (7/25) at week 96, and 32% (8/25) at week 120. The occurrences of adverse events were similar at week 48 and week 96. CONCLUSION: The extended-course Peg-IFNa-2a plus ADV combination therapy achieved a 100% virological response and better rates of HBsAg seroconversion than 48 weeks of therapy, without a decrease in safety.

Extended treatment with peginterferon α-2a in combination with lamivudine or adefovir for 96 weeks yields high rates of HBeAg and HBsAg seroconversion.

OBJECTIVE: The study aimed to investigate the efficacy and safety of peginterferon α-2a (PEG IFNα-2a) in combination with lamivudine or adefovir in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). METHODS: In total, 47 patients with HBeAg-positive CHB received either PEG IFNα-2a (135 µg once weekly) plus lamivudine (100 mg daily) or adefovir (10 mg daily). All patients completed 96 weeks of therapy and were followed up for a further 24 weeks. RESULTS: Baseline characteristics and treatment efficacy of the two groups were similar. All patients achieved hepatitis B virus (HBV) DNA <500 copies/mL at 96 weeks, and none had a virological rebound after stopping the therapy. The rate of HBeAg seroconversion was 46.8% at 48 weeks, increased to 74.5% at 96 weeks, and kept at 72.3% at 120 weeks. Hepatitis B surface antigen (HBsAg) seroconversion rate was 6.4% at 48 weeks, increased to 21.3% at 96 weeks, and kept at 27.7% at 120 weeks. CONCLUSIONS: Extended treatment with PEG IFNα-2a with lamivudine or adefovir for 96 weeks is a promising strategy to achieve high rates of sustainable HBeAg and HBsAg seroconversion and HBV DNA suppression in patients with HBeAg-positive CHB.