Adult ; Aged ; Carcinoma, Hepatocellular ; epidemiology ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Neoplasms ; epidemiology ; Male ; Middle Aged ; Nucleosides ; administration & dosage ; therapeutic use

To evaluate the efficacy and safety of pegylated-interferon (Peg-IFN) treatment as monotherapy or in combination with nucleoside analogues (NAs) for treating chronic hepatis B (CHB) infection.Searches of PubMed, OVID, EMBASE, and the Chinese Medical (WanFang, CNKI, and VIP) databases were conducted to identify all relevant randomized controlled trials published since January 1990. Twelve studies comparing Peg-IFN monotherapy to NA combination therapy (lamivudine (LAM), n =8); adefovir (ADV), n = 4) met the inclusion criteria (treatment duration, range: 48-52 weeks; follow-up, range: 24 weeks to three years). Meta-analysis was performed with RevMan 5.0 using the fixed-effects and random-effects models. Patients who had received combination therapy had a higher biochemical response rate at the end of treatment than those who had received monotherapy (51.1% vs. 38.9%, odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.33-2.01, P less than 0.01). Subgroup analysis of Peg-IFN combination therapies with LAM or ADV indicated that neither NA type significantly enhanced the increased efficacy of combination therapy compared to monotherapy. The combination therapy subgroups also had higher virologic response rates at the end of treatment than the monotherapy subgroups (LAM: 65.9% vs. 34.9%, OR = 3.57, 95% CI: 1.83-6.95, P less than 0.01; ADV: 74.6% vs. 46.2%, OR = 3.66, 95% CI: 2.13-6.30, P less than 0.01). Moreover, the combination therapy group had a higher sustained biochemical response rate at the end of follow-up than the monotherapy group (47.6% vs. 42.1%, OR = 1.28, 95% CI: 1.05-1.55, P less than 0.05). The LAM combination therapy subgroup had a significantly higher biochemical response rate than the monotherapy subgroup, but there was no significant difference between the LAM and ADV combination therapy subgroups. At the end of follow-up, the ADV combination therapy subgroup had a significantly lower rate of hepatitis B e antigen (HBeAg) than the monotherapy subgroup, but there was no significant difference between the ADV and LAM combination therapy subgroups for HbeAg reduction. The combination therapy group and monotherapy group showed no statistically significant differences in HBsAg reduction or occurrence of severe adverse events. Peg-IFN/NA combination therapy produces a higher biochemical response rate in CHB patients than PEG-IFN monotherapy. Moreover, Peg-IFN/ADV combination therapy produces a greater reduction in HBeAg than Peg-IFN monotherapy.
Adenine ; administration & dosage ; analogs & derivatives ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferons ; administration & dosage ; adverse effects ; therapeutic use ; Lamivudine ; administration & dosage ; Nucleosides ; administration & dosage ; adverse effects ; therapeutic use ; Organophosphonates ; administration & dosage ; Polyethylene Glycols ; administration & dosage ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

Adenocarcinoma ; pathology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Nucleosides ; administration & dosage ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; Pyridazines ; administration & dosage ; pharmacology ; Stomach Neoplasms ; pathology

Antiviral Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; administration & dosage ; therapeutic use ; Nucleosides ; administration & dosage ; therapeutic use ; Polyethylene Glycols ; administration & dosage ; therapeutic use

Administration, Oral ; Adult ; Alanine Transaminase ; blood ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferons ; administration & dosage ; therapeutic use ; Male ; Nucleosides ; administration & dosage ; therapeutic use ; Pyrimidinones ; administration & dosage ; therapeutic use ; Retreatment ; Thymidine ; analogs & derivatives ; Treatment Outcome ; Virus Replication ; drug effects

BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.
Adolescent ; Adult ; Alanine Transaminase/analysis ; Antiviral Agents/administration & dosage/adverse effects/*therapeutic use ; Drug Resistance, Viral ; Female ; Hepatitis B e Antigens/analysis ; Hepatitis B virus/drug effects/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Korea ; Lamivudine/administration & dosage/adverse effects/therapeutic use ; Male ; Middle Aged ; Nucleosides/administration & dosage/adverse effects/*therapeutic use ; Pyrimidinones/administration & dosage/adverse effects/*therapeutic use ; Treatment Outcome

Antiviral Agents ; administration & dosage ; therapeutic use ; Apoptosis ; drug effects ; Disease Progression ; Drug Combinations ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Hepatic Stellate Cells ; drug effects ; Hepatitis, Chronic ; complications ; drug therapy ; pathology ; Humans ; Liver ; drug effects ; pathology ; Liver Cirrhosis ; drug therapy ; pathology ; prevention & control ; Medicine, Chinese Traditional ; Nucleosides ; administration & dosage ; therapeutic use ; Phytotherapy

OBJECTIVETo evaluate the safety and efficacy of the combined therapy with entecavir (ETV) and adefovir (ADV) in patients with chronic hepatitis B (CHB) who experienced failure of treatment with single or multiple nucleoside analogs, and analyze the factors that affect the patients response to the treatment.

METHODSForty-five CHB patients who experienced treatment failure with sequential or/and combined nucleoside analogs received the combined therapy with entecavir and adefovir lasting for at least 6 months. The viroloigcal response (VR), biochemical response (BR) and combined response (CR) at 24 and 48 weeks of the treatment were evaluated. Univairante analysis was used to identify the factors that affect the response to the anti-viral therapy.

RESULTSThe VR, BR and CR were 67.7%, 77.8% and 57.8% at 24 weeks, as compared to 76.2%, 78.6% and 61.9% at 48 weeks, respectively. The VR differed significantly between patients with a baseline HBV DNA level [lg(copies/ml)] of 3-6 and those with a level over 6 (85.2% vs 40%, Z=-4.796, P=0.037) at 48 weeks. The presence and absence of cirrhosis at the initial treatment significantly affected the BR at 24 weeks (17.1% vs 82.9%, P=0.048) and at 48 weeks (23.8% vs 76.2%, P=0.023).

CONCLUSIONEntecavir combined with adefovir is an effective rescue therapy in CHB patients after failure of treatment with nucleoside analogs. Patients with a lower baseline HBV DNA level without cirrhosis may have better response to the combined treatment.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Guanine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Nucleosides ; therapeutic use ; Organophosphonates ; administration & dosage ; therapeutic use ; Treatment Failure

OBJECTIVETo investigate the efficacy of telbivudine on intrauterine hepatitis B virus (HBV) infection during the last stage of pregnancy.

METHODS61 pregnant chronic hepatitis B (CHB) patients were enrolled and 31 patients were treated by telbivudine 600 mg once daily, 30 patients in the control group were not received antiviral treatment. Maternal HBV DNA level and the HBsAg positive rate in newborns were investigated.

RESULTSThe levels of serum HBV DNA in patients treated with Telbivudine were significantly reduced (t = 19.09, P less than 0.01). Compared with the control group, serum HBV DNA levels were significantly lower in telbivudine treated patients than those in the control group before parturition (t = 23.64, P less than 0.01). The infection rate of 7-month newborns were 0 and 13.33% (4/30), in telbivudine group and control group, respectively (x2 = 4.29, probability value less than 0.05).

CONCLUSIONSTelbivudine treatment can block intrauterine infection in pregnant chronic hepatitis B patients.

Administration, Oral ; Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; drug therapy ; transmission ; virology ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Nucleosides ; pharmacology ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; virology ; Pyrimidinones ; pharmacology ; therapeutic use ; Thymidine ; analogs & derivatives ; Treatment Outcome