Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infant, Newborn ; Male ; Organophosphonates ; adverse effects ; therapeutic use ; Paternal Exposure ; Pregnancy

OBJECTIVETo investigate 3-year antiviral efficacy and side effect of adefovir dipivoxil (ADV) on the old patients with hepatitis B chronic infection.

METHODS31 HBeAg-negative chronic hepatitis B virus infected old patients (include 8 patients with chronic hepatitis B and 23 patients with liver cirrhosis) with serum HBV DNA levels > 1000 copies/ml, and ALT > 2 times the upper limit of normal, without company with other liver diseases, cancer, renal dysfunction, and autoimmune disease. All the patients were treated with ADV orally (10 mg once daily) for 36 months. HBV DNA and biochemical and blood routine indexes were checked after treated.

RESULTSerum total bilirubin, direct bilirubin, alamine aminotransferase, aspartate aminotransferase and load of HBV DNA decrease significantly after therapy (P < 0. 001). Other biochemical indexs and blood routine are no significant changes (P > 0.05).

CONCLUSIONThe way to treat with ADV is safe and effective for old patients with chronic hepatitis B virus infection.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Aged ; Aged, 80 and over ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; physiopathology ; virology ; Humans ; Male ; Organophosphonates ; adverse effects ; therapeutic use ; Time Factors

BACKGROUNDThe most frequently used therapy for post-transplantation recurrence of hepatitis B virus (HBV) infection is lamivudine, but this drug is associated with a high resistance rate due to YMDD mutant. In preliminary reports, adefovir dipivoxil (ADV) has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation (LT) is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin (HBIG) in patients with YMDD mutant before LT.

METHODSFrom March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant YMDD mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs (HBIG), HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation.

RESULTSThe median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma (HCC). There was significant difference (10.98% vs. 2.26%, P < 0.05) in YMDD mutant rate between the patients with HBV-DNA over 10(6) copies/ml and those with HBV-DNA less than 10(6) copies/ml. Fifteen patients (93.8%) had undetectable HBV-DNA at 4 weeks and 1 (6.3%) at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients.

CONCLUSIONADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA-Directed DNA Polymerase ; genetics ; Drug Resistance, Viral ; Hepatitis B ; prevention & control ; Humans ; Lamivudine ; therapeutic use ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Mutation ; Organophosphonates ; therapeutic use ; Recurrence

OBJECTIVETo investigate the levels of HBsAg in predicting the efficacy of peglated interferon-alpha 2a combined with adefovir dipivoxil (ADV), in HBeAg-positive chronic hepatitis B patients.

METHODSThis trial enrolled 62 HBeAg-positive chronic hepatitis B patients with detectable HBsAg for at least 6 months prior to screening, serum HBV DNA levels of at least 100 000 IU/ml. The efficacy assessment: viral suppression below 100 IU/ml. The patients with HBV DNA < or = 100 IU/ml after 24 weeks therapy were divided into group A, in which monotherapy continued; While the rest were divided into group B, in which ADV was combined until week 48. In group B, at the end-of-treatment, the patients with HBV DNA < or = 100 IU/ml were divided into group B1, the rest were divided into group B2.

RESULTSThere was no significant difference on the baseline characteristics of patients between B1 and B2. There was significant difference on the levels of HBsAg at 12-week and 24-week between B1 and B2; while there was no significant difference on the levels of HBeAg.

CONCLUSIONSThe levels of HBsAg at 12-week and 24-week would be predictors to evaluate the efficacy of combined therapy in HBeAg-positive chronic hepatitis B patients.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; adverse effects ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; isolation & purification ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Male ; Organophosphonates ; adverse effects ; therapeutic use ; Recombinant Proteins ; Treatment Outcome

OBJECTIVETo compare the efficacy and safety of the common antivirals, including adefovir dipivoxil (ADV), pegylated-interferon alpha-2a (peg-IFN) and lamivudine (LAM), used as combination therapies to treat chronic hepatitis B (CHB) patients with positivity for the hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) harboring the ADV-resistance mutation, rtN236T, and to explore the factors associated with curative outcome.

METHODSSixty-five adult CHB patients (age range: 20-60 years) who were unresponsive to ADV therapy (HBeAg-positive; HBV DNA >or= 10(5) copies/ml), LAM-naive, and tested positive for the rtN236T HBV mutation were enrolled in the study and randomly divided into two treatment groups: Group A (n = 33), who were administered ADV (10 mg/day, orally) plus peg-IFN (180 microg/week, subcutaneous injection) for 48 weeks; and Group B (n = 32 patients), who received the ADV plus LAM (100 mg/day, orally) for 48 weeks followed by continued LAM treatment for an additional 24 weeks. Pre- (baseline), during and post-treatment measurements of HBV viral loads and hepatitis B markers were made by quantitative PCR and electrochemiluminescence assays, respectively. All patients underwent liver biopsies to determine the histological activity index (HAI) and treatment response regarding inflammation and fibrosis stage. The rates of virological response (VR), HBeAg-negativity, HBeAg seroconversion, and alanine aminotransferase (ALT) normalization were calculated, and the significance of differences between groups were assessed by Student's t-test and Chi2 test.

RESULTSThere were no significant differences between the two groups in regards to sex, age, or baseline levels of HBV DNA, ALT, and total bilirubin (P > 0.05). At weeks 24 and 48 of treatment and 24 after treatment end, group A showed significantly higher (vs. group B, P < 0.05) rates of reduced HBV DNA viral loads (81.8%, 90.9%, and 75.8% vs. 53.1%, 56.2%, and 59.4%), VR (48.5%, 60.6%, and 42.4% vs. 31.3%, 34.4%, and 31.3%), HBeAg-negativity (39.4%, 60.6%, and 54.5% vs. 12.5%, 37.5%, and 37.5%), HBeAg seroconversion (27.3%, 54.5%, and 48.5% vs. 6.3%, 15.6%, and 18.8%), and ALT normalization (72.7%, 84.8%, and 78.8% vs. 46.9%, 56.3%, and 46.9%). After 48 weeks of treatment, group A showed significantly improved HAI (vs. group B, P < 0.05). With the exception of treatment-related increased creatinine (P < 0.05), group A showed significantly higher rates of adverse reactions; although, none was serious enough to threaten patient safety or necessitate early termination of the treatment regimen. Twenty-four weeks after treatment completion, five patients had HBV viral loads of >or= 2log10 copies/ml and four had < or= 500 copies/ml, and ALT was normalized in 28 patients. The four patients in group A with HBV DNA < or= 500 copies/ml and elevated ALT during treatment did not show HBeAg seroconversion.

CONCLUSIONPeg-IFN plus ADV combination therapy produced better outcomes than the ADV plus LAM combination therapy in regards to HBV viral loads, VR rate, HBeAg-negative rate, HBeAg seroconversion rate, ALT normalization rate, and HAI, but was associated with a higher rate of adverse reactions (none of which were severe). Lack of HBeAg seroconversion was associated with higher virus load and ALT levels.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Drug Resistance, Viral ; genetics ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Lamivudine ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Mutation ; Organophosphonates ; adverse effects ; therapeutic use ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Recombinant Proteins ; adverse effects ; therapeutic use ; Young Adult

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Female ; Hepatitis B virus ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Male ; Organophosphonates ; adverse effects ; therapeutic use ; Pregnancy ; Pregnancy Trimesters

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

OBJECTIVETo evaluate the efficacy and safety of 48 weeks adefovir dipivoxil (ADV) treatment for chronic hepatitis patients with cirrhosis in their decompensation period.

METHODSSixty-two chronic hepatitis patients with cirrhosis in their decompensation period were randomly put into two groups. An adefovir dipivoxil (ADV) group: 32 patients treated with 10 mg of ADV a day; and a lamivudine (LMV) group: 30 patients treated with 100 mg of LMV a day. The course of treatment lasted 48 weeks. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alb, TBil, HBeAg, HBV DNA, PCIII, IVC, LN, and HA, renal function, Child-Pugh scores and drug adverse reactions during the treatment of the two groups were checked, compared and analyzed.

RESULTSThe ratios of recovery for liver functions and the negativity rate of HBV DNA, HBeAg, including sero-conversion rate of HBeAg/HBeAb, were increased with prolongation of the treatment period; however, the differences between the two groups were not statistically significant (P > 0.05). Two patients treated with lamivudine suffered from YMDD variation at the 48th week; the ratio of variation was 6.7%. No YMDD variation happened in the ADV group. On the 24th week of the treatment, the levels of the serum markers of hepatic fibrosis declined obviously, compared with those prior to the treatment (P < 0.01). There were no significant statistical differences of those levels between the two groups (P > 0.05). No significant differences of Child-Pugh scores were noticed between the two groups (P > 0.05). No drug related renal function impairment was found during the treatment. Two patients of each group had adverse drug reactions but all were mild.

CONCLUSIONThe efficacy and safety of adefovir dipivoxil and lamivudine treatment for the above patients were similar, but the ratio of emerging virus-resistant strains was lower in the adefovir dipivoxil treatment group.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; adverse effects ; therapeutic use ; Drug Resistance, Viral ; Female ; Hepatitis, Chronic ; drug therapy ; Humans ; Lamivudine ; adverse effects ; therapeutic use ; Liver Cirrhosis ; drug therapy ; Male ; Middle Aged ; Organophosphonates ; adverse effects ; therapeutic use

OBJECTIVETo investigate the efficacy of the 96-week antiviral therapy with adefovir dipivoxil in patients with chronic hepatitis B.

METHODS80 patients with chronic hepatitis B received the antiviral therapy of adefovir dipivoxil (ADV, 10 mg/d). At the 12th week, 19 cases without early viral response (EVR, HBV DNA drop < 2 log10copies/ml) switched to the therapy of other nucleoside analogues. Aminotransferase (ALT) normalization, HBV DNA negative, HBeAg loss and HBeAg seroconvertion were accessed at the 96th week.

RESULTSAt week 96, ALT normalization and HBV DNA negative in 61 patients with ADV therapy were 85.25% (52/61) and 95.08% (58/61); and HBeAg loss and HBeAg seroconvertion were 52.52% (17/33) and 42.42% (14/33) respectively. While for the other 19 patients switching to other nucleoside analogues, ALT normalization and HBV DNA negative came to 57.89% (11/19) and 68.42% (13/19). Both HBeAg loss and HBeAg seroconvertion were 58.33% (7/12).

CONCLUSIONLong term ADV antiviral therapy is effective to inhibit HBV DNA replications and benefits patients with chronic hepatits B. Switching to another nucleoside analogue is an optimal alternative if there is no EVR at week 12 in ADV therapy.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; DNA, Viral ; analysis ; Drug Resistance, Viral ; genetics ; Female ; Genotype ; Hepatitis B e Antigens ; analysis ; Hepatitis B virus ; drug effects ; immunology ; pathogenicity ; Hepatitis B, Chronic ; drug therapy ; Humans ; Kidney Function Tests ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; adverse effects ; therapeutic use ; Renal Insufficiency ; etiology ; Young Adult

Adefovir dipivoxil is commonly used for treatment of chronic hepatitis B. The renal toxicity of adefovir dipivoxil is dose- and time-related, occurring often in patients with a daily dose over 30 mg and those with impaired renal function. We report a case of chronic hepatitis B with a history of taking adefovir dipivoxil at 10 mg/day for 4 years. The patient complained of lumbosacral and joint pain and had the diagnosis of ankylosing spondylitis (AS) or spondyloarthropathy in several hospitals before admission in our hospital. A diagnosis of acquired Fanconi syndrome and hypophosphatemia osteomalacia associated with progressive muscular weakness was made eventually. We reviewed the literature and found reports of only fewer than 10 similar cases. Clinical attention should be given to kidney damage induced by adefovir dipivoxil.
Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Bone Diseases, Metabolic ; chemically induced ; complications ; congenital ; Fanconi Syndrome ; chemically induced ; complications ; Hepatitis B, Chronic ; drug therapy ; Humans ; Hypophosphatemia ; chemically induced ; complications ; Male ; Muscle Weakness ; chemically induced ; complications ; Organophosphonates ; adverse effects ; therapeutic use ; Osteomalacia ; chemically induced ; complications ; Young Adult