Original Article
Adefovir Dipivoxil for the Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis B
N Engl J Med 2003; 348:808-816February 27, 2003
- Abstract
Background
In preclinical and phase 2 studies, adefovir dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains.
Methods
We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of adefovir dipivoxil (172 patients), 30 mg of adefovir dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group.
Results
After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement (53 percent [P<0.001], 59 percent [P<0.001], and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 [P<0.001], 4.76 [P<0.001], and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent [P<0.001], 39 percent [P<0.001], and 0 percent, respectively), normalization of alanine aminotransferase levels (48 percent [P<0.001], 55 percent [P<0.001], and 16 percent, respectively), and HBeAg seroconversion (12 percent [P=0.049], 14 percent [P=0.01], and 6 percent, respectively). No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene. The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo; however, there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day.
Conclusions
In patients with HBeAg-positive chronic hepatitis B, 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and increased the rates of HBeAg seroconversion. The 10-mg dose has a favorable risk–benefit profile for long-term treatment. No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene.
Media in This Article
Figure 1
Mean Change from Base Line in Serum Levels of Hepatitis B Virus (HBV) DNA.Table 1
Base-Line Characteristics of the Patients.Article Activity
- Article
More than 350 million people worldwide have chronic hepatitis B virus (HBV) infection.1 Effective treatments are required to prevent progression of chronic hepatitis B to cirrhosis, hepatocellular carcinoma, and death. Treatment with interferon alfa requires parenteral administration and can cause side effects, such as influenza-like symptoms, anorexia, and depression, that require an adjustment in the dose or discontinuation of therapy.2 The risk of progressive liver damage decreases in patients who have hepatitis B e antigen (HBeAg) seroconversion after interferon therapy. Lamivudine suppresses HBV replication and improves histologic liver findings.3 However, lamivudine resistance has been reported in up to 32 percent of patients after one year of therapy4 and in 66 percent after four years.5 Some patients with lamivudine resistance have had a severe exacerbation of hepatitis and progressive liver disease.6 Therefore, well-tolerated antiviral agents that provide clinical benefit without inducing resistance are needed to manage chronic hepatitis B.
Adefovir dipivoxil (Hepsera, Gilead Sciences) is an oral prodrug of adefovir, an analogue of adenosine monophosphate. The active intracellular metabolite, adefovir diphosphate, inhibits HBV DNA polymerase at levels much lower than those needed to inhibit human DNA polymerases. In phase 2 studies, daily doses of 30 mg and 60 mg of adefovir dipivoxil inhibited HBV replication, reducing serum HBV DNA by approximately 4 log copies per milliliter after 12 weeks.7 Adefovir dipivoxil has also been efficacious in patients with lamivudine-resistant HBV.8
We elected to evaluate in a double-blind, placebo-controlled study the effects of 10-mg and 30-mg doses of adefovir dipivoxil in patients with HBeAg-positive chronic hepatitis B on the basis of the results of phase 2 studies, which showed that the antiviral activity of doses greater than or equal to 30 mg was similar. During the long-term, phase 2 study, data indicated that the 30-mg dose was associated with mild, reversible nephrotoxicity after 32 weeks. Therefore, we amended the primary end point for this study before the analysis and unblinding, to compare a 10-mg dose of adefovir dipivoxil with placebo. We report the 48-week results, but the study is ongoing and will continue for up to 5 years. When the study was designed, lamivudine was still an investigational agent; therefore, placebo was selected as the control.
Methods
Study Design
From March 1999 to March 2000, patients were recruited from 78 centers in North America, Europe, Australia, and Southeast Asia and randomly assigned in a 1:1:1 ratio to receive 10 mg of adefovir dipivoxil per day, 30 mg of adefovir dipivoxil per day, or placebo. The central randomization scheme was stratified according to seven geographic regions. Permuted blocks (with a block size of six) were used in each stratum. The placebo and adefovir dipivoxil tablets were formulated to be indistinguishable from one another in appearance and taste.
The study was conducted in compliance with the Declaration of Helsinki and approved by appropriate local regulatory bodies. All patients provided written informed consent. Liver biopsy was performed at base line and week 48. Biopsy specimens obtained within six months before randomization could be used if they had been obtained more than six months after the completion of prior hepatitis B therapy. Patients were evaluated every four weeks.
Clinical data were collected, monitored, and entered into a data base by Quintiles. Laboratory tests were conducted by Covance. The sponsor held the data and conducted the statistical analyses, which were predefined; the academic investigators had full access to the data and contributed substantially to the design of the study, the collection of the data, the analysis and interpretation of the data, and the drafting of the manuscript. All authors approved the final draft of the manuscript.
Patients
Male and female patients 16 to 65 years of age who had hepatitis B e antigen–positive chronic hepatitis B and compensated liver disease were eligible for the study. Chronic hepatitis B was defined by the presence of serum hepatitis B surface antigen for at least six months, a serum HBV DNA level of at least 1 million copies per milliliter (measured with the Roche Amplicor Monitor polymerase-chain-reaction [PCR] assay), and a serum alanine aminotransferase level that was 1.2 to 10 times the upper limit of the normal range. Patients were required to have a prothrombin time that was no more than one second above the normal range, a serum albumin level of at least 3 g per deciliter, a total bilirubin level of no more than 2.5 mg per deciliter (43 μmol per liter), a serum creatinine level of no more than 1.5 mg per deciliter (133 μmol per liter), and an adequate blood count. Women of childbearing potential were eligible if they had a negative pregnancy test and were using effective contraception.
Criteria for exclusion included a coexisting serious medical or psychiatric illness; immune globulin, interferon, or other immune- or cytokine-based therapies with possible activity against HBV disease within 6 months before screening; organ or bone marrow transplantation; recent treatment with systemic corticosteroids, immunosuppressants, or chemotherapeutic agents; a serum alpha-fetoprotein level of at least 50 ng per milliliter; evidence of a hepatic mass; liver disease that was not due to hepatitis B; prior therapy for more than 12 weeks with a nucleoside or nucleotide analogue with activity against HBV; and seropositivity for human immunodeficiency virus or hepatitis C or D virus.
End Points
The primary efficacy end point was histologic improvement, defined as a reduction of at least two points in the Knodell necroinflammatory score with no concurrent worsening of the Knodell fibrosis score 48 weeks after base line.9 The liver-biopsy specimens were evaluated by an independent histopathologist who was unaware of the patients' treatment assignments or of the timing of liver biopsy. Ranked assessments of necroinflammatory activity and fibrosis were also performed (and scored as improved, no change, or worse).
Secondary end points included the change from base line in serum HBV DNA levels, the proportion of patients with undetectable levels of HBV DNA, the effect of treatment on the alanine aminotransferase level, and the proportion of patients with loss or seroconversion of HBeAg. Serum HBV DNA levels were measured by the Roche Amplicor HBV Monitor PCR assay (lower limit of detection, 400 copies per milliliter), and the values were log-transformed with use of a base 10 scale.
Safety Analysis
The primary safety analysis included all patients who received at least one dose of study medication and all events that occurred during treatment or within 30 days after the discontinuation of study drug. The severity of adverse events and laboratory abnormalities was graded according to the Common Toxicity Criteria of the National Institute of Allergy and Infectious Diseases.10
Detection of HBV Polymerase Mutations
All serum samples obtained at base line and week 48 were examined in a blinded fashion. HBV DNA was isolated and amplified by PCR. The positive and negative strands of the HBV polymerase gene spanning the polymerase–reverse-transcriptase domain (amino acids 349 to 692) were sequenced. The HBV sequences of the samples obtained at base line and week 48 from the same patient were aligned with the MegAlign program (DNAStar).
Statistical Analysis
The study was designed to enroll 166 patients per group, with 90 percent power to detect an absolute difference of 20 percent (50 percent vs. 30 percent) between the group given 10 mg of adefovir dipivoxil and the placebo group, assuming that 25 percent of patients would have missing biopsy specimens that would be considered treatment failures and that 8 percent of patients would have missing base-line biopsy specimens, on the basis of a two-sided type I error rate of 0.05. The study had 79 percent power to detect an absolute difference of 10 percent (16 percent vs. 6 percent) in the rate of seroconversion between the group given 10 mg of adefovir dipivoxil and the placebo group, assuming that 10 percent of patients would have missing values (which were counted as treatment failures). Patients who received at least one dose of study medication were included in the analyses. Patients with missing or unassessable base-line liver-biopsy specimens were prospectively excluded from the primary efficacy analysis. Patients with missing or unassessable data at 48 weeks were considered not to have had responses. The unstratified Cochran–Mantel–Haenszel test was used to compare each of the adefovir dipivoxil groups with the placebo group. All P values were two-sided. No adjustments were made for multiple comparisons. All serum HBV DNA results below the lower limit of detection (less than 400 copies per milliliter) were analyzed as being 400 copies per milliliter. No interim analyses were performed other than safety-data summaries, which were prepared every six months for a review by the independent external data-monitoring committee.
Results
Characteristics of the Patients
Among the 515 patients who were enrolled, 172 were randomly assigned to receive 10 mg of adefovir dipivoxil per day, 173 to receive 30 mg per day, and 170 to receive placebo. Four patients took no study medication (one in the 10-mg group and three in the placebo group). Of the remaining 511 patients, base-line biopsy specimens were available for 168 patients in the 10-mg group, 165 in the 30-mg group, and 161 in the placebo group. There were no significant differences in demographic or HBV disease characteristics (Table 1Table 1
Base-Line Characteristics of the Patients.) or previous anti-HBV treatments among the groups. A total of 123 patients (24 percent) had received treatment with interferon alfa.Histologic Response
The primary analysis was based on the 329 patients (97 percent) in the group given 10 mg of adefovir dipivoxil and the placebo group for whom base-line liver-biopsy specimens were available. Histologic improvement was seen in 53 percent of patients in the group given 10 mg of adefovir dipivoxil, 25 percent of those in the placebo group (P<0.001) (Table 2Table 2
Histologic Improvement and Changes in Necroinflammatory Activity and Fibrosis from Base Line to Week 48.), and 59 percent of those in the group given 30 mg of adefovir dipivoxil (P<0.001). The results were not changed by the addition of the four patients who underwent randomization but who did not take any study medication.After 48 weeks, patients who received 10 mg of adefovir dipivoxil per day had a median reduction in the Knodell necroinflammatory score of two points and those who received 30 mg per day had a median reduction of three points, as compared with no change in the placebo group (P<0.001 for both comparisons) (Table 2). On ranked assessment, higher percentages of patients in the 10-mg group and the 30-mg group than in the placebo group had improvements in necroinflammatory activity and fibrosis, and a higher percentage of patients in the placebo group had worsening of necroinflammatory activity and fibrosis (P<0.001 for each comparison).
Virologic Response
At week 48, serum HBV DNA levels had decreased by a median of 3.52 log copies per milliliter in the group given 10 mg of adefovir dipivoxil and 4.76 log copies per milliliter in the 30-mg group, as compared with 0.55 log copies per milliliter in the placebo group (P<0.001 for each comparison) (Table 3Table 3
Virologic and Biochemical Responses at Week 48. and Figure 1Figure 1Mean Change from Base Line in Serum Levels of Hepatitis B Virus (HBV) DNA.). Twenty-one percent of the patients in the 10-mg group and 39 percent of those in the 30-mg group had undetectable serum levels of HBV DNA, as compared with 0 percent of the patients in the placebo group (P<0.001 for each comparison). Loss of HBeAg occurred in 24 percent of the patients in the 10-mg group and 27 percent of those in the 30-mg group, as compared with 11 percent of the patients in the placebo group (P<0.001 for each comparison). HBeAg seroconversion occurred in 12 percent of the patients in the 10-mg group and 14 percent of those in the 30-mg group, as compared with 6 percent of the patients in the placebo group (P=0.049 and P=0.011, respectively).Biochemical Response
Median reductions in serum alanine aminotransferase levels at week 48 were 51 IU per liter in the 10-mg group and 54 IU per liter in the 30-mg group, as compared with 17 IU per liter in the placebo group (P<0.001 for each comparison) (Table 3). Forty-eight percent of the patients who received 10 mg of adefovir dipivoxil per day and 55 percent of those who received 30 mg per day had normal alanine aminotransferase values at week 48, as compared with 16 percent of those who received placebo (P<0.001 for both comparisons).
Resistance Profile
The polymerase–reverse transcriptase domain of the HBV polymerase gene was sequenced from serum samples obtained at base line and week 48 in 381 patients with detectable serum HBV DNA at both times. No mutations occurred at higher than background frequencies (less than 1.6 percent). Seven different novel substitutions were found at conserved sites in the HBV polymerase in seven patients (four of whom received adefovir dipivoxil and three of whom received placebo). All four of the patients who received adefovir dipivoxil had significant reductions in serum HBV DNA levels at week 48. In vitro phenotypic analyses demonstrated that viruses containing any of the seven substitutions remained fully susceptible to adefovir.
Safety
Similar percentages of patients in each group discontinued the study prematurely: 7 percent of those given 10 mg of adefovir dipivoxil per day and 8 percent of those given 30 mg per day and those given placebo. The incidence of severe (grade 3 or 4) clinical adverse events was similar: 10 percent in patients who received 10 mg of adefovir dipivoxil per day, 9 percent in those who received 30 mg per day, and 8 percent in the placebo group. The safety profile of the 10-mg group was similar to that of placebo with respect to all reported adverse events except asthenia (25 percent in the 10-mg group vs. 19 percent in the placebo group) and diarrhea (13 percent vs. 8 percent) (Table 4Table 4
Adverse Events Reported by at Least 10 Percent of Patients in the Group Given 30 mg of Adefovir Dipivoxil per Day.). Anorexia (10 percent) and pharyngitis (40 percent) occurred more frequently in the 30-mg group. Adverse events leading to the discontinuation of the study drug occurred in 2 percent of the patients in the 10-mg group, 3 percent of those in the 30-mg group, and less than 1 percent of those in the placebo group. These events included increased alanine aminotransferase or aspartate aminotransferase levels, weight loss, and rash in the 10-mg group; nausea, abdominal pain, headache, Fanconi-like syndrome, amblyopia, and myocardial infarction in the 30-mg group; and nausea in the placebo group.There was no significant change in median serum creatinine levels at week 48 in the 10-mg group and the placebo group; the 30-mg group had a median increase of 0.2 mg per deciliter (18 μmol per liter). There were no increases from base line of 0.5 mg per deciliter (44 μmol per liter) or greater in the serum creatinine level (confirmed by two consecutive laboratory assessments) in the 10-mg group or the placebo group, but 8 percent of patients in the 30-mg group had such an increase (P<0.001). In all cases, renal function normalized with a dose reduction or an interruption of treatment. The maximal reported serum creatinine level was 1.8 mg per deciliter (159 μmol per liter) in a patient in the 30-mg group. There was a median increase in serum phosphorus of 0.1 mg per deciliter (0.03 mmol per liter) in the 10-mg group and the placebo group and a median decrease of 0.1 mg per deciliter in the 30-mg group. There were no confirmed instances of serum phosphorus levels below 2.0 mg per deciliter (0.65 mmol per liter). The incidence of grade 3 or 4 laboratory abnormalities was similar in the adefovir dipivoxil and placebo groups, except that aspartate aminotransferase and alanine aminotransferase levels were higher in the placebo group.
Increases in alanine aminotransferase levels to more than 10 times the upper limit of the normal range occurred in 10 percent of patients in the group given 10 mg of adefovir dipivoxil per day, 8 percent of those given 30 mg per day, and 19 percent of those given placebo. Concurrent changes in total bilirubin levels, serum albumin levels, or the prothrombin time were not seen in any patient in the 10-mg or 30-mg group. In the placebo group, one patient had a concurrent increase in the total bilirubin level to greater than 2.5 mg per deciliter and to at least 1 mg per deciliter (17.1 μmol per liter) above the base-line value, and one had a concurrent decrease in the serum albumin level (to less than 3.0 g per liter).
After week 48, all patients were reassigned to new treatment groups for the second 48 weeks of the study. All patients in the placebo group received 10 mg of adefovir dipivoxil per day. Patients in the 10-mg group were randomly assigned to receive either continued treatment with 10 mg per day or placebo. All patients in the 30-mg group received placebo.
An interim analysis of data from the second 48-week period showed a continued antiviral, serologic, and biochemical response in patients who continued to receive 10 mg of adefovir dipivoxil per day (median duration of additional therapy, 16 weeks). By week 72, 46 percent of patients had fewer than 400 copies of serum HBV DNA per milliliter, 75 percent had normalization of alanine aminotransferase levels, 44 percent had loss of HBeAg, and 23 percent had HBeAg seroconversion. Safety data from the second 48-week period were similar to those in the first 48 weeks.
Discussion
In patients with chronic hepatitis B, 48 weeks of treatment with adefovir dipivoxil resulted in significant histologic improvement, reduced serum HBV DNA levels, and increased normalization of alanine aminotransferase levels and HBeAg seroconversion, as compared with placebo. These results are similar to those in the 52-week pivotal clinical trials of lamivudine.3,4 Lai et al. reported significant histologic improvement in 56 percent of patients after one year of treatment with lamivudine, although the development of serum HBV DNA polymerase mutations was associated with increases in alanine aminotransferase and HBV DNA.3 Dienstag et al. reported histologic improvement in 52 percent of patients who received 100 mg of lamivudine per day; anti-HBeAg antibodies developed in 17 percent, and 32 percent lost serum HBeAg.4
The patients in this study were from North America, Europe, Australia, and Southeast Asia; the majority were Asian. The two pivotal trials of lamivudine included predominantly white patients in the United States4 or only Chinese patients.3 Several studies have found regional and ethnic differences in response to both HBV infection and treatments for hepatitis B.11 The histologic improvement in our patients was similar among the geographic regions; therefore, our results may be more representative of the global population of patients with chronic hepatitis B. However, black patients were not well represented.
The efficacy profile of the 10-mg and 30-mg doses of adefovir dipivoxil was similar, except for differences in the magnitude of the decrease in serum HBV DNA levels and the percentage of patients with undetectable serum HBV DNA levels at 48 weeks. Both doses were well tolerated. However, the increases in serum creatinine levels in the 30-mg group limit the long-term use of this dose and instead favor the 10-mg dose. No adefovir-associated resistance mutations were identified during 48 weeks of treatment, which is consistent with findings from other studies evaluating up to 60 weeks of treatment.12,13
In our study, treatment with 10 mg of adefovir dipivoxil daily was well tolerated and significantly improved histologic findings in the liver, reduced serum HBV DNA levels, normalized alanine aminotransferase levels, and induced HBeAg loss and seroconversion in a diverse population. The favorable resistance profile of adefovir dipivoxil during 48 weeks of therapy is an advantage, since many patients with chronic hepatitis B require long-term therapy.
Supported by Gilead Sciences.
Drs. Wulfsohn, Xiong, and Brosgart and Mr. Fry are employees of Gilead Sciences and report equity ownership in Gilead Sciences. Drs. Marcellin, Tong, and Goodman report having served as consultants to Gilead Sciences. Dr. Marcellin reports having served as a paid lecturer for Gilead Sciences.
Source Information
From the Service d'Hépatologie, INSERM Unité 481, and Centre de Recherches Claude Bernard sur les Hépatites Virales, Hôpital Beaujon, Clichy, France (P.M.); the Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (T.-T.C.); the Division of Gastroenterology, National University Hospital, Singapore (S.G.L.); the Liver Center, Huntington Medical Research Institutes, Pasadena, Calif. (M.J.T.); the Department of Medicine, Monash University and Monash Medical Centre, Melbourne, Australia (W.S.); the Division of Gastroenterology, Virginia Commonwealth University Health System, Richmond (M.L.S.); the Center for Liver Diseases, University of Miami School of Medicine, and the Miami Veterans Affairs Medical Center, Miami (L.J.); the Armed Forces Institute of Pathology, Washington, D.C. (Z.G.); and Gilead Sciences, Foster City, Calif. (M.S.W., S.X., J.F., C.L.B.).
Address reprint requests to Dr. Marcellin at the Service d'Hépatologie, INSERM Unité 481, and Centre de Recherches Claude Bernard sur les Hépatites Virales, Hôpital Beaujon, 100 Blvd. du Général Leclerc, 92110 Clichy, France, or at marcellin@bichat.inserm.fr.
Other members of the Adefovir Dipivoxil 437 Study Group are listed in the Appendix.
Appendix
In addition to the authors, the Adefovir Dipivoxil International Investigator 437 Study Group includes the following: N. Afdhal and C. O'Conner (Beth Israel Deaconess Medical Center, Boston); P. Andreone and C. Cursaro (Policlinico S. Orsola, Bologna, Italy); P. Angus and R. Vaughan (Austin and Repatriation Medical Centre, Melbourne, Australia); V. Bain and K. Gutfreund (University of Alberta, Edmonton, Alta., Canada); K. Barange and M. Duffant (Hôpital Purpan, Toulouse, France); E. Barnes (Royal Free Hospital, London); M. Bennett and J. Pressman (Medical Association Research Group, San Diego, Calif.); D. Bernstein (North Shore University Hospital, Manhasset, N.Y.); F. Bonino and B. Coco (Azienda Ospedaliera Pisana, Pisa, Italy); M. Borum and S. Schuck (George Washington University Medical Center, Washington, D.C.); M. Bourliere and S. Benali (Hôpital Saint Joseph, Marseilles, France); N. Boyer and C. Castelnau (Hôpital Beaujon, Clichy, France); R. Brown and S. Scales (Columbia–Presbyterian Medical Center, New York); P. Buggisch and J. Peterson (Universitätskrankenhaus Eppendorf, Hamburg, Germany); G. Cooksley and G. MacDonald (Royal Brisbane Hospital, Brisbane, Australia); P. Couzigou and D. Foucner (Hôpital Haut-Leveque, Pessac, France); D. Crawford (Princess Alexandra Hospital, Brisbane, Australia); A. Der (Monash Medical Center, Melbourne, Australia); P. Desmond and A. Boussioutas (St. Vincent's Hospital, Melbourne, Australia); A. DiBisceglie and B. Bacon (Saint Louis University Medical Center, St. Louis); D. Dieterich and D. Goldman (Liberty Medical Group and New York University School of Medicine, New York); G. Dusheiko and the Royal Free Viral Hepatitis Group (Royal Free Hospital, London); J. Enriquez and A. Gallego (Hospital Santa Creu i Sant Pau, Barcelona, Spain); S. Esposito and J. Lemieszewski (Hepatobiliary Associates of New York, Bayside); R. Esteban and M. Buti (Hospital Vall d'Hebron, Barcelona, Spain); T. Faust and K. Wherity (University of Chicago Hospital Medical Center, Chicago); A. Francavilla and F. Malcangi (Azienda Ospedaliera Consorziale Policlinico, Bari, Italy); M. Fried and C. Nakayama (University of North Carolina School of Medicine, Chapel Hill); R. Gilson and M. Lascar (University College of London Medical Centre, London); R. Gish and H. Trinh (California Pacific Medical Center, San Francisco); S. Gordon and S. Colar (William Beaumont Hospital, Royal Oak, Mich.); M. Gregor and S. Kaiser (Eberhard-Karl-Universität, Tübingen, Germany); J. Heathcote (Toronto Western Hospital, Toronto); D. Imagawa (University of California, Irvine, Orange); I. Jacobson (Cornell University School of Medicine, New York); J. Rooney, C. James, R. Fallis, A. Jain, S. Chen, J. Ma, A. Hsing, S. Nonaka-Wong, and M. Kraus (Gilead Sciences, Foster City, Calif.); C.-M. Jen (National Cheng Kung University Hospital, Tainan, Taiwan); K. Kaita (University of Manitoba Health Sciences Centre, Winnipeg, Man., Canada); G. Koval and H. Parrish (West Hills Gastroenterology Associates, Portland, Oreg.); K. Kowdley (University of Washington Hepatology Center, Seattle); I. Kronborg and A. Nicoll (Western Hospital, Melbourne, Australia); P. Kullavanijaya and J. Amonrattanakosol (Chulalongkorn University Hospital, Bangkok, Thailand); J. Lao-Tan and L. Garcia (Cebu Doctors Hospital, Cebu City, Philippines); Y.-F. Liaw and R.-N. Chien (Chang Gung Memorial Hospital, Taipei, Taiwan); A. Lok and P. Richtmyer (University of Michigan Medical Center, Ann Arbor); P. Luengrojanakul and T. Tanwandee (Siriraj Hospital, Bangkok, Thailand); M. Manns and A. Schueler (Medizinische Hochschule Hannover, Hannover, Germany); P. Martin and V. Peacock (UCLA Medical Center, Los Angeles); G. McCaughan and S. Strasser (Royal Prince Alfred Hospital, Sydney, Australia); J. McHutchison and P. Pockros (Scripps Clinic, La Jolla, Calif.); I. Merican and S. Lachmanan (Hospital Kuala Lumpur, Kuala Lumpur, Malaysia); R. Mohamed (University of Malaya, Kuala Lumpur, Malaysia); R. Naccarato and S. Fagiuoli (Azienda Ospedaliera di Padova, Padua, Italy); M. Nelson and C. Higgs (Chelsea and Westminster Hospital, London); G. Pastore (Azienda Ospedaliera Consorziale, Bari, Italy); R. Perrillo and C. Denham (Alton Ochsner Medical Clinic, New Orleans); S. Pol and H. Fontaine (Hôpital Necker, Paris); C. Riely and D. Litley (University of Tennessee Medical Group, Memphis); M. Rizzetto and M. Lagget (Azienda Ospedaliera San Giovanni Battista, Turin, Italy); M. Rodriguez and M. Espiga (Hospital Central de Asturias, Oviedo, Spain); V. Rustgi and P. Lee (Metro Clinical Trials, Fairfax, Va.); S. Sacks and J. Farley (Viridae Clinical Sciences, Vancouver, B.C., Canada); D. Samuel and C. Feray (Hôpital Paul Brousse, Villejuif, France); J. Sasadeusz and M. Gioupouki (Royal Melbourne Hospital, Melbourne, Australia); D. Shaw and M. Le Mire (Royal Adelaide Hospital, Adelaide, Australia); D. Shelton (Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va.); M. Sherman and A. Bartolucci (Toronto General Hospital, Toronto); E. Schiff and A. Siebert (University of Miami, Miami); J. Sollano and F. Dy (Santo Tomas University Hospital, Manila, Philippines); P. Thuluvath (Johns Hopkins Hospital, Baltimore); L. Tong (Huntington Medical Research Institutes, Pasadena, Calif.); C. Trepo and M. Maynard (Hôtel Dieu, Lyons, France); J.-C. Trinchet and N. Carrie (Hôpital Jean Verdier, Bondy, France); D. Vetter and S. Metzger (Hôpital Civil de Strasbourg, Strasbourg, France); J. Vierling and J. Clarke-Platt (Cedars–Sinai Medical Center, Los Angeles); E. Wakil and N. Bzowej (Sutter Institute for Medical Research, Sacramento, Calif.); T. Warnes (Manchester Royal Infirmary, Manchester, United Kingdom); T. Wright and A. Kwong (San Francisco Veterans Affairs Medical Center, San Francisco); Y.-Y. Young (National University Hospital, Singapore); and J.-P. Zarski and V. Leroy (Centre Hospitalier Universitaire de Grenoble–Hôpital Albert Michallon, Grenoble, France).
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Citing Articles
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Xiao-Guang Li, Bao-Ming Liu, Jie Xu, Xue-En Liu, Hai Ding, Tong Li. (2012) Discrepancy of potential antiviral resistance mutation profiles within the HBV reverse transcriptase between nucleos(t)ide analogue-untreated and -treated patients with chronic hepatitis B in a hospital in China. Journal of Medical Virology 84:2, 207-216
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Maria C Segovia, Wadih Chacra, Stuart C Gordon. (2012) Adefovir dipivoxil in chronic hepatitis B: history and current uses. Expert Opinion on Pharmacotherapy 13:2, 245-254
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Mika Kurokawa, Naoki Hiramatsu, Tsugiko Oze, Takayuki Yakushijin, Masanori Miyazaki, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Hisashi Ishida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Sadaharu Iio, Yoshinori Doi, Akira Yamada, Masahide Oshita, Akira Kaneko, Kiyoshi Mochizuki, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Yoshiaki Inui, Kazuhiro Katayama, Harumasa Yoshihara, Yasuharu Imai, Eijirou Hayashi, Norio Hayashi, Tetsuo Takehara. (2012) Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection. Journal of Gastroenterology
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Michael P Manns, Ulus S Akarca, Ting-Tsung Chang, William Sievert, Seung Kew Yoon, Naoky Tsai, Albert Min, Andreas Pangerl, Suzanne Beebe, Miao Yu, Suchat Wongcharatrawee. (2012) Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901. Expert Opinion on Drug Safety1-8
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Tsunamasa Watanabe, Fuminaka Sugauchi, Shigeru Kusumoto, Noboru Shinkai, Etsuko Iio, Kentarou Matsuura, Atsunori Kusakabe, Tomokatsu Miyaki, Syunsuke Nojiri, Yasuhito Tanaka. (2012) A case report of successful therapy with tenofovir for a multi-drug resistant chronic hepatitis B patient complicated with malignant lymphoma. Kanzo 53:1, 35-41
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Henry Lik-Yuen Chan, Vincent Wai-Sun Wong. 2012. Hepatitis B. , 540-563.
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Don C. Rockey, Scott L. Friedman. 2012. Hepatic Fibrosis and Cirrhosis. , 64-85.
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Anna S. F. Lok, Francesco Negro. 2011. Hepatitis B and D. , 537-581.
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Jian Hong Zhong, Le Qun Li, Liu Cheng Wu, Le Qun Li. 2011. Lamivudine with or without adefovir dipivoxil for postoperative hepatocellular carcinoma. .
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Basile Njei, Sushil Kumar, Eugene J Kongnyuy, Basile Njei. 2011. Adefovir dipivoxil for chronic hepatitis B. .
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Basile Njei, Sushil Kumar, Eugene J Kongnyuy, Basile Njei. 2011. Adefovir dipivoxil versus other antiviral drugs for chronic hepatitis B. .
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J. Fung, C.-L. Lai, W.-K. Seto, M.-F. Yuen. (2011) Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B. Journal of Antimicrobial Chemotherapy 66:12, 2715-2725
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Michael Chang, Sammy Saab. (2011) Interferon for Hepatitis B: Which Populations Benefit the Most. Current Hepatitis Reports 10:4, 285-291
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Yuk-Fai Lam, Man-Fung Yuen, Wai-Kay Seto, Ching-Lung Lai. (2011) Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety. Current Hepatitis Reports 10:4, 235-243
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Olivier Lada, Tarik Asselah, Patrick Marcellin. (2011) Hepatitis B virus Resistance to Antivirals : Diagnosis and Management. Current Hepatitis Reports 10:4, 244-254
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Natravis Cox, Hans Tillmann. (2011) Emerging pipeline drugs for hepatitis B infection. Expert Opinion on Emerging Drugs 16:4, 713-729
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M. Trapero-Marugán, R. Moreno-Otero. (2011) Tratamiento de las hepatitis virales. Medicine - Programa de Formación Médica Continuada Acreditado 10:92, 6249-6254
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Bettina E. Hansen, Vincent Rijckborst, Martijn J. ter Borg, Harry L.A. Janssen. (2011) HBV DNA suppression in HBeAg-positive chronic hepatitis B patients treated with peginterferon or placebo. Journal of Medical Virology 83:11, 1917-1923
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W. S. Ayoub, E. B. Keeffe. (2011) Review article: current antiviral therapy of chronic hepatitis B. Alimentary Pharmacology & Therapeutics 34:10, 1145-1158
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Spilios Manolakopoulos, Athanasia Striki, Melanie Deutsch, Maria Mela, Ioannis Ketikoglou, Dimitrios Tzourmakliotis, Emanuel K. Manesis, George V. Papatheodoridis. (2011) Long-term adefovir plus lamivudine therapy does not decrease creatinine clearance in HBeAg-negative chronic hepatitis B patients. Liver International 31:10, 1525-1532
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Katrin Hochdörffer, Giuseppina Di Stefano, Hiroshi Maeda, Felix Kratz. 2011. Liver Tumor Targeting. , 1519-1568.
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E. Sheen, H. N. Trinh, T. T. Nguyen, S. T. Do, P. Tran, H. A. Nguyen, K. K. Nguyen, R. T. Garcia, M. H. Nguyen. (2011) The efficacy of entecavir therapy in chronic hepatitis B patients with suboptimal response to adevofir. Alimentary Pharmacology & Therapeutics 34:7, 767-774
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J. W. Park, H. S. Kim, D. D. Seo, J. S. Jang, W. G. Shin, K. H. Kim, M. K. Jang, J. H. Lee, H. Y. Kim, D. J. Kim, M. S. Lee, C. K. Park. (2011) Long-term efficacy of entecavir in adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance. Journal of Viral Hepatitis 18:10, e475-e481
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R. R. Razonable. (2011) Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus. Mayo Clinic Proceedings 86:10, 1009-1026
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Chih-Lin Lin, Jia-Horng Kao. (2011) Recent advances in the treatment of chronic hepatitis B. Expert Opinion on Pharmacotherapy 12:13, 2025-2040
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Mauro Viganò, Pietro Lampertico, Massimo Colombo. (2011) Drug safety evaluation of adefovir in HBV infection. Expert Opinion on Drug Safety 10:5, 809-818
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Matteo Ruggeri, Americo Cicchetti, Antonio Gasbarrini. (2011) The cost-effectiveness of alternative strategies against HBV in Italy. Health Policy 102:1, 72-80
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Maximilian Lee, Emmet B. Keeffe. (2011) Hepatitis B: Modern End Points of Treatment and the Specter of Viral Resistance. Gastroenterology Clinics of North America 40:3, 495-505
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William W. L. Wong, Gloria Woo, E. Jenny Heathcote, Murray Krahn. (2011) Cost effectiveness of screening immigrants for hepatitis B. Liver International 31:8, 1179-1190
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Zeng Minde, Mao Yimin, Yao Guangbi, Hou JinLin, Wang Hao, Ren Hong, Wang Yuming, Zhou Xiaqiu, Xu Daozhen, Chen Yagang, Niu Junqi, Chen Youming, Wang Yaozong, Jonathan Dixon, Keith Barker. (2011) Five years of treatment with adefovir dipivoxil in Chinese patients with HBeAg-positive chronic hepatitis B. Liver Internationaln/a-n/a
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Hong Joo Kim, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Woo Kyu Jeon, Byung Ik Kim. (2011) The influence of YMDD mutation patterns on clinical outcomes in patients with adefovir add-on lamivudine combination treatment. Liver Internationaln/a-n/a
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Marco Montagnani, Marina Giandinoto, Andrea Lisotti, Silvia Galli, Francesco Azzaroli, Federica Buonfiglioli, Laura Turco, Rita Aldini, Giuseppe Mazzella. (2011) High Dose Lamivudine in HBV-Related Cirrhotic Patients with Unsatisfactory Response After Adefovir Add-On. Digestive Diseases and Sciences
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Erik De Clercq. 2011. Discovery and Development of Tenofovir Disoproxil Fumarate. , 85-101.
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Richard Wilber, Bruce Kreter, Marc Bifano, Stephanie Danetz, Lois Lehman-McKeeman, Daniel J. Tenney, Nicholas Meanwell, Robert Zahler, Helena Brett-Smith. 2011. Discovery and Development of Entecavir. , 401-416.
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Na-Na Du, Xin Li, Yu-Ping Wang, Fei Liu, Yan-Xin Liu, Chun-Xin Li, Zong-Gen Peng, Li-Mei Gao, Jian-Dong Jiang, Dan-Qing Song. (2011) Synthesis, structure−activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators. Bioorganic & Medicinal Chemistry Letters 21:16, 4732-4735
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Wen Xie, Guangfeng Shi, Hongfei Zhang, Guiming Zhao, Zujiang Yu, Zhenwei Lang, Hong Zhao, Jie Yan, Jun Cheng. (2011) A randomized, multi-central, controlled study of patients with hepatitis B e antigen-positive chronic hepatitis B treated by adefovir dipivoxil or adefovir dipivoxil plus bicyclol. Hepatology International
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Erik De Clercq. (2011) The clinical potential of the acyclic (and cyclic) nucleoside phosphonates. The magic of the phosphonate bond. Biochemical Pharmacology 82:2, 99-109
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M. J. Sonneveld, R. Zoutendijk, H. L. A. Janssen. (2011) Hepatitis B surface antigen monitoring and management of chronic hepatitis B. Journal of Viral Hepatitis 18:7, 449-457
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Yoon-Seon Lee, Young-Hwa Chung, Jeong A. Kim, Young Joo Jin, Won Hyung Park, Sung Eun Kim, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young Suk Lim, Han Chu Lee, Yung Sang Lee, Dong Jin Suh. (2011) The rtL180M Mutation of Hepatitis B Virus Closely Associates with Frequent Virologic Resistance to Adefovir Dipivoxil Therapy. Journal of Gastroenterology and Hepatologyno-no
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W. Chotiyaputta, C. Hongthanakorn, K. Oberhelman, R. J. Fontana, T. Licari, A. S. F. Lok. (2011) Adherence to nucleos(t)ide analogues for chronic hepatitis B in clinical practice and correlation with virological breakthroughs. Journal of Viral Hepatitisno-no
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Chanunta Hongthanakorn, Watcharasak Chotiyaputta, Kelly Oberhelman, Robert J. Fontana, Jorge A. Marrero, Tracy Licari, Anna S. F. Lok. (2011) Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. Hepatology 53:6, 1854-1863
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S.-t. Law, K. K. Li, Y. Y. Ho. (2011) Nephrotoxicity, including acquired Fanconi’s syndrome, caused by adefovir dipivoxil - is there a safe dose?. Journal of Clinical Pharmacy and Therapeuticsno-no
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Joseph K. Lim, Mindie H. Nguyen. (2011) The Role of Hepatic Steatosis in Chronic Hepatitis B Infection. Current Hepatitis Reports 10:2, 134-141
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Mashu Aizawa, Akihito Tsubota, Kiyotaka Fujise, Keiko Tatsuzawa, Midori Kono, Sadayori Hoshina, Hisao Tajiri. (2011) Clinical course and predictive factors of virological response in long-term lamivudine plus adefovir dipivoxil combination therapy for lamivudine-resistant chronic hepatitis B patients. Journal of Medical Virology 83:6, 953-961
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Richard L. Mackman, Tomas Cihlar. 2011. Acyclic and Cyclic Nucleoside Phosphonates. , 91-128.
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Stefan Mauss, Florian Berger, Natalie Filmann, Dietrich Hueppe, Julia Henke, Petra Hegener, Christoph Athmann, Guenther Schmutz, Eva Herrmann. (2011) Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B. Journal of Hepatology
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Anna S. F. Lok. 2011. Hepatitis B. , 367-392.
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Yun Xia, Hui Luo, Jian Ping Liu, Christian Gluud, Yun Xia. 2011. Phyllanthus species for chronic hepatitis B virus infection. .
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Victor R. Guarino. 2011. The Molecular Design of Prodrugs by Functional Group. , 31-60.
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Yuan Gao, Hui Zu, Jianjun Zhang. (2011) Enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation. Journal of Pharmacy and Pharmacology 63:4, 483-490
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Moon-Chan Kim, Seok Won Jung, Jung Woo Shin, Neung Hwa Park. (2011) The Level of HBV DNA at Month 12 Is an Important Predictor of Virological Breakthrough During Adefovir Monotherapy in Chronic Hepatitis B Patients with Lamivudine Resistance. Digestive Diseases and Sciences 56:4, 1215-1221
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Shuang Wu, Kenichi Fukai, Fumio Imazeki, Makoto Arai, Tatsuo Kanda, Yutaka Yonemitsu, Osamu Yokosuka. (2011) Initial Virological Response and Viral Mutation with Adefovir Dipivoxil Added to Ongoing Lamivudine Therapy in Lamivudine-Resistant Chronic Hepatitis B. Digestive Diseases and Sciences 56:4, 1207-1214
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Pin-Nan Cheng, Wen-Chun Liu, Hung-Wen Tsai, I-Chin Wu, Ting-Tsung Chang, Kung-Chia Young. (2011) Association of intrahepatic cccDNA reduction with the improvement of liver histology in chronic hepatitis B patients receiving oral antiviral agents. Journal of Medical Virology 83:4, 602-607
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Vincenza Calvaruso, Antonio Craxì. (2011) Fibrosis in chronic viral hepatitis. Best Practice & Research Clinical Gastroenterology 25:2, 219-230
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Hellan Kwon, Anna S. Lok. (2011) Hepatitis B therapy. Nature Reviews Gastroenterology & Hepatology
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V. Rijckborst, M. J. Sonneveld, H. L. A. Janssen. (2011) Review article: chronic hepatitis B - anti-viral or immunomodulatory therapy?. Alimentary Pharmacology & Therapeutics 33:5, 501-513
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J. Inoue, Y. Ueno, Y. Wakui, H. Niitsuma, K. Fukushima, Y. Yamagiwa, M. Shiina, Y. Kondo, E. Kakazu, K. Tamai, N. Obara, T. Iwasaki, T. Shimosegawa. (2011) Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern. Journal of Viral Hepatitis 18:3, 206-215
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Mauro Viganò, Pietro Lampertico. (2011) Antiviral drugs for HBV liver disease. Expert Opinion on Biological Therapy 11:3, 285-300
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Tatyana A. Shamliyan, James R. Johnson, Roderick MacDonald, Aasma Shaukat, Jian-Min Yuan, Robert L. Kane, Timothy J. Wilt. (2011) Systematic Review of the Literature on Comparative Effectiveness of Antiviral Treatments for Chronic Hepatitis B Infection. Journal of General Internal Medicine 26:3, 326-339
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Janna Huskey, Alexander C. Wiseman. (2011) Chronic viral hepatitis in kidney transplantation. Nature Reviews Nephrology 7:3, 156-165
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Erik De Clercq. (2011) A 40-Year Journey in Search of Selective Antiviral Chemotherapy*. Annual Review of Pharmacology and Toxicology 51:1, 1-24
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Ray M. Merrill, Bradley D. Hunter. (2011) Seroprevalence of markers for hepatitis B viral infection. International Journal of Infectious Diseases 15:2, e78-e121
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Basile Njei, Eugene J Kongnyuy, Linda Kibot, Basile Njei. 2011. Adefovir dipivoxil for chronic hepatitis B. .
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Usama Elewa, Ana Maria Sandri, W. Ray Kim, Fernando C. Fervenza. (2011) Treatment of Hepatitis B Virus-Associated Nephropathy. Nephron Clinical Practice 119:1, c41-c49
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Milan J. Sonneveld, Harry L. A. Janssen. (2011) Chronic hepatitis B: peginterferon or nucleos(t)ide analogues?. Liver International 31, 78-84
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George V. Papatheodoridis. (2011) Treatment of HBeAg-negative chronic hepatitis B patients with nucleos(t)ide analogues. Liver International 31, 95-103
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Hui Lu, Da Geng, Fei Shen, Jing Zhang, Bing Lu, Li Ma. (2011) Optimization of adefovir therapy in chronic hepatitis B according to baseline predictors and on-treatment HBV DNA: a 5-Year prospective study. Virology Journal 8:1, 444
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Chau-Ting Yeh, Tiffany Chen, Chao-Wei Hsu, Yi-Cheng Chen, Ming-Wei Lai, Kung-Hao Liang, Tse-Ching Chen. (2011) Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B. BMC Cancer 11:1, 398
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Nancy Leung. (2011) Treatment of HBeAg-positive chronic hepatitis B with nucleos(t)ide analogues. Liver International 31, 85-89
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Prodromos. Hytiroglou. 2011. Hepatitis B. , 215-224.
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Osamu Yokosuka, Masayuki Kurosaki, Fumio Imazeki, Yasuji Arase, Yasuhito Tanaka, Kazuaki Chayama, Eiji Tanaka, Hiromitsu Kumada, Namiki Izumi, Masashi Mizokami, Masatoshi Kudo. (2011) Management of hepatitis B: Consensus of the Japan Society of Hepatology 2009. Hepatology Research 41:1, 1-21
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Soon Sun Kim, Jae Youn Cheong, Sung Won Cho. (2011) Current Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B. Gut and Liver 5:3, 278
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Shu-Shan Zhao, Lan-Hua Tang, Xia-Hong Dai, Wei Wang, Rong-Rong Zhou, Li-Zhang Chen, Xue-Gong Fan. (2011) Comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B: A Systematic Review. Virology Journal 8:1, 111
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Itaru Ozeki, Yoshiyasu Karino, Jun Akaike, Rikuumi Kimura, Tomohiro Arakawa, Tomoaki Nakashima, Yasuaki Kuwata, Takumi Ohmura, Takahiro Sato, Joji Toyota. (2011) Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Kanzo 52:2, 102-111
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Helen Dakin, Carrie Fidler, Christie Harper. (2010) Mixed Treatment Comparison Meta-Analysis Evaluating the Relative Efficacy of Nucleos(t)ides for Treatment of Nucleos(t)ide-Naive Patients with Chronic Hepatitis B. Value in Health 13:8, 934-945
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Helen S. Te. (2010) Antiviral Therapy: Analysis of Long-term Efficacy and Safety. Current Hepatitis Reports 9:4, 214-222
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Tetsuya Hosaka, Fumitaka Suzuki, Masahiro Kobayashi, Miharu Hirakawa, Yusuke Kawamura, Hiromi Yatsuji, Hitomi Sezaki, Norio Akuta, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Hiromitsu Kumada. (2010) HBcrAg is a predictor of post-treatment recurrence of hepatocellular carcinoma during antiviral therapy. Liver International 30:10, 1461-1470
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W. Chotiyaputta, A. S. F. Lok. (2010) Endpoints of hepatitis B treatment. Journal of Viral Hepatitis 17:10, 675-684
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Gloria Woo, George Tomlinson, Yasunori Nishikawa, Matthew Kowgier, Morris Sherman, David K.H. Wong, Ba Pham, Wendy J. Ungar, Thomas R. Einarson, E. Jenny Heathcote, Murray Krahn. (2010) Tenofovir and Entecavir Are the Most Effective Antiviral Agents for Chronic Hepatitis B: A Systematic Review and Bayesian Meta-analyses. Gastroenterology 139:4, 1218-1229.e5
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Yun-Fan Liaw, George K. K. Lau, Jia-Horng Kao, Edward Gane. (2010) Hepatitis B e Antigen Seroconversion: A Critical Event in Chronic Hepatitis B Virus Infection. Digestive Diseases and Sciences 55:10, 2727-2734
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Shi-Bin Xie, Jian-Yun Zhu, Zhang Ying, Li-Jiao Zeng, Ma Chao, Min-Qiang Lu. (2010) Prevention and Risk Factors of the HBV Recurrence After Orthotopic Liver Transplantation: 160 Cases Follow-Up Study. Transplantation 90:7, 786-790
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W. Ray Kim, John J. Poterucha. 2010. Hepatitis B and C. , 186-199.
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Piero Luigi Almasio, Calogero Cammà, Vito Di Marco, Antonio Craxì. 2010. Hepatitis B: Prognosis and Treatment. , 448-464.
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Chanunta Hongthanakorn, Anna S.F. Lok. (2010) New Pharmacologic Therapies in Chronic Hepatitis B. Gastroenterology Clinics of North America 39:3, 659-680
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Lior H Katz, Ran Tur-Kaspa, Daniel G Guy, Mical Paul, Lior H Katz. 2010. Lamivudine or adefovir dipivoxil alone or combined with immunoglobulin for preventing hepatitis B recurrence after liver transplantation. .
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Chiaki Okuse, Hiroshi Yotsuyanagi, Norie Yamada, Masaru Okamoto, Hiroki Ikeda, Minoru Kobayashi, Yasunobu Fukuda, Hideaki Takahashi, Yoshihiko Nagase, Yuka Suzuki, Kotaro Matsunaga, Toshiya Ishii, Nobuyuki Matsumoto, Kazuhiko Koike, Michihiro Suzuki, Fumio Itoh. (2010) Effect of nucleoside analog-interferon sequential therapy on patients with acute exacerbation of chronic hepatitis B. Hepatology Research 40:5, 461-469
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Markus Peck-Radosavljevic, Johann Deutsch, Peter Ferenci, Ivo Graziadei, Harald Hofer, Heidemarie Holzmann, Wolf-Dietrich Huber, Herman Laferl, Andreas Maieron, Rudolf Stauber, Wolfgang Vogel. (2010) 4. Österreichischer Konsensusbericht zur Diagnose und Therapie der Hepatitis B 2009. Wiener klinische Wochenschrift 122:9-10, 280-302
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Milan J. Sonneveld, Harry L. A. Janssen. (2010) Pros and Cons of Peginterferon Versus Nucleos(t)ide Analogues for Treatment of Chronic Hepatitis B. Current Hepatitis Reports 9:2, 91-98
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R. B. Takkenberg, C. J. Weegink, H. L. Zaaijer, H. W. Reesink. (2010) New developments in antiviral therapy for chronic hepatitis B. Vox Sanguinis 98:4, 481-494
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Ester Lopez-Suñé, Montse Tuset, Montse Laguno, Asunción Moreno, José M. Miró. (2010) Características de los fármacos antivíricos activos frente al virus de la hepatitis y el virus de la influenza: actualización 2009. Enfermedades Infecciosas y Microbiología Clínica 28:4, 253.e1-253.e17
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Hai-Tang Xie, Guang-Ji Wang, Mei-Juan Xu, Yuan-Wei Jia, Hao Li, Jian-Guo Sun, Peng Li. (2010) A New LC–MS–MS Method for Quantitative Analysis of Adefovir, and Its Use for Pharmacokinetic Studies in Healthy Chinese Volunteers. Chromatographia 71:7-8, 587-593
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Wolfram H. Gerlich, Michael Kann. 2010. Hepatitis B. .
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Bao-Ming Liu, Tong Li, Jie Xu, Xiao-Guang Li, Jian-Ping Dong, Ping Yan, Jing-Xian Yang, Ling Yan, Zhi-Yong Gao, Wen-Peng Li, Xie-Wen Sun, Yu-Hua Wang, Xiu-Juan Jiao, Chun-Sheng Hou, Hui Zhuang. (2010) Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naïve Chinese patients. Antiviral Research 85:3, 512-519
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Brian Rha, David Kimberlin, Richard Whitley. 2010. Antiviral Therapy. , 210-225.
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, Sang Hoon Ahn, Henry L. Y. Chan, Pei-Jer Chen, Jun Cheng, Mahesh K. Goenka, Jinlin Hou, Seng Gee Lim, Masao Omata, Teerha Piratvisuth, Qing Xie, Hyung Joon Yim, Man-Fung Yuen. (2010) Chronic hepatitis B: whom to treat and for how long? Propositions, challenges, and future directions. Hepatology International 4:1, 386-395
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L. J. Liu, J. H. Wang, S. C. Du, J. H. Tian, R. F. Yang, L. Wei. (2010) rtE218G, a novel hepatitis B virus mutation with resistance to adefovir dipivoxil in patients with chronic hepatitis B. Journal of Viral Hepatitis 17, 66-72
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J. Sun, J. L. Hou. (2010) Management of chronic hepatitis B: experience from China. Journal of Viral Hepatitis 17, 10-17
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S. W. Cho, K. H. Koh, J. Y. Cheong, M. H. Lee, S. P. Hong, W. D. Yoo, S.-O. Kim. (2010) Low efficacy of entecavir therapy in adefovir-refractory hepatitis B patients with prior lamivudine resistance. Journal of Viral Hepatitis 17:3, 171-177
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M. Ganesan, K. M. Muraleedharan. (2010) Synthesis of β-Hydroxyphosphonate and 1,2-Dihydroxy Acyclic Nucleoside Analogs via 1,3-Dipolar Cycloaddition Strategy. Nucleosides, Nucleotides and Nucleic Acids 29:2, 91-96
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Hyun Woong Lee, Heon Ju Lee, Jae Seok Hwang, Joo Hyun Sohn, Jae Young Jang, Ki Jun Han, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Yong Han Paik, Chun Kyon Lee, Kwan Sik Lee, Chae Yoon Chon, Kwang-Hyub Han. (2010) Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B. Hepatology 51:2, 415-421
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Chin W Jung, Jennifer Tan, Nelly Tan, Melissa N Kuo, Ashwin Ashok, Samantha J Eells, Loren G Miller. (2010) Evidence for the insufficient evaluation and undertreatment of chronic hepatitis B infection in a predominantly low-income and immigrant population. Journal of Gastroenterology and Hepatology 25:2, 369-375
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Si Nafa Si Ahmed, Marie Ecochard, Fabien Zoulim. (2010) End points of therapy in chronic hepatitis B. Expert Review of Gastroenterology & Hepatology 4:1, 37-49
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Yanfang Jiang, Wanyu Li, Lei Yu, Jingjing Liu, Guijie Xin, Hongqing Yan, Pinghui Sun, Hong Zhang, Damo Xu, Junqi Niu. (2010) Enhancing the antihepatitis B virus immune response by adefovir dipivoxil and entecavir therapies. Cellular and Molecular Immunology 8:1, 75-82
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Masashi Mizokami, Eiji Tanaka, Kazuaki Chayama, Yasuhito Tanaka, Masayuki Kurosaki, Namiki Izumi, Yasuji Arase, Hiromitsu Kumada, Fumio Imazeki, Osamu Yokosuka, Masatoshi Kudo. (2010) JSH Consensus Kobe 2009: Diagnosis and Treatment of Hepatitis B. Kanzo 51:5, 243-260
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Themistoklis G Vassiliadis, Olga Giouleme, Georgios Koumerkeridis, Haralabos Koumaras, Konstantinos Tziomalos, Kalliopi Patsiaoura, Nikolaos Grammatikos, Alexandros Mpoumponaris, Dimitrios Gkisakis, Konstantinos Theodoropoulos, Athanasia Panderi, Panagiotis Katsinelos, Nikolaos Eugenidis. (2010) Adefovir plus lamivudine are more effective than adefovir alone in lamivudine-resistant HBeAg - chronic hepatitis B patients: A 4-year study. Journal of Gastroenterology and Hepatology 25:1, 54-60
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Mashu Aizawa, Akihito Tsubota, Kiyotaka Fujise, Ken-ichi Sato, Masashi Baba, Masashi Takamatsu, Yoshihisa Namiki, Toshifumi Ohkusa, Hisao Tajiri. (2010) Overlap/Switch to Adefovir Monotherapy for Lamivudine-resistant Patients Who Responded to Combination Therapy: A Pilot Controlled Study. Internal Medicine 49:12, 1067-1072
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Erik H.C.J. Buster, Bettina E. Hansen, George K.K. Lau, Teerha Piratvisuth, Stefan Zeuzem, Ewout W. Steyerberg, Harry L.A. Janssen. (2009) Factors That Predict Response of Patients With Hepatitis B e Antigen–Positive Chronic Hepatitis B to Peginterferon-Alfa. Gastroenterology 137:6, 2002-2009
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Premashis Kar, Mohammad Asim, Manash Pratim Sarma, Pralhad S. Patki. (2009) HD-03/ES: A promising herbal drug for HBV antiviral therapy. Antiviral Research 84:3, 249-253
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C.P. Strassburg, M. Cornberg. (2009) Diagnostik und Therapie der Hepatitis. Der Internist 50:12, 1358-1368
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