Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: Two double-blind, randomized, placebo-controlled studies

Izzedine, Hassane; Hulot, Jean‐Sébastien; Launay-Vacher, Vincent; Marcellini, Patrick; Hadziyannis, Stephanos J.; Currie, G. A.; Brosgart, Carol; Westland, Christopher; Arterbrun, Sarah; Deray, Gilbert

doi:10.1111/j.1523-1755.2004.00866.x

Cited by 145 publications

(110 citation statements)

References 11 publications

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“…Adefovir dipivoxil and entecavir are effective in treating lamivudine-resistant disease, best studied in the liver transplant population (170 -174). Adefovir dipivoxil can be nephrotoxic (175). Combination therapy is undergoing evaluation.…”

Section: Hbvmentioning

confidence: 99%

Viral Infection in the Renal Transplant Recipient

Kotton

Fishman²

2005

Journal of the American Society of Nephrology

200

181

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Viruses are among the most common causes of opportunistic infection after transplantation and the most important. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Viral infection, both symptomatic and asymptomatic, causes the "direct effects" of invasive disease and "indirect effects," including immune suppression predisposing to other opportunistic infections and oncogenesis. Rapid and sensitive microbiologic assays for many of the common viruses after transplantation have replaced, for the most part, serologic testing and in vitro cultures for the diagnosis of infection. Furthermore, quantitative molecular tests allow the individualization of antiviral therapies for prevention and treatment of infection. This advance is most prominent in the management of cytomegalovirus, Epstein-Barr, hepatitis B, and hepatitis C viruses. Diagnostic advances have not been accompanied by the development of specific and nontoxic anti-viral agents or effective antiviral vaccines. Vaccines, where available, should be given to patients as early as possible and well in advance of transplantation to optimize the immune response. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections.

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Section: Hbvmentioning

confidence: 99%

Viral Infection in the Renal Transplant Recipient

Kotton

Fishman²

2005

Journal of the American Society of Nephrology

200

181

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“…2 Nevertheless, in 2004, together with Issendine et al 3 we brought into clinical attention and stressed the potential for NA nephrotoxicity. With the newer compounds ETV and TDF, this topic has been expanded and lactic acidosis and side effects on bone mineral density (BMD) have been added.…”

Section: Sirs the Review Article By Lampertico Et Almentioning

confidence: 99%

Letter: long‐term safety of nucleoside and nucleotide analogues in HBV‐monoinfected patients

Hadziyannis

2016

Aliment Pharmacol Ther

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of nucleos(t)ide analogues in HBV infection offers detailed and properly selected information on this clinically important topic. Actually, the presented and discussed data have been derived from numerous studies on this topic covering more than a decade for entecavir (ETV) and at least of 8 years for tenofovir (TDF). However, numerous gaps in our knowledge on this important topic still exist.In the early studies of long-term administration of adefovir dipivoxil (ADV) in chronic hepatitis B (CHB), the low 10 mg dose was initially found to be quite safe. brought into clinical attention and stressed the potential for NA nephrotoxicity. With the newer compounds ETV and TDF, this topic has been expanded and lactic acidosis and side effects on bone mineral density (BMD) have been added. The review by Lampertico et al. 1 of long-term safety of nucleos(t)ide analogues is brilliant being not only critical and detailed, but also based on the actual and potential pathophysiological mechanisms of these side effects. Moreover, the authors make practical proposals on how to monitor patients subjected to nucleos(t)ide analogue therapy for possible nephrotoxicity and on further therapeutic decision making. However, they look rather overoptimistic regarding potential nephrotoxicity of the newer nucleos(t)ide analogue tenofovir alafenamide, 4 which, as stressed by Peterson, 5 even if it finally proves absolutely safe, this is going to take many years to become properly documented. And the same seems true for another new compound, besoifovir. Currently, the AASLD suggests 7 no preference between ETV and TDF regarding potential long-term risks for renal and bone complications. However, in real life preferences do exist, being mostly determined by national and regional agreements on availability and local prices of NAs. The clinically important point is how to handle neprotoxicity and/or bone side effects in the particular subset of TDF treated patients that are harbouring lamivudine resistant mutants. I personally think that at least in noncirrhotic patients with evidence of nephrotoxicity, cessation of nucleos(t)ide analogue therapy could also be considered. After all, two most recent systematic reviews clearly support the safety of this approach. 8,9 Of course substitution of TDF by a newer compound without potential renal and bone side effects would be clinically welcomed. Finally, I wonder why the authors do not make any suggestion for studies applying ab initio TDF doses lower than the currently administered one, at least to patients of older age and/or with comorbidities.In view of the above, I feel that in the near future the topic of renal nephrotoxicity and of other side effects of nucleos(t)ide analogues, may remain controversial in its handling in clinical practice. Thus, long-term nucleos(t)ide analogue therapy may continue to be dominated by national and local conditions and preferences rather than by international suggestions and guidelines, at least up to the time that curable anti-HBV therapies become available. AC...

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“…Seven RCTs involving 1,613 subjects were conducted to assess the summary risk estimates of nephrotoxicity during ADV treatment in CHB patients (3,(9)(10)(11)(12)(13)(14). Pooled data from these RCTs showed no differences between the control therapy and ADV treatment [Peto OR, 1.781; 95% confidence interval (CI), 0.637-4.979; Z=1.10; P=0.271; Fig.…”

Section: Characteristics Of the Enrolled Studies And Qualitymentioning

confidence: 99%

“…Subsequently, 17 studies met all the inclusion criteria following a systematic review ( Fig. 1) (3,(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Of the 17 studies, seven were RCTs (3,(9)(10)(11)(12)(13)(14), four were cohort studies (15)(16)(17)(18) and the remaining six were single-arm studies (5,(19)(20)(21)(22)(23).…”

Section: Characteristics Of the Enrolled Studies And Qualitymentioning

confidence: 99%

“…The baseline characteristics and quality assessment of the publications are shown in Tables I-III. Thirty-five percent of the studies were performed in multiple countries (3,(9)(10)(11)(12)15), 41.2% were in Asia (5,16-18,21-23) and 23.5% were in Europe (13,14,19,20). Of the studies included, the follow-up period of six studies lasted for ~1 year (3,9-12,18), 10 for 2-5 years (5,(14)(15)(16)(17)(19)(20)(21)(22)(23) and one for <7.5 years (13).…”

Section: Characteristics Of the Enrolled Studies And Qualitymentioning

confidence: 99%

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Association between adefovir dipivoxil treatment and the risk of renal insufficiency in patients with chronic hepatitis B: A meta-analysis

et al. 2015

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Abstract. Adefovir dipivoxil (ADV) is an effective antiviral drug against hepatitis B virus. The renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B (CHB) remains controversial. The present meta-analysis was therefore performed to evaluate the renal safety of ADV treatment in patients with CHB. Two independent investigators searched MEDLINE, Embase and China National Knowledge Infrastructure databases for eligible studies published in English or Chinese until June 1, 2014. The Peto odds ratios (Peto ORs) or the rates of each study were analyzed. Seven randomized controlled trials (RCTs), four cohort studies and six single-arm studies were identified. ADV treatment was not associated with a higher incidence of nephrotoxicity in RCTs [Peto OR, 1.781; 95% confidence interval (CI), 0.637-4.979; P=0.271] but appeared to increase nephrotoxicity significantly in cohort studies (Peto OR, 2.682; 95% CI, 1.470-4.894; P=0.001); the significant increase was further observed in CHB patients receiving long-term ADV treatment in cohort studies (Peto OR, 2.275; 95% CI, 1.127-4.593; P=0.022). The analysis based on single-arm studies showed that the rate of renal dysfunction in the ADV-treated patients was 10.6% (95% CI, 0.059-0.185); the subgroup analysis with the standard of createnine levels showed a lower rate (6.9%, 95% CI, 0.013-0.298) than those in the overall studies. In conclusion, although current evidence indicated a positive link between treatment with ADV in CHB patients and an increased risk of renal dysfunction, optimally designed studies are required for definitive conclusions.

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Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: Two double-blind, randomized, placebo-controlled studies

Cited by 145 publications

References 11 publications

Viral Infection in the Renal Transplant Recipient

Viral Infection in the Renal Transplant Recipient

Letter: long‐term safety of nucleoside and nucleotide analogues in HBV‐monoinfected patients

Association between adefovir dipivoxil treatment and the risk of renal insufficiency in patients with chronic hepatitis B: A meta-analysis

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