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Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures.

Abstract

AIM

To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures.

METHODS

A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo).

RESULTS

All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects.

CONCLUSION

TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.

    , , , , , ,

    Source

    World journal of gastroenterology 18:47 2012 Dec 21 pg 6996-7002

    MeSH

    Adenine
    Adult
    Antiviral Agents
    Creatinine
    Drug Tolerance
    Female
    Genotype
    Hepatitis B, Chronic
    Humans
    Lamivudine
    Male
    Middle Aged
    Mutation
    Organophosphonates
    Phenotype
    Phosphorus
    Reverse Transcriptase Inhibitors
    Tenofovir
    Treatment Outcome

    Pub Type(s)

    Clinical Trial
    Journal Article

    Language

    eng

    PubMed ID

    23322999

    Citation

    TY - JOUR T1 - Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures. AU - Kim,Yu Jin, AU - Sinn,Dong Hyun, AU - Gwak,Geum-Youn, AU - Choi,Moon Seok, AU - Koh,Kwang Cheol, AU - Paik,Seung Woon, AU - Yoo,Byung Chul, AU - Lee,Joon Hyeok, PY - 2012/04/03/received PY - 2012/05/31/revised PY - 2012/06/08/accepted PY - 2013/1/17/entrez PY - 2013/1/17/pubmed PY - 2013/12/18/medline KW - Chronic hepatitis B KW - Tenofovir KW - Treatment failure SP - 6996 EP - 7002 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 18 IS - 47 N2 - AIM: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures. METHODS: A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo). RESULTS: All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects. CONCLUSION: TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/23322999/Tenofovir_rescue_therapy_for_chronic_hepatitis_B_patients_after_multiple_treatment_failures_ L2 - http://www.wjgnet.com/1007-9327/full/v18/i47/6996.htm ER -