Prime

Type your tag names separated by a space and hit enter

Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies.

Abstract

AIM

To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients.

METHODS

Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively.

RESULTS

Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log10 IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log10 IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors.

CONCLUSION

If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    ,

    Hyoung Su Kim, Myoung Kuk Jang, Ji Won Park, Department of Internal Medicine, Hallym University College of Medicine, Seoul 134-701, South Korea.

    Source

    World journal of gastroenterology 21:38 2015 Oct 14 pg 10874-82

    MeSH

    Adenine
    Adult
    Aged
    Antiviral Agents
    DNA, Viral
    Drug Resistance, Viral
    Drug Therapy, Combination
    Female
    Guanine
    Hepatitis B, Chronic
    Humans
    Lamivudine
    Male
    Middle Aged
    Organophosphonates
    Viral Load
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26478678

    Citation

    TY - JOUR T1 - Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies. AU - Kim,Hyoung Su, AU - Yim,Hyung Joon, AU - Jang,Myoung Kuk, AU - Park,Ji Won, AU - Suh,Sang Jun, AU - Seo,Yeon Seok, AU - Kim,Ji Hoon, AU - Kim,Bo Hyun, AU - Park,Sang Jong, AU - Lee,Sae Hwan, AU - Kim,Sang Gyune, AU - Kim,Young Seok, AU - Lee,Jung Il, AU - Lee,Jin-Woo, AU - Kim,In Hee, AU - Kim,Tae Yeob, AU - Kim,Jin-Wook, AU - Jeong,Sook-Hyang, AU - Jung,Young Kul, AU - Park,Hana, AU - Hwang,Seong Gyu, AU - ,, PY - 2015/02/02/received PY - 2015/05/13/revised PY - 2015/07/18/accepted PY - 2015/10/20/entrez PY - 2015/10/20/pubmed PY - 2016/4/28/medline KW - Adefovir KW - Chronic hepatitis B KW - Entecavir KW - Lamivudine KW - Resistance SP - 10874 EP - 82 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 21 IS - 38 N2 - AIM: To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients. METHODS: Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively. RESULTS: Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log10 IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log10 IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors. CONCLUSION: If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/26478678/Management_of_entecavir_resistant_chronic_hepatitis_B_with_adefovir_based_combination_therapies_ L2 - http://www.wjgnet.com/1007-9327/full/v21/i38/10874.htm ER -