RESUMEN
BACKGROUND: Hepatitis B s antigen (HBsAg) seroclearance is regarded as the optimal virological end-point. AIM: To investigate the dynamic changes in serum cytokine levels around the time of HBsAg seroclearance. METHODS: This was a case-control study. Consecutive patients with chronic hepatitis B (CHB) who lost HBsAg were matched with those remained positive for HBsAg with same age, gender, HBeAg status and presence of cirrhosis in 1:2 ratio. Relevant serum cytokines [interleukin (IL)-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, IL-15, IL-21 interferon-γ, tumour necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-inducible protein 10 (IP-10)] were assayed at the time (Year 0) and 3 years before (Year -3) HBsAg seroclearance. RESULTS: Seventy-one and 142 CHB patients who did and did not achieve HBsAg seroclearance were included. Mean age was 48 ± 11 years; 76% were male, 20% had positive HBeAg, 99 (46%) patients received anti-viral therapy, and mean baseline HBV DNA was 3.78 ± 2.28 log IU/mL vs. 4.36 ± 2.13 log IU/mL respectively (P = 0.05). In those who achieved HBsAg seroclearance, serum IL-15 and GM-CSF levels decreased significantly from Year -3 to Year 0 (P = 0.017 and 0.05 respectively). When compared to controls, only serum IP-10 level was significantly lower at Year 0 than at Year -3 in patients with HBsAg seroclearance. Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance. There was no correlation between serum IP-10 and HBsAg levels around the time of HBsAg seroclearance. CONCLUSION: Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance.
Asunto(s)
Citocinas/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/inmunología , Adulto , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Humanos , Interleucina-10/metabolismo , Interleucinas , Cirrosis Hepática/inmunología , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Tenofovir disoproxil fumarate has been used in chronic hepatitis B patients with suboptimal virologic response to nucleos(t)ide analogues. The efficacy of tenofovir switch therapy has not been well studied in Asian patients. AIM: To evaluate the efficacy of tenofovir switch therapy in nucleos(t)ide-experienced patients, and identify the factors associated with treatment response of tenofovir switch therapy. METHODS: Nucleos(t)ide-experienced hepatitis B e antigen-positive and -negative patients prescribed with tenofovir were retrospectively identified and recruited for prospective analysis. Hepatitis B virus (HBV) DNA and other biochemical parameters were monitored in regular 3-6 monthly follow-up visits. Primary efficacy endpoint was maintained-virologic response with tenofovir switch therapy, defined as undetectable HBV DNA (<20 IU/mL) until the last follow-up visit. RESULTS: An overall of 214/252 (84.9%) patients achieved maintained-virologic response after 22 (7-55) months of tenofovir switch therapy. On multivariate analysis, a lower HBV DNA level at the time of switching to tenofovir was an independent factor associated with treatment efficacy. Maintained-virologic response after switching to tenofovir was achieved in 177/190 (93.2%) patients with HBV DNA <20 000 IU/mL vs. 37/62 (59.7%) patients with HBV DNA ≥20 000 IU/mL (P < 0.001). Absence of genotypic resistance to lamivudine or adefovir dipivoxil was not associated with improved treatment outcome. CONCLUSIONS: Tenofovir switch therapy is an effective treatment strategy in nucleos(t)ide-experienced chronic hepatitis B patients. However, in patients with HBV DNA ≥20 000 IU/mL at the time of switching to tenofovir, the chance of achieving maintained undetectable HBV DNA is significantly reduced.