RESUMO
BACKGROUND & AIMS: It was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with <2log hepatitis B virus (HBV) DNA decline at week 12 of a 48-week peginterferon alfa-2a (PEG-IFN) treatment course achieved a sustained response (SR). We aimed at validating this stopping rule in two independent trials. METHODS: HBeAg-negative patients receiving 48 or 96 weeks of PEG-IFN in the phase III registration trial (N=85) and PegBeLiver study (N=75) were stratified according to the presence of any HBsAg decline and/or 2log HBV DNA decline at week 12. SR was defined as HBV DNA <2000IU/ml and normal alanine aminotransferase 24 weeks after treatment. RESULTS: The original PARC trial included 102 patients (genotype A/D/other: 14/81/7), 25 (25%) had an SR. The validation dataset consisted of 160 patients (genotype A/B/C/D/other: 10/18/34/91/7), 57 (36%) achieved an SR. The stopping rule performed well across the two studies (p=0.001) and its negative predictive value [NPV] was 95% in the validation dataset harbouring genotypes A-D. Its performance was best for genotype D. Moreover, among the 34 patients treated for 96 weeks, none of the 7 (21%) without HBsAg decline and with <2log HBV DNA decline at week 12 achieved an SR (NPV 100%). CONCLUSIONS: We confirmed in two independent studies that the combination of HBsAg and HBV DNA levels at week 12 identifies HBeAg-negative patients with a very low chance of SR to either 48 or 96 weeks of PEG-IFN therapy.
Assuntos
DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B/sangue , Hepatite B/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Suspensão de Tratamento , Adulto , Antivirais/uso terapêutico , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) represents a severe condition that requires prophylaxis with specific immunoglobulin and lamivudine. Few studies have addressed the efficiency of other effective antiviral drugs posttransplantation or their impact on early renal function after transplantation. Herein, we have reported experience among seven transplanted patients prescribed Telbivudin (600 mg/d) while on the waiting list followed by treatment for 3 months after OLT. METHODS: Our series consisted of men with HBV-related end-stage liver disease. Once the patient started antiviral treatment, the viral load decreased rapidly while on the waiting list. All patients were evaluated for liver and renal functions immunosuppressive drug trough levels, CPK before (T0), as well as at 1 month (T1), and 3 months after liver transplant (T3). RESULTS: All patients received a CNI-based regimen. Their mean creatinine clearance (MDRD) was 72.5 mL/min at T0, 69.2 mL/min at T1, and 71.0 mL/min at T3. Neither CPK or serum transaminase levels increased throughout the study. Once HBV-DNA was cleared while on the waiting list, it remained negative throughout the follow-up period. CONCLUSION: Telbivudin prophylaxis for HBV was safe and effective without any significant deleterious effect on liver or renal function tests after liver transplantation.