المؤلفون: MARRONE, A.¹ (AUTHOR), ZAMPINO, R.¹ (AUTHOR), KARAYANNIS, P.² (AUTHOR), CIRILLO, G.³ (AUTHOR), CESARO, G.¹ (AUTHOR), GUERRERA, B.¹ (AUTHOR), RICCIOTTI, R.¹ (AUTHOR), MIRAGLIA DEL GIUDICE, E.³ (AUTHOR), UTILI, R.⁴ (AUTHOR), ADINOLFI, L. E.¹ (AUTHOR), RUGGIERO, G.¹ (AUTHOR)

المصدر: Alimentary Pharmacology & Therapeutics. Oct2005, Vol. 22 Issue 8, p707-714. 8p. 3 Charts.

مصطلحات موضوعية: *HEPATITIS B virus, *DRUG resistance, *VIRUS inhibitors, *ANTIVIRAL agents, *LIVER diseases, *VIRAL hepatitis, *GENETIC mutation, *THERAPEUTICS

مستخلص: Background : Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. Aim : To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. Methods : Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. Results : ‘Polymerase region’: M204V/I variants were found in all group A patients, but in none of group B1 ( P = 0.0007) and in four of nine of group B2 (44%; P = 0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. ‘Core promoter’: the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P = 0.03) of group B1 and one of nine (11%; P = 0.002) of group B2 patients. ‘Precore’: the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five ( P = 0.004) of group B1 and one of nine (11%; P = 0.002) of group B2. Conclusions : Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation. [ABSTRACT FROM AUTHOR]

المؤلفون: Zampino, R¹, Marrone, A¹, Cirillo, G², del Giudice, E. Miraglia², Utili, R¹, Karayiannis, P³, Liang, T. J⁴, Ruggiero, G¹

المصدر: Journal of Viral Hepatitis. May2002, Vol. 9 Issue 3, p183-188. 6p.

مصطلحات موضوعية: *HEPATITIS B, *VIRAL hepatitis, *INTERFERONS

مستخلص: We analysed the hepatitis B virus (HBV) core-promoter (CP) and precore (PC) regions before, during and after interferon treatment in young Caucasian cancer survivors who had acquired HBV infection during chemotherapy for malignancies. Fourteen patients with chronic hepatitis B [hepatitis B e antigen (HBeAg) /HBV-DNA positive] received α-2a interferon (IFN), 5 MU/m2 t.i.w. for 12 months. HBV CP and PC region sequences were analysed following polymerase chain reaction (PCR) amplification. Sera from responders were studied at: T0 (before starting IFN), T1 [at alanine aminotransferase (ALT) peak preceding HBeAg seroconversion], T2 (at ALT normalization), T3 (at end of IFN) and T4 (at one year after IFN) and in nonresponders at time points T0 , T3 and T4 . Amplified HBV-DNA was cloned and sequenced automatically. Six of 14 patients (43%) responded to IFN treatment. Five of the six (83%) responders displayed the double CP mutation A1762T/G1764A always in association with a T1753C change. None of the nonresponders showed these mutations at any time point. The G1896A change creating the PC stop codon mutation was never detected in any of the patients. In our cancer survivors, IFN-induced HBeAg/anti-HBe seroconversion appeared to correlate with CP mutations and was not influenced by previous chemotherapy. These mutations in addition to low HBV DNA levels and elevated ALT can be considered favourable factors of response to IFN-induced anti-HBe seroconversion. [ABSTRACT FROM AUTHOR]