Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B

Brunetto, M.R.; Giarin, M.; Saracco, Giorgio Maria; Oliveri, Filippo; Calvo, Pierluigi; Capra, G; Randone, A; Abate, Maria Lorena; Manzini, Paola; Capalbo, M; Piantino, P; Verme, G; Bonino, Ferruccio

doi:10.1016/0016-5085(93)90903-p

Cited by 185 publications

(122 citation statements)

References 25 publications

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“…37 At baseline, approximately half of the patients exhibited wild-type HBV and half exhibited precore stop mutants. Spontaneous HBV clearance occurred in 28% of patients infected with HBV with wild-type precore regions and none of those with precore stop mutations.…”

Section: Mutations In the Precore/core Regionmentioning

confidence: 99%

Clinical relevance of hepatitis B viral mutations

et al. 2000

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Section: Mutations In the Precore/core Regionmentioning

confidence: 99%

Clinical relevance of hepatitis B viral mutations

et al. 2000

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“…Data from previous studies in similar patient populations indicate that more than 95% of patients in the Mediterranean area are infected with the 1896 precore mutant variant. Brunetto et al 8 analyzed sera from 58 Italian patients with anti-HBe-positive chronic hepatitis B and found that precore mutant HBV was the prevalent virus in 97% of these patients. Laras et al 9 found that 100% (31 of 31) of a group of HBeAg-negative patients from Greece harbored the 1896 precore mutation and 20 (64%) also had a G to A mutation at nucleotide 1899.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 It is estimated that more than 95% of patients with HBeAgnegative chronic hepatitis B in the Mediterranean area are infected with the 1896 precore mutant HBV. 8,9 The persistence of viremia in patients with precore mutant HBV infection is frequently accompanied by persistent or intermittent elevations in serum aminotransferases. 8,10 This often leads to the complications of progressive liver disease including cirrhosis and hepatocellular carcinoma.…”

mentioning

confidence: 99%

“…8,9 The persistence of viremia in patients with precore mutant HBV infection is frequently accompanied by persistent or intermittent elevations in serum aminotransferases. 8,10 This often leads to the complications of progressive liver disease including cirrhosis and hepatocellular carcinoma. 11,12 Precore mutant chronic hepatitis B exists world wide but is particularly common in Mediterranean Europe and in Asia.…”

mentioning

confidence: 99%

“…17,18 Several studies have shown that the presence of precore mutations correlates with suboptimal responses to interferon therapy and is associated with a high rate of relapse. 8,10,19,20 Furthermore, alfa-interferon must be given by subcutaneous injection and has potentially doselimiting side effects. Therefore, there is clearly a need to evaluate alternative therapies for this group of chronic hepatitis B patients.…”

mentioning

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Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis befficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis befficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis befficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-posi

et al. 1999

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This placebo controlled, double-blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n ‫؍‬ 60) or placebo for 26 weeks (n ‫؍‬ 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26. The primary efficacy endpoint was loss of serum HBV DNA plus normalization of alanine transaminase (ALT) at week 24. A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6%) (P F .001). Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60% of lamivudine-treated patients with liver biopsy specimens available showed histological improvement (H2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis. At week 52, 27% of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepatitis B. (HEPATOLOGY 1999;29:889-896.)

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Analysis of hepatitis B virus genotypes and pre-core region variability during interferon treatment of HBe antigen negative chronic hepatitis B

et al. 1996

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The clinical importance of hepatitis B virus (HBV) genome variability has been reported recently. One example is the occurrence of hepatitis B virus pre-core mutants, which arise during spontaneous or interferon-induced seroconversion from HBeAg to anti-HBe and are thought to be selected by immune pressure. A survey of HBV pre-core mutants and viral genotypes in 35 HBeAg negative patients during interferon therapy was carried out to understand viral pathogenesis in this form of chronic hepatitis B. Seventeen patients responded to interferon therapy as assessed by the sustained normalization of serum ALT levels and the significant decrease of viremia levels. The response rate to interferon was independent of both initial serum viral DNA level and interferon doses. During interferon therapy, a significant decrease of M0 (wild-type pre-core sequence at pos. 1887-1908), M1 (TGG to TAG at pos. 1896) or M2 (TGG to TAG at pos. 1896, and GGC to GAC at pos. 1899) positive viral genomes was found in 48%, 42%, and 33% of patients, respectively. A higher response rate to interferon therapy was observed in patients infected with HBV genotype A (70%) or M0 positive strains (75%) as compared to patients infected with genotype D/E (40%) or M1/M2 positive strains (44%). The data support the hypothesis that pre-core defective HBV represent viral mutants with an increased capacity to resist exogenous alpha interferon. These findings emphasize that characterization of HBV genome variability prior to interferon therapy may help to predict antiviral response in HBeAg negative patients.

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Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B

Cited by 185 publications

References 25 publications

Clinical relevance of hepatitis B viral mutations

Clinical relevance of hepatitis B viral mutations

Analysis of hepatitis B virus genotypes and pre-core region variability during interferon treatment of HBe antigen negative chronic hepatitis B

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