with interferon of chronic hepatitis B associated with antibody to hepatitis B e antigen


Filippo Olivesi, Albert0 Demartini, Torrani Cerenzia snd Fertuccio

Pierluigi Bonino


Paola Manzini,


Divslon o,G‘, MolmroeHospilal, Torino. rm,y


of HBV replication

(serum HBV-DNA

and intrahepatic HBcAg)

and markers

of HBV-induced

(IgM anti-

HBc positive) liver disease in anti-HBe-positive patients characterize a peculiar form of chronic hepatitis B. This form of hepatitis B prevails in the Mediterranean Basin, Middle and Far East and is associated with the infection of an HBV variant that lacks the capacity to produce HBeAg. We analysed the results of interferon treatment of 90 patients with chronic anti-HBe-positive hepatitis iacluded in four randamided controlled trials. Interferon inhibited viral replication to undetectable lswls and ALT normalized in about 70% of patients. However, the effect was transient in the majority of cscs and hepatt:is B relapsed in 41 to 90% of patients. A discrepancy in the rate of relapser could be explained by a significant difference in patients populations with a higher prevalence ofcirrhotic pat;ents in studies with poorer response. Therefore, in advanced anti-HBe-positive chronic hepatitis B, interferon shows a lower efficacy than in HBeAg-positive patients. The earlier treatment starts, the more efficacious is the response to interferon. Future clinical trials should focus on higher doses far longer periods, repeated courses or on combination therapy with nucleoside analogs or immune-stimulant drugs.

can start at two different

codons (AT&)

which are sepa-

Chronic hepatitis B, defined by persistence of productive HBV infertion (HBV-DNA in serum and hepatitis B core antigen (HBcAg) in liver) and antiviral immune response (IgM anti-HBc antibody), is not only present in hepatitis B e antigen (HBeAg)-positive patients (1). but also in HBeAg-negative patients with the homologous antibody (anti-HBe) (2-7). Usually seroconversion from

rated by 87 nucleotides coding for 29 amino acid residues, named the pre-C region. Translation starting at the second ATG produces a nucleocapsid protein (HBcAg), while starting at the first ATG determines the synthesis of a precursor protein of HBeAg in which a signal peptide (pre-C) and a carboxy terminal sequence are cleaved off

HBeAg to anti-HBe results in loss of viraemia and in the extinguishment of histological activity. In some anti-HBewsitive oatients serum HBV-DNA. intraheDatic HBcAe and HBV-induced (IgM anti-HBc positive) liver disease persist (2-7). Recent findings have shown that a peculiar HBV variant, which lacks the capacity to release HBeAg into the blood, is responsible for anti-HBe-positive hep atitis B (8-17). HBeAg is a non-structural, secretory protein. encoded by the C gene of HBV-DNA. Translation of the C gene

during maturation and secretion (18.19). A peculiar genetic variation, responsible for the lack of secretion of HBeAe. was found in most (97%) HBV-DNAs so far characterized from patients with anti-HBe-positive chronic hepatitis B (S-17). This variation consists of a single base change from a tryptophan (TFG) codon to a nonsense codon (TAG) in the pre-C region and results in a cessation of translation of the signal peptide, preventing secretion of HBeAg (8-17). Whether chronic anti-HBepositive hepatitic originates invariably from a HBeAg




form by positive relectmn of HBeAg defectwc virus or it evolves from ao acute heparitis due to HBV variant remains unknown. Whtcheve: the origin of tbvs form of chronic hepatitis B might be, it presents a peculiar natural coarse with unirequent spontaneous remiwon and a propensity to rapid transition to cirrhosis (7). These features

ALT to normal vabtes. Sanrantonio et al. included 18 p”liens (median age 32 years) in a study wth lymphoblastold interferon (IO MU. three times weekly for 24 weeks) (22). Ten patients were treated and eight wved al comroB. At the end of treatment. serum HBV-DNA wac undetectable (less than I pg/ml) in all treated patients

indicate an urgent need for therapy. We analysed in thn review the results of four randomized controlled trials using interferon with a follow-up of at least 12 months after the end of treatment. Fattovich et al. (20) enrolled 60 patients (median age 35 year

Treatment with interferon of chronic hepatitis B associated with antibody to hepatitis B e antigen.

Persistence of HBV replication (serum HBV-DNA and intrahepatic HBcAg) and markers of HBV-induced (IgM anti-HBc positive) liver disease in anti-HBe-pos...
255KB Sizes 0 Downloads 0 Views