Pegylated interferons for chronic hepatitis B

Divisione di Gastroenterologia, Instituto di Clinica Medica Policlinico, University di Palermo, Piazzale Delle Cliniche 2, 90127 Palermo, Italy.
Antiviral Research (Impact Factor: 3.94). 11/2003; 60(2):87-9. DOI: 10.1016/j.antiviral.2003.08.015
Source: PubMed


Conventional interferon therapy has been used for the treatment of chronic hepatitis B (CHB) for many decades. However, the use of interferon has been limited by its short half-life and high incidence of dose-related side effects. A meta-analysis investigating the short- and long-term consequences of interferon therapy showed that, whilst interferon therapy was beneficial in the short term, resulting in normalization of alanine aminotransferase (ALT) levels, loss of HBeAg, 'e' seroconversion and suppression of hepatitis B virus (HBV) DNA, the long-term benefits were less substantial. Pegylation of interferon (peginterferon alpha-2a [40 kDa]) led to improved pharmacokinetic and pharmacodynamic profiles, which translated to superior efficacy compared with conventional, nonpegylated interferon, in the treatment of chronic hepatitis C. A phase II study investigated the safety and efficacy of peginterferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B. The results demonstrated a rapid and dramatic reduction in HBV DNA levels, HBeAg clearance and normalization of ALT with peginterferon alpha-2a (40 kDa) compared with conventional interferon. Furthermore, peginterferon alpha-2a (40 kDa) conferred a notably improved treatment response in patients with 'difficult-to-treat' hepatitis B infection. In conclusion, peginterferon alpha-2a (40 kDa) is a promising emerging therapy for CHB.

3 Reads
  • Source
    • "Occasionally, a prolonged benign course is marked by increased serum transaminase value for more than 16 weeks, relapses are rare. Cholestatic hepatitis with prolonged deep jaundice and pruritus is unusual (Craxi and Cooksley, 2003). Physical examination reveals mild tender hepatomegaly in over 70% of cases. "
    [Show abstract] [Hide abstract]
    ABSTRACT: SUMMARY & CONCLUSION HBV is a Hepatotropic DNA-containing virus, discovered in 1966 by Blumberg. The virion of hepatitis B (Dane particle) consists of surface and core with a diameter of 42 nm (Kumar and Agrawal, 2004). The protein composition of HBV particles; either surface protein (HBs proteins) composed of LHBs (largest Hepatitis B proteins), MHBs (middle Hepatitis B proteins), SHBs (small Hepatitis B proteins) or core proteins; composed of HBc protein and HBe protein. The world health organization (WHO, 2004) estimated that 2 billion people have been infected by HBV worldwide; of these more than 300 millions are chronically infected carriers of whom 25% are at risk of serious illness and eventually death from cirrhosis or hepatocellular carcinoma. The prevalence of HBV infection varies markedly throughout regions of the world; highly endemic in South East Asia, moderately endemic in Eastern and Southern Europe and low endemic areas as in North America (Tsai, 2004). Concerning transmission of HBV; there is peri-natal transmission, sexual contact, blood and blood products, parentral drug abuse, opportunities for parentral infection, transmission in high endemic areas, exposure of unknown origin is still present. As regards clinical presentation and sequelae; HBV can present as acute infection, fulminant hepatic failure (FHF), chronic hepatitis, extra-hepatic manifestations, post hepatitis B cirrhosis or combinations with HDV or HCV. Occult HBV infection is characterized by the presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Concerning the diagnosis of acute and chronic hepatitis B; the advances in molecular biology techniques led to the development of hybridization and polymerase chain reaction (PCR) assays for direct determination of HBV DNA. The diagnosis of HBV infection can also be made by the detection of HBsAg or HBcAg in liver tissues by immunohistochemical staining and of HBV DNA by Southern hybridization, in-situ hybridization, or PCR. Treatment of chronic hepatitis B include Interferon therapy, nucleoside analogues such as Lamivudine, Adefovir Dipivoxil, Entecavir, Famciclovir, Emtricitabine/ coviracil, Combination therapy, Therapeutic vaccine, Gene therapy and Immunotherapy. Prophylaxis against viral B infection is highly recommended using vaccination alone or combined with hepatitis B immunoglobulin for infants and individuals at risk of exposure.
  • Source
    • "Interferon is supplemented with polyethylene glycol (PEG) which prolongs its half-life resulting in sustained antiviral response rates. Two types of PEG-IFN have been studied for HBV therapy, PEG-IFN α-2a having a large 40 kDa PEG branched and PEG-IFN α-2b with a 12 kDa PEG molecule [27]. Buster and Janssen [22] reported HBV treatment response of 19-35% by administration of peg-IFN. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis B virus (HBV) is one of the leading health problem with up to 350 million affected people worldwide including 4.5 million only in Pakistan. It has mortality rate of 0.5 to 1.2 million per year worldwide. Pakistan lies in the endemic region with 3-5% HBV carrier rate in the country. The present article reviews the literature on the treatment response of HBV prevalent in Pakistani population. The average treatment response of Lamivudine and interferon-α is 25.81% and 47.95%, respectively. Peg-Interferon was shown to be not effective against the HBV/HCV (hepatitis C virus)/HDV (hepatitis Delta virus) co-infection. The present study reveals that interferon-α is the most effective therapy available for HBV infection prevalent in Pakistani population. Genotype C & D are the most common HBV genotypes in Pakistan and are associated with increased severity and less response to interferon therapy. This poses a great challenge for physicians and researchers and further studies are needed to describe the outcome of the current therapies recommended against HBV infection in Pakistani population.
    Virology Journal 01/2011; 8(1):20. DOI:10.1186/1743-422X-8-20 · 2.18 Impact Factor
  • Source
    • "PEG-IFN is administered once weekly, resulting in a relatively continuous drug exposure during the dosing interval. Two types of PEG-IFN have been developed: a small linear 12-kDa PEG, linked to IFN α-2b (PEG-IFN α-2b), and a large branched 40-kDa PEG, linked to IFN α-2a (PEG-IFN α-2a) [16]. These molecules have different characteristics due to their difference in size and structure. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the introduction of new nucleos(t)ide analogues in recent years, peginterferon is still recommended as a potential first-line treatment option by current practice guidelines for the management of chronic hepatitis B. Peginterferon offers the advantage of higher sustained off-treatment response rates compared to nucleos(t)ide analogues because of its immunomodulatory effects. Sustained transition to the inactive hepatitis B surface antigen (HBsAg) carrier state can be achieved in about 30% of hepatitis B e antigen (HBeAg)-positive patients and 20% of HBeAg-negative patients. Recent studies have focused on identification of pretreatment and on-treatment factors that allow the selection of patients who are likely to achieve a sustained response to peginterferon therapy in order to avoid the side-effects and costs associated with unnecessary treatment. Future studies need to address whether specific virologic benchmarks can guide individualized decisions concerning therapy continuation and whether peginterferon combined with new potent nucleos(t)ide analogues improves treatment outcomes.
    Current Hepatitis Reports 11/2010; 9(4):231-238. DOI:10.1007/s11901-010-0055-1
Show more