Pegylated interferons for chronic hepatitis B.
ABSTRACT 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.
SourceAvailable from: Hesham N Mustafa[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.
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ABSTRACT: Introduction Condylomata acuminatum is a viral disease characterized by anogenital lesions. Routine therapeutic procedures are tissue destructive. There is evidence to indicate that interferon (IFN) alpha is effective in the treatment of this disease. Patients and methods To evaluate the biological properties, efficacy and tolerability of a new albumin-free recombinant IFN alpha-2b formulation in patients with condylomata acuminatum, 30 patients with a clinical and histopathological diagnosis of this disease were randomly assigned to receive daily intramuscular injections of IFN alpha-2b in three different short therapeutic regimens: 3 × 106 IU for 7 days; 5 × 106 IU for 4 days or 10 × 106 IU for 2 days. All the groups received approximately the same total dose (20 × 106 IU). The primary endpoint consisted of the IFN-induced pharmacodynamic markers β2M and 2’-5’ oligoadenylate synthetase (OAS), which were measured before the first administration and 24 hours after the final dose. Efficacy was evaluated 1 week after each treatment was concluded by comparing the number and diameter (largest and smallest) of the lesions with those of the initial lesions. Additionally, all patients were followed-up for 1 year. Results Serum β2M levels were increased in all patients. A dose-dependent pattern was observed for 2’-5’ OAS, since its induction was significantly higher in patients treated with 10 × 106 IU. The number of lesions was reduced in 12 patients and was increased in only two patients. In more than 60% of the patients, both diameters of the lesions were reduced, but a significant reduction was only observed with the lowest but most often repeated dose. When the groups were analyzed together, these values were also significantly lower at the end of treatment. Overall, 14 patients (46.7%) responded to the treatment. The most common adverse effects were fever, headache, chills and myalgias, none of which were serious. During follow-up, a sustained response was obtained in 62.5% of the responders evaluated with no other clinical interventions. Conclusions This new formulation clearly induces the classical biological markers of IFN in patients with condylomata acuminatum. The results also suggest that a rapid and sustained clinical response can be obtained with a short therapeutic regimen of IFN alpha. Larger, controlled studies should be performed.Piel 07/2009; 24(6):292-299. DOI:10.1016/S0213-9251(09)71644-2
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ABSTRACT: Although chronic hepatitis B (CHB) is a global health threat, it is now a preventable and treatable disease. Seven agents have been approved for the treatment of CHB. Although many patients prefer potent long-term nucleos(t)ide analogues (NAs) as the first-line therapy because they are convenient to use and well-tolerated, a finite duration of pegylated interferon (PEG-IFN) is still an attractive strategy because it provides higher rates of off-therapy host immune control over hepatitis B virus (HBV) compared with NAs. In addition, the rates of HBeAg/HBsAg loss or seroconversion increase over time in patients who respond to PEG-IFN therapy. Nevertheless, these benefits are limited to 30% of all patients, and significant adverse effects are still a concern. Therefore, patients who can benefit most from PEG-IFN therapy should be more carefully selected according to baseline host and viral predictors, such as age, ALT level, viral load, HBV genotype and HBV mutants. In addition, on-treatment predictors including HBV DNA, HBeAg and HBsAg kinetics, can help decide who should continue or discontinue PEG-IFN and shift to NA. Understanding these factors can help determine personalized PEG-IFN therapy for CHB patients. In the near future, the treatment paradigm of CHB should be tailored on the basis of viral (HBV DNA level, HBV genotype and HBV mutants) and host (age, gender, ALT level and host genetic polymorphisms) factors, disease status (stage of fibrosis and comorbidities) and the selection of antiviral agents (immunomodulatory effect, antiviral potency, adverse effects and rate of drug resistance).Liver international: official journal of the International Association for the Study of the Liver 02/2014; 34 Suppl 1:112-9. DOI:10.1111/liv.12400 · 4.41 Impact Factor