Hepatitis chronic

BFNs are classified into three groups a, (3, and y, and the different classes are produced from different cell types. Recombinant BFN-a is used in the treatment of chronic hepatitis B and C. 

Interferon alfacon-1 (Inferax ), interferon alfa-2b (IntronA ), and interferon alfa-2a (Roferon -A) are applied in the treatment of chronic hepatitis B and C and some malignancies, especially hairy cell leukemia. IFN-a proteins induce the expression of antiviral, antiproliferative and immunomodulatory genes. 

Successful treatment with IFN-a also includes patients with chronic hepatitis B virus (HBV) infections. Despite the availability of an efficient vaccine, chronic... 

HBV infection remains a major worldwide public health problem. The World Health Organization estimates that there are still 350 million chronic carriers of the vims, who are at risk of developing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The success of IFN-a treatment - mainly performed as combined treatment with adenine-arabinoside - has been measured by the normalization of liver enzymes, loss of HBe antigen and of detectable viral DNA in the serum of patients. It has been estimated from several clinical trials that as many as 40% of treated HBV patients would respond to therapy with IFN-a or combined treatment with nucleoside analogues and IFN-a. 

Hoofnagle JH, Seeff LB (2006) Peginterferon and ribavirin for chronic hepatitis C. New Engl J Med 355 2444-2451... 

Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, Dienstag JL, Heathcote EJ, Little NR, Griffiths DA et al, (2003) Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 125 1714-1722... 

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C a randomised trial. Lancet 358 958-965... 

Han Nl, Lee YS, Choi H, Choi JY, Yun SK, Cho SH, Han JY, Yang JM, Ahn BM, Choi SW, Lee CD, Cha SB, Sun HS, Park DH (2002) PCNA expression and electron microscopic study of acinus-forming hepatocytes in chronic hepatitis B. Korean J Intern Med 17 100-106 Herve F, Urien S, Albengres E, Duche JC, TiUement IP (1994) Drug binding in plasma. A summary of recent trends in the study of drug and hormone binding. Qin Pharmacokinet 26 44-58... 

Stauber RE, Stadlbauer V (2006) Novel approaches for therapy of chronic hepatitis C, J Clin Virol 36 87-94... 

Adefovir in its prodrug form, adefovir dipivoxil, is indicated in the treatment of chronic HBV infections (chronic hepatitis B), where, if administered orally as a single dose of lOmg per day, HBV DNA load is reduced significantly (>31ogio) over a 1- or 2-year period (Hadziyannis et al. 2005). 

In addition to the NRTI lamivudine (3TC) and the NtRTI adefovir dipivoxU and tenofovir disoproxil fumarate (which has been recently licensed for the treatment of chronic hepatitis B), two other nucleoside analogues, that is, entecavir and L-dT (tel-bivudine) (Fig.4aa), have been licensed for the treatment of HBV infections. Two other compounds 3 -Val-L-dC (valtorcitabine) and L-FMAU (clevudine) (Fig. 4aa) are in clinical development for the treatment of HBV infections, and yet two other compounds, that is, racivir and elvucitabine (Fig. 3), yield potential for the treatment of both HBV and HIV infections. 

Zoulim F (2006) Entecavir a new treatment option for chronic hepatitis B. J Clin Virol 36 8-12... 

Abstract In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindemnann. Subsequently, the IFN-a gene was cloned, fully sequenced and IFN-a was produced in recombinant form. Recombinant IFN-a is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections. 

Different forms of IFN-a have been available for the treatment of chronic hepatitis B and C, including IFN-a2a and IFN-a2b. The administered dose was 3-5 megaunits three times a week subcutaneously. 

Table 3 Pharmacological parameters of pegylated IFN-a molecules approved for the treatment of chronic hepatitis C...

The choice of IFN-a as a potential treatment for chronic hepatitis C in 1986 was empirical (Hoofnagle et al. 1986). At this time, the causative agent of chronic non-A, non-B hepatitis had not yet been identified, and there was no way of evaluating HCV replication or, thus, the antiviral activity of a drug. In the first cohort of 10 patients with chronic non-A, non-B hepatitis treated with IFN-a, a significant decline in alanine aminotransferase (ALT) levels was observed in 8 patients, and liver histology had improved at the end of therapy in the three patients who were biopsied (Hoofnagle et al. 1986). Ten years later, 5 of the 10 patients were free of infection (Lau et al. 1998). 

Several studies have tested IFN-p for chronic hepatitis C, achieving response rates similar to those obtained with IFN-a and with similar or fewer adverse effects (Barbaro et al. 1999 Castro et al. 1997 Habersetzer et al. 2000 Montalto et al. 

IFN-a was first nsed empirically in chronic hepatitis B in 1986 (Peters et al. 1986). The effect of hnman recombinant IFN-a on lymphocyte proliferation and differentiation was stndied in 18 patients with chronic hepatitis B. Inhibition of immnnoglob-nlin synthesis was observed, and the anthors postnlated that the immnnomodnlatory effect of IFN-a could be important in the therapentic response of chronic hepatitis B (Peters et al. 1986). The first study to evaluate the antiviral efficacy of IFN-a involved nine patients, who received different doses administered three times a week for two weeks. Two of them entered snstained remission, with nndetectable HBV DNA, loss of HBeAg, and ALT normalization (Dooley et al. 1986). Two forms of IFN-a have been used in the treatment of chronic hepatitis B, namely standard and pegylated IFN-a. 

Drugs such as ribavirin that may directly reduce FIDV replication and specific inhibitors of HBV replication such as lamivudine and adefovir dipivoxU have been tested in combination with IFN-a in patients with chronic hepatitis D. 

Thus, ribavirin is ineffective in chronic hepatitis D, whether given alone or in combination with IFN-a. 

A recent randomized multicenter trial compared the efficacy of pegylated lFN-a2a monotherapy, adefovir monotherapy, and the pegylated lFN-a2a/adefovir combination administered for 48 weeks to patients with chronic hepatitis D. Adefovir did not inhibit HDV replication, and the combination had no additional benefit compared with pegylated IFN-a monotherapy in terms of the HDV RNA level (Yurdaydin et al. 2006). 

Akarca US, Ersoz G, Gunsar F, Karasu Z, Santas E, Yuce G, Batur Y (2004) Interferon-lamivudine combination is no better than lamivudine alone in anti-HBe-positive chronic hepatitis B. Antivir Ther 9 325-334... 

Bain VG, Kaita KD, Yoshida EM, Swain MG, Heathcote EJ, Neumann AU, FisceUa M, Yu R, Osborn BE, Cronin PW, Ereimuth WW, McHutchison JG, Subramanian GM (2006) A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 44 671-678... 

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