Hepatitis B treatment

Chronic hepatitis B Treatment of chronic hepatitis B in adults with active viral replication and persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. 

During the last 10 years, hepatitis B treatment has made significant progresses. For example, two biologies have been approved by the FDA, namely, interferon-a (IFN-a) and Pegylated-interferon-a (PEG-IFN-a). Also on the market are five small molecule... 

Wang, J.P., Feng, S.S., Wang, S., Cben, Z.Y., 2010. Evaluation of cationic nanoparticles of biodegradable copolymers as siRNA delivery system for hepatitis B treatment. International Journal of Pharmaceutics 400 (1—2), 194—200. 

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. 

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

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

Hepatocellular carcinoma (HCC) develops in patients with chronic liver diseases associated with hepatitis B and hepatitis C vims infections with high incidences. Here, an acyclic retinoid has been shown to suppress the posttherapeutic recurrence after interferon-y or glycerrhicin treatment in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induced the disappearance of serum lectin-reactive a-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of... 

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... 

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. 

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. 

In conclusion, IFNs have proven to be invaluable tools in the fight against chronic viral hepatitis. In these indications, their antiviral properties play a major role and it remains unclear whether their immunomodulatory properties are also important. Disappointing results obtained with purely immunomodulatory molecules, such as interleukins or Toll-like receptor agonists suggest that, if immunomodulation plays any role, potent inhibition of viral replication is also needed. The role of IFNs in the treatment of viral infections other than hepatitis B and C remains elusive. 

Flink HJ, van Zonneveld M, Hansen BE, de Man RA, Schalm SW, Janssen HL (2006b) Treatment with Peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B HBsAg loss is associated with HBV genotype. Am J Gastroenterol 101 297-303... 

Hong SH, Cho O, Kim K, Shin HJ, Kotenko SV, Park S (2007) Effect of interferon-lambda on replication of hepatitis B virus in human hepatoma cells. Virus Res 126 245-249 Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di BiscegUe A, Peters M, Waggoner JG, Park Y, Jones EA (1986) Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 315 1575-1578 Horiike N, Onji M (2003) Combination therapy with interferon-alpha and ribavirin as im-munomodulators in patients with chronic hepatitis C. J Gastroenterol 38 302-304... 

Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL (2006) A treatment algorithm for the management of chronic hepatitis B virus infection in the United States an update. Clin Gastroenterol Hepatol 4 936-962 Kim KI, Sasase N, Taniguchi M, Mita K, Kinoshita K, Togitani T, Shikata M, Kimura N, Izawa S, Ohtani A, Nakao K, Muramoto Y, Kim SR, Nabeshima S, Ishii F, Tanaka K, Hayashi Y (2005) Interferon-beta induction/interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C. Int J Clin Pharmacol Res 25 71-76... 

Munoz R, Castellano G, Eernandez I, Alvarez MV, Manzano ML, Marcos MS, Cuenca B, Solis-Herruzo JA (2002) A pilot study of beta-interferon for treatment of patients with chronic hepatitis B who failed to respond to alpha-interferon, J Hepatol 37 655-659... 

Sarin SK, Sood A, Kumar M, Arora A, Amrapurkar D, Sharma BC, Konar A, Chawla YK, Jain RK, Nanda V, Kumar A, Hissar S, Lavate P, Lahoti D (2007) Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B. Am J Gastroenterol 102 96-104... 

Shi M, Wang RS, Zhang H, Zhu YF, Han B, Zhang Y, Jin LJ, Yang ZJ, Xu YP (2006) Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigennegative Chinese patients and its suppression of lamivudine-resistant mutations, J Antimicrob Chemother 58 1031-1035... 

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