Hepatitis C, chronic

Antibodies against HCV (anti-HCV) in the blood indicate infection with the HCV. If the infection persists for more than 6 months and viral replication is confirmed by HCV RNA levels, then the person has chronic hepatitis C. Chronic disease may be due to an ineffective host immune system against the HCV. Cytotoxic T lymphocytes are ineffective in eradicating the HCV, thus allowing persistent damage to hepatic cells. Therefore, immunocompromised individuals are less likely to eliminate HCV.12... 

Mycosis fungoidesb Condyloma acuminata0 Chronic hepatitis B Hepatitis C Chronic hepatitis D... 

Hepatitis C, chronic myelogenous leukemia, hairy cell leukemia... 

Roferon-A Interferon alfa-2a Hoffman- LaRoche 6/1986 Hairy cell leukemia/ AIDS-related Kaposi s sarcoma/hepatitis C/chronic myelogenous leukemia E. coli... 

Similar to HBV, infections with hepatitis C virus (HCV) have a high rate of progression from an acute to a chronic state that frequently leads to cirrhosis or hepatocellular carcinoma [2]. Monotherapy for HCV infection with IFN-a or combined therapy with ribavirin and IFN-a is associated with initial rates of response as high as 40%. The rates of sustained responses are, however, lower and also depend on the viral genotype. In patients infected with HCV genotype 2 or 3, the response was maximal after 24 weeks of treatment, whereas patients infected with genotype 1 -the most frequent in the USA and Europe - required a minimum treatment course of 48 weeks for an optimal outcome. 

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... 

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

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... 

Reiser M, Hinrichsen H, Benhamou Y, Reesink HW, Wedemeyer H, Avendano C, Riba N, Yong CL, Nehmiz G, Steinmann GG (2005) Antiviral efficacy of NS3-seiine protease inhibitor BlLN-2061 in patients with chronic genotype 2 and 3 hepatitis C, Hepatology 41 832-835... 

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

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. 

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). 

HCV infection is rarefy diagnosed in the acute phase, as most acutely infected individuals are asymptomatic. Between 50% and 90% of patients develop chronic infection, however, and this warrants early therapy. After occupational exposure with a known date, treatment should not be started before the acute episode characterized by alanine aminotransferase elevation, but it should always be started within 24 weeks after the onset of symptoms. The optimal treatment schedule for acute hepatitis C is controversial. Pegylated IFN-a monotherapy at the standard dose for 24 weeks yielded SVR rates close to 100% in symptomatic patients referred to tertiary care centers (De Rosa et al. 2006 Jaeckel et al. 2001 Santantonio et al. 2005 Wiegand et al. 2006). Shorter therapy may be envisaged (Calleri et al. 2007). Combination with ribavirin is recommended if a first course of pegylated IFN-a monotherapy fails to eradicate the infection. Viral elimination appears to be independent of the HCV genotype and the HCV RNA level (Calleri et al. 2007 De Rosa et al. 2006 Jaeckel et al. 2001). 

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. 

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... 

Bain VG, Marotta P, Kaita K, Yoshida E, Swain MG, Bailey R, Neumann AU, Cronin PW, McHutchison JG, Pulkstenis E, Subramanian GM (2007) Comparable antiviral response rates with albumin interferon alpha-2b dosed at Q2W or Q4W intervals in naive subjects with genotype 2 or 3 chronic hepatitis C. J Hepatol 46 S7... 

Balan V Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfleld RR, Davis GL, Neumann AU, Osborn BE, Ereimuth WW, Subramanian GM (2006) A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy, Antivir Ther 11 35 5... 

Barbaro G, Di Lorenzo G, Soldini M, Giancaspro G, PeUiceUi A, Grisorio B, Barbarini G (1999) Intravenous recombinant interferon-beta versus interferon-alpha-2b and ribavirin in combination for short-term treatment of chronic hepatitis C patients not responding to interferon-alpha. Scand J Gastroenterol 34 928-933... 

Bocher WO, Schuchmann M, Link R, Hillenbrand H, Rahman F, Sprinzl M, Mudter J, Lohr HF, Galle PR (2006) Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon-alpha therapy. Liver Int 26 319-325... 

BriUanti S, Garson J, FoU M, Whitby K, Deaville R, Masci C, MigUoU M, Barbara L (1994) A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology 107 812-817... 

Castro A, Suarez D, Inglada L, CarbaUo E, Dominguez A, Diago M, Such J, Del Olmo JA, Perez-Mota A, Pedreira J, Quiroga JA, Carreno V (1997) Multicenter randomized, controlled study of intramuscular administration of interferon-beta for the treatment of chronic hepatitis C. J Interferon Cytokine Res 17 27-30... 

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