Viral genotyping

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. 

Simmonds, P et al. (1994). A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 19, 1321-1324 (Letter). 

Peginterferon alfa-2a/Ribavirin tablet combination The recommended dose of peginterferon alfa-2a when used in combination with ribavirin tablets is 180 meg (1 mL vial or 0.5 mL prefilled syringe) subcutaneously once weekly. The recommended dose of ribavirin and duration for the peginterferon alfa-2a/ribavirin tablet combination therapy is based on viral genotype. 

E. Therapeutic response A randomized trial compared treatment with PEG-Intron, once weekly, to treatment with Intron A (interferon alfa-2b), three times weekly, in 1219 previously untreated adults with chronic hepatitis from HCV infection. Patients were treated for 48 weeks. Response to treatment was defined as undetectable HCV RNA (less than 100 copies per ml) and normalization of the liver enzyme alanine aminotransferase (ALT) at 24 weeks post-treatment. Response rates to the l.Opg/kg PEG-Intron doses and to Intron A were 24% and 12%. Patients receiving PEG-Intron with viral genotype 1 had a response rate of 14%, while patients with other viral genotypes had a 45% response rate. 

Siimnonds P, Alberti A, Alter HJ, et al. A proposed systemforthe nomenclature of hepatitis C viral genotypes. Hepatology 1994 19 1321-1324. Heintges T, Wands JR. Hepatitis C virus Epidemiology and transmission. Hepatology 1997 26 521-526. 

DATABASE COMPARISON AND RESULTS TYPICAL RESULTS OF BACTERIAL AND VIRAL GENOTYPING... 

Interim results from the SPRINT-1 phase 2 trial of boceprevir (SCH 503034) have been released. In subjects who received boceprevir plus interferon-a and ribavirin, viral RNA loads were suppressed at week 12 in between 70 and 79% of subjects infected with genotype 1 HCV, compared with only 34% in the interferon-o/ ribavirin standard of care arm (www.sch-plough.com/schering plough/news/release. jsp releaseID = 1064540). However, it is not yet known if this enhanced early response will translate into sustained response. 

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). 

Detailed sub-analyses of a variety of clinical trials have provided information about host and viral factors influencing the virologic response in the treatment of chronic hepatitis C. The most important factors include the HCV genotype, HCV RNA concentration at baseline, age, weight, gender, ethnicity, liver enzymes, and stage of fibrosis (Mihm et al. 2006 Pawlotsky 2005). 

HavUr DV, Richman DD (1996) Viral dynamics of HIV implications for drug development and therapeutic strategies. Ann Intern Med 124(11) 984—994 Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, Foms X, Erhardt A, Cronlein J, Chaves RL, Yong CL, Nehmiz G, Steinmann GG (2004) Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype I patients. Gastroenterology 127(5) 1347-1355... 

Johansen, K., Mannerqvist, K., Allard, A., Andersson, Y., Burman, L. G., Dillner, L., Hedlund, K. O., Jonsson, K., Kumlin, U., Leitner, T., Lysen, M., Thorhagen, M., et al. (2008). Norovirus strains belonging to the GII.4 genotype dominate as a cause of nosocomial outbreaks of viral gastroenteritis in Sweden 1997-2005. Arrival of new variants is associated with large nation-wide epidemics. /. Clin. Virol. 42,129-134. 

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