Hepatitis genotypes

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. 

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... 

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). 

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... 

Enomoto M, Tamori A, Kohmoto MT, Hayashi T, Jomura H, Habu D, Sakaguchi H, Takeda T, Kawada N, Seki S, Shiomi S, Koh N, Nishiguchi S (2007) Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection. J Interferon Cytokine Res 27 201-207... 

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... 

Fig. 1 Sustained virologic response rates from pivotal trials in patients with chronic hepatitis C according to treatment regimen and HCV genotype. For references see text...

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). 

Diago M, Hassanein T, Rodes J, Ackrill AM, Sedarati F (2004) Optimized virologic response in hepatitis C virus genotype 4 with peginterferon-alpha2a and ribavirin. Ann Intern Med 140(l) 72-73... 

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... 

Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, Sarrazin C, Harvey J, Brass C, Albrecht J (2004) Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 40(6) 993-999... 

Zeuzem S, Buti M, Ferenci P, Sped J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O, NovieUo S, Brass C, Albrecht J (2006) Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol 44(1) 97-103... 

For HIV HIV RNA, baseline HIV genotypic resistance test For HIV treatment Hepatitis B tests (hepatitis B surface antibody and antigen, hepatitis B envelope antigen, and HBV DNA), liver function tests... 

If a patient has renal or hepatic impairment or a poor metabolizer genotype, adjust chemotherapy doses if necessary. 

Interferon-a is currently the only agent of proven clinical efficacy in the treatment of hepatitis C however, only 10 to 51% of patients enrolled in clinical trials showed a sustained improvement (Davis et al., 1989 Di Bisceglie et al, 1989). Current interferon-a therapy is, typically, 3 million units, thrice weekly, given subcutaneously for 12 months. Both HCV genotype and pretreatment viral load have been shown to influence the response to interferon (Lau et al., 1993 Yoshioka et al., 1992). 

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