HEPATITIS-C VIRUS - BIOLOGICAL AND CLINICAL CONSEQUENCES OF GENETIC-HETEROGENEITY

Hepatitis C Virus infection accounts for the majority of post-transfus ion and sporadic hepatitis. In Western Europe, anti-HCV is detected in 0.4-1.5% of healthy blood donors. There is a high frequency of progre ssive chronic hepatitis, ranging from 50 to 80%, which leads to cirrho sis in 20-50% of patients after 10-20 years. Viremic patients with min imal biochemical abnormalities may have chronic liver disease histolog ically. There is growing evidence that virological features of HCV are associated with different clinical manifestations and response to the rapy. The RNA genome consists of a 5' and 3' Untranslated Region, a st ructural domain encoding the core and envelope proteins, and a non-str uctural domain. Different HCV isolates show a high sequence heterogene ity, which has led to the classification of currently six genotypes an d several subtypes. There is a marked difference in the geographic dis tribution of HCV genotypes, with types 1, 2 and 3a being most frequent ly found in western countries. In The Netherlands, subtype 1b accounts for approximately 60% of all cases of chronic HCV. Serologic diagnosi s based on recombinant C-100 antigens (first generation immunoassays) only reliably detected type 1, due to the heterogeneity of the NS4 reg ion; inclusion of more conserved proteins c22 and c33 (second generati on assays) has largely improved sensitivity of anti-HCV testing. Genot ype 1b is associated with more severe liver disease and with lower res ponse rates for antiviral therapy, compared with types 2 and 3. Quasis pecies nature and escape mutants may enable viral persistence and the development of chronic liver disease. As cross-reactivity between geno types is unlikely, prevention of HCV disease may be dependent on the d evelopment of multivalent vaccines.