SIRS, We read with great interest the review article by Wantuck et al. discussing the epidemiology and treatment outcomes of hepatitis C virus (HCV) genotypes 4 through 6.1 HCV genotype 5 (HCV-5) is an uncommon genotype with few reports outside South Africa, including a cluster of the infection described in Greece.
2Although a fixed 48-week course of pegylated interferon (PegIFN) and ribavirin is currently recommended, this suggestion is not based on solid evidence.1 Indeed, most therapeutic data come from retrospective studies with small sample sizes and extreme heterogeneity regarding treatment modalities (e.g. use of standard interferon) and patient sampling (e.g. inclusion of relapsers). As stated by Wantuck et al., HCV-5 has been claimed to be an easier to treat genotype (as compared with HCV genotype 1), showing response rates similar to genotypes 2 and 3. However, this has been questioned by other reports showing an overall response more similar to genotype 1.3 Clearly, comparison with other HCV genotypes is not a solid basis for standardising treatment of HCV-5. Prospective trials, to date hampered by obvious difficulties in patient sampling, are urgently needed to establish the optimal therapeutic strategy for HCV-5. This includes assessment of the potential cost utility of a response-guided approach, as originally adopted for HCV genotype 1 and recently proposed for genotype 6. Including 27 treatment-na€ ıve patients with HCV-5 infection, we have prospectively assessed the efficacy of combined anti-viral treatment showing a sustained viral response (SVR) of 63%.3 Congruently with previous reports, our patients were more frequently females of advanced age, characterised by high baseline viraemia and advanced hepatic fibrosis. Albeit adequately powered studies are warranted for definitive conclusions, it seems that neither these factors nor IL-28B polymorphisms, known to adversely affect treatment of other HCV genotypes, 4 impact therapy of HCV-5. 5 In our study, 16/27 patients (59.3%) had undetectable HCV-RNA by week 24, all but one of whom (85.2%) went on to achieve a 48-week response. 3 Nevertheless, a substantial relapse rate, in our setting as high as 26.1%, may decisively discourage a fixed shortening of treatment duration to 24 weeks. However, our finding of an excellent predictive value of early viral dynamics on SVR offers a brand new perspective: a response-guided schedule may be a viable option for patients with HCV-5 infection. More intuitively, a 24-week course may be enough for those achieving a negative viral load by week 4 of treatment, as indicated by the high positive predictive value (93.8%) of this variable on sustained virological response.3 Contrarily, adoption of a stopping rule may be the most reasonable option for patients in whom HCV-RNA remains positive by week 12 of therapy, as these patients are unlikely to respond to the 48-week treatment.
3In conclusion, before attempting to evaluate the newly approved (but costly) protease inhibitors boceprevir and telaprevir or newer age...
