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Hepatitis C genotype 6: A concise review and response-guided therapy proposal.

ABSTRACT: Hepatitis C genotype 6 is endemic in Southeast Asia [prevalence varies between 10%-60% among all hepatitis C virus (HCV) infection], as well as also sporadically reported outside the area among immigrations. The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5'-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred. Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response (SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4 (RVR). In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic direct-acting antivirals have completed phase II/III studies (sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype 6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR (representing > 70% of patients) are suitable for 24-wk treatment with expected SVR rates > 80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy, and a detectable HCV RNA at week 12 (with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia, wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.

SUBMITTER: Bunchorntavakul C

PROVIDER: S-EPMC3782687 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Hepatitis C genotype 6: A concise review and response-guided therapy proposal.

Bunchorntavakul Chalermrat C Chavalitdhamrong Disaya D Tanwandee Tawesak T

World journal of hepatology 20130901 9

Hepatitis C genotype 6 is endemic in Southeast Asia [prevalence varies between 10%-60% among all hepatitis C virus (HCV) infection], as well as also sporadically reported outside the area among immigrations. The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5'-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred. Risk factors and clinical course of HCV genotype 6 do not differ considerably from othe ...[more]

PMID: 24073301

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Project description:Background/Aims The addition of protease inhibitors to standard of care (SOC) dramatically increases treatment response in Hepatitis C Virus (HCV) genotype 1 patients. Moreover, Interleukin 28B (IL28B) genotyping helps predict responsiveness for these patients. However, the economic implications of incorporating IL28B genotyping in HCV genotype 2 or 3 infected patients are unknown. This study used a treatment algorithm that included IL28B genotype-guided therapy to examine the short and long-term cost-effectiveness of utilizing these single-nucleotide polymorphisms in treatment-naïve HCV genotype 2 or 3 infected patients. Methods A treatment algorithm was constructed to reflect a therapy regimen for treatment-naïve patients with HCV genotype 2 or 3 infection using pegylated-interferon, ribavirin, and telaprevir. To examine the role of the IL28B gene in affecting costs and health outcomes, a decision tree was derived from the treatment algorithm in order to populate a predictive cost model for therapy using our treatment algorithm. Results Expected short-term costs of therapy following our algorithm were $21,648.92 and $47,972.84 for the CC and TT genotypes at rs12979860, respectively, and $47,972.84 and $21,648.92 for patients with the CT genotype at rs12979860 and the TG/GG and TT genotypes at rs8099917, respectively. Predicted costs among patients undergoing SOC therapy were $20,758.92. Sustained virologic response (SVR) rates for genotypes 2/3 were predicted to occur in 82.2% (8,220 of 10,000) of patients overall—88.83% (8,883 of 10,000) and 65.91% (6,591 of 10,000) for the CC and TT genotypes at rs12979860 and 81.01% (8,101 of 10,000) overall for patients with the CT genotype at rs12979860 [72.08% (7,208 of 10,000) and 86.78% (8,678 of 10,000) for the TG/GG and TT genotypes at rs8099917]. Markov modeling predicted a 27.29 quality-adjusted life-expectancy (QALE) after following our treatment algorithm while adding $7,766.51 in long-term costs. The model predicted only a 26.65 QALE after SOC therapy (while adding $9,599.05 in long-term costs). Conclusions Although short-term treatment costs of an IL28B genotype-guided approach exceed those of SOC for treatment-naïve HCV genotype 2/3 infected patients, Markov modeling suggests that lower long-term costs and improved health outcomes may be achieved by the proposed algorithm and provides a dominant cost-effective strategy for treating this population of HCV infected patients.

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Hepatitis C genotype 6: A concise review and response-guided therapy proposal.

Publications

Hepatitis C genotype 6: A concise review and response-guided therapy proposal.

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