The prevalence of hepatitis C virus (HCV) in Asia is 0.5% to 4.7%, with three different genotypes predominating, depending on the geographic region: genotype 1b in East Asia, genotype 3 in South and Southeast Asia, and genotype 6 in Indochina. Official approval for direct-acting antiviral agents (DAAs) in Asia lags significantly behind that in the West, such that in most countries the mainstay of therapy is still pegylated interferon and ribavirin (PR). Because the interleukin-28B genetic variant, associated with a high sustained virologic response (SVR), is common in Asians, this treatment is still acceptable in Asian patients with HCV infections. A roadmap for HCV therapy that starts with PR and takes into account those DAAs already approved in some Asian countries can provide guidance as to the best strategies for management, particularly of genotype 1 and 3 infections, based on SVR rates. Sofosbuvir and PR are likely to be the initial therapies for genotype 1 and 3 disease, although in the former these drugs may be suboptimal in patients with cirrhosis (62% SVR) and the extension of treatment to 24 weeks may be required. For difficult to treat genotype 3 infections in treatment-experienced patients with cirrhosis, a combination of sofosbuvir and PR result in an 83% SVR and is, therefore, currently the optimal treatment regimen. Treatment failure is best avoided since data on rescue therapies for DAA failure are still incomplete.
Antiviral Agents/adverse effects/*therapeutic use ; Asia/epidemiology ; Drug Therapy, Combination ; Genotype ; Hepacivirus/*drug effects/genetics ; Hepatitis C/diagnosis/*drug therapy/epidemiology/genetics ; Humans ; Interleukins/genetics ; National Health Programs ; Practice Guidelines as Topic ; Prevalence ; Time Factors ; Treatment Outcome

INTRODUCTION: Despite the widespread use of transient elastography for non-invasive assessment of liver fibrosis, the optimal cut-off liver stiffness measurement (LSM) values remain unclear. This study aimed to validate the optimal cut-off LSM values for significant fibrosis and cirrhosis in patients with chronic liver disease (CLD). METHODS: Prospective multicentre data of CLD patients who underwent paired liver biopsy and LSM was analysed to determine the optimal cut-off LSM values for predicting significant fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4). A high-quality cohort was selected by excluding those with failed LSM and invalid LSM readings. RESULTS: Of the 481 patients recruited, 322 fulfilled the pre-defined quality criteria. CLD aetiology was chronic hepatitis B (CHB) in 49%, non-alcoholic steatohepatitis (NASH) in 16% and chronic hepatitis C (CHC) in 12%. Area under the receiver operating characteristic curve for LSM was 0.775 (95% confidence interval [CI] 0.724-0.826) for significant fibrosis and 0.810 (95% CI 0.738-0.882) for cirrhosis. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 13 kPa for cirrhosis in the general cohort. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 12 kPa for cirrhosis for both CHB and CHC, while the corresponding values for NASH were 11 kPa and 15 kPa. CONCLUSION Optimal cut-off LSM values should be selected based on disease aetiology. In Singapore, the optimal cut-off LSM values for CHB and CHC are 9 kPa for significant fibrosis and 12 kPa for cirrhosis. Optimal cut-off values for NASH require further validation.