High Therapeutic Efficiency of LDV/SOF in Asian Patients with CHC Genotype 1 Infection

( Young-suk Lim ),( Henry Lik Yuen Chan ),( Yock Young Dan ),( Mei Hsuan Lee ),( Ming-lung Yu ),( Marta Silva ),( Jorge Felix ),( Zobair M. Younossi ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Current Asian treatment practices for Chronic Hepatitis C (CHC) Genotype (GT) 1 patients use regimens containing pegylated inferferon and ribavirin (PR). As interferon-free regimens become the standard of care in most Western countries, it is necessary to understand the potential impact of an all-oral, PR-free single-tablet regimen of Ledipasvir/Sofosbuvir (LDV/SOF) on Asian CHC patients. The aim of this study was to estimate long-term health outcomes of LDV/SOF therapy in 4 Asian countries: Taiwan, South Korea, Singapore, Hong Kong. Methods: A hypothetical cohort of 10,000 adult patients/country was modeled with a hybrid decision tree and Markov state-transition model capturing the natural history of CHC and treatment implications over a lifetime. Efficacy was based on randomized controlled trials; country-specific demographics, HCV-related epidemiology and treatment data were retrieved from literature. Therapeutic efficiency was defined as the number of advanced liver disease (ALD) cases averted (decompensated cirrhosis, hepatocellular carcinoma, liver transplants, HCV-related deaths) with LDV/SOF relative to PR or no treatment (NT) in treatment-naive patients. The differing immunomodulatory and anti-tumor effects of the therapies were not modeled. Results: A 12 week regimen of LDV/SOF compared to PR/NT is estimated to substantially impact CHC disease burden by reducing the incidence of ALD (Table 1): -90.6% / -94.2% vs. PR/NT (Taiwan), -92.5% / -95.7% (South Korea), -93.3% / -96.2% (Singapore), -93.4% / -96.3% (Hong Kong). Conclusions: LDV/SOF is a highly effective treatment associated with potentially more favorable health outcomes when compared with current treatment practices or no treatment for GT1 CHC Asian patients.

PE-164: Impact of Ledipasvir/Sofosbuvir on the Work Productivity of Chronic Hepatitis C Patients in Asia

( Young-suk Lim ),( Henry Lik Yuen Chan ),( Yock Young Dan ),( Mei Hsuan Lee ),( Eliza Kruger ),( Seng Tan5,Zobair M. Younossi ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: To estimate the work productivity gains associated with LDV/SOF treatment for CHC in Hong Kong, Singapore, South Korea and Taiwan. Methods: The model captures anticipated impact of LDV/SOF on productivity loss over a one-year time horizon from a societal perspective for each country. A literature review was performed to identify country- specific inputs and expert advice was solicited to verify key variables. Patients enter the model post-treatment, having achieved SVR12, or not. Absenteeism and presenteeism rates were estimated based on the Work Productivity and Activity Index-Specific Health Problem (WPAI-SHP) data collected from the Phase III ION trials (US participants only) at baseline and at 12 weeks with rates assumed to remain unchanged from baseline for patients not achieving SVR. Sensitivity analyses were performed on key variables. Results: Total Work productivity loss due to not treating CHC was highest in Taiwan at US$349M ($355 per capita) given high prevalence of HCV, followed by US$146M ($358) in Korea, US$17M ($914) in Singapore and US$11M ($351) in Hong Kong. Treatment with LDV/SOF resulted in estimated productivity gains of $138 million, $58.7 million, $6.8 million and $4.5 million in Taiwan, Korea, Singapore and Hong Kong respectively. Conclusions: CHC imposes a significant indirect economic burden. Our model demonstrates that treatment of HCV GT1 patients with LDV/SOF is likely to result in significant cost savings due to an improvement in presenteeism versus no treatment across 4 Asian countries. This indirect economic gain should be considered when assessing the benefits of treating CHC.

review : A 2015 roadmap for the management of hepatitis C virus infections in Asia

( Seng Gee Lim ),( Yock Young Dan ) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.4

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 inIndochina. 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 provideguidance 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.

A Systematic Review of the Extrahepatic Manifestations of Hepatitis C Infection in East Asia

( Zobair M. Younossi ),( Linda Henry ),( Janus Ong ),( Atsushi Tanaka ),( Yuichiro Eguchi ),( Masashi Mizokami ),( Young-suk Lim ),( Yock Young Dan ),( Ming-lung Yu ),( Maria Stepanova ),( Sooji Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Chronic hepatitis C (CHC) infection causes a systemic infection with hepatic and extrahepatic manifestation (EHMs). Although the prevalence of EHMs in Western countries is well described, the same is not well known in East Asian countries. We performed a systematic review to quantify the prevalence of selected EHMs among CHC patients in East Asia. Methods: PubMed, Medline, and Japan databases searched (1990-Dec 2016) with “hepatitis c virus” “chronic hepatitis C”, “extrahepatic manifestations”, and respective EHM’s. Data were collected and reviewed by two per PRISMA guidelines. EHMs were by ICD-9 codes or clinically: depression:BDI-2 score>19, chronic kidney disease (CKD): eGFR of < 60 mL/ min/1.73 m2 per MDRD, diabetes (DM):fasting blood glucose level > 126 mg/dL. Pooled prevalence determined by random effects models. Results: 75 articles were identified. After applying inclusion and exclusion criteria, 23 articles remained (Japan=6; China=3, Korea= 4, Taiwan=9, Asia=1) with a total of 468,656 subjects (n= 51,160 CHC and n= 417,496 non-HCV controls). HCV patient age ranged from 44-70 (mean age 55), 50% were male (range 0%-67%), and over 80% of diagnosis was established through positive HCV anti-body. CHC subjects had higher risk of lymphoma (n=2) 4.6% vs. 2.3%, OR=1.79 (1.47-2.19), P<0.0001; DM (n=11) 16.7% vs. 9.4%, OR=1.84 (1.52-2.21), P<0.0001; SS (n=2) 9.6% vs. 3.5%, OR=9.80 (1.25-76.56), P=0.0295; LP (n=5) 8.2% vs. 4.2%, OR=2.45 (1.36-4.41), P=0.0027; depression (n=1) 51.6% vs. 27.7%, OR=2.77 (1.25-6.15), P=0.0121; CKD (n=5) 3.8% vs. 1.7%, OR=2.00 (1.09-3.70), P=0.026; RA (n=2) 0.9% vs. 0.3%, OR=2.41 (1.54-3.76), P=0.0001; CVA (n=2) 25.3% vs. 19.3%, hazard ratio 1.38 (1.24-1.53), P<0.05; IHD (n=1) 25.3% vs 11.6%, OR=1.76 (1.04-2.96), P=0. 0.034. Additionally, the prevalence of MC (symptomatic and asymptomatic; n=1) in CHC was 46.9% in CHC vs. 1.9% in general population with a risk ratio of 24.7 (17.2-32.2). Conclusions: Our review found that CHC in East Asia is associated with increased risk for EHMs.