Current Status of HBV in Asia : Epidemiology of Hepatitis B in Thailand

( Tawesak Tanwandee ) 대한간학회 2004 Clinical and Molecular Hepatology(대한간학회지) Vol.10 No.1(S)

Economic Evaluation and Budget Impact Analysis of the Surveillance Program for Hepatocellular Carcinoma in Thai Chronic Hepatitis B Patients

Sangmala, Pannapa,Chaikledkaew, Usa,Tanwandee, Tawesak,Pongchareonsuk, Petcharat Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: The incidence rate and the treatment costs of hepatocellular carcinoma (HCC) are high, especially in Thailand. Previous studies indicated that early detection by a surveillance program could help by down-staging. This study aimed to compare the costs and health outcomes associated with the introduction of a HCC surveillance program with no program and to estimate the budget impact if the HCC surveillance program were implemented. Materials and Methods: A cost utility analysis using a decision tree and Markov models was used to compare costs and outcomes during the lifetime period based on a societal perspective between alternative HCC surveillance strategies with no program. Costs included direct medical, direct non-medical, and indirect costs. Health outcomes were measured as life years (LYs), and quality adjusted life years (QALYs). The results were presented in terms of the incremental cost-effectiveness ratio (ICER) in Thai THB per QALY gained. One-way and probabilistic sensitivity analyses were applied to investigate parameter uncertainties. Budget impact analysis (BIA) was performed based on the governmental perspective. Results: Semi-annual ultrasonography (US) and semi-annual ultrasonography plus alpha-fetoprotein (US plus AFP) as the first screening for HCC surveillance would be cost-effective options at the willingness to pay (WTP) threshold of 160,000 THB per QALY gained compared with no surveillance program (ICER=118,796 and ICER=123,451 THB/QALY), respectively. The semi-annual US plus AFP yielded more net monetary benefit, but caused a substantially higher budget (237 to 502 million THB) than semi-annual US (81 to 201 million THB) during the next ten fiscal years. Conclusions: Our results suggested that a semi-annual US program should be used as the first screening for HCC surveillance and included in the benefit package of Thai health insurance schemes for both chronic hepatitis B males and females aged between 40-50 years. In addition, policy makers considered the program could be feasible, but additional evidence is needed to support the whole prevention system before the implementation of a strategic plan.

Safety and Efficacy of Elbasvir/Grazoprevir in Asian Participants with Hepatitis C Virus Genotypes 1 and 4 Infection

( Wei Lai ),( Hiromitsu Kumada ),( Ponni Perumalswami ),( Tawesak Tanwandee ),( Wendy Cheng ),( Jeong Heo ),( Pin Nan Cheng ),( Peggy Hwang ),( Sheng Mei Mu ),( Xu Min Zhao ),( Michael Robertson ),( B 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is emerging in the Asia-Pacific region. We conducted an integrated analysis of the safety and efficacy of elbasvir (EBR)/grazoprevir (GZR) in self-identified Asian participants who were enrolled in 11 EBR/GZR phase 2/3 studies. Methods: All participants received EBR/GZR 50 mg/100 mg alone for 12 weeks or in combination with ribavirin (RBV) for 16 weeks. The primary endpoint of all studies was sustained virologic response (HCV RNA < 15 IU/mL) 12 weeks after end of therapy (SVR12). Results: A total of 780 Asian participants with HCV GT1 or 4 infection were included (GT1b, n=715; GT1non-b, n=63; GT4, n=2). Most participants were enrolled from Japan (n=366, 46.9%), mainland China (n=146, 18.7%), Taiwan (n=109, 14.0%) and South Korea (n=90, 11.5%). Overall, 12.4% of participants had cirrhosis, and 20.4% were treatment-experienced. SVR12 was achieved by 756/780 (96.9%, 95% CI 95.5-98.0) of all Asian participants, including 748/772 (96.9%, 95% CI 95.4- 98.0) who received EBR/GZR for 12 weeks and 8/8 (100%, 95% CI 63.1-100.0) who received EBR/GZR + RBV for 16 weeks. The frequency of safety events among Asian participants was: any adverse event (AE), 58.1% (453/780), drug-related AEs, 23.6% (184/780), serious AEs, 2.6% (20/780), and discontinuation due to an AE, 0.9% (7/780). Fifteen participants (1.9%) had elevated ALT/AST levels that met the criteria for an event of clinical interest (ALT/AST >3× baseline and >100 U/L), 3 of whom discontinued treatment. The efficacy and safety profile of EBR/GZR was comparable to that observed among non-Asians. Conclusions: The combination of EBR/GZR was safe and highly effective in this large population of Asian participants with primarily HCV GT1b infection. Late transaminase elevations were reported in approximately 2% of participants, which is consistent with the safety profile of EBR/GZR in non-Asians.

Efficacy and Safety of Elbasvir/Grazoprevir in Treatment- Naive Subjects with Chronic HCV GT 1, GT 4 and GT 6 Infection (C-CORAL): A Phase III Randomized Multinational Clinical Trial

( Do Young Kim ),( Lai Wei ),( Konstantin Zhdanov ),( Eduard Burnevich ),( I-Shyan Sheen ),( Jeong Heo ),( Van Kinh Nguyen ),( Tawesak Tanwandee ),( Pin-Nan Cheng ),( Won Young Tak ),( Svetlana Kizhlo 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatitis C virus (HCV) contributes significantly to the overall liver disease burden in the Asia Pacific region and Russia where the seroprevalence rates vary from 1-5% and genotype (GT) 1b accounts for about half of infections. The efficacy and safety of the fixed-dose combination of elbasvir (EBR) 50 mg and grazoprevir (GZR) 100 mg has been demonstrated in a broad population of HCV-infected subjects and supports evaluation in this region where clinical experience with direct-acting antivirals is limited. EBR/GZR is approved in the United States for treatment of HCV GT1 and 4 infection. Methods: C-CORAL is a double-blind placebo-controlled, Phase 3 trial that randomized treatment-naive HCV GT1, 4 or 6 infected subjects in a 3:1 ratio to an immediate treatment group (ITG; 12 wks of EBR/GZR) or deferred treatment group (DTG; 12 wks of placebo, followed by 12 wks of EBR/GZR). Subjects were enrolled in an ex-China cohort that included subjects from Korea, Taiwan, Vietnam, Thailand, Australia, and Russia; and a second cohort enrolled subjects from China. The primary endpoints include the % of patients in the ITG who achieved SVR12 and a comparison of the safety and tolerability of EBR/GZR in the ITG vs placebo in the DTG. We will present the efficacy results of the ITG and safety results of the ITG and DTG in both cohorts. Results: To date, data from the ex-China cohort are available. In this cohort, a total of 250 subjects were enrolled in the ITG and 86 in the DTG. Mean age (±SD) was 50 ±12 years, 57% were females, 59% were Asian, 74% were GT1b, and 19% were cirrhotic. SVR12 in the ITG was 92.8% (table). Eighteen subjects in the ITG did not achieve SVR12: 11 were relapses, 6 were on-treatment failures (all GT6) and 1 GT1b subject withdrew consent. The incidence of adverse events (AEs) was generally comparable between the ITG vs the DTG including drug-related AEs (21.2% vs 19.8%) and serious AEs (0.8% vs 1.2%; none considered drug-related). During treatment with EBR/GZR or placebo 2/250 (0.8%) subjects in the ITG and 11/86 (12.8%) subjects in the DTG had an ALT value >5x ULN and greater than baseline. One subject in the ITG withdrew after meeting a trial specific discontinuation criterion for elevated ALT, which was not considered drug related. Updated safety and efficacy data will be presented for the ITG for both the ex-China and China study cohorts. Conclusions: A 12-week regimen of EBR/GZR is effective and well-tolerated in GT1 and GT4-infected, treatment-naive patients in the Asia Pacific/Russia region.

Efficacy and Safety of Elbasvir/Grazoprevir in Treatment- Naive Subjects with Chronic HCV GT 1, GT 4 and GT 6 Infection (C-CORAL): A Phase III Randomized Multinational Clinical Trial

( Jeong Heo ),( Lai Wei ),( Konstantin Zhdanov ),( Eduard Burnevich ),( I-Shyan Sheen ),( Van Kinh Nguyen ),( Tawesak Tanwandee ),( Pin-Nan Cheng ),( Do Young Kim ),( Won Young Tak ),( Svetlana Kizhlo 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatitis C virus (HCV) contributes significantly to the overall liver disease burden in the Asia Pacific region and Russia where the seroprevalence rates vary from 1-5% and genotype (GT) 1b accounts for about half of infections. The efficacy and safety of the fixed-dose combination of elbasvir (EBR) 50 mg and grazoprevir (GZR) 100 mg has been demonstrated in a broad population of HCV-infected subjects and supports evaluation in this region where clinical experience with direct-acting antivirals is limited. EBR/GZR is approved in the United States for treatment of HCV GT1 and 4 infection. Methods: C-CORAL is a double-blind placebo-controlled, Phase 3 trial that randomized treatment-naïve HCV GT1, 4 or 6 infected subjects in a 3:1 ratio to an immediate treatment group (ITG; 12 wks of EBR/GZR) or deferred treatment group (DTG; 12 wks of placebo, followed by 12 wks of EBR/GZR). Subjects were enrolled in an ex-China cohort that included subjects from Korea, Taiwan, Vietnam, Thailand, Australia, and Russia; and a second cohort enrolled subjects from China. The primary endpoints include the % of patients in the ITG who achieved SVR12 and a comparison of the safety and tolerability of EBR/GZR in the ITG vs placebo in the DTG. We will present the efficacy results of the ITG and safety results of the ITG and DTG in both cohorts. Results: To date, data from the ex-China cohort are available. In this cohort, a total of 250 subjects were enrolled in the ITG and 86 in the DTG. Mean age (±SD) was 50 ±12 years, 57% were females, 59% were Asian, 74% were GT1b, and 19% were cirrhotic. SVR12 in the ITG was 92.8% (table). Eighteen subjects in the ITG did not achieve SVR12: 11 were relapses, 6 were on-treatment failures (all GT6) and 1 GT1b subject withdrew consent. The incidence of adverse events (AEs) was generally comparable between the ITG vs the DTG including drug-related AEs (21.2% vs 19.8%) and serious AEs (0.8% vs 1.2%; none considered drug-related). During treatment with EBR/GZR or placebo 2/250 (0.8%) subjects in the ITG and 11/86 (12.8%) subjects in the DTG had an ALT value >5x ULN and greater than baseline. One subject in the ITG withdrew after meeting a trial specific discontinuation criterion for elevated ALT, which was not considered drug related. Updated safety and efficacy data will be presented for the ITG for both the ex-China and China study cohorts. Conclusions: A 12-week regimen of EBR/GZR is effective and well-tolerated in GT1 and GT4-infected, treatment-naïve patients in the Asia Pacific/Russia region.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region

Do Young Kim,Bao Nguyen Toan,Chee-Kiat Tan,Irsan Hasan,Lyana Setiawan,Ming-Lung Yu,Namiki Izumi,Nguyen Nguyen Huyen,Pierce Kah-Hoe Chow,Rosmawati Mohamed,Stephen Lam Chan,Tawesak Tanwandee,Teng-Yu Lee 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.2

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.