Changes in Markers of Liver Function in HCV 1b Patients with Compensated Cirrhosis Treated with Ombitasvir/Paritaprevir/ Ritonavir plus Dasabuvir with Ribavirin

( Jeong Heo ),( Yan Luo ),( Wan-long Chuang ),( Jidong Jia ),( Kwang-hyub Han ),( Ming-lung Yu ),( Hong Tang ),( Young-suk Lim ),( Cheng-yuan Peng ),( Min Xu ),( Maorong Wang ),( Bo Fu ),( Niloufar Mo 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Patients chronically infected with HCV are at risk of developing extrahepatic manifestations of HCV as well as progressing to compensated or decompensated cirrhosis and HCC. Although current treatments have high rates of SVR, relatively little is known about possible regression of liver fibrosis after achieving an SVR. The ONYX-II trial examined the efficacy and safety of ombitasvir/paritaprevir/ritonavir plus dasabuvir + ribavirin (RBV) in Asian patients with HCV genotype 1b infection and compensated cirrhosis. Here we report changes in key markers of liver fibrosis and function. Methods: Patients with chronic HCV GT1b infection and compensated cirrhosis were enrolled in China, South Korea and Taiwan and received 12 weeks of OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) with weight-based RBV. The primary objective of ONYX-II was to assess efficacy (SVR12) and safety of the regimen. Changes in markers of liver fibrosis and function between baseline (BL) and post-treatment week (PTW) 12 are presented. Results: Overall, 104 patients were enrolled and treated in ONYX-II. All patients (104/104, 100%) achieved SVR12. BL and PTW12 data for FibroTest score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin, platelet count and alpha fetoprotein (AFP) are shown in Table 1. All selected parameters showed numerical improvements between BL and PTW12. Mean ALT and AST levels returned to within normal range and FibroTest scores demonstrated a numerical improvement, suggesting improvement in liver status. The complete set of data between BL and PTW12 will be presented for these parameters and other liver composite parameters at the conference. Conclusions: Measurement of key liver function markers during the ONYX-II trial showed a numerical improvement within 12 weeks of completion of treatment in HCV GT1b-infected patients with compensated cirrhosis. Further follow-up of these patients will determine the long-term durability of these changes.

Partial oxidation reforming of biomass fuel gas over nickel-based monolithic catalyst with naphthalene as model compound

Tie Jun Wang,Chen Guang Wang,Tie Jun Wang,Yan Gao,Chuang Zhi Wu,Long Long Ma 한국화학공학회 2008 Korean Journal of Chemical Engineering Vol.25 No.4

With naphthalene as biomass tar model compound, partial oxidation reforming (with addition of O2) and dry reforming of biomass fuel gas were investigated over nickel-based monoliths at the same conditions. The results showed that both processes had excellent performance in upgrading biomass raw fuel gas. Above 99% of naphthalene was converted into synthesis gases (H2+CO). About 2.8 wt% of coke deposition was detected on the catalyst surface for dry reforming process at 750 oC during 108 h lifetime test. However, no coke deposition was detected for partial oxidation reforming process, which indicated that addition of O2 can effectively prohibit the coke formation. O2 can also increase the CH4 conversion and H2/CO ratio of the producer gas. The average conversion of CH4 in dry and partial oxidation reforming process was 92% and 95%, respectively. The average H2/CO ratio increased from 0.95 to 1.1 with the addition of O2, which was suitable to be used as synthesis gas for dimethyl ether (DME) synthesis.

Impact of Hepatoprotective Medications on the Safety and Efficacy of OBV/PTV/r plus DSV ± Ribavirin in HCV GT1b-infected Asian Patients

( Wan-long Chuang ),( Yan Luo ),( Jeong Heo ),( Gui-qing Wang ),( Ming-lung Yu ),( Yoon Jun Kim ),( Qing Xie ),( Cheng-yuan Peng ),( Mingxiang Zhang ),( Yan Huang ),( Wenjing Lu ),( Linda M. Fredrick 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatoprotective medications (HPMs) are commonly used in patients with chronic liver disease, especially across Asia. The phase 3 ONYX-I and ONYX-II studies evaluated the safety and efficacy of the 3-DAA regimen of ombitasvir and paritaprevir/ritonavir (OBV/PTV/r) plus dasabuvir (DSV) ± ribavirin (RBV) in an exclusively HCV GT1b-infected Asian population. This post-hoc analysis evaluated the impact of HPM use in patients treated with OBV/PTV/r + DSV ± RBV in these studies. Methods: ONYX-I and ONYX-II enrolled patients in China, South Korea and Taiwan. SVR12, treatment-emergent adverse events (AEs), and alanine transaminase (ALT) normalization, as well as mean changes in ALT over time were assessed in patients using vs not using HPMs. HPM use defined as all medications administered during any treatment period. Results: Overall, 11% (36/325) of non-cirrhotic and 57% (59/104) of cirrhotic patients were receiving HPMs, with ursodeoxycholic acid being the most commonly used in both non-cirrhotic (5.2% [17/325]) and cirrhotic (14.4% [15/104]) patients. SVR12 rates were high (99.7- 100%) in both non-cirrhotic and cirrhotic patients irrespective of HPM use. The regimen was generally well tolerated, with low rates of SAEs and AEs leading to treatment discontinuation (Table). Of patients with ALT above normal at baseline (BL), 100% vs 95% of non-cirrhotic and 98% vs 89% of cirrhotic patients using or not using HPMs, respectively, had normal ALT values at end of treatment (EOT). Mean ALT levels during treatment declined rapidly and similarly with and without HPM use; mean changes from BL to EOT were -38.8 and -37.0 U/L, respectively, in non-cirrhotic and -54.2 and -66.6 U/L, respectively, in cirrhotic patients. Conclusions: OBV/PTV/r + DSV ± RBV achieved high SVR12 and was generally well tolerated regardless of HPM use. HPM use had no impact on the safety profile of OBV/PTV/r + DSV therapy in Asian HCV infected subjects.

Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in CHC and CHB Coinfection Patients: A Phase 3 Study in Taiwan

( Chun-Jen Liu ),( Wan-Long Chuang ),( I-Shyan Sheen ),( Horng-Yuan Wang ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ting-Tsung Chang ),( Benede tta Massetto ),( Jenny Yang ),( Gregory Camus ),( Fangqiu Zh 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Patients co-infected with HCV and HBV have more rapid progression and worse outcomes than mono-infected patients. Taiwan has among the highest prevalence of chronic HCV/HBV coinfection in Southeast Asia. This study evaluated the safety and efficacy of an all-oral treatment with ledipasvir(LDV)/sofosbuvir(SOF) for 12 weeks in chronic HCV and HBV coinfection. Methods: Patients with or without compensated cirrhosis chronic HCV GT1/GT2 and HBV (HBsAg+) treatment naïve were enrolled into open-label, receiving LDV 90 mg/SOF 400 mg(QD) for 12 weeks. The primary efficacy endpoint is SVR12. HBV DNA was monitored at all study visits and it will be monitored for 2 years post-treatment. Results: A total of 111 patients (68[61%] with GT1 and 43[39%] with GT2) were enrolled and treated. The majority were female(62%), treatment naive(67%), and non-cirrhotic(85%), with a mean age of 55 years and mean BMI of 24.5kg/m2. All but one was HBeAg negative. Mean baseline HBV DNA was 2.1 log10IU/mL. SVR4 was 100%(111/111). The mean change in HBV DNA ranged from -0.06 log10IU/mL at week 1 to +0.49 log10IU/mL at follow-up visit 4; HBV DNA kinetics are shown in Fig 1. 60(54%) patients had an increase in HBV DNA> 10 x BL or became HBV DNA > LLOQ. No patients had ALT ≥ 2 X baseline. No patients discontinued treatment due to adverse events (AEs). Three patients had serious AEs(optic neuritis, post procedural bleeding and duodenal ulcer bleeding; none was considered drug related). Conclusions: In chronic HCV/HBV infection patients, LDV/SOF for 12 weeks resulted in an SVR4 rate of 100%. Although most patients had an increase in HBV DNA during treatment, this was not associated with ALT elevations ≥2 X baseline, and no patients started HBV therapy to date. This all-oral, interferon-free regimen was well tolerated, supporting its potential as a treatment option for HCV/HBV co-infected patients.

Comparison of Efficacy and Safety of Ombitasvir/Paritaprevir/ Ritonavir and Dasabuvir ± Ribavirin between Asian and Western HCV GT1b-Infected Patients

( Lai Wei ),( Yan Luo ),( Wang-long Chuang ),( Seung Woon Paik ),( Ming-lung Yu ),( Linda M Fredrick ),( Andrew Campbell ),( Roger Trinh ),( Jeffrey Enejosa ),( Nancy S Shulman ),( Jeong Heo ),( Nilou 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: ONYX-I and ONYX-II are Phase 3 studies exploring the PK, safety, and efficacy of the 3-DAA ± ribavirin regimen in a HCV GT1b-infected Asian population. Comparable PK exposures of the 3-DAA regimen between the Asian and predominantly Caucasian (thereafter referred to as “Western”) HCV GT1-infected patients in other studies have been published. Methods: We compared the safety/efficacy profiles of the 3-DAA regimen (+ ribavirin for patients with compensated cirrhosis) in Asian patients in ONYX-I and -II Phase 3 studies conducted in China, Taiwan, and South Korea with Western patients enrolled in PEARL-II (treatment-experienced), PEARL-III (treatment-naive), and TURQUOISE-II (compensated cirrhosis) Phase 3 studies conducted exclusively in North America, Europe, and Australia. Results: Among treatment-naive non-cirrhotic patients, sustained virologic response at post treatment week 12 (SVR12) was achieved by 99.5% (183/184; 95% CI 97.0-99.9) of Asian patients compared with 99.0% (207/209; 95% CI 97.7-100) of Western patients (GT1b). In non-cirrhotic treatment-experienced patients, SVR12 was achieved by 100% (141/141; 95% CI 97.4-100) of Asian patients and 100% (91/91; 95% CI 95.9-100) of Western patients (GT1b). Among cirrhotic patients, SVR12 was achieved by 100% (104/104; 95% CI 96.4-100) of Asian patients compared with 98.5% (67/68; 95% CI 95.3-100) of Western patients (GT1a and -1b-infected patients). The majority of Asian and Western patients with or without cirrhosis had at least 1 treatment-emergent adverse event (TEAE). A low percentage of Asian and Western patients (<4%) experienced serious TEAEs. TEAEs leading to treatment discontinuation, in both Asian and Western patients, were rare. No patients without cirrhosis and 1 subject with cirrhosis discontinued treatment due to a TEAE. Only 1 death occurred across the studies, which was not due to a TEAE. Conclusions: The safety/efficacy profiles were consistent between the Asian and Western HCV GT1b-infected patients treated with OBV+PTV/r + DSV.