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.

Sofosbuvir and Ledipasvir is Associated with High Sustained Virologic Response and Improvement of Health- Related Quality-of-Life in East-Asians with Hepatitis C

( Zobair Younossi ),( Maria Stepanova ),( Linda Henry ),( Kwanghyub Han ),( Sang Ahn ),( Youngsuk Lim ),( Wanloung Chuang ),( Jia Horng Kao ),( Nguyen Kinh ),( Ching Lung Lai ),( Man Fung Yuen ),( Hen 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: We aim to assess HRQL in east Asian (EA) HCV patients treated with different anti-HCV sofosbuvir (SOF)-based regimens. Methods: 1070 EA HCV subjects were enrolled in two phase 3 clinical trials [China: 55.6%, S. Korea: 20.7%, Taiwan: 16.1%, Vietnam: 4.7%, and Hong Kong: 2.9%]. Patients received IFN+SOF+RBV for 12 weeks (n=155, GT 1 and 6) or SOF+RBV for 12-24 weeks (n=531, GT 1, 2, 3 and 6) or IFN-free RBV-free LDV/SOF (n=384, GT1 only). The SVR-12 rates were 95.5%, 96.0%, and 99.2%, respectively (P=0.008). EA HCV patients completed Short Form-36 before, during, and after treatment and HRQL scores compared between regimens. Results: Baseline HRQL scores were similar between treatment groups. After 2 weeks of treatment, HRQL scores for the IFN+RBV- containing regimen became significantly lower as compared to the IFN-free regimens (average decline up to -11.2 points, P<0.0001). By the end of treatment, IFN-treated group experienced significant declines in most HRQL scores (up to -13.3 points, P<0.02 for 7/8 HRQL scales). Patients on SOF+RBV had milder HRQL impairments (up to -5.4 points, P<0.05 for 5/8 scales). However, patients receiving LDV/SOF had improvement in their HRQL scores (up to +4.3 points by the end of treatment, P<0.001 for 3/8 scales). Achieving SVR-12 with IFN+RBV+ SOF and SOF+RBV was associated with improvement in General Health (GH) and Vitality (VT) (up to +2.9 points, P<0.05), while SVR-12 with LDV/SOF was associated with improvement in Physical Functioning, GH, VT, Mental Health, and Role Emotional (up to +5.9 points, P<0.03). In multivariate analysis, receiving IFN was independently associated with HRQL impairment during treatment (β: -10.4 to -17.3 points, P<0.0001). Conclusions: Treatment of EA HCV patients with IFN or RBV containing regimens is associated with HRQL impairment, while treatment with LDV/SOF is associated with improvement of HRQL during treatment. SVR-12 was associated with greater improvements in HRQL.

In response to: Steatotic liver disease-know your enemies

Michael H. Le,Linda Henry,Mindie H. Nguyen 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

Economic Gains Related to Hepatocellular Carcinoma and Decompensated Cirrhosis Reduction in Japan is expected from Treatment of Chronic Hepatitis C

( Zobair M. Younossi ),( Atsushi Tanaka ),( Yuichiro Eguchi ),( Linda Henry ),( Rachel Beckerman ),( Masashi Mizokami ),( Sooji Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Japanese chronic hepatitis C (CHC) patients are at greater risk for hepatocellular carcinoma (HCC). Highly effective oral Direct Acting Antiviral (DAA) regimens for CHC can lead to high SVR rates that reduce CHC complications and costs. This study estimated the economic benefit of CHC cure by reducing HCC and decompensated cirrhosis (DCC) in Japan. Methods: A hypothetical cohort of 10,000 HCV GT1b Japanese patients with a mean age of 70 was modeled with a hybrid decision tree and Markov model capturing the natural history of HCV infection over a lifetime horizon. It was assumed that 15% of the cohort had cirrhosis and 20% were treatment-experienced. Treatment compared approved all-oral DAAs vs. no treatment (NT) with efficacy based on randomized controlled trials. Transition rates and costs were obtained from Japan-specific data. DCC, HCC and quality-adjusted life years (QALYs) were projected. QALYs were monetized using a willingness to pay (WTP) threshold which varied from ¥4 to ¥6 million. The incremental savings associated with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. Results: DAA treatment avoided 1583 cases of HCC and 1162 cases of DCC, saving ¥618,076 and ¥251,329 per treated patient; respectively. Treatment leads to avoidance of 2745 cases of CHC complications and associated savings of ¥869,405 per treated patient. Additionally, DAA treatment lead to an additional 1.59 QALYs gained per patient treated. The indirect economic gains associated with treatment-related QALY improvements were estimated to be ¥6,360,000, ¥7,950,000 and ¥9,540,000 per patient at WTP thresholds of ¥4 million, ¥5 million and ¥6 million. Total economic savings of HCV GT1 treatment with DAAs (vs. NT) was ¥7,229,405, ¥8,819,405and ¥10,409,405 at these different WTP thresholds. Conclusions: Treatment of HCV GT1b with all Oral DAAs in Japan can lead to significant savings related to avoidance of HCC and DCC.

Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach

Michael H. Le,Yee Hui Yeo,Biyao Zou,Scott Barnet,Linda Henry,Ramsey Cheung,Mindie H. Nguyen 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.4

Background/Aims: Due to increases in obesity and type 2 diabetes, the prevalence of nonalcoholic fatty liver disease (NAFLD) has also been increasing. Current forecast models may not include non-obese NAFLD. Here, we used the Bayesian approach to forecast the prevalence of NAFLD through the year 2040. Methods: Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were performed for age, gender, presence of metabolic syndrome, region, and smoking status. Sensitivity analysis was conducted for clinical setting and study quality. Results: The forecasted 2040 prevalence was 55.7%, a three-fold increase since 1990 and a 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged <50 years and ≥50 years, the 2040 prevalence were not significantly different (56.7% vs. 61.5%, P=0.52). There was a significant difference in 2040 prevalence by sex (males: 60% vs. 50%) but the trend was steeper for females (annual percentage change: 2.5% vs. 1.5%, P=0.025). There was no difference in trends overtime by region (P=0.48). The increase rate was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, P=0.003) and smokers (1.4% vs. 1.1%, P=0.011). There was no difference by clinical/community setting (P=0.491) or study quality (P=0.85). Conclusions: By 2040, over half the adult population is forecasted to have NAFLD. The largest increases are expected to occur in women, smokers, and those without metabolic syndrome. Intensified efforts are needed to raise awareness of NAFLD and to determine long-term solutions addressing the driving factors of the disease.