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( Ming-lung Yu ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Chia-yen Dai ),( Wan-long Chuang ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma (HCC) over time. We aimed to explore their impac at the initiation of antiviral therapy on HCC among chronic hepatitis C (CHC) patients. Methods: A total of 1281 biopsy-proven CHC patients receiving interferon- based therapy were followed for a mean period of 5.5 years. Results: The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients who were <40 years old (7.7 % vs. 0.5%, P=0.1), but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P<0.001) and >55 years old (15.1% vs. 7.9%, P=0.03). Compared with SVR, non-SVR was independently predictive of HCC in patients 40-55 years old (hazard ratio [HR]/95% confidence intervals [CI]: 10.92/3.78-31.56, P<0.001) and >55 years old (HR/CI: 1.96/1.06-3.63, P=0.03) but not in patients <40 years old (HR/CI: 2.76/0.41-18.84, P=0.3). The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%, P=0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%, P<0.001) or F4 (33.5% vs. 8.4%, P=0.002). Compared with SVR, non-SVR was independently predictive of HCC in patients with F2-3 (HR/CI: 4.36 /2.10-9.03, P<0.001) and F4 (HR/CI: 3.84/1.59-9.30, P=0.03) but not in those with F0-1 (HR/CI: 1.53/ 0.49-4.74, P=0.47). Conclusions: Delayed HCV clearance for patients with CHC > 40 years old or with a fibrosis stage > 2 increases the risk of HCC over time.
( Ming Lung Yu ),( Chung-feng Huang ),( Chia-yen Dai ),( Jee-fu Huang ),( Wan-long Chuang ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: MHC class I chain-related A (MICA) genetic variants and its serum level (sMICA) were associated with hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) in untreated cohorts. The dynamic changes of serial sMICA levels regarding anti-HCV treatment and consequent HCC development is elusive. Methods: Single nucleotide polymorphism rs2596542 of MICA and serial sMICA levels were tested in chronic hepatitis C (CHC) patients with sustained virological response after antiviral treatment. Forty-two patients who developed HCC and another 84 age-, sex- and cirrhosis-propensity score matched non-HCC controls were compared. Serial sMICA levels were measured at three-time points: within 6 months of pretreatment (pre-sMICA), 6 months after the end of treatment (post-sMICA) and last visit before HCC occurrence or not (last-sMICA). Results: Compared to patients without HCC occurrence, those with HCC had lower platelet counts, higher levels of post-sMICA (197.4+398.0 pg/mL vs. 57.6+89.6 pg/mL, P=0.03) and last-sMICA (320.4+508.4 pg/mL vs. 37.7+140.2 pg/mL, P<0.001). Cox regression analysis revealed that last-sMICA is the only factor predictive of HCC development (hazard ratio [HR]/ 95 % confidence intervals [CI.]: 2.27 (per 1 log pg/mL increase)/1.672-3.082, P<0.001). Patients without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P=0.001). In contrast, HCC patients had an increased trend of sMICA levels (trend P=0.024). MICA rs2596542 GG genotype carriers without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P<0.001). However, HCC patients who carried GG genotype had a substantially increased trend of sMICA levels (trend P=0.06). Nevertheless, both trends were not observed in A allele carriers with or without HCC development. t three-time points: within 6 months of pretreatment (pre-sMICA), 6 months after the end of treatment (post-sMICA) and last visit before HCC occurrence or not (last-sMICA). Conclusions: Serial sMICA levels could serve as a surrogate marker for HCC development in CHC patients with SVR. The clinical utility is restricted to MICA rs2596542 GG genotype carriers. CA (320.4+508.4 pg/mL vs. 37.7+140.2 pg/mL, P<0.001). Cox regression analysis revealed that last-sMICA is the only factor predictive of HCC development (hazard ratio [HR]/ 95 % confidence intervals [CI.]: 2.27 (per 1 log pg/mL increase)/1.672-3.082, P<0.001). Patients without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P=0.001). In contrast, HCC patients had an increased trend of sMICA levels (trend P=0.024). MICA rs2596542 GG genotype carriers without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P<0.001). However, HCC patients who carried GG genotype had a substantially increased trend of sMICA levels (trend P=0.06). Nevertheless, both trends were not observed in A allele carriers with or without HCC development. t three-time points: within 6 months of pretreatment (pre-sMICA), 6 months after the end of treatment (post-sMICA) and last visit before HCC occurrence or not (last-sMICA).
( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.
( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.
( Ming-lung Yu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Since the first directly acting antivirals (DAA) approved in 2011, the progress of DAA in HCV treatment is moving from IFN (IFN)-containing regimens to IFN-free regimens in 2013, which are currently standard-of-care. Currently, there are 14 DAAs approved in the treatment of HCV and at 9 major combination regimens are applied in the clinical practice for HCV treatment. The regimens include: 1) sofosbuvir-based therapy: sofosbuvir plus weight-based dose of RBV for HCV-2 with 12-week regimen with SVR12 rate of 90%-95%; 12-week sofosbuvir-based therapies, plus ledipasvir or simeprevir or daclatasvir, with the SVR12 rates of > 90% for HCV-1-4 patients and 12 weeks of sofosbuvir/velpatasvir for all HCV genotype with SVR12 rates of 95%-99%. 2) Protease inhibitor-based therapy, including 24-week daclatasvir plus asunaprevir for HCV-1b with SVR rates of 85%-90%; PrOD regimen (co-formulated paritaprevir/r [NS3/4A PI boosted by ritonavir]/Ombitasvir and Dasabuvir) +- RBV for 12 weeks with SVR rates of 90%-95% for HCV-1/4 patients; 12-16 week of elbasvir/grazoprevir HCV-1/ 4 with SVR12 rate of > 90%; and 8-12 weeks of glecaprevir/pibrentasvir for all genotype with SVR rate of 96-99%. However, concerning the efficacy of DAA on HCV patients with pre-existing hepatocellular carcinoma (HCC), there is no data available from clinical trials. Most of the data come from real-world clinical practice and the results are conflict among different studies due to heterogeneity in study population, regimens, baseline patient characteristic and hepatic fibrosis. Nevertheless, there is a trend showing that the SVR12 rate was lower among patients with active HCC when compared to those achieving curative therapy for HCC. Further well controlled, large-scaled studies are needed to clarify the controversial.
( Ming-lung Yu ),( Ming-lun Yeh ),( Chi-yi Chen ),( Pin-nan Cheng ),( Ming-jong Bair ),( Jyh-jou Chen ),( Ching-chu Lo ),( Chi-ming Tai ),( Ching-yang Tsai ),( Kuo-chih Tseng ),( Chien-hung Chen ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Insufficient data regarding the treatment strategy for partial response to nucleot(s)ide analogue (NUC) raised the aim of investigating tenofovir alafenamide (TAF) switching for chronic hepatitis B (CHB) patients with advanced fibrosis and partial response to other NUCs. Methods: CHB patients with advanced fibrosis (stage 3 or 4) and under NUC (except TAF) therapy with detectable hepatitis B virus (HBV) DNA for >52 weeks are enrolled to TAF 25 mg/day for 96 weeks. The objectives are viral suppression, alanine aminotransferase (ALT) normalization and safety. Results: From Feb. 2019, 34 patients, including 21 (61.8%) with entecavir, 10 (29.4%) TDF and 3 (8.8%) lamivudine or adefovir, were enrolled (15 [44.1%] male, median 53 years). The fibroscan demonstrated a mean of 10.5 kPa (7 [20.6%] cirrhotic). Sixteen (47.1%) patients were HBV e antigen positive, seven (20.6%) had YMDD mutation. The median HBV DNA level declined from 68.5 IU/mL at enrollment to 27.0 IU/mL at 4<sup>th</sup> week, and undetectable at 12<sup>th</sup>, 24<sup>th</sup>, 36<sup>th</sup> week, respectively, after TAF switching, with undetectable HBV DNA in 14/34 (41.2%), 17/33 (51.5%), 15/25 (60.0%), and 9/15 (60.0%) patients and rate of ALT normalization (≤40 U/L) of 85.3%, 85.3%, 84.8%, 92.0%, and 80.0%, respectively, after TAF switching. (figure 1) Two patients experienced transient virological breakthrough and another one developed at the final time follow up. Serum creatinine and eGFR levels were stable after TAF switching (figure 1). Two patients early terminated including one at 12<sup>th</sup> week due to personal reason, and another one accidently died at 20<sup>th</sup> week due to acute heart attack. Others suffered only mild degrees of adverse events which were considered unrelated to treatment. Conclusions: The preliminary results demonstrated the TAF switching is effective and safe in viral suppression for CHB patients with advanced fibrosis and partial virologic responses to other NUCs.
Wolbachia in field populations of Forcipomyia taiwana (Diptera: Ceratopogonidae) in Taiwan
Yu-Der Wen,Wei-Lung Wang,Chung-Chi Lin,Wei-Ming Liou 한국응용곤충학회 2011 Journal of Asia-Pacific Entomology Vol.14 No.3
Wolbachia pipientis is an endosymbiotic alpha-proteobacterium that is found in numerous insects and arthropods. Only a few studies have been made on Wolbachia in blood-sucking midges. In this study, we identified and determined the molecular characteristics of Wolbachia strains in Forcipomyia taiwana (Shiraki),a blood-suckingmidge found in Taiwan and southern China. Our results indicate that all F. taiwana individuals captured in Nantou County, Taiwan were infected with Wolbachia strains closely related to the A-supergroup wAlbA. Moreover, 2 individuals captured at low-abundance locations were also infected with a B-supergroup Wolbachia strain. We observed that 63% F. taiwana individuals captured at the low-abundance locations harbored the wAlbA-like strain which has a particular substitution pattern (D51G, T84A, and A85V) in the Wolbachia surface protein. Taken together, our results indicate that distinct Wolbachia strains exist in F. taiwana populations in the field.
Jian-Shian Lin,Ming-Hua Chung,Chen-Ming Chen,Fuh-Shyang Juang,Yu-Sheng Tsai,Shu-Wei Chang,Shun-Hsi Wang,Teh-Chao Liao,Lung-Chang Liu 한국물리학회 2010 Current Applied Physics Vol.10 No.5
UV-curable organic/inorganic hybrid composites with gas barrier and heat-dissipating capability have been successfully fast synthesized with microwave irradiation and utilized for the encapsulation of top-emitting organic light-emitting diodes (TEOLEDs). Experimental results manifest that lab-made organic/inorganic hybrid composites can effectively not only obstruct the invasion of moisture as well as oxygen in the atmosphere into the device but also lower the temperature of device. Therefore, the lifetimes of TEOLEDs with their encapsulation are 2.2 folds longer than those without encapsulation.
Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy
Chung-Feng Huang,Ming-Lung Yu 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.3
The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.