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We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti-HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter [PM 2.5 ], nitrogen dioxide [NO 2 ], ozone [O 3 ] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05-4.77; p < 0.001), smoking (OR, 1.79; 95% CI, 1.16-2.74; p = 0.01), age (OR, 1.04; 95% CI, 1.02-1.05; p < 0.001) and PM 2.5 (OR, 1.10; 95% CI, 1.05-1.16; p < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM 2.5 (β: 0.134; 95% CI: 0.025, 0.243; p = 0.02). There was a dose-dependent relationship between different fibrotic stages and the PM 2.5 level (the PM 2.5 level in patients with fibrotic stages 0, 1-2 and 3-4: 27.9, 28.4, and 29.3 μg/m 3 , respectively; trend p < 0.001). Exposure to PM 2.5 , as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dose-dependent correlation between PM 2.5 levels and the severity of hepatic fibrosis., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background and Aim: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its interplay with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of liver disease severity is elusive., Methods: A mass surveillance program was conducted in a viral hepatitis endemic area. The objective was to identify MAFLD/non-MAFLD subjects with advanced liver disease., Results: Two thousand two hundred and forty-two (41.7%) of the 5378 subjects were identified as having MAFLD, and 375 (7.0%) had advanced liver disease. The proportions of anti-HCV and HBsAg seropositivity were 19.3% and 9.7%, respectively. The proportions of advanced fibrosis in subjects with non-viral hepatitis (NBNC), HBV and HCV infection were 2.8%, 5.7% and 23.4%, respectively. Subjects with MAFLD had a significantly higher proportion of advanced fibrosis (8.7% vs 5.7%, P < 0.001). Factors associated with advanced fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 4.8/3.7-6.0, P < 0.001), male sex (OR/CI: 1.3/1.0-1.7, P = 0.019), anti-HCV seropositivity (OR/CI: 5.9/4.6-7.5, P = 0.019), MAFLD-lean metabolic dysregulation (MS) (OR/CI: 2.6/1.3-5.2, P = 0.005; compared with the non-MAFLD group) and MAFLD-diabetes (OR/CI: 1.5/1.1-2.1, P = 0.008; compared with the non-MAFLD group). MAFLD did not aggravate liver disease severity in patients with viral hepatitis. However, among NBNC subjects, factors associated with advanced liver disease included MAFLD-lean MS group (OR/CI: 9.1/2.4-34.6, P = 0.001; compared with non-MAFLD group) and MAFLD-DM group (OR/CI: 2.0/1.2-3.2, P = 0.004; compared with non-MAFLD group)., Conclusions: MAFLD patients with diabetes and metabolic dysregulation had a higher risk of advanced liver disease. The effect was more significant in non-viral hepatitis subjects in a community level., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti-HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post-treatment follow-up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy-three (4.9%) individuals were seropositive for anti-HCV antibodies. Of the 73 anti-HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty-three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post-treatment follow-up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient-centered and integrated outreach program facilitated HCV care in this marginalized population., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objectives: Metabolic syndrome (MetS) and hepatitis C virus (HCV) are associated with a higher risk of impaired pulmonary function (iPF). This study aimed to investigate the relationships among MetS, iPF, and viral hepatitis., Methods: This community-based study enrolled participants undergoing annual health check-ups in southern Taiwan between March and December 2019. We performed multivariable logistic regression analyses adjusted for demographics and characteristics to identify the factors associated with iPF., Results: A total of 2337 participants completed examinations, of whom 928 (39.7%) had iPF. The participants with iPF were elderly (68.8  ±  12.8 years old) and predominately female (63%). MetS increased the risk of iPF (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.27-1.81, p  < 0.001). Beyond age (OR 1.03, 95% CI 1.02-1.04) and smoking (OR 1.309, 95% CI 1.004-1.705), female sex (OR 0.74, 95% CI 0.59-0.93) and high education level (OR 0.96, 95% CI 0.94-0.98, p  < 0.001) protected against iPF. HCV was not significantly associated with iPF (OR 1.17, 95% CI 0.90-1.52, p   =  0.235) in multivariable analysis. MetS was associated with a higher risk of iPF in the non-HBV/HCV group (OR 1.86, 95% CI 1.54-2.26) and HBV alone group (OR 3.44, 95% CI 1.89-6.28), but not in the HCV alone group (OR 1.02, 95% CI 0.64-1.62)., Discussion: MetS was an independent predictor of iPF, especially the restrictive type, and had different effects in the HBV/non-viral hepatitis and HCV groups. Female sex and education were inversely associated with iPF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Gaps in linkage-to-care remain the barriers toward hepatitis C virus (HCV) elimination in the directly-acting-antivirals (DAA) era, especially during SARS Co-V2 pandemics. We established an outreach project to target HCV micro-elimination in HCV-hyperendemic villages., Methods: The COMPACT provided "door-by-door" screening by an "outreach HCV-checkpoint team" and an "outreach HCV-care team" for HCV diagnosis, assessment and DAA therapy in Chidong/Chikan villages between 2019 and 2021. Participants from neighboring villages served as Control group., Results: A total of 5731 adult residents participated in the project. Anti-HCV prevalence rate was 24.0% (886/3684) in Target Group and 9.5% (194/2047) in Control group (P < 0.001). The HCV-viremic rates among anti-HCV-positive subjects were 42.7% and 41.2%, respectively, in Target and Control groups. After COMPACT engagement, 80.4% (304/378) HCV-viremic subjects in the Target group were successfully linked-to-care, and Control group (70% (56/80), P = 0.039). The rates of link-to-treatment and SVR12 were comparable between Target (100% and 97.4%, respectively) and Control (100% and 96.4%) groups. The community effectiveness was 76.4% in the COMPACT campaign, significantly higher in Target group than in Control group (78.3% versus 67.5%, P = 0.039). The community effectiveness decreased significantly during SARS Co-V2 pandemic in Control group (from 81% to 31.8%, P < 0.001), but not in Target group (80.3% vs. 71.6%, P = 0.104)., Conclusions: The outreach door-by-door screen strategy with decentralized onsite treatment programs greatly improved HCV care cascade in HCV-hyperendemic areas, a model for HCV elimination in high-risk marginalized communities in SARS Co-V2 pandemic., (Copyright © 2023. Published by Elsevier B.V.)

Hepatitis C virus (HCV) eradication through antivirals ameliorates metabolic profiles. The changes in 2-h plasma glucose (2HPG) levels by oral glucose tolerance test (OGTT), in chronic hepatitis C (CHC) patients who receive directly acting antivirals (DAAs) was elusive. Five hundred and thirty-three CHC patients who achieved sustained virological response (SVR, undetectable HCV RNA throughout 3 months after the end-of-treatment) by DAAs were consecutively enrolled. Pre- and posttreatment 2HPG levels and glucose status were compared. The proportion of patients with improved, worsened, and stable 2HPG was 14.4% (n = 77), 18.6% (n = 99), and 67.0% (n = 357), respectively. Compared with patients with worsening 2HPG, those with improved 2HPG had a higher proportion of cirrhosis (45.5% vs. 24.2%, p = 0.004) and higher pretreatment 2HPG levels (175.3 vs. 129.5 mg/dl, p < 0.001). High baseline 2HPG was independently associated with improved 2HPG in multivariate analysis (odds ratio [OR]/CI: 1.05/1.03-1.06, p < 0.001). When baseline 2HPG was not taken into account, cirrhosis was the only factor independently associated with improved 2HPG status (OR/CI: 2.58/1.29-5.15, p = 0.007). Linear regression analysis revealed that factors independently correlated to changes in 2HPG levels were female sex (β: 8.78; 95% CI:2.34, 15.22; p = 0.01), diabetes (β: -27.72; 95% CI: -50.16, -5.28; p = 0.02), liver cirrhosis (β: -8.91; 95% CI: -16.75, -2.20; p = 0.01), and genotype 1 of HCV (β: -0.12; 95% CI: -15.19, -2.43; p = 0.01). 2HPG improved after HCV eradication by DAAs, particularly in cirrhotic patients., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, link-to-care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire-based interviews for HCV. The rates of disease awareness, accessibility, and anti-HCV therapy were evaluated in anti-HCV-seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti-HCV seropositive. Of these 1789 anti-HCV-seropositive participants, data of 594 participants from questionnaire-based interviews in 2005-2018 were analyzed for HCV care cascades. Overall, 24.9% of anti-HCV-seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB-4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link-to-care, and treatment uptake in the HCV care cascade in an HCV-hyperendemic area, even in the initial era of direct-acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients and analyze the associated factors of persistent cryoglobulinemia., Methods: Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy., Results: Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio [OR]- 4.13, 95% Confidence Interval [95% CI]- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy., Conclusions: The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance., Competing Interests: The authors have declared that no competing interests exist.

Background: Hepatitis C virus (HCV) infection is associated with a higher risk of chronic kidney disease (CKD). This study investigates the relationship among HCV, CKD, and understudied confounders, such as unhealthy behaviors and metabolic disturbances., Methods: This cross-sectional study was conducted as part of a community health promotion program in an HCV endemic area of Taiwan from June to December 2019. Multivariable logistic regression analyses adjusted for demographic and clinical characteristics were performed to investigate the association between CKD and HCV seropositivity., Results: Of 2387 participants who underwent health check-ups, the mean age was 64.1 years old; females predominated (63.2%), and 306 (12.8%) subjects were seropositive for HCV. CKD, defined as a lower estimated glomerular filtration rate (eGFR) was associated with unhealthy dietary habits, metabolic syndrome, and HCV. Less frequent exercise, higher waist circumference (WC) and HbA1c all affected risk of CKD; HCV increased risk of CKD by 44% compared to non-HCV (OR 1.44, 95% confidence interval (CI) 1.05-1.98) in the multivariable analysis. In the HCV group, lower eGFR was also significantly associated with the severity of metabolic syndrome (MetS) (median eGFR was 86.4, 77.1, and 64.5 mL/min/1.73 m 2 for individuals with three and five MetS components, respectively)., Conclusions: Beyond metabolic disturbance and irregular exercise, HCV seropositivity is independently associated with CKD in a community survey. Healthy lifestyle promotion might protect against renal function decline in HCV; however, the mechanisms underlying the association need further large-scale investigation.

Background and Aims: Scarce data are available on in-hospital hepatitis C virus (HCV) micro-elimination strategies. This pilot study was prospectively conducted to assess the outcomes of HCV in-hospital micro-elimination program (HCV-HELP) in a single center in Taiwan., Methods: The study included the HCV reflex test for plans A (hospital personnel), B (outpatient surveillance), C (a call-back system for anti-HCV+ patients), and D (surveillance of cancer patients prior to chemotherapy). The primary outcome measurement was that > 80% of eligible patients were enrolled in linkage-to-treat; the secondary outcome measurement was the surveillance efficacy., Results: We recruited 930, 6072, 2376 and 233 participants into plans A, B, C, and D, respectively, from Oct 2020 to May 2021. The anti-HCV-seropositivity prevalences were 0.22% for plan A, 4.3% for B, and 3.9% for D. Two staff members were identified as HCV-viremic in plan A; these staff members successfully achieved a sustained virological response (SVR). We identified 39, 95 and 2 HCV-viremic patients in plans B, C, and D, respectively. Of these 138 HCV-viremic patients, 135 (97.8%) received direct-acting antiviral therapy, and 134 achieved SVR. Two 4-month phases were stratified to compare efficacies in the liver clinic. In the late phase, the adjusted number of HCV-viremic patients was 4.36/10,000 outpatient visits (90/200,689), which was 3.18-fold higher than that of the early phase (1.37/10,000 outpatient visits [30/212,658], odds ratio 3.18; 95% confidence interval 2.10-4.81, p < 0.0001)., Conclusion: HCV micro-elimination is achievable at the hospital level as per the structured HCV-HELP study., (© 2021. Asian Pacific Association for the Study of the Liver.)

Background/purpose: Hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) infections affect patient morbidity and mortality and challenge infection control procedures within dialysis facilities. Thus, updated information on the yearly infection trends in the dialysis population is pivotal to preventing and improving the management of these infectious diseases., Methods: This study used reimbursement data from the Taiwan National Health Insurance Research Database. Long-term hemodialysis (HD) patients were defined as those receiving regular HD for more than 3 months. Treated HBV, HCV, and TB cases were defined according to the diagnosis codes, together with specified prescriptions. Liver malignancy and liver-related mortality were determined by the disease diagnosis., Results: The long-term HD population in Taiwan grew from 57,539 in 2010 to 74,203 in 2018. The mean number of treated HBV, HCV, and TB cases in the HD population was 254 (3.9 per thousand HD patients), 136 (2.0 per thousand), and 165 (2.6 per thousand), respectively. An increasing trend of treated viral hepatitis and a mildly decreasing trend in treated TB were observed. Liver outcome showed an increasing trend in liver malignancy prevalence and a stationary trend of liver-related mortality. Treated HBV and TB, liver malignancy, and liver-associated mortality were higher in men than women (all p < 0.001). The burden of liver complications was higher in southern Taiwan., Conclusion: The increasing yearly trend of treated HBV and HCV and a stable trend of treated TB provide evidence for further infection control management and risk population identification of the HD population., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The association between the biomarkers of environmental exposure, oxidative stress, and health-related behaviors in community residents living in an endemic viral hepatitis area and near petrochemical industrial complexes remains unclear. From a health promotion perspective, healthcare providers must know what to do for residents concerned about their health and living environment, especially for individual-level and modifiable risk factors. Therefore, we aimed to explore the factors associated with urinary 1-hydroxypyrene (1-OHP) and malondialdehyde (MDA)., Methods: A community-based, cross-sectional study was conducted between July 2018 and February 2019 in western coastal Yunlin County, Taiwan. All participants lived within a 10 km radius of a large petrochemical complex and did not work in the factory. This study was conducted with the local hospital through annual community health screening. Biological samples were collected and biomarkers determined and quantified in the central laboratory of the collaborating hospital., Results: A total of 6335 adult residents completed the study. The mean age was 47.7 (SD = 16) years. Out of the total population, 56.4% were female, 30.1% had metabolic syndrome (MetS), and 16.8% and 14.3% had hepatitis B virus antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) positivity, respectively. The median 1-OHP and MDA level was 0.11 and 0.9 μg/g creatinine with an interquartile range of 0.07-0.18, and 0.4-1.5, respectively. The MDA levels correlated with specific diseases. The multivariable ordinal logistic regression model revealed that female sex, smoking, betel nut use, HBsAg, and anti-HCV positivity were associated with higher 1-OHP levels. In men, MetS was associated with higher 1-OHP levels and regular exercise with lower 1-OHP levels. High MDA levels were associated with smoking, betel nut users, HBsAg, and anti-HCV positivity., Conclusions: The findings highlight the importance of initiating individualized health promotion programs for residents near petrochemical factories, especially for adults with substance-use and cardiometabolic risk factors. Furthermore, it is crucial to provide further treatment to patients with viral hepatitis.

Background: Prisoners are at risk of hepatitis C virus (HCV) infection, especially among the people who inject drugs (PWID). We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals (DAA) regimen, 12 wk of sofosbuvir/velpatasvir, in a PWID-dominant prison in Taiwan., Aim: To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan., Methods: HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen, 12 wk of sofosbuvir/ velpatasvir, from two cohorts in Penghu Prison, either identified by mass screen or in outpatient clinics, in September 2019. Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group. The primary endpoint was sustained virological response (SVR12, defined as undetectable HCV ribonucleic acid (RNA) 12 wk after end-of-treatment)., Results: A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign; 91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/ pibrentasvir before mass screening were enrolled as a control. The HCV micro-elimination group had significantly lower proportion of diabetes, hypertension, hyperlipidemia, advanced fibrosis and chronic kidney diseases, but higher levels of HCV RNA. The SVR12 rate was comparable between the HCV micro-elimination and control groups, 95.8% (203/212) vs 94.5% (86/91), respectively, in intent-to-treat analysis, and 100% (203/203) vs 98.9% (86/87), respectively, in per-protocol analysis. There was no virological failure, treatment discontinuation, and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group., Conclusion: Outreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen, sofosbuvir/velpatasvir, provides successful strategies toward HCV micro-elimination among prisoners., Competing Interests: Conflict-of-interest statement: No author had reported a potential conflict of interest relevant to this work., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme., Design: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up)., Results: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively., Conclusion: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population., Clinicaltrialsgov Identifier: NCT03803410 and NCT03891550., Competing Interests: Competing interests: M-LY: research support from Abbvie, Abbott, BMS, Gilead, Merck and Roche. Consultant for Abbvie, Abbott, Ascletis, BMS, Gilead, J&J, Merck, Novartis, Pharmaessential and Roche. Speaker for Abbvie, Abbott, Ascletis, BMS, Gilead, Merck, Pharmaessential and Roche. C-FH: speaker for Abbvie, BMS, Gilead, Merck and Roche., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Community-based screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for hepatitis elimination. This study attempted to increase screening accessibility and efficacy by using alternative tools., Design: Population-based prospective cohort study., Setting: Hepatitis elimination program at Yunlin County, Taiwan., Participants: All 4552 individuals participated in 60 screening sessions of a community-based HBV and HCV screening project in five rural townships with approximately 95 000 inhabitants in central-western Taiwan., Interventions: To increase accessibility, 60 outreach screening sessions were conducted in 41 disseminative sites. Quantitative HBV surface antigen (qHBsAg) and anti-HCV testing with reflex HCV core antigen (HCV Ag) tests were employed as alternative screening tools., Main Outcome Measures: Calculate village-specific prevalence of HBsAg, anti-HCV and HCV Ag and establish patient allocation strategies according to levels of qHBsAg HCV Ag and alanine aminotransferase (ALT)., Results: Of 4552 participants, 553, 697 and 290 were positive for HBsAg, anti-HCV and HCV Ag, respectively; 75 of them had both HBsAg and anti-HCV positivity. The average (range) number of participants in each screening session was 98 (31-150). The prevalence rates (range) of HBsAg, anti-HCV and HCV Ag were 12.1% (4.3%-19.4%), 15.3% (2.6%-52.3%) and 6.4% (0%-30.2%), respectively. The HCV Ag positivity rate among anti-HCV-positive participants was 42% (0%-100%). Using cut-off values of >200 IU/mL for qHBsAg, >3 fmol/L for HCV Ag and >40 IU/mL for ALT as criteria for patient referral, we noted an 80.2% reduction in referral burden. Three villages had high anti-HCV prevalences of 52.3%, 53.8% and 63.4% with corresponding viraemic prevalences of 23.2%, 30.1% and 22% and thus constituted newly identified HCV-hyperendemic villages., Conclusion: Outreach hepatitis screening increases accessibility for residents in rural communities. Screening HBV and HCV through qHBsAg and HCV Ag tests provides information concerning viral activities, which might be conducive to precise patient allocation in remote communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P < .001). The HCV treatment rate increased from 2.3% (5/217) in 2012 to 21.7% (49/226) in 2019 (P < .001). In the sequential analysis of the 490 patients who participated in both screens, 17 of the 55 HCV-viremic patients became HCV RNA seronegative, including 13 by antivirals and four spontaneously. By contrast, one anti-HCV-seropositive but nonviremic patient became viremic, and six anti-HCV-seronegative patients became anti-HCV-seropositive in 2019. The annual incidence of new HCV was 0.2%/year. Seven HBsAg-seropositive patients experienced HBsAg loss (1.25%/year). Two patients had new anti-HBc seropositivity (new HBV exposure: 0.57%/year). The seroprevalence of viral hepatitis decreased in an 8-year follow-up but remained prevalent, and the treatment of HCV infection was underutilized in uraemic patients. Additional efforts are needed to enhance the HCV treatment uptake of uraemic patients. Clinical Trial IDs: NCT03803410, NCT01766895., (© 2021 John Wiley & Sons Ltd.)

Background/purpose: The HCV core antigen (HCV Ag) assay displays high sensitivity and strong correlation with HCV RNA. However, the feasibility of anti-HCV reflex HCV Ag screening in a community-wide setting is rarely discussed., Methods: We performed a two-phase community-based hepatitis C screen in an HCV-prone area of central Taiwan. During the training phase, all participants were test for anti-HCV, HCV Ag and HCV RNA to validate sensitivity, specificity, and accuracy of HCV Ag. During the validation phase, an anti-HCV reflex HCV Ag screen was conducted based on the results of training phase. Outcomes of the study were presented as positive and negative predictive values (PPV and NPV)., Results: Of 935 training phase participants, the rate of positive anti-HCV and HCV Ag were 175 (18.7%) and 78 (8.3%), respectively. Test sensitivity, specificity, and accuracy of HCV Ag were 97.1%, 98.6%, and 97.8%, respectively. During validation phase, only anti-HCV-positive serum samples were tested for HCV Ag. Of 1932 participant, 285 (14.8%) were anti-HCV-positive. 133 (46.7%) of the 285 anti-HCV-positive samples were HCV Ag-positive. PPV and NPV were 98.4% and 99.3%, respectively. Across the entire participant sample, a significant linear correlation between HCV Ag and HCV RNA concentration was noted (r 2  = 0.93, p-value<0.001) following log-log transformation., Conclusion: Anti-HCV reflex HCV Ag screening is a feasible strategy for aiding HCV-prone communities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10-0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13-0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04-40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

Objectives: Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. Tzukuan, located in the southwestern area of Taiwan, is an HCV hyperendemic area (>30%). This study aimed to assess the changing epidemiological characteristics of HCV infection and to evaluate the long-term outcomes after the implementation of public health strategies for two decades., Design: A population-based retrospective cohort study., Setting: A comprehensive care programme was implemented, namely COMPACT Study, in Tzukuan since 1997., Participants: A total of 10 714 residents participated the screening., Outcome Measures: The HCV status, demographic and clinical profiles of the participants were recorded and validated annually from 2000 through 2019., Results: The HCV infection prevalence rates were 21.1% (1076/5099) in 2000-2004, 18.8% (239/1269) in 2005-2009, 14.1% (292/2071) in 2010-2014 and 10.3% (234/2275) in 2015-2019 (p for trend test <0.0001). Among them, 1614 underwent repeated tests during the follow-up period. The annual incidence rates were 0.54% in 2005-2009, 0.4% in 2010-2014 and 0.22% in 2015-2019, respectively (p=0.01). In addition to old age, lower education level was a major risk factor for HCV infection across different periods. HCV infection prevalence rate among those illiterates reached 40.9%, followed by 28.5% in those with elementary school level, and <10% in those with high school or higher levels. The major risk factor has shifted from iatrogenic exposure in 2000-2009 to household transmission after 2010., Conclusions: HCV infection has been decreasing and the epidemiological features are changing in the hyperendemic area by continuing education, prevention and treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population., Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan., Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10)., Conclusion: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Data on direct-acting antiviral agent (DAA) treatment for mixed genotype hepatitis C virus (HCV) infection are scant. This study examined the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) and ledipasvir/sofosbuvir (LDV/SOF) for mixed HCV genotype infection in a real-world setting in Taiwan. We analysed the data from all patients with mixed HCV genotype infections treated with GLE/PIB or LDV/SOF from 2017 to 2019 in three Chang Gung Memorial Hospitals in Taiwan. The primary treatment outcome was sustained virologic response 12 weeks after treatment cessation (SVR12). Adverse events (AEs) were also evaluated. A total of 5190 HCV patients received DAA treatment during this time period. Among them, 116 patients (2.2%) had mixed infections of any 2 or 3 genotypes of 1a, 1b, 2, 3 and 6. Fifty-four patients received GLE/PIB and 62 received LDV/SOF. SVR12 rates for LDV/SOF vs GLE/PIB therapy were 96.6% (56/58) vs 100% (51/51) by the per-protocol analysis and 90.3% (56/62) vs 94.4% (51/54) by the evaluable population analysis. Two patients with 1b + 6 and 1b + 2 genotype infections in the LDV/SOF group had relapse. Evaluating the GLE/PIB vs LDV/SOF groups for the most common AEs revealed pruritus (16.7% vs 4.8%), abdominal discomfort (5.6% vs 8%) and fatigue (5.6% vs 4.8%). One patient with AE-related treatment discontinuation presented with liver decompensation after 4-week GLE/PIB therapy. DAA-related significant laboratory abnormalities occurred in two patients with >3× elevated bilirubin level in the GLE/PIB group. GLE/PIB and LDV/SOF are well tolerated and achieve high SVR12 rates for patients with mixed HCV genotype infection., (© 2020 John Wiley & Sons Ltd.)

Background: Hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma globally. The advent of direct-acting antivirals (DAAs) with high cure rates provides an opportunity to reduce the rising HCV disease burden. However, few studies have explored the side effects and physiological benefits of DAA therapy in rural areas. The aim of this study was to investigate the subjective reports of discomfort, patient feedback about the course of treatment, and physiological changes after DAA treatment in HCV patients. Methods: A descriptive, prospective, comparative cohort study was conducted from January to August 2019 in western coastal Yunlin County, Taiwan. Data regarding demographic characteristics, subjective discomfort levels, and physiological responses were collected through face to face interviews and from medical records by a cooperating hospital. Results: Six-hundred-and-twenty-three participants with an active HCV infection were identified; 555 (89.1%) had completed treatment, and sustained virologic response was achieved in 99.6% (n = 553). The mean age was 64.9 (standard deviation = 13.1) years, and 35% of patients experienced discomfort during DAA treatment, including fatigue, itching, and dizziness. After three months of treatment, physiological markers, including body weight ( p < 0.001), waist circumference ( p < 0.05), blood pressure ( p < 0.001), alanine aminotransferase ( p < 0.001), and aspartate aminotransferase ( p < 0.001), had significantly improved. Almost all participants provided positive feedback about the treatment experience and reported manageable side effects. Conclusions: The findings showed that, in an endemic rural area, DAA treatment had a high cure rate and improved physiological markers with few discomforts. These results can be used to reduce the barriers HCV patients face in adopting new medications.

Aims: To explore the effectiveness of an oral hygiene programme combined with home phone counselling on hepatitis C patients during antiviral treatment., Background: Hepatitis C virus infection is the leading cause of liver diseases. Evidence indicates that the antiviral treatment for hepatitis C virus infection has been successful, albeit its many side effects, such as discomfort symptoms of oral ulcers, which, in turn, leads to discontinued treatment. Inappropriate oral hygiene may worsen the side effects and increase the risk of dropping out of the treatment., Design: A quasi-experimental pre-post-test design was used., Methods: The oral hygiene programme was based on a standardized protocol of oral health care combined with home phone counselling. The participants were recruited from an outpatient clinic between August 2016 and July 2017. The generalized estimating equation was used for repeated measures of oral health behaviour, oral health status and discomfort symptoms., Findings: Thirty-four participants completed this study. The findings indicated that the oral hygiene programme significantly improved tooth brushing, use of dental floss and oral comfort. The result showed that the participants' oral health status significantly improved in 3 months., Conclusions: This pilot study supports the finding that an oral hygiene programme can reduce oral discomfort, improve oral hygiene behaviour, and enhance the oral health status of hepatitis C patients receiving treatment. This is a simple and low-cost programme, which can be performed at home easily and boosts the completion of antiviral treatment., (© 2018 John Wiley & Sons Ltd.)

Background: We aimed to investigate the long-term outcomes in hepatitis B (HBV)/hepatitis C virus (HCV) dual-infected patients after anti-HCV therapy., Methods: A total of 192 HBV/HCV dual-infected patients who had received pegylated interferon treatment were recruited. The investigation outcomes included HBV DNA ≥2000 IU/mL, with or without alanine aminotransferase (ALT) ≥2-fold the upper limit of normal, and hepatitis B surface antigen (HBsAg) seroclearance., Results: Four (2.1%) patients developed early HBV reactivation before the end of treatment. Fifty (26.6%) of the remaining patients had an episode of HBV DNA ≥2000 IU/mL in a mean follow-up of 68.8 months. The risk was 4.6 per 100 person years. Only 19 (10.1%) patients developed concomitant ALT flare with oral HBV antiviral therapy; the risk was 1.7 per 100 person years. Despite HBV flare, 67 (34.9%) patients had a favorable outcome of HBsAg seroclearance. The probability was 5.7 per 100 person years. A pretreatment HBV DNA level of 300 IU/mL served as an independent predictor for all the outcomes. The combined pretreatment HBV DNA level and HCV response further enhanced the prediction of HBV flare and HBsAg seroclearance., Conclusions: A pretreatment HBV DNA level of 300 IU/mL predicts HBV flare and HBsAg seroclearance after anti-HCV therapy., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: Early low bone mass is a risk factor for osteoporotic fractures associated with multiple factors, including menopause and chronic liver diseases. Hepatitis C virus (HCV) also plays a major role in chronic liver disease and has many extrahepatic consequences, such as decreased bone mineral density (BMD). This study aimed to examine the hypothesis that HCV seropositivity is independently associated with menopausal BMD loss., Methods: This community-based, cross-sectional study was based in two rural townships in Yunlin County, Taiwan. A total of 636 menopausal women aged 45-80 years who underwent annual health checks were included. Viral markers of HCV, dual-energy X-ray absorptiometry and fracture risk assessment tool (FRAX) scores were measured. Logistic regression analysis was performed to assess the association between various predictors and the presence of low BMD., Results: The participants (median age: 65 years) had a HCV seropositivity rate of 32.2%. BMD was significantly lower in the HCV-seropositive participants in different anatomic locations than in the seronegative individuals (lumbar spine: -1.5 vs -1.1; total hip: -0.9 vs -0.6; femoral neck: -1.2 vs -1.0; p<0.05). HCV-seropositive subjects had higher rates of major osteoporotic fractures (11.3%±7.6%vs 9.0±6.8%; p<0.001) and hip fractures (3.4%±4.7%vs 2.3±4.9%; p=0.006) and a higher risk of lower BMD (osteopenia and osteoporosis) based on a multivariable regression analysis (adjusted OR: 1.8; 95% CI 1.16 to 2.81; p=0.009)., Conclusions: HCV infection may be an independent risk factor for menopausal BMD loss and fractures predicted by FRAX., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) have rarely been studied because they rarely accept interferon-based therapy (IBT) and have been difficult to follow up. We investigated long-term outcomes of IBT on the population., Methods: This population-based cohort study used the Taiwan National Health Insurance Research Database as its data source. HCV patients diagnosed with CKD between Jan. 1, 2003, and Dec. 31, 2013, were selected. They were then divided into two groups based on whether they had undergone IBT. All-cause mortality, acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke, and new-onset dialysis were evaluated using a Cox proportional hazard regression analysis after propensity score matching., Results: We enrolled 9872 HCV patients with CKD: 1684 patients in the treated cohort and 8188 patients in the untreated cohort. The annual incidence of all-cause mortality (19.00 vs. 42.89 events per 1000 person-years; p < 0.001) and the incidences of hemorrhagic stroke (1.21 vs. 4.19 events per 1000 person-years; p = 0.006) were lower in the treated cohort. New-onset dialysis was also lower in the treated cohort (aHR: 0.31; 95% CI: 0.20-0.48; p < 0.001)., Conclusion: Antiviral therapy might provide protective benefits on all-cause mortality, hemorrhagic stroke, and new-onset dialysis in HCV-infected patients with CKD.

The impact of sex on metabolic alterations in individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains elusive.A community-based study was performed to assess sex, age, body mass index, the lipid profile, blood pressure, glucose, alanine aminotransferase, HBV surface antigen (HBsAg), and HCV antibody levels, smoking and alcohol drinking habits, and cardiometabolic diseases, including diabetes, hypertension, cardiovascular events, and renal diseases. The HCV-RNA level and genotype were further assessed in HCV antibody-positive subjects, and the hepatitis B e antigen and HBV-DNA levels were further examined in HBsAg-positive subjects.Among the 10,959 adults enrolled, 1949 (17.8%) and 1536 (14.0%) were HBV and HCV-infected, respectively. Univariate and multivariate analyses showed that the lipid profile and hypertension were independently associated with HCV infection (95% confidence intervals of odds ratios [OR 95% CI]: total cholesterol [TC] = 0.508-0.677; triglycerides = 0.496-0.728; hypertension = 0.669-0.937), but not with HBV infection. Consistently, HCV, but not HBV infection, was negatively associated with the TC and triglyceride levels (OR 95% CI for TC: 0.450-0.601; triglycerides: 0.443-0.671). Generalized linear models revealed that HCV infection, sex, and age interactively affected the lipid profile (OR 95% CI TC = 1.189-1.385; triglycerides = 1.172-5.289). Age-stratification analysis showed that the lipid levels were lower in both the HCV-positive females aged ≥49 years (TC, P < 0.001; triglycerides, P = 0.001) and males of all ages (TC, P < 0.001; triglycerides, P < 0.001) compared with their sex and age-matched HCV-negative counterparts. HCV infection was associated with a higher body mass index (≥49 years, β = 0.405, P = 0.002) and increased rates of cardiovascular events (<49 years, OR 95% CI 1.23-9.566), diabetes (≥49 years, OR 95% CI 1.114-1.932), and renal diseases (≥49 years, OR 95% CI 1.23-9.55), and with a lower rate of hypertension (≥49 years, OR 95% CI 0.616-0.964) in the females, but not in the males, as determined by multivariate analyses.Only HCV infection was associated with metabolic alterations in this HBV/HCV-hyperendemic area. Females aged ≥49 years and males of all ages exhibited HCV-associated hypolipidemia. HCV-associated cardiometabolic diseases were evident only in the females. Sex dimorphism in HCV-associated metabolic complications warrants personalized follow-up of HCV-positive patients.

Background: The optimal therapeutic strategy for hepatitis B virus (HBV) e antigen (HBeAg)-seropositive and hepatitis C virus (HCV) dually infected patients remains unknown. We aimed to elucidate the effectiveness of peginterferon (Peg-IFN)/ribavirin (RBV) with and without lamivudine (LAM) combination therapy in the clinical settings., Patients and Methods: Nine patients seropositive for HBV surface antigen, HBeAg, antibodies to HCV and HCV RNA for >6 months were treated with Peg-IFN/RBV with (n = 5) and without (n = 4) a 12-month LAM add-on therapy at treatment week 12. The treatment duration of Peg-IFN/RBV was 24 weeks (HCV genotype 1 [HCV-1] with rapid virological response [RVR] or HCV-2) or 48 weeks (HCV-1 without RVR). Primary endpoints included HBeAg loss and HCV-sustained virological response (SVR)., Results: All of the nine patients had undetectable HCV RNA at treatment weeks 4 and 12 and end-of-Peg-IFN/RBV therapy. However, SVR was achieved in 100% of patients treated with triple therapy, compared with only 50% in those with Peg-IFN/RBV therapy (P = 0.167). The 3-year durability of HCV SVR was 100%. HBeAg loss and HBV DNA <2000 IU/mL at 6 months post-LAM treatment were found in 100% and 40% of patients treated with triple therapy, compared with none of the four patients with Peg-IFN/RBV therapy achieved any HBV responses. Of the five patients with triple therapy, four had persistent HBeAg loss during 3-year follow-up period; one developed HBeAg seroreversion 15 months after treatment., Conclusion: For HBeAg-positive HBV/HCV dually infected patients, Peg-IFN/RBV was effective for HCV eradication. Add-on LAM might promote HBeAg loss in the clinical setting., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.

Background: Evidence indicates that hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the leading causes of liver cirrhosis and hepatocellular carcinoma. Antiviral treatments have recently been reported as successful cures. However, the prevalence rates of HBV or HCV infection, unhealthy behaviors and receipt of adequate treatment in disabled adults have not been described. The aim of this study was to examine the prevalence of HBV or HCV carriers, receipt of antiviral treatment, and early detection of unhealthy behaviors in disabled adults in Taiwan., Methods: A population-based, cross-sectional study was conducted between July and December 2013 with 845 community-dwelling adults with disabilities aged >20 years. Statistical analyses included descriptive statistics, Chi-squared tests, and stepwise regression analysis., Results: The prevalence of HBV and HCV infections was 12.9 and 14.1 %, respectively. HCV carriers tended to be older (p < 0.001) and with a lower education (p < 0.001). The majority of HBV/HCV carriers did not know the type of hepatitis infection and did not receive adequate antiviral treatment. After adjusting for potential confounding variables, regression analysis showed that the factors significantly associated with elevated liver function were HCV infection (p < 0.001), HBV infection (p = 0.001), high fasting blood glucose levels (p = 0.001), overweight (p = 0.003), older age (p = 0.027), and alcohol drinking (p = 0.028)., Conclusions: There was a high prevalence of HCV infection among adults with disabilities; few received adequate antiviral treatment or early detection of unhealthy behaviors for the prevention of liver cancer. Clinicians can provide health education to help the participants and caregivers better understand the relationships between specific risk factors and liver health and can encourage HBV and HCV carriers to undergo annual physical check-ups and receive adequate treatment, as covered by the national health insurance.

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the leading causes of liver cirrhosis and hepatocellular carcinoma. Little is known about the relationship between health-related behaviors and health status among HBV or HCV carriers., Objective: The purpose of this study was to explore the relationship between health status (eg, specific biomarkers) and health-related behaviors (eg, alcohol consumption) in individuals with or without HBV or HCV infection., Methods: A cross-sectional descriptive design was used, and a community-based health screening survey was conducted between August 2011 and July 2012 in Taiwan., Results: In total, 6 805 community residents 20 years or older participated in the study. The HBV and HCV infection rate was 18.7% and 20.8%, respectively, and HBV/HCV infections were significantly associated with current alcohol use, smoking, and self-medication. Multivariate analysis indicated that HBV/HCV infection, overweight status, higher fasting blood sugar level, higher systolic blood pressure, and 3 unhealthy habits were independent risk factors for abnormal liver function., Conclusion: Our findings suggest that both HBV and HCV carriers are more likely to have unhealthy habits and a poor health status. In addition to some factors that cannot be modified, being overweight, drinking alcohol, betel nut chewing, smoking, and self-medication are all risk factors for poor liver health among both hepatitis carriers., Implications for Practice: For clinicians, the results could be applied by providing more education to help the community better understand the relationships between specific risk factors and liver health, encouraging hepatitis carriers in rural areas to undergo annual physical check-ups.

Background: Chronic kidney disease (CKD) and hepatitis C virus (HCV) infection are closely linked and both increase patient mortality. The association of HCV and risk of developing end-stage renal disease (ESRD) has not been analyzed with competing risk model., Method: We enrolled a prospective cohort of 4,185 patients (mean age, 62 years; 41% female) registered in the CKD integrated care program at two affiliated hospitals of Kaohsiung Medical University in Taiwan between November 11, 2002 and May 31, 2009. With competing risk model, we analyzed the association of HCV infection, defined by seropositive of anti-HCV antibody, and hepatitis B virus (HBV) infection, defined by seropositive of HBV surface antigen, with the risk of entering ESRD., Results: The prevalence of HCV infection was 7.6% and it increased with the CKD stages (trend test, P<0.001), while the prevalence of HBV infection was 7.4% and no specific trend among CKD stages (tend test, P = 0.1). During the 9,101 person-year follow-up period, there were 446 death and 1,205 patients entering ESRD. After adjusting death as the competing risk, the estimated 5-year cumulative incidence rate of ESRD among patients with and without HCV infection were 52.6% and 38.4%, respectively (modified log-rank, P<0.001). Multivariable analysis showed that HCV infection, but not HBV infection, had higher risk of developing ESRD compared with cases without infection (HCV, HR: 1.32, 95% CI: 1.07-1.62; HBV, HR: 1.10, 95% CI: 0.89-1.35). Subgroup analyses showed consistent results., Conclusions: With death-adjusted competing risk analysis, HCV infection is associated with an increased risk of developing ESRD in CKD cohort.

Background: Hepatitis C virus (HCV) infection is a serious disease worldwide and it leads to several serious hepatic sequels. Some studies find possible correlation between HCV and ischemic heart disease in retrospective observations. Based on lacked community-based evidence, the study aims to assess correlation between ischemic heart disease and chronic HCV infection via electrocardiogram (ECG) because its abnormalities is strongly associating with cardiovascular disease mortality., Methods: The population was from one community health examination in December 2010 in a southern village of Taiwan. A total of 9856 participants were evaluated and finally 5015 eligible residents with age older than 40 years were included. The baseline characteristics and laboratory data in nonischemic ECG and ischemic ECG groups were compared, and multivariate-adjusted analysis was used to evaluate the risks to ischemic ECG., Results: The higher prevalence of hypertension, metabolic syndrome and even HCV infection (25.3% versus 11.6%; P < 0.001) in ischemic ECG group than those in nonischemic ECG group. In the multivariate adjusted analysis, HCV infection would lead to a 1.759-fold risk to ischemic ECG when compared with non-HCV subjects., Conclusions: HCV was strongly associated with ischemic ECG findings in this community study, and it could be a nonconventional risk factor for coronary artery disease.

The aim of this study is to explore the prevalence of hepatitis C virus (HCV) infection among injection drug users (IDUs) with and without human immunodeficiency virus (HIV) infection in southern Taiwan. For 562 IDUs (265 anti-HIV negative, 297 anti-HIV positive), we analyzed liver function, anti-HIV antibody, anti-HCV antibody, HCV viral loads, and hepatitis B surface antigen (HBsAg). HIV RNA viral loads and CD4 cell count for anti-HIV-seropositive IDUs and the HCV genotype for HCV RNA-seropositive IDUs were measured. The seroprevalence rates of anti-HIV, anti-HCV, and HBsAg were 52.8%, 91.3%, and 15.3%, respectively. All the anti-HIV-seropositive IDUs were positive for HIV RNA. Anti-HCV seropositivity was the most important factor associated with HIV infection (odds ratio [OR], 25.06; 95% confidence intervals [CI], 8.97-74.9), followed by male gender (OR, 6.12; 95% CI, 4.05-9.39) and HBsAg seropositivity (OR, 1.90; 95% CI, 1.11-3.34). Among IDUs positive for anti-HCV, 80.7% had detectable HCV RNA. HCV viremia after HCV exposure was strongly related to HIV infection (OR, 6.262; 95% CI, 1.515-18.28), but negatively correlated to HBsAg seropositivity (OR, 0.161; 95% CI, 0.082-0.317). HCV genotype 6 was the most prevalent genotype among all IDUs (41.0%), followed by genotypes 1 (32.3%), 3 (12.8%), and 2 (5.6%). In conclusion, about half IDUs were infected with HIV and >90% with HCV infection. Male and seropositivity for HBsAg and anti-HCV were factors related to HIV infection among our IDUs. HIV was positively correlated, whereas hepatitis B co-infection was negatively correlated with HCV viremia among IDUs with HCV exposure. Different HCV molecular epidemiology was noted among IDUs.

Background/aims: The impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown., Methods: On-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin., Results: Forty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%)., Conclusions: Peginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR.

Background: Injecting drug users (IDUs) in Taiwan contributed significantly to an HIV/AIDS epidemic in 2005. In addition, studies that identified risk factors of HCV/HIV co-infection among IDUs were sparse. This study aimed to identify risk factors of HCV/HIV co-infection and HCV mono-infection, as compared with seronegativity, among injecting drug users (IDUs) at a large methadone maintenance treatment program (MMTP) in Taipei, Taiwan., Methods: Data from enrollment interviews and HCV and HIV testing completed by IDUs upon admission to the Taipei City Hospital MMTP from 2006-2010 were included in this cross-sectional analysis. HCV and HIV testing was repeated among re-enrollees whose HCV or HIV test results were negative at the preceding enrollment. Backward stepwise multinomial logistic regression was used to identify risk factors associated with HCV/HIV co-infection and HCV mono-infection., Results: Of the 1,447 IDUs enrolled, the prevalences of HCV/HIV co-infection, HCV mono-infection, and HIV mono-infection were 13.1%, 78.0%, and 0.4%, respectively. In backward stepwise multinomial regression analysis, after controlling for potential confounders, syringe sharing in the 6 months before MMTP enrollment was significantly positively associated with HCV/HIV co-infection (adjusted odds ratio [AOR]=27.72, 95% confidence interval [CI] 13.30-57.76). Incarceration was also significantly positively associated with HCV/HIV co-infection (AOR=2.01, 95% CI 1.71-2.37) and HCV mono-infection (AOR=1.77, 95% CI 1.52-2.06), whereas smoking amphetamine in the 6 months before MMTP enrollment was significantly inversely associated with HCV/HIV co-infection (AOR=0.44, 95% CI 0.25-0.76) and HCV mono-infection (AOR=0.49, 95% CI 0.32-0.75). HCV seroincidence was 45.25/100 person-years at risk (PYAR; 95% CI 24.74-75.92/100 PYAR) and HIV seroincidence was 0.53/100 PYAR (95% CI 0.06-1.91/100 PYAR) among re-enrolled IDUs who were HCV- or HIV-negative at the preceding enrollment., Conclusions: IDUs enrolled in Taipei MMTPs had very high prevalences of HCV/HIV co-infection and HCV mono-infection. Interventions such as expansion of syringe exchange programs and education regarding HCV/HIV prevention should be implemented for this high-risk group of drug users.

Background: Taiwan has a growing HIV/AIDS epidemic that has recently shifted to an increase among injection drug users (IDUs). This study aimed to measure the prevalence and incidence and identify the correlates of HIV infection among IDUs in a large methadone maintenance treatment program (MMTP) in Taipei, Taiwan., Methods: Data from intake interviews and HIV testing completed by IDUs upon admission to the Taipei City Hospital MMTP in 2007-2010 were included in this analysis. HIV testing was repeated semi-annually among maintained clients who were HIV-negative during MMTP admission., Results: Of 1444 IDUs admitted, 85.9% were male, median age was 40 years, and mean years of injecting was 14.3 (range: 1-64). The prevalence of HIV, HCV, and HIV/HCV co-infection was 13.4%, 91.1%, and 13.2%, respectively. In multivariable analysis, HIV infection was associated with sharing syringes during the 6 months prior to admission (OR = 14.76, 95% CI 10.31-21.13), homelessness (OR = 6.46, 95% CI 1.49-28.00), and lifetime number of MMTP admissions (OR = 1.76, 95% CI 1.30-2.38) and times incarcerated (OR = 1.10, 95% CI 1.03-1.18). HIV seroincidence was 1.15/100 person-years at risk (95% CI .62-8.77/100 PY) among IDUs who were HIV-negative at first admission., Conclusions: Taiwanese IDUs in MMTP have a high HIV prevalence, which was associated with syringe sharing and other factors related to social marginalization. Our findings highlight the importance of harm reduction programs, including syringe exchange, along with HIV-prevention education.

Background: Both interleukin-28B genetic variants and on-treatment virological responses are factors predictive of treatment outcome in hepatitis C virus genotype 1 (HCV-1) patients. We aimed to compare the clinical significance of the two factors., Methods: Rs8099917 genotype and on-treatment responses were determined in 182 HCV-1 patients with 48-week peginterferon/ribavirin., Results: Comparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, 46.2% vs. 19.2%, P=0.01) and sustained virological response (SVR, 85.3% vs. 42.3%, P<0.001) rates. Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/95% confidence intervals [OR/CI]: 4.25/1.39-13.01). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 57.22/6.23-525.37), followed by the carriage of rs8099917 TT genotype (OR/CI: 10.06/3.12-32.44). However, while on-treatment factors were taken into account, the cEVR was the most important determinant to an SVR (OR/CI:54.98/9.07-333.38), whereas the influence of rs8099917 genotype became non-significant in non-RVR patients., Conclusions: Rs8099917 TT genotype is significantly independently predictive of on-treatment virological responses, which were the major determinants of an SVR, in Asian HCV-1 patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major causes of liver disease in Taiwan and have a great impact on the health of this country. This study investigated the seroprevalence of HBV and HCV in southern Taiwan. Screening programs were performed from September 1999 to August 2005 for community-based surveillance of liver disease. A total of 28,797 adults from southern Taiwan, including Kaohsiung City (n = 14,036), Kaohsiung County (n = 7,713), and Pingtung County (n = 7,048) were participated. The mean age was 50.3 ± 14.6 years (range, 20-97 years), with 41.0% were men. Hepatitis B surface antigen (HBsAg), antibody to HCV (anti-HCV), and liver function tests were performed. Among the 28,797 adults, the prevalence of HBsAg(+) was 15.1% and that for anti-HCV(+) was 8.6%. The seroprevalence of HBsAg in Kaohsiung County was 18.2%, which was higher than in Kaohsiung City (14.7%, p < 0.001) or Pingtung County (12.5%, p < 0.001). The seroprevalence of anti-HCV in Kaohsiung County was 17.2%, which was higher than in the other regions (Kaohsiung City = 5.8%, p < 0.001; Pingtung County = 4.6%, p < 0.001). The prevalence of dual HBsAg and anti-HCV was 1.1% (323 patients). Tzukuan Township in Kaohsiung County was endemic for HBsAg (19.1%, 1,026/5,375 patients), anti-HCV (22.4%, 1,203/5,375 patients), and dual HBsAg/anti-HCV (3.6%, 191/5,375 patients). Subjects with anti-HCV(+) were older and had higher alanine transaminase levels than their HBsAg(+) counterparts (p < 0.001 and p < 0.001, respectively). The current study shows the epidemiological characteristics of HBV and HCV infections among adults in southern Taiwan. Viral hepatitis infections remain widely endemic in this region., (Copyright © 2010 Elsevier. Published by Elsevier B.V. All rights reserved.)

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may lead to nephropathy. However, the association between different types of viral hepatitis and chronic kidney disease (CKD) is not well established., Study Design: Cross-sectional study., Setting & Participants: A large-scale community study with 54,966 adults in a Taiwanese county endemic for HBV and HCV infection., Predictor: HCV infection alone, HBV infection alone, HBV/HCV coinfection, and neither., Outcomes: Proteinuria (urine protein, >or=1+), low (<60 mL/min/1.73 m(2)) estimated glomerular filtration rate (eGFR), and CKD (proteinuria or eGFR <60 mL/min/1.73 m(2))., Measurements: HBV and HCV infection were defined as a seropositive test result for hepatitis B surface antigen and HCV antibody. Proteinuria was assessed using a repeated dipstick method. eGFR was computed using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation., Results: Mean age of the study group was 60.8 years. Prevalences of HCV infection alone, HBV infection alone, HBV/HCV coinfection, and neither were 9.4%, 9.9%, 0.9%, and 79.8%, respectively. 2,994 (5.4%), 7,936 (14.5%), and 9,602 (17.5%) participants had proteinuria, low eGFR, and CKD, respectively. Multivariate logistic regression analyses showed that HCV infection alone (OR, 1.26; 95% CI, 1.17-1.38), but not HBV infection alone (OR, 1.04; 95% CI, 0.96-1.14) or HBV/HCV coinfection (OR, 1.12; 95% CI, 0.87-1.45), was an independent risk factor for CKD. The prevalence of HCV seropositivity was higher in later CKD stages, changing from 8.5% in CKD stage 1 to 14.5% in CKD stages 4-5. Adjusted ORs for HCV infection alone were 1.14 (95% CI, 1.003-1.300) for proteinuria and 1.30 (95% CI, 1.20-1.42) for low eGFR., Limitations: The definition of CKD status requires a 3-month duration of low eGFR or kidney damage; this was presumed, not documented, in this study., Conclusions: HCV infection, but not HBV infection, was associated significantly with prevalence and disease severity of CKD in this HBV and HCV endemic area.

Background & Aims: Hepatitis C virus (HCV) infection has been shown to be associated with a low platelet count. This study aimed to elucidate the association between virologic status and platelet count in individuals with HCV infection., Methods: A large-scale survey, enrolling 11,239 residents, was conducted in the Kaohsiung area of Taiwan. Serum HCV RNA and non-invasive markers of fibrosis (FibroTest) were tested for antibody to HCV (anti-HCV)-positive subjects. The platelet counts of age- and sex-matched, biopsy-proven, hospital-based patients and community-based patients with minimal fibrosis were compared., Results: Anti-HCV was positive in 703 (6.2%) subjects and was significantly associated with older age, female sex, abnormal alanine aminotransferase (ALT) value and low platelet count (<150,000/microl). The independent factors significantly associated with low platelet count were abnormal ALT value (odds ratio [OR]: 3.70, 95% confidence intervals [CI]: 2.18-6.28) and positive HCV RNA (OR: 2.00, 95% CI: 1.01-3.97). After adjustment for the fibrosis, HCV RNA remained significantly associated with platelet counts., Conclusions: Our results evaluating the association between platelet count and HCV viremia and taking the influences of fibrosis into consideration implicate that platelets may be affected directly by HCV.

Background/aims: To evaluate the association of virologic status with serum cholesterol and triglyceride levels in individuals with hepatitis C virus (HCV) infection., Methods: We conducted a large scale community-based study enrolling 11,239 residents in an area endemic for hepatitis B virus (HBV) and HCV infection in southern Taiwan. Overall, 703 (6.3%), 1,536 (13.7%), 84 (0.7%) and 9,084 (80.8%) subjects were sero-positive for anti-HCV antibody (anti-HCV), hepatitis B surface antigen (HBsAg), and both anti-HCV and HBsAg, and negative for anti-HCV and HBsAg, respectively., Results: By multivariate logistic analyses, the independent factors significantly associated with elevated serum cholesterol level were older age, female, negative for diabetes, anti-HCV or HBsAg and elevated triglyceride levels. The independent factors significantly associated with elevated serum triglyceride level were male, positive for diabetes, negative for anti-HCV or HBsAg, higher body mass index (BMI) and elevated cholesterol levels. Of 642 anti-HCV-positive subjects that have HCV RNA tested by standardized automated qualitative PCR assay, 478 (74.5%) were positive for HCV RNA. By multivariate logistic analyses, the independent factors associated with elevated serum cholesterol level were female, elevated serum triglyceride levels, negative for diabetes or HCV RNA. The independent factors associated with elevated serum triglyceride levels were elevated serum cholesterol levels, positive for diabetes, higher BMI and negative for HCV RNA. Diabetes, lower cholesterol and triglyceride levels were independent factors associated with positive HCV RNA., Conclusions: Based on the result of this large scale community study, HCV viremia appears to be associated with lower serum cholesterol and triglyceride levels which implies that HCV itself might play a significant role on serum lipid profile of patients with chronic HCV infection.

Background: Polymerase chain reaction (PCR) methods play an essential role in providing data relating to diagnosis, monitoring and treatment of hepatitis C virus (HCV) infection. The real-time reverse transcription PCR (RT-PCR) assay is an established and promising tool in terms of quantifying HCV RNA for clinical application. This study aimed to evaluate the performance characteristics of a real-time RT-PCR-based test in a clinical setting., Methods: Validation and reproducibility tests were performed using a standard panel. Sera from 197 chronic HCV patients were analyzed by the real-time RT-PCR assay and the results were compared with the Versant bDNA3.0 assay (bDNA3.0)., Results: The real-time RT-PCR assay showed an acceptable linear response (r2=0.989-0.995) in the serial dilutions regarding genotypes 1b, 2a, 2b and 1b+2a. HCV viral loads were quantifiable in all 197 patients (100%) by the real-time RT-PCR assay and in 194 (98.5%) by the bDNA3.0. HCV RNA quantification values measured by the real-time RT-PCR and bDNA3.0 assays were positively correlated (Pearson's correlation coefficient r=0.734, p<0.001). The real-time RT-PCR assay values were on average 0.13 logs higher than the bDNA3.0 results. The correlation coefficients with genotypes 1b, 2a, 2b and mixed were 0.737, 0.711, 0.791 and 0.766, respectively (p<0.01)., Conclusions: The real-time RT-PCR assay showed comparable performance with bDNA3.0 regarding quantification of HCV viral loads with genotype 1 and 2 HCV infections.