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Introduction: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). Methods: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. Results: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. Conclusion: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) can progress to cirrhosis, but there are limited noninvasive tools available to estimate cirrhosis risk, including in patients receiving antiviral therapy. This study developed and validated a simple model to assess risk in CHB patients.Methods: The derivation cohort included 3000 CHB patients from 6 centers in the United States, with 52.60% receiving antiviral therapy. External validation was performed for 4552 CHB individuals from similar cohorts in Taiwan, with 21.27% receiving therapy. Cox proportional hazards regression analyses were used to screen predictors and develop the risk score for cirrhosis. Areas under receiver operating characteristic curves (AUROCs) were calculated for predictive value.Results: Sex, age, diabetes, antiviral treatment status/duration, hepatitis B e-antigen, and baseline alanine aminotransferase/aspartate aminotransferase levels were significantly associated with increased cirrhosis risk. A 13-point risk score was developed based on these predictors. The AUROCs for predicting cirrhosis risk were 0.82 at 3 years, 0.85 at 5 years, and 0.89 at 10 years in the derivation cohort, and 0.82, 0.79, and 0.77 in the validation cohort, respectively.Conclusions: We developed and validated a simple cirrhosis prediction model with an independent external cohort that can be applied to both treatment-naive and treatment-experienced CHB patients in diverse settings and locations. [ABSTRACT FROM AUTHOR]

Background/Aims: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. Methods: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. Results: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0–1, 2–3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ–AZ–Moderna (39.2%), followed by Moderna–Moderna–Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34–0.72, P < 0.001), female sex (OR/CI: 1.85/1.30–2.63, P = 0.001), Moderna–Moderna-based vaccination (compared to AZ–AZ-based vaccination, OR/CI: 6.49/3.90–10.83, P < 0.001), BNT–BNT-based vaccination (compared to AZ–AZ-based vaccination, OR/CI: 7.91/1.82–34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34–0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (β: − 0.083; 95% CI: − 0.094–0.011, P = 0.014) independently correlated with low IgG spike antibody levels. Conclusions: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR. [ABSTRACT FROM AUTHOR]

Introduction: Pangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL. Methods: This study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed. Results: In total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4–5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p < 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status. Conclusion: SOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities. [ABSTRACT FROM AUTHOR]

The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving. [ABSTRACT FROM AUTHOR]

Background/aims: Direct‐acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)‐infected patients. The real‐world treatment outcome in Taiwanese patients on a nationwide basis is elusive. Methods: The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end‐of‐treatment). Results: A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype‐1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment‐naïve noncirrhotic, treatment‐naïve cirrhotic, treatment‐experienced noncirrhotic and treatment‐experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment‐experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment‐naïve noncirrhotic patients (94.8%) and treatment‐experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence < 60% (adjusted odds ratio [aOR]/95% confidence interval [CI]: 117.1/52.4‐261.3, P <.001), followed by GT3/GT2 (aOR/CI: 5.78/2.25‐14.9, P =.0003 and aOR/CI: 1.55/1.05‐2.29, P =.03, compared with GT1), active hepatocellular carcinoma (aOR/CI: 4.29/2.57‐7.16, P <.001), the use of sofosbuvir/ribavirin (aOR/CI: 2.51/1.67‐3.77, P <.001) and daclatasvir/asunaprevir (aOR/CI: 3.29/1.94‐5.58, P <.001), decompensated liver cirrhosis (aOR/CI: 2.50/1.20‐5.22, P =.02) and high HCV viral loads (aOR/CI: 2.16/1.57‐2.97, P <.001). Conclusions: DAAs are highly effective in treating Taiwanese HCV patients in the real‐world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis C virus (HCV) genotyping is a pivotal tool for epidemiological investigation, guiding management and antiviral treatment. Challenge existed in identifying subtypes of genotype-1 (G-1) and genotype (GT) of indeterminate. Recently, the Abbott HCV RealTime Genotype Plus RUO assay (HCV GT Plus) has been developed aiming to overcome the limitations. We aimed to evaluate the performance of the assay compared with 5' UTR sequencing in clinical samples. Materials and methods: Eligible individuals were treatment chronic hepatitis C patients that were enrolled consecutively in a medical center and two core regional hospitals in southern Taiwan from Oct 2017 through Aug 2018. The patient with genotype 1 without subtype and indeterminate previously genotyped by Abbott RealTime HCV GT II will further determinate by Abbott HCV RealTime HCV GT Plus. All of the genotype results were validated by 5' UTR sequencing as a reference standard. Results: A total of 100 viremic CHC patients were recruited, including 63 G-1 patients (male: 28), and 37 patients (male: 15) of indeterminate genotyped by Abbott RealTime HCV GT II assay (HCV GT II), respectively. The detection rate of 63 GT1 samples without subtype were 93.7% (59/63), 37 indeterminate samples without genotype were 62.2 (23/37) by HCV GT Plus. 5' UTR sequencing confirmed HCV GT Plus characterized results for 84.7% (50/59) of type1, with 100% (4/4), 82.8 (24/29) and 84.6% (22/26) for 1a, 1b and type6; 65.2% (15/23) of indeterminate with 100% (3/3) and 60% (12/20) for 1b and type 6 samples, respectively. Conclusions: The Abbott RealTime HCV GT Plus RUO assay provides additional performance in GT detection. [ABSTRACT FROM AUTHOR]

Background and Aim: The serial serologic changes of hepatitis D virus (HDV) infection among chronic hepatitis B virus (HBV) infected patients who received oral nucleotide/nucleoside analogues are elusive. Methods: Serum anti‐HDV and HDV RNA among chronic hepatitis B (CHB) patients were tested at the time of initiating anti‐HBV therapy and subsequently during the follow‐up period. Results: The seropositive rate of anti‐HDV and HDV RNA among 2850 CHB patients, was 2.7% and 0.9%, respectively. Factors associated with anti‐HDV seropositivity were platelet counts (odds ratio [OR]/95% confidence intervals [CI]: 0.995/0.992–0.999; P = 0.006), HBV DNA levels (OR/CI: 0.81/0.70–0.94; P = 0.005), and hepatitis B e‐antigen (HBeAg) seropositivity (OR/CI: 0.22/0.05–0.95; P = 0.04). The only factor associated with HDV RNA positivity among anti‐HDV seropositive patients was age (OR/CI: 0.95/0.90–1.00; P = 0.03). The spontaneous clearance rate of serum anti‐HDV antibody was 3.0 per 100 person‐years with a median follow‐up period of 3.5 years (range 2–12 years), whereas the seroclearance rate of HDV RNA was 4.3 per 100 person‐years among anti‐HDV seropositive patients after a median follow‐up period of 6.0 years (range 2–11 years). A baseline anti‐HDV titer < 0.5 cut‐off index was the only factor predictive of anti‐HDV seroclearance (hazard ratio [HR]/CI: 30.11/3.73–242.85; P = 0.001). Conclusions: HDV infection was not common among patients treated for HBV in Taiwan. Seroclearance of anti‐HDV and HDV RNA did occur over time, albeit the chance is rare. [ABSTRACT FROM AUTHOR]