RESUMEN
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.
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Unidades de Hemodiálisis en Hospital/organización & administración , Hepatitis C/prevención & control , Diálisis Renal , Uremia/terapia , Viremia/prevención & control , Viremia/virología , Antivirales/uso terapéutico , Carbamatos/uso terapéutico , Combinación de Medicamentos , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Humanos , Tamizaje Masivo , Proyectos Piloto , Estudios Seroepidemiológicos , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , TaiwánRESUMEN
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.
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Hepatitis B , Hepatitis C , Hepatitis Viral Humana , Hepacivirus/genética , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C , Humanos , Diálisis Renal , Estudios Seroepidemiológicos , Taiwán/epidemiologíaRESUMEN
BACKGROUND AND AIM: Hepatitis B virus (HBV) surface antigen (HBsAg) seroreversion usually occurs during immunosuppressive therapy. The risk and factors of HBsAg seroreversion from resolved HBV infection in the general population remained unclear. METHODS: This retrospective study enrolled subjects with resolved HBV infection and who had received at least two times of screening in a longitudinal community screening program. HBsAg, hepatitis B surface antibody (anti-HBs), and hepatitis C virus antibody (anti-HCV) were tested every time in all subjects. The primary endpoint was HBsAg seroreversion. RESULTS: Of the 7630 subjects enrolled, 5158 (67.6%) subjects had positive anti-HBs at baseline. HBsAg seroreversion occurred in 84 subjects during 42 815-person-year follow-up with an annual incidence of 0.2% and a 10-year cumulative risk of 1.9%. Anti-HBV treatment-experienced subjects had a significantly higher risk of HBsAg seroreversion than anti-HBV treatment-naive subjects (83/310 [26.8%] vs 1/7320 [0.01%], P < 0.001). Lower rates of positive anti-HBs and anti-HCV were observed in anti-HBV treatment-experienced subjects who developed HBsAg seroreversion. Both positive anti-HBs (hazard ratio/95% confidence interval: 0.56/0.348-0.903, P = 0.017) and positive anti-HCV (hazard ratio/95% confidence interval: 0.08/0.030-0.234, P < 0.001) were independent factors of HBsAg seroreversion in anti-HBV treatment-experienced subjects. Less than 5% of the HBsAg seroreverters had clinical hepatitis flare at HBsAg seroreversion. The HBsAg titer was low, and only transient reappeared in most of the HBsAg seroreverters. CONCLUSIONS: Subjects with resolved HBV infection were at a minimal risk of HBsAg seroreversion, unless with prior anti-HBV treatment experience. Fortunately, even with a reappearance of HBsAg, it was transient and clinically non-relevant.
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Antígenos de Superficie de la Hepatitis B , Hepatitis B , Hepatitis B/inmunología , Hepatitis B/terapia , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIM: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.
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Hepatitis B , Hepatitis C Crónica , Isquemia Miocárdica , Comorbilidad , Femenino , Hepacivirus , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis C/epidemiología , Hepatitis C Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Diálisis Renal/efectos adversosRESUMEN
BACKGROUND: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. METHODS: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. RESULTS: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49-283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51-3.15, P < 0.001), detectable HBV DNA at year 1 (OR/CI: 1.99/1.36-2.92, P < 0.001), diabetes (OR/CI: 1.75/1.10-2.78, P = 0.02), body mass index (BMI) (OR/CI: 1.13/1.09-1.18, P < 0.001) and age (OR/CI: 0.97/0.96-0.98, P < 0.001). Among patients who were seronegative for HBV DNA at year 1, the strongest factor associated with ALT abnormality was HDV RNA seropositivity at year 1 (OR/CI: 30.00/3.28-274.05, P = 0.003), followed by liver cirrhosis (OR/CI: 1.83/1.21-2.75, P = 0.004), BMI (OR/CI: 1.16/1.11-1.21, P < 0.001) and age (OR/CI: 0.97/0.96-0.99, P < 0.001). Similarly, the impact of HDV RNA seropositivity on ALT abnormality was noted in patients without detectable HBV DNA but not in those with hepatitis B viremia at treatment year 2 (OR/CI: 10.16/1.33-77.74, P = 0.03). CONCLUSION: HDV infection played an important role in ALT abnormality in CHB patients receiving 1-year and 2-year NAs. The impact was particularly noted in patients who had successfully suppressed HBV DNA.
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Hepatitis B Crónica , Virus de la Hepatitis Delta , Nucleósidos/uso terapéutico , Nucleótidos/uso terapéutico , Alanina Transaminasa , ADN Viral , Femenino , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis D , Virus de la Hepatitis Delta/genética , Humanos , Estudios Longitudinales , MasculinoRESUMEN
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.
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Anticuerpos Antivirales/sangre , Coinfección/diagnóstico , Coinfección/virología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Hepatitis D/diagnóstico , Hepatitis D/virología , Nucleósidos/análogos & derivados , Nucleósidos/administración & dosificación , ARN Viral/sangre , Pruebas Serológicas , Administración Oral , Factores de Edad , Femenino , Estudios de Seguimiento , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/inmunología , Humanos , Masculino , Persona de Mediana Edad , Taiwán , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: The features of non-viral, nonalcohol hepatocellular carcinoma (NBNC-HCC) remain elusive. The aim of this study was to investigate this clinical characteristics and overall survival of NBNC-HCC compared to hepatitis B- (HBV-HCC) and hepatitis C-related (HCV-HCC) HCC. METHODS: We analyzed the etiologies, fibrosis stages, clinical data, and outcomes of newly diagnosed patients with HCC. RESULTS: A total of 1777 HCC patients were recruited, including 332 patients with NBNC-HCC, 682 patients with HBV-HCC, 680 patients with HCV-HCC, and 83 patients with HBV/HCV HCC. Patients with NBNC-HCC were older (69.9 ± 11.9 years). Patients with NBNC-HCC exhibited a higher prevalence of diabetes (43.9%) compared to the HBV-HCC (27.1%, p < 0.05) and HCV-HCC (30.2%, p < 0.05) groups. Compared to patients from the viral-related HCC groups, patients with NBNC-HCC exhibited a significantly lower fibrosis stage. NBNC-HCC patients exhibited a higher proportion of Barcelona Clinic Liver Cancer (BCLC) classification stage C and stage D compared to patients from the HBV-HCC and HCV-HCC groups. With a mean of 2.33 ± 2.31 years of follow-up, the median survival of patients with NBNC-HCC was 1.75 (95% CI 1.33-2.17) years, which was significantly lower than that of patients with HBV-HCC (p = 0.041) and HCV-HCC (p < 0.001). CONCLUSIONS: Patients with NBNC-HCC have a higher risk of diabetes than patients with HCC of viral etiologies. Although patients with NBNC-HCC exhibited a milder fibrosis stage, their more advanced HCC stages and worse overall survival should be taken into consideration in clinical care.
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Carcinoma Hepatocelular/terapia , Cirrosis Hepática/patología , Neoplasias Hepáticas/terapia , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Antineoplásicos/uso terapéutico , Aspartato Aminotransferasas/sangre , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Ablación por Catéter , Quimioembolización Terapéutica , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Hepatectomía , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Hipertensión/epidemiología , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Obesidad/epidemiología , Recuento de Plaquetas , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia , Albúmina Sérica/metabolismo , Índice de Severidad de la Enfermedad , Sorafenib/uso terapéutico , Tasa de SupervivenciaRESUMEN
BACKGROUND AND AIMS: Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients. METHODS: We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020. RESULTS: Eighty-six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6-4.6). The most frequently reported adverse events were hand-foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8-17.0) and the median progression-free survival (PFS) was 4.2 months (95% CI, 3.7-4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP < 400 ng/ml exhibited a markedly longer median OS, median PFS, and higher DCR compared with their counterparts (15.7 vs. 8.1 months, 4.6 vs. 3.7 months, 60.9% vs. 27.5%, respectively). Despite possessing high baseline AFP levels, patients with early AFP response (>10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP < 400 ng/ml. CONCLUSIONS: The results of this real-world study verified the tolerability and efficacy of regorafenib treatment for uHCC patients who failed prior sorafenib therapy, especially for those with lower baseline AFP levels or with early AFP response.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Terapia Recuperativa , Sorafenib/uso terapéutico , alfa-Fetoproteínas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/sangre , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/efectos adversos , Piridinas/efectos adversos , Factores de Riesgo , Análisis de Supervivencia , TaiwánRESUMEN
BACKGROUND: Chronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development. AIM: To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy. METHODS: One hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment. RESULTS: HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSION: Downregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Citocinas , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Factores de Riesgo , Respuesta Virológica Sostenida , Factor de Necrosis Tumoral alfaRESUMEN
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.
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Hepatitis C Crónica , Hepatitis C , Antivirales/efectos adversos , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , PrisionesRESUMEN
BACKGROUND/AIMS: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without. METHODS: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation. RESULTS: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001). CONCLUSION: The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.
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Hepatitis C , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hospitales , Humanos , Masculino , Persona de Mediana Edad , TaiwánRESUMEN
BACKGROUND: The World Health Organization (WHO) set out to eliminate hepatitis C virus (HCV) infection by 2030, a goal Taiwan might achieve before 2025. Using effective direct antiviral agents (DAAs) against chronic hepatitis C (CHC) in Taiwan, the treatment of CHC has been initiated in rural areas. Here, we aimed to elucidate the clinical and virological characteristics of HCV infection, and the treatment efficacy of DAAs in patients from Pingtung county in southern Taiwan. METHODS: A total of 152 chronic hepatitis patients treated with DAAs were consecutively enrolled. Baseline characteristics and therapeutic efficacy were evaluated. RESULTS: HCV genotype 2 was the most common viral genotype (39.5%), followed by 1b (36.8%), 6 (10.5%), and 1a (9.2%). The sustained virological response (SVR) rate was 98.7%. Hakka patients accounted for 22.4% of the study cohort, of which 14.7% had HCV genotype 6. There were no differences in clinical characteristics between Hakka and non-Hakka patients. Patients with HCV genotype 6 were younger in age (OR/CI: 0.95/0.91-1.00, p = 0.04) and composed of more people who inject drugs (PWID) (OR/CI: 17.6/3.6-85.5, p <0.001), when compared with other patients. CONCLUSION: We demonstrated that DAA therapy can achieve a 98.7% SVR rate among CHC patients in Pingtung county of southern Taiwan, with a relative higher prevalence of genotype 6. The most important factor attributed to genotype 6 infection was PWID.
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Genotipo , Hepatitis C Crónica/fisiopatología , Factores Raciales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/farmacología , Antivirales/uso terapéutico , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Taiwán , Adulto JovenRESUMEN
BACKGROUND/AIMS: Undetectable HCV RNA 12 weeks after the end of treatment (SVR12) has been the valid efficacy endpoint in the era of direct-acting antivirals (DAAs). Its concordance with SVR4 and SVR24 and long-term durability is unknown in Taiwanese chronic hepatitis C (CHC) patients. METHODS: A total of 1080 CHC patients who received all-oral DAAs and an achieved end-of-treatment virological response (EOTVR), defined as undetectable HCV RNA at the end of therapy, were consecutively enrolled. HCV RNA was monitored 4, 12, and 24 weeks after EOT. Patients who achieved SVR24, defined as undetectable HCV RNA 24 weeks after EOT, were followed annually for assessing SVR durability. RESULTS: Eleven (1.02%) patients experienced HCV RNA reappearance after EOT. The most frequent timing of RNA reappearance was observed at SVR4 (n = 7), followed by SVR12 (n = 3) and SVR 24 (n = 1). The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 in predicting SVR12 were 99.7% and 100%, respectively, whereas the PPV and NPV of SVR12 in predicting SVR24 were 99.9% and 100%, respectively. Pyrosequencing confirmed delayed relapse rather than reinfection for the patient who had detectable HCV RNA at SVR24. Among 978 patients who achieved SVR24, after a median follow-up period of 17.3±8.2 months, the SVR durability is 100% up to a 4-year follow-up. CONCLUSION: Achievement of SVR12 provides excellent durability of HCV seroclearance after DAA therapy. On-demand HCV RNA beyond SVR12 should be recommended for patients with unexplainable abnormal liver function or high-risk behaviors.
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Antivirales/administración & dosificación , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Respuesta Virológica Sostenida , Adulto , Anciano , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/genética , Carga ViralRESUMEN
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.
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Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/aislamiento & purificación , Abuso de Sustancias por Vía Intravenosa/complicaciones , Coinfección/sangre , Coinfección/diagnóstico , Coinfección/epidemiología , Femenino , Genotipo , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis B/sangre , Hepatitis B/diagnóstico , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis C/sangre , Hepatitis C/diagnóstico , Hepatitis D/sangre , Hepatitis D/diagnóstico , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/inmunología , Humanos , Masculino , Persona de Mediana Edad , Prisioneros/estadística & datos numéricos , Estudios Seroepidemiológicos , Taiwán/epidemiología , Carga Viral/métodosRESUMEN
Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11-19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35-24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03-6.54, P < 0.001), male gender (HR/CI 2.69/1.29-5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03-1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04-19.09, P = 0.04) and BMI (HR/CI 1.11/1.03-1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.
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Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis D Crónica/complicaciones , Virus de la Hepatitis Delta/genética , Neoplasias Hepáticas/epidemiología , Nucleósidos/uso terapéutico , Adulto , Factores de Edad , Carcinoma Hepatocelular/virología , Coinfección , Femenino , Hepatitis B Crónica/complicaciones , Humanos , Incidencia , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Profilaxis Pre-Exposición , ARN Viral/genética , Estudios Retrospectivos , Caracteres Sexuales , Análisis de Supervivencia , Taiwán/epidemiologíaRESUMEN
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.
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Hepatitis C , Anciano , Antivirales/uso terapéutico , Interacciones Farmacológicas , Femenino , Hepacivirus , Hepatitis C/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal , Sofosbuvir/uso terapéuticoRESUMEN
By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients' blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants.