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BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.
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BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.
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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.
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BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.
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Ácidos Aminoisobutíricos , Bencimidazoles , Benzopiranos , Carbamatos , Ciclopropanos , Hepatitis C Crónica , Hepatitis C , Compuestos Heterocíclicos de 4 o más Anillos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Neoplasias Hepáticas , Prolina/análogos & derivados , Sulfonamidas , Humanos , Anciano , Sofosbuvir/uso terapéutico , Sofosbuvir/farmacología , Antivirales , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Taiwán/epidemiología , Quinoxalinas/uso terapéutico , Hepatitis C/tratamiento farmacológico , Hepatitis C/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Bilirrubina , GenotipoRESUMEN
BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
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Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Humanos , Hepacivirus/genética , Inteligencia Artificial , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , ARNRESUMEN
BACKGROUND: Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. METHODS: The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. RESULTS: Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. CONCLUSIONS: In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.
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Hepatitis C Crónica , Humanos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Taiwán/epidemiología , Hepacivirus/genética , Cirrosis Hepática/epidemiología , Respuesta Virológica Sostenida , Quinoxalinas/efectos adversos , Antivirales/efectos adversos , Sistema de Registros , Prolina , GenotipoRESUMEN
BACKGROUND/PURPOSE: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS: Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION: LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.
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Hepatitis C Crónica , Sofosbuvir , Antivirales/efectos adversos , Bencimidazoles , Quimioterapia Combinada , Femenino , Fluorenos , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Sistema de Registros , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Taiwán , Uridina MonofosfatoRESUMEN
To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of <150 × 103/µL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/µL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99-1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06-1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58-0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98-0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71-0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.
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Antivirales/uso terapéutico , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Anciano , Femenino , Hepacivirus , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recuento de Plaquetas , Estudios Retrospectivos , Respuesta Virológica Sostenida , Trombocitopenia/sangre , Trombocitopenia/tratamiento farmacológicoRESUMEN
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.
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BACKGROUND & AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.
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Hepatitis C Crónica , Insuficiencia Renal Crónica , Insuficiencia Renal , Antivirales/uso terapéutico , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Tasa de Filtración Glomerular , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Riñón/fisiología , Masculino , Sistema de Registros , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal Crónica/complicaciones , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
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.
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Ácidos Aminoisobutíricos/uso terapéutico , Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Ciclopropanos/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Lactamas Macrocíclicas/uso terapéutico , Leucina/análogos & derivados , Prolina/análogos & derivados , Pirrolidinas/uso terapéutico , Quinoxalinas/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Combinación de Medicamentos , Femenino , Hepatitis C/virología , Humanos , Leucina/uso terapéutico , Masculino , Persona de Mediana Edad , Prolina/uso terapéutico , Estudios Prospectivos , Sistema de Registros , Respuesta Virológica Sostenida , Taiwán , Resultado del TratamientoRESUMEN
Hepatocellular carcinoma (HCC) is a relatively chemo-resistant tumor. Several multi-kinase inhibitors have been approved for treating advanced HCC. However, most HCC patients are highly refractory to these drugs. Therefore, the development of more effective therapies for advanced HCC patients is urgently needed. Stathmin 1 (STMN1) is an oncoprotein that destabilizes microtubules and promotes cancer cell migration and invasion. In this study, cancer genomics data mining identified STMN1 as a prognosis biomarker and a therapeutic target for HCC. Co-expressed gene analysis indicated that STMN1 expression was positively associated with cell-cycle-related gene expression. Chemical sensitivity profiling of HCC cell lines suggested that High-STMN1-expressing HCC cells were the most sensitive to MST-312 (a telomerase inhibitor). Drug-gene connectivity mapping supported that MST-312 reversed the STMN1-co-expressed gene signature (especially BUB1B, MCM2/5/6, and TTK genes). In vitro experiments validated that MST-312 inhibited HCC cell viability and related protein expression (STMN1, BUB1B, and MCM5). In addition, overexpression of STMN1 enhanced the anticancer activity of MST-312 in HCC cells. Therefore, MST-312 can be used for treating STMN1-high expression HCC.
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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.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Persona de Mediana Edad , Sistema de Registros , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Taiwán/epidemiología , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Introduction: Hepatitis C is one of the leading causes of chronic liver disease. The direct-acting-antivirals has revolutionized the chronic hepatitis C treatment. DAAs can achieve a sustained virological response rate >95% in different populations.Area covered: This review summarizes the pharmacokinetics, pharmacodynamics, efficacy, and safety of Elbasvir/Grazoprevir (EBR/GZR).Expert opinion: EBR/GZR is a combination of NS5A and NS3/4A inhibitors. The performance in the EBR/GZR combination's safety and tolerability is appreciated in clinical treatment. EBR/GZR also has a higher barrier to resistance-associated substitutions. Based on clinical trials and real-world experience, elbasvir/grazoprevir is effective in the HCV GT1, 4 infections.
Asunto(s)
Antivirales/administración & dosificación , Benzofuranos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/administración & dosificación , Quinoxalinas/administración & dosificación , Antivirales/efectos adversos , Antivirales/farmacología , Benzofuranos/efectos adversos , Benzofuranos/farmacología , Combinación de Medicamentos , Farmacorresistencia Viral , Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Imidazoles/efectos adversos , Imidazoles/farmacología , Quinoxalinas/efectos adversos , Quinoxalinas/farmacología , Respuesta Virológica SostenidaRESUMEN
AIM: To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography. METHODS: One hundred and seventy-six patients with an episode of acute hepatitis flare (ALT value > 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups (viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h (median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed RESULTS: Enlarged lymph nodes (width ≥ 5mm) were noticeable in 110 (62.5%) patients, mostly in acute on chronic hepatitis B (54.5%). The viral group had a higher prevalence rate (89/110 = 80.9%) and larger nodal size (median, 7 mm) than those of the non-viral group (21/66 = 31.8%; median, 0 mm) (P < 0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups (P < 0.01), and between acute hepatitis A and non-hepatitis A viral groups (P < 0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis (P < 0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%. CONCLUSION: Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare.