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1.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
2.
Medicine (Baltimore) ; 100(33): e27000, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414987

RESUMO

ABSTRACT: Intermediate-stage hepatocellular carcinoma (HCC) is heterogeneous in terms of tumor size, number, and effects on liver function. Various noninvasive models have been proposed to assess functional hepatic reserve or fibrosis severity in patients with HCC. This study assessed the feasibility of 10 noninvasive models and compared their prognostic ability for patients with intermediate-stage HCC.This study retrospectively enrolled 493 patients with intermediate-stage HCC who received treatment at China Medical University Hospital from January 2012 to November 2018. Demographic data, clinical features, and factors associated with overall survival (OS) were recorded at baseline. Receiver-operating characteristic curve analysis and the DeLong method were respectively employed to evaluate and compare the models' OS prediction performance.Of the 493 patients, 373 (75.7%) were male, and 275 (55.8%) had liver cirrhosis (LC). The median age was 64 years (interquartile range: 55-72). Most patients had tumor volume ≤50% (n = 424, 86.0%), and the maximum tumor size was 6.0 (4.0-8.5) cm. The median α-fetoprotein was 36.25 (6.13-552.91) ng/mL. The patients underwent transarterial chemoembolization (TACE, n = 349) or surgery (n = 144). The median follow-up period was 26.07 (9.77-48.27) months. Across the 10 models, the albumin-bilirubin (ALBI) score had the highest area under the receiver operating characteristic curve (AUROC) (0.644, 95% confidence interval: 0.595-0.693) in all patients. In subgroup analyses, the Lok index, platelet-albumin-bilirubin score, ALBI score, and Lok index had the highest AUROC values in patients without cirrhosis, with cirrhosis, undergoing TACE, and undergoing surgery, respectively. Multivariate Cox regression analysis revealed that independent predictors of longer OS were ALBI grade 1 in all patients, patients with LC, and patients undergoing TACE and Lok index grade 1 in patients without LC and patients undergoing surgery.Among the 10 noninvasive models, ALBI score exhibited the highest diagnostic value in predicting OS for all patients, patients with cirrhosis, and those undergoing TACE, and Lok index grade exhibited the highest diagnostic value in predicting OS in patients without cirrhosis and those undergoing surgery.


Assuntos
Carcinoma Hepatocelular/mortalidade , Valor Preditivo dos Testes , Prognóstico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Taiwan/epidemiologia
3.
Hepatol Int ; 15(5): 1109-1121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34365587

RESUMO

BACKGROUND AND AIM: The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. METHODS: A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44 years. RESULTS: Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65 year-old, BMI ≥ 27 kg/m2, FIB-4 ≥ 3.25, eGFR < 60 ml/min/1.73 m2, and non-HCV SVR, but not HBV co-infection. CONCLUSION: Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

4.
J Formos Med Assoc ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34452785

RESUMO

BACKGROUND: The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy. METHODS: Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated. RESULTS: Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73-4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35-4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards. CONCLUSIONS: In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34333150

RESUMO

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.

6.
Cancers (Basel) ; 13(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34359658

RESUMO

In the RESORCE study, regorafenib after sorafenib therapy improved survival in patients with advanced hepatocellular carcinoma (HCC). In total, 88 patients with unresectable HCC who received sorafenib-regorafenib sequential therapy were enrolled. The objective response rate and disease control rate were 19.3% and 48.9%, respectively, for regorafenib therapy (median duration: 8.1 months). Median progression-free survival (PFS) after regorafenib therapy was 4.2 months (95% CI: 3.2-5.1). The median overall survival (OS; from initiation of either sorafenib or regorafenib) was not reached in this cohort. According to multivariate Cox regression analyses, albumin-bilirubin (ALBI) grade at the initiation of regorafenib therapy is an independent predictor of disease control, PFS, and OS. Moreover, the combination of ALBI grade 2 and an alpha-fetoprotein (AFP) level of ≥20 ng/mL was an independent predictor of PFS (hazard ratio (HR): 3.088, 95% CI: 1.704-5.595; p < 0.001) for regorafenib therapy, and OS for both regorafenib (HR: 3.783, 95% CI: 1.316-10.88; p = 0.014) and sorafenib-regorafenib sequential (HR: 4.603, 95% CI: 1.386-15.29; p = 0.013) therapy. A combination of ALBI grade and AFP level can be used to stratify patients with unresectable HCC by PFS and OS probability for sorafenib-regorafenib sequential therapy.

7.
Hepatol Int ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34382132

RESUMO

BACKGROUND AND AIMS: Whether herbal and dietary supplements (HDS) are safer than Western conventional drugs is controversial. The aim of this study was to explore the characteristics and risk factors for HDS-induced liver injury (HILI) in Taiwan. METHODS: This is a 9-year multi-center prospective study conducted in Taiwan from 2011 to 2019. Patients with HILI were compared to those with conventional drug-induced liver injury (CILI). RESULTS: A total of 1,297 patients were enrolled, of whom 285 (22.0%) had HILI and 1,012 (78.0%) had CILI. Compared to the CILI group, the HILI group had higher initial serum alanine aminotransferase, alkaline phosphatase (ALP), peak ALP and bilirubin levels, and higher rates of jaundice, ascites, encephalopathy, coagulopathy, sepsis and acute liver failure. In addition, the HILI group had a higher mortality rate than the CILI group (12.6 vs. 8.0%, p = 0.016). Hepatitis B carrier status, elevated baseline liver biochemical tests and the use of crude herbs (without processing) were associated with an increased risk of HILI-related mortality (adjusted hazard ratios [95% confidence intervals]: 2.90 [1.43-5.99], 2.40 [1.01-5.68] and 2.94 [1.45-5.97], respectively). CONCLUSIONS: HDS are popular and incriminated in more than one-fifth of drug-induced liver injuries in Taiwan. The patients with HILI were more severe than those with CILI in terms of liver biochemical tests, complications and mortality. Hepatitis B carriers, those with elevated baseline liver tests and crude herb users may have a higher risk of HILI-related mortality. The prudent use of HDS is suggested in these high-risk subjects.

8.
J Ultrasound Med ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415630

RESUMO

OBJECTIVES: Direct-acting antiviral agents achieve a high cure rate, resulting in early hepatic necroinflammatory resolution and sustained fibrosis regression. This study aimed to obtain longitudinal, concurrent within-subject measurements of liver stiffness (LS) and spleen stiffness (SS) and their correlates over time. METHODS: Participants with hepatitis C (n = 592) receiving direct-acting antiviral-based therapy were monitored through point shear-wave elastography from the treatment baseline (TW0) across follow-up visits in terms of LS and SS. RESULTS: Generalized linear mixed modeling indicated that all LS values (2301 visits) were negatively correlated with the follow-up times (all P < .05) from TW0 to 24 weeks (PW24) after the end of treatment (EOT) and positively correlated with baseline LS values (P < .001). The slopes of declines (preceding minus next) differed significantly (P < .001) between TW0-TW4 (treatment week 4) (0.060 [-0.050 to 0.225] meter/second/month [m/s/mo]) and TW4-EOT (0.010 [-0.030 to 0.075] m/s/mo). All SS values (1704 visits) were negatively correlated with time only at PW24 (P < .001) and positively correlated with baseline SS values (P < .001). The slopes of the SS values differed significantly (P < .001) only between EOT-PW12 (-0.010 [-0.110 to 0.083] m/s/mo) and PW12-PW24 (0.043 [-0.063 to 0.160] m/s/mo). CONCLUSIONS: The biphasic fast-to-slow decline in LS occurred early in the on-treatment phase, which is consistent with the resolution of hepatic necroinflammation. The slow-to-fast decline in SS occurred off treatment. Future studies should investigate the association with regressions in liver fibrosis and portal hypertension.

9.
Clin Mol Hepatol ; 27(4): 575-588, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34255961

RESUMO

BACKGROUND/AIMS: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. METHODS: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. RESULTS: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). CONCLUSION: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

10.
Liver Int ; 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34153177

RESUMO

BACKGROUND & AIMS: Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR. METHODS: We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020. RESULTS: A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P < .003). Chronic kidney disease with high-dose allopurinol also contributed to high mortality (78.9%) in cases of allopurinol-induced DILI with SCAR. The HLA-B*5801 was associated with a high risk and mortality of allopurinol-induced DILI with SCAR. Likewise, the HLA-B*1502 was closely related to carbamazepine-induced DILI with SCAR. CONCLUSIONS: DILI patients combined with SCAR are common and have a high mortality in Taiwan. Allopurinol is the leading incriminated drug. Jaundice, acute kidney injury and SJS/TEN are risk factors of mortality. HLA-B*5801, chronic kidney disease and high drug dosage also contribute to high mortality in allopurinol-induced DILI with SCAR.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34089852

RESUMO

BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

12.
J Clin Invest ; 131(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060491

RESUMO

Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that α2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and α2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant [KD]: 1.95 × 10-10 ± 0.21 × 10-10 M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via α2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in CD14+ cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.


Assuntos
Apresentação do Antígeno , Carcinoma Hepatocelular/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Neoplasias Hepáticas/imunologia , Células Mieloides/imunologia , Proteínas de Neoplasias/imunologia , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética
14.
J Gastroenterol Hepatol ; 36(10): 2884-2892, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33963615

RESUMO

BACKGROUND AND AIM: It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications (DLD or HCC). RESULTS: Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46 798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2-7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4-32.4) in those without SVR (hazard ratio [HR]: 0.22, P < 0.001). The 10-year cumulative incidence rates of liver-related complications were 21.4% (95% CI: 11.1-37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1-86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001). CONCLUSIONS: Hepatitis C virus eradication with PR therapy decreased the incidence of new-onset LC in noncirrhotic patients and the incidence of liver-related complications in cirrhotic patients with CHC.

15.
J Infect Dis ; 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33999179

RESUMO

BACKGROUND: Long-term incidences and baseline determinants of functional cure (HBsAg seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. METHODS: This is an international multicenter cohort study of treatment-naïve chronic hepatitis B (CHB) patients who initiated on ETV or TDF without baseline malignancy. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. RESULTS: The analysis included 4,769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26,614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% CI, 1.54 -- 2.88%) and an annual rate of 0.22% (95% CI, 0.17--0.28%). Baseline predictors included low-level viremia with HBV DNA <2,000 IU/mL (adjusted sub-distribution HR [aSHR], 3.14; 95% CI, 1.80--5.49), elevated serum alanine aminotransferase (ALT) >200 U/L (aSHR, 3.68; 95% CI, 2.07--6.53), serum bilirubin (aSHR, 1.11 per mg/dL; 95% CI, 1.06--1.17), and fatty liver (aSHR, 1.84; 95% CI, 1.03--3.29). CONCLUSION: HBsAg seroclearance rarely occurs in CHB patients treated with ETV or TDF and is associated with low-level viremia, ALT flare, bilirubin level, and fatty liver.

16.
Liver Int ; 41(6): 1265-1277, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33655714

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Pessoa de Meia-Idade , Sistema de Registros , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Taiwan/epidemiologia , Falha de Tratamento , Resultado do Tratamento
17.
Hepatol Int ; 15(2): 338-349, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33677787

RESUMO

BACKGROUND: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. METHODS: Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. RESULTS: The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6-96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8-99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. CONCLUSIONS: SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.

18.
J Gastroenterol Hepatol ; 36(8): 2247-2254, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33624849

RESUMO

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is associated with impaired renal function. The aim of this study is to explore the risk of and factors associated with end-stage renal diseases (ESRD) under maintenance dialysis among HCV patients after anti-HCV therapy. METHODS: A total of 12 696 HCV-infected patients with interferon-based therapy, including 9679 (76.2%) achieving sustained virological response (SVR), were enrolled from 23 hospitals in Taiwan. RESULTS: During a mean follow-up period of 5.3 years (67 554 person-years), the annual incidence of 4.1/10 000 person-years, 4.0/10 000 and 4.7/10 000 person-years among SVR patients and non-SVR patients, respectively. History of diabetes and baseline estimated glomerular filtration rate < 60 mL/min/m2 , instead of SVR, were the significant risk factors for developing ESRD with maintenance dialysis after anti-HCV therapy (adjusted hazard ratio 7.75 and 9.78). CONCLUSION: Diabetes and baseline impaired renal function were strongly associated with progression to ESRD with maintenance dialysis among chronic HCV-infected patients after antiviral therapy.

19.
Hepatol Int ; 15(1): 105-113, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33547557

RESUMO

BACKGROUND AND AIMS: Fibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy. METHODS: A total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study. All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate. We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients. RESULTS: A total of 48 patients developed HCC after a mean follow-up of 6.98 years. FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value. When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval: 2.48-9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC. Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B < 10 + 1-year FIB-4 < 1.30. CONCLUSIONS: In non-cirrhotic CHB patients receiving prolonged NA therapy, 1-year FIB-4 < 1.30 is useful for identifying those with minimal HCC risk by combining with female sex or low PAGE-B score.

20.
Gut ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408122

RESUMO

OBJECTIVE: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5. DESIGN: 191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed. RESULTS: The SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations. CONCLUSION: SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.

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