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BACKGROUND: The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence. METHODS: Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models. RESULTS: The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors. CONCLUSION: This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Humans , Male , Aged , Aged, 80 and over , Female , Carcinoma, Hepatocellular/pathology , Interferons/therapeutic use , Antiviral Agents/therapeutic use , Liver Neoplasms/pathology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , alpha-Fetoproteins , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Risk FactorsABSTRACT
BACKGROUND: The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan. METHODS: Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models. RESULTS: The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047). CONCLUSION: Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Humans , Male , Middle Aged , Aged , Female , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Antiviral Agents/therapeutic use , Liver Neoplasms/etiology , Liver Neoplasms/drug therapy , Liver Cirrhosis/complications , Risk FactorsABSTRACT
Background: Adequate bowel cleansing is important for colonoscopy performance evaluation. Current bowel cleansing evaluation scales are subjective, with a wide variation in consistency among physicians and low reported rates of accuracy. We aim to use machine learning to develop a fully automatic segmentation method for the objective evaluation of the adequacy of colon preparation. Methods: Colonoscopy videos were retrieved from a video data cohort and transferred to qualified images, which were randomly divided into training, validation, and verification datasets. The fecal residue was manually segmented. A deep learning model based on the U-Net convolutional network architecture was developed to perform automatic segmentation. The performance of the automatic segmentation was evaluated on the overlap area with the manual segmentation. Results: A total of 10,118 qualified images from 119 videos were obtained. The model averaged 0.3634 s to segmentate one image automatically. The models produced a strong high-overlap area with manual segmentation, with 94.7% ± 0.67% of that area predicted by our AI model, which correlated well with the area measured manually (r = 0.915, p < 0.001). The AI system can be applied in real-time qualitatively and quantitatively. Conclusions: We established a fully automatic segmentation method to rapidly and accurately mark the fecal residue-coated mucosa for the objective evaluation of colon preparation.
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BACKGROUND: This study investigates the association between daily sitting time and subclinical atherosclerosis by using coronary computed tomography angiography (CCTA). METHODS: The study enrolled 203 subjects (age 57.6 ± 8.8 years) who underwent CCTA at annual medical checkups. Sitting time was categorized as < 5 hours/day (short), 5 to 9 hours/day (moderate) and ≥10 hours/d (long). We analyzed the coronary calcium score, plaque characteristics, and severity of coronary artery stenosis, including the segment involvement score (SIS) and segment stenosis score (SSS). RESULTS: Subjects with longer sitting times tended to be male gender and have lower levels of high-density lipoprotein cholesterol (p for trend < 0.05). In addition, those with longer sitting time had higher SIS (1.2 ± 1.5 vs. 1.6 ± 2.1 vs. 2.3 ± 2.0 for short, moderate, and long sitting time, respectively) (p for trend = 0.015) and SSS (1.4 ± 2.0 vs. 1.9 ± 2.7 vs. 2.7 ± 2.6) (p for trend = 0.015), suggesting longer sitting time-correlated with the severity of coronary atherosclerosis. When considering the coronary plaque patterns, subjects with shorter sitting time (<5 hours/d) tended to have more calcified plaque and subjects with longer sitting time (≥10 hours/d) had more mixed plaque (p for trend = 0.018). After adjusting for age, gender, comorbidities, body mass index, and lipid profiles, increased sitting time was independently associated with the presence of mixed plaque, suggesting longer sitting time may be associated with higher risk of the formation of vulnerable plaque. CONCLUSION: Longer sitting time was linked to the severity of subclinical atherosclerosis and the presence of high-risk vulnerable plaque in the general population.
Subject(s)
Coronary Artery Disease , Plaque, Atherosclerotic/epidemiology , Sitting Position , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Plaque, Atherosclerotic/physiopathology , Surveys and Questionnaires , Taiwan/epidemiology , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: For patients with hepatitis C virus (HCV)-related decompensated cirrhosis, poor prognosis was documented due to the development of portal hypertension-related complications and hepatocellular carcinoma. Sofosbuvir-based direct-acting antiviral agents (DAAs) has revolutionized the treatment landscape of HCV, particularly in this subpopulation. To date, real-world efficacy, tolerability, and safety profiles for Taiwanese HCV-related decompensated cirrhosis treated by DAAs have not been reported. METHODS: Between December 2015 and June 2020, 50 consecutive HCV-related Child-Turcotte-Pugh (CTP) classes B or C cirrhotics treated by sofosbuvir-based DAAs (with daclatasvir: 7, with ledipasvir: 32, with velpatasvir: 10, with ledipasvir then shifted to velpatasvir: 1) were enrolled. Forty-seven (94%) patients used DAAs in combination with low-dose ribavirin. SVR12 was defined by undetectable HCV RNA (<15 IU/mL) at treatment end and 12 weeks after the completion of therapy. RESULTS: The mean age of the enrolled patients was 68.1 ± 11.2 years, 18% of the patients were CTP class C, and the baseline HCV RNA level was 5.42 ± 1.2 log10 IU/mL. The genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with an unclassified HCV genotype. After DAAs treatment, the rates of undetectable HCV RNA at week 4 and at the end of the treatment were 88.9% and 98.0%, respectively. Subjective adverse events were reported by 42.0% of the patients, but they were generally mild and could be relieved by medications. One patient did not finish therapy due to sepsis with multiple organ dysfunction. The overall SVR12 rate was 96.0% (CTP class B: 97.6%, CTP class C: 88.9%). A significant improvement in hepatic functional reserve was noted after successful antiviral therapy. CONCLUSION: For patients with HCV-related decompensated cirrhosis, which has been considered a contraindication for interferon-based therapy, sofosbuvir-based all-oral DAAs provided high treatment efficacy, acceptable safety, and good tolerability.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Outcome Assessment, Health Care , Safety , Sofosbuvir/administration & dosage , Treatment Outcome , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Sustained Virologic Response , TaiwanABSTRACT
BACKGROUND: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is common because the two pathogens share their transmission route. Studies have suggested that coinfection is associated with accelerated hepatic fibrosis, increased hepatic decompensation, and hepatocellular carcinoma development. Historically, the sustained virological response (SVR) rates for patients undergoing pegylated interferon (PEG-IFN)-based therapy are poor owing to advanced liver disease, immune dysfunction, and poor medical adherence. This study aimed to investigate the efficacy and safety of oral direct-acting antivirals (DAAs) in HCV-HIV-coinfected patients. METHODS: Between January 2017 and February 2020, 52 consecutive HCV-HIV-coinfected patients treated with oral DAAs (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 7; daclatasvir and asunaprevir: 1; glecaprevir and pibrentasvir: 15; and sofosbuvir-based drugs: 29) were enrolled. The DAA regimen was selected based on the genotype/subtypes, patient characteristics, potential drug-drug interaction profiles, and health insurance reimbursement criteria. SVR12 was defined as undetectable HCV RNA (<15 IU/mL) at the end of therapy and 12 weeks after therapy completion. RESULTS: The mean age of the enrolled patients was 42 ± 10.2 years; 92.3% of the patients were male and 32.7% had advanced fibrosis or cirrhosis. Nine (17.3%) patients had failed previous IFN therapy. The genotype distribution was as follows: 1a: 8; 1b: 23; 2: 14; 3: 1; and 6: 6. The baseline HCV RNA level before DAA administration was 6.56 ± 0.9 log10 IU/mL, and 67.3% of patients had baseline HCV RNA >2 000 000 IU/mL. After posttreatment follow-up, all 52 patients (100%) achieved SVR12. Subjective and laboratory adverse events during therapy were generally mild, and none of the patients terminated therapy early. CONCLUSION: A highly effective treatment response and good tolerability were achieved using the oral DAAs for the HCV-HIV-coinfected patient population, which has been considered difficult to treat using IFN-based therapy in the past with urgent unmet medical needs.
Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Drug Therapy, Combination , Drug Tolerance , Hepacivirus/drug effects , Hepatitis C/drug therapy , Adult , Coinfection/drug therapy , Female , Humans , Liver Cirrhosis , Male , Middle Aged , Sustained Virologic Response , Treatment OutcomeABSTRACT
BACKGROUND: Direct-acting antivirals (DAA) improve sustained virological response (SVR) rates with normalization of liver enzymes in patients with hepatitis C. However, liver inflammation may persist despite virus eradication. We aimed to investigate the rate and risk factors for persistent elevated aminotransferase levels in patients with advanced fibrosis after DAA-induced SVR. METHODS: From January 2017 to April 2018, chronic hepatitis C patients with advanced fibrosis and SVR after DAA treatment at the Taipei Veterans General Hospital were prospectively enrolled. Persistent liver inflammation after SVR was defined as an increase in levels of alanine aminotransferase (ALT) (>40 U/L) at SVR12. RESULTS: A total of 461 patients were included (57.9% females, mean age 64 years, 69.6% genotype 1b, 46.4% cirrhosis). At SVR12, there was a decline in ALT levels (90.5 ± 80.8 U/L to 25.3 ± 26.5 U/L) from baseline levels. Persistent liver inflammation at SVR12 was detected in 45 patients (9.8%). The presence of cirrhosis, markers of impaired liver functions, history of interferon-based therapy, steatosis, and elevated ALT levels at baseline was associated with persistent liver inflammation after SVR12. Results of multivariate analysis indicated that levels of baseline serum total bilirubin (odds ratio [OR]: 2.605, 95% CI: 1.158-5.858), international normalized ratio (OR: 14.389, 95% CI: 1.754-118.049), ALT (OR: 1.006, 95% CI: 1.003-1.009), and the presence of steatosis (OR: 3.635, 95% CI: 1.716-7.698) were independent predictors of persistent liver inflammation at SVR12. CONCLUSION: Persistent liver inflammation is not uncommon in chronic hepatitis C patients with advanced fibrosis after DAA-induced SVR. It is associated with impaired baseline liver function and steatosis. Long-term follow-up is required to assess the implication of liver inflammation on disease progression.
Subject(s)
Fibrosis/drug therapy , Fibrosis/pathology , Hepatitis C, Chronic , Inflammation/drug therapy , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Female , Hepacivirus/drug effects , Hepatitis C, Chronic/complications , Humans , Liver Cirrhosis , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND/PURPOSE: Predictors of long-term outcomes of peginterferon (PegIFN) therapy for patients with chronic hepatitis B (CHB) remain to be explored. This study aimed to evaluate the predictive value of virological and immunological biomarkers and outcomes of PegIFN for CHB. METHODS: 57 HBeAg-negative CHB patients receiving 48 weeks of PegIFN therapy were prospectively followed for a median period of 5.3 years after the end of treatment (EOT). Serum CXCL9 and IP-10 levels were measured. Flow cytometry analysis for T cell subsets was performed in 23 patients. Factors associated with long-term outcomes were analyzed. RESULTS: The cumulative incidences of virological relapse, clinical relapse and HBsAg loss at year 7 were 18.1%, 0%, 31.6%, respectively, in patients with sustained off-treatment virological response (SVR), and 100%, 67.4%, 6.7%, respectively, in patients without SVR. By multivariate analysis, baseline CXCL9 > 80 pg/mL (hazard ratio (HR) = 0.418, p = 0.018) and on-treatment HBsAg declines were associated with a lower risk of virological relapse. Non-SVR was the only predictor of clinical relapse. CXCL9 >200 pg/mL (HR = 8.154, p = 0.038) and HBsAg <750 IU/mL (HR = 10.507, p = 0.036) were baseline predictors of HBsAg loss, while HBsAg decline >1 log at EOT (HR = 23.296, p = 0.005) was the on-treatment predictor of HBsAg loss. In subgroup patients with available PBMC, populations of T cell subsets correlated with virological and clinical relapses in univariate analysis. CONCLUSION: Baseline serum CXCL9 and HBsAg levels could predict HBsAg loss after PegIFN therapy for HBeAg-negative CHB. Combining virological and immunological biomarkers could predict long-term outcomes of PegIFN therapy for HBeAg-negative CHB.
Subject(s)
Hepatitis B e Antigens , Hepatitis B, Chronic , Antiviral Agents/therapeutic use , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha , Leukocytes, Mononuclear , Polyethylene Glycols/therapeutic use , Recombinant Proteins/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with cardiovascular disease (CVD). However, whether the steatosis severity of NAFLD is independently associated with coronary artery atherosclerosis is still controversial. METHODS: Consecutive Taiwanese individuals (1502) who received coronary computed tomography angiography (CCTA) and abdominal sonography as part of a general routine health evaluation were enrolled. The association between steatosis severity, coronary atherosclerosis involvement and various plaque patterns were analysed. RESULTS: Compared with non-steatosis, NAFLD subjects had more cardiovascular risk factors that correlated with the severity of steatosis (P for the trend <.05). The presence of atherosclerotic plaques correlated with the severity of steatosis (none: 53%, mild: 64.1%, and moderate to severe: 66.9%; P for the trend <.001). Parameters of coronary atherosclerosis, including atheroma burden obstructive score (ABOS), segment involvement score (SIS) and segment stenosis score (SSS), were higher in the moderate to severe steatosis group. After adjusting for major confounding factors, the severity of steatosis still correlated with the mixed plaque pattern (P = .043). Subgroup analysis of the risk of the presence of overall coronary and mixed plaques showed a significant association with increasing severity of steatosis, especially among these who were <65 years old, male, without metabolic syndrome, and with lower low-density lipoprotein choleseterol values. CONCLUSION: In this general population, steatosis severity of NAFLD is associated with coronary artery atherosclerosis burden. Furthermore, steatosis severity correlated with the risk of the presence of coronary plaques, especially high-risk plaques, and was independent of traditional risk factors.
Subject(s)
Coronary Artery Disease , Non-alcoholic Fatty Liver Disease , Plaque, Atherosclerotic , Aged , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Humans , Male , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/epidemiology , Risk Factors , Severity of Illness IndexABSTRACT
BACKGROUND: Few studies have reported on the clustering pattern of CVD risk factors, including sedentary behavior, systemic inflammation, and cadiometabolic components in the general population. OBJECTIVE: We aimed to explore the clustering pattern of CVD risk factors using exploratory factor analysis to investigate the underlying relationships between various CVD risk factors. METHODS: A total of 5606 subjects (3157 male, 51.5±11.7 y/o) were enrolled, and 14 cardiovascular risk factors were analyzed in an exploratory group (n = 3926) and a validation group (n = 1676), including sedentary behaviors. RESULTS: Five factor clusters were identified to explain 69.4% of the total variance, including adiposity (BMI, TG, HDL, UA, and HsCRP; 21.3%), lipids (total cholesterol and LDL-cholesterol; 14.0%), blood pressure (SBP and DBP; 13.3%), glucose (HbA1C, fasting glucose; 12.9%), and sedentary behavior (MET and sitting time; 8.0%). The inflammation biomarker HsCRP was clustered with only adiposity factors and not with other cardiometabolic risk factors, and the clustering pattern was verified in the validation group. CONCLUSION: This study confirmed the clustering structure of cardiometabolic risk factors in the general population, including sedentary behavior. HsCRP was clustered with adiposity factors, while physical inactivity and sedentary behavior were clustered with each other.
Subject(s)
Cardiometabolic Risk Factors , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies/methods , Adiposity , Adult , Biomarkers/blood , Blood Glucose , Blood Pressure , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cluster Analysis , Factor Analysis, Statistical , Female , Humans , Inflammation/metabolism , Male , Metabolic Syndrome/epidemiology , Middle Aged , Risk Factors , Sedentary Behavior , Sitting Position , Taiwan/epidemiology , Triglycerides/blood , Waist CircumferenceABSTRACT
AIM: Coronary atherosclerotic plaques can be detected in asymptomatic subjects and are related to low-density lipoprotein cholesterol (LDL) levels in patients with coronary artery disease. However, researchers have not yet determined the associations between various plaque characteristics and other lipid parameters, such as HDL-C and TG levels, in low-risk populations. METHODS: One thousand sixty-four non-diabetic subjects (age, 57.86±9.73 years; 752 males) who underwent coronary computed tomography angiography (CCTA) were enrolled and the severity and patterns of atherosclerotic plaques were analyzed. RESULTS: Statin use was reported by 25% of the study population, and subjects with greater coronary plaque involvement (segment involvement score, SIS) were older and had a higher body mass index (BMI), blood pressure, unfavorable lipid profiles and comorbidities. After adjusting for comorbidities, only age (ß=0.085, pï¼0.001), the male gender (ß=1.384, pï¼0.001), BMI (ß=0.055, p=0.019) and HbA1C levels (ß=0.894, pï¼0.001) were independent factors predicting the greater coronary plaque involvement in non-diabetic subjects. In the analysis of significantly different (ï¼50%) stenosis plaque patterns, age (OR: 1.082, 95% CI: 10.47-1.118) and a former smoking status (OR: 2.061, 95% CI: 1.013-4.193) were independently associated with calcified plaques. For partial calcified (mixed type) plaques, only age (OR: 1.085, 95% CI: 1.052-1.119), the male gender (OR: 7.082, 95% CI: 2.638-19.018), HbA1C levels (OR: 2.074, 95% CI: 1.036-4.151), and current smoking status (OR: 1.848, 95% CI: 1.089-3.138) were independently associated with the risk of the presence of significant stenosis in mixed plaques. CONCLUSIONS: A higher HbA1c levels is independently associated with the presence and severity of coronary artery atherosclerosis in non-diabetic subjects, even when LDL-C levels are tightly controlled.
Subject(s)
Biomarkers/blood , Coronary Artery Disease/epidemiology , Coronary Vessels/pathology , Glycated Hemoglobin/analysis , Plaque, Atherosclerotic/epidemiology , Cholesterol, LDL/blood , Coronary Artery Disease/blood , Coronary Artery Disease/etiology , Coronary Vessels/metabolism , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Plaque, Atherosclerotic/blood , Plaque, Atherosclerotic/etiology , Predictive Value of Tests , Risk Factors , Severity of Illness Index , Taiwan/epidemiologyABSTRACT
BACKGROUND: Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS: A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS: Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION: Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Organ Transplantation/adverse effects , Administration, Oral , Aged , Alanine Transaminase/blood , Antiviral Agents/adverse effects , Female , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , RNA, Viral/blood , Retrospective Studies , Sustained Virologic ResponseABSTRACT
BACKGROUND/PURPOSE: The impact of non-alcoholic fatty liver disease (NAFLD) on the prevalence of chronic kidney disease (CKD) is not fully elucidated. We aimed to assess the correlation between NAFLD and CKD in a large population study. METHODS: We included consecutive subjects who had received health check-up service at Taipei Veterans General Hospital from 2002 to 2009. NAFLD was diagnosed with abdominal ultrasound, and advanced liver fibrosis was determined with NAFLD fibrosis score (NAFLD-FS). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. RESULTS: Among the 29,797 subjects enrolled in this study, NAFLD and CKD were diagnosed in 44.5% and 20.2% of the population, respectively. Subjects with NAFLD had a higher proportion of CKD compared to those without NAFLD (24.1% vs. 17.1%, p < 0.001). However, NAFLD was not related to CKD with an odds ratio (OR) of 1.015 (95% confidence interval [CI] 0.954-1.081, p = 0.630) after multivariate analyses. Nevertheless, further analyses revealed that among patients with NAFLD, those with advanced fibrosis were more likely to have CKD after adjusting for confounding factors (OR 2.284, 95% CI 1.513-3.448, p < 0.001). CONCLUSION: NAFLD per se was not a risk factor for CKD, but NAFLD patients with advanced fibrosis faced a higher possibility of CKD. Hence, patients with NAFLD and advanced fibrosis should be screened for CKD and prompted to receive treatment if the diagnosis was made.
Subject(s)
Non-alcoholic Fatty Liver Disease/epidemiology , Renal Insufficiency, Chronic/epidemiology , Adult , Aged , Female , Glomerular Filtration Rate , Humans , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Prevalence , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Taiwan/epidemiology , UltrasonographyABSTRACT
BACKGROUND/PURPOSE: Although the lung function test has played an important role in respiratory care for a long time, valid spirometry reference values in the Chinese population in Taiwan remain to be elucidated. METHODS: 2963 healthy Taiwanese subjects aged 21 to 88 years (1765 males, 59.6%) from February 2015 to February 2017 were enrolled. The subjects attempted to meet the 2005 American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines when performing forced expiratory spirograms. We would like to establish the spirometry predictive equations for forced expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC, and lower limit of normal (LLN) in Taiwan and compare with other Asian populations. RESULTS: We established the spirometry predictive equations using a linear model for the entire population, using age and height as independent variables, which best predicted all spirometry parameters for sea level and highland subjects. We found that the values of FEV1 and FVC for the Taiwanese subjects in our study were systematically lower than those reported in South Korea, Japan, and China, but higher than the values in Yang's 1993 and Pan's 1997 Taiwan study. CONCLUSION: This study addressed the up-to-date spirometry reference equations and values for a healthy adult Chinese population in Taiwan.
Subject(s)
Forced Expiratory Volume , Spirometry , Vital Capacity , Adult , Age Factors , Aged , Aged, 80 and over , Asian People/statistics & numerical data , Body Height , Female , Healthy Volunteers , Humans , Linear Models , Male , Middle Aged , Prospective Studies , Reference Values , Sex Factors , Taiwan , Young AdultABSTRACT
BACKGROUND: Current evidence supports the beneficial effect of physical activity in reducing adverse events, however studies on Asian populations are limited and have reported inconsistent findings. The aim of this study was to investigate the association between physical activity and the development of cardiovascular disease, diabetes, hypertension and malignancy in a large Asian cohort. We also investigated interactions between the intensity of physical activity, environmental exposure and biochemical markers. METHODS: Subjects who received annual checkups at Taipei Veterans General Hospital were invited to join this study. Information on physical activity was evaluated using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Associations between the occurrence of clinical events including cardiovascular events, diabetes and malignancies and the intensity of physical activity, biochemical markers, imaging findings, personality trait evaluations and nutrition were evaluated. RESULTS: In the initial stage of this study, a total of 1010 patients enrolled, 626 (62%) were male, 74 (7.4%) had diabetes, 183 (18.3%) had hypertension, and 220 (21.8%) were smokers. The total cholesterol was 202.1 ± 36.2 mg/dL and low-density lipoprotein-cholesterol was 125.7 ± 32.9 mg/dL, including 49.3 ± 13.1 mg/dL for serum high-density lipoprotein-cholesterol and 120.7 ± 70.7 mg/dL for triglycerides. The fasting glucose level was 93.8 ± 21.9 mg/dL, and HbA1c was 5.7 ± 0.7%. All information collected will be incorporated with future events to analyze the relationship between biochemical parameters, physical activity and future adverse events. CONCLUSIONS: These findings will contribute to the understanding of the value of physical activity in determining future cardiovascular and non-cardiovascular events in Asian populations.
ABSTRACT
BACKGROUND: Based on the previously published results, 12 weeks of sofosbuvir (SOF) 400 mg/day plus ribavirin (RBV), the current direct antiviral agent regimen reimbursed by Bureau-of National-Health-Insurance (BNHI) of Taiwan for genotype-2 chronic hepatitis C (CHC), is suboptimal in efficacy, especially for difficult-to-treat subpopulations such as liver cirrhosis, previous interferon (IFN) treatment failure, and high viral-load. This study aimed to evaluate the efficacy and safety of SOF plus daclatasvir (DCV) for Taiwanese genotype-2 CHC patients. METHODS: Between March 2017 and December 2018, a total of 50 consecutive genotype-2 CHC patients who completed 12 weeks combination of SOF (400 mg/day) plus DCV (60 mg/day) with or without RBV by investigators were enrolled for analyses. When RBV was added, weight-based (800-1200 mg/day) approach was applied. Sustained virological response (SVR12) was defined by undetectable HCV RNA (<15 IU/mL) at the end and 12 weeks after completion of therapy. RESULTS: The mean age was 62.0 ± 11.4 years, 16 (32.0%) of them were males and 20 (40.0%) of them failed to previous IFN. Severity of liver diseases was as follows: ≤F2 fibrosis: 24.0%; F3 fibrosis: 40.0%, Child-Pugh A cirrhosis: 30.0%; and Child-Pugh B-C cirrhosis: 6.0%. The mean baseline HCV RNA level was 6.19 ± 0.91 log10 IU/mL and 30 (60.0%) had baseline HCV RNA ≥ 2 million IU/mL. The rates of undetectable HCV RNA (<15 IU/mL) at weeks 2, 4, and end-of-treatment were 40%, 94%, and 100%, respectively. Majority (66.7%) of patients with detectable HCV RNA at week 2 belonged to low-level viremia (<50 IU/mL). Subjective adverse events (AEs) and laboratory abnormalities were more common for patients combining RBV. Grades of AEs were generally mild and all patients finished therapy without interruption. After post-treatment follow-up, all 50 patients (100%) achieved SVR12. CONCLUSION: Our real-world cohort of Taiwan showed that a 12-week SOF/DCV-based treatment was well-tolerated and highly effective for genotype-2 CHC patients with or without liver cirrhosis.
Subject(s)
Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Imidazoles/administration & dosage , Ribavirin/administration & dosage , Sofosbuvir/administration & dosage , Adult , Aged , Carbamates , Drug Therapy, Combination , Female , Genotype , Hepacivirus/classification , Hepatitis C, Chronic/virology , Humans , Imidazoles/adverse effects , Male , Middle Aged , Pyrrolidines , RNA, Viral/blood , Retrospective Studies , Ribavirin/adverse effects , Sofosbuvir/adverse effects , Valine/analogs & derivativesABSTRACT
BACKGROUND: Treatment of chronic hepatitis C (CHC) evolved rapidly due to the invention of interferon-free direct antiviral agents. Previous clinical trials showed combination therapy with paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin (RBV) can cure over 95% of genotype 1 CHC patients, regardless with cirrhosis or not. However, real-world data regarding the efficacy and safety of PrOD-based therapy in Asian HCV genotype 1 CHC patients are limited, especially for advanced-fibrotic patients who failed previous therapy with pegylated interferon (PEG-IFN) plus RBV. METHODS: Between January and October 2017, 60 advanced fibrotic (≥F3) genotype 1 CHC patients who failed previous therapy with PEG-IFN and received PrOD-based therapy for 12 weeks were retrospectively enrolled. Weight-based RBV 800 to 1200 mg/d was added for genotype 1b patients with cirrhosis and all genotype 1a patients. Sustained virological response (SVR) was defined by undetectable HCV RNA at the end and 12 weeks after the completion of therapy. RESULTS: The mean age was 63.2 ± 9.3 years, 26 (43.3%) of them were males and 20 (33.3%) were diagnosed to have liver cirrhosis. The mean baseline HCV RNA level was 6.19 ± 0.88 log10 IU/mL and 86.7% (52/60) of patients were infected by HCV genotype 1b. After PrOD-based therapy, the rates undetectable HCV RNA (<15 IU/mL) at week 2, 4, and 12 were 61.7%, 90.0%, and 100%, respectively; 69.6% (16/23) of patients with detectable HCV RNA at week 2 were < 100 IU/mL. Pruritus, fatigue, headache, insomnia, and dizziness were the most common patient-reported adverse events. Grade 2 hyperbilirubinemia were found in 21.6% (13/60) of patients during study period and all belonged to unconjugated hyperbilirubinemia. After posttherapy follow up, all 60 patients (100%) achieved SVR. CONCLUSION: Our real-world data in Taiwan revealed that PrOD-based rescue therapy is well-tolerated and highly effective for genotype 1 CHC patients with advanced fibrosis failing previous therapy with PEG-IFN plus RBV.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Aged , Antiviral Agents/adverse effects , Drug Therapy, Combination , Female , Genotype , Hepacivirus/classification , Hepatitis C, Chronic/complications , Humans , Interferon-alpha/administration & dosage , Male , Middle Aged , Polyethylene Glycols/administration & dosage , Recombinant Proteins/administration & dosage , Retrospective Studies , Ribavirin/administration & dosage , Sustained Virologic ResponseABSTRACT
BACKGROUND: Bilirubin is a potential endogenous inhibitor of atherosclerosis. We investigated the association of bilirubin and cardiovascular (CV) and all-cause mortality including potential improvements in bilirubin risk reclassification in asymptomatic diabetic patients. METHODS: We enrolled 2936 asymptomatic diabetic subjects. The serum bilirubin was measured, and future CV and all-cause death were the primary endpoints. RESULTS: The follow-up period was 5.4⯱â¯3.0 y. There were 218 deaths including 95 cardiovascular deaths. The occurrence of CV death and all-cause death were negatively correlated with increasing serum bilirubin quintiles and actual bilirubin values. Serum bilirubin was negatively associated with incident cardiovascular death (hazard ratio: 0.26, 95% CI, 0.11-0.61, pâ¯=â¯.01) and all-cause death (hazard ratio: 0.30, 95% CI, 0.17-0.51, pâ¯≤.001). The addition of bilirubin for cardiovascular death increased the C-statistic from 0.713 (95% CI, 0.664-0.762) to 0.729 (95% CI, 0.681-0.776) (Pâ¯=â¯.008) and showed an integrated discrimination improvement (IDI) of 0.012 (Pâ¯<â¯.0171) with 8.57% improvement in net reclassification analysis (Pâ¯=â¯.0224). These results suggest additional predictive value is possible via total bilirubin levels for future CV deaths in diabetic patients. In terms of all-death, the addition of bilirubin significantly increased the C-statistic (from 0.769 to 0.78, Pâ¯=â¯.0064)-a 3.52% net reclassification improvement (Pâ¯=â¯.0307). It did not improve the IDI (pâ¯=â¯.1505). CONCLUSIONS: Higher serum concentrations of bilirubin are associated with a decreased risk of developing CV and all-cause death in diabetic patients. Bilirubin improved the risk prediction of cardiovascular death but provided only a slightly better prediction of all-cause death than conventional risk factors.
Subject(s)
Bilirubin/blood , Cardiovascular Diseases/blood , Diabetes Mellitus/blood , Female , Humans , Male , Middle Aged , Risk Factors , Survival AnalysisABSTRACT
Background: The long-term incidence and factors associated with hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients receiving peginterferon is rarely reported. Methods: From 2004 to 2016, 233 HBeAg-negative CHB patients who completed 48 weeks of peginterferon treatment from 3 medical centers in Taiwan were retrospectively enrolled. Results: During a median follow-up of 7.4 years, 27 cases achieved HBsAg loss. The cumulative incidences of HBsAg loss and HBsAg seroconversion at 3, 5, 10 years after peginterferon treatment were 4.7%, 9.4%, 14.2%, and 3.5%, 6.4%, 12.5%, respectively, in overall patients, and 15.9%, 29.1%, 37.3%, and 13.1%, 19%, 30.6%, respectively, in patients achieving sustained off-treatment virological response (SVR). By multivariate analysis, age (<35 years; hazard ratio [HR] = 3.742, P = .007), baseline HBsAg levels (<1250 IU/mL; HR = 4.849, P = .002), HBsAg decline at week 24 (≥1 log; HR = 5.660, P = .002), and achieving SVR (HR = 8.546, P = .006) were predictors of HBsAg loss. After achieving SVR, HBsAg loss rates were higher than 30% in 5 years among patients with either younger age or lower HBsAg at baseline. Conclusions: HBsAg loss rate continues to increase after peginterferon treatment in HBeAg-negative CHB patients with SVR. Age, baseline HBsAg levels, on-treatment HBsAg decline, and achieving SVR are factors associated with long-term HBsAg loss.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens/immunology , Hepatitis B e Antigens/immunology , Hepatitis B virus/immunology , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Follow-Up Studies , Hepatitis B virus/drug effects , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/virology , Humans , Incidence , Liver/metabolism , Liver/virology , Male , Middle Aged , Recombinant Proteins/therapeutic use , Retrospective Studies , Taiwan/epidemiologyABSTRACT
BACKGROUND: Previous studies have shown that uremia patients under hemodialysis (HD) have a significantly higher occurrence of peptic ulcer bleeding (PUB) than healthy controls and that elderly patients remain at high risk of peptic ulcer disease (PUD) and PUB. Here we aimed to identify the risk factors for PUB in aging (≥65-years-old) uremic patients under regular HD. METHODS: Using data from the National Health Insurance Research Database of Taiwan, we compared 18,252 aging regular HD patients and 17,883 age-, gender-, and medication-matched patients without kidney disease (control group). The log-rank test was performed to analyze the differences in accumulated hazard of PUB between the two groups. Cox proportional hazard regressions were performed to evaluate independent risk factors for PUB between the two groups and identify risk factors of PUB in aging HD patients. RESULTS: In a 7-year follow-up, aging HD patients had significantly higher incidences of PUB than the matched controls (p < 0.001 by the log-rank test). By Cox proportional hazard regression analysis, HD (hazard ratio [HR] = 4.61; 95% confidence intervals [CI] 4.03-5.27) was independently associated with increased risk of PUB. Age, diabetes mellitus (DM), history of uncomplicated PUD, cirrhosis, and use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids were risk factors for PUB in aging HD patients. CONCLUSION: Aging HD patients are associated with higher risk of PUB. The use of NSAIDs and corticosteroids and co-morbidities including DM, history of uncomplicated PUD, and cirrhosis were identified as risk factors for PUB in these patients.