Effective Antiviral Activity of the Tyrosine Kinase Inhibitor Sunitinib Malate against Zika Virus

Background@#(Introduction): Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broadspectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. @*Materials and Methods@#This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. @*Results@#Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC 50 ) value of 0.015 μM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 μM, and a substantial decrease in the titer of intracellular infectious particles by 1 μM. @*Conclusion@#The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

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). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

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). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Bupropion for Interferon-Alpha-Induced Depression in Patients with Hepatitis C Viral Infection: An Open-Label Study

Interferon (IFN)-alpha therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-alpha-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores< or =7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

Statin use and risk of lung cancer in males: a case-control study in Taiwan

To explore the association between statin use and lung cancer risk in men in Taiwan. A nested case-control study. Data from the Taiwan National Health Insurance Program, 2000 to 2010 Two thousand two hundred and ninety male patients aged 20 years or older with newly diagnosed lung cancer as cases and 9160 male subjects without lung cancer as controls. The association between statin use and lung cancer risk was estimated After adjustment for confounders including pulmonary tuberculosis, chronic obstructive pulmonary disease, asbestosis and tobacco use, multivariate logistic regression showed the adjusted odds ratio of lung cancer was 0.79 for the statins-use group [95% CI: 0.68, 0.91], when compared with no use of statins. We found an association between statin use and lung cancer risk in men in Taiwan

Cardiovascular disease and colorectal cancer: a population-based observation in Taiwan

To explore the relationship between cardiovascular disease and colorectal cancer in Taiwan. Population-based cohort study. Using database of the Taiwan National Health Insurance program from 2000 to 2006, 89,034 patients [35 years or older] with newly diagnosed cardiovascular disease [CVD] which included coronary artery disease, heart failure, cerebrovascular disease, peripheral atherosclerosis, or hypertension, and 89,034 control subjects without CVD were studied. The incidence of colorectal cancer at the end of 2009 and the association with CVD and other co-morbidities were determined. The incidence of colorectal cancer was 1.19-fold higher in the CVD group compared with the non-CVD group [10.87 Vs 9.11 per 10,000 person-years, 95%CI = 1.05-1.36]. After adjustment for covariates, no association was found between CVD and colorectal cancer [95%CI = 0.87-1.13]. Men [HR = 1.53, 95%CI = 1.34-1.75], increasing age [HR = 1.07, 95%CI = 1.06-1.07], and colorectal adenoma [HR = 1.80, 95%CI = 1.06-3.05] were associated with colorectal cancer. No association between cardiovascular disease and colorectal cancer is found. Men, increasing age, and colorectal adenoma correlate with the increased risk of colorectal cancer

Kidney cancer and diabetes mellitus: a population-based case-control study in Taiwan

<p><b>INTRODUCTION</b>The purpose of this study was to explore whether diabetes mellitus (DM) correlates with the risk of kidney cancer in Taiwan.</p><p><b>MATERIALS AND METHODS</b>We designed a population-based case-control study from the Taiwan National Health Insurance Database, which consisted of 116 patients with newly diagnosed kidney cancer as cases and 464 subjects without kidney cancer as controls in 2000 to 2009. Both cases and controls were aged ≥20 years. Baseline comorbidities were compared between kidney cancer cases and controls.</p><p><b>RESULTS</b>Multivariable analysis showed no association was detected between DM and kidney cancer (OR 1.06, 95% CI, 0.58 to 1.94). Hypertension (OR 2.05, 95% CI, 1.23 to 3.42), chronic kidney diseases (OR 2.57, 95% CI, 1.23 to 5.37), cystic kidney diseases (OR 18.6, 95% CI, 1.84 to 187.6) and kidney stones (OR 4.02, 95% CI, 2.43 to 6.66) were significant comorbidities associated with increased risk of kidney cancer. Use of alpha-glucosidase inhibitor was associated with increased risk of kidney cancer (OR 4.31, 95% CI, 1.07 to 17.3).</p><p><b>CONCLUSION</b>DM does not correlate with the risk of kidney cancer. Hypertension, chronic kidney diseases, cystic kidney diseases, kidney stones and use of alpha-glucosidase inhibitors are associated with kidney cancer.</p>

Thrombocytopenia and its related factors: a hospital-based, cross-sectional study

<p><b>INTRODUCTION</b>The objective of this study was to explore the association between thrombocytopenia and its related factors.</p><p><b>MATERIALS AND METHODS</b>This was a hospital-based, cross-sectional study. We retrospectively analysed the medical records of all patients who received periodic health examinations at a medical centre located at Taichung in Taiwan between 2000 and 2004. In all, 5585 subjects were included for further analysis. A complete physical examination, laboratory survey and abdominal ultrasonography were performed on each subject. The t-test, chi-square test and multivariate logistic regression analysis were used.</p><p><b>RESULTS</b>The subjects consisted of 3123 men (55.9%) and 2462 women (44.1%). The mean age was 49.4 +/- 12.3 years (range, 20 to 87). The overall prevalence of thrombocytopenia was found to be 0.5%, higher in men than in women (0.6% vs 0.4%, P = 0.504). After controlling for the other covariates, multivariate logistic regression analysis exhibited that the factors significantly related to thrombocytopenia were increasing age (OR, 1.04; 95% CI, 1.004-1.08), anti-HCV positive (OR, 5.24; 95% CI, 2.08-13.20), liver cirrhosis (OR, 7.93; 95% CI, 2.28-27.62), and splenomegaly (OR, 18.86; 95% CI, 6.86-51.87).</p><p><b>CONCLUSION</b>It is advisable to further check the hepatic status, if thrombocytopenia is noted.</p>

Association between rectosigmoid adenomas and cardiovascular risk factors: a hospital-based, cross-sectional study

<p><b>INTRODUCTION</b>Little was known about the association between colorectal adenomas and cardiovascular risk factors in Taiwan. The aim of this study was to assess the association between rectosigmoid adenomas and related factors.</p><p><b>MATERIALS AND METHODS</b>This was a hospital-based, cross-sectional study. We analysed subjects receiving self-referred health examinations at 1 medical centre in Taiwan between 2001 and 2004. In total, 4413 subjects were enrolled in this study. There were 2444 men (55.4%) and 1969 women (44.6%). The mean age was 49.3 +/-12.3 years (range, 20 to 87). All subjects underwent a 60-cm flexible sigmoidoscopic examination and laboratory survey. Adjusted odds ratio (OR) and 95% confidence interval (CI) were expressed using a multivariate logistic regression analysis.</p><p><b>RESULTS</b>In the fi nal model, increasing age (OR, 1.05; 95% CI, 1.03-1.06), hypertriglyceridemia (OR, 1.49; 95% CI, 1.07-2.07), and alcohol consumption (OR, 2.11; 95% CI, 1.47-3.04) were the risk factors for rectosigmoid adenomas in men. Increasing age was the only risk factor for rectosigmoid adenomas in women (OR, 1.03; 95% CI, 1.01-1.06).</p><p><b>CONCLUSION</b>Age, hypertriglyceridemia and alcohol consumption are associated with rectosigmoid adenomas in men, and only age is significantly associated with rectosigmoid adenomas in women.</p>