1.Safety considerations for withdrawal of nucleos(t)ide analogues in patients with chronic hepatitis B: First, do no harm
Yao-Chun HSU ; Cheng-Hao TSENG ; Jia-Horng KAO
Clinical and Molecular Hepatology 2023;29(4):869-890
Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.
2.14-1 Gender differences in seasonal variation of risk factors for acute myocardial infarction in eastern Taiwan
Chih-Wei LEE ; Chien-Hui HUANG ; Chiao-Yu SHIH ; Yu-Zu WU ; Tseng-Hao TSENG
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2014;77(5):525-525
Objectives: The purposes of this study were to determine whether men and women differ in risk factors for acute myocardial infarction (AMI) during the four seasons of the year. Materials and methods: Medical records of 2,086 (women: 693) patients hospitalized with a confirmed AMI were reviewed retrospectively from the region’s only medical center in eastern Taiwan. The onset date of 544 patients (women: 178) was in spring, 493 patients (women: 165) in summer, 474 patients (women: 155) in autumn, and 575 patients (women: 195) in winter. Risk factors of age, percentage of smoking (smoking%), percentage of diabetes (diabetes%), percentage of hypertension (hypertension%), total cholesterol, and body mass index were assessed. In each season, logistic regression model was used to calculate the odds ratio (OR) and 95% conference interval (CI) of women compared to men by risk factors. Results: In spring, women presented significantly higher values in age (OR 1.022; 95%CI 1.012-1.031 ) and diabetes% (OR2.373;95%CI 1.554-3.625), significantly lower in smoking% (OR 0.187;95%CI 0.145-0.240). In summer, women presented significantly lower values in body mass index (OR 0.907;95%CI 0.856-0.960) and smoking% (OR 0.222; 95%CI 0.134-0.367). In autumn, women presented significantly higher values in age (OR 1.033;95%CI 1.012-1.053) and total cholesterol (OR 1.009;95%CI 1.004-1.013), significantly lower in smoking% (OR 0.168;95%CI 0.098-0.289). In winter, women presented significantly higher values in diabetes% (OR 1.845;95%CI 1.250-2.725), hypertension% (OR1.550;95%CI 1.001-2.402), and total cholesterol (OR 1.008;95%CI 1.004-1.012), significantly lower in smoking% (OR 0.188;95%CI 0.119-0.297). Conclusion: The differences between women and men in risk factors for AMI did present seasonal variation in eastern Taiwan. This finding would provide further insight into medical climatology in preventing serious cardiovascular events.
3.Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation
Ying-Nan TSAI ; Jia-Ling WU ; Cheng-Hao TSENG ; Tzu-Haw CHEN ; Yi-Ling WU ; Chieh-Chang CHEN ; Yu-Jen FANG ; Tzeng-Huey YANG ; Mindie H. NGUYEN ; Jaw-Town LIN ; Yao-Chun HSU
Clinical and Molecular Hepatology 2024;30(1):98-108
Background/Aims:
Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR).
Methods:
This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR.
Results:
The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81).
Conclusions
Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.
4.Mechanism of tonifying Qi by traditional Chinese medicine from mitochondrial dynamics.
Ruo-Yuan GAO ; Jing-Ran GAO ; Hao-Yu ZHAO ; Tian LAN ; Yii-der TSENG
China Journal of Chinese Materia Medica 2023;48(13):3684-3692
According to the traditional Chinese medicine(TCM) theory, Qi is the essential component maintaining life. Mitochondria are the cellular organelles that generate energy. Qi exhibits abundant common characteristics in bioenergetics compared with mitochondria which control the cellular energy through fusion and fission. Studies have proven that the qi-tonifying function of Chinese medicinal plants and their components facilitates mitochondrial fusion, therefore enhancing ATP synthesis. These studies provide a framework for deciphering the pharmacological mechanisms of Qi-tonifying herbs. This article introduces the common source and function shared by Qi and mitochondria and the regulatory effects of herbal remedies on energy from mitochondria dynamics. This review aims to interpret the connotation of tonifying qi in TCM theory based on the modern biomedical theory.
Medicine, Chinese Traditional
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Drugs, Chinese Herbal/pharmacology*
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Qi
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Mitochondrial Dynamics
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Plants, Medicinal