Clinical Experience of Patients With Hepatitis C Treated With Direct-Acting Antivirals After Heart Transplantation.

BACKGROUND: Hepatitis C increases the mortality and morbidity of patients after heart transplant. Direct-acting antivirals (DAAs) are the primary drugs for hepatitis C treatment. However, such drugs are expensive and frequently unaffordable for patients. In DAA treatment, the assessment of drug interaction is crucial. METHODS: We investigated a retrospective case series study from January 2017 to December 2019. Sustained virologic response 12 (SVR12) was used to assess the effectiveness of DAA treatment. Data on patients' demographic information, timing of hepatitis C virus (HCV) infection (before or after heart transplant), HCV genotypes and viral loads, DAAs used (branded drugs or generic drugs), and drug interaction assessments were collected. RESULTS: Fifteen heart transplant patients received hepatitis C treatments during the study period, 11 of whom were infected because their donors had hepatitis C. After DAA treatment, HCV was undetectable in all patients, and 93.3% of them achieved SVR12. Nine patients used the generic sofosbuvir/velpatasvir, and 88.9% of them achieved SVR12. A total of 256 drugs were used with DAAs; 51 records of drug interactions were noted, 3 of which were contraindications, and the remaining records were potential interactions. Patients who used sofosbuvir or elbasvir/grazoprevir experienced fewer drug interactions. CONCLUSIONS: DAA treatment is effective for hepatitis C treatment in patients after heart transplant. Patients who cannot afford branded drugs because of their prices can use generic drugs as an alternative. Drug interactions must be surveyed during DAA treatment.

Citrus flavonoids suppress IL-5 and ROS through distinct pathways in PMA/ionomycin-induced EL-4 cells.

Interleukin-5 (IL-5) strongly initiates the asthmatic inflammatory response, which affects 300 million patients with asthma annually worldwide, through oxidative stress generation. Citrus flavonoids have beneficial properties, such as anti-inflammatory and antioxidant properties, but the precise molecular mechanism of the inhibition of the asthmatic inflammatory response is still unclear. This study aimed to investigate the underlying mechanisms of ROS and IL-5 reduction with citrus flavonoid treatment in PMA/ionomycin-induced EL-4 cells. Our results showed that hesperetin and gardenin A dramatically suppressed ROS and IL-5 production through distinct pathways. Interestingly, hesperidin induced HO-1 expression through the transcription factor Nrf2 coupled with the PI3K/AKT or ERK/JNK signaling pathway, consequently downregulating NFAT activity and IL-5 secretion. Likewise, gardenin A induced HO-1 expression and subsequently suppressed IL-5 production by reducing NFAT activity and upregulating PPARγ in EL-4 cells, suggesting that inducing HO-1 expression may inhibit asthmatic inflammation. Altogether, hesperidin and gardenin A have great potential for regulating the asthma-associated immune responses through antioxidant properties.