Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments.

In this editorial, we discussed the apparent discrepancy between the findings described by Colapietro et al, in their case report and data found in the literature. Colapietro et al reported a case of hepatitis B virus (HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton's tyrosine kinase (BTK) inhibitor therapy. First of all, we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response, focusing our attention on the protective role of anti-HBs. We then carefully analyzed literature data on the risk of HBV reactivation (HBVr) in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies. Based on literature data, we suggested that several factors may contribute to the different risks of HBVr: The type of hematologic malignancy; the type of therapy (BTK inhibitors, especially second-generation, seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors); previous exposure to an anti-CD20 as first-line therapy; and ethnicity and HBV genotype. Therefore, the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis: Should we consider further implications?

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology. The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis. Here, we recapitulated the complexity of the renin-angiotensin system, discussed the role of hepatic stellate cell (HSC) autophagy in liver fibrogenesis, and analyzed the possible implications in the development of hepatocarcinoma (HCC). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis, whereas their involvement in HCC is more evident in experimental conditions than in human studies. Angiotensin-converting enzyme 2 (ACE2), and its product Angiotensin (Ang) 1-7, not only regulate HSC autophagy and liver fibrosis, but they also represent potential targets for unexplored applications in the field of HCC. Finally, ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. In this case, Ang 1-7 acts binding to the MasR, and its agonists could modulate this pathway. However, since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively, we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

Comparison of Transient Elastography and Point Shear Wave Elastography for Analysis of Liver Stiffness: A Prospective Study.

Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been introduced as a simple alternative non-invasive test. Therefore, we aimed to compare the results of these two techniques. One hundred and eighty-four consecutive patients attending our outpatient ultrasound clinic were recruited. LSM was performed by both Fibroscan and pSWE. Statistical analysis was conducted by Spearman's test for correlation and linear regression. Bland-Altman graphs and ROC curves were drawn with area under the curve (AUC). Overall, the correlation of LS between Fibroscan and pSWE was substantial (r = 0.68, p < 0.001). Linear regression showed a coefficient b= 0.94 ± 0.02. The Bland-Altman plot found a bias of -0.10, with only 11 values exceeding the 95% confidence interval. When only considering patients with a LSM of > 10 kPa (n = 31), we found an excellent r = 0.79 (0.60-0.90, p < 0.001). A cutoff of 12.15 kPa for pSWE had sensitivity = 74.2% and specificity = 99.3% to detect relevant fibrosis, with an AUC = 0.98. The highest correlation was observed for hepatitis C (r = 0.91) and alcoholic liver disease (ALD)(r = 0.99). In conclusion, pSWE shows LSM estimation in agreement with Fibroscan in most cases, and the best concordance was observed for hepatitis C and ALD, and for higher ranges of LS.

Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol.

Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (Fs6 and Fs14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) (Fs18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-ß-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, FS18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-ß-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups.