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Iron chelation therapy in the management of thalassemia: the Asian perspectives

Viprakasit V, Lee-Lee C, Chong QT, Lin KH, Khuhapinant A

Int. J. Hematol., 2009 Nov;90(4):435-445.
PMID: 19862602 DOI: 10.1007/s12185-009-0432-0

Worldwide, thalassemia is the most commonly inherited hemolytic anemia, and it is most prevalent in Asia and the Middle East. Iron overload represents a significant problem in patients with transfusion-dependent beta-thalassemia. Chelation therapy with deferoxamine has traditionally been the standard therapeutic option but its usage is tempered by suboptimal patient compliance due to the discomfort and demands associated with the administration regimen. Therefore, a great deal of attention has been focused on the development of oral chelating agents. Deferiprone, even though available for nearly two decades in Asia with recent encouraging data on cardiac iron removal and long-term efficacy, has serious adverse effects including agranulocytosis and neutropenia which has impeded it from routine clinical practice. A novel oral chelator; deferasirox is effective throughout a 24 h dosing period and both preclinical and clinical data indicate that it successfully removes both hepatic and cardiac iron. In Asia, optimal management of severe thalassemia patients and the availability and access to oral iron chelators still presents a major challenge in many countries. In this regard, the development and implementation of consensus guidelines for management of Asian patients with transfusion-dependent thalassemia will be a major step towards improving and maintaining the continuity of patient care.
Rapidly increasing liver progenitor cell numbers in human regenerating liver after portal vein ligation and liver partition

Lin KH, Hsu HT, Teng TH, Lin PY, Ko CJ, Hsieh CE, et al.

Malays J Pathol, 2017 Dec;39(3):289-291.
PMID: 29279592

BACKGROUND: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitor cells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells. Although liver progenitor cell proliferation during the regenerative process has been observed in animal models of severe liver injury, it has never been observed in vivo in humans because it is unethical to take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitor cells and the roles they play in liver regeneration. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy so that major hepatectomy can be performed safely. This staged procedure allows for liver biopsy specimens to be taken before and after the liver begins to regenerate.
CASE PRESENTATION: The liver progenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatic tumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number of liver progenitor cell under high magnification examination by stain of immunomarkers. This is the first in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.
Short-term vasoactive agent treatment driven by physicians' preference in acute esophageal variceal bleeding in a tertiary center

Chuah YY, Hsu PI, Tsai WL, Yu HC, Tsay FW, Chen WC, et al.

PeerJ, 2019;7:e7913.
PMID: 31720102 DOI: 10.7717/peerj.7913

Background: Vasoactive drugs are frequently used in combination with endoscopic variceal ligation (EVL) in treatment of acute esophageal variceal bleeding (EVB). The aim of study was to assess physicians' preference of vasoactive agents in acute EVB, their reasons of preference and efficacy and safety of these short course regimens.
Methods: Cirrhotic patients with suspected EVB were screened (n = 352). Eligible patients were assigned based on the physician's preference to either somatostatin (group S) or terlipressin (group T) followed by EVL. In group S, intravenous bolus (250 µg) of somatostatin followed by 250 µg/hour was continued for three days. In group T, 2 mg bolus injection of terlipressin was followed by 1 mg infusion every 6 h for three days.
Results: A total of 150 patients were enrolled; 41 in group S and 109 in group T. Reasons for physician preference was convenience in administration (77.1%) for group T and good safety profile (73.2%) for group S. Very early rebleeding within 49-120 h occurred in one patient in groups S and T (p = 0.469). Four patients in group S and 14 patients in group T have variceal rebleeding episodes within 6-42 d (p = 0.781). Overall treatment-related adverse effects were compatible in groups S and T (p = 0.878), but the total cost of terlipressin and somatostatin differed i.e., USD 621.32 and USD 496.43 respectively.
Conclusions: Terlipressin is the preferred vasoactive agent by physicians in our institution for acute EVB. Convenience in administration and safety profile are main considerations of physicians. Safety and hemostatic effects did not differ significantly between short-course somatostatin or terlipressin, although terlipressin is more expensive.
Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox

Viprakasit V, Ibrahim H, Ha SY, Ho PJ, Li CK, Chan LL, et al.

Int. J. Hematol., 2011 Mar;93(3):319-328.
PMID: 21374076 DOI: 10.1007/s12185-011-0789-8

Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356