螯合疗法(iron chelation therapy)抗肝纤维化治疗?

StephenW

http://www.gastrojournal.org/article/PIIS001650851101170X/fulltext
Chelation Therapy for Secondary Iron Overload: Is the Primary Effect Less Iron or Less Liver Fibrosis?

• Paul C. Adams
  

螯合疗法可能成铁超负荷不相关的其他肝脏疾病的抗肝纤维化治疗。是否有药理作用，
可用于除铁以外延伸,逆转肝纤维化？

The treatment of secondary iron overload in iron-loading anemias has been a challenging task. Because patients are unable to tolerate iron depletion by phlebotomy, chelation treatment has been the mainstay of therapy. The parenteral chelator, deferoxamine, has been cumbersome, expensive, and potentially toxic and this has led to the development of oral iron chelators such as deferasirox (Exjade, Novartis, Basel, Switzerland). The concept has been to administer chronic chelation therapy to increase biliary excretion of iron such that iron excretion exceeds the constant influx of iron that may be secondary to increased intestinal iron absorption and the need for frequent blood transfusions. Iron reduction has been considered to be beneficial to the liver, heart, and other organs by reducing the toxicity of excess iron with free radical formation. In the current study by Deugnier et al,1 a significant reduction in liver fibrosis has been demonstrated in paired liver biopsies in a large sample of thalassemia patients treated with deferasirox. The patient group included a subgroup of patients with hepatitis C (14%), although viral loads and antiviral treatment information were not available. The startling observation in this study is that the reduction of liver fibrosis in not strongly associated with a reduction in liver iron concentration. In fact, 36% of patients on chelation therapy were considered to be a failure of iron reduction. Even in this subgroup of patients, 30% had a reduction in liver fibrosis of 2 Ishak stages, which was a higher percentage than in the group of patients (n = 134) who demonstrated liver iron reduction.
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螯合疗法可能成铁超负荷不相关的其他肝脏疾病的抗肝纤维化治疗。是否有药理作用，
可用于除铁以外延伸,逆转肝纤维化？

"A tantalizing possibility raised by this study is whether chelation therapy could become an antifibrotic therapy in other liver diseases not associated with iron overload. Is there a pharmacologic effect that extends beyond iron removal that could be used to reverse hepatic fibrosis? There has been a research interest in other antifibrotic therapies in liver diseases9 (Table 1). The most dramatic improvements in liver fibrosis have been in the use of nucleoside analogues in the treatment of chronic hepatitis B,10 where chronic viral suppression has led to patients no longer requiring being listed for liver transplantation. Antiviral therapies for hepatitis C have had less pronounced effects on fibrosis,11, 12 but a new era of direct acting antiviral agents (protease inhibitors) for hepatitis C may start to show further benefits on fibrosis. Colchicine has been tried in a variety of liver diseases such as alcoholic hepatitis, and primary biliary cirrhosis with inconsistent results.13 Peroxisome proliferator-activated receptors agonists showed promise in experimental studies14 and in steatohepatitis.15 There are other approaches to iron reduction that do not use chelation. Phlebotomy has been demonstrated to reduce liver fibrosis in hemochromatosis (Table 2).16, 17 Newer approaches would include hepcidin agonist molecules18 or antisense molecules that can block non-heme iron absorption in the intestine."



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