Phase <scp>II</scp> clinical trial of phlebotomy for non‐alcoholic fatty liver disease

Beaton, Melanie; Chakrabarti, Subrata; Levstik, Mark; Speechley, Mark; Marotta, Paul; Adams, Paul C.

doi:10.1111/apt.12255

Cited by 74 publications

(84 citation statements)

References 45 publications

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“…This is also supported by the indistinguishable responses of single Hjv -/-and double Hfe -/-Hjv -/-mice to dietary iron loading 2 and is in line with recent biochemical data suggesting that HFE stimulates hepcidin expression by stabilizing ALK3, a type I bone morphogenetic protein receptor. 3 It is known that HJV functions as a bone morphogenetic protein coreceptor that enhances the bone morphogenetic protein signaling pathway.…”

Section: Iron Regulation Of Hepcidin Through Hfe and Hjv: Common Or Dsupporting

confidence: 89%

“…For example, the study referenced by Ryan et al as being controlled was actually a single-arm study. 2 Our prospective, multicenter, randomized, controlled trial, being the largest study of this type, was unable to detect any effect of iron reduction on liver steatosis, serum markers of liver injury, lipid peroxidation, insulin resistance, or quality-of-health measures.…”

Section: Replymentioning

confidence: 83%

“…Residual induction of hepatic hepcidin mRNA was evident in both Hjv -/-and Hfe -/-Hjv -/-genotypes after 4-week feeding with a high-iron diet. 2 Importantly, this was…”

Section: Iron Regulation Of Hepcidin Through Hfe and Hjv: Common Or Dmentioning

confidence: 97%

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et al. 2015

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Section: Iron Regulation Of Hepcidin Through Hfe and Hjv: Common Or Dsupporting

confidence: 89%

Section: Replymentioning

confidence: 83%

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et al. 2015

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“…In contrast to hemoch romatosis patients, NAFLD subjects have impaired iron mobilisation from storage sites and may there fore develop anemia in response to phlebotomy treatment. We therefore recommend close monitoring of serum ferritin, TfS and hemoglobin at each visit for the period of time while these patients are on phlebotomy treatment [26,153] .…”

Section: What Is the Therapeutic Potential Of Modulating Iron Stores mentioning

confidence: 99%

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Aigner

Weiss

Datz

2014

WJH

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Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the "dysmetabolic iron overload syndrome". Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxylradicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.

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“…Fujita et al [26] showed that iron reduction resulting from a-combination of phlebotomy and a low iron diet resulted not only in improvement of ALT levels but also normalization of hepatic levels of 8-OHdG in 11 NASH patients. In a phase Ⅱ trial on 31 patients with NAFLD, phlebotomy resulted in a significant improvement in the NAFLD activity score (NAS), AST and ALT [27] . In a phase Ⅲ trial, Valenti et al [28] studied 38 NAFLD patients randomized to phlebotomy (n = 21) or [16] 2007 Open labeled 35/40 Chronic hepatitis C…”

Section: Iron Depletion Therapymentioning

confidence: 99%

Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy

Miyanishi

Hoki

Tanaka

et al. 2015

WJH

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Oxidative stress has been investigated in the context of alcoholic liver injury for many years and shown to be a causal factor of chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson' s disease, and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays an important role in hepatocarcinogenesis. In cases with persistent hepatitis due to failure of hepatitis C virus eradication, or chronic liver disease, such as NASH, the treatment of which remains unestablished, it is important to reduce serum alanine aminotransferase levels and prevent liver fibrosis and development of hepatocellular carcinoma. This also suggests the importance of antioxidant therapy. Among treatment options where it would be expected that anti-inflammatory activity plays a role in their confirmed efficacy for chronic hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko-To, and vitamin E can all be considered antioxidant therapies. To date, however, the ability of these treatments to prevent cancer has been confirmed only in CHC. Nevertheless, anti-inflammatory and antifibrotic effects have been demonstrated in other liver diseases and these therapies may potentially be effective for cancer prevention.

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Phase II clinical trial of phlebotomy for non‐alcoholic fatty liver disease

Abstract: SUMMARYBackground Elevated iron indices are described in non-alcoholic fatty liver disease and iron reduction has been suggested as a potential therapy.

Cited by 74 publications

References 45 publications

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Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy

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