Effect of iron reduction by phlebotomy in Japanese patients with nonalcoholic steatohepatitis: A pilot study☆

Sumida, Yoshio; Kanemasa, Kazuyuki; Fukumoto, Kohei; Yoshida, Naohisa; Sakai, Kyoko; Nakashima, Tomoki; Okanoue, Takeshi

doi:10.1016/j.hepres.2006.08.003

Cited by 56 publications

(51 citation statements)

References 38 publications

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“…Iron is considered a putative element that interacts with oxygen radicals in inducing liver damage and fibrosis [12]. High rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH patients [12], and removal of excess iron by repeated phlebotomy may be of therapeutic benefit for both chronic hepatitis C patients [23] and NASH patients [24]. In steatotic livers, saturation of b-oxidation by excess free fatty acids will ultimately lead to generation of hydrogen peroxide, which in turn can be converted to highly reactive hydroxyl radicals in the presence of free iron [13,25].…”

Section: Discussionmentioning

confidence: 99%

Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation

et al. 2009

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596-0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.

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Section: Discussionmentioning

confidence: 99%

Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation

et al. 2009

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“…According to Fargion et al [111], in 42 NAFLD patients, serum transaminase levels were significantly decreased after a 4-month hypocaloric diet, and a further reduction was observed after phlebotomies. Sumida et al [112] also reported that phlebotomy decreased serum transaminase activities in Japanese patients with biopsy-proven NASH. Riquelme et al [113] reported that a 52-year-old nonobese woman with biopsy-proven NASH obtained not only improvement in transaminase activities but also complete resolution of fatty infiltration and inflammatory changes in liver histology after iron depletion therapy (long-term phlebotomy with a low-iron diet).…”

Section: Metformin Cq: Are Biguanides Effective For Patients With Nafmentioning

confidence: 94%

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

et al. 2015

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Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various noninvasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary.Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 to January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.

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“…According to Fargion et al [23] , HOMA-IR and ALT were significantly reduced after phlebotomy in 42 patients with NAFLD. Sumida et al [24] also reported that aspartate aminotransferase (AST) and ALT were reduced by phlebotomy in 9 Japanese patients with NASH. Valenti et al [25] reported that 64 NAFLD patients treated by phlebotomy achieved significant reduction in insulin resistance compared with 64 NAFLD patients who underwent lifestyle modifications only.…”

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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Effect of iron reduction by phlebotomy in Japanese patients with nonalcoholic steatohepatitis: A pilot study☆

Cited by 56 publications

References 38 publications

Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation

Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy

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