Increased duodenal iron absorption through up‐regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis

Hoki, Toshifumi; Miyanishi, Koji; Tanaka, Shingo; Takada, Kohichi; Kawano, Yutaka; Sakurada, Akira; Sato, Masanori; Kubo, Tomohiro; Sato, Tsutomu; Sato, Yasushi; Takimoto, Rishu; Kobune, Masayoshi; Kato, Junji

doi:10.1002/hep.27774

Cited by 67 publications

(67 citation statements)

References 41 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Estimates of liver iron concentration by MRI were in the middle of the normal range at 23 µmol/g. In the study of Hoki et al, mean serum ferritin was 182 µg/L, and of the 40 patients reported, there were only 2 of 40 (5%) with 3+ iron staining and none with 4+ staining. Therefore, it may not be surprising that iron reduction therapy had no obvious benefits given that the patients did not have iron overload.…”

supporting

confidence: 89%

The (II)logic of iron reduction therapy for steatohepatitis

Adams

2015

Hepatology

View full text Add to dashboard Cite

A tool in the technique of logic that dates back to Aristotle is the use of a syllogism to prove an arguable point. In the context of iron reduction for steatohepatitis, it could unfold as follows:Major premise: An elevated serum ferritin can be associated with liver iron overload.Minor premise: Steatohepatitis is often associated with an elevated serum ferritin.Conclusion: Steatohepatitis can be associated with liver iron overload.The strength of the conclusion depends on the power or accuracy of the major and minor premise. There is no doubt that steatohepatitis patients usually have an elevated serum ferritin. However, the major premise that a high serum ferritin is an indicator of liver iron overload is where the problem begins with steatohepatitis (Fig. 1A). The overinterpretation of serum ferritin is a major clinical problem that leads to the overdiagnosis of hemochromatosis and or iron overload. 1,2Therapeutic bleeding has a long tradition in medieval medicine, and previous studies have shown reductions in liver transaminases postphlebotomy in a variety of liver diseases not commonly associated with iron overload. The assessment of liver iron overload is traditionally done by liver biopsy and, ideally, liver iron concentration. Semiquantitative iron staining (Prussian Blue 0-4) has usually shown that only those with 3 or 41 staining will have elevations in liver iron concentration. Magnetic resonance imaging (MRI) scanning is a noninvasive indirect estimate of liver iron stores. In the study of Adams et al., 3 the treated patients had a mean serum ferritin of 255 mg/L, which is within the reference range. Estimates of liver iron concentration by MRI were in the middle of the normal range at 23 mmol/g. In the study of Hoki et al., 4 mean serum ferritin was 182 mg/L, and of the 40 patients reported, there were only 2 of 40 (5%) with 31 iron staining and none with 41 staining. Therefore, it may not be surprising that iron reduction therapy had no obvious benefits given that the patients did not have iron overload. There are still investigators that emphasize the regional distribution of iron in fatty liver disease in macrophages, rather than hepatocytes, and speculate that this could be contributing to oxidative stress. It is important to remember that it is very difficult to induce liver fibrosis in experimental animals with massive iron loading, and there are clinical patients with extreme iron overload without fibrosis or cirrhosis (Fig. 1B). The findings in these studies are similar to a study in 43 patients by Beaton et al.5 that did paired liver biopsies before and after phlebotomy therapy. Only 2 of 43 (5%) patients had an elevated liver iron concentration initially and there were no beneficial effects on a range of histological parameters, including fibrosis. Serum ferritin decreased with phlebotomy therapy as liver iron concentration decreased from the normal range to the low normal range. There was not a strong correlation between liver inflammation, Creactive protein, body mass index, and serum fe...

show abstract

supporting

confidence: 89%

The (II)logic of iron reduction therapy for steatohepatitis

Adams

2015

Hepatology

View full text Add to dashboard Cite

show abstract

“…Similarly, it has recently been reported that increased iron absorption despite high hepcidin levels occurs in patients with nonalcoholic steatohepatitis possibly associated with mild iron overload, compared to that observed in patients with simple steatosis . This was associated with upregulation of duodenal iron absorption again via induction of Divalent Metal Transporter‐1 . Although our study was not designed and powered to test an impact of liver damage on iron metabolism, we did not detect any difference in iron absorption between patients with steatohepatitis and simple steatosis, suggesting that altered iron metabolism in DIOS is not a consequence of liver damage.…”

Section: Discussionmentioning

confidence: 38%

Section: Discussionmentioning

confidence: 82%

Hepcidin resistance in dysmetabolic iron overload

Rametta

Dongiovanni

Pelusi

et al. 2016

Liver International

View full text Add to dashboard Cite

show abstract

“…Hoki et al . [43] studied 40 subjects with a mean serum ferritin level of 182 μg/L. Only 5% had + 3 iron staining, and none had + 4 staining.…”

Section: Discussionmentioning

confidence: 99%

Outcome of phlebotomy for treating nonalcoholic fatty liver disease: A systematic review and meta-analysis

Jaruvongvanich

Riangwiwat

Sanguankeo

et al. 2016

Saudi J Gastroenterol

View full text Add to dashboard Cite

Background/Aims:No medications have been approved for managing nonalcoholic fatty liver disease (NAFLD). Lifestyle intervention is the mainstay for its treatment. Hyperferritinemia, which appears to be associated with the severity of liver injury and insulin resistance, is frequently observed in patients with NAFLD.Patients and Methods:We conducted a systematic review and meta-analysis of the outcomes of four interventional trials regarding the effect of phlebotomy in patients with NAFLD versus the outcomes of NAFLD patients who did not undergo phlebotomy. Primary outcome was the pooled mean difference (MD) of the homeostasis model assessment of insulin resistance (HOMA-IR). The secondary outcomes were the changes in liver enzymes and the lipid profile.Results:Four interventional studies involving 438 participants were included in the meta-analysis. HOMA-IR was lower in patients who underwent phlebotomy, with an MD of 0.84 [95% confidence interval (CI) 0.01 to 1.67, I2 = 72%]. Phlebotomy also significantly reduced the alanine aminotransferase (MD = 10.05, 95% CI 7.19–12.92, I2 = 34%) and triglyceride (MD = 9.89, 95% CI 4.96–14.83, I2 = 22%) levels and increased the high-density cholesterol level (MD = 3.48, 95% CI 2.03–4.92, I2 = 18%).Conclusion:Phlebotomy decreased insulin resistance and liver transaminase levels in patients with NAFLD. In addition, it improved their lipid profile.

show abstract

Increased duodenal iron absorption through up‐regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis

Cited by 67 publications

References 41 publications

The (II)logic of iron reduction therapy for steatohepatitis

The (II)logic of iron reduction therapy for steatohepatitis

Hepcidin resistance in dysmetabolic iron overload

Outcome of phlebotomy for treating nonalcoholic fatty liver disease: A systematic review and meta-analysis

Contact Info

Product

Resources

About