Variability in Hepatic Iron Concentration in Percutaneous Needle Biopsy Specimens From Patients With Transfusional Hemosiderosis

Butensky, Ellen; Fischer, Roland; Hudes, Mark; Schumacher, Laurie; Williams, Roger A.; Moyer, Thomas P.; Vichinsky, Elliott; Harmatz, Paul

doi:10.1309/puuxegxdlh26nxa2

Cited by 48 publications

(51 citation statements)

References 30 publications

(24 reference statements)

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“…No complications were observed with liver biopsy, extending the record of safety of liver biopsy in expert hands [3][4][5]. These results corroborate previous observations from these and other investigators [5][6][7] that support chemical measurement of the iron concentration in a liver-biopsy specimen as the reference standard for measurement of the hepatic iron concentration. Still, dissonance in the details must be acknowledged; no standard method for liver biopsy procedure, specimen processing and analysis has been established.…”

supporting

confidence: 85%

“…The biopsy needle (cutting needle or Menghini needle with saline flushing), exposure to saline, formalin, and fixation solutions, use of iron-free containers, specimen processing (fresh or paraffin-embedded; methods of deparaffinization and of digestion), methods of analysis (colorimetric, atomic absorption spectroscopy, inductively coupled plasma mass spectroscopy), and other factors differ among published studies and potentially influence results [5,6]. Hepatic iron concentrations measured in deparaffinized samples were a mean of 23% greater than those in desiccated tissue from fresh liver specimens [6]. The minimum weight for an adequate liver sample for analysis remains uncertain; evidence has been provided both for thresholds of 0.4 mg dry weight [8,9] and for 1 mg dry weight [1,4,5].…”

mentioning

confidence: 99%

“…Still, dissonance in the details must be acknowledged; no standard method for liver biopsy procedure, specimen processing and analysis has been established. The biopsy needle (cutting needle or Menghini needle with saline flushing), exposure to saline, formalin, and fixation solutions, use of iron-free containers, specimen processing (fresh or paraffin-embedded; methods of deparaffinization and of digestion), methods of analysis (colorimetric, atomic absorption spectroscopy, inductively coupled plasma mass spectroscopy), and other factors differ among published studies and potentially influence results [5,6]. Hepatic iron concentrations measured in deparaffinized samples were a mean of 23% greater than those in desiccated tissue from fresh liver specimens [6].…”

mentioning

confidence: 99%

“…Nonetheless, a critical role for biopsy will be to calibrate candidate MRI techniques for measurement of liver iron. To serve as a trustworthy standard, a uniform protocol for liver biopsy procedure, specimen processing and analysis is needed to permit meaningful interlaboratory comparisons [6]. The results from Urru and associates [1] in this issue of the Journal indicate that such a protocol is feasible.…”

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confidence: 99%

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Reference method for measurement of the hepatic iron concentration

Brittenham

2015

American J Hematol

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What should be the reference method for measurement of the hepatic iron concentration? In this issue of the American Journal of Hematology, Urru and colleagues [1] present further evidence that, in patients with thalassemia major and transfusional iron overload, chemical measurement of the iron concentration in a desiccated liver-biopsy specimen obtained by percutaneous biopsy is highly reproducible, as judged by measurement in a successive specimen, provided that two conditions are met. The first condition is the absence of cirrhosis, defined in this study as Ishak scores [2] of 5 or 6, because, with cirrhosis, the iron distribution within the liver is no longer uniform. The second condition is that the liver-biopsy specimen is adequate, 1 mg dry weight; variability increases with smaller samples. No complications were observed with liver biopsy, extending the record of safety of liver biopsy in expert hands [3][4][5]. These results corroborate previous observations from these and other investigators [5][6][7] that support chemical measurement of the iron concentration in a liver-biopsy specimen as the reference standard for measurement of the hepatic iron concentration. Still, dissonance in the details must be acknowledged; no standard method for liver biopsy procedure, specimen processing and analysis has been established. The biopsy needle (cutting needle or Menghini needle with saline flushing), exposure to saline, formalin, and fixation solutions, use of iron-free containers, specimen processing (fresh or paraffin-embedded; methods of deparaffinization and of digestion), methods of analysis (colorimetric, atomic absorption spectroscopy, inductively coupled plasma mass spectroscopy), and other factors differ among published studies and potentially influence results [5,6]. Hepatic iron concentrations measured in deparaffinized samples were a mean of 23% greater than those in desiccated tissue from fresh liver specimens [6]. The minimum weight for an adequate liver sample for analysis remains uncertain; evidence has been provided both for thresholds of 0.4 mg dry weight [8,9] and for 1 mg dry weight [1,4,5]. Reports of variability in the hepatic iron concentration in different areas of the liver have generally been restricted to studies of cirrhotic livers [10][11][12]; data are lacking in patients with transfusional iron overload without cirrhosis. Even so, the close relationship observed between the hepatic iron concentration and total body iron stores [4] in transfused patients with thalassemia who were free of cirrhosis suggests that the extent of variability is limited.An alternative view of the reference method for measurement of the hepatic iron concentration is that magnetic resonance imaging (MRI), recommended in a variety of guidelines, has become the de facto technique. Nonetheless, since acceptance of the manuscript by Urru et al.[1] for publication, a painstaking systematic review and meta-analysis of this use of MRI has appeared, [13] concluding that "measurements of liver iron concentration by ...

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confidence: 99%

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confidence: 99%

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Reference method for measurement of the hepatic iron concentration

Brittenham

2015

American J Hematol

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“…There are of course limitations in our study: only two biopsies per patient were performed and we cannot exclude different iron concentration in different liver areas (for example within the subcapsular zone or differences between the left and the right lobes); moreover, the issue of interlaboratory reproducibility and the problem related to overestimation of the paraffin embedded specimens were not addressed here [13].…”

Section: Discussionmentioning

confidence: 99%

Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

et al. 2014

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Determination of liver iron concentration is essential to predict iron related tissue damage and to guide chelation therapy. To assess the reliability of a single biopsy iron concentration determination in representing the whole liver iron concentration, we conducted a prospective study performing two immediately successive liver biopsies from 61 noncirrhotic, iron overloaded thalassemia patients, directing the needle to different direction from the same skin cut. The correlation among sample biopsies was determined by both regression analysis and the Bland-Altman method. The results showed that overall correlation between the two samples was high (Pearson's coefficient of correlation r 5 0.970, P < 0.0001; 95% CI 0.951-0.981; R 2 5 0.941). To evaluate if sample dimension had an impact on the analysis we analyzed separately biopsy couples were both sample gross weight were 1 mg dry weight (n 5 16) from the others [one or both had a specimen gross weight <1 mg dry weight (n 5 45)]. In the first case, correlation coefficient r was equal to 0.998 (P < 0.0001; 95% CI: 0.995-0.999; R 2 5 0.996) while in the latter was 0.960 (P < 0.0001; 95% CI: 0.928-0.977; R 2 5 0.921). In no instance second specimen prediction interval was outside the interval implying different prognostic and therapeutic decision if both liver samples gross weight were 1 mg dry weight. The Bland-Altman plot analysis showed the same trend observed using Pearson's correlation coefficient in the analyzed sample categories. Hepatic iron concentration determined in "good quality" biopsy specimen (i.e. sample gross weight 1 mg dry weight) is a reliable indicator of whole liver iron concentration.

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Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders

et al. 2018

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Determination of iron accumulation is crucial in diagnosing the occurrence and progression of many liver‐ and iron‐related diseases. Thus far, little is known about the profiles of iron deposition in different liver zones, particularly under conditions with disordered iron homeostasis. Here, uneven iron distribution in livers of patients with hereditary hemochromatosis (HH) is uncovered, showing the region with the highest iron concentration near the entrance site of the portal vein and hepatic artery in contrast to the sites with the lowest iron concentration close to the distal edge. Distinct iron distribution profiles are also found throughout liver zones in wild‐type mice and various mouse models with iron metabolism disorders, including hemochromatosis (Hfe−/−), iron deficiency, and inflammation. Of note, similar findings observed in HH patients are further demonstrated in Hfe−/− mice. Moreover, the zones with greater iron accumulation appear to be more sensitive to iron changes, e.g., there is iron increase upon iron overload and iron loss in response to iron deficiency. Mechanistic investigation manifests that these differential iron changes in liver zones are subjected to the regulation by the hepcidin–ferroportin axis. Additionally, the data corroborate the reliability of magnetic resonance imaging (MRI) in recognizing the differential iron deposition profiles among liver zones.

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Variability in Hepatic Iron Concentration in Percutaneous Needle Biopsy Specimens From Patients With Transfusional Hemosiderosis

Cited by 48 publications

References 30 publications

Reference method for measurement of the hepatic iron concentration

Reference method for measurement of the hepatic iron concentration

Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders

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