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

Abstract

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.

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.…”

“…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.…”

“…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. Inevitably, MRI will increasingly be used for clinical purposes but, as the systematic review [13] and editorial [14] emphasize, much more work is needed to provide consistent, clinically reliable results.…”

Can multi-slice or navigator-gated R2* MRI replace single-slice breath-hold acquisition for hepatic iron quantification?

“…Therefore, close monitoring of iron concentration in patients is essential to determine the appropriate dose and efficacy of chelation therapy [8]. Needle biopsy was used to determine hepatic iron concentration (HIC) until magnetic resonance imaging (MRI) methods emerged to replace this invasive procedure; needle biopsy is susceptible to sampling variation [9, 10] and can cause pain and infection [11–13]. …”

Radial Ultrashort TE Imaging Removes the Need for Breath-Holding in Hepatic Iron Overload Quantification by R2* MRI

“…The traditional reference standard for assessing HIC is liver biopsy [11], but this procedure is invasive and painful, has sampling variability [12], and is associated with risks such as bleeding and infection [13]. In recent years, R2* MRI has been increasingly used as a noninvasive alternative to liver biopsy for HIC quantification.…”