Clinical application of several rapidly evolving technologies-next-generation DNA sequencing, biomarker discovery, and targeted cytokine blockade-has been particularly beneficial to understanding an ...expanding spectrum of genetically defined autoinflammatory diseases.1 Our understanding of the pathways that cause hemophagocytic disorders, such as macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH), is evolving similarly. MAS and HLH are life-threatening sepsis-like conditions notable for hyperferritinemia, acute cytopenias, and hepatitis. If not promptly recognized and treated, they can progress to consumptive coagulopathy, hemophagocytosis, multiorgan failure, and high mortality. HLH is classically associated with genetic defects in cytotoxicity, whereas MAS is observed as a complication of rheumatic diseases.1
Summary The Fontan operation is a widely used palliative procedure in patients with single ventricle anatomy that results in liver injury. As timely identification of liver fibrosis may result in ...management changes to Fontan patients, the aim of our study was to identify clinically meaningful semi-quantitative/quantitative pathologic parameters for biopsy assessment. We performed a retrospective review of 74 liver needle biopsies from Fontan patients. Fibrosis was assessed using quantitative % collagen deposition (%CD) by Sirius red image analysis, METAVIR, congestive hepatic fibrosis score (CHFS), sinusoidal fibrosis (SF) score, and sinusoidal dilation score. Contemporaneous laboratory, hemodynamic, and ultrasound data were collected. Centrilobular and peri-sinusoidal fibrosis was observed in all cases, with 39.2% high grade. Portal fibrosis was observed in 93.2%, with 36.2% high grade (METAVIR F3-F4). Cirrhosis was observed in 5.4%. %CD was increased over control tissue (p<0.001) and correlated with time from Fontan (r=0.3, p=0.009) and prothrombin time (PT) (r=0.25, p=0.034). Mildly elevated PT/INR was the only measure of liver function consistently associated with multiple high-grade fibrosis scores (METAVIR p=0.046, SF p=0.018). Abnormal liver echotexture on ultrasound was associated with high grade CHFS (p=0.03). Pathologic gradings and %CD correlated with each other (r=0.48-0.8, p<0.001). Hepatic fibrosis in Fontan patients in our study is universally present, appears to be time dependent, and correlates with few laboratory measurements of liver function. Careful assessment of needle liver biopsies lends a more meaningful measure of liver fibrosis in the Fontan patient than clinical and laboratory data, allowing for appropriate changes to patient management.
To the Editor: We would like to thank Haugk and colleagues for their letter and the opportunity to address their questions as they move forward with developing a liver biopsy surveillance program for ...adults with failing Fontan circulation. The strength of the Sirius red stain is that its contrast lends itself better to computer discrimination than the trichrome stain, although the trichrome stain (in our experience) allows better morphologic distinction of all the components in a liver biopsy. In our experience, there were a few patients receiving anticoagulation prior to and following the liver biopsy procedure in whom there were minor bleeding issues and one re-admission with more significant bleeding.
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