- Email: [email protected]
Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan circulation—reply
Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan circulation—reply Lea F. Surrey MD, Pierre Russo MD, Jack Rychik MD, David J. Goldberg MD, Kathryn Dodds CRNP, Michael L. O’Byrne MDMSCE, Andrew C. Glatz MDMSCE, Elizabeth B. Rand MD, Henry C. Lin MD PII: DOI: Reference:
S0046-8177(17)30213-7 doi: 10.1016/j.humpath.2017.04.029 YHUPA 4250
To appear in:
Human Pathology
Received date: Accepted date:
13 April 2017 29 April 2017
Please cite this article as: Surrey Lea F., Russo Pierre, Rychik Jack, Goldberg David J., Dodds Kathryn, O’Byrne Michael L., Glatz Andrew C., Rand Elizabeth B., Lin Henry C., Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan circulation—reply, Human Pathology (2017), doi: 10.1016/j.humpath.2017.04.029
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan
T
circulation—reply
RI P
To the Editor:
SC
We would like to thank Haugk and colleagues for their letter and the opportunity to
NU
address their questions as they move forward with developing a liver biopsy surveillance program for adults with failing Fontan circulation.
MA
We acknowledge the problem of apparent preserved synthetic liver function despite fibrosis on liver biopsy; however, we did not consider correlating histology findings with non-
ED
invasive fibrosis scores. One of the goals of the study [1] was to examine the utility of
PT
quantitative Sirius red staining in the context of established clinical parameters in our population. The Fib-4 and APRI scores were developed for adult patients with portal-based fibrosis
CE
(Hepatitis C). While these scores are starting to be applied to select populations in the pediatric
AC
setting, such as cystic fibrosis, they have not been well validated for pediatric populations. We feel that this additional comparison would be of limited value in our cohort at this time as the goal of this study was to validate the utility of Sirius red staining as a measure of fibrosis. However, comparison in an adult population would certainly be of interest. Haugk and colleagues raise a valid point regarding the apparent sensitivity of Sirius red staining. 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. It is thus unlikely, in our opinion, that Sirius red will replace the trichrome stain in standard practice. One of the purposes
ACCEPTED MANUSCRIPT of our study was to compare Sirius red quantitation with routine standard staging of biopsies, which typically uses trichrome. Our aim was not to compare morphologic staging of Sirius red
T
and trichrome; therefore, Sirius red was only used for quantitative analysis. Nonetheless, we feel
RI P
that our results reflect that standard staging and Sirius red quantitative analysis match fairly well. We do acknowledge the potential risk of liver biopsy in our surveillance patient
SC
population, of which the major risk is bleeding. To minimize this risk, the activated clotting time
NU
is checked prior to the biopsy to insure that it is less than 200 seconds (with protamine given and rechecked if over 200 seconds). All biopsies were performed percutaneously by staff
MA
interventional radiologists under ultrasound guidance in order to directly visualize the section of liver being biopsied and avoid large vessels. As part of the procedure, the biopsy track is filled
ED
with gel-foam to further minimize bleeding risk. Overnight observation along with pre- and post-
PT
procedure hemoglobin comparisons were used to assess for bleeding. Other risks to consider would be cardiac anesthesia. In our experience, there were a few patients receiving
CE
anticoagulation prior to and following the liver biopsy procedure in whom there were minor
AC
bleeding issues and one re-admission with more significant bleeding. However, there was no significant bleeding in any patient who was not receiving anticoagulation. No patients had adverse events related to anesthesia.
Lea F. Surrey MD Pierre Russo MD Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 E-mail address: [email protected]
ACCEPTED MANUSCRIPT
Jack Rychik MD
RI P
T
David J. Goldberg MD Kathryn Dodds CRNP
NU
SC
Division of Cardiology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104
Michael L. O’Byrne MD MSCE
MA
Division of Cardiology, Children’s National Medical Center and Department of Pediatrics, The
PT
ED
George Washington University School of Medicine and Health Sciences, Washington DC 20037
Andrew C. Glatz MD MSCE
AC
CE
Division of Cardiology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104
Elizabeth B. Rand MD Henry C. Lin MD
Division of Gastroenterology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104
Reference [1] Surrey LF, Russo P, Rychik J, et al. Prevalence and characterization of fibrosis in surveillance liver biopsies of patients with Fontan circulation. HUM PATHOL 2016;57:106-15.
S0046-8177(17)30213-7 doi: 10.1016/j.humpath.2017.04.029 YHUPA 4250
To appear in:
Human Pathology
Received date: Accepted date:
13 April 2017 29 April 2017
Please cite this article as: Surrey Lea F., Russo Pierre, Rychik Jack, Goldberg David J., Dodds Kathryn, O’Byrne Michael L., Glatz Andrew C., Rand Elizabeth B., Lin Henry C., Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan circulation—reply, Human Pathology (2017), doi: 10.1016/j.humpath.2017.04.029
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Defining the role of liver biopsy in the assessment of liver fibrosis in patients with Fontan
T
circulation—reply
RI P
To the Editor:
SC
We would like to thank Haugk and colleagues for their letter and the opportunity to
NU
address their questions as they move forward with developing a liver biopsy surveillance program for adults with failing Fontan circulation.
MA
We acknowledge the problem of apparent preserved synthetic liver function despite fibrosis on liver biopsy; however, we did not consider correlating histology findings with non-
ED
invasive fibrosis scores. One of the goals of the study [1] was to examine the utility of
PT
quantitative Sirius red staining in the context of established clinical parameters in our population. The Fib-4 and APRI scores were developed for adult patients with portal-based fibrosis
CE
(Hepatitis C). While these scores are starting to be applied to select populations in the pediatric
AC
setting, such as cystic fibrosis, they have not been well validated for pediatric populations. We feel that this additional comparison would be of limited value in our cohort at this time as the goal of this study was to validate the utility of Sirius red staining as a measure of fibrosis. However, comparison in an adult population would certainly be of interest. Haugk and colleagues raise a valid point regarding the apparent sensitivity of Sirius red staining. 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. It is thus unlikely, in our opinion, that Sirius red will replace the trichrome stain in standard practice. One of the purposes
ACCEPTED MANUSCRIPT of our study was to compare Sirius red quantitation with routine standard staging of biopsies, which typically uses trichrome. Our aim was not to compare morphologic staging of Sirius red
T
and trichrome; therefore, Sirius red was only used for quantitative analysis. Nonetheless, we feel
RI P
that our results reflect that standard staging and Sirius red quantitative analysis match fairly well. We do acknowledge the potential risk of liver biopsy in our surveillance patient
SC
population, of which the major risk is bleeding. To minimize this risk, the activated clotting time
NU
is checked prior to the biopsy to insure that it is less than 200 seconds (with protamine given and rechecked if over 200 seconds). All biopsies were performed percutaneously by staff
MA
interventional radiologists under ultrasound guidance in order to directly visualize the section of liver being biopsied and avoid large vessels. As part of the procedure, the biopsy track is filled
ED
with gel-foam to further minimize bleeding risk. Overnight observation along with pre- and post-
PT
procedure hemoglobin comparisons were used to assess for bleeding. Other risks to consider would be cardiac anesthesia. In our experience, there were a few patients receiving
CE
anticoagulation prior to and following the liver biopsy procedure in whom there were minor
AC
bleeding issues and one re-admission with more significant bleeding. However, there was no significant bleeding in any patient who was not receiving anticoagulation. No patients had adverse events related to anesthesia.
Lea F. Surrey MD Pierre Russo MD Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 E-mail address: [email protected]
ACCEPTED MANUSCRIPT
Jack Rychik MD
RI P
T
David J. Goldberg MD Kathryn Dodds CRNP
NU
SC
Division of Cardiology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104
Michael L. O’Byrne MD MSCE
MA
Division of Cardiology, Children’s National Medical Center and Department of Pediatrics, The
PT
ED
George Washington University School of Medicine and Health Sciences, Washington DC 20037
Andrew C. Glatz MD MSCE
AC
CE
Division of Cardiology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104
Elizabeth B. Rand MD Henry C. Lin MD
Division of Gastroenterology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104
Reference [1] Surrey LF, Russo P, Rychik J, et al. Prevalence and characterization of fibrosis in surveillance liver biopsies of patients with Fontan circulation. HUM PATHOL 2016;57:106-15.