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Reversibiliteit van cirrose Joanne Verheij, MD, PhD Department of Pathology Academic Medical Center Amsterdam

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Page 1: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Reversibiliteit van cirrose

Joanne Verheij, MD, PhD

Department of Pathology

Academic Medical Center

Amsterdam

Page 2: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Disclosure

Geen (potentiële) belangenverstrengeling

Page 3: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Liver acinus, normal architecture

Zone 1: surrounds portal tract

Zone 3: surrounds central vein

Page 4: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Metavir

F0

F4F3

F2F1

Faria SC, RSNA 2009

Page 5: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Standish, Gut 2006 “An appraisal of the histopathological assessment of liver fibrosis”

Page 6: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

CIRROSE

René Laënnec (1781-1826) in “De l’auscultation médiate ou Traité du Diagnostic

des Maladies des Poumons et du Coeur’’(1819).

“Le foie réduit au tiers de son volume se trouvait caché dans la

région qu’il occupe; incisé, il paraissait entièrement composé d’une

multitude de grains de la grosseur d’un frain de chènevis ou de

millet, de couleur jaune ou jaune roux.”

Page 7: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Histopathology, April 2013

Page 8: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

75/139 (49%) reversal of cirrhosis (n=23 F3; n= 26 F2, n= 23 F1 and n= 3 F0)

~ age !

Page 9: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate
Page 10: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Lancet 2013

Page 11: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Limitations

Biopsy length

Sampling error

Interobserver variability

Inclusion criteria (compensated vs decompensated liver disease)

Correlation decrease histological stage with outcome (liver

related disease, portal hypertension and occurrence HCC)?

Page 12: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate
Page 13: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate
Page 14: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

“cirrhosis is more than just widespread liver fibrosis”….

“…cirrhosis is indeed basically a vascular disease….”

Page 15: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Determinants of irreversiblity:

- persistence and intensity initiating injury

- morphological characteristics nodules and septa: cross-linking collagen, elastin-rich scars

- vascular remodeling: neoangiogenesis, sinusoidal capillarization, loss of metabolic zonation

Cirrhosis encompasses a pathological spectrum, being dynamic and

bidirectional

Point at which cirrhosis is irreversible not established yet!

Page 16: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate
Page 17: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Hepatic repair complex

Page 18: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate
Page 19: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Hytiroglou P et al. Beyond "cirrhosis": a proposal from the International Liver

Pathology Study Group. Am J Clin Pathol. 2012

Page 20: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate
Page 21: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate

Simple semiquantitative fibrosis score not adequately represents complexity

of the pathophysiological process leading to cirrhosis.

A classification of cirrhosis based on key pathogenetic mechanisms reflecting

the complexity of the disease rather than just fibrosis becomes now

fundamental..

Liver biopsy in the advanced phase of disease: quantitative/morphometric

methods for more precise prognostic information?

Page 22: Joanne Verheij, MD, PhD Department of Pathology Academic ...regist2.virology-education.com/2015/nlhepdag15/S1_2_Verheij.pdf · CIRROSE René Laënnec (1781-1826) in “De l’auscultationmédiate