joanne verheij, md, phd department of pathology academic...

Reversibiliteit van cirrose

Joanne Verheij, MD, PhD

Department of Pathology

Academic Medical Center

Amsterdam

Disclosure

Geen (potentiële) belangenverstrengeling

Liver acinus, normal architecture

Zone 1: surrounds portal tract

Zone 3: surrounds central vein

Metavir

F0

F4F3

F2F1

Faria SC, RSNA 2009

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

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.”

Histopathology, April 2013

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

~ age !

Lancet 2013

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)?

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

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

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!

Hepatic repair complex

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

Pathology Study Group. Am J Clin Pathol. 2012

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?