Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 13, Number 1, February 2020, pages 32-39

Histologic Lesions of Porto-Sinusoidal Vascular Disease Following Phlebotomy in Hemochromatosis

Figure 1. Representative images of histologic features evaluated. (a) Shunt vessels (*) herniating into the liver parenchyma (Masson’s trichrome, × 200). (b) Increased number of portal vessels: multiple portal vein branches (*) are present in a portal tract (hematoxylin and eosin (H&E), × 200). (c) Obliterative portal venopathy (H&E, × 300). (d) Rudimentary portal tract: hypoplastic portal tract in which the lumen of the bile duct is smaller than the diameter of the surrounding hepatocytes (Masson’s trichrome, × 300). (e) Central vein clustering (H&E, × 100). (f) Sinusoidal dilatation (H&E, × 200). (g) Incomplete fibrous septa (Masson’s trichrome, × 100). (h) Anisocytosis (H&E, × 200).

**Table 1.** Histological Features of Liver Biopsies and Definition [10, 20]
Histological features	Definition
^aThe presence/absence of each feature was documented.
Portal tract changes
P1: Portal inflammation	Presence of mononuclear cells with or without interface activity^a
P2: Bile ductular proliferation	Multiple bile ductules in a portal tract^a
P3: Shunt vessel (periportal)	Portal venous branches communicating with and herniating into the surrounding liver parenchyma^a
P4: Increased number of portal vessels	Multiple portal vein branches in a portal tract^a
P5: Obliterative portal venopathy	Phlebosclerosis; partial or complete obliteration of the portal venous lumen^a
P6: Rudimentary portal tract	Hypoplastic portal tract in which the lumen of the bile duct is smaller than the diameter of the surrounding hepatocytes^a
Lobular changes
L1: Central vein clustering	Increased central veins per lobule, arbitrarily defined as four or more CVs per lobule at medium (× 10) magnification^a
L2: Sinusoidal dilatation	Dilated sinusoids^a
L3: Iron granularity	The magnifications at which the granules are seen (naked eye, × 2, × 4, × 10, × 20, × 40)
L4: Iron zonation	Localization of iron granules: zone 1, zone 2 or zone 3
L5: Incomplete septa	Thin fibrous septum arising from a portal tract blindly ending in the lobule^a
L6: Perisinusoidal fibrosis	Fibrosis of zone 3 sinusoids^a
L7: Fibrosis	METAVIR fibrosis stage: F1, F2, F3, F4
L8: Anisocytosis	Size variation in hepatocytes as a surrogate for nodular regeneration^a
Total number of portal tracts in the sample
Features of fatty liver disease (> 5% of steatosis and ballooning degeneration)

Table 1. Histological Features of Liver Biopsies and Definition [10, 20]

Histological features

Definition

^aThe presence/absence of each feature was documented.

Portal tract changes

P1: Portal inflammation

Presence of mononuclear cells with or without interface activity^a

P2: Bile ductular proliferation

Multiple bile ductules in a portal tract^a

P3: Shunt vessel (periportal)

Portal venous branches communicating with and herniating into the surrounding liver parenchyma^a

P4: Increased number of portal vessels

Multiple portal vein branches in a portal tract^a

P5: Obliterative portal venopathy

Phlebosclerosis; partial or complete obliteration of the portal venous lumen^a

P6: Rudimentary portal tract

Hypoplastic portal tract in which the lumen of the bile duct is smaller than the diameter of the surrounding hepatocytes^a

Lobular changes

L1: Central vein clustering

Increased central veins per lobule, arbitrarily defined as four or more CVs per lobule at medium (× 10) magnification^a

L2: Sinusoidal dilatation

Dilated sinusoids^a

L3: Iron granularity

The magnifications at which the granules are seen (naked eye, × 2, × 4, × 10, × 20, × 40)

L4: Iron zonation

Localization of iron granules: zone 1, zone 2 or zone 3

L5: Incomplete septa

Thin fibrous septum arising from a portal tract blindly ending in the lobule^a

L6: Perisinusoidal fibrosis

Fibrosis of zone 3 sinusoids^a

L7: Fibrosis

METAVIR fibrosis stage: F1, F2, F3, F4

L8: Anisocytosis

Size variation in hepatocytes as a surrogate for nodular regeneration^a

Total number of portal tracts in the sample

Features of fatty liver disease (> 5% of steatosis and ballooning degeneration)

**Table 2.** Summary of Results
Variable	Pre-phlebotomy (N = 22)	Post-phlebotomy (N = 29)	P value
^aMean length of biopsy core and number of portal tracts were evaluated in biopsy specimens without cirrhosis and tumor. ^bStudent’s t-test. ^cFisher’s exact test. CS: combined score; F3 and F4: METAVIR fibrosis stage F3 and F4; PSVD: porto-sinusoidal vascular disease; SV: shunt vessel.
Mean length of biopsy core^a	2.5 cm	2.6 cm
Mean number of portal tracts^a	12	14
Iron index	8.3	4.3	0.010^b
CS of vascular changes	3.3	4.0	0.160^b
CS (cases with advanced fibrosis (F3, F4) excluded)	3.6 (n = 14)	4.8 (n = 21)	0.029^b
CS (cases with risk factors for PSVD further excluded)	3.6 (n = 9)	4.8 (n = 18)	0.034^b
High-grade SV (≥ 50% of portal tracts with SV, excluding cases with advanced fibrosis)	7% (n = 14)	38% (n = 21)	0.056^c
Coexisting fatty liver disease	64%	48%	> 0.05^c

Table 2. Summary of Results

Variable

Pre-phlebotomy (N = 22)

Post-phlebotomy (N = 29)

P value

^aMean length of biopsy core and number of portal tracts were evaluated in biopsy specimens without cirrhosis and tumor. ^bStudent’s t-test. ^cFisher’s exact test. CS: combined score; F3 and F4: METAVIR fibrosis stage F3 and F4; PSVD: porto-sinusoidal vascular disease; SV: shunt vessel.

Mean length of biopsy core^a

2.5 cm

2.6 cm

Mean number of portal tracts^a

Iron index

8.3

4.3

0.010^b

CS of vascular changes

3.3

4.0

0.160^b

CS (cases with advanced fibrosis (F3, F4) excluded)

3.6 (n = 14)

4.8 (n = 21)

0.029^b

CS (cases with risk factors for PSVD further excluded)

3.6 (n = 9)

4.8 (n = 18)

0.034^b

High-grade SV (≥ 50% of portal tracts with SV, excluding cases with advanced fibrosis)

7% (n = 14)

38% (n = 21)

0.056^c

Coexisting fatty liver disease

64%

48%

> 0.05^c