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

Background: Phlebotomy induces regression of liver fibrosis in genetic hemochromatosis. We assessed the histologic changes in pre-phlebotomy and post-phlebotomy liver biopsies from patients with mutation as a model to study regression of fibrosis. We aimed to show that phlebotomy-induced histologic lesions overlap with porto-sinusoidal vascular disease (PSVD, also known as idiopathic non-cirrhotic portal hypertension), histologically.

Methods: A total of 51 biopsies (22 pre-phlebotomy and 29 post-phlebotomy) were reviewed, and three variables were studied: iron index indicative of the amount of accumulated iron (range 0 to 18), the combined score of vascular changes reflecting the presence of histological lesions that are described in PSVD (range 0 to 9) and the high-grade shunt vessel by calculating the proportion of portal tracts with shunt vessels, with a cutoff of 50%. Two-tailed Student's -test and Fisher's exact test were performed to compare the means of two variables and frequencies of the histologic lesions in two groups, respectively. A P-value < 0.05 was considered statistically significant.

Results: The iron index was higher in the pre-phlebotomy compared to post-phlebotomy group (P = 0.01). Compared to the pre-phlebotomy group, the combined score was higher in the post-phlebotomy group when the cases of advanced fibrosis were excluded (P = 0.023) and remained higher when patients with risk factors for PSVD were further excluded (P = 0.034). The high-grade shunt vessel tended to be more common in the post-phlebotomy group when advanced fibrosis was excluded; however, the statistical significance was marginal (P = 0.056).

Conclusions: Phlebotomy reduces hepatic iron load and induces histologic lesions of PSVD in patients with mutation. Our data support a postulation that some of the histologic lesions of PSVD represent vascular remodeling following a regression of fibrosis and may not be reflective of risk factors or etiopathogenesis of PSVD. Regressed fibrosis and PSVD may not be reliably distinguished in a limited sample, therefore warranting cautious interpretation in the right clinical context.