Chronic liver disease and hepatic calcium-oxalate deposition in patients with primary hyperoxaluria type I

Abstract

Patients with primary hyperoxaluria type I (PH I) are prone to develop early kidney failure. Systemic deposition of calcium-oxalate (CaOx) crystals starts, when renal function declines and plasma oxalate increases. All tissue, but especially bone, heart and eyes are affected. However, liver involvement, as CaOx deposition or chronic hepatitis/fibrosis has never been reported. We examined liver specimen from 19 PH I patients (aged 1.5 to 52 years at sample collection), obtained by diagnostic biopsy (1), at autopsy (1), or transplantation (17). With polarization microscopy, birefringent CaOx crystals located in small arteries, but not within hepatocytes were found in 3/19 patients. Cirrhosis was seen in one, fibrosis in 10/19 patients, with porto-portal and nodular fibrosis (n = 1), with limitation to the portal field in 8 and/or to central areas in 5 patients. Unspecific hepatitis features were observed in 7 patients. Fiber proliferations were detectable in 10 cases and in one sample transformed Ito-cells (myofibroblasts) were found. Iron deposition, but also megakaryocytes as sign of extramedullary erythropoiesis were found in 9, or 3 patients, respectively. Overall, liver involvement in patients with PH I was more pronounced, as previously described. However, CaOx deposition was negligible in liver, although the oxalate concentration there must be highest.

Figure 1

Severe systemic oxalosis in patient 11 (autopsy). (A) The oxalate crystals in the skin caused vascular ischemic necrosis, which became superinfected in the course of the disease. (B) The damage of the myocardium, caused by CaOx deposition, finally led to heart failure and consecutively death. (C/D) Birefringent CaOx deposits in the bone marrow and in the kidney. CaOx = calcium-oxalate.

Figure 2

Calcium-oxalate deposition in the liver as typical birefringent crystals detected by polarization microscopy in two patients (A) patient 10, (B) patient 11. The crystals were located in small arteries, but not within hepatocytes.

Figure 3

(A) Small deposits are visible in the center of the image (patient 17), which are apparently fragmented crystalloid structures with pale grayish color within a portal field (the part above in the picture is still columnar epithelium of a bile duct also included); (HE, 40x). (B) The crystalloid structures appear optically polarized birefringent. (Polarization, HE 40x).

Figure 4

The routine stains showed different types of fibrosis in the biopsy specimen: (A) Tiny porto-portal fibrosis together with a lymphocytic infiltration of the portal fields and the adjoining parenchyma in the sense of an interface-hepatitis (patient 5). (B) In the autopsy case (patient 11) fibrosis was very advanced towards a cirrhotic remodeling. (C, D) Porto-portal fibrosis together with a nodular fibrosis (patient 10).