Nodular regenerative hyperplasia, portal vein thrombosis, and avascular hip necrosis due to hyperhomocysteinaemia

Abstract

A male patient with portal hypertension, portal vein thrombosis, spontaneous splenorenal shunt formation, and encephalopathy, thought to have post-hepatitis B cirrhosis, is described. His condition deteriorated and necessitated liver transplantation. In the explant liver, nodular regenerative hyperplasia with pronounced vascular lesions both in portal venules and in arterioles was found instead of classical cirrhosis. Two years post-transplant he developed bilateral ischaemic femur head necrosis. The three disorders (portal vein thrombosis, nodular regenerative hyperplasia, and ischaemic hip necrosis) seemed to be due to a common vasculopathy induced by hyperhomocyteinaemia. Genetic studies showed that he carried a mutation in the gene encoding for formation of methylenetetrahydrofolate reductase. Treatment with folic acid combined with pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) normalised his serum homocysteine levels. N odular regenerative hyperplasia of the liver is characterised by the presence of diffuse rather small regenerative nodules in the absence of fibrosis. It is thought to result from occlusion of the terminal branches of hepatic arterioles and portal venules, secondary to endothelial cell damage. [1][2][3] It is associated with systemic and vascular disorders such as systemic lupus erythematodes, progressive systemic sclerosis, Sjögren's syndrome, polyarteritis nodosa, rheumatoid arthritis, 1 2 4 5 and with coagulopathies such as anticardiolipin and antiphospholipid antibodies or factor V Leiden mutation. 4 6 7 An association with myeloproliferative and lymphoproliferative disorders has also been described.We describe a patient with nodular regenerative hyperplasia of the liver and portal vein thrombosis, eventually requiring liver transplantation. This was followed by bilateral avascular necrosis of his femur heads. In looking for coagulopathies, it was demonstrated that this patient had hyperhomocysteinaemia of intermediate grade. Further study documented that he was a heterozygote for the methylenetetrahydrofolate reductase gene C677T mutation. To our knowledge this is the first report of nodular regenerative hyperplasia associated with hyperhomocysteinaemia. CASE REPORTA 51 year old male with mild psoriasis, for which he never received any medication that could induce portal hypertension, was evaluated for possible liver transplantation. He had initially been seen at the haematology clinic for suspected myelodysplasia because of a marked splenomegaly with leuco-and thrombocytopenia (table 1). Further investigations established the presence of an atrophic right liver lobe (atrophy of segments 4 and 5) and a hypertropic caudate and left liver lobe, with portal vein thrombosis and a spontaneous splenorenal shunt. He had pronounced oesophageal varices with a variceal pressure of 20.6 mm Hg and a hepatic portal vein pressure gradient of 25 mm Hg, mild encephalopathy (ammonia levels above 80 mM; normal values ,50 mM), and osteopenia. He was thought to have post-hepatitis B cirrhosis as...

Prevalence and clinical significance of nodular regenerative hyperplasia in liver biopsies

“…Therefore, although NRH probably results from different levels of circulatory impairment, complications represented by symptomatic PHT do not depend on a specific triggering disease. Some limitations of this study should be noted, including the lack of systematic laboratory screening for inherited or acquired forms of thrombophilia; it is known that prothrombotic disorders are one of the causal factors in NRH .…”

Incidence of nodular regenerative hyperplasia in inflammatory bowel disease patients treated with azathioprine

“…A depletion in glutathione may be the consequence of malnutrition secondary to malabsorption 22, 23. NRH has also been associated with thrombotic risk factors such as hyperhomocysteinemia 24. In this context, one could speculate that a deficit in vitamin B 12 secondary to ileal damage could favor the onset of hepatic vascular lesions through the occurrence of hyperhomocysteinemia.…”

Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine

“…11 NRH has been associated with thrombotic risk factors such as hyperhomocysteinaemia. 33 In this context, it can be speculated that a deficit in vitamin B-6, folates, and vitamin B-12 secondary to ileal stenosis (strongly associated with an increased risk of intestinal resection) could favour the onset of hepatic vascular lesions through the occurrence of hyperhomocysteinaemia. It has been proposed that the development of NRH may be dependent on high levels of 6-TGN.…”