Severe Hypercholesterolemia Associated with Decreased Hepatic Triglyceride Lipase Activity and Pseudohyponatremia in Patients after Allogeneic Stem Cell Transplantation

Abstract

A 55-year-old woman with Ph-negative acute lymphoblastic leukemia in primary induction failure received allogeneic peripheral blood stem cell transplantation from her HLA-compatible sister. Pseudohyponatremia developed due to extreme hypercholesterolemia of 4091 mg/dL accompanied by lipoprotein X and lipoprotein Y. The hypercholesterolemia was caused by cholestasis due to chronic GVHD and ischemic cholangiopathy. In addition, we found that hepatic triglyceride lipase (HTGL) activity was severely decreased, which could be another novel factor causing extreme hypercholesterolemia after allogeneic transplantation. The total cholesterol has been gradually decreasing followed by the improvement of cholestasis with bezafibrate, ursodeoxycholic acid and prednisone treatments, and by a slight increase in HTGL-protein. To our knowledge, this is the first report to describe the association of decreased HTGL with extreme hypercholesterolemia after allogeneic transplantation.

Planar xanthoma due to cholestasis in graft versus host disease

“…Patchy hyperpigmentation, poikiloderma, vitiligo, erythema, atrophy, alopecia, multiple follicular papules, ulcers of the legs and dystrophic nail changes may occur. Gastrointestinal symptoms, a Sjogren‐like syndrome, polymyositis, abnormal liver function, primary biliary cirrhosis and other organ changes also occur in chronic GVHD 5 . In our case, as irregular‐margined hyperpigmentation and mild pityriasis were observed on proximal areas such as the upper arms, trunk, back and face, we diagnosed chronic GVHD.…”

Treatment of Dyslipidemia in Allogeneic Hematopoietic Stem Cell Transplant Patients

“…20 There is also one case report of utilizing bezafibrate in combination with ursodeoxycholic acid for severe lipoprotein X-mediated hypercholesterolemia caused by GVHD and cholestasis. 69 Fibrates act as agonists for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) a transcription factor that upregulates lipolysis, reduces secretion of very low-density lipoprotein particles, increases free fatty acid uptake by the liver, and increases HDL plasma levels. 70 Treatment with fibrates result in a 30–60% reduction in triglycerides, making these agents particularly attractive in the setting of sirolimus-induced dyslipidemia or lipoprotein-X mediated hypercholesterolemia, which are characteristically triglyceride-predominant conditions.…”

Untitled

“…Pseudohyponatremia was uncommonly reported in cases with cholestasis resulting from GVHD or other causes such as drug induced cholestasis. 22 This laboratory artifact may be induced by hyperlipoproteinemias including Lipoprotein X, and observed by indirect potentiometry. In fact, laboratory sodium analysis assumes that plasma water content is constant.…”