title: Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.
abstract: The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.
authors: Katriina Nemes, Fredrik Åberg, Helena Isoniemi, University of Helsinki and Helsinki University Central Hospital, Transplantation and Liver Surgery Clinic, Meilahti Hospital, P.O. BOX 340, FI-00029 HUS, Finland.
authors: Katriina
authors: K
authors: Nemes
authors: Katriina Nemes, Fredrik Åberg, Helena Isoniemi, University of Helsinki and Helsinki University Central Hospital, Transplantation and Liver Surgery Clinic, Meilahti Hospital, P.O. BOX 340, FI-00029 HUS, Finland.
authors: Fredrik
authors: F
authors: Åberg
authors: Katriina Nemes, Fredrik Åberg, Helena Isoniemi, University of Helsinki and Helsinki University Central Hospital, Transplantation and Liver Surgery Clinic, Meilahti Hospital, P.O. BOX 340, FI-00029 HUS, Finland.
authors: Helena
authors: H
authors: Gylling
authors: Katriina Nemes, Fredrik Åberg, Helena Isoniemi, University of Helsinki and Helsinki University Central Hospital, Transplantation and Liver Surgery Clinic, Meilahti Hospital, P.O. BOX 340, FI-00029 HUS, Finland.
authors: Helena
authors: H
authors: Isoniemi
keywords: Apolipoprotein B-100; Cholestanol; Cholestasis; Cholesterol metabolism; Donor; Lipoprotein-X; Liver transplantation; Low density lipoprotein receptor mutation; Non-cholesterol sterols