NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease.
BACKGROUND
We recently examined the distribution of abdominal fat, dietary intake and biochemical data in patients with nonalcoholic fatty liver disease (NAFLD) and found that non-obese NAFLD patients did not necessarily exhibit insulin resistance and/or dysregulated secretion of adipocytokines. However, dietary cholesterol intake was superabundant in non-obese patients compared with obese patients, although total energy and carbohydrate intake was not excessive. Therefore, excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver injury.


METHODS
We reviewed a year of follow-up data of non-obese NAFLD patients treated with Niemann-Pick C1 like 1 inhibitor ezetimibe to evaluate its therapeutic effect on clinical parameters related to NAFLD. Without any dietary or exercise modification, 10 mg/day of ezetimibe was given to 8 patients. In 4 of 8 patients, ezetimibe was administered initially. In the remaining 4 patients, medication was switched from ursodeoxycholic acid to ezetimibe.


RESULTS
In each patient, body mass index was maintained under 25 kg/m2 during the observation period. Serum ALT levels significantly decreased within 6 months and in 4 patients levels reached the normal range (<30 U/L), which was accompanied with at least a 10% decrease in serum total cholesterol and LDL-cholesterol. However, ultrasonographic findings of fatty liver did not show obvious improvement for a year.


CONCLUSIONS
We conclude that the cholesterol absorption inhibitor ezetimibe can suppress hepatic injury in non-obese patients with NAFLD and that ezetimibe may offer a novel treatment for NAFLD.
Enjoji
Munechika
M
Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan. enjoji@adm.fukuoka-u.ac.jp
Machida
Kazuyuki
K
Kohjima
Motoyuki
M
Kato
Masaki
M
Kotoh
Kazuhiro
K
Matsunaga
Kazuhisa
K
Nakashima
Manabu
M
Nakamuta
Makoto
M
D054392:Adipokines / Q000378:metabolism; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry; D002784:Cholesterol / Q000378:metabolism; D000069438:Ezetimibe; D005234:Fatty Liver / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008099:Liver / Q000293:injuries; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis; D014580:Ursodeoxycholic Acid / Q000737:chemistry
D054392:Adipokines; D000924:Anticholesteremic Agents; D001384:Azetidines; D002241:Carbohydrates; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D000069438:Ezetimibe