著者

Yujiro Nakano Chikara Komiya Hitomi Shimizu Hiroyuki Mishima Kumiko Shiba Kazutaka Tsujimoto Kenji Ikeda Kenichi Kashimada Sumito Dateki Koh-ichiro Yoshiura Yoshihiro Ogawa Tetsuya Yamada

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.67, no.11, pp.1099-1105, 2020 (Released:2020-11-28)

参考文献数

27

被引用文献数

3 3

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Sitosterolemia is caused by homozygous or compound heterozygous gene mutations in either ATP-binding cassette subfamily G member 5 (ABCG5) or 8 (ABCG8). Since ABCG5 and ABCG8 play pivotal roles in the excretion of neutral sterols into feces and bile, patients with sitosterolemia present elevated levels of serum plant sterols and in some cases also hypercholesterolemia. A 48-year-old woman was referred to our hospital for hypercholesterolemia. She had been misdiagnosed with familial hypercholesterolemia at the age of 20 and her serum low-density lipoprotein cholesterol (LDL-C) levels had remained about 200–300 mg/dL at the former clinic. Although the treatment of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors was ineffective, her serum LDL-C levels were normalized by ezetimibe, a cholesterol transporter inhibitor. We noticed that her serum sitosterol and campesterol levels were relatively high. Targeted analysis sequencing identified a novel heterozygous ABCG5 variant (c.203A>T; p.Ile68Asn) in the patient, whereas no mutations were found in low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), or Niemann-Pick C1-like intracellular cholesterol transporter 1 (NPC1L1). While sitosterolemia is a rare disease, a recent study has reported that the incidence of loss-of-function mutation in the ABCG5 or ABCG8 gene is higher than we thought at 1 in 220 individuals. The present case suggests that serum plant sterol levels should be examined and ezetimibe treatment should be considered in patients with hypercholesterolemia who are resistant to HMG-CoA reductase inhibitors.

著者

Akira Sato Michio Sata Kenji Ikeda Takashi Kumada Namiki Izumi Yasuhiro Asahina Yukio Osaki Kazuaki Chayama Shuichi Kaneko Akito Sakai Morikazu Onji Yoichi Hiasa Takumi Omura Itaru Ozeki Osamu Yokosuka Shuichiro Shiina Mariko Itsubo Shuhei Nishiguchi Katsuharu Hirano Tatsuya Ide Shotaro Sakisaka Takahiro Yamasaki Isao Hidaka Masatoshi Tanaka Soo Ryang Kim Takafumi Ichida

出版者

一般社団法人 日本内科学会

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.52, no.24, pp.2701-2706, 2013 (Released:2013-12-15)

参考文献数

32

被引用文献数

4 14

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Objective We attempted to elucidate the clinical features of chronic hepatitis C patients who develop hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) to interferon (IFN) therapy. Methods The clinical features of 130 patients at 19 hospitals who developed HCC after obtaining an SVR were retrospectively reviewed. Results Overall, 107 (82%) of the 130 patients were men, with 92 (71%) being ≥60 years of age and 76, 38 and 16 developing HCC within 5, 5-10 and 10-16.9 years after IFN therapy, respectively. Before receiving IFN therapy, 92 (71%) patients had cirrhosis and/or a low platelet count (<15×104 cells/μL). Lower albumin (<3.9 g/dL) and higher alpha fetoprotein (AFP) (≥10 ng/mL) levels were identified in a multivariate analysis to be independent variables of the development of HCC within five years after IFN therapy. Among 4,542 SVR patients, HCC occurred in 109 (2.4%) during a 5.5-year follow-up period, thus resulting in an occurrence rate of 4.6% for men and 0.6% for women. Conclusion SVR patients with lower albumin or higher AFP levels require careful assessments to prevent early HCC development after IFN therapy. HCC occurrence within >10 years of IFN therapy is not uncommon, and the risk factors remain uncertain, thus suggesting that all SVR patients should undergo long-term follow-up examinations for HCC development.