Seko Yuya, Sumida Yoshio, Tanaka Saiyu, Mori Kojiroh, Taketani Hiroyoshi, Ishiba Hiroshi, Hara Tasuku, Okajima Akira, Yamaguchi Kanji, Moriguchi Michihisa, Mitsuyoshi Hironori, Kanemasa Kazuyuki, Yasui Kohichiroh, Minami Masahito, Imai Shunsuke, Itoh Yoshito
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
Hepatol Res. 2015 Oct;45(10):E53-61. doi: 10.1111/hepr.12456. Epub 2014 Dec 30.
Some cases with non-alcoholic fatty liver disease (NAFLD), particularly non-alcoholic steatohepatitis (NASH), can ultimately progress to liver cirrhosis. However, studies to clarify factors predictive of histological change in patients with NASH remain scarce. Our aim is to determine predictors of histological progression in Japanese patients with biopsy-proven NASH.
This retrospective cohort study enrolled 52 patients with NASH who underwent serial liver biopsies. Histological evaluation included NAFLD activity score (NAS) and liver fibrosis. The median interval between initial and second liver biopsies was 968 days. An alanine aminotransferase (ALT) response was defined as a decrease of 30% or more from baseline.
Of 52 patients, NAS was ameliorated in 30.8%, deteriorated in 30.8% and remained unchanged in 38.4%. Liver fibrosis was improved in 25.0% of patients, progressed in 25.0% and remained stable in 50.0%. Multivariate analysis identified ALT non-response as a predictor of deterioration of NAS (hazard ratio [HR], 5.85; P = 0.031) and progression of liver fibrosis (HR, 4.50; P = 0.029). The mean annual rate of fibrosis was 0.002 stages/year overall, increasing to 0.15 stages/year in ALT non-responders.
A lack of reduction in serum ALT level by at least 30% from baseline was a predictor for histological progression in patients with NASH. Serum ALT level is a better predictor of histological change than insulin resistance or bodyweight and can be a valid index in treatment. Serum ALT should be strictly controlled to prevent liver histological progression in patients with NASH.
一些非酒精性脂肪性肝病(NAFLD)病例,尤其是非酒精性脂肪性肝炎(NASH),最终可能发展为肝硬化。然而,关于明确NASH患者组织学变化预测因素的研究仍然很少。我们的目的是确定经活检证实的日本NASH患者组织学进展的预测因素。
这项回顾性队列研究纳入了52例接受系列肝脏活检的NASH患者。组织学评估包括NAFLD活动评分(NAS)和肝纤维化。首次和第二次肝脏活检的中位间隔时间为968天。丙氨酸氨基转移酶(ALT)反应定义为较基线水平降低30%或更多。
52例患者中,NAS改善的占30.8%,恶化的占30.8%,不变的占38.4%。25.0%的患者肝纤维化得到改善,25.0%的患者肝纤维化进展,50.0%的患者肝纤维化保持稳定。多因素分析确定ALT无反应是NAS恶化(风险比[HR],5.85;P = 0.031)和肝纤维化进展(HR,4.50;P = 0.029)的预测因素。总体肝纤维化的年均进展率为每年0.002期,ALT无反应者增加至每年0.15期。
血清ALT水平未从基线至少降低30%是NASH患者组织学进展的预测因素。血清ALT水平比胰岛素抵抗或体重更能预测组织学变化,并且可以作为治疗中的有效指标。应严格控制血清ALT水平以防止NASH患者肝脏组织学进展。