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. 2020 Mar;55(3):353-362.
doi: 10.1007/s00535-019-01645-y. Epub 2019 Nov 25.

Transition in the etiology of liver cirrhosis in Japan: a nationwide survey

Hirayuki Enomoto  1 , Yoshiyuki Ueno  2 , Yoichi Hiasa  3 , Hiroki Nishikawa  1   4 , Shuhei Hige  5 , Yasuhiro Takikawa  6 , Makiko Taniai  7 , Toru Ishikawa  8 , Kohichiroh Yasui  9 , Akinobu Takaki  10 , Koichi Takaguchi  11 , Akio Ido  12 , Masayuki Kurosaki  13 , Tatsuya Kanto  14 , Shuhei Nishiguchi  15   16 ; Japan Etiology of Liver Cirrhosis Study Group in the 54th Annual Meeting of JSH
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Transition in the etiology of liver cirrhosis in Japan: a nationwide survey

Hirayuki Enomoto et al. J Gastroenterol. 2020 Mar.

Abstract

Background: To assess the recent real-world changes in the etiologies of liver cirrhosis (LC) in Japan, we conducted a nationwide survey in the annual meeting of the Japan Society of Hepatology (JSH).

Methods: We investigated the etiologies of LC patients accumulated from 68 participants in 79 institutions (N = 48,621). We next assessed changing trends in the etiologies of LC by analyzing cases in which the year of diagnosis was available (N = 45,834). We further evaluated the transition in the real number of newly identified LC patients by assessing data from 36 hospitals with complete datasets for 2008-2016 (N = 18,358).

Results: In the overall data, HCV infection (48.2%) was the leading cause of LC in Japan, and HBV infection (11.5%) was the third-most common cause. Regarding the transition in the etiologies of LC, the contribution of viral hepatitis-related LC dropped from 73.4 to 49.7%. Among the non-viral etiologies, alcoholic-related disease (ALD) and nonalcoholic steatohepatitis (NASH)-related LC showed a notable increase (from 13.7 to 24.9% and from 2.0 to 9.1%, respectively). Regarding the real numbers of newly diagnosed patients from 2008 to 2016, the numbers of patients with viral hepatitis-related LC decreased, while the numbers of patients with non-viral LC increased.

Conclusions: HCV has remained the main cause of LC in Japan; however, the contribution of viral hepatitis as an etiology of LC is suggested to have been decreasing. In addition, non-viral LC, such as ALD-related LC and NASH-related LC, is suggested to have increased as etiologies of LC in Japan.

Keywords: Cirrhosis; Etiology; Nationwide survey; Viral hepatitis.

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Conflict of interest statement

Yoshiyuki Ueno received honoraria from AbbVie and EA-Pharma. Koichi Takaguchi has received honoraria from AbbVie. Masaki Kurosaki received honoraria from Gilead, AbbVie, Bayer, Otsuka and Eisai. Tatsuya Kanto received honoraria from MSD and Gilead. Shuhei Nishiguchi received honoraria from AbbVie and Gilead and research grants from AbbVie, Toray and EA-Pharma. The other authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Flowchart of the current study. We first assessed the total nationwide data of all LC patients (N = 48,621). Then, we excluded the data of patients whose records did not include information on the year of diagnosis and evaluated the transition in the distribution of the etiologies of LC (N = 45,834). To assess the general trends in the etiologies of LC, we classified the patients into four groups (–2007, 2008–2010, 2011–2013, and 2014–)
Fig. 2
Fig. 2
In the current survey, we attempted to assess the transition in the real number of patients newly diagnosed with LC. Most of the participating hospitals presented data up to 2016, as the complete data of 2017 were unavailable before the deadline for abstract submission (December 2017). Among the participating hospitals, 36 were able to provide the number of LC patients newly diagnosed each year from 2008 to 2016 without missing any years (N = 18,358). We analyzed the data to assess the transition of newly identified LC patients in the same hospitals in 2008–2016
Fig. 3
Fig. 3
Overall results of the collected data on the etiologies of LC. A total of 48,621 cases were finally provided to analyze the etiologies of LC in Japan. In this cohort, 29,951 (61.6%) patients were men, and 18,670 (38.4%) were women. HCV infection was the leading cause of LC in Japan, and HBV infection (11.5%) was the third-most common cause. Although alcoholic-related liver disease (19.9%) and NASH (6.3%) were contributory causes of LC in Japan, viral hepatitis, particularly HCV, was the major cause
Fig. 4
Fig. 4
Geographic differences in the etiologies of LC. The etiologies of LC in all LC patients in the different geographic areas are shown. HCV-related LC was the leading cause of LC in all areas
Fig. 5
Fig. 5
Transition of the distribution regarding the etiologies of LC. The transition in the distribution of the etiologies of LC. The ratio of HCV-related LC was notably decreased during the last decade, and that of HBV-related liver cirrhosis has also gradually declined. The ratio of non-viral LC surpassed that of HCV-related LC in patients who were diagnosed in and after 2014
Fig. 6
Fig. 6
The transition in the number of patients who were diagnosed with LC. The numbers of newly diagnosed LC patients were identified according to the year of diagnosis, and a total of 18,358 patients were analyzed. The real numbers of patients with HBV-related and HCV-related LC decreased and the real number of patients with non-viral LC increased in 2008–2016. The percentages of the etiologies are shown in the graph bars
Fig. 7
Fig. 7
The transition in the number of patients who were diagnosed with non-viral LC. In agreement with the increase in the number of non-viral LC patients (Fig. 5), the complete sets of annual data from 36 hospitals revealed that the real numbers of patients newly diagnosed with alcoholic-related LC, NASH-related LC and cryptogenic LC were suggested to increase in 2008–2016. The percentages of the etiologies are shown in the graph bars
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