Characteristic Features of Nonalcoholic Fatty Liver Disease in Japan with a Focus on the Roles of Age, Sex and Body Mass Index

Abstract

This review provides an update on the characteristics of nonalcoholic fatty liver disease (NAFLD), with a focus on the effects of age, sex, and body mass index. Age is a risk factor for NAFLD progression; however, extremely old patients have unique features, namely, the associations between metabolic comorbidities and NAFLD are weaker and NAFLD is not a risk factor for mortality. The prevalence of NAFLD is higher in men than in premenopausal women, whereas the reverse is true after menopause. Thus, before menopause, estrogen may have protective effects against NAFLD. Our hospital data showed that over 25% of male patients with NAFLD and almost 40% of female patients with NAFLD, especially elderly patients, were nonobese. Although histological steatosis and activity were associated with body mass index, the prevalence of nonalcoholic steatohepatitis was not. The prevalence of advanced fibrosis showed a significant sex difference. Advanced fibrosis was significantly more frequent among severely obese men but the prevalence was lower among severely obese women. This difference could be because a substantial proportion of severely obese women were premenopausal; thus, estrogen may have much stronger effects on the development of fibrosis than on obesity. Further studies are required to develop tailored management strategies.

Keywords: Age; Body mass index; Lean NAFLD; Non-alcoholic fatty liver disease; Obesity; sex difference.

Fig. 1

Distribution of patients with nonalcoholic fatty liver disease by mild or advanced fibrosis status with respect to age and sex. In the older generation, advanced fibrosis was more common than mild fibrosis in both sexes. Data was obtained from Tokyo Women’s Medical University in 1991 to 2018 (n=811: 406 men and 359 women).

Fig. 2

Etiology of nonviral hepatocellular carcinoma (HCC) with respect to age based on a nationwide survey in 2009.41 Among patients aged over 80 years, the percentage of cryptogenic HCC was increasing, and the prevalence of obesity, type 2 diabetes, and cirrhosis was significantly lower in this patient group. NAFLD, nonalcoholic fatty liver disease; ALD, alcoholic liver disease.

Fig. 3

Percentage of male and female patients with a diagnosis of nonalcoholic fatty liver disease (NAFLD), cirrhosis, or hepatocellular carcinoma (HCC). Our hospital data showed a male predominance in all patients with NAFLD, although a female predominance was noted in patients with cirrhosis. A male predominance was noted in patients with HCC.

Fig. 4

Percentage of nonalcoholic fatty liver disease patients with advanced fibrosis in the younger and older groups with respect to sex. The frequencies for both sexes were similar.

Fig. 5

Percentage of nonobese, obese, and severely obese patients with nonalcoholic fatty liver disease with respect to age and sex.27 For both sexes, severely obese patients were more common in the younger generation, and nonobese patients were more common in the older generation. Data was obtained from Tokyo Women’s Medical University in 1991 to 2018 (n=762). BMI, body mass index.