Distribution of bmi, serum alt, hepatic steatosis and liver fibrosis in asians with non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of 108 studies with 2,260,207 individuals

Abstract

Background: NAFLD prevalence has increased recently in Asia. The BMI cut‐off for obesity was also lower for Asians, and Asians with NAFLD may also have different characteristics compared to previously studied NAFLD populations. Thus, we aimed to characterize the demographic, weight, and ALT distribution of Asians with NAFLD and its correlations with steatosis and fibrosis severity, which can inform screening, diagnosis and preventive strategies. Methods: We performed a systematic review in which all studies except one were from 2000 to January 17, 2019 using Pubmed, EMBASE, and the Cochrane Library databases. We screened 4,995 studies and included 108 studies (2,260,207 NAFLD patients), that identified NAFLD by US (in about 90% of the studies) or other noninvasive methods in the remainder excluded cohorts with persons with other liver diseases (ie. viral hepatitis) and alcohol >30 g/day for men and >20 g/day for women. We used random effects model to estimate the pooled means for variables of interest such age, ALT, and BMI. Further, we performed bootstrap modeling using the data derived from these articles to simulate a cohort of 10,000 resamples to estimate the proportion of NAFLD population with normal (≤30 U/L for men, ≤19 U/L for women, Prati et al) vs. elevated ALT. We also obtained individual patient data from five Asian NAFLD cohorts (Hong Kong, Japan, and Taiwan, N=5997) to validate our meta‐analytic results. Results: The overall NAFLD cohort had mean age of 52.1 (51.4‐52.9) years, with about 35% having moderate/severe steatosis on US, and 15% with advanced fibrosis (Table 1). Mean BMI (kg/m2) was 26.5, which increases by increasing degree of hepatitis steatosis: 25.8 with mild steatosis, 27.9 with moderate, 31.3 in severe. The mean ALT (U/L) was 31.8 overall, with higher level in males vs. females (37.8 vs. 28.2 IU/mL), obese vs. non‐obese persons, in severe hepatic steatosis cases vs. moderate vs. mild, and interestingly higher ALT was observed in those without advanced fibrosis vs. advanced fibrosis cases. All analyses had significant heterogeneity with I2 >70%. Bootstrap modeling showed that the majority of NAFLD Asians of both sexes had ALT below or within 1.5x normal (ALT <45 U/L in 73.7% males, <28 U/L in 52.6% female) Analysis of individual patient data obtained showed similar mean values for age, BMI, and ALT (56.3 years, 25.5 kg/m2, 38.1 U/L, respectively). Conclusion: We found that BMI was <25 in about one‐quarter of Asians with NAFLD, hepatic steatosis was moderate/severe in about one‐third, and advanced fibrosis in about 15%. While both BMI and ALT increase with increasing severity of hepatitis steatosis and obesity, ALT was actually lower in those with advanced fibrosis vs not and either normal to minimally elevated (1.5x ULN) in one‐half to three‐quarter of NAFLD patients overall, suggesting that ALT level may not be a good indicator for the presence or severity of NAFLD in Asians.