Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka
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While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean.
In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case–control study between lean NAFLD cases and lean non-NAFLD controls.
Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample.
Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.
KeywordsFatty liver Non-alcoholic fatty liver disease NAFLD Lean Lean NAFLD Risk factors
This work was supported by grants from the National Center for Global Health and Medicine, Tokyo, Japan and the Ministry of Higher Education of Sri Lanka. We thank those who have continuously supported the Ragama Health Study. We also thank many physicians for their assistance in collecting the DNA samples and accompanying clinical information, extracting DNA and preparing the analytical data.
MAN, NK, AK and HJdeS conceptualized and designed the study. AK, SdeS, MAN, ASD, APDeS, ARW and HJdeS were involved in the establishment of the Ragama Health Study cohort and its follow-up. KRP, SKCES, SKK, TACLP and KV collected data. TF and NK performed genotyping. TF, NK, AK analyzed the data assisted by MAN, AP and HJdeS. MAN, AK, NK and HJdeS prepared the manuscript. APDeS, ASD and ARW were substantially involved in revision of the manuscript. All authors checked the final manuscript before submission.
Compliance with ethical standards
Conflict of interest
Madunil Anuk Niriella, A. Kasturiratne, A. Pathmeswaran, S. T. De Silva, K. R. Perera, S. K. C. E. Subasinghe, S. K. Kodisinghe, T. A. C. L. Piyaratna, K. Vithiya, A. S. Dassanayaka, A. P. De Silva, A. R. Wickramasinghe, F. Takeuchi, N. Kato and H. J. de Silva declare no conflict of interest.
Ethical approval for the study was obtained from the Ethical Review Committees of the Faculty of Medicine, University of Kelaniya and NCGM.
Informed consent was obtained from all participants in RHS.
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