Serum Vitamin E Levels of Adults with Nonalcoholic Fatty Liver Disease: An Inverse Relationship with All-Cause Mortality in Non-Diabetic but Not in Pre-Diabetic or Diabetic Subjects.

Peiling Tsou,Chang-Jiun Wu

doi:10.3390/jcm8071057

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing health threat worldwide. Vitamin E supplementation is recommended for nonalcoholic steatohepatitis (NASH) patients, but only for non-diabetic subjects. We aimed to investigate whether serum vitamin E levels differently impact long-term prognosis in diabetic versus non-diabetic NAFLD individuals. A total of 2404 ultrasonographically defined NAFLD individuals from National Health and Nutrition Examination Survey (NHANES) III were stratified by their glycemic statuses into diabetic (N = 662), pre-diabetic (N = 836) and non-diabetic (N = 906), and the relationship between serum vitamin E levels and all-cause mortality was analyzed. The serum vitamin E concentrations were 31.1 ± 14.1, 26.7 ± 9.6, and 24.7 ± 9.8 µmol/L and vitamin E: total cholesterol ratios were 5.16 ± 1.70, 4.81 ± 1.46, and 4.80 ± 1.34 µmol/mmol in in diabetic, pre-diabetic, and non-diabetic groups, respectively. Of 2404 NAFLD subjects, 2403 have mortality information and 152 non-diabetic, 244 pre-diabetic, and 342 diabetic participants died over a median follow-up period of 18.8 years. Both serum vitamin E levels and vitamin E: total cholesterol ratios were negatively associated with all-cause mortality after adjusting for possible confounders in non-diabetic subjects (HR = 0.483, and 0.451, respectively, p < 0.005), but not in either diabetic or pre-diabetic subjects. In NAFLD individuals, both serum vitamin E and lipid-corrected vitamin E were (1) higher in the diabetic group; and (2) negatively associated with all-cause mortality only in the non-diabetic group. Further investigations are warranted to elucidate the underlying mechanism of this inverse association of serum vitamin E concentration with all-cause mortality in non-diabetic but not pre-diabetic or diabetic subjects.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease in the United States, affecting an estimated 30% of the population
NAFLD encompasses a broad pathological spectrum of phenotypes ranging from hepatic steatosis with no evidence of hepatocellular injury, non-alcoholic fatty liver (NAFL), to nonalcoholic steatohepatitis (NASH)—the progressive form of fatty liver disease associated with inflammation and cellular injury, which can lead to NASH-related cirrhosis and hepatocellular carcinoma [4,5]
The number of patients with NASH on the transplantation waiting list increased by 170% from 2004 to 2013, the largest absolute and relative increase compared with other etiologies [6]

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease in the United States, affecting an estimated 30% of the population. NAFLD encompasses a broad pathological spectrum of phenotypes ranging from hepatic steatosis with no evidence of hepatocellular injury, non-alcoholic fatty liver (NAFL), to nonalcoholic steatohepatitis (NASH)—the progressive form of fatty liver disease associated with inflammation and cellular injury, which can lead to NASH-related cirrhosis and hepatocellular carcinoma [4,5]. Clinical evidence strongly supports the role of lifestyle modification as a primary therapy for the management of NAFLD and NASH [7]. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Several phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies [10,11]

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