The effects of metabolic status on non‐alcoholic fatty liver disease‐related outcomes, beyond the presence of obesity

Abstract

Summary Background Metabolically healthy obesity (MHO) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non‐alcoholic fatty liver disease (NAFLD)‐related outcomes compared with non‐obese subjects with a few metabolic risks. Aim To define the impact of the metabolic status on the NAFLD‐related outcomes, beyond the presence of obesity. Methods We designed a multicentre cross‐sectional study, including 1058 biopsy‐proven NAFLD patients. Metabolically healthy status was strictly defined by the lack of metabolic risk factors (diabetes mellitus, low HDL, hypertriglyceridemia, arterial hypertension). Non‐alcoholic steatohepatitis (NASH) and significant fibrosis (F2‐F4) were identified by liver biopsy. Chronic kidney disease epidemiology collaboration equation was calculated for kidney function and the atherogenic index of plasma (AIP) for cardiovascular risk. Results Metabolically healthy (OR 1.88; P = 0.050) and unhealthy obesity (OR 3.47: P < 0.0001), and unhealthy non‐obesity (OR 3.70; P < 0.0001) were independently associated with NASH together with homeostatic model assessment (HOMA), ALT, and platelets. Significant fibrosis was more frequently observed in the presence of adverse metabolic conditions in obese (OR 3.89; P = 0.003) and non‐obese patients (OR 3.92; P = 0.002), and independently associated with platelets, albumin, ALT, HOMA, and age. The number of metabolic factors determined the risk of NASH and significant fibrosis. Glomerular filtration rate was lower in unhealthy (91.7 ± 18) than healthy metabolism (95.6 ± 17) (P = 0.007). AIP was higher in adverse metabolic conditions (P = 0.0001). Metabolically unhealthy non‐obesity showed higher liver damage (NASH 55.8% vs 42.4%; P < 0.05; significant fibrosis 31.7% vs 11.4%; P < 0.0001) and cardiovascular risk (P < 0.0001) than healthy obesity. Conclusions Metabolic unhealthy status showed a greater impact on NASH, significant fibrosis, kidney dysfunction, and atherogenic profile than obesity. However, metabolically healthy obesity was not a full healthy condition. We should focus our messages especially on patients with adverse metabolic conditions.

Impact of a structured lifestyle programme on patients with metabolic syndrome complicated by non‐alcoholic fatty liver disease

“…They were also more likely to have hyperTG, low HDL‐C and higher HOMA‐IR. These unique characteristics underscore the importance of central adiposity and insulin resistance in NAFLD as metabolic health has been independently associated with risk of NASH and significant fibrosis . Despite having more pronounced metabolic derangements at baseline, NAFLD patients were equally likely to respond to the lifestyle programme.…”

“…These unique characteristics underscore the importance of central adiposity and insulin resistance in NAFLD as metabolic health has been independently associated with risk of NASH and significant fibrosis. 29,30 Despite having more pronounced metabolic derangements at baseline, NAFLD patients were equally likely to respond to the lifestyle programme. This finding is of note given concerns that NAFLD patients may have different uptake and response rates to lifestyle changes stemming from different baseline motivation to change and lower confidence to exercise.…”

Natural history of NASH and HCC

“…In particular, NASH resolved in 90% of the patients who lost ≥10% of their weight and fibrosis regressed in 45%. However, a subsequent multicentre cross‐sectional study of 1058 biopsy‐proven NAFLD patients, emphasized the importance of distinguishing obesity from metabolic status . A metabolically healthy status was defined in that study by the absence of diabetes, low HDL, hypertriglyceridemia and arterial hypertension.…”

Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies

“…The association between obesity and liver disease is considered to be driven largely by associated metabolic abnormalities, primarily insulin resistance (Ampuero et al, ; Gutierrez‐Grobe et al, ).…”