Metabolically healthy versus unhealthy obesity and risk of fibrosis progression in non‐alcoholic fatty liver disease

Kim, Yejin; Chang, Yoosoo; Cho, Yong Kyun; Ahn, Joong Kyong; Shin, Hocheol; Ryu, Seungho

doi:10.1111/liv.14184

Cited by 33 publications

(32 citation statements)

References 45 publications

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“…Our finding is consistent with those of previous studies, [37][38][39] Conversely, Chen et al found that by using FIB-4 score to evaluate the risk for advanced fibrosis, higher BMI was not a risk factor (OR, 0.72 [0.37-1.40]) and Miyaaki et al stated that although there were more obese cases in the group with severe fibrosis, the association was not statistically significant (mild:severe = 67%:78%; p = 0.23). 28 These findings were contrary to our study, which showed that the effect of obesity on more advanced fibrosis was significant.…”

Section: Discussionsupporting

confidence: 94%

“…41 In addition, Kim et al reported that in sex-stratified analysis, fibrosis progression was stronger in men than in women (HR for BMI ≥30 kg/m 2 compared with BMI 18.5-22.9 kg/m 2 in men was 4.83 [4.31-5.43] and 3.49 [2.90-4.20] in women), which was opposite from our finding. 38 Their study composed of mainly premenopausal women, which estrogen may play a protective role, while ours are elder women with postmenopausal status. 29,38,42 In our study, there are some differences in the results of advanced fibrosis assessed by NFS and FIB-4 scores (Tables 2 and 4).…”

Section: Discussionmentioning

confidence: 94%

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The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan

Lee

Hwang

Hsu

et al. 2021

DMSO

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Purpose: To examine the association between different phenotypes of obesity or metabolic syndromes and liver fibrosis score in a Taiwanese elderly population with fatty liver. Patients and Methods: This cross-sectional study included 1817 participants aged ≥65 years with fatty liver diagnosed by sonography. We used ethnicity-specific criteria for body mass index and metabolic syndrome, and to define obesity phenotypes as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Correlated fibrosis severity was calculated using the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 (FIB-4). Fibrosis severity was divided into two categories according to NFS (no-to-mild fibrosis and advanced fibrosis, defined as NFS ≤ 0.676 and >0.676, respectively) and FIB-4 score (no-to-mild fibrosis and advanced fibrosis, defined as FIB-4 score ≤2.67 and >2.67, respectively). Results: Compared with that in the MHNO group, the associated risk (odds ratio [OR], 95% confidence interval [CI]) of advanced fibrosis by NFS was 2.43 (1.50-3.93), 2.35 (1.25-4.41), and 6.11 (3.90-9.59), whereas that of advanced fibrosis by FIB-4 score was 1.34 (0.83-2.18), 2.37 (1.36-4.13), and 1.38 (0.82-2.31) in the MUNO, MHO, and MUO groups, respectively. Conclusion: Both metabolic syndrome and obesity were positively associated with more advanced fibrosis according to NFS. The detrimental effect of obesity appears to be more than metabolic abnormalities per se in the elderly with more advanced fibrosis severity according to the FIB-4 score.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 94%

The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan

Lee

Hwang

Hsu

et al. 2021

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“…Nearly all of them (98%) had at least one metabolic dysfunction feature, with large WC and prediabetes being the commonest. A recent large Korean (n = 648) cohort study demonstrated that BMI was positively associated with worsening of hepatic fibrosis regardless of metabolic health status in patients with NAFLD 26 . Taken together, it seems to be reasonable to include overweight/obesity as a sole risk criteria in the MAFLD definition.…”

Section: Discussionmentioning

confidence: 99%

MAFLD identifies patients with significant hepatic fibrosis better than NAFLD

Yamamura

Eslam

Kawaguchi

et al. 2020

Liver International

303

320

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Background & Aims Diagnostic criteria for metabolic associated fatty liver disease (MAFLD) have been proposed, but not validated. We aimed to compare the diagnostic accuracy of the MAFLD definition vs the existing NAFLD criteria to identify patients with significant fibrosis and to characterize the impact of mild alcohol intake. Methods We enrolled 765 Japanese patients with fatty liver (median age 54 years). MAFLD and NAFLD were diagnosed in 79.6% and 70.7% of patients respectively. Significant fibrosis was defined by FIB‐4 index ≥1.3 and liver stiffness ≥6.6 kPa using shear wave elastography. Mild alcohol intake was defined as <20 g/day. Factors associated with significant fibrosis were analysed by logistic regression and decision‐tree analyses. Results Liver stiffness was higher in MAFLD compared to NAFLD (7.7 vs 6.8 kPa, P = .0010). In logistic regression, MAFLD (OR 4.401; 95% CI 2.144‐10.629; P < .0001), alcohol intake (OR 1.761; 95% CI 1.081‐2.853; P = .0234), and NAFLD (OR 1.721; 95%CI 1.009‐2.951; P = .0463) were independently associated with significant fibrosis. By decision‐tree analysis, MAFLD, but not NAFLD or alcohol consumption was the initial classifier for significant fibrosis. The sensitivity for detecting significant fibrosis was higher for MAFLD than NAFLD (93.9% vs 73.0%). In patients with MAFLD, even mild alcohol intake was associated with an increase in the prevalence of significant fibrosis (25.0% vs 15.5%; P = .0181). Conclusions The MAFLD definition better identifies a group with fatty liver and significant fibrosis evaluated by non‐invasive tests. Moreover, in patients with MAFLD, even mild alcohol consumption is associated with worsening of hepatic fibrosis measures.

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“…As final consideration, the energy expenditure, observed in obese patients as a consequence of a systemic, low-grade, inflammatory process, may explain progression from obesity to MS, independent of the presence of NAFLD. I should point out that excess adiposity per se, even without accompanying metabolic health status, may contribute to fibrosis progress [49]. Recent data confirm that both FFM and FM are significant contributors to BMR [50].…”

Section: Discussionmentioning

confidence: 99%

Is There a Link between Basal Metabolic Rate, Spleen Volume and Hepatic Growth Factor Levels in Patients with Obesity-Related NAFLD?

Tarantino

Citro

Conforti³

et al. 2019

JCM

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Background: Recent pieces of research point to a link between basal metabolic rate (BMR) and non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). The spleen in obese patients is associated with the cardiovascular system. Enlargement of the spleen is suggestive of nonalcoholic steatohepatitis (NASH). Patients with NASH present an increase in growth factor (HGF) as well as those with advanced heart failure. Interleukin-16 and interleukin-12p40 levels were found to correlate significantly with BMI, and waist circumference. Aim: We tried to find a relationship between BMR, spleen length and HGF. Methods: We analysed retrospective data from 80 obese patients with NAFLD. We evaluated indices of indirect calorimetry by the bioimpendance analysis; carotid intima-media thickness (IMT), spleen length (SLD) and HS by ultrasonography; serum HGF, IL-16, IL-12p40 and IL-6 concentrations by a magnetic bead-based multiplex immunoassays and the severity of NAFLD by BARD score > 2. Results: HGF levels of the obese were higher than those of controls, p < 0.001. At linear regression, BMR was foreseen by spleen length (p < 0.001), which was predicted by HGF (p = 0.04). BMR was predicted by IL-16 (p = 0.005), which predicted HGF, p = 0.034. Only fat mass, among other factors, predicted early atherosclerosis, p = 0.017; IL-12p40 did not predict IMT, HGF and BMR (p = 0.57, 0.09 and 0.59, respectively). The BARD score > 2 was negatively predicted by BMR and FFM (p =0.032 and 0.031, respectively), at the logistic regression. Interesting findings at the extended regression (mediation effect) were: IL-16 was likely causal in predicting BMR by HGF levels; HGF was influential in predicting BMR by SLD level. HS was predicted by SLD in males (p = 0.014), of advanced age (p < 0.001) and by BMR (p < 0.001). IL-6 concentrations, but not BMR were influential in the prediction of HS by SLD. Conclusion: These data reinforce the concept that the immune system is a sensor of the metabolic state, showing a link between HGF levels and BMR, which is mediated by IL-16 (cytokine inducing a cascade of inflammatory factors), and ascertaining the influential effect of the spleen, as main immune organ.

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Metabolically healthy versus unhealthy obesity and risk of fibrosis progression in non‐alcoholic fatty liver disease

Cited by 33 publications

References 45 publications

The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan

The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan

MAFLD identifies patients with significant hepatic fibrosis better than NAFLD

Is There a Link between Basal Metabolic Rate, Spleen Volume and Hepatic Growth Factor Levels in Patients with Obesity-Related NAFLD?

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