Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yoshitsugu; Akita, Tomoyuki; Tanaka, Junko

doi:10.1002/hep4.1105

Cited by 45 publications

(41 citation statements)

References 37 publications

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“…We acknowledge that there is no currently available longitudinal data to examine the correlation between worsening noninvasive fibrosis markers and histological progression of fibrosis stage over time. NFS and FIB‐4 are the most widely used noninvasive fibrosis markers in the setting of NAFLD . However, these non‐invasive fibrosis markers include variables in the formula that may affect the association between obesity and fibrosis progression.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Chang

Cho

et al. 2019

Liver International

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Background & Aims Little is known about the impact of metabolically healthy obesity on fibrosis progression in non‐alcoholic fatty liver disease (NAFLD). We investigated the association of body mass index (BMI) category, body fat percentage and waist circumference with worsening of noninvasive fibrosis markers in metabolically healthy and unhealthy individuals with NAFLD. Methods A cohort study was performed on 59 957 Korean adults with NAFLD (13 285 metabolically healthy and 46 672 metabolically unhealthy individuals) who were followed for a median of 7.7 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homoeostasis model assessment of insulin resistance <2.5. Progression from low to intermediate or high probability of advanced fibrosis was assessed using the NAFLD fibrosis score (NFS). Results During 339 253.1 person‐years of follow‐up, 9857 subjects with low NFS at baseline progressed to intermediate or high NFS. Among metabolically healthy individuals, the multivariable‐adjusted HRs (95% CI) for NFS worsening comparing BMIs 23‐24.9, 25‐29.9 and ≥30 with a BMI of 18.5‐22.9 kg/m2 were 1.19 (1.00‐1.42), 1.79 (1.52‐2.10) and 3.52 (2.64‐4.69), respectively, whereas the corresponding HRs (95% CI) in metabolically unhealthy individuals were 1.37 (1.24‐1.52), 2.18 (1.99‐2.39) and 4.26 (3.83‐4.75). A similar trend was observed in the analyses using body fat and waist circumference. Conclusion In the large‐scale cohort of young and middle‐aged individuals with NAFLD, BMI was positively associated with worsening of noninvasive fibrosis marker regardless of metabolic health status. Excess adiposity per se, even without accompanying metabolic health status, may contribute to fibrosis progression in NAFLD.

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Section: Discussionmentioning

confidence: 99%

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

Kim

Chang

Cho

et al. 2019

Liver International

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“…Assessment of hepatic steatosis has great clinical importance. In patients with NAFLD, the degree of hepatic fibrosis is the most important factor related to mortality . However, it has also been reported that hepatic steatosis can progress to non‐alcoholic steatohepatitis and clinically significant fibrosis.…”

Section: Introductionmentioning

confidence: 99%

“…In patients with NAFLD, the degree of hepatic fibrosis is the most important factor related to mortality. 7,8 However, it has also been reported that hepatic steatosis can progress to non-alcoholic steatohepatitis and clinically significant fibrosis. In hepatitis C, hepatic steatosis is associated with more severe fibrosis and rapid disease progression.…”

Section: Introductionmentioning

confidence: 99%

Liver stiffness does not affect ultrasound‐guided attenuation coefficient measurement in the evaluation of hepatic steatosis

Tada

Kumada

Toyoda

et al. 2019

Hepatology Research

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Aim Recently, a new method has been developed to diagnose hepatic steatosis with attenuation coefficients based on the ultrasound‐guided attenuation parameter (UGAP). We investigated whether fibrosis identified by hepatic stiffness measurements based on magnetic resonance elastography (MRE) affects attenuation coefficient measurement using UGAP for the evaluation of hepatic steatosis. Methods A total of 608 patients with chronic liver disease were analyzed. Correlations between magnetic resonance imaging‐determined proton density fat fraction (PDFF) or MRE value and attenuation coefficients were evaluated. In addition, the interaction between hepatic fibrosis and the attenuation coefficient was analyzed. Results The correlation coefficient (r) between PDFF values and attenuation coefficient values was 0.724, indicating a strong relationship. Conversely, the r between MRE values and attenuation coefficient values was −0.187, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P‐values for PDFF, MRE, and PDFF × MRE were < 0.001, 0.277, and 0.903, respectively. In patients with non‐alcoholic fatty liver disease (n = 169), the r between PDFF values and attenuation coefficient values was 0.695, indicating a moderate relationship. Conversely, the r between MRE values and attenuation coefficient values was −0.068, indicating almost no relationship. In the multiple regression assessment of the effect of PDFF and MRE on the attenuation coefficient based on UGAP, the P‐values for PDFF, MRE, and PDFF × MRE were <0.001, 0.948, and 0.706, respectively. Conclusion UGAP‐determined attenuation coefficient was weakly affected by liver stiffness, an indicator of hepatic fibrosis.

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“…Similarly, Lazo et al 8 found no association between ultrasound diagnosed NAFLD and increased risk of all-cause, cardiovascular or cancer mortality outcomes. In addition, reports from studies with ultrasound diagnosed FLD suggest increased scores of algorithm-based assessed markers of fibrosis are associated with different mortality outcomes among NAFLD subjects 9–11. However, reports from studies using algorithm-based surrogate of fatty liver suggest disparate associations 12–15.…”

Section: Introductionmentioning

confidence: 99%

Association of fatty liver disease with mortality outcomes in an Eastern Finland male cohort

Olubamwo

Virtanen

Pihlajamäki

et al. 2019

BMJ Open Gastroenterol

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ObjectiveFatty liver disease (FLD) has been associated with extrahepatic morbidity outcomes. However, reports on the association of FLD, assessed using fatty liver index (FLI), with mortality outcomes have been inconsistent. Our objective was to examine the effect of metabolic factors (blood pressure, insulin, fasting glucose, lipoproteins) on the associations of FLI with mortality outcomes among middle-aged men.Study designProspective cohort study.MethodsOur subjects were 1893 men at baseline from 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Multivariable Cox regression models were used to analyse the association of baseline FLI, with the HRs for all-cause, disease, cardiovascular, non-cardiovascular and cancer mortality outcomes.ResultsThe mean FLI in the FLI categories were 16.2 in the low and reference category (FLI<30), 43.4 in the intermediate FLI category (FLI=30–<60) and 77.5 in the high FLI (FLD) category (FLI≥60). Over an average follow-up of 20 years, 848 disease deaths were recorded through Finnish national cause of death register. In models adjusted for constitutional, lifestyle and inflammatory factors, for the high (FLI≥60) vs low (FLI<30) FLI category, the HRs (95% CI) for mortality outcomes were 1.50 (1.26–1.78) for all-cause mortality; 1.56 (1.31–2.86) for disease mortality; 1.51 (1.18–1.94) for cardiovascular disease (CVD) mortality; 1.42 (1.12–1.80) for non-CVD mortality and 1.45 (1.02–2.07) for cancer mortality. With further adjustment for metabolic factors, the HRs were 1.25 (1.01–1.53) for all-cause mortality; 1.26 (1.02–1.56) for disease mortality; 1.06 (0.78–1.43) for CVD mortality; 1.46 (1.09–1.94) for non-CVD mortality and 1.49 (0.97–2.29) for cancer mortality.ConclusionHigh FLI (FLD) is associated with increased risks of mortality outcomes. The FLI-CVD mortality association can be largely explained by metabolic factors. Persons with FLD should be monitored for metabolic deterioration and extrahepatic morbidity to improve their prognoses.

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Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease

Cited by 45 publications

References 37 publications

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

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

Liver stiffness does not affect ultrasound‐guided attenuation coefficient measurement in the evaluation of hepatic steatosis

Association of fatty liver disease with mortality outcomes in an Eastern Finland male cohort

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