Liver fibrosis and fatty liver as independent risk factors for cardiovascular disease

Tamaki, Nobuharu; Kurosaki, Masayuki; Takahashi, Yuka; Itakura, Yoshie; Inada, Kento; Kirino, Sakura; Yamashita, Koji; Sekiguchi, Shuhei; Hayakawa, Yuka; Osawa, Leona; Higuchi, Masakazu; Takaura, Kenta; Maeyashiki, Chiaki; Kaneko, Shun; Yasui, Yutaka; Tsuchiya, Kaoru; Nakanishi, Hiroyuki; Itakura, Jun; Izumi, Namiki

doi:10.1111/jgh.15589

Cited by 51 publications

(40 citation statements)

References 43 publications

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“… 9 , 10 Emerging data from recent studies have suggested that liver stiffness on MRE may be associated with liver-related outcomes. 11 – 14 Other NITs including the FIB-4 score (fibrosis index based on the 4 factor) and NAFLD Fibrosis Score (NFS) have demonstrated associations with liver-related events and death; 15 – 17 however, when used alone, they have only modest discriminatory ability. Similarly, vibration-controlled transient elastography (VCTE) is associated with liver-related events among patients with chronic advanced liver disease, 18 but has limited discriminatory ability for liver-related events in patients with less advanced disease.…”

Section: Introductionmentioning

confidence: 99%

Prognostic utility of magnetic resonance elastography and MEFIB index in predicting liver-related outcomes and mortality in individuals at risk of and with nonalcoholic fatty liver disease

Ajmera

Nguyen

Tamaki

et al. 2022

Therap Adv Gastroenterol

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Background: Magnetic resonance elastography (MRE) is an accurate biomarker of liver fibrosis; however, limited data characterize its association with outcomes. We aimed to evaluate the association between liver stiffness (LS) on MRE and liver-related outcomes. Methods: This is a longitudinal, retrospective analysis of subjects at risk of NAFLD who had MRE assessment. LS was estimated using MRE, and liver fat was assessed using magnetic resonance imaging proton density fat fraction. Univariable and multivariable survival and regression analyses were used to assess the association between LS on MRE and liver-related outcomes including a cumulative primary outcome of hepatic decompensation, hepatocellular carcinoma (HCC), or death. Results: In all, 265 patients (68% women) with a mean age of 50 (±18) years and 44% Hispanic ethnicity and 45.3% with NAFLD were included. A total of 76 liver-related events or death occurred, and there was 453 person-years of follow-up time in 97 patients with available follow-up. Each 1-kPa increase in LS was associated with 2.20-fold (95% CI: 1.70–2.84, p < 0.001) increased odds of prevalent hepatic decompensation or HCC. A positive MEFIB index, a combination of MRE ⩾ 3.3 kPa and FIB-4 ⩾ 1.6, had a strong association with the primary outcome compared with those without, HR = 21.8 (95% CI: 4.28–111.4, p < 0.001). The MEFIB index had a sensitivity of 75% and specificity of 90%, and a negative score was associated with 98% negative predictive value for incident liver-related events or death. Conclusion: LS assessed by MRE is associated with hepatic decompensation and death, and the MEFIB combination of MRE with FIB-4 may have high negative predictive value for liver-related events.

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Section: Introductionmentioning

confidence: 99%

Prognostic utility of magnetic resonance elastography and MEFIB index in predicting liver-related outcomes and mortality in individuals at risk of and with nonalcoholic fatty liver disease

Ajmera

Nguyen

Tamaki

et al. 2022

Therap Adv Gastroenterol

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“…In our study, the high CVD risk of lean-MAFLD compared to OW-MAFLD might be due to the in uence of brotic burden. Several previous studies have revealed that advanced liver brosis in patients with FLD is not only a major risk factor for liver cancer or liver-speci c mortality but is also closely related to CVD risk [21,22]. Indeed, in this study, lean-MAFLD with advanced brosis had an increased CVD risk compared to OW-MAFLD without advanced brosis, whereas lean MAFLD without advanced brosis did not.…”

Section: Discussionmentioning

confidence: 43%

Long-Term Cardiovascular outcomes Differ Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

Lee

Lim

Kim

et al. 2022

Preprint

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Background & Aims: The new metabolic dysfunction-associated fatty liver disease (MAFLD) criteria include three distinct subtypes: MAFLD with diabetes mellitus (DM), overweight/obese (OW), or lean/normal weight with metabolic dysfunction. We investigated whether long-term cardiovascular disease outcomes differ across the MAFLD subtypes.Methods: From a nationwide health screening database, we included 8,412,730 participants (48.6% male) aged 40-64 years, free of cardiovascular disease history, between 2009 and 2010. Participants were categorized into non-MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. The primary outcome was a composite cardiovascular disease event, including myocardial infarction, ischemic stroke, heart failure, or cardiovascular disease-related death. The presence of advanced liver fibrosis was estimated using a BARD score ≥2. Results: Among the study participants, 3,087,640 (36.7%) had MAFLD, among which 2,424,086 (78.5%), 170,761 (5.5%), and 492,793 (16.0%) had OW-MAFLD, lean-MAFLD, and DM-MAFLD, respectively. Over a median follow-up period of 10.0 years, 169,433 new cardiovascular disease events occurred. With the non-MAFLD group as reference, multivariable-adjusted hazard ratios (95% confidence intervals) for cardiovascular disease events were 1.16 (1.15-1.18), 1.23 (1.20-1.27), and 1.82 (1.80-1.85) in the OW-MAFLD, lean-MAFLD, and DM-MAFLD groups, respectively. Participants with lean-MAFLD or DM-MAFLD had a higher cardiovascular disease risk than those with OW-MAFLD, irrespective of metabolic abnormalities or comorbidities. The presence of advanced liver fibrosis was significantly associated with a higher cardiovascular disease risk in each MAFLD subtype.Conclusion: Long-term cardiovascular disease outcomes differed across the MAFLD subtypes. Further studies are required to investigate whether preventive or therapeutic interventions should be optimized according to the MAFLD subtypes.

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“…In another study including 458 patients with biopsy‐proven NAFLD and fibrosis stage 3 or 4, CVD incidence was higher in patients with F3 than those with F4 111 . Among studies investigating the general population, an increased FIB‐4 score was associated with increased risk of CVD 112,113 . In a study that used MRE as a noninvasive marker, CVD incidence was higher in patients with moderate‐advanced fibrosis (MRE: 3.0–4.7 kPa) than those with cirrhosis including decompensation cirrhosis (MRE >4.7 kPa) 97 .…”

Section: Prediction Of Prognosis Using Noninvasive Markersmentioning

confidence: 99%

“…111 Among studies investigating the general population, an increased FIB-4 score was associated with increased risk of CVD. 112,113 In a study that used MRE as a noninvasive marker, CVD incidence was higher in patients with moderate-advanced fibrosis (MRE: 3.0-4.7 kPa) than those with cirrhosis including decompensation cirrhosis (MRE >4.7 kPa). 97 One possible reason for this discrepancy is the distribution of liver fibrosis among studies.…”

Section: Noninvasive Markers and Cardiovascular Eventsmentioning

confidence: 99%

Noninvasive assessment of liver fibrosis and its clinical significance in nonalcoholic fatty liver disease

Tamaki

Kurosaki

Huang

et al. 2022

Hepatology Research

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Liver fibrosis is the most important prognostic factor in patients with nonalcoholic fatty liver disease (NAFLD). Several noninvasive markers for fibrosis, including blood‐based markers and imaging based‐markers have been developed. Indirect fibrosis markers (e.g., fibrosis‐4 index and NAFLD fibrosis score) consist of standard laboratory data and clinical parameters. Given its availability and high negative predictive value for advanced fibrosis, these markers are suitable for screening at primary care. Blood‐based fibrogenesis markers (enhanced liver fibrosis and N‐terminal propeptide of type 3 collagen), ultrasound‐based modalities (vibration‐controlled transient elastography, point shear wave elastography [SWE], and two‐dimensional SWE), and magnetic resonance elastography have high diagnostic accuracy for liver fibrosis and are suitable for diagnosing liver fibrosis at secondary care centers. Sequential use of these markers can increase diagnostic accuracy and reduce health care costs. Furthermore, combining noninvasive makers may assist in identifying candidates for pharmacological trials and reducing screening failure. Emerging data suggest that these noninvasive markers are associated with liver‐related events (hepatocellular carcinoma and decompensation) and mortality. Furthermore, delta change in noninvasive markers over time is also associated with time‐course change in fibrosis, liver‐related event risk, and mortality risk. However, the association between liver fibrosis and cardiovascular disease (CVD) risk is still controversial. CVD risk may decrease in patients with decompensated liver disease and noninvasive markers may be useful for assessing CVD risk in these patients. Therefore, noninvasive markers may be utilized as measures of fibrosis as well as real‐time prognostic tools, in place of liver biopsy.

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Liver fibrosis and fatty liver as independent risk factors for cardiovascular disease

Cited by 51 publications

References 43 publications

Prognostic utility of magnetic resonance elastography and MEFIB index in predicting liver-related outcomes and mortality in individuals at risk of and with nonalcoholic fatty liver disease

Prognostic utility of magnetic resonance elastography and MEFIB index in predicting liver-related outcomes and mortality in individuals at risk of and with nonalcoholic fatty liver disease

Long-Term Cardiovascular outcomes Differ Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

Noninvasive assessment of liver fibrosis and its clinical significance in nonalcoholic fatty liver disease

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