Cardiovascular Morbidity and Mortality Related to Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Bisaccia, Giandomenico; Ricci, Fabrizio; Khanji, Mohammed Y; Sorella, Anna; Melchiorre, Eugenia; Iannetti, Gian Domenico; Galanti, Kristian; Mantini, Cesare; Pizzi, Andrea Delli; Tana, Claudio; Renda, Giulia; Fedorowski, Artur; Caterina, Raffaele De; Gallina, Sabina

doi:10.1016/j.cpcardiol.2023.101643

Cited by 24 publications

(15 citation statements)

References 53 publications

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“…Moreover, a recent systematic review and meta‐analysis of 33 cohorts from 12 countries shows that NAFLD (now MASLD) was associated with the incidence of CVD events but not with CVD death. Interestingly, they found that the risk of CVD mortality was significantly higher in the Western cohort than in the East 33 . A possible reason for these results may be associated with the difference in genetic susceptibility and various lifestyle and dietary habits 33 .…”

Section: Discussionmentioning

confidence: 98%

Hepatic inflammation and fibrosis are profiles related to mid‐term mortality in biopsy‐proven MASLD: A multicenter study in Japan

Tsutsumi,

Kawaguchi,

Fujii

et al. 2024

Aliment Pharmacol Ther

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SummaryAimsA multi‐stakeholder consensus has proposed MASLD (metabolic dysfunction‐associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid‐term mortality of patients with biopsy‐proven MASLD in Japan.MethodsWe enrolled 1349 patients with biopsy‐proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data‐mining analysis.ResultsThe prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty‐five patients with MASLD died. Of these, liver‐related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9‐fold and 1.8‐fold risk of mortality, respectively. In the decision‐tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid‐term prognosis of patients with MASLD.ConclusionsIn patients with biopsy‐proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver‐related events. Hepatic inflammation and fibrosis were significant factors influencing mid‐term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.

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Section: Discussionmentioning

confidence: 98%

Hepatic inflammation and fibrosis are profiles related to mid‐term mortality in biopsy‐proven MASLD: A multicenter study in Japan

Tsutsumi,

Kawaguchi,

Fujii

et al. 2024

Aliment Pharmacol Ther

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“…decompensated cirrhosis and hepatocellular carcinoma). In the second meta‐analysis incorporating 10 cohort studies (for a total of 13 629 NAFLD patients), Bisaccia et al 13 . reported a 50% increased risk of cardiovascular mortality (random effects odds ratio 1.50, 95% CI 1.12–2.00, p = .006, I 2 = 0) over a mean follow‐up of 9.1 years, as well as comparable risks for all‐cause mortality and major adverse cardiovascular and cerebrovascular events.…”

Section: Discussionmentioning

confidence: 99%

“…decompensated cirrhosis and hepatocellular carcinoma). In the second meta-analysis incorporating 10 cohort studies (for a total of 13 629 NAFLD patients), Bisaccia et al 13 reported a 50% increased risk of cardiovascular mortality (random effects odds ratio 1.50, 95% CI 1.12-2.00, p = .006, I 2 = 0) over a mean follow-up of 9.1 years, as well as comparable risks for all-cause mortality and major adverse cardiovascular and cerebrovascular events. Finally, in the third meta-analysis incorporating 12 cohort studies (for a total of 26 329 patients with NAFLD), Huang et al 14 reported a 39% increased risk of all-cause mortality (random effects RR 1.39, 95% CI 1.08-1.82, p = .10, I 2 = 43%).…”

Section: At Present the Long-term Prognosis Of Lean Patients Withmentioning

confidence: 99%

“…4,11 Remarkably, recent meta-analyses showed that patients with lean NAFLD have an increased risk of adverse clinical outcomes compared to those with non-lean NAFLD. [12][13][14] Although it is known that NAFLD is a risk factor for GI cancers 15,16 ; a knowledge gap still exists on the differential prognosis between lean and non-lean NAFLD individuals and on the specific contribution of various risk factors, such as diabetes mellitus, advanced fibrosis, hypertension and smoking to this association. Indeed, understanding the prognostic factors, especially by recognizing the differential risk of GI cancers in relation to the presence of obesity, may likely improve the management of lean NAFLD patients and reinforce the knowledge about the heterogeneity of obesity.…”

Section: Introductionmentioning

confidence: 99%

“…Lean NAFLD, first observed in Asian countries, accounts for approximately 20% of NAFLD population 6 and has gained considerable scientific interest in a debate on the impact of genetic factors 7–10 and the BMI‐based definition of obese phenotype in determining NAFLD 4,11 . Remarkably, recent meta‐analyses showed that patients with lean NAFLD have an increased risk of adverse clinical outcomes compared to those with non‐lean NAFLD 12–14 …”

Section: Introductionmentioning

confidence: 99%

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Gastrointestinal cancers in lean individuals with non‐alcoholic fatty liver disease: A systematic review and meta‐analysis

Souza,

Diaz,

Barchetta

et al. 2023

Liver International

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Background & AimsObesity and non‐alcoholic fatty liver disease (NAFLD) are known risk factors for gastrointestinal (GI) cancers. However, GI carcinogenesis in lean NAFLD patients remains unclear. This systematic review and meta‐analysis aims to investigate the association between lean NAFLD and GI cancer risk.MethodsPubMed, Embase and Cochrane Library databases were systematically searched (from inception date to April 2023) for cohort studies assessing GI cancers in lean (body mass index [BMI] < 25 kg/m2 or < 23 kg/m2 in Asians) and non‐lean (BMI ≥25 kg/m2 or ≥ 23 kg/m2 in Asians) NAFLD individuals. Data from eligible studies were extracted, and meta‐analysis was carried out using a random effects model to obtain risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup analyses, meta‐regressions and sensitivity analyses were also performed. This study was registered in PROSPERO (CRD42023420902).ResultsEight studies with 56,745 NAFLD individuals (11% were lean) and 704 cases of incident GI cancers were included. Lean NAFLD was associated with higher risk of hepatic (RR 1.77, 95% CI 1.15–2.73), pancreatic (RR 1.97, 95% CI 1.01–3.86) and colorectal cancers (RR 1.53, 95% CI 1.12–2.09), compared to non‐lean NAFLD. No significant differences were observed for oesophagus, gastric, biliary and small intestine cancers.ConclusionsThis study shows that lean NAFLD patients have an increased risk of liver, pancreatic and colorectal cancers compared to non‐lean NAFLD patients, emphasizing the need to explore tailored cancer prevention strategies for this specific patient group. Further research is required to explore the mechanisms underlying the association between lean NAFLD and specific GI cancers.

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Liver, Heart, Death… Can This Sequence Be Broken?

Manka

2023

Dig Dis Sci

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Cardiovascular Morbidity and Mortality Related to Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Cited by 24 publications

References 53 publications

Hepatic inflammation and fibrosis are profiles related to mid‐term mortality in biopsy‐proven MASLD: A multicenter study in Japan

Hepatic inflammation and fibrosis are profiles related to mid‐term mortality in biopsy‐proven MASLD: A multicenter study in Japan

Gastrointestinal cancers in lean individuals with non‐alcoholic fatty liver disease: A systematic review and meta‐analysis

Liver, Heart, Death… Can This Sequence Be Broken?

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