Non-invasive predictors of prognosis of Asian patients with histopathologically-confirmed lean nonalcoholic fatty liver disease

Iritani, Soichi; Akuta, Norio; Kawamura, Yusuke; Kajiwara, Akira; Kasuya, Kayoko; Fujiyama, Shunichiro; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saito, Satoshi; Suzuki, Fumitaka; Arase, Yasuji; Ikeda, Kenji; Suzuki, Yoshiyuki; Kumada, Hiromitsu

doi:10.1186/s12876-020-01509-3

Cited by 12 publications

(18 citation statements)

References 30 publications

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“…There were 38 studies 43,45,46,59‐91,211,212 (40 cohorts; 2,361,275 participants) of cancer populations (Table S3); 17 cohorts were in East Asia, 10 cohorts in North America, 7 in Europe, 2 were international cohorts, 2 were in West Asia, and 1 each in South America and Africa. Mean age of participants ranged from 17 to 75 years.…”

Section: Resultsmentioning

confidence: 99%

Associations between body mass index and all‐cause mortality: A systematic review and meta‐analysis

2023

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SummaryFasting insulin and c‐reactive protein confound the association between mortality and body mass index. An increase in fat mass may mediate the associations between hyperinsulinemia, hyperinflammation, and mortality. The objective of this study was to describe the “average” associations between body mass index and the risk of mortality and to explore how adjusting for fasting insulin and markers of inflammation might modify the association of BMI with mortality. MEDLINE and EMBASE were searched for studies published in 2020. Studies with adult participants where BMI and vital status was assessed were included. BMI was required to be categorized into groups or parametrized as non‐first order polynomials or splines. All‐cause mortality was regressed against mean BMI squared within seven broad clinical populations. Study was modeled as a random intercept. β coefficients and 95% confidence intervals are reported along with estimates of mortality risk by BMIs of 20, 30, and 40 kg/m2. Bubble plots with regression lines are drawn, showing the associations between mortality and BMI. Splines results were summarized. There were 154 included studies with 6,685,979 participants. Only five (3.2%) studies adjusted for a marker of inflammation, and no studies adjusted for fasting insulin. There were significant associations between higher BMIs and lower mortality risk in cardiovascular (unadjusted β −0.829 [95% CI −1.313, −0.345] and adjusted β −0.746 [95% CI −1.471, −0.021]), Covid‐19 (unadjusted β −0.333 [95% CI −0.650, −0.015]), critically ill (adjusted β −0.550 [95% CI −1.091, −0.010]), and surgical (unadjusted β −0.415 [95% CI −0.824, −0.006]) populations. The associations for general, cancer, and non‐communicable disease populations were not significant. Heterogeneity was very large (I2 ≥ 97%). The role of obesity as a driver of excess mortality should be critically re‐examined, in parallel with increased efforts to determine the harms of hyperinsulinemia and chronic inflammation.

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Section: Resultsmentioning

confidence: 99%

Associations between body mass index and all‐cause mortality: A systematic review and meta‐analysis

2023

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“…Several studies have reported that the incidence of advanced fibrosis and liver-related events in these patients is similar to or worse than that in patients with fatty liver who are overweight/obese. [51][52][53] In addition, a higher risk for ASCVD and higher all-cause mortality has been reported in patients with fatty liver in the context of normal weight than that in patients who are overweight/obese. [53][54][55] Patients with lean/normal weight fatty liver have been reported to progress to advanced liver disease, ASCVD, and liver-related mortality, independent of PNPLA3 genotype.…”

Section: Validity Of the Mafld Definition For People Who Are Lean/normal Weightmentioning

confidence: 99%

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region

et al. 2022

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Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in lean/normal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and nonspecialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in lean/normal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.

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“…First, we excluded the Asian studies using the BMI cut-off by the WHO criteria. [22][23][24] Second, we systematically removed each study, one by one and analysed the results to verify if any single study had a significant impact on the overall findings. Subgroup analyses and sensitivity analyses were conducted exclusively when there were ≥4 eligible cohort studies, while meta-regressions were performed exclusively when there were ≥6 eligible cohort studies.…”

Section: Data Synthesis and Analysismentioning

confidence: 99%

“…Ultimately, 8 studies were included in this systematic review and meta-analysis. 11,[22][23][24][26][27][28][29] The main characteristics of the 8 eligible cohort studies are summarized in Table S1. A total of 56 745 NAFLD individuals were included in the final analysis (31.2% were women; mean age 52.8 years; mean BMI 30.2 kg/m 2 ).…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…The median duration of follow-up was 8.9 (IQR: 6.5-11) years. Four eligible cohort studies were carried out in Asia (Japan, China and Hong Kong), [22][23][24]28 three ones were carried out in Europe (Sweden, France, Italy, United Kingdom and Spain) 11,27,29 and a study was carried out in the United States. 26 The study by Younes et al 11 was a multicentre study.…”

Section: Characteristics Of Included Studiesmentioning

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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Non-invasive predictors of prognosis of Asian patients with histopathologically-confirmed lean nonalcoholic fatty liver disease

Cited by 12 publications

References 30 publications

Associations between body mass index and all‐cause mortality: A systematic review and meta‐analysis

Associations between body mass index and all‐cause mortality: A systematic review and meta‐analysis

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region

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

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