Genomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study

Zheng, Melanie; Huang, Daniel Q.; Konkwo, Chigoziri; Agrawal, Saaket; Khera, Amit V.; Loomba, Rohit; Vilarinho, Sílvia; Ajmera, Veeral

doi:10.1016/j.jhepr.2023.100692

Cited by 10 publications

(19 citation statements)

References 24 publications

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“…Type 2 lean NAFLD is a broad category of patients without visceral adiposity, where hepatic steatosis is secondary to monogenic disorders, such as hypobetalipoproteinaemia and lysosomal acid lipase deficiency. A prospective study by Zheng et al 42 . enrolling 124 NAFLD patients found monogenic disorders in nearly 33% of normal weight individuals with NAFLD who did not have visceral adiposity.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…It is expected that there are yet undiagnosed HFI cases among these populations. Indeed, a case of HFI was recently identified by whole exome sequencing among lean, adult patients with non‐alcoholic fatty liver disease 20 . However, before these tools can be implemented in clinical practice, they need to be replicated and validated.…”

Section: Discussionmentioning

confidence: 99%

Development of tools to facilitate the diagnosis of hereditary fructose intolerance

et al. 2023

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Although hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism that classically presents at infancy, the diagnosis is often missed or delayed. In this study, we aimed to develop tools to facilitate the diagnosis of HFI. The intake of fructose‐containing food products, that is, fruit, fruit juice and sugar‐sweetened beverages, was assessed by a 3‐day food diary in adult HFI patients (n = 15) and age, sex, and BMI‐matched controls (n = 15). Furthermore, glycosylation of transferrin was examined using high‐resolution mass spectrometry and abnormally glycosylated transferrin was expressed as ratio of normal glycosylated transferrin. We found that the sensitivity and specificity of the 3‐day food diary for the intake of at least one fructose‐containing food product were both 100%. Both mono‐glyco:diglyco transferrin and a‐glyco+mono‐glyco:di‐glyco transferrin were greater in HFI patients and had a high‐discriminatory power (area under the receiver operating characteristic curve: 0.97 and 0.94, respectively). In this well‐characterized cohort of adult HFI patients, the 3‐day food questionnaire and the glycosylation pattern of transferrin are valuable tools to facilitate the recognition and diagnosis of HFI in adult patients.

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“…Indeed, since the frequency of pathogenic APOB mutations has been estimated between 1:700 and 1:3000, FHBL-SD2 may be underdiagnosed and participate in SLD development and progression notably in patients without metabolic syndrome components as recently suggested by others. 12,13 Lipid profiles need to be evaluated with caution in cirrhotic patients knowing that low LDLc and HDLc serum levels may be related to liver failure.…”

Section: Ta B L Ementioning

confidence: 99%

Combination of heterozygous APOB gene mutation with PNPLA3 and TM6SF2 variants promotes steatotic liver disease, cirrhosis and HCC development

Chouik,

Di Filippo,

Radenne

et al. 2024

Liver International

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Genomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study

Cited by 10 publications

References 24 publications

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

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

Development of tools to facilitate the diagnosis of hereditary fructose intolerance

Combination of heterozygous APOB gene mutation with PNPLA3 and TM6SF2 variants promotes steatotic liver disease, cirrhosis and HCC development

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