Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis

Alkhouri, Naim; Alisi, Anna; Okwu, Vera; Matloob, Ammar; Ferrari, Federica; Crudele, Annalisa; Vito, Rita De; López, Rocío; Feldstein, Ariel E.; Nobili, Valério

doi:10.1007/s10620-015-3614-z

Cited by 24 publications

(16 citation statements)

References 25 publications

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“…The major features of these trials were summarised in Table 1 . After the whole presented workflow, 14 studies were admitted to our meta-analysis [ 9 – 11 , 20 – 30 ]. Input for NAFLD patients was carried only when a control group was not included in the study (i.e.…”

Section: Resultsmentioning

confidence: 99%

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Association of serum ferritin with non-alcoholic fatty liver disease: a meta-analysis

Lü²,

Geng

et al. 2017

Lipids Health Dis

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BackgroundA growing number of studies reported the connection between the level of serum ferritin (SFL) and non-alcoholic fatty liver disease (NAFLD). However, such connection was still disputable. The aim of our meta-analysis was to estimate SFL between the groups as below: patients with NAFLD against control group; non-alcoholic steatohepatitis (NASH) patients against control group; non-alcoholic fatty liver (NAFL) patients against a control group and NASH patients vs NAFL patients.MethodsWe screened the studies in PubMed, EMBASE, the Cochrane Database and the Cochrane Central register controlled trials from the beginning to July 10, 2016 to find the studies indicated the connection between SFL and NAFLD (NAFL and/or NASH). Fourteen published studies which evaluate the SFL in NAFLD patients were selected.ResultsHigher SFL was noticed in NAFLD patients against control group (standardized mean difference [SMD] 1.01; 95% CI 0.89, 1.13), NASH patients against control group (SMD 1.21; 95% CI 1.00, 1.42), NAFL patients against control group (SMD 0.51; 95% CI 0.24, 0.79) and NASH patients against NAFL patients (SMD 0.63; 95% CI 0.52, 0.75). These results remained unaltered actually after the elimination of studies which were focused on paediatric or adolescent populations. Higher SFL was presented in NAFLD patients against the control group (SMD 1.08; 95% CI 0.95, 1.20) in adults and NASH patients against NAFL patients in adults (SMD 0.74; 95% CI 0.62, 0.87). The connection between SFL and NASH against NAFL group in paediatric or adolescent populations was observed inconsistently (SMD 0.10; 95% CI -0.18, 0.38).ConclusionsThe level of SFL was elevated in patients with NAFLD (NAFL and/or NASH) compared with the controls. Compared with NAFL, The level of SFL was increased in NASH. The result remained unaltered actually after the elimination of studies focused on paediatric or adolescent populations.

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Section: Resultsmentioning

confidence: 99%

“…Three studies compared SFL between NAFLD patients and controls, but they didn’t carry independent evidence on both NAFL and NASH [ 9 , 21 , 28 ]. Ten studies compared SFL between NAFL and NASH patients [ 10 , 11 , 20 , 22 , 23 , 25 – 27 , 29 , 30 ] (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Association of serum ferritin with non-alcoholic fatty liver disease: a meta-analysis

Lü²,

Geng

et al. 2017

Lipids Health Dis

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“…It has been reported that Fas, Fas ligand (FasL), and caspase 8 mRNA activation are important contributing factors to NAFLD[ 19 ]. Another study showed that children with NASH had significantly higher levels of soluble Fas and soluble FasL than those in the “not NASH” group[ 20 ]. Fas apoptosis inhibitory molecule (FAIM), a ubiquitously expressed antiapoptotic protein, functions as a mediator of Akt signaling[ 21 ].…”

Section: Apoptosis and The Activation Of Caspases In The Progression mentioning

confidence: 99%

Apoptosis and non-alcoholic fatty liver diseases

Kanda

Matsuoka

Yamazaki

et al. 2018

WJG

210

145

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The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.

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“…Newly proposed markers: Serum potassium levels show an inverse relationship with the presence of aggressive disease (NASH and fibrosis) in children with NAFLD[ 57 ]. Markers of the extrinsic pathway of hepatocyte apoptosis [ e.g ., circulating soluble Fas and Fas ligand (sFasL) levels] that are elevated in children with NASH may be potential novel biomarkers[ 58 ]. Plasma cathepsin D (CatD) holds a high diagnostic value for distinguishing pediatric patients with hepatic inflammation from children with simple steatosis.…”

Section: Non-invasive Indirect Diagnosis Of Nafldmentioning

confidence: 99%

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Clemente

Mandato

Poeta

et al. 2016

WJG

164

160

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Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.

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Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis

Abstract: Markers of the extrinsic pathway of hepatocyte apoptosis are elevated in children with NASH. sFasL and the NASH apoptosis score are potential novel biomarkers for NASH.

Cited by 24 publications

References 25 publications

Association of serum ferritin with non-alcoholic fatty liver disease: a meta-analysis

Association of serum ferritin with non-alcoholic fatty liver disease: a meta-analysis

Apoptosis and non-alcoholic fatty liver diseases

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

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