Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease

Papagianni, Marianthi

doi:10.4254/wjh.v7.i4.638

Cited by 73 publications

(78 citation statements)

References 111 publications

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“…In addition, it was found to be a predictor of advanced fibrosis in children with HCV infection; this was a unique finding because unlike in adults, no correlation between liver steatosis and fibrosis had previously been confirmed in pediatric patients with CHC [10]. Noninvasive markers of steatosis have been studied in patients with nonalcoholic fatty liver disease (NAFLD) but not in patients with CHC [18]. The results of our study suggest that biomarkers that include the BMI z-score perform excellently for diagnosing significant steatosis in children with CHC.…”

Section: Discussionmentioning

confidence: 99%

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

et al. 2017

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BackgroundThere is a need for validation of noninvasive alternatives to liver biopsy for the evaluation of fibrosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the diagnostic performance of serum biomarkers modified by the body mass index z-score (BMI z-score) for the detection of fibrosis and steatosis in children with CHC.MethodsThirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC underwent liver biopsy. Fibrosis was scored using a 5-point METAVIR scale (≥2 = significant fibrosis). For all the children, the following noninvasive markers were calculated: The aspartate transaminase (AST)-to-platelets ratio index (APRI), the modified APRI (M-APRI: BMI z-score × APRI), the Fibrosis-4 index (FIB-4), the modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The area under the receiver operator characteristic curve (AUROC) was calculated to detect significant fibrosis and steatosis.ResultsIn the histopathological evaluation, 22/30 (73%) patients presented with fibrosis, and 8/30 (27%) presented with steatosis. For the detection of significant fibrosis, the AUROCs for M-APRI, M-FIB-4 and B-AST were 0.842, 0.823, and 0.848, respectively. For significant steatosis, the AUROCs were more than 0.9 for all markers that included the BMI z-score. B-AST, with a cut-off of 92.8, showed 71% sensitivity and 95% specificity for detecting significant fibrosis. For predicting severe steatosis, B-AST had 100% sensitivity and 92% specificity. Negative values of all three markers that included BMI z-scores excluded all patients with both significant fibrosis and significant steatosis.ConclusionsIncluding the BMI z-score in serum biomarker formulas enhances their diagnostic ability to detect significant fibrosis and steatosis. B-AST may thus act as an effective alternative to liver biopsy.

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Section: Discussionmentioning

confidence: 99%

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

et al. 2017

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“…14, 23, 24 Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for non-invasive quantitative assessment of hepatic steatosis and fibrosis. 25–30 Thus, they may be suitable alternatives to liver biopsy for diagnosing NALFD, for identifying at risk populations (NASH and those with hepatic fibrosis), and for assessing response to therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice

Dulai

Sirlin

Loomba

2016

Journal of Hepatology

290

262

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Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms.

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“…Even if liver biopsy is considered the diagnostic gold standard, the availability of non‐invasive markers to be used in NAFLD patients to predict NASH and/or severity of fibrosis represents a relevant medical need . To date, the diagnosis of NASH in clinical practice by using non‐invasive scores is difficult because of the lack of well‐performing and well‐validated tools . Furthermore, novel‐proposed NASH blood biomarkers, such as CK18‐Asp396 fragments, showed low sensitivity for NASH detection .…”

Section: Introductionmentioning

confidence: 99%

“…To date, the diagnosis of NASH in clinical practice by using non‐invasive scores is difficult because of the lack of well‐performing and well‐validated tools . Furthermore, novel‐proposed NASH blood biomarkers, such as CK18‐Asp396 fragments, showed low sensitivity for NASH detection . Different scores are available for the non‐invasive assessment of fibrosis (eg ‘aspartate aminotransferase (AST)‐to‐platelet ratio index’ (APRI) and the ‘four factors‐based fibrosis index’ (FIB‐4); some of them are very easy to use and implement in clinical practice even if there are limitations such as false‐positive results and high uncertainty areas .…”

Section: Introductionmentioning

confidence: 99%

Serum coding and non‐coding RNAs as biomarkers of NAFLD and fibrosis severity

Mauro

Scamporrino

Petta

et al. 2019

Liver International

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Background & Aims In patients with non‐alcoholic fatty liver disease (NAFLD), liver biopsy is the gold standard to detect non‐alcoholic steatohepatitis (NASH) and stage liver fibrosis. We aimed to identify differentially expressed mRNAs and non‐coding RNAs in serum samples of biopsy‐diagnosed mild and severe NAFLD patients with respect to controls and to each other. Methods We first performed a whole transcriptome analysis through microarray (n = 12: four Control: CTRL; four mild NAFLD: NAS ≤ 4 F0; four severe NAFLD NAS ≥ 5 F3), followed by validation of selected transcripts through real‐time PCRs in an independent internal cohort of 88 subjects (63 NAFLD, 25 CTRL) and in an external cohort of 50 NAFLD patients. A similar analysis was also performed on liver biopsies and HepG2 cells exposed to oleate:palmitate or only palmitate (cellular model of NAFL/NASH) at intracellular/extracellular levels. Transcript correlation with histological/clinical data was also analysed. Results We identified several differentially expressed coding/non‐coding RNAs in each group of the study cohort. We validated the up‐regulation of UBE2V1, BNIP3L mRNAs, RP11‐128N14.5 lncRNA, TGFB2/TGFB2‐OT1 coding/lncRNA in patients with NAS ≥ 5 (vs NAS ≤ 4) and the up‐regulation of HBA2 mRNA, TGFB2/TGFB2‐OT1 coding/lncRNA in patients with Fibrosis stages = 3‐4 (vs F = 0‐2). In in vitro models: UBE2V1, RP11‐128N14.5 and TGFB2/TGFB2‐OT1 had an increasing expression trend ranging from CTRL to oleate:palmitate or only palmitate‐treated cells both at intracellular and extracellular level, while BNIP3L was up‐regulated only at extracellular level. UBE2V1, RP11‐128N14.5, TGFB2/TGFB2‐OT1 and HBA2 up‐regulation was also observed at histological level. UBE2V1, RP11‐128N14.5, BNIP3L and TGFB2/TGFB2‐OT1 correlated with histological/biochemical data. Combinations of TGFB2/TGFB2‐OT1 + Fibrosis Index based on the four factors (FIB‐4) showed an Area Under the Curve (AUC) of 0.891 (P = 3.00E‐06) or TGFB2/TGFB2‐OT1 + Fibroscan (AUC = 0.892, P = 2.00E‐06) improved the detection of F = 3‐4 with respect to F = 0‐2 fibrosis stages. Conclusions We identified specific serum coding/non‐coding RNA profiles in severe and mild NAFLD patients that possibly mirror the molecular mechanisms underlying NAFLD progression towards NASH/fibrosis. TGFB2/TGFB2‐OT1 detection improves FIB‐4/Fibroscan diagnostic performance for advanced fibrosis discrimination.

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Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease

Cited by 73 publications

References 111 publications

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice

Serum coding and non‐coding RNAs as biomarkers of NAFLD and fibrosis severity

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