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Record W4407110618 · doi:10.7759/cureus.78421

Efficacy of Non-invasive Biomarkers in Diagnosing Non-alcoholic Fatty Liver Disease (NAFLD) and Predicting Disease Progression: A Systematic Review

2025· review· en· W4407110618 on OpenAlexaboutno aff
Sheenam Garg, Mansey Varghese, Fahmida Shaik, Fnu Jatin, Dheerja Sachdeva, Fathima Wafa Eranhikkal, Sweta Sahu, Salma Younas

Bibliographic record

VenueCureus · 2025
Typereview
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsnot available
Fundersnot available
KeywordsMedicineFatty liverDiseaseAlcoholic liver diseaseInternal medicineSteatohepatitisGastroenterologyPathologyCirrhosis

Abstract

fetched live from OpenAlex

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, with significant global prevalence and a strong association with metabolic syndrome, obesity, and diabetes. Early diagnosis and prediction of disease progression are critical for effective management. Non-invasive biomarkers have emerged as promising alternatives to liver biopsy, offering safer and more accessible diagnostic and prognostic options. This systematic review evaluates the efficacy of non-invasive biomarkers in diagnosing NAFLD and predicting disease progression, focusing on diagnostic accuracy, clinical utility, and limitations. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including studies published between 2010 and 2024. Databases such as PubMed, Embase, and Scopus were searched using relevant keywords and Boolean operators. Inclusion criteria comprised studies evaluating adults (18+) with NAFLD using non-invasive biomarkers, compared to liver biopsy or other standards, and reporting diagnostic metrics such as sensitivity, specificity, and area under the curve (AUC). Data were extracted systematically, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) and the Newcastle-Ottawa Scale. The nine studies include a range of biomarkers such as serum markers (Pro-C3, NIS4), imaging techniques (MRI-PDFF, cT1), and composite scores (cTAG, NFS). Diagnostic accuracy was high, with area under the curve (AUC) values ranging from 0.81 to 0.90 for detecting significant fibrosis and at-risk non-alcoholic steatohepatitis (NASH). Imaging tools such as MRI-PDFF offered superior reproducibility and whole-liver assessments, while composite biomarkers such as NIS4 demonstrated robust sensitivity but moderate specificity. Notable heterogeneity in populations and methodologies was observed. Non-invasive biomarkers show comparable diagnostic performance to liver biopsy while offering significant advantages in safety, scalability, and patient adherence. However, gaps remain, including the need for validation in diverse populations and improved specificity for advanced fibrosis. Integrating non-invasive biomarkers into clinical practice could revolutionize NAFLD management by enabling early diagnosis, guiding treatment, and reducing reliance on invasive methods. Future research should focus on validating these tools across diverse cohorts and developing novel biomarkers to address existing limitations.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: Systematic review
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.044
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.003
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0040.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.358
Teacher spread0.329 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designSystematic review
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes1
Has abstractyes

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