ArticleJournal of hepatology2023
Longitudinal changes in fibrosis markers are associated with risk of cirrhosis and hepatocellular carcinoma in non-alcoholic fatty liver disease.
Article in Journal of hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 5 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Clinical Outcomes and Non-Invasive Testing in Metabolic Dysfunction-Associated Steatohepatitis With Cirrhosis: A Systematic Review.Liver international : official journal of the International Association for the Study of the Liver · 2026Pooled it
- The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease.Hepatology international · 2025Guideline
- KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease.Clinical and molecular hepatology · 2024Guideline
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Obesity facts · 2024Guideline
- Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Pooled it
- Effect of empagliflozin on liver fibrosis and steatosis in patients with type 2 diabetes and non-alcoholic fatty liver disease: a randomized clinical trial.BMC endocrine disorders · 2025Trial
- Predicting PD-L1 + CD8 - status in non-small cell lung cancer tissue from clinical indicators using machine learning.Chinese medical journal · 2026Article
- Validation of Texas Hepatocellular Carcinoma Consortium Risk Index in the Hepatocellular Carcinoma Early Detection Strategy Study.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026Article
- MAFLD/MASLD: Past, Present, and Future.Journal of gastroenterology and hepatology · 2026Review
- Impact of nonalcoholic fatty liver disease on the response to pegylated interferon-α therapy in patients with chronic hepatitis B.Microbiology spectrum · 2026Article
- A combi-elasto ultrasound based deep learning model on liver fibrosis staging for suspected MASLD/MASH patients.BMC medical imaging · 2026Article
- Discordant FIB-4 and liver stiffness in metabolic dysfunction-associated steatotic liver disease as related to histology and liver-related events in a global cohort: Editorial on "Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement".Clinical and molecular hepatology · 2026Article
- Article
- Prediction of trajectories and outcomes in early-stage metabolic dysfunction-associated steatotic liver disease: a narrative review.EClinicalMedicine · 2026Review
- Association of high risk of liver fibrosis in patients with serious outcomes of adverse drug reactions.European journal of clinical pharmacology · 2026Article
- Risk Assessment and Prediction of Hepatocellular Carcinoma in Noncirrhotic Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Novel biomarkers for alcohol-associated liver disease and their implications across clinical settings.Clinical and molecular hepatology · 2026Review
- Diagnostic Value of MR Elastography and MRI-Proton Density Fat Fraction in Cirrhosis Based on Explant Liver Histology.Journal of gastroenterology and hepatology · 2026Article
- Dynamic immune response and its influencing factors in COVID-19 patients with non-alcoholic fatty liver disease: A cohort study.World journal of hepatology · 2026Article
- Dynamic FIB-4 Score Changes and HCC Risk in Patients with MASLD and Elevated Liver Enzymes: A Nationwide Cohort Study.Liver cancer · 2026Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsCurrently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD.
methodsWe conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced fibrosis (low-risk FIB-4 <1.45, indeterminate-risk FIB-4 1.45-2.67, and high-risk FIB-4 >2.67). We used landmark Fine-Gray competing risks models to determine the effects of change in FIB-4 between NAFLD diagnosis date and 3-year landmark time on the subsequent risk of HCC and a composite endpoint.
resultsAmong the 202,319 patients with NAFLD in the 3-year landmark analysis, 473 progressed to HCC at an incidence rate of 0.28 per 1,000 person years (PY) (95% CI 0.26-0.30). The incidence rate of the composite endpoint was 1.31 per 1,000 PY (95% CI 1.25-1.37). At baseline, 74.7%, 21.4%, and 3.8% of patients had a low, indeterminate, and high FIB-4, respectively. Compared to patients who were at stable low FIB-4 at both time points, the risk of HCC and that of the composite endpoint was higher for all other subgroups with the highest risk in patients with persistently high FIB-4 (HCC adjusted sub-distribution hazard ratio 57.7, 95% CI 40.5-82.2 and composite endpoint hazard ratio 28.6, 95% CI 24.6-33.2).
conclusionLongitudinal changes in FIB-4 were strongly associated with progression to cirrhosis and HCC. IMPACT AND IMPLICATIONS: Tools to stratify the risk of HCC development in patients with NAFLD are currently lacking. The fibrosis-4 (FIB-4) score is a widely available non-invasive test for liver fibrosis, a primary determinant of the development of cirrhosis and HCC. In a large retrospective cohort of patients with NAFLD, we found that serial changes in FIB-4 over time were strongly associated with progression to cirrhosis and HCC. Integrating serial measurements of non-invasive tests for fibrosis into the care pathway for patients with NAFLD could help tailor HCC risk prevention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.