Next Article in Journal
The Resistance to Traction Forces Differs Substantially Between Intestinal Parts, but Not Between In- and Outbred Strains of Mice
Previous Article in Journal
How Do Immigration Status and Cultural Factors Influence Rates of H. pylori Among Self-Identified Hispanics Living in the United States?
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Gastroenterology Insights
Volume 17
Issue 1
10.3390/gastroent17010011
gastroent-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

The Role of Primary Care and Noninvasive Testing in the Early Diagnosis of Metabolic-Associated Steatotic Liver Disease (MASLD)

by
Alina Mihaela Constantin
1,
Mirela Maria Nedelescu
2,*,
Raluca Tatar
3,4,*,
Corina Silvia Pop
1,5,
Andrea Elena Neculau
6,
Sorina Maria Aurelian
1,7,
Corina Oancea
8,
Justin Aurelian
9,
Sandra Monica Gîdei
1,7 and
Irina Mihaela Stoian
2
1
Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
2
Discipline Hygiene and Medical Ecology, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Dr. Leonte Street, 050463 Bucharest, Romania
3
Department of Plastic Reconstructive Surgery, “Grigore Alexandrescu” Clinical Emergency Hospital for Children, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
4
Department of Plastic Reconstructive Surgery and Burns, “Grigore Alexandrescu” Clinical Emergency Hospital for Children, 010621 Bucharest, Romania
5
Department of Internal Medicine 2 and Gastroenterology, Bucharest University Emergency Hospital, 050098 Bucharest, Romania
6
Department of Fundamental, Prophylactic and Clinical Sciences, Faculty of Medicine, Transilvania University of Brasov, 500019 Brasov, Romania
7
Department of Geriatrics, Hospital of Chronic Diseases “Sf. Luca”, 041915 Bucharest, Romania
8
Department of Physical Medicine and Rehabilitation, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050659 Bucharest, Romania
9
Department of Nursing, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
*
Authors to whom correspondence should be addressed.
Gastroenterol. Insights 2026, 17(1), 11; https://doi.org/10.3390/gastroent17010011
Submission received: 8 December 2025 / Revised: 8 January 2026 / Accepted: 2 February 2026 / Published: 6 February 2026
(This article belongs to the Section Liver)
Browse Figure
Versions Notes

Abstract

Chronic liver disease is one of the leading causes of morbidity and mortality worldwide. Cirrhosis of the liver is the most advanced form of chronic liver disease and the 12th leading cause of death worldwide. The incidence of liver cirrhosis is increasing significantly each year due to the increased prevalence of metabolic syndrome associated with fatty liver disease. Liver biopsy has been traditionally considered the “gold standard” method for the evaluation of tissue lesions (e.g., liver fibrosis in patients with chronic liver disease), and it is still accepted as such. However, it is an invasive and costly method with potential risks for patients. Thus, we decided to evaluate the importance of non-invasive tests (NIT) and the combinations of NIT used for the diagnosis and staging of liver fibrosis in metabolic-associated steatotic liver disease—MASLD—and how the primary care physician is involved in these stages. In this context, primary care physicians will be the first in contact with these patients, who could initiate early, well-targeted treatment to prevent disease progression and complications, which could reduce the number of costly consultations and specialist investigations.

1. Introduction

In 2016, the World Health Organization (WHO) Global Health Sector Strategy on Human Health called for and aimed to eliminate hepatitis by 2030 by scaling up prevention, testing (invasive and non-invasive) and treatment of this liver disease. The elimination of hepatitis as a public health threat has been defined as a 90% reduction in the incidence of the disease and a 65% reduction in mortality compared to the 2015 baseline [1,2].
In addition to viral hepatitis, excessive alcohol consumption and metabolic dysfunction-associated fatty liver disease (MASLD) are other leading causes of liver cirrhosis; in some cases, they can also lead to liver cancer and may subsequently require liver transplantation in these patients [3]. The importance of these causes will increase, as the proportion of cases due to hepatitis B, C and D virus infections declines with hepatitis B immunization and advances in antiviral therapy.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as the presence of hepatic steatosis in individuals with at least one metabolic risk factor (e.g., obesity, dyslipidemia, increased blood pressure) and minimal or no alcohol consumption) [4]. In recent years, a multi-society panel of international experts recommended that the old terminology of “non-alcoholic fatty liver disease (NAFLD)” be replaced with the new one, “metabolic dysfunction-associated steatotic liver disease (MASLD),” emphasizing the key metabolic factors that contribute to steatohepatitis and chronic liver disease progression [5]. Metabolic dysfunction-associated steatohepatitis (MASH) is a histologically defined subset of MASLD that is characterized by the presence of hepatic steatosis with inflammatory damage to hepatocytes. These conditions have emerged as growing concerns for human health, as their prevalence is steadily increasing globally with the growing concern in this field [5,6].
MASLD is the most common cause of chronic liver disease that affects approximately 30% of adults worldwide, with numbers rising significantly and being projected to hit over 55% by 2040, with the increasing prevalence of obesity and type 2 diabetes [7,8].
The traditional approach to diagnosing these conditions has been based on liver biopsy—an invasive procedure that remains the “gold standard”. However, liver biopsy is associated with a number of limitations and potential complications that may occur, sampling variability and low patient acceptability [9].
Over the last 20 years, researchers have been developing and using non-invasive assessment methods—NIT—which have high applicability and can help in early and accurate diagnosis, as well as correct and effective monitoring of chronic liver diseases [10,11,12].
Primary care services, through primary care physicians (PCP), who are qualified, trained and competent in early diagnosis of liver diseases, have a very important role in referring these patients to other physicians who can provide specialized care (gastro-enterologists, diabetologists, endocrinologists, etc.), helping to provide the correct staging and therapeutic management of diseases and complications that may occur in patients with chronic liver diseases.
Considering all these issues, we aimed to evaluate the role of the PCP in the diagnosis and monitoring of chronic liver disease associated with metabolic dysfunction—MASLD—as well as the place of non-invasive assessment methods and their combinations, recommended by the PCP for the diagnosis and staging of chronic liver diseases and for accurate monitoring of these patients.

2. Materials and Methods

We performed a comprehensive review of the literature, using the PUBMED and EMBASE databases, looking at the relationship between the evaluation of non-invasive assessment methods, which can accurately diagnose and monitor the progression of chronic liver diseases.
To achieve the objectives of this research, we used the following search keywords: (1) “non-invasive evaluation” AND “chronic liver disease”; (2) “non-invasive testing” AND “non-alcoholic fatty liver disease (NAFLD)”; and (3) “non-invasive testing” AND “metabolic dysfunction-associated steatotic liver disease “MASLD”. Subsequently, we decided on the selection of the materials and considered only those scientific articles that were directly related to the proposed aim.
The information we used as references for this paper was selected on the basis of answers to several primary questions (used as inclusion criteria):
(PQ1) Is there a direct link between the recommendation of “non-invasive assessment” AND “chronic liver disease”?
(PQ2) Was there, in the past, a direct link between the recommendation of “non-invasive assessments” AND “non-alcoholic fatty liver disease (NAFLD)”?
(PQ3) Is there currently a direct link between the recommendation of “non-invasive assessments” AND metabolic dysfunction-associated steatotic liver disease “MASLD”?
From this main set of three questions (PQ), a secondary set of supplementary questions (SQ) was developed, which helped us to search and select the articles that formed the basis of the present study:
(SQ1) What are the indications for the use of currently available NIT for monitoring patients with metabolic dysfunction-associated steatotic liver disease ‘MASLD’?
(SQ2) How are serum biomarkers used as non-invasive tests for liver fibrosis staging?
(SQ3) How is transient elastography (TE) used as an NIT for liver fibrosis staging?
(SQ4) How is TE used as an NIT compared to serum biomarkers [SBMk] for staging liver fibrosis?
(SQ5) How important is and what additional results can the combination of serum biomarkers [SBMk] and TE provide for liver fibrosis staging?
(SQ6) How are the new elastographic methods used as non-invasive tests in comparison with TE for liver fibrosis staging?
(SQ7) What is the role of the PCP regarding the diagnosis, staging and monitoring of patients with simple steatosis and patients with metabolic dysfunction-associated steatohepatitis (MASH)?
(SQ8) What is the role of the PCP in the use of non-invasive tests for patients with simple steatosis and/or patients with metabolic dysfunction-associated steatohepatitis (MASH)?
All results selected from the search were evaluated both qualitatively and in terms of their relevance to the paper; thus, only articles that we considered relevant and that answered the selection questions were used.
The databases returned 98 scientific articles. Finally, we selected 65 articles for our analysis (following screening and selection, following the inclusion criteria) in order to describe the link between non-invasive assessment, NAFLD, MASLD and chronic liver disease.
These articles, in which we found general information and specific, quantifiable information that answered our questions by following the use of key terms, were published as follows:
  • Between 2015 and 2024 for first research—PQ1 (with 15 eligible scientific articles and guidelines);
  • Between 2009 and 2025 for second research—PQ2 (with 24 eligible scientific articles and guidelines);
  • Between 2022 and 2025 for third research—PQ3 (with 26 eligible scientific articles and guidelines).
All duplicate studies were eliminated after the first stage of screening.

3. Results

Non-alcoholic fatty liver disease (NAFLD) has recently been renamed metabolic-associated fatty liver disease (MASLD), highlighting the presence of cardiometabolic risk factors as a positive diagnostic criterion, and is considered the most common chronic liver disease in the adult population worldwide, affecting approximately 30% of adults [13,14]. Non-alcoholic steatohepatitis has also recently been replaced by metabolic dysfunction-associated steatohepatitis (MASH).
Most of the selected studies and guidelines have evaluated the steps for the diagnosis of hepatic steatosis-associated metabolic dysfunction in metabolic-associated fatty liver disease (MASLD) and assessment by non-invasive testing in these individuals [15,16].
Metabolic risk factors (prediabetes status, type 2 diabetes mellitus, increased inflammation, obesity/overweight, age ≥ 50 years) are frequently associated with MASLD and the likelihood of progression to cirrhosis or liver cancer [17,18,19].
The current guidelines recommend non-invasive evaluation of MASLD in patients with metabolic risk factors and consider the diagnosis of MASLD in the presence of hepatic steatosis on the one hand and at least one component of the metabolic syndrome (pre-diabetes status, type 2 diabetes mellitus, increased inflammation, obesity/overweight, age ≥ 50 years) on the other hand [11,20,21].
After excluding alcohol consumption in these patients, as well as exposure to hepatotoxic drugs, hepatitis B surface antigen testing or hepatitis C virus antibody testing, measurement of à jeun blood glucose value and measurement of serum lipids, ferritin and iron follow [22].
Non-invasive methods used to assess liver fibrosis in patients with MASLD have also gained ground in the last 20 years because of their potential to complement and/or replace invasive methods (which may be used in these patients) [23,24,25,26,27,28,29,30]. They are easy to use, can be easily repeated and they evaluate the whole liver (as a whole), while liver biopsy evaluates only a liver fragment. Standard liver biopsy performed under ultrasound control is not sufficient nor ideal for the diagnosis of liver fibrosis, but it has an important role in differentiating the staging [31,32].
The non-invasive assessment methods are based on two different approaches: a “biological” approach—based on the quantification of biomarkers in serum samples—and a “physical” approach—based on the measurement of liver stiffness (LS) [18]. The most commonly used NIT for liver fibrosis assessment, together with their advantages and disadvantages, are presented in Table 1.
The biological approach refers to the use of biomarkers, which can be quantified in serum samples. These biomarkers have the potential to differentiate between simple steatosis and more advanced forms of the disease, such as non-alcoholic steatohepatitis and liver fibrosis. Based on information from the selected studies, the diagnostic strategy could be based on the use of serologic tests [AST to platelet ratio index (APRI) and Fibrosis Index-4 (FIB-4) for liver fibrosis or assessment of the Cytokeratin 18 antibody (CK18)]; a combination of serologic tests (APRI and FIB-4) with the use of ultrasonography; and the “physical” approach, including the following methods: ELF (enhanced liver fibrosis)—a new testing method—MRE (magnetic resonance elastography), MRI-PDFF (magnetic resonance imaging-derived proton density fat fraction), and the conventional ultrasound method, FibroScan and LiverMultiScan [9,10,33,34,35]. The components, cut-off values, and the clinical use and relevance of the most common serum biomarkers are revealed in Table 2.
Fibroscan or transient elastography (TE) is the first-line imaging test for patients with suspected MASLD. It is an ultrasound-based method that allows for non-invasive quantification of liver fibrosis [37]. TE is a technological achievement that allows for ultrasound to provide complementary information by accurately measuring tissue elasticity, which is assessed by the speed of propagation of waves in the tissue. It can be performed by a physician (including the PCP) who has knowledge of ultrasound through an imaging course, as well as in the day hospital setting (by a gastroenterologist or diabetologist), with the main aim of checking liver stiffness. Stiff areas in the liver are a sign of scar tissue (liver fibrosis), which can be caused by chronic liver disease [38].
There are numerous advantages of TE: it is a simple, rapid, and reproducible test; it is a painless, non-invasive test that is necessary for the assessment of liver fibrosis staging; the result is immediately available to the patient; and the test can be repeated at any time, as many times as necessary, particularly for treatment evaluation [39].
Additional tests are performed when TE results indicate alternative or coexisting causes of liver damage. Advances in imaging techniques, such as vibration-controlled TE and parameter-controlled attenuation, provide valuable information on liver stiffness and fat content in patients with non-alcoholic fatty liver disease [40,41].
According to international guidelines, patients at risk of advanced liver fibrosis and major liver damage, who may have associated pre-diabetes, type 2 diabetes mellitus and/or overweight or obesity, should be initially examined in primary care clinics (by the family doctor) and subsequently by physicians from other specialties (gastroenterology, diabetes and nutrition, cardiology, endocrinology) [42].
FIB-4 is recommended as the first-line implemented test because of its good negative predictive value (NPV) for advanced liver fibrosis [18]. However, FIB-4 is suboptimal to identify patients in order to be referred to liver centers, because about one-fifth may be false negatives at FIB-4, instead having an LSM ≥ 8 Kpa, which is a sign of the advanced liver fibrosis [43,44].
Some non-invasive tests for fibrosis assessment appear to be less accurate in patients with type 2 diabetes mellitus and added overweight/obesity. Obesity may also affect the performance of TE and abdominal ultrasonography, while magnetic resonance imaging may not be feasible at all in some patients with severe obesity [45,46,47,48].
A summary of our findings according to the search strategy is presented below.

3.1. Studies Linking “Non-Invasive Assessment” and “Chronic Liver Disease”

Experimental/epidemiological studies and guidelines evaluating patients with chronic liver disease suggest that the use of non-invasive tests should be tailored to the setting and adapted to clinical needs (patient screening, liver fibrosis staging, patient monitoring) [49]. Conventional ultrasonography and, in the absence of liver steatosis, the controlled attenuation parameter—CAP—have been proposed as non-invasive investigations to be used at the triage stage in large, unselected populations [50,51]. In addition, according to the results obtained in terms of detection and classification of hepatic steatosis, MRI-PDFF (nuclear magnetic resonance—proton density fat fraction) is the most accurate non-invasive method and the most appropriate method used for the evaluation and follow-up of selected patients in clinical trials [52,53,54,55,56,57,58].
The results of these studies consider that none of the non-invasive imaging determinations can reliably differentiate simple steatosis from non-alcoholic steatohepatitis (however, magnetic resonance imaging—MRI-based modalities—are promising) [59,60,61,62].
A conclusion from these studies was that magnetic resonance elastography—MRE, TE, FIB-4 and nonalcoholic fatty liver disease fibrosis score—NFS are considered the most accurate and validated methods in terms of identifying advanced fibrosis.
Also, at the stage of excision of advanced fibrosis in primary care, FIB-4 and nonalcoholic fatty liver disease fibrosis score, NFS are the most suitable as first-line tools [63,64,65]. TE and MRE are recommended as the most suitable tools for specialists selecting patients for liver biopsy [66].
Likewise, studies provide increasing evidence on the link between serum markers and liver stiffness measured by TE, which accurately identifies the subgroup of patients with NAFLD who are at higher risk of liver complications, liver transplantation or even death [67,68].

3.2. Studies Linking “Non-Invasive Testing” and “Non-Alcoholic Fatty Liver Disease (NAFLD)”

The studies and guidelines retrieved from databases suggested that, although ultrasonography was the most widely used test for “fatty liver” diagnosing, numerous other available non-invasive tests had their roles in the evaluation of NAFLD [33,34,69,70,71,72,73,74,75,76,77,78,79].
In addition, in epidemiologic studies, the attenuation parameter used for the simultaneous diagnosis of hepatic steatosis and liver stiffness measurement was performed in patients with other chronic liver diseases [79].
The studies also examined the relationship between high-accuracy magnetic resonance imaging (MRI) used for the diagnosis and quantification of hepatic steatosis and liver fibrosis [76]. The results of the studies conducted in patients with NAFLD considered that it was necessary to develop further research on the use of non-invasive tests, particularly for the selection of patients to receive pharmacologic treatment, and to monitor the response of these patients to the treatment that had already been used. Fibrotic non-alcoholic steatohepatitis has, over time, become a target of diagnostic interest, and new scores for its diagnosis have emerged that incorporate imaging biomarkers [76,80].
The degree of liver fibrosis has also been considered important, being the main predictor of liver morbidity and mortality in patients with NAFLD [81].

3.3. Studies Linking “NIT” with Metabolic Dysfunction-Associated Steatotic Liver Disease “MASLD”

Studies published in recent years, between 2022 and 2025, suggest that liver biopsy still remains the gold standard for the diagnosis of “at risk” MASH (although there is an increased risk of complications post-liver biopsy and it is less desired by these patients) [82,83,84,85,86,87,88,89].
On the other hand, current advances in the development of non-invasive imaging techniques, new diagnostic methods developed in clinical trials and the biochemical characteristics of LDLH/MASH underline the development and increasing use of different non-invasive imaging techniques in this category of patients [90].
Abdominal ultrasonography is considered the main diagnostic method for liver steatosis. Also, MRI-PDFF is currently considered very important for quantifying steatosis [91].
Recent clinical studies suggest the use of imaging markers (targeting specific receptors or transporters in MASH compared to plain steatotic liver) as the most promising alternative for further non-invasive investigations [90].
The current results of ongoing studies explore the development and validation of a combination of non-invasive imaging investigations (FibroscanTM and MRE), together with serum biomarkers and anthropomorphic features associated with MASLD [92].
It is also considered that the use of these non-invasive imaging tools could eliminate the need for repeated invasive biopsies to monitor the progression of the MASLD on the one hand, and the medical and surgical effects on the other hand. Lifestyle modification in these patients (in addition to the use of the non-invasive imaging tools mentioned) could aim to prevent the progression of MASLD to cirrhosis and hepatocellular carcinoma [93].
The conclusion of these studies was that there is a current need to develop and use non-invasive tests for both diagnosis and monitoring of MASH, especially in the context of the recent emergence of direct liver-directed therapy for ‘at-risk’ MASH (i.e., MASH with NAS ≥ 4 and liver fibrosis stage ≥ F2) [94,95].
Although most testing methods have proven their usefulness, some important factors may influence the non-invasive evaluation of MASLD, such as the availability for testing and the cost of the actual testing, performed at the request of the primary care physicians outside the field of hepatology, who are involved in the clinical care of patients with MASLD [20,21,22,23,24].

3.4. Role of the Primary Care Physician in the Early Diagnosis and Management of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

In this study, we also aimed to highlight the importance of the PCP within the early diagnosis and management of patients with metabolic dysfunction-associated steatotic liver disease, in order to prevent disease progression and complications, such as cirrhosis and hepatic cancer.
The PCP is the first step in the early diagnosis of patients with metabolic dysfunction associated with hepatic steatosis within the MASLD. Basically, it is assumed that the PCP knows the patient and his medical and personal history best, and he should be the first to know the information about the presence of metabolic risk factors in these patients (presence of hypertension, type 2 diabetes mellitus, obesity—body mass index (BMI) > 30 kg/m3, age ≥ 50 years or serum aminotransferases (ALT or AST) > 2 times the upper limit of normal) [19,25]. The PCP is the one who should be able to monitor the patient, over time, through regular and frequent office visits. Thus, PCP should be the first to help in early detection and staging of the disease, in order to be able to further decrease the risk of complications and disease progression to cirrhosis or liver carcinoma [96]. In addition, PCP is the one who should be aware of the patient’s living conditions, as well as the patient’s ability to follow the recommended treatment and the patient’s adherence/compliance to treatment.
The first step is to obtain a detailed history, including information on the alcohol consumption or lack of it in these patients. At the beginning of the history, the PCP can discuss and document the alcohol consumption of these patients. These kinds of discussions are quite sensitive and may not obtain all the expected answers immediately. Thus, over time and during the patient’s follow-up, it is important to gently revisit this topic for clarification [88,97].
The effective and proactive intervention of the PCP has a very important role in the subsequent course of the patient with chronic liver disease. The PCP is also aware of the patient’s family history, genetic inheritance and predisposition to develop certain conditions over time, including MASLD [98].
The PCP is aware that simple steatosis, a benign condition, can develop over time into metabolic dysfunction-associated steatohepatitis (MASH) [99], whose diagnosis includes the presence of hepatic steatosis (by imaging, biomarkers, or biopsy); at least one cardiometabolic risk factor; limited history of alcohol intake (no more than two drinks per day in women or three drinks per day in men); and serology to exclude hepatitis B and C [100].
Therefore, it is very important to monitor the patient by keeping track of possible changes that may occur, such as: increased blood pressure, increased serum triglycerides and LDL-C, and decreased HDL-C (serum high-density lipoprotein cholesterol). Also, in the same patients, it is important to monitor both central adiposity (modified by weight gain in the patient, who may be obese or just overweight) and impaired glucose tolerance (in patients with prediabetes) or elevated blood glucose values in patients with type 2 diabetes mellitus [88,101].
Based on minimal determinations (results obtained from a venous blood sample) and using a calculator, in accordance with the guidelines, the PCP can calculate the liver fibrosis score and/or calculate the risk that the patient has liver fibrosis at that time.
The role of the PCP is also very important when deciding to refer a patient with simple steatosis or steatohepatitis associated with metabolic dysfunction (MASH) to other medical specialties: cardiology, gastroenterology, diabetes and nutrition, endocrinology, and others [102]. The vast majority of patients with MASLD are monitored both by their primary care physician (PCP) and in non-hepatologic settings (cardiology, endocrinology, pulmonology, renal diseases, etc.).
For example, according to results from clinical trials, about 2/3 of patients with impaired glucose tolerance or type 2 diabetes already have metabolic dysfunction when they see their diabetologist [103,104,105].
According to current guidelines [18], screening is recommended in the management of MASLD/MASH in:
  • Adult patients with prediabetes, type 2 diabetes mellitus, increased insulin resistance, overweight/obesity, family history of liver cirrhosis, presence of alcohol consumption in history, and age ≥ 50 years;
  • Pediatric patients with obesity, type 2 diabetes mellitus, polycystic ovary syndrome, but it is not recommended in type 1 diabetes mellitus.
Important aspects in the management of MASLD/MASH are: weight loss in these patients (the target is ≥10% of body weight; sometimes bariatric surgery is necessary), lifestyle modification (diet, especially Mediterranean diet, and physical activity are recommended; alcohol restriction is also recommended), and implementation of current standards of care in patients with comorbidities, etc. Subsequently, after a 6-month interval of lifestyle adjustment and monitoring of risk factors, non-invasive testing is resumed [106,107,108]. Incorporating a gluten-free diet, in addition to lifestyle changes, in patients with nonalcoholic fatty liver disease could be beneficial for improving components of the metabolic syndrome [109]. Another reported treatment intervention by a randomized, clinical trial was the use of phlebotomy in order to decrease liver stiffness and progression to cirrhosis for NAFLD patients with iron overload [110].
The assessment of the risk of liver fibrosis and the diagnostic strategy in accordance with the risk of progression to advanced fibrosis are presented in Figure 1.
The use of the FIB-4 index for the screening of advanced liver fibrosis is recommended for high-risk populations, such as those with type 2 diabetes and other metabolic risk factors [111]. FIB-4 is a well-validated index used to risk stratify patients with non-alcoholic fatty liver disease into high, indeterminate and low risk of developing cirrhosis. FIB-4 thresholds guide the PCP within liver fibrosis risk assessment in MASLD, as follows: a value below 1.3 represents a low risk (observation, consider re-evaluation in 2–3 years), between 1.3 and 2.67 indicates an indeterminate/”gray zone” (further investigation with second-line tests VCTE/FibroScan), and >2.67 indicates high risk (referral to hepatologist is recommended). In addition, these thresholds help primary care providers triage patients efficiently, potentially reducing unnecessary specialist referrals [112].
As mentioned before, in the case of a calculated value of FIB-4 > 1.3, guidelines recommend using a second test (e.g., NFS, ELF) to increase accuracy [113,114]. Usually, in primary care settings, the most effective strategy is using FIB-4 or NFS to identify low-risk patients (avoiding unnecessary referrals), then using elastography to confirm high-risk patients. In addition, the FIB-4 index and NFS are considered the most common and effective non-invasive tools used to screen for advanced fibrosis in patients with MASLD [115].
Thus, depending on the results when calculating the FIB-4 index, we could have the following categories of patients:
(a) Patients with FIB-4 who indicate a low risk of advanced liver fibrosis by FIB-4 or LSM: These patients should be re-evaluated every 1–3 years (depending on individual risk factors) and they should take measures to correct their lifestyle and keep their metabolic disorders under control.
(b) Patients with FIB-4 who indicate an indeterminate-to-high risk of advanced liver fibrosis: These patients are subsequently recommended to have liver stiffness measurement (LSM) by fibrosis measurements (e.g., vibration-controlled transient elastography—VCTE) or fibrosis-specific serum tests (depending on local availability).
Other serum biomarkers used to identify steatohepatitis include cytokeratin-18 (CK-18). The fragment CK-18 is linked to programmed hepatocyte damage and death, and its use for the diagnosis of MASH is currently being investigated. However, CK-18 has low specificity when used alone, whereas the combination of CK-18 with interleukin-6 (IL-6) and adiponectin was reported to have higher sensitivity and specificity. Also, a two-step approach, using CK-18 in conjunction with the FIB-4 index, significantly improves a MASH diagnosis [116,117].
The MAFLD Fibrosis Score (MFS) is another non-invasive tool designed to identify advanced liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease, outperforming older scores by using routine blood tests and clinical data like age, body mass index, AST, GGT, platelets, International Normalized Ratio (INR), and diabetes status to guide further assessment, potentially avoiding liver biopsies [118].
Nevertheless, professional training of medical staff is relevant and essential for the current situation. The consequences of not identifying and staging cases of chronic liver disease (viral, alcoholic, non-alcoholic) at an early stage progressively reduce the chances of cure for these patients and create future socio-economic pressures that will require substantial financial resources, which are impossible to assess now. Thus, continuous testing and early detection of chronic liver diseases are key determinants for the population and the socio-economic environment.

3.5. Further Research Directions

When assessing available diagnostic and monitoring options for highly prevalent chronic diseases, it is important to also acknowledge the costs that are associated with these options. At the same time, not all the tests and imaging techniques are currently available in every medical setting around the world, so their actual use may be limited. Further research should focus on assessing how the local availability and associated costs are influencing the spread and extensive use of NIT for chronic liver disease diagnostics and follow-up. In addition, there is a need for research on the validation and implementation of simple algorithms in real-world clinical practice (including in resource-limited countries), an analysis of the cost-effectiveness of such programs, and the development of educational modules for implementing screening and monitoring methods, dedicated specifically to PCP.

4. Conclusions

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently considered the most common chronic liver disease. With late diagnosis, MASLD represents an important cause that may lead to serious complications (liver cirrhosis and hepatocellular carcinoma), leading to significant healthcare costs and reduced quality of life.
In the primary care settings, patients display associated conditions (obesity, type 2 diabetes, high cholesterol), which are likely predisposing them to MASLD. The PCP has a central and significant role in early diagnosis of the patient with chronic liver disease and the subsequent follow-up, in order to send high-risk patients (with fibrosis/MASH) for specialist care.
Thus, it is very important that PCP make appropriate use of non-invasive tests that can complement or replace liver biopsy, which is considered the “gold standard”, but is an invasive method. Non-invasive tests have the advantage that they are easy to use and easy to apply and can evaluate the whole liver, unlike liver biopsy, which can only evaluate a liver fragment. Commonly used non-invasive tests for assessment of advanced liver fibrosis are represented by FIB-4, NFS, ELF tests and transient elastography. Most accurate non-invasive assessment is performed by imaging methods such as magnetic resonance elastography, and a combination of tests is the recommended approach for improving the diagnostic accuracy.

Author Contributions

Conceptualization, A.M.C., I.M.S. and M.M.N.; methodology, A.M.C., M.M.N. and R.T.; software, I.M.S. and R.T.; validation, C.S.P. and A.E.N.; formal analysis, A.M.C., I.M.S. and R.T.; investigation, A.M.C., A.E.N. and M.M.N.; resources, M.M.N., I.M.S., R.T., J.A. and S.M.G.; data curation, A.M.C., A.E.N., C.O. and S.M.A.; writing—original draft preparation, A.M.C., I.M.S. and M.M.N.; writing—review and editing, M.M.N., R.T. and S.M.A.; visualization, I.M.S., S.M.A., J.A. and S.M.G.; supervision, C.S.P., S.M.A., C.O. and A.E.N.; project administration, A.M.C., and C.S.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
ALTalanine Aminotransferase
ASTaspartate Aminotransferase
CK8cytokeratin 8 antibody
GGTgamma-glutamyl transferase
MASLDmetabolic dysfunction-associated fatty liver disease
NAFLDnon-alcoholic fatty liver disease
PCPprimary care physician
MASHmetabolic dysfunction-associated steatohepatitis
NITnon-invasive tests
MFSmetabolic-associated fatty liver disease fibrosis score
FIB-4fibrosis-4 index
LSMliver stiffness measurement
NFSnonalcoholic fatty liver disease fibrosis score
TEtransient elastography
MREmagnetic resonance elastography
NASNAFLD activity score
VCTEvibration-controlled transient elastography
ELF
MRI-PDFF		enhanced liver fibrosis
magnetic resonance imaging-derived proton density fat fraction

References

  1. World Health Organization. Combating Hepatitis B and C to Reach Elimination by 2030; WHO: Geneva, Switzerland, 2016; Available online: https://iris.who.int/bitstream/handle/10665/206453/WHO_HIV_2016.04_eng.pdf (accessed on 10 October 2025).
  2. World Health Organization. Global Health Sector Strategy on Viral Hepatitis, 2016–2021; WHO: Geneva, Switzerland, 2016; Available online: http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf (accessed on 10 October 2025).
  3. Matteoni, C.; Younossi, Z.; Gramlich, T.; Boparai, N.; Liu, Y.; Mccullough, A. Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity. Gastroenterology 1999, 116, 1413–1419. [Google Scholar] [CrossRef] [PubMed]
  4. Tholey, D. Metabolic Dysfunction–Associated Liver Disease (MASLD). In Merck Manual Professional Version. Available online: https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/metabolic-dysfunction-associated-liver-disease-masld. (accessed on 14 October 2025).
  5. Eslam, M.; Newsome, P.N.; Sarin, S.K.; Anstee, Q.M.; Targher, G.; Romero-Gomez, M.; Zelber-Sagi, S.; Wong, V.W.-S.; Dufour, J.-F.; Schattenberg, J.M.; et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J. Hepatol. 2020, 73, 202–209. [Google Scholar] [CrossRef] [PubMed]
  6. Chrysavgis, L.; Cholongitas, E. From NAFLD to MASLD: What does it mean? Expert Rev. Gastroenterol. Hepatol. 2024, 18, 217–221. [Google Scholar] [CrossRef] [PubMed]
  7. Le, M.H.; Yeo, Y.H.; Zou, B.; Barnet, S.; Henry, L.; Cheung, R.; Nguyen, M.H. Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach. Clin Mol Hepatol 2022, 28, 841–850. [Google Scholar] [CrossRef]
  8. Chan, W.; Chuah, K.; Rajaram, R.B.; Lim, L.; Ratnasingam, J.; Vethakkan, S.R. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review. J. Obes. Metab. Syndr. 2023, 32, 197–213. [Google Scholar] [CrossRef]
  9. Abdelhameed, F.; Kite, C.; Lagojda, L.; Dallaway, A.; Chatha, K.K.; Chaggar, S.S.; Dalamaga, M.; Kassi, E.; Kyrou, I.; Randeva, H.S. Non-invasive scores and serum biomarkers for fatty liver in the era of metabolic dysfunction-associated steatotic liver disease (MASLD): A comprehensive review from NAFLD to MAFLD and MASLD. Curr. Obes. Rep. 2024, 13, 510–531. [Google Scholar] [CrossRef]
  10. Bassal, T.; Basheer, M.; Boulos, M.; Assy, N. Nonalcoholic fatty liver disease—A concise review of noninvasive tests and biomarkers. Metabolites 2022, 12, 1073. [Google Scholar] [CrossRef]
  11. Cusi, K.; Budd, J.; Johnson, E.; Shubrook, J. Making Sense of the Nonalcoholic Fatty Liver Disease Clinical Practice Guidelines: What Clinicians Need to Know. Diabetes Spectr. 2024, 37, 29–38. [Google Scholar] [CrossRef]
  12. Bera, C.; Hamdan-Perez, N.; Patel, K. Non-invasive evaluation of liver fibrosis in patients with hepatitis B. J. Clin. Med. 2024, 13, 1046. [Google Scholar] [CrossRef]
  13. Celsa, C.; Veneziano, M.; Di Giorgio, F.M.; Cannova, S.; Lombardo, A.; Errigo, E.; Landro, G.; Simone, F.; Sinagra, E.; Calvaruso, V. Non-invasive diagnostic tests for portal hypertension in patients with HBV and HCV-related cirrhosis: A comprehensive review. Medicine 2024, 60, 690. [Google Scholar] [CrossRef]
  14. Sanyal, A.J.; Castera, L.; Wong, V.W.S. Non-invasive Assessment of Liver Fibrosis in NAFLD. Clin. Gastroenterol. Hepatol. 2023, 21, 2026–2039. [Google Scholar] [CrossRef] [PubMed]
  15. Westfall, E.C.; Jeske, R.; Bader, A.R. Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management, American Academy of Family Physicians. Available online: https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html (accessed on 24 October 2025).
  16. Song, R.; Li, Z.; Zhang, Y.; Zhang, Y.; Tan, J.; Chen, Z. Comparison of NAFLD, MAFLD, MASLD and pure-MASLD characteristics and mortality outcomes in United States adults. Liver Int. 2024, 44, 1051–1060. [Google Scholar] [CrossRef] [PubMed]
  17. Cusi, K.; Abdelmalek, M.F.; Apovian, C.M.; Balapattabi, K.; Bannuru, R.R.; Barb, D.; Bardsley, J.K.; Beverly, E.A.; Corbin, K.D.; ElSayed, N.A.; et al. Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) in People With Diabetes: The Need for Screening and Early Intervention. A Consensus Report of the American Diabetes Association. Diabetes Care 2025, 48, 1057–1082. [Google Scholar] [CrossRef] [PubMed]
  18. EASL—European Association for the Study of the Liver, Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis—2021 update. J. Hepatol. 2021, 75, 659–689. [CrossRef]
  19. Alnees, M.; Awwad, M.; Najajra, D.; Darwish, A.; Heih, O.; Al-Ali, T.; Abu Hamdeh, N.; Abdullah, A.; Ahmad, J.; Jarrar, K.; et al. Predictive factors for metabolic syndrome in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). BMC Gastroenterol. 2025, 25, 562. [Google Scholar] [CrossRef]
  20. Sterling, R.K.; Patel, K.; Duarte-Rojo, A.; Asrani, S.K.; Alsawas, M.; Dranoff, J.A.; Fiel, M.I.; Murad, M.H.; Leung, D.H.; Levine, D.; et al. AASLD—American Association for the Study of Liver Diseases, Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis. Hepatology 2024, 81, 321–357. [Google Scholar] [CrossRef]
  21. Lee, C.-M.; Yoon, E.L.; Kim, M.; Kang, B.-K.; Cho, S.; Nah, E.-H.; Jun, D.W. Prevalence, distribution, and liver fibrosis burden of different subtypes of steatotic liver disease in primary care. Hepatology 2024, 79, 1393–1400. [Google Scholar] [CrossRef]
  22. Castera, L.; Friedrich-Rust, M.; Loomba, R. Non-invasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology 2019, 156, 1264–1281. [Google Scholar] [CrossRef]
  23. Soresi, M.; Giannitrapani, L.; Cervello, M.; Licata, A.; Montalto, G. Non invasive tools for the diagnosis of liver cirrhosis. World J. Gastroenterol. 2014, 20, 18131–18150. [Google Scholar] [CrossRef]
  24. Wang, J.-L.; Jiang, S.-W.; Hu, A.-R.; Zhou, A.-W.; Hu, T.; Li, H.-S.; Fan, Y.; Lin, K. Non-invasive diagnosis of non-alcoholic fatty liver disease: Current status and future perspective. Heliyon 2024, 10, e27325. [Google Scholar] [CrossRef]
  25. Vidal-González, D.; Uribe, M.; Montalvo-Javé, E.E.; Nuño-Lámbarri, N. Assessment of non-alcoholic fatty fatty liver disease by non-invasive methods: Present and future perspectives. Rev. Med. Hosp. Gen. Méx. 2020, 83, 135–143. [Google Scholar] [CrossRef]
  26. Dyson, J.K.; Anstee, Q.M.; McPherson, S. Nonalcoholic fatty liver disease: A practical approach to diagnosis and staging. Frontline Gastroenterol. 2014, 5, 211–218. [Google Scholar] [CrossRef] [PubMed]
  27. Dennis, A. Quantitative imaging tests for nonalcoholic fatty liver disease: Which, when and why. Transl. Gastroenterol. Hepatol. 2023, 8, 1. [Google Scholar] [CrossRef]
  28. Rosato, V.; Masarone, V.; Aglitti, A.; Persico, M. Diagnostic conundrum in non-alcoholic fatty liver disease. Explor. Med. 2020, 1, 259–286. [Google Scholar] [CrossRef]
  29. Boursier, J.; Francque, S. Non-invasive Tests of Liver Fibrosis and Their Combination in NAFLD: From Selected Patients to Real-Life Populations. Hepatology 2019, 70, 1500–1502. [Google Scholar] [CrossRef]
  30. Chandra Kumar, C.V.; Skantha, R.; Chan, W.-K. Non-invasive assessment of metabolic dysfunction-associated fatty liver disease. Ther. Adv. Endocrinol. Metab. 2022, 13, 1–17. [Google Scholar] [CrossRef]
  31. Papastergiou, V.; Tsochatzis, E.; Burroughs, A.K. Non-invasive assessment of liver fibrosis. Ann. Gastroenterol. 2012, 25, 218–231. [Google Scholar]
  32. Cheng, J.K.; Wong, G.H. Advances in the diagnosis and treatment of liver fibrosis. Hepatoma Res. 2017, 3, 156–169. [Google Scholar] [CrossRef][Green Version]
  33. Kogachi, S.; Noureddin, M. Non-invasive Evaluation for Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis. Clin. Ther. 2021, 43, 455–472. [Google Scholar] [CrossRef]
  34. Estes, C.; Anstee, Q.M.; Arias-Loste, M.T.; Bantel, H.; Bellentani, S.; Caballeria, J.; Colombo, M.; Craxi, A.; Crespo, J.; Day, C.P.; et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J. Hepatol. 2018, 69, 896–904. [Google Scholar] [CrossRef]
  35. Younossi, Z.M.; Noureddin, M.; Bernstein, D.; Kwo, P.; Russo, M.; Shiffman, M.L.; Younes, Z.; Abdelmalek, M. Role of Noninvasive Tests in Clinical Gastroenterology Practices to Identify Patients With Nonalcoholic Steatohepatitis at High Risk of Adverse Outcomes: Expert Panel Recommendations. Am. J. Gastroenterol. 2021, 116, 254–262. [Google Scholar] [CrossRef] [PubMed]
  36. Bernstein, D.; Kovalic, A.J. Noninvasive assessment of fibrosis among patients with nonalcoholic fatty liver disease [NAFLD]. Metabol. Open 2022, 13, 100158. [Google Scholar] [CrossRef] [PubMed]
  37. Da Silva, L.C.M.; de Oliveira, J.T.; Tochetto, S.; de Oliveira, C.P.M.S.; Sigrist, R.; Chammas, M.C. Ultrasound elastography in patients with fatty liver disease. Radiol. Bras. 2020, 53, 47–55. [Google Scholar] [CrossRef] [PubMed]
  38. Somnay, K.; Wadgaonkar, P.; Sridhar, N.; Roshni, P.; Rao, N.; Wadgaonkar, R. Liver Fibrosis Leading to Cirrhosis: Basic Mechanisms and Clinical Perspectives. Biomedicines 2024, 12, 2229. [Google Scholar] [CrossRef]
  39. Castera, L.; Forns, X.; Alberti, A. Non-invasive evaluation of liver fibrosis using transient elastography. J. Hepatol. 2008, 48, 835–847. [Google Scholar] [CrossRef]
  40. Mikolasevic, I.; Orlic, L.; Franjic, N.; Hauser, G.; Stimac, D.; Milic, S. Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease—Where do we stand? World J. Gastroenterol. 2016, 22, 7236–7251. [Google Scholar] [CrossRef]
  41. Zenovia, S.; Stanciu, C.; Sfarti, C.; Singeap, A.M.; Cojocariu, C.; Girleanu, I.; Dimache, M.; Chiriac, S.; Muzica, C.M.; Nastasa, R.; et al. Vibration-Controlled Transient Elastography and Controlled Attenuation Parameter for the Diagnosis of Liver Steatosis and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease. Diagnostics 2021, 11, 787. [Google Scholar] [CrossRef]
  42. Beer, S.; Babel, J.; Martin, N.; Blank, V.; Wiegand, J.; Karlas, T. Non-invasive assessment of steatohepatitis indicates increased risk of coronary heart disease. PLoS ONE 2023, 18, e0286882. [Google Scholar] [CrossRef]
  43. Viganò, M.; Pugliese, N.; Cerini, F.; Turati, F.; Cimino, V.; Ridolfo, S.; Rocchetto, S.; Foglio, F.; Terrin, M.; La Vecchia, C.; et al. Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers. Int. J. Mol. Sci. 2022, 23, 12489. [Google Scholar] [CrossRef]
  44. Moini, M.; Onofrio, F.; Hansen, B.E.; Adeyi, O.; Khalili, K.; Patel, K. Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease. Sci. Rep. 2021, 11, 19275. [Google Scholar] [CrossRef]
  45. Elghannam, M.T.; Hassanien, M.H.; Elray, A.A.; Abu-Taleb, H.M.; Ameen, Y.A.; Elattar, G.M.; Turky, E.A.; Eltalkawy, M.D. Hepatic fibrosis in morbidly obese patients: Fibroscan accuracy. Explor. Dig. Dis. 2025, 4, 100575. [Google Scholar] [CrossRef]
  46. Caussy, C.; Chen, J.; Alquiraish, M.H.; Cepin, S.; Nguyen, P.; Hernandez, C.; Yin, M.; Bettencourt, R.; Cachay, E.R.; Jayakumar, S.; et al. Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients with Nonalcoholic Liver Disease. Clin. Gastroenterol. Hepatol. 2018, 16, 1974–1982. [Google Scholar] [CrossRef] [PubMed]
  47. Boursier, J.; Canivet, C.M.; Costentin, C.; Lannes, A.; Delamarre, A.; Sturm, N.; Le Bail, B.; Michalak, S.; Oberti, F.; Hilleret, M.-N.; et al. Impact of Type 2 Diabetes on the Accuracy of Noninvasive Tests of Liver Fibrosis With Resulting Clinical Implications. Clin. Gastroenterol. Hepatol. 2023, 21, 1243–1251. [Google Scholar] [CrossRef] [PubMed]
  48. Ito, T.; Nguyen, V.H.; Tanaka, T.; Park, H.; Yeh, M.L.; Kawanaka, M.; Arai, T.; Atsukawa, M.; Yoon, E.L.; Tsai, P.C.; et al. Poor diagnostic efficiency of noninvasive testing for advanced fibrosis in obese or younger than 60 years of age patients with diabetic NAFLD. Clin. Gastroenterol. Hepatol. 2023, 21, 1013–1022. [Google Scholar] [CrossRef]
  49. Pose, E.; Piano, S.; Thiele, M.; Fabrellas, N.; Tsochatzis, E.A.; Ginès, P. Moving diagnosis of liver fibrosis into the community. J. Hepatol. 2025, 83, 258–270. [Google Scholar] [CrossRef]
  50. Lupșor-Platon, M.; Stefănescu, H.; Mureșan, D.; Florea, M.; Szász, M.E.; Maniu, A.; Badea, R. Noninvasive assessment of liver steatosis using ultrasound methods. Med. Ultrason. 2014, 16, 236–245. [Google Scholar] [CrossRef]
  51. Golabi, P.; Sayiner, M.; Fazel, Y.; Koenig, A.; Henry, L.; Younossi, Z.M. Current complications and challenges in nonalcoholic steatohepatitis screening and diagnosis. Expert Rev. Gastroenterol. Hepatol. 2015, 10, 63–71. [Google Scholar] [CrossRef]
  52. Caussy, C.; Reeder, S.B.; Sirlin, C.B.; Loomba, R. Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials. Hepatology 2018, 68, 763–772. [Google Scholar] [CrossRef]
  53. Dulai, P.S.; Sirlin, C.B.; Loomba, R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J. Hepatol. 2016, 65, 1006–1016. [Google Scholar] [CrossRef]
  54. Kang, K.A.; Lee, S.R.; Jun, D.W.; Do, I.-G.; Kim, M.S. Diagnostic performance of a novel ultrasound-based quantitative method to assess liver steatosis in histologically identified nonalcoholic fatty liver disease. Med. Ultrason. 2023, 25, 7–13. [Google Scholar] [CrossRef]
  55. Chen, J.L.; Duan, S.J.; Xie, S.; Yao, S.K. Diagnostic accuracy of noninvasive steatosis biomarkers with magnetic resonance imaging proton density fat fraction as gold standard. World J. Radiol. 2025, 17, 104272. [Google Scholar] [CrossRef]
  56. Kavvadas, D.; Rafailidis, V.; Liakos, A.; Sinakos, E.; Partovi, S.; Papamitsou, T.; Prassopoulos, P. Quantitative Ultrasound for Hepatic Steatosis: A Systematic Review Highlighting the Diagnostic Performance of Ultrasound-Derived Fat Fraction. Diagnostics 2025, 15, 2640. [Google Scholar] [CrossRef] [PubMed]
  57. Caussy, C.; Johansson, L. Magnetic resonance-based biomarkers in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Endocrinol. Diabetes Metab. 2020, 3, e00134. [Google Scholar] [CrossRef] [PubMed]
  58. Wang, X.M.; Zhang, X.J.; Ma, L. Diagnostic performance of magnetic resonance technology in detecting steatosis or fibrosis in patients with non-alcoholic fatty liver disease: A meta-analysis. Medicine 2018, 97, E10605. [Google Scholar] [CrossRef] [PubMed]
  59. Lee, S.S.; Park, S.H. Radiologic evaluation of nonalcoholic fatty liver disease. World J. Gastroenterol. 2014, 20, 7392–7402. [Google Scholar] [CrossRef]
  60. Papagianni, M.; Sofogianni, A.; Tziomalos, K. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease. World J. Hepatol. 2015, 7, 638–648. [Google Scholar] [CrossRef]
  61. Piazzolla, V.A.; Mangia, A. Noninvasive Diagnosis of NAFLD and NASH. Cells 2020, 9, 1005. [Google Scholar] [CrossRef]
  62. Altamirano, J.; Qi, Q.; Choudhry, S.; Abdallah, M.; Singal, A.K.; Humar, A.; Bataller, R.; Borhani, A.A.; Duarte-Rojo, A. Non-invasive diagnosis: Non-alcoholic fatty liver disease and alcoholic liver disease. Transl. Gastroenterol. Hepatol. 2020, 5, 31. [Google Scholar] [CrossRef]
  63. Schreiner, A.D.; Zhang, J.; Durkalski-Mauldin, V.; Livingston, S.; Marsden, J.; Bian, J.; Mauldin, P.D.; Moran, W.P.; Rockey, D.C. Advanced liver fibrosis and the metabolic syndrome in a primary care setting. Diabetes Metab. Res. Rev. 2021, 37, e3452. [Google Scholar] [CrossRef]
  64. Park, H.; Yoon, E.L.; Ito, T.; Jo, A.J.; Kim, M.; Lee, J.; Kim, H.L.; Arai, T.; Atsukawa, M.; Kawanaka, M.; et al. Diagnostic Performance of the Fibrosis-4 Index and Nonalcoholic Fatty Liver Disease Fibrosis Score in Lean Adults With Nonalcoholic Fatty Liver Disease. JAMA Netw. Open. 2023, 6, e2329568, Erratum in: JAMA Netw. Open. 2023, 6, e2336365. https://doi.org/10.1001/jamanetworkopen.2023.36365. [Google Scholar] [CrossRef]
  65. Thallapureddy, K.; Twitchell, D.; Ott, K.; Pedicone, L.D.; Owo, C.; Kumar, N.; Gelfond, J.; Shankar, N.; Goros, M.; Kwok, D.; et al. The accuracy of FibroScan, FIB-4, and nonalcoholic fatty liver disease fibrosis score in predicting biopsy-defined fibrosis and steatosis across all fibrosis stages in patients with metabolic dysfunction associated steatotic liver disease. Medicine 2025, 104, e42016. [Google Scholar] [CrossRef] [PubMed]
  66. Park, C.C.; Nguyen, P.; Hernandez, C.; Bettencourt, R.; Ramirez, K.; Fortney, L.; Hooker, J.; Sy, E.; Savides, M.T.; Alquiraish, M.H.; et al. Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterology 2017, 152, 598–607.e2. [Google Scholar] [CrossRef] [PubMed]
  67. Mosaad, A.; Elalfy, H.; Amer, T.; Arafa, M. Transient Elastography and its Correlation with Biochemical Scores in patients with Metabolic associated fatty liver disease. Med. J. Viral Hepat. 2022, 6, 22–28. [Google Scholar] [CrossRef]
  68. Thong, V.D.; Quynh, B.T.H. Correlation of Serum Transaminase Levels with Liver Fibrosis Assessed by Transient Elastography in Vietnamese Patients with Nonalcoholic Fatty Liver Disease. Int. J. Gen. Med. 2021, 14, 1349–1355. [Google Scholar] [CrossRef]
  69. Wang, J.; Qin, T.; Sun, J.; Li, S.; Cao, L.; Lu, X. Non-invasive methods for evaluation of liver fibrosis in patients with non-alcoholic fatty liver disease. Front. Physiol. 2022, 13, 1046497. [Google Scholar] [CrossRef]
  70. Alkhouri, N.; McCullough, A.J. Non-invasive diagnosis of NASH and hepatic fibrosis within the NAFLD spectrum. Gastroenterol. Hepatol. 2012, 8, 661–668. [Google Scholar]
  71. Taylor, R.S.; Taylor, R.J.; Bayliss, S.; Hagström, H.; Nasr, P.; Schattenberg, J.M.; Ishigami, M.; Toyoda, H.; Wong, V.W.S.; Peleg, N.; et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020, 158, 1611–1625. [Google Scholar] [CrossRef]
  72. Harrison, S.A. Use of Noninvasive Tests (NITs) in Patients with Non-alcoholic Steatohepatitis (NASH). Gastroenterol. Hepatol. 2020, 16, 4–8. Available online: https://www.gastroenterologyandhepatology.net/supplements/noninvasive-tests-nits-in-the-management-of-nonalcoholic-steatohepatitis-nash/ (accessed on 6 November 2025).
  73. Loomba, R. Evolving Strategies for the Management of Non-alcoholic Steatohepatitis (NASH). Gastroenterol. Hepatol. 2020, 16, 9–13. Available online: https://www.gastroenterologyandhepatology.net/supplements/noninvasive-tests-nits-in-the-management-of-nonalcoholic-steatohepatitis-nash/ (accessed on 6 November 2025).
  74. Harrison, S.A.; Anstee, Q.M.; Loomba, R. Non-invasive Tests (NITs) in the Management of Non-alcoholic Steatohepatitis (NASH): A Q&A Discussion. Gastroenterol. Hepatol. 2020, 16, 13–14. Available online: https://www.gastroenterologyandhepatology.net/supplements/noninvasive-tests-nits-in-the-management-of-nonalcoholic-steatohepatitis-nash/ (accessed on 8 November 2025).
  75. National Institute for Health and Care Excellence. NICE Guidance. Non-Alcoholic Fatty Liver Disease (NAFLD): Assessment and Management (NG49). Available online: www.nice.org.uk/guidance/ng49 (accessed on 10 November 2025).
  76. Long, M.T.; Gandhi, S.; Loomba, R. Advances in non-invasive biomarkers for the diagnosis and monitoring of non-alcoholic fatty liver disease. Metabolism 2020, 111, 154259. [Google Scholar] [CrossRef] [PubMed]
  77. Wilkins, T.; Tadkod, A.; Hepburn, I.; Schade, R.R. Non-alcoholic Fatty Liver Disease: Diagnosis and Management. AFP 2013, 88, 35–42. [Google Scholar]
  78. Wattacheril, J.J.; Abdelmalek, M.F.; Lim, J.K.; Sanyal, A.J. AGA Clinical Practice Update on the Role of Non-invasive Biomarkers in the Evaluation and Management of Non-alcoholic Fatty Liver Disease: Expert Review. Gastroenterology 2023, 165, 1080–1088. [Google Scholar] [CrossRef] [PubMed]
  79. De Lédinghen, V.; Vergniol, J.; Capdepont, M.; Chermak, F.; Hiriart, J.B.; Cassinotto, C.; Merrouche, W.; Foucher, J.; le Bail, B. Controlled attenuation parameter (CAP) for the diagnosis of steatosis: A prospective study of 5323 examinations. J. Hepatol. 2014, 60, 1026–1031. [Google Scholar] [CrossRef] [PubMed]
  80. Li, G.; Zhang, X.; Zhang, X.; Lin, H.; Liang, L. Non-invasive tests of non-alcoholic fatty liver disease. Chin. Med. J. 2022, 135, 532–546. [Google Scholar] [CrossRef]
  81. Akshintala, D.; Chugh, R.; Amer, F.; Cusi, K. Nonalcoholic Fatty Liver Disease: The Overlooked Complication of Type 2 Diabetes; Feingold, K.R., Ahmed, S.F., Anawalt, B., Eds.; MDText.com, Inc.: South Dartmouth, MA, USA, 2000. Available online: https://www.ncbi.nlm.nih.gov/books/NBK544043/ (accessed on 10 November 2025).
  82. Frączek, J.; Sowa, A.; Agopsowicz, P.; Migacz, M.; Dylińska-Kala, K.; Holecki, M. Non-Invasive Tests as a Replacement for Liver Biopsy in the Assessment of MASLD. Medicina 2025, 61, 736. [Google Scholar] [CrossRef]
  83. Younossi, Z.M.; de Avila, L.; Petta, S.; Hagström, H.; Kim, S.U.; Nakajima, A.; Crespo, J.; Castera, L.; Alkhouri, N.; Zheng, M.-H.; et al. Global performance of non-invasive tests in MASLD: Insights from the G-MASLD study. Hepatology, 2025; in press. [Google Scholar] [CrossRef]
  84. Mózes, F.E.; Lee, J.A.; Vali, Y.; Alzoubi, O.; Staufer, K.; Trauner, M.; Paternostro, R.; E Stauber, R.; Holleboom, A.G.; van Dijk, A.-M.; et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: A meta-analysis of each participant’s data. Lancet Gastroenterol. Hepatol. 2023, 8, 704–713. [Google Scholar] [CrossRef]
  85. Novielli, F.; De Matteis, C.; Moschetta, A.; Crudele, L. Non-invasive assessment of liver fibrosis in MASLD: The need of sex-adjusted scores. Expert Rev. Gastroenterol. Hepatol. 2025, 19, 1081–1100. [Google Scholar] [CrossRef]
  86. Younossi, Z.M.; Paik, J.M.; Henry, L.; Pollock, R.F.; Stepanovaa, M.; Nader, F. Economic evaluation of non-invasive test pathways for high-risk metabolic dysfunction-associated steatotic liver disease (MASLD) in the United Kingdom (UK). Ann. Hepatol. 2025, 30, 101789. [Google Scholar] [CrossRef]
  87. Beyazal Polat, H.; Beyazal, M.; Arpa, M.; Kızılkaya, B.; Ayaz, T.; Gündoğdu, Ö.L.; Konur, K.; Polat, Z.; Beyazal Çeliker, F.; Atasoy, H. Exploring the Prevalence and Risk Factors of MASLD in Patients with Newly Diagnosed Diabetes Mellitus: A Comprehensive Investigation. J. Clin. Med. 2025, 14, 3513. [Google Scholar] [CrossRef]
  88. Chan, W.-K.; Petta, S.; Noureddin, M.; Goh, G.B.B.; Wong, V.W. Diagnosis and non-invasive assessment of MASLD in type 2 diabetes and obesity. Aliment. Pharmacol. Ther. 2024, 59, S23–S40. [Google Scholar] [CrossRef]
  89. Zou, H.; Ma, X.; Zhang, F.; Xie, Y. Comparison of the diagnostic performance of twelve non-invasive scores of fatty liver disease non-invasive scores associated with metabolic dysfunction. Lipids Health Dis. 2023, 22, 145. [Google Scholar] [CrossRef] [PubMed]
  90. Cathcart, J.; Barrett, R.; Bowness, J.S.; Mukhopadhya, A.; Lynch, R.; Dillon, J.F. Accuracy of Non-Invasive Imaging Techniques for the Diagnosis of MASH in Patients with MASLD: A Systematic Review. Liver Int. 2025, 45, e16127. [Google Scholar] [CrossRef] [PubMed]
  91. Jia, S.; Zhao, Y.; Liu, J.; Guo, X.; Chen, M.; Zhou, S.; Zhou, J. Magnetic Resonance Imaging-Proton Density Fat Fraction vs. Transient Elastography-Controlled Attenuation Parameter in Diagnosing Non-alcoholic Fatty Liver Disease in Children and Adolescents: A Meta-Analysis of Diagnostic Accuracy. Front. Pediatr. 2022, 9, 784221. [Google Scholar] [CrossRef] [PubMed]
  92. Yang, A.; Zhu, X.; Zhang, L.; Zhang, D.; Jin, M.; Lv, G.; Ding, Y. Evaluating the efficacy of 8 non-invasive models in predicting MASLD and progression: A prospective study. BMC Gastroenterol. 2024, 24, 365. [Google Scholar] [CrossRef]
  93. Sheikh, M.Y.; Younus, M.F.; Shergill, A.; Hasan, M.N. Diet and Lifestyle Interventions in Metabolic Dysfunction-Associated Fatty Liver Disease: A Comprehensive Review. Int. J. Mol. Sci. 2025, 26, 9625. [Google Scholar] [CrossRef]
  94. Fichez, J.; Mouillot, T.; Vonghia, L.; Costentin, C.; Moreau, C.; Roux, M.; Delamarre, A.; Francque, S.; Zheng, M.H.; Boursier, J. Non-invasive tests for fibrotic MASH for reducing screen failure in therapeutic trials. JHEP Rep. 2025, 7, 101351. [Google Scholar] [CrossRef]
  95. de Jong, V.D.; Alings, M.; Bruha, R.; Cortez-Pinto, H.; Dedoussis, G.V.; Doukas, M.; Francque, S.; Fournier-Poizat, C.; Gastaldelli, A.; Hankemeier, T.; et al. Global research initiative for patient screening on MASH (GRIPonMASH) protocol: Rationale and design of a prospective multicentre study. BMJ Open 2025, 15, e092731. [Google Scholar] [CrossRef]
  96. Nguyen, A.L.T.; Milley, K.; Druce, P.; Qama, A.; McNamara, M.; Wong, J.; Karnchanachari, N.; de Graaff, B. Surveillance for liver cancer in primary care: A systematic review of the evidence. Aust. J. Gen. Pract. 2023, 52, 801–807. [Google Scholar] [CrossRef]
  97. Wong, V.W.-S.; Wong, G.L.-H.; Chan, R.S.-M.; Shu, S.S.-T.; Cheung, B.H.-K.; Li, L.S.; Chim, A.M.-L.; Chan, C.K.-M.; Leung, J.K.-Y.; Chu, W.C.-W.; et al. Beneficial effects of lifestyle intervention in non- obese patients with non- alcoholic fatty liver disease. J. Hepatol. 2018, 69, 1349–1356. [Google Scholar] [CrossRef]
  98. Lemke, A.A.; Thompson, J.; Hulick, P.J.; Sereika, A.W.; Johnson, C.; Oshman, L.; Dunnenberger, H.M. Primary care physician experiences utilizing a family health history tool with electronic health record-integrated clinical decision support: An implementation process assessment. J. Community Genet. 2020, 11, 339–350. [Google Scholar] [CrossRef]
  99. Lekakis, V.; Papatheodoridis, G.V. Natural history of metabolic dysfunction-associated steatotic liver disease. Eur. J. Intern. Med. 2024, 122, 3–10. [Google Scholar] [CrossRef] [PubMed]
  100. Rinella, M.E.; Neuschwander-Tetri, B.A.; Siddiqui, M.S.; Abdelmalek, M.F.; Caldwell, S.; Barb, D.; Kleiner, D.E.; Loomba, R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 2023, 77, 1797–1835. [Google Scholar] [CrossRef] [PubMed]
  101. Iser, D.; Ryan, M. Fatty liver disease, A practical guide for GPs. Aust. Fam. Physician 2013, 42, 444–447. [Google Scholar] [PubMed]
  102. Wong, V.W.; Zelber-Sagi, S.; Cusi, K.; Carrieri, P.; Wright, E.; Crespo, J.; Lazarus, J.V. Management of NAFLD in primary care settings. Liver Int. 2022, 42, 2377–2389. [Google Scholar] [CrossRef]
  103. Mohamed-Mohamed, H.; Pardo-Moreno, T.; Jimenez-Palomares, M.; Perez-Ardanaz, B.; Sánchez-Lara, E.M.; Vazquez-Lara, M.D.; de La Mata-Fernandez, M.; García-Morales, V.; Ramos-Rodríguez, J.J. Impaired Glucose Tolerance and Altered Body Composition in Obese Young Adults: A Case–Control Study. Biomedicines 2025, 13, 1569. [Google Scholar] [CrossRef]
  104. Oancea, C.; Banu, C.; Ciobanu, L.P.; Nedelescu, M.; Aurelian, J.; Gȋță, C.D.; Aurelian, S.M. Serum liver markers associated with features of metabolic syndrome in the working-age population. Farmacia 2025, 73, 628–636. [Google Scholar] [CrossRef]
  105. Ramírez-Mejía, M.M.; Qi, X.; Abenavoli, L.; Romero-Gómez, M.; Eslam, M.; Méndez-Sánchez, N. Metabolic dysfunction: The silenced connection with fatty liver disease. Ann. Hepatol. 2023, 28, 101138. [Google Scholar] [CrossRef]
  106. Diaz, L.A.; Arab, J.P.; Idalsoaga, F.; Perelli, J.; Vega, J.; Dirchwolf, M.; Carreño, J.; Samith, B.; Valério, C.; Moreira, R.O.; et al. Updated recommendations for the management of metabolic dysfunction–associated steatotic liver disease (MASLD) by the Latin American working group. Ann. Hepatol. 2025, 30, 101903. [Google Scholar] [CrossRef]
  107. Arab, J.P.; Dirchwolf, M.; Álvares-Da-Silva, M.R.; Barrera, F.; Benítez, C.; Castellanos-Fernandez, M.; Castro-Narro, G.; Chavez-Tapia, N.; Chiodi, D.; Cotrim, H.; et al. Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease. Ann. Hepatol. 2020, 19, 674–690. [Google Scholar] [CrossRef] [PubMed]
  108. Simancas-Racines, D.; Annunziata, G.; Verde, L.; Fascì-Spurio, F.; Reytor-González, C.; Muscogiuri, G.; Frias-Toral, E.; Barrea, L. Nutritional Strategies for Battling Obesity-Linked Liver Disease: The Role of Medical Nutritional Therapy in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Management. Curr. Obes. Rep. 2025, 14, 7. [Google Scholar] [CrossRef] [PubMed]
  109. Jazayeri, M.; Zarrin, R.; Mohammadi, A.; Pashaei, M.R.; Ahmadpour, S. Effects of gluten-free diet on metabolic syndrome components and anthropometric indices in patients with nonalcoholic fatty liver disease: An open-label randomized clinical trial. Arab. J. Gastroenterol. 2025; in press. [Google Scholar] [CrossRef] [PubMed]
  110. Hormati, A.; Khanyabi, A.; Ahmadpour, S.; Alemi, F.; Sarkeshikian, S.S.; Afifian, M.; Mohammadbeig, A.; Ghadir, M.R. Outcome of Phlebotomy on Improvement of Liver Enzymes and Steatosis in Non-Alcoholic Fatty Liver Disease: A Randomized, Controlled Trial. J. Adv. Med. Biomed. Res. 2022, 30, 493–500. [Google Scholar] [CrossRef]
  111. Canivet, C.M.; Boursier, J. Screening for Liver Fibrosis in the General Population: Where Do We Stand in 2022? Diagnostics 2022, 13, 91. [Google Scholar] [CrossRef]
  112. Eslam, M.; Fan, J.-G.; Yu, M.-L.; Wong, V.W.-S.; Cua, I.H.; Liu, C.-J.; Tanwandee, T.; Gani, R.; Seto, W.-K.; Alam, S.; et al. 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. Hepatol. Int. 2025, 19, 261–301. [Google Scholar] [CrossRef]
  113. Chen, M.; Guo, C.; Ouyang, K.; Liu, N. Diagnostic role of the fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score as a noninvasive tool for liver fibrosis scoring. Medicine 2024, 103, e40214. [Google Scholar] [CrossRef]
  114. Kang, Y.-W.; Baek, Y.-H.; Moon, S.-Y. Sequential Diagnostic Approach Using FIB-4 and ELF for Predicting Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease. Diagnostics 2024, 14, 2517. [Google Scholar] [CrossRef]
  115. Park, H.; Yoon, E.L.; Kim, M.; Lee, J.; Kim, J.H.; Cho, S.; Jun, D.W.; Nah, E.H. Comparison of diagnostic performance between FIB-4 and NFS in metabolic-associated fatty liver disease era. Hepatol. Res. 2022, 52, 247–254. [Google Scholar] [CrossRef]
  116. Zhang, X.; Li, J.; Jiang, L.; Deng, Y.; Wei, L.; Li, X. Serum Cytokeratin-18 levels as a prognostic biomarker in advanced liver disease: A comprehensive meta-analysis. Clin. Exp. Med. 2024, 24, 160. [Google Scholar] [CrossRef]
  117. Tadokoro, T.; Kawanaka, M.; Takahashi, H.; Aishima, S.; Zhao, W.; Yano, R.; Takuma, K.; Nakahara, M.; Oura, K.; Fujita, K.; et al. A Noninvasive Method of Diagnosing Metabolic Dysfunction-Associated Steatohepatitis Using Cytokeratin-18 Fragment and FIB-3 Index. Diagnostics 2025, 15, 1023. [Google Scholar] [CrossRef]
  118. Cheung, J.T.K.; Zhang, X.; Wong, G.L.; Yip, T.C.; Lin, H.; Li, G.; Leung, H.H.; Lai, J.C.; Mahadeva, S.; Mustapha, N.R.N.; et al. MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease. Aliment. Pharmacol. Ther. 2023, 58, 1194–1204. [Google Scholar] [CrossRef]
Gastroent 17 00011 g001
Figure 1. The diagnostic strategy in accordance with the risk of progression to advanced fibrosis assessed by (FIB-4) and metabolic-associated fatty liver disease fibrosis score (MFS). (a) Low and (b) indeterminate or high.
Figure 1. The diagnostic strategy in accordance with the risk of progression to advanced fibrosis assessed by (FIB-4) and metabolic-associated fatty liver disease fibrosis score (MFS). (a) Low and (b) indeterminate or high.
Gastroent 17 00011 g001
Table 1. Advantages and disadvantages of using non-invasive tests.
Table 1. Advantages and disadvantages of using non-invasive tests.
Non-Invasive TestsAdvantagesDisadvantages
Serum biomarkers/algorithms
Fibrosis-4 index (FIB-4)Highly accessible, low-cost tools ideal, for primary care to rule out advanced fibrosisLess reliable for those under 35 or over 65 years
Suboptimal accuracy for mild-to-moderate fibrosis
NAFLD Fibrosis Score (NFS)High availabilityLower performance in diabetic patients
Elastography and imaging methods
Transient Elastography (TE)Validated, reproducible.
Offers quantitative stiffness measurements, reducing subjective interpretation.
Moderate accuracy for fibrosis staging		Obesity, acute inflammation, ascites, or cholestasis can affect results
Magnetic Resonance Elastography (MRE)Whole-liver assessment
High accuracy		Not suitable for routine primary care screening due to time and cost.
Iron overload limitations
Table 2. Non-invasive serum biomarkers/scores—components, cut-off values, and their clinical use and relevance [11,18,36].
Table 2. Non-invasive serum biomarkers/scores—components, cut-off values, and their clinical use and relevance [11,18,36].
ScoreComponentsCut-Off ValuesClinical Use and Relevance
Fibrosis-4 index (FIB-4)Age, AST, ALT, platelet countLow risk of advanced fibrosis: <1.3
Indeterminate risk: 1.3–2.67
High risk: >2.67		Widely used first-line screening for advanced fibrosis. For patients over 65 years, a higher cut-off (e.g., 2.0 or 1.72) may be more appropriate to improve specificity.
AST to Platelet Ratio Index (APRI)AST, platelet countLow risk for advanced fibrosis: <0.5
Indeterminate risk: 0.5–1.5
High risk: >1.5		Used to assess fibrosis. Primarily validated for viral hepatitis (HCV/HBV).
FibroTestα2-macroglobulin, haptoglobin, Apo A1, GGT, Total Bilirubin (+Age, Sex, ALT)High risk for advanced fibrosis: >0.58
Likely excludes advanced fibrosis: <0.58		High accuracy for detecting significant fibrosis and cirrhosis.
NAFLD Fibrosis Score (NFS)Age, BMI, hyperglycemia, AST/ALT ratio, platelet count, albuminLikely excludes advanced fibrosis: <−1.455
Intermediate risk: −1.455–0.675
High risk: >0.675		Specifically for metabolic dysfunction-associated steatotic liver disease (MASLD).
Enhanced Liver Fibrosis Test (ELF)Hyaluronic acid, PIIINP, TIMP-1Low risk: <7.7
Intermediate risk: 7.7–9.8 or 10.35
High risk: >9.8 or 10.35		Measures serum markers of liver matrix turnover
Has a lower false-positive rate than FIB-4
ALT (alanine aminotransferase); AST (aspartate aminotransferase); BMI (body mass index); GGT (gamma-glutamyl transferase); Apo A1 (Apolipoprotein A1); PIIINP (procollagen type III); and TIMP-1 (tissue inhibitor of metalloproteinase 1).
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Constantin, A.M.; Nedelescu, M.M.; Tatar, R.; Pop, C.S.; Neculau, A.E.; Aurelian, S.M.; Oancea, C.; Aurelian, J.; Gîdei, S.M.; Stoian, I.M. The Role of Primary Care and Noninvasive Testing in the Early Diagnosis of Metabolic-Associated Steatotic Liver Disease (MASLD). Gastroenterol. Insights 2026, 17, 11. https://doi.org/10.3390/gastroent17010011

AMA Style

Constantin AM, Nedelescu MM, Tatar R, Pop CS, Neculau AE, Aurelian SM, Oancea C, Aurelian J, Gîdei SM, Stoian IM. The Role of Primary Care and Noninvasive Testing in the Early Diagnosis of Metabolic-Associated Steatotic Liver Disease (MASLD). Gastroenterology Insights. 2026; 17(1):11. https://doi.org/10.3390/gastroent17010011

Chicago/Turabian Style

Constantin, Alina Mihaela, Mirela Maria Nedelescu, Raluca Tatar, Corina Silvia Pop, Andrea Elena Neculau, Sorina Maria Aurelian, Corina Oancea, Justin Aurelian, Sandra Monica Gîdei, and Irina Mihaela Stoian. 2026. "The Role of Primary Care and Noninvasive Testing in the Early Diagnosis of Metabolic-Associated Steatotic Liver Disease (MASLD)" Gastroenterology Insights 17, no. 1: 11. https://doi.org/10.3390/gastroent17010011

APA Style

Constantin, A. M., Nedelescu, M. M., Tatar, R., Pop, C. S., Neculau, A. E., Aurelian, S. M., Oancea, C., Aurelian, J., Gîdei, S. M., & Stoian, I. M. (2026). The Role of Primary Care and Noninvasive Testing in the Early Diagnosis of Metabolic-Associated Steatotic Liver Disease (MASLD). Gastroenterology Insights, 17(1), 11. https://doi.org/10.3390/gastroent17010011

Article Metrics

Back to TopTop