Liver biopsy is currently the reference standard for the identification and staging of liver fibrosis, but its role has significantly declined because of several limitations such as invasiveness of the procedure, sampling errors, and intra- and interobserver variability.
Liver fibrosis is staged on the basis of severity: no fibrosis (FO), mild fibrosis (F1), significant fibrosis (F2), advanced fibrosis (F3), cirrhosis) (F4).
The advent of non-invasive tests (NITs) has now replaced the role of liver biopsy.
These approaches can overcome the limitations of liver biopsy.
Non-invasive liver tests allow the diagnosis of advanced fibrosis or cirrhosis in patients before liver complications develop.
The increasing occurrence of steatotic liver disease in up to 30% of the adult population worldwide has made these tests essential for risk stratification.
Imaging-based elastography and serum biomarkers are currently the two main NITs for liver fibrosis staging.
Assessments include serology based tests such as the fibrosis-4 (FYB-4) index, NAFLD fibrosis score (NFS), and enhanced liver fibrosis (ELF), or imaging based test such as vibration controlled transient elastography (VCTE) and magnetic resonance elastography (MRE).
FIB-4 index combines patient age with a basic laboratory tests aspartate amino transferase, ALT, and platelet count to predict liver fibrosis and cirrhosis.
FIB-4 is recommended as an initial risk stratification tool (followed by VCTE or ELF) in patients at risk for MASLD.
FIB-4 has good sensitivity and a negative predictive value greater than 90% to rule out advanced fibrosis when used in low risk populations.
The use of FIB-four to screen for advanced fibrosis is supported by several studies with an FIB-4 of less than 1.3 reliably ruling out advanced fibrosis.
The NFL score combines patient characteristics of age, body mass index, and basic laboratory tests of glucose, aspartate aminotransferase, ALT, albumin, and platelet count.
The ELF scoring system is based on serum tests of inflammatory markers, namely hyaluronic acid, procollagen III, amino terminal peptide, and tissue inhibitor of matrix metalloproteinase 1.
The Enhanced Liver Fibrosis (ELF) score is a non-invasive test that combines three serum biomarkers: hyaluronic acid, procollagen III amino-terminal peptide, and tissue inhibitor of metalloproteinase 1.
It is used to assess the degree of liver fibrosis in patients with chronic liver diseases, including chronic hepatitis C virus (HCV) infection.
It is calculated using an algorithm that integrates the levels of these biomarkers to provide a single numerical value indicative of fibrosis severity.
In comparison to the Aspartate Aminotransferase to Platelet Ratio Index (APRI) score, the ELF score generally demonstrates superior diagnostic accuracy for liver fibrosis.
APRI is mainly used in patient with viral hepatitis for the diagnosis of either significant fibrosis, or cirrhosis.
Studies have shown that the ELF score has a higher area under the receiver operating characteristic curve compared to APRI, indicating better performance in distinguishing between different stages of fibrosis.
The American Gastroenterological Association (AGA) has noted that while APRI is useful, other non-invasive methods like transient elastography (TE) and ELF score may offer better diagnostic performance for liver fibrosis.
In summary, the ELF score is generally more accurate than the APRI score in assessing liver fibrosis, particularly in patients with chronic hepatitis C virus infection.
Liver stiffness can be measured by a variety of ultrasound based elastography techniques with magnetic resonance elastography.
VCTE is a non-invasive ultrasound based diagnostic modality that detects liver fibrosis and cirrhosis through liver stiffness measurement.
VCTE uses pulse echo ultrasound acquisition to follow the propagation of a shear wave in the liver parenchyma, and to measure its velocity, the latter being directly related to tissue stiffness, the stiffer the tissue, the faster the shear wave propagates.
VCTE accuracy is limited by operator experience, morbid obesity, narrow intercostal space and ascites.
MRE is based on magnetic resonance technique using sheer wave to detect liver fibrosis with very high accuracy.
A VCTE cutoff score of less than 7.7 kPa excludes advanced fibrosis and is 100% sensitive: 100% negative predictive value and leads to 45% fewer liver biopsies.
There are significantly strong positive correlations of liver steatosis values assessed among the three elastography techniques.
There is a moderate-to-strong correlation between imaging methods and non-invasive serum fibrosis scores.
A liver stiffness measurement of less than 15 kPa combined with a platelet count higher than 150,000 per cubic millimeter can rule our clinically significant portal hypertension with greater than 90% sensitivity.
A liver stiffness measurement greater than 25kPa is highly specific for clinically significant portal hypertension in patients with cirrhosis, and treatment with carvedilol may be considered.
In patients with intermediate liver stiffness measurements 15 to 25kPa combining liver, stiffness measurement, and platelet count, can be used to identify patients more likely to have clinically significant portal hypertension.
Non-invasive tests for liver fibrosis are more desirable and used to improve the diagnosis and prognostication of chronic liver disease of various etiologies.
However, data on the correlations among three elastography techniques in patients with CLD patients are scarce.
MRE can be considered the most accurate NIT for detecting liver fibrosis, especially in advanced fibrosis and cirrhosis.
MRE outperforms TE and SWE in detecting stage 4 liver fibrosis in patients with NAFLD.
MRE has an advantage over TE or SWE in that it visualizes the whole liver rather than just small hepatic areas.
MRE out performs ultrasound illest autography for ruling in earliest stages of fibrosis of F2 or greater, but has similar accuracy for ruling in advanced fibrosis of F3 and F4.
MRE is currently accepted as the most precise NIT for evaluating liver fibrosis, however, ,TE, SWE, APRI, and FIB-4 had a good correlation and can be used particularly in centers with limited availability of MRE.
Liver necroinflammation influences the increase in liver stiffness as evaluated by imaging-based elastography.
Viral eradication results in a reduced proportion of patients with advanced fibrosis by 13%, 28%, and 11% based on TE, SWE, and MRE, respectively.
The reduction of liver stiffness values and serum fibrosis scores after viral eradication were partly caused by the decrease in liver inflammation rather than liver fibrosis regression.
TE, SWE, and MRE have been extensively validated in a large number of studies.
In conclusion, TE, SWE, MRE, APRI, and the FIB-4 index have a good correlation.
Using MRE as the reference standard, all studied NITs have high diagnostic accuracies for detecting liver fibrosis.