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Cheng et al. Advances in liver fibrosis

(3G), which does not take hyaluronate into account. biochemical methods to increase the accuracy in
Therefore, the cost has been reduced but with similar determining the degree of fibrosis. Both types of
effectiveness. [64] FibroMeter , both 2G and 3G, has methods can play a supplementary role to each other.
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been shown with high fibrosis classification accuracy. [65] For example, the performance of ELF improves with
Besides, it appears to have a good predictive value the assistance of transient elastography. [80] With the
towards the occurrence of severe fibrosis in those use of ELF-LSM algorithm, a significant proportion of
with NAFLD [66] and chronic hepatitis B or C. [67] Even patients can avoid liver biopsy. [69] Another example
though the hyaluronate-free FibroMeter 3G is in use is Hui Index and transient elastography. Since LSM
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nowadays, the cost is still high compared to common result is confounded in patients with elevated ALT,
parameters (e.g. FIB-4 or NFS). [68] Hui index, a score independent of ALT level, is a good
choice for supplementation of transient elastography.
Enhanced liver fibrosis Studies have shown that the combinations can help
Enhanced liver fibrosis (ELF) score is an algorithm predict hepatic event-free survival in chronic hepatitis
consists of 3 direct markers in blood, namely procollagen B patients. [81] Another combination for assessment of
III amino terminal peptide (PIIINP), hyaluronic acid liver fibrosis in CHB patients is Forns index (another
and tissue inhibitor of metalloproteinase I (TIMP-I). [69] ALT-free index)-LSM algorithm. [82] FibroMeter and
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ELF can be a good prognostic factor for the clinical transient elastography combined together can help
outcomes of patients with chronic liver disease. The improve diagnostic accuracy and avoid liver biopsy in
increase in one point in ELF can lead to doubling of CHC patients. [83] For the diagnosis of cirrhosis in CHC
the risk of clinical outcomes in patients, especially patients, using the algorithm FibroTest and transient
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liver-related clinical outcomes. [70] ELF results are even elastography improves the performance. However, this
similar when using fresh blood or cryopreserved blood. combination does not show extra benefit for diagnosis
Therefore, it has a high predictive value for identifying of advanced fibrosis compared to the sole use of
patients with risk to develop progressive chronic liver FibroTest .
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disease at an early stage. [71] It is sensitive in identifying
advanced fibrosis or cirrhosis, but not for lower fibrosis Non-invasive tests - from diagnostic to
stage. [72,73] Meanwhile, it is noted that different factors prognostic
can influence the result of ELF score, with the most Portal hypertension and related complications
significant factor being age. [74] Other factors include The role of all these non-invasive tests is moving from
low CD4+ T-cell count, co-existing extra-hepatic
fibrosis, etc. [75] Therefore, the results of ELF should be diagnostic to prognostic. They are useful to predict
interpreted with particular clinical context. liver-related complications and hence the prognosis
of patients with chronic liver diseases. For example,
Novel serum markers a LSM with 13.6 kPa can be a predictive value the
There are some other novel serum fibrosis markers presence of portal hypertension. [85] Combing LSM with
that raise the attention of the clinicians. Glycosylated APRI or Fibroindex increases the sensitivities for portal
Wisteria floribunda agglutinin-positive Mac-2 binding hypertension predication. [85] Liver stiffness with ARFI
protein (WFA -M2BP) is a marker which is related to greater than 2.34 m/s indicates a poor liver reserve
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fibrosis-related glyco-alteration. It can be measured by function. [86] Assessment of spleen loss modulus by
a glycan-based immunoassay, FastLec-Hepa. A cut- MRE is a good method for recognizing patients with
off index would be calculated based on the measured severe portal hypertension or esophageal varices
value. [76] It is found to be useful for detecting early stages with high bleeding tendency. [87] Combing LSM and
of fibrosis in chronic hepatitis B patients in a recent spleen stiffness measurement (SSM) may exclude
study. [77] Another novel marker, YKL-40 (CHI3L1), is an the presence of large esophageal varices with high
emerging inflammation biomarker which was shown sensitivity [88] and can be adopted in the risk stratification
to be related to the early stage of liver fibrosis. [78] In and variceal screening strategy. [89]
NAFLD patients, macrophages in liver were showed to
express YKL-40. This makes YKL-40 be possible as a Survival
biomarker as liver fibrosis. [79] However, further studies Survival for chronic liver disease can be predicted
need to be conducted to show the effectiveness and using non-invasive test. LSM [90,91] or FibroTest has
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impact of both biomarkers on making the diagnosis or a high prognostic value for patients with chronic viral
management of patients with liver fibrosis due to any hepatitis. [92,93] The usage of LSM and Hui index for
chronic liver diseases. predicting hepatic-event free survival in CHB patients
is shown to be accurate. [81] FibroMeter is shown to
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Combination of different approaches be useful for assessment of liver prognosis in CHC
It is common for using both radiological and patients with milder disease. [94] ELF score can be used
160 Hepatoma Research ¦ Volume 3 ¦ August 08, 2017