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Cheng et al. Advances in liver fibrosis
management in order to prevent further liver damage. is obtained. Sampling error can be minimized by either
This article focuses on the up-to-date approaches for obtaining a specimen of sufficient size (at least 2 cm
diagnosis, both invasive and non-invasive, and latest in length) or from different lobes, which may not be
development in treatments of liver fibrosis, particularly feasible all the time. [14] Well reported complications
in NAFLD patients for whom a handful of clinical trials from liver biopsy examination include pain, [15]
are currently ongoing. bleeding such as wound bleeding, intraperitoneal
hemorrhage, hemobilia or hemothorax, [15] transient
DIAGNOSIS OF LIVER FIBROSIS acute hypotension or vasovagal syncope. [16] Fatal
complications like uncontrolled bleeding, bacteremia
There are varieties of methods for making the diagnosis and sepsis are rare but still possible. [17] In patients with
of liver fibrosis, which can be classified into invasive HCC, liver biopsy also carries a risk of spreading the
and non-invasive approaches. cancer cells. [18]
Invasive approach - liver biopsy examination Non-invasive approach
For invasive approach, it refers to liver biopsy Radiological assessments are either ultrasonographic-
examination, which provides liver tissue for based [e.g. transient elastography, acoustic radiation
a histopathological assessment of liver. Liver force impulse (ARFI) imaging and shear wave
biopsy examination can be done percutaneously, elastography (SWE)] or magnetic resonance (MR)-
transvenously (either transjugularly or transfemorally), based [i.e. MR elastography (MRE)].
or surgically (open or laparoscopic operations). [6]
Indications for liver biopsy are for diagnostic and/or Ultrasonographic based
prognostic purposes, as well as for treatment planning. [7] Transient elastography
Transient elastography (Fibroscan , Echosens, Paris,
®
Liver biopsy is still regarded as the gold standard France) assesses liver stiffness measurement (LSM)
for liver fibrosis assessment in various chronic liver by transmitting shear wave followed by ultrasound wave
diseases. [8,9] Apart from general histological staging, through a probe putting on the skin overlying the liver
liver biopsy can also provide information concerning parenchyma. The velocity of the shear wave passing
morphometry, which can provide additional information through the liver parenchyma is calculated by Doppler
on the distribution and the exact quantity of liver technique. The higher the velocity, the stiffer the liver
fibrosis. [10] A recent quantitative tool called qFibrosis parenchyma is. As mentioned by the manufacturer, for
utilized 87 parameters aiming for combining the results an examination to be considered as reliable, it requires
of collagen patterns, collagen architectural features at least 10 successful attempts and the ratio of
and statistical analysis of features of respective interquartile range to median of those measurements
collagen patterns into a single index. This requires an should be less than 0.3. [19] LSM reflects the degree
unstained biopsy sample for the automated analysis of liver fibrosis. [20] It can even identify those with no
of liver fibrosis staging. [11] All these evidences illustrate or minimal fibrosis and differentiate them from those
that liver biopsy plays an important role in the diagnosis with severe fibrosis or cirrhosis. [21] It has been proved
of liver fibrosis. useful across different liver disease entity (e.g. chronic
hepatitis B and C, autoimmune hepatitis). [22] However,
Apart from liver fibrosis staging, liver biopsy can provide LSM by transient elastography is found to be less
different information important for the management reliable in obese patients. [23,24] It can be less accurate
of the clinicians. For example, in cases of NAFLD, in certain situation, e.g. severe acute exacerbation of
the degree of necroinflammation and steatosis can hepatitis, [25] post-treatment fibrosis stages in CHB [26] or
be determined by liver biopsy so corresponding chronic hepatitis C (CHC) patients. [27]
management can be provided for this potentially
reversible situation. [12] Liver biopsy is also helpful in ARFI imaging
diagnosing adverse drug reaction and classification ARFI is another technique for estimating liver fibrosis. It
of liver tumors. [13] Yet, the most common reason for is implemented in current ultrasound scanner, without
conducting a liver biopsy is for assessing the liver acquirement of external equipment. The conventional
fibrosis in patients with chronic viral hepatitis and ultrasound probe automatically produces an acoustic
NAFLD. “push” pulse for generating shear-wave which passes
through the tissue. The wave propagation speed is
Such a direct and useful method bears quite a few assessed. Again, higher the speed, higher the liver
limitations. Sampling error is a major limitation for liver stiffness measurement is. [28,29] There are several
biopsy as only 1/50,000 of the whole liver parenchyma advantages for ARFI. As it is a function of the ultrasound
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