Non invasive markers of hepatic fibrosis

Non-invasive Markers of Hepatic Fibrosis

Basic Anatomy:

.Parenchymal  cell or Hepatocyte that  comprise about 60% (171,000  cells in each milligram of normal human liver)

•The sinusoidal cells comprise the rest (31,000 cells in each milligram of  human liver )

 (endothelial cells, Kupffer cells, hepatic   stellate cells and pit cells)

 

Normal liver has a connective tissue matrix which
includes:

.Type IV (non - fibrillary) collagen

•Glycoproteins(including fi bronectin and laminin)

•Proteoglycans(including heparan sulphate)

 

 Definition of Cirrhosis:

Cirrhosis is characterised by diffuse hepatic fibrosis and nodule formation.

 

 Pathogenic mechanisms in hepatic fibrosis

 

•Stellate cell activation occurs under the influence of cytokines

•Once stellate cells become activated, they can perpetuate their own activation

•Normally- Synthesis Type  IV collagen

•When Activated-Synthesis  Type I collagen

 

 Stages Of Fibrosis

 

 

 Detection of Fibrosis:

 1. Invasive Method-liver biopsy
  2. Noninvasive Methods

 Non invasive Markers are

Serum Markers

            Direct(Class I)

            Indirect(Class II)

  Imaging

 

 Features of an ideal marker of liver fibrosis:

 

•Liver specific

•◈Levels not influenced by alterations in liver, renal, or reticuloendothelial function

•◈Measurement of one or more of the following processes: Stage of fibrosis, imbalance of activity of ECM (fibrogenesis vs. degradation)

•◈Easy to perform

 

 

 Commonl used non patented formula;

•AST to Platelet Ratio (APRI) = AST (/ULN)/platelet (10⁹/L) x 100

•Forns Index = 7.811 - 3.131 x ln(platelet count) + 0.781 x ln(GGT) + 3.467 x ln(age) - 0.014 x (cholesterol)

•Lok index = -5.56 - 0.0089 x platelet (10³/mm3) + 1.26 x AST/ALT ratio = 5.27 x INR

•Goteborg University Cirrhosis Index (GUCI) = AST x prothrombin - INR x 100/platelet

•Fibroindex = 1.738 - 0.064 x (platelets [10⁴/mm3]) + 0.005 x (AST [IU/L]) + 0.463 x (gamma globulin [g/dl])

 •Hui score = 3.148 + 0.167 x BMI + 0.088 x bilirubin - 0.151 x albumin - 0.019 x platelet 

•Zeng score = -13.995 + 3.220 log(α-2-macroglobulin) + 3.096 log(age) + 2.254 log(GGT) + 2.437 log(hyaluronate)

 •NAFLD Fibrosis Score (NFS) = (-1.675 + 0.037 x age (yr) + 0.094 x BMI (kg/m²) + 1.13 x IFG/diabetes (yes = 1, no = 0) + 0.99 x AST/ ALT ratio - 0.013 x platelet count (x10⁹/L) - 0.66 x albumin [g/dl])  

•BARD score (BMI ≥28 = 1; AST/ALT ratio ≥0.8 = 2; diabetes = 1; score ≥2, odds ratio for advanced fibrosis = 17)

 

There are some patented formula such as Fibro test,Hepascore,ELF etc. 

 

                 Imaging

 

•Conventional ultrasound: Volume, Nodularity, Echotexture, portal hypertension with its secondary signs of splenomegaly, ascites and portosystemic venous collaterals

    US can identify diffuse parenchymal disease, but cannot

    reliably distinguish fat from fibrosis

•Conventional CT and MRI have higher specificity and

sensitivity than conventional ultrasound for the diagnosis of cirrhosis

 

 Liver elastography techniques:

 

•Non Invasive

•Elastographic methods of the liver can be done using US waves or MRI

 

 

USG baed Elasography:

1. Strain elastography (or quasi-static elastography):

2. Shear waves elastography (SWE):

(a) Transient elastography (TE; FibroScan)

(b) Point shear wave elastography (SWE) using acoustic

radiation force impulse (ARFI) quantification including

virtual touch quantification (VTQ) from Siemens and ElastPQ from Philips.

(c) 2D real-time shear wave elastography—supersonic

shear imaging (SSI), the Aixplorer system and SSI,

 but also more recently the systems from GeneralElectric and Toshiba

 

 Transient elastography (TE; FibroScan)

 

•Includes

          Mechanical vibrator

          Single-channel US transducer

•The mechanical vibrator generates a low frequency wave at 50 Hz to generate shear stress in the target tissue at a length of 4 cm, and the velocity of the shear wave can then be measured using an US signal

 •The results are expressed in kilopascals (kPa),  

•range from 1.5 to 75 kPa with 

 •normal values around 5 kPa, 

 •higher in men and in patients with low or high body mass index

 

Precaution during elastograpghy:

 

Fasting 4-6 hours.

Supine or slight 30° Left lateral position

Right arm elevated

Shallow breath  hold

10 measurement are taken

9-11th  Intercostal space

6cm depth of liver  tissue is measured

 

                                                               ARFI

•Relies on a high-frequency spheric compression wave focused on a spot ,which is then absorbed as acoustic energy.

•The absorbed acoustic energy causes the tissue to expand, which createsrto the ultrasound beam axis

•The shear-wave displacement created by the push pulse is recorded by a 2D ultrasound probe using a series of tracking pulse

  •Results are reported as shear-wave speed in meters per second, at a range of 0.5– 5 m/s in abdominal applications

 

 

 

                2D real-time shear wave elastography

 

•Combination of  

           A radiation force induced in tissues by focused ultrasonic beams

           And a very high frame rate ultrasound imaging sequence

•Capable of catching in real time the transient propagation of resulting shear waves

•A wide range of values (2–150 kPa)  

•Its failure rate is significantly lower than that of TE  

•The size of the ROI can be chosen by the operator  

•Results expressed either in m/sec or in kPa

 

              MR Elastography

•MRE is a three step technique

             1) generating mechanical waves in tissue;

             2) imaging the waves with a special MRI sequence, and

             3) processing the wave information to generate

        elastograms, which are images that quantitatively depict tissue 

      stiffness

•MRE is not affected by obesity  ascites or bowel interposition between liver and anterior abdominal wall  all of which may limit the application of ultrasound-based quantitative elastography. 

 

Thanks For Reading. 

Reference:

1.Davidson's Priiple and paractice of Mdcine,23rd edition

2. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests
for evaluation of liver disease severity and prognosis,Journal of Hepatology 2015 vol. 63 j 237–264

3.Asian-Pacific Association for the Study of the Liver (APASL)
consensus guidelines on invasive and non-invasive assessment
of hepatic fibrosis: a 2016 update,Hepatol Int (2017) 11:1–30
DOI 10.1007/s12072-016-9760-3

4.Non invasive markers of hepatic fibrsis,Baranova et al. BMC Gastroenterology 2011, 11:91
http://www.biomedcentral.com/1471-230X/11/91

5.Noninvasive Diagnostic and Prognostic Assessment
Tools for Liver Fibrosis and Cirrhosis in Patients with
Chronic Liver Disease,http://dx.doi.org/10.5772/intechopen.68317