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LIVER FIBROSIS ASSEMENT ISGTNCON 2015
DR. V.G.MOHAN PRASAD, M.D., D.M., (GASTRO)
PAST PRESIDENT OF INDIAN SOCIETY OF GASTROENTEROLOGYPAST PRESIDENT, SGEI
ADJUNCT PROFESSOR TAMIL NADU DR.MGR MEDICAL UNIVERSITY
CHAIRMANVGM HOSPITAL - INSTITUTE OF GASTROENTEROLOGY
COIMBATORE
Fibrosis in Chronic Viral Hepatitis B
• F0 : lobular, no fibrous tissue
• F1-F3 : fibrosis (periportal, then briding)
• F4 : Cirrhosis = annular fibrosis + architectural remodeling (lobule nodule)
CIRRHOSIS REVERSION // REGRESSION F4 F3, F2 or F1 (nodular lobule)
Poor patient compliance
Limited usefulness for dynamic follow-up
Risk of complications typical of invasive procedures (Pain, bleeding, mortality)
Sampling errors
Limitations of Liver Biopsy
sampling error is common because only 1/50,000 of the organ is analyzed
3 different samples were obtained:The same result in 3 biopsy were present in:
- 50% of Cirrhosis- 54% of HCC- 55% of Metastatic Cancers- 18.8% of Hepatic Granuloma
Sampling error and intra-observer variation (Lancet: 1989;1-253-5)
Two samples: right lobe and single needle biopsy (HAI score):
- 34.5% difference≥4 in necroinflamatory score- 38% difference≥1 in fibrosis score- 20% difference≥2 in fibrosis score
Mean difference for NI= 2.4 scoreMean difference for FI= 0.6 score
Sampling Error 2Scand J Gastroenterol 2003-38 (4) 427
These limitations may lead to an underestimation of cirrhosis, especially when LB specimens are small or fragmented
Consequence
We need a Test to be more representative of liverAnd less invasive
• 3.5 MHz ultrasound transmitted from the vibrator toward the tissues • pulse-echo ultrasound acquisitions are performed which is directly related to tissue stiffness. • The harder the tissue, the faster the shear wave propagates• The operator, assisted by ultrasound time-motion images• liver portion at least 6 cm thick and free of large vascular structures• The measurement depth is between 25 and 65 mm below the skin surface
FibroScan
100 times larger than liver biopsy
Acoustic radiation force impulse(ARFI)
Sono-elastography that evaluates liver elasticity
Utilizes acoustic waves to interrogate the mechanical stiffness of liver
Can be used during standard US examination of liver
Excellent tool
Requires an expensive software
Not available in most centres
Expensive
Excellent in obese
MR ELASTOGRAPHY
Safe Fast screening Acceptability by patients Longitudinal follow-up Efficacy of therapeutic treatments Prognostic evaluation Excellent Intera and inter observation Accurate
Advantages of Elastography
Fibroscan and liver LTX and PHTLIVER TRANSPLANTATION 12:1791-1798, 2006
Hepatitis C recurrence is the first cause of graft loss in liver transplant programs Frequent liver biopsies= Routine follow-up of HCV-infected patients after LT
Relationship between fibrosis stage and liver stiffness
Optimal liver stiffness cutoff values (>8.50 kPa for fibrosis >F2, and >12.5 kPa for F4)
none of the few cases with liver stiffness below the cutoff value and significant fibrosis in the liver biopsy had bridging fibrosis (F3) or cirrhosis
Correlation between liver stiffness measured byTE and HVPG
Pearson correlation, 0.84; P < 0.001).
The area under the curve for diagnosis of portal hypertension (HVPG 6 mm Hg) was 0.93. Only a few cases with liverstiffness below 8.74 kPa had portal hypertension and, outstandingly, none of them had significant portal hypertension(HVPG 10 mm Hg) or bridging fibrosis or cirrhosis.
Accuracy of Fibro Scan
7.9KP for marked fibrosis (F>2 sensitivity 72%, specificity 84%)
10.3KP for severe fibrosis (F>3, sensitivity 76%, specificity 90%)
11.9 for cirrhosis (sensitivity 91% and specificity 89%)
Reproducibility of transient elastography Gut 2007;56:968–973
The overall interobserver agreement ICC was 0.98 (95% CI 0.977 to 0.987)
TE and different causes of cirrhosisHepatology 2006;44,1511:7
Corresponding areas under the ROC were 0.95 (95% CI: 0.93-0.97) in the whole population
0.96 (95% CI: 0.77-0.96)
0.90 (95% CI: 0.77-0.96)
0.96 (95% CI : 0.90-0.98)
Markedly overweight or obese patients
LS measurement can be influenced by hepatic inflammation (In acute HAV)
Extra Hepatic cholestasis influences liver stiffness score
Limitation
Elastography and other Non-invasive tests Journal of Hepatology 50 (2009) 59–68
L. Caste´ra et al. /
AST/ALT ratio (AAR)
APRI test: uses platelet count and AST
“FIB 4 index” utilizes age, AST, ALT, and platelet count
“NAFLD fibrosis score” includes:- BMI- Presence of DM- Albumin
Panel of markers/Scoring systemsIdentification of fibrosis
“Fibrotest” (BioPredictive) taking into account:- GGT- Haptoglobulin- Bilirubin- Apolipoprotein A1- α2 macroglobulin
“Fibro Spect” taking into account:- Hyaluronic acid- Tissue inhibited matrix metalloproteinase Inhibitor1- α2 macroglobulin
168 patients with Fatty liver on Ultrasound underwent
Fibroscan (TE) and Philips shear wave elastography (SWE)
Mean Fibroscan TE score was 9.2 Mean Philips SWE score was 9.1
TE AND SWE
By paired t test, the correlation of TE and SWE values was highly significant (p-0.000).
CORRELATION OF TE AND SWE VALUES
1 13 25 37 49 61 73 85 97 1091211331451570
10
20
30
40
50
60
70
80
Series 1Series 2
CONCORDANCE OF TE AND SWE
ARFI S1 [n=148]
ARFI S2 [n=12]
ARFI S3[n=5] ARFI S4 [n=3]
Fibroscan S1 [n=148]
Fibroscan S2 [n=12]
Fibroscan S3[n=5]
Fibroscan S4 [n=3]
0.00 - 1.00
0.41891891891892
0.364864864864868
0.108108108108108
0.108108108108108
0.412162162162163
0.37837837837838
0.101351351351351
0.108108108108108
1.10 - 2.00
0.0833333333333335
0 0.25 0.666666666666667
0.0833333333333335
0 0.166666666666667
0.750000000000002
2.10 - 3.00
0 0 0.2 0.8 0 0 0 1
>3.00 0 0 0 1 0 0 0 1
10%
30%
50%
70%
90%
110%
Asscoiation of ARFI & FS with their difference
In 17.85% (30/ 168) patients, Fibroscan TE and Philips SWE detected F3 / F4 Fibrosis missed by ultrasound (showed only fatty liver)
USG vs TE / SWE
NO FIB32ROSCAN TE PHILIPS SWE USG ABDOMEN
1 20.4 18.2 GR I FATTY LIVER
2 48 50.2 GR I FATTY LIVER
3 38 36.4 GR I FATTY LIVER
4 28.4 26.4 GR II FATTY LIVER
5 75 74.6 GR II FATTY LIVER
6 45.7 46.2 GR II FATTY LIVER
7 24 22.3 GR II FATTY LIVER
8 29.1 26.3 GR II FATTY LIVER
9 21.5 19.6 GR I FATTY LIVER
10 19.2 20.2 GR II FATTY LIVER
11 23.3 22.2 GR II FATTY LIVER
12 16.9 16.2 GR I FATTY LIVER
13 26.3 25.6 GR II FATTY LIVER
14 43.5 40.2 GR II FATTY LIVER
15 20.9 20.1 GR I FATTY LIVER
16 14.8 12.3 GR I FATTY LIVER
17 11.5 12.5 GR I FATTY LIVER
18 13.1 12.3 GR I FATTY LIVER
19 14 13.6 GR I FATTY LIVER
20 12.6 13.4 GR I FATTY LIVER
21 10.9 9.8 GR I FATTY LIVER
22 10.2 10.1 GR I FATTY LIVER
23 11.5 12.5 GR I FATTY LIVER
24 11.9 11 GR I FATTY LIVER
25 10.1 10.1 GR I FATTY LIVER
26 10.4 11.1 GR I FATTY LIVER
27 11.3 10.2 GR I FATTY LIVER
28 11.3 12 GR I FATTY LIVER
29 10.1 11.2 GR I FATTY LIVER
30 11.7 10.3 GR I FATTY LIVER
Fibroscan and SWE, are thus able to detect patients with significant fibrosis in many cases, where ultrasound showed only Gr I-II fatty liver.
USG vs TE / SWE
Case1- Treatment of NAFLD which included hepatoprotectives
Caused a reduction of fibroscan score from 8 to 5.7 after 10 months.
FIBROSCAN SCORES DECREASE WITH TREATMENT
Case Mr.S
31/10/2013 Height-173 Weight-70 BMI-23.39 BP-120/80 Pulse-80
27/08/2014 Height-173 Weight-78.6 BMI-25.37 BP-150/100 Pulse-78
FIBROSCAN SCORE DECREASE WITH TREATMENT Case 2- Treatment of NAFLD caused
reduction in fibroscan score from 9.6 to 7.9 after 12 months.
12/15/14
Baseline
•Mrs.K-48yrs/F•CLD-HCV-Genotype-3
•Rxed with PEGIFN for 24wks•Baseline HCV Viral load-
1.2million/ml•ETVR: HCVNot Detected
6Mo Post Rx
12/15/14
Mr.K-46/METOH+HCV related Cirrhosis with PHT, UGI Bleed Fundal Glue+EVBL Rxed with Hepatoprotectives and
ETOH abstinence
PresentBaseline
Liver Biopsy is still the gold standard for assessing fibrosis
HOWEVER TE will suffice in the vast majority , avoiding further
invasive investigations (ie, hepatic hemodynamics or biopsy).
TE is a useful tool for initial screening and on-treatment follow-up of NAFLD ,AFLD, HBV and HCV subjects and has been validated in several trials.
Conclusion