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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

Why do we need to assess fibrosis?

Prognosis becomes worse

F1-------F4

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)

CIRRHOSIS : REGRESSION AFTER ANTIVIRAL TREATMENT

Reversibility of fibrosis in cirrhotics is possible,....but.........

We need to reverse fibrosis before it is too late.

How do we assess fibrosis?

A) Liver Biopsy

B) Elastography

Fibroscan

ARFI

MR Elastography

C)Serum Markers

Invasive Diagnosis – why bother?

Liver biopsy- gold standard

Not always easy

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

Relationship between fibrosis stage and HVPG

PHT cut of (>6 mm Hg)

significant PHT (>10 mm Hg)

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.

TE : Fibrosis and PHT

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)

The intraobserver agreement

The intraobserver agreement ICC was 0.98 for both raters

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

Gut 2009;58;157-160

No Liver biopsy

No Fibroscan

Serum markers

How are they related ?

How do they measure ?

Current status ?

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

VGM HOSPITAL DATA ON

FIBROSCAN AND SHEAR WAVE ELASTOGRAPHYIN

NAFLD

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

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

NAFLDTRANSABDOMINAL ULTRASOUND

Vs ELASTOGRAPHY

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


4 28.4 26.4 GR II FATTY LIVER

5 75 74.6 GR II FATTY LIVER


7 24 22.3 GR II FATTY LIVER

















24 11.9 11 GR I FATTY LIVER




28 11.3 12 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

VGM HOSPITAL EXPERIENCE

SERIAL FIBROSCAN SCORES ON FOLLOW UP

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

See you in Ooty in August 2015 for Mid Term Rural CME….

See you in Coimbatore for Endoscopy Workshop in October 2015….!

Thanks Folks……..!

Health & Medicine

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