5 Liver Fibrosis Assessment Dr. V.G. Mohanprasad

DR. V.G.MOHAN PRASAD, M.D., D.M., (GASTRO)

PAST PRESIDENT OF INDIAN SOCIETY OF GASTROENTEROLOGY

PAST PRESIDENT, SGEI

ADJUNCT PROFESSOR TAMIL NADU DR.MGR MEDICAL UNIVERSITY

CHAIRMAN

VGM HOSPITAL - INSTITUTE OF GASTROENTEROLOGY

COIMBATORE

Why do we need to assess fibrosis?

Prognosis becomes worse

F1-------F4

• F0 : lobular, no fibrous tissue

• F1-F3 : fibrosis (periportal, then briding)

• F4 : Cirrhosis = annular fibrosis + architectural remodeling (lobule nodule)

CIRRHOSIS REVERSION // REGRESSIONF4 F3, F2 or F1

(nodular lobule)

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 errorssampling 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

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 score

Mean difference for FI= 0.6 score

These limitations may lead to an underestimation of cirrhosis, especially when LB specimens are small or fragmented

We need a Test to be more representative of liver

And 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

100 times larger than liver biopsy

Sono-elastography that evaluates liver elasticity

Utilizes acoustic waves to interrogate themechanical 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

Safe Fast screening Acceptability by patients Longitudinal follow-up Efficacy of therapeutic treatments Prognostic evaluation Excellent Intera and inter observation Accurate

Hepatitis C recurrence is the first cause of graft loss in liver transplantprograms Frequent liver biopsies= Routine follow-up of HCV-infectedpatients after LT

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 theliver biopsy had bridging fibrosis (F3) or cirrhosis

PHT cut of (>6 mm Hg)

significant PHT (>10 mm Hg)

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.

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%)

The overall interobserver agreement ICC was 0.98 (95% CI 0.977 to 0.987)

The intraobserver agreement ICC was 0.98 for both raters

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 (Inacute HAV)

Extra Hepatic cholestasis influences liver stiffness score

Gut 2009;58;157-160

No Liver biopsy

No Fibroscan

How are they related ?

How do they measure ?

Current status ?

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

“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 Ultrasoundunderwent

Fibroscan (TE) and

Philips shear wave elastography (SWE)

Mean Fibroscan TE score was 9.2

Mean Philips SWE score was 9.1

By paired t test, the correlation of TE and SWEvalues was highly significant (p-0.000).

0

10

20

30

40

50

60

70

80

1

11

21

31

41

51

61

71

81

91

10

1

11

1

12

1

13

1

14

1

15

1

16

1

Series 1

Series 2

S1 [n=148] S2 [n=12] S3[n=5] S4 [n=3] S1 [n=148] S2 [n=12] S3[n=5] S4 [n=3]

ARFI Fibroscan

0.00 - 1.00 42% 36% 11% 11% 41% 38% 10% 11%

1.10 - 2.00 8% 0% 25% 67% 8% 0% 17% 75%

2.10 - 3.00 0% 0% 20% 80% 0% 0% 0% 100%

>3.00 0% 0% 0% 100% 0% 0% 0% 100%

0%

20%

40%

60%

80%

100%

120%

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)

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 patientswith significant fibrosis in many cases, whereultrasound showed only Gr I-II fatty liver.

Case1- Treatment of NAFLD which included

hepatoprotectives

Caused a reduction of fibroscan score from

8 to 5.7 after 10 months.

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

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 Detected6Mo Post Rx

12/15/14

Mr.K-46/METOH+HCV related Cirrhosis with PHT, UGI Bleed Fundal Glue+EVBLRxed 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 furtherinvasive investigations (ie, hepatic hemodynamics orbiopsy).

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.

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

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

5 Liver Fibrosis Assessment Dr. V.G. Mohanprasad

Health & Medicine