THE RELATIONSHIP BETWEEN

FIB-4, FIBRO-Q, ALPHA-FETOPROTEIN

AND LIVER STIFFNESS
IN CHRONIC HEPATITIS B

Goutama F, Waleleng B J, Lasut P

 Chapter 1

Introduction
 1.1 BACKGROUND
1/3 world population have exposed HBV
350-400 million have HBV infection

Many complications:
HEPATITIS B Fibrosis
Cirrhosis
Hepatocelular Carcinoma

Gold Standard: Liver Biopsy

Non invasive diagnostic tool:
FIBROSIS Fibrosis marker like
Fibrosis Index Based on Four Factor (FIB-4)
Fibro-Quotient (Fibro-Q)
 Marker for HCC

Alpha- Increase of AFP:

Fetoprotein Chronic liver disease
Malignancy outside of hepar
(AFP)
Liu et all:
AFP can use as indirect biomarker for fibrosis

LS is measured by Transient Elastography (TE)

Liver
Stiffness TE is non-invasive, ultrasound-based, easy and can use
for diagnostic tool for fibrosis
 .2. I.2. PROBLEMS

1. Is there a relationship between FIB-4 and LS in chronic hepatitis B

2. Is there a relationship between Fibro-Q and LS in chronic hepatitis B
3. Is there a relationship between FIB-4 and AFP in chronic hepatitis B
4. Is there a relationship between Fibro-Q and LS in chronic hepatitis B
5. Is there a relationship between AFP and LS in chronic hepatitis B
 I.3. AIM OF THE STUDY

1.3.1 General Purpose 1.3.2 Specific Purpose

1. To find out relationship between FIB-4 and LS

in chronic hepatitis B
2. To find out relationship between Fibro-Q and
To find out the relationship LS in chronic hepatitis B
between FIB-4, FibroQ, 3. To find out relationship between FIB-4 and
AFP and LS in chronic AFP in chronic hepatitis B
hepatitis B 4. To find out relationship between Fibro-Q and
LS in chronic hepatitis B
5. To find out relationship between AFP and LS in
chronic hepatitis B
 I.4. THE BENEFITS OF RESEARCH

1.4.1 Scientific benefit

This study is expected to provide an understanding of the relationship
between FIB-4, FibroQ, AFP and LS in chronic hepatitis B

1.4.2 Clinical benefits

By knowing the relationship between FIB-4, FibroQ, AFP and LS in
chronic hepatitis B, it is hoped diagnostic, treatment and prevent
complications in chronic hepatitis B
 Chapter 2

Literature Review
 Hepatitis B
Definition
Chronic Hepatitis B = Persistensi VHB more then 6 months

Epidemiology
Globally (WHO)
VHB: 350-400 million
Death: 650.000/year

Indonesia 4-20% population VHB

5 years incidence VHB without treatment to HCC 8-20%
 Fibrosis Index Based on Four Factors (FIB-4)
• Biomarker non invasive for fibrosis
• Have 4 Parameters: Age, AST, ALT, Trombosit
FIB-4 = Age (years) x AST(U/L)
Trombosit (109/L) x √ALT (U/L)

FibroQutient (Fibro-Q)
• Biomarker non invasive for fibrosis
• Have 5 Parameters: Age, AST, ALT, Trombosit, PT INR
FibroQ : 10 x Age (years) x AST (U/L) x PT INR
Trombosit (109/L) x ALT (U/L)
 Alpha-Fetoprotein (AFP)
• Marker For HCC
• Liu et all: AFP can use as indirect biomarker for liver
fibrosis
• Ahmari et all: AFP can use as predictor for liver fibrosis
• AFP high score also mean inflammation or chronic
liver disease.
 Liver Stiffness

• LS measured with TE
• Fast, non invasive,
harmless, can apply in
outpatient clinic
 Chapter 3

Theory Frameworks, Concepts, Research

Variables, and Hypothesis
III. 1.THEORY FRAMEWORK
III. 2. CONCEPTUAL FRAMEWORK

III. 3. VARIABLES OF THE STUDY

FIB-4
Fibro-Q
AFP
Liver Stiffness with TE
III.4. HYPOTHESES OF THE STUDY

1. There is a relationship between FIB-4 and LS in chronic

hepatitis B
2. There is a relationship between Fibro-Q and LS in
chronic hepatitis B
3. There is a relationship between FIB-4 and AFP in chronic
hepatitis B
4. There is a relationship between Fibro-Q and LS in
chronic hepatitis B
5. There is a relationship between AFP and LS in chronic
hepatitis B
 Chapter 4

Research Methodology
IV.1. STUDY DESIGN
An observational analytic design, cross sectional study

IV.2. TIME AND LOCATION OF RESEARCH

 RSUP Prof. dr. R.D. Kandou Hospital, Manado
 January 2021 – June 2021

IV.3. STUDY POPULATION AND SAMPLE

 Population:
 Hepatitis B Patients
 Sample:
 Consecutive sampling
IV.
IV.4. STUDY CRITERIA

Inclusion Criteria:
• Hepatitis B patients 18 - 50 y.o.
• Willing to be involved in study by signing informed consent form

Exclusion Criteria:
• 1. Cirrhosis
• 2. HCC
• 3. Co-infection Hepatitis C
• 4. Alcoholic liver disease
IV.5 SAMPLE SIZE

n=number of sample
N= number of sample
Zα= level of significance type I, Zα = 1,96
Zβ= level of significance type II, Zβ = 0,84
r= research precision

Based on the calculation using the formula, the minimum sample size is
29 samples
VII.1 OPERATIONAL DEFINITION

1. Chronic Hepatitis B
Hepatitis B infection that does not resolve spontaneously and develop into chronic
hepatitis B is experienced by sufferers for more then 6 months
Dx Criteria : laboratory exam and medical record
Objective criteria: HbsAg and HBV DNA positif
2. Fibrosis Index Based on Four Factor

Algorithm for fibrosis

Dx Criteria : Laboratory exam and algorithm calculation

FIB-4 = Age (years) x AST(U/L)

Trombosit (109/L) x √ALT (U/L)

Objective criteria FIB-4 increase when above 3.25

3. FibroQuotient

Algorithm for fibrosis

Dx Criteria : Laboratory exam and algorithm calculation

FibroQ : 10 x Age (years) x AST (U/L) x PT INR

Trombosit (109/L) x ALT (U/L)

Objective criteria FibroQ increase when above 1.6

4. Alpha-Fetoprotein:
Laboratory examination to screening HCC, high score of AFP linked to hepar
inflammation

Method of examination: Laboratory Exam

Objective criteria:
normal range <10 ng/mL
high range 10-400 ng/mL hepar inflammation
highest range >400 ng/mL probably HCC
5. Liver Stiffness

Liver Stiffness exam use transient elastography and result with kiloPascal (kPa)

Dx Criteria: examination with transient elastography (Fibroscan)

Objective criteria:
F0-F1 : 2.5 - 7.2 kPa F2 : >7.2 - 8.1 kPa
F2-F3 : >8.1 - 10.5 kPa F3 : >10.5 - 11 kPa
F3-F4 : >11 - 18.2 kPa F4 : >18.2 kPa
F0-F1 : non significant fibrosis
>= F2 : significant fibrosis
F4 : cirrhosis
 .
IV.9. SCHEMATIC TRIAL DESIGN

Stage 1
Chronic Hepatitic B patients based on anamnesis, physical examination, supporting examination,
and medical record

Exclusion Criteria

Agree and Sign the informed consent

Stage 2
Fib-4, FibroQ, AFP, LS with TE

Stage 3
Data Analysis
IV.10. RESEARCH ETHICS

An ethical clearance application containing an attachment (medical

research ethic form), a research flow, an informed consent form, and
detailed information for a prospective subject will be submitted to
the Ethics Committee
IV once the proposal has been approved
IV.11. DATA ANALYSIS

1. Descriptive statistical analysis to see description of research

variables to obtain the min, max, average, median, standard
deviation & distribution of all variables.
2. To assess correlation between FIB-4, FibroQ, AFP and LS.
Use spearmen correlation if the data distribution not normal
and use pearson correlation if the data distribution normal.
THANK YOU