HEPATIC FIBROSIS:

UPDATE CLINICAL DIAGNOSIS AND TREATMENT

UNGGUL BUDIHUSODO
DIVISION OF HEPATOLOGY

OMNI MEDICAL CENTER

INTRODUCTION

• Hepatic Fibrosis = excesive accumulation of fibrillar

extracellular matrix (ECM) in the liver
• Previous stage of liver scarring
• The most severe scarring is liver cirrhosis (LC)
• HF is a progressive condition (F1  F4)
• Diagnosis in early stage may arrest/slow down
progression to LC
FIBROGENESIS AND FIBROLYSIS
CELLS AND CYTOKINES
CAUSES OF HEPATIC FIBROSIS

• Chronic Hepatitis B or C
• Nonalcoholic Fatty Liver Disease (NAFLD) or Nonalcoholic
Steatohepatitis (NASH)
• Alcoholic Steatohepatitis (ASH)
• Autoimmune Hepatitis (AIH)
• Drug-induced Liver Injury (DILI)
• Iron Overload
• etc
DIAGNOSIS OF HEPATIC FIBROSIS

• Acute Hepatitis : ECM can be decomposed (fibrolysis) 

prevent ECM accumulation  prevent the development HF
• Chronic Hepatitis : Prolonged injury (necroinflamation) promote
the development of fibrosis (fibrogenesis)
• Required examination that can quickly evaluate the progresion
stage, easily and accurately to provide consistent results
LIVER BIOPSY

• Remains the gold standard for assessing the presence,

stage progresion (severity of chronic hepatitis)
• Invasive procedure
• Requires hospitalization
• Inconvenience
• Potentially dangerous
 METAVIR SCORING SYSTEM
Activity Score : Fibrosis Stages :
A0 : No activity F0 : No Fibrosis
A1 : Mild activity F1 : Portal fibrosis without septa
A2 : Moderate activity F2 : Portal fibrosis with few septa
A3 : Severe activity F3 : Numerous septa w/o cirrhosiss
F4 : Cirrhosiss
NON-INVASIVE METHODS

• Accuracy problem
• Time consuming (some methods)
• Problem of consistency
TRANSIENT ELASTOGRAPHY (TE)

• Uses low-frequency sound waves

• Measures liver stiffness (in KPa)
• The scarred tissue in HF makes the liver stiffer
• Significant fibrosis with cut-off value ≥ 8.5 KPa
• Value > 12.5 KPa  advanced LC
SERUM BIOMARKERS

• The most popular : APRI and FIB-4

• APRI : AST Platelet Ratio Index
• FIB-4 required AST, ALT, Platelet and Age
• APRI & FIB-4 = indirect surrogate markers of HF
• Comparable to TE in assesing HF
APRI

Interpretation :
Meta analysis 40 study score greater than 1.0 predicting cirrhosis
(specificity 72%, sensitivity 76%)
Normal : APRI < 0.5
F4 : APRI > 1.5
FIB-4

Interpretation :
FIB-4 < 1.45 non advance fibrosis
FIB-4 > 3.25 advance fibrosis (F4)
TREATMENT OF HF

• No specific anti fibrotic therapy

• Treatment option depend upon the underlying illness
• Chronic Hep C : Direct Action Antiviral (DAA)
• ASH : stop drinking
• NASH : life style modification
COMPLEMENTARY AND ALTERNATIVE
MEDICINE (CAM)

• E.g Milk Thistle, Schizandra, Compound 861

• Many local studies : benefits for HF treatment
• Strong anti-oxidant, anti inflamatory, detoxification, etc
• Reduce inflamation  reduce fibrogenesis
• Nurul akbar, et. al (2005) Coumpond 861 reduce
fibrosis stages
CONCLUSION

• Hepatic fibrosis occurs in most types of Chronic Liver

Disease
• Hepatic fibrosis can be diagnosed by invasive or
non-invasive procedures
• No specific anti fibrotic medications for HF
• Treatment of HF depend upon the underlying disease
• CAM may have benefits in treating HF