Updated approach

2. Definition :
Chronic hepatitis represents a group of liver diseases of variable
aetiologies and severity in which :
• Liver tissue shows persistent necro-inflammatory activity ( portal inflammation,
interface hepatitis, parenchymal inflammation,and necrosis ) lasting longer than 6
months.
•Associated with progressive fibrosis that ultimately leads to liver cirrhosis

3.  Terminology : Terminology has evolved
• In the past, chronic persistent hepatitis, chronic lobular hepatitis and chronic active hepatitis
denoted the severity of chronic hepatitis.
Current recommendations are to indicate "chronic hepatitis,“
• The severity of necroinflammatory activity (grade)
• The extent of fibrosis (stage) and
• The etiology.

5. Haemochromatosis
NAFLD
Bacterial e.g TB & brucellosis , etc…

7. To describe a case :
Each diagnosis in a liver biopsy for chronic hepatitis should include:
• Statement that it is chronic hepatitis.
• Grade of necroinflammatory activity (name of the scoring system used)
• Stage of activity (name of the scoring system used)
• Known or suspected etiology
Examples:
• Chronic hepatitis B, Metavir, grade 2/4 and stage 2/4 (fibrous septa)
• Chronic hepatitis, Batts-Ludwig, grade 2/4 and stage 4/4 (cirrhosis), compatible with hepatitis C.

9. Regardless of etiology, chronic hepatitis is
characterized by these features, to variable
degrees:
 Portal inflammation
 Interface hepatitis
 Parenchymal inflammation and necrosis
 Fibrosis &Cirrhosis (in many cases)

11. •Portal inflammation:
• Hallmark of chronic hepatitis, ranges from mild and patchy to prominent and diffuse
• Lymphocytes are the predominant component, often with variable plasma cells
• Minor component is scattered macrophages, neutrophils and eosinophils
• Lymphoid follicles may be present, particularly in hepatitis C infection
•Interface hepatitis:
• Also known as piecemeal necrosis
• Important feature of chronic viral hepatitis characterized by:
• Mononuclear inflammatory infiltrate involving hepatocytes located at (and disrupting) the limiting plate
• Injury or necrosis of periportal hepatocytes
•Lobular necroinflammatory activity:
• Hepatocyte necrosis is usually variable in severity and spotty in distribution
• Apoptotic hepatocytes (acidophil bodies) are usually more centered on periportal areas and
mononuclear cells tend to cluster around dying hepatocytes
Pattern of Inflammatory infiltration

12. The distribution and pattern of damage may differ according to the aetiology

13. The distribution and pattern of damage may differ according to the aetiology

14. •Fibrosis:
 Progressive fibrosis of limiting plate leads to enlargement of portal tracts and stellate
periportal fibrous extension
 May lead to portal - portal or portal - central fibrous bridging, culminating in cirrhosis, which
is usually micronodular or mixed micronodular and macronodular type

15. The stellate cell: a key cell implicated in
fibrogenesis. Hepatic stellate cells (HSCs)
located between parenchymal cells and
sinusoidal endothelial cells .
In a normal state, HSCs appear as quiescent
vitamin A-storing cells.
When activated via several stimuli (infection,
alcohol, cytokines, etc.) they acquire a
proliferative myofibroblast phenotype. In
pathological conditions such as chronic
hepatitis C, HSCs lose vitamin A and
synthesise a large amount of extracellular
matrix components including collagen,
proteoglycan and adhesive glycoproteins.
Kupffer cells, the resident liver macrophages,
remove material from the portal circulation.

17. •Patients have a wide spectrum of clinical manifestations, from asymptomatic to
symptomatic decompensated cirrhosis.
•Many patients are asymptomatic or have mild nonspecific complaints such as fatigue.

18. •Physical findings are typically few; may include hepatomegaly or other stigmata of
chronic liver disease, such as palmar erythema.

20. •Serum enzyme levels usually fluctuate but may be elevated 2x to 10x.
•Many patients with mild chronic hepatitis C have persistently normal serum
aminotransferase levels.
•Alkaline phosphatase and bilirubin levels are usually normal, except in stages of hepatic
decompensation.

21. The patient may present by extrahepatic manifestationof the underlying cause
e.g
 Hepatotropic viral hepatitis e.g CHBV & HCV.
 NAFLD & NASH
 Autoimmune hepatitis.
 Hemochromatosis.
 Wilson`s disease. etc….

22. The patient may present by extrahepatic manifestations of the underlying cause

23. Abdominal obesity , HTN , NIDDM ,,, suggest NASH.
Bronzed skin , DM , arthropathy ,,,suggest > Haemochromatosis.
Hypothyroidism , vitiligo , Other autoimmune features ,,,suggest > AIH
Neuropsychatric manifestations , hemolytic anaemia , Kayser – flisher ring
Suggest ,,,, >Wilson`s disease.
The patient may present by extrahepatic manifestations of the underlying cause

25. History
Thorough examination
Laboratory diagnosis
 Liver function test
 Serology
 RNA detection by PCR
 Non-invasive techniques
 Imaging studies.
 Invasive – Biopsy.

26. Evidence of Chronic hepatitis.
Possible Aetiology.
Grading and staging.
Aim of investigations

27. Evidence of Chronic hepatitis

28. 1- Viral hepatitis : ( Serologic markers for HCV , HBV , HDV) and Molecular diagnosis ( PCR ).
2- NAFLD : FBS , Fasting lipid profile , Uric a , etc…………………………………………………………………..
3-Autoimmune hepatitis : serum IG , ANA , ASMA , anti LKM, ……….etc…………………………………
4-Hemochromatosis : Iron profile ( serum ferritin , transferrin saturation, etc…..)……………….
5-Wilson`s disease : cupper studies ( serum & urinary cupper , serum ceruloplasmin )…………
6- Alfa one antitrypsin deficiency… serum activity of alfa-1antitrypsin……………………………….
Tests for the Aetiology

29. Serology of HBV

31. _ +
Serology of HBV

35.  Is not a routine.
 If after serology still unknown Etiology.
 Occasionally for grading and staging .

38. To detect Complications ( HCC )

44. Recommendations for the use of nucleos(t)ide analogues in clinical practice

48. Classes of direct Acting Antiviral Drugs for Chronic HCV
Replicase Inhibitors

51. Ombitasvir, Paritaprevir and Ritonavir

55. After

56. Accordingly :
NASH………………………………………………………………………………………………………………………
Autoimmune………………………………………………………………………………………………………….
Hemochromatosis………………………………………………………………………………………………..
Wilson`s…………………………………………………………………..………………………………………………...