CHRONIC HEPATITIS a comprehensive lecture.pptx

Updated approach

1. Dr AbdelRahman A Moukhtar Chronic Hepatitis 2019

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 Definition and terminologies

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.

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

5. Etiologies

6. 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. Proper diagnosis

7. PATHOLOGY of CHRONIC HEPATITIS

8. 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)

9. 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

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

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

12. 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

13. 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.

14. Clinical Presentation

15. 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. Clinical picture

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

17. Clinical picture

18. Clinical picture 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 .

19. 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….

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

21. 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

22. DIAGNOSIS

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

24. Evidence of Chronic hepatitis . Possible Aetiology . Grading and staging. Aim of investigations Investigations

25. Evidence of Chronic hepatitis

26. 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

27. Serology of HBV

28. _ + Serology of HBV Serologic diagnosis of chronic viral Hepatitis

29. Serologic diagnosis of chronic viral Hepatitis

30. Serologic diagnosis of chronic viral Hepatitis

31. Serologic diagnosis of chronic viral Hepatitis

32. Liver Biopsy Is not a routine. If after serology still unknown Etiology. Occasionally for grading and staging .

33. Non invasive alternatives to liver Biopsy

34. Non invasive alternatives to liver Biopsy

35. Non invasive alternatives to liver Biopsy To detect Complications ( HCC )

36. TREATMENT

37. Treatment of Chronic HBV

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

39. TTT of HCV in the Era of DAAS

40. Treatment of Chronic Hepatitis C Classes of direct Acting Antiviral Drugs for Chronic HCV Replicase Inhibitors

41. Ombitasvir , Paritaprevir and Ritonavir

42. After

43. Accordingly : NASH……………………………………………………………………………………………………………………… Autoimmune…………………………………………………………………………………………………………. Hemochromatosis……………………………………………………………………………………………….. Wilson`s…………………………………………………………………..………………………………………………... Treatment of non – viral Chronic hepatitis