1. CHRONIC HEPATITIS

2. The contours of the liver and spleen as well as the gall bladder in the right and left hypochondrium

3. THE ANATOMY OF THE PORTAL VENOUS SYSTEM

4. CHRONIC HEPATITIS
Chronic hepatitis is generally defined as disease that has lasted for 6 months or longer

5. Inflammation Walls of scar tissue begin to form
Healthy liver cells become trapped
by a wall of scar tissue

6. CYTOLYTIC SYNDROME alanine aminotransferase increased,
aspartate aminotransferase increased
Increased LDH
Increased ferritin
Hyperbilirubiemia

7. Cholestasis abdominal mass (e.g. cancer)
Alkaline phosphatase
elevations of serum bile acid levels
elevated levels of Gamma Glutamyl Transferase [GGT]
itchiness (pruritus). Pruritus is the primary symptom of cholestasis
jaundice.
pale stool. This symptom implies obstructive cholestasis.
dark urine
abdominal mass (e.g. cancer)
biliary atresia and other pediatric liver diseases
biliary trauma
congenital anomalies of the biliary tract
gallstones
intrahepatic cholestasis of pregnancy (obstetric cholestasis)
primary biliary cirrhosis, an autoimmune disorder
primary sclerosing cholangitis, associated with inflammatory bowel disease
some drugs, (e.g. flucloxacillin and erythromycin)
ABCC2 gene polymorphism

8. Hepatocellular insufficiency
Mesenchymal inflammation
Hepatocellular insufficiency
Hyper-γ globulinemia
CRP
ESR
Albumin
Transferrine
Cholesterol
protro,mbine
Cholinesterasa
Α-lipoproteins
Hyperbilirubinemia

9. Signs of CLD

10. CHRONIC HEPATITIS CLASSIFICATION
Chronic Viral Hepatitis B
Chronic Viral Hepatitis C
Chronic Viral Hepatitis D
Chronic Viral Hepatitis nonidentificated
Autoimmune Hepatitis (type 1, 2 ,3)
Toxic Hepatitis, Drug-Induced Hepatitis
Cryptogenic Hepatitis
Alcoholic Hepatitis
Metabolic Hepatitis
Cholestatic Hepatitis
Nonspecific Reactive Hepatitis

11. Grades of Inflammation and Stages of Fibrosis on Liver Biopsies

12. CHRONIC HEPATITIS CLASSIFICATION ACCORDING TO SEVERITY (level of Aminotransferases)

13. CHRONIC HEPATITIS COMPLICATIONS
HEPATIC ENCEPHALOPATHY
VARICEAL BLEEDING
ASCITES
GLOMERULONEPHRITIS
OTHERS

14. General Concepts Hepatitis = 'inflammation of the liver'.
six medically important viruses are commonly described as “hepatitis viruses”:
HAV,HBV,HCV,HDV,HEV,HGV.

15. Viral Hepatitis - Historical Perspectives
Enterically
transmitted
“Infectious” A E
Viral hepatitis
NANB
Parenterally
transmitted
“Serum” B D C
F, G, TTV
? other 2

16. CHRONIC VIRAL HEPATITIS
5 to 10% of cases of hepatitis В (with or without hepatitis D virus co-infection)
and about 75% of cases of hepatitis C become chronic.
Infection with hepatitis A virus or hepatitis E virus is not a cause of Chronic Hepatitis.

17. HBV : Structure

18. HBV Structure & Antigens
Dane particle
HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr)
HBcAg = inner core protein (a single serotype)
HBeAg = secreted protein; function unknown

20. Possible Outcomes of HBV Infection
Acute hepatitis B infection
3-5% of adult-acquired infections
95% of infant-acquired infections
Chronic HBV infection
Chronic hepatitis
12-25% in 5 years
Cirrhosis
6-15% in 5 years
20-23% in 5 years
Hepatocellular carcinoma
Liver failure
Death
Liver transplant
Death

21. Laboratory Diagnosis

24. CHRONIC VIRAL HEPATITIS
Hepatitis B virus and hepatitis C virus are the major causes of chronic hepatitis in the world.
Approximately 80% of individuals infected with HCV will become chronic carriers, of whom a majority will develop a degree of liver damage ranging from fatty liver to cirrhosis.
Chronic HBV and HCV infection predispose patients to developing hepatocellular carcinoma.

29. Natural History of Hep C
20%
Clear the
Virus
Only 20% will
show symptoms
Initially !
Chronic
Infection
Acute
Infection
Healthy
Liver
80% Virus
Continues
to Damage
Liver
Adapted from Lauer and Walker, NEJM 2001

30. Natural History Con’t Liver Chronic Cirrhosis Cancer Hepatitis 20-30%
1-4%/year
Cirrhosis
20-30%
Chronic
Hepatitis
Most symptoms begin to show only when liver is more severely damaged

32. AUTOIMMUNE HEPATITIS Patients with severe disease who are
treated with corticosteroids have a 10-year
survival rate of 60% to 70%,
whereas untreated patients have a survival rate of less than 30%.

33. Autoimmune Hepatitis Histology
Lymphoplasmacytic infiltrate
Interface hepatitis
Portal inflammation and invasion of limiting plate

34. Autoimmune Hepatitis Histology
Prominent lobular infiltrate composed of mononuclear and plasma cells
Lobular infiltrate

35. Autoimmune Hepatitis Histology
Prominent plasma cells appreciated in this specimen
Plasma cells

36. DRUG-INDUCED CHRONIC HEPATITIS
Hepatotoxic drugs:
- Paracetamol
- Isoniazid
- Oestrogens
- Antibiotics
-Methotrexate
-others

37. Variety of liver diseases
DIVERSITY
> 1000 Hepatotoxic drugs
Diverse
mechanisms
Variety of liver diseases

38. METABOLIC ACTIVATION Drug CYP Reactive metabolite (Low Amounts)
(High Amounts)
Extensive
covalent
binding
 GSH
Protein
Immune reactions
Direct toxicity

39. MITOCHONDRIAL DYSFUNCTION
Drugs
 Beta-
oxidation
 Respi-
ration
Steatosis
Cell dysfunction
Cell death
Lactic acidosis

40. FATTY LIVER Fat droplets appear in the cytoplasm of hepatocytes;
they may appear a few days after an alcohol binge, but are almost always present in heavy drinkers (> 80 g of alcohol per day for > 5 years).
Fatty liver may occur, however, with obesity, diabetes mellitus, starvation and chronic hepatitis C virus infection
Fatty Liver

41. ALCOHOLIC HEPATITIS
Alcohol abuse is a massive international problem which has huge resource implications both for the community as a whole and also for health care.
Alcohol is enjoyed by many and used safely by the majority of people who drink it.
Alcohol abuse may be denied or not recognized by individuals or their families and friends.
Alcohol damages not only the liver, but many other organs also.

42. Effects of alcohol abuse

43. Mechanisms of liver injury
Alcoholic Hepatitis
Mechanisms of liver injury
Free radicals
Oxidative injury
Heat
Gut Permeability Endotoxaemia Kupfer cell activation
Gultathione
depletion
ROS &
Free radicals
TNFα
Genetics
Polymorphisms
Male vs Female
Race
Alcohol dehydrogenase (ADH)
Peroxisomal Catalase
Miscrosomal ethanol-oxidising system (CYP 2E1)
Damage
Ethanol
Acetaldehyde
Altered membrane proteins
Neoantigens formation
Impaired cytoskeletal transport
Stimulation of HSC
Immunological injury
Damage to cell
membranes
Acetate
Acetaldehyde
dehydrogenase
TNFα IL-1, IL-8
Downregulated in
chronic alcohol use

44. ALCOHOLIC HEPATITIS
Alcoholic liver disease may develop in women after less alcohol consumption than is necessary to cause hepatitis or cirrhosis in men.
Daily alcohol consumption of approximately 50 g for 10 to 15 years is associated with alcoholic liver disease
in women, whereas
80 g is associated
with alcoholic cirrhosis
in men.

45. Pathology of Alcoholic Hepatitis
Mallorys Hyaline
Centrilobular necrosis
Fatty change
Hepatocyte ballooning
PMN infiltrate
Pericellular fibrosis

46. ALCOHOLIC HEPATITIS
Alcoholic hepatitis refers to the pathologic Mallory stain findings of alcoholic hyalin surrounded by polymorphonuclear cell inflammation

47. CHRONIC HEPATITIS DIAGNOSIS
LABORATORY SYNDROMES:
Cytolitic syndrome (↑AST, ↑ALT, ↑GGT, ↑Bilirubin )
Cholestatic syndrome (↑conjugated Bilirubin, ↑Alkaline phosphatase, ↑GGT, ↑cholesterol)
Liver cellular insufficiency syndrome (↓Albumine, ↓prothrombin, ↓cholesterol, ↓fibrinogen)
Mesenchyme-inflammatory syndrome (↑ESR,
↑ﻻ-globulins, ↑timol test ↑Le, ↑C-react. protein)
Hypersplenism (anemia, thrombocytopenia, leukocytopenia)

48. CHRONIC VIRAL HEPATITIS TREATMENT
ANTIVIRAL THERAPY (Interferon therapy, Lamivudine therapy)
Corticosteroids are contraindicated, because viral replication is enhanced

50. Prednisolone (mg) and Azathioprine (mg/kg) combination therapy
Autoimmune Hepatitis
Week
Monotherapy
Prednisolone, mg
Prednisolone (mg) and Azathioprine (mg/kg) combination therapy
Prednisolone Azathioprine 1 50
50-150 2 40 3 30 4 20 5 25 15 6
12,5
7,8 10

51. HEPATOPROTECTORS Ursodezoxycholic acid Plant
Carsil, Legalon, Hepabene, Chofitol
Essential phospholipids
Essentiale, Enerliv
Aminoacids
Glutargin, Citrarginin
α- lipoic acid
Berlithion
Ursodezoxycholic acid
Ursofalc, Ursosan
Synthetic
Thiotriazolin, Antral
Animal
Vitohepat, Sirepar
Homeopathic
Halstena