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CHRONIC HEPATITIS. The contours of the liver and spleen as well as the gall bladder in the right and left hypochondrium. THE ANATOMY OF THE PORTAL VENOUS SYSTEM. CHRONIC HEPATITIS. Chronic hepatitis is generally defined as disease that has lasted for 6 months or longer. Inflammation.

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slide2
The contours of the liver and spleen as wellas the gall bladder in the right and left hypochondrium
slide4

CHRONIC HEPATITIS

Chronic hepatitis is generally defined as disease that has lasted for 6 months or longer

inflammation
Inflammation

Walls of

scar

tissue

begin to

form

Healthy liver cells become trapped

by a wall of scar tissue

cytolytic syndrome
CYTOLYTIC SYNDROME
  • alanine aminotransferase increased,
  • aspartate aminotransferase increased
  • Increased LDH
  • Increased ferritin
  • Hyperbilirubiemia
c holestasis
abdominalmass (e.g. cancer)

biliaryatresiaandotherpediatricliverdiseases

biliarytrauma

congenitalanomaliesofthebiliarytract

gallstones

intrahepaticcholestasisofpregnancy (obstetriccholestasis)

primarybiliarycirrhosis, anautoimmunedisorder

primarysclerosingcholangitis, associatedwithinflammatoryboweldisease

somedrugs, (e.g. flucloxacillinanderythromycin)

ABCC2 genepolymorphism

Alkalinephosphatase

elevations of serum bile acid levels

elevatedlevelsofGammaGlutamylTransferase [GGT]

itchiness (pruritus). Pruritus is the primary symptom of cholestasis

jaundice.

pale stool. This symptom implies obstructive cholestasis.

darkurine

Cholestasis
h epatocellular insufficiency

Mesenchymal inflammation

Hepatocellularinsufficiency
  • Hyper-γ globulinemia
  • CRP
  • ESR
  • Albumin
  • Transferrine
  • Cholesterol
  • protro,mbine
  • Cholinesterasa
  • Α-lipoproteins
  • Hyperbilirubinemia
chronic hepatitis classification
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
chronic hepatitis complications
CHRONIC HEPATITISCOMPLICATIONS
  • HEPATIC ENCEPHALOPATHY
  • VARICEAL BLEEDING
  • ASCITES
  • GLOMERULONEPHRITIS
  • OTHERS
general concepts
General Concepts
  • Hepatitis = 'inflammation of the liver'.
  • six medically important viruses are commonly described as “hepatitis viruses”:

HAV,HBV,HCV,HDV,HEV,HGV.

slide15

Viral Hepatitis - Historical Perspectives

Enterically

transmitted

“Infectious”

A

E

Viral hepatitis

NANB

Parenterally

transmitted

B

D

C

“Serum”

F, G, TTV

? other

chronic v iral hepatitis
CHRONIC VIRALHEPATITIS
  • 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 ChronicHepatitis.
hbv structure antigens
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

slide20

Possible Outcomes of HBV Infection

Acute hepatitis B infection

3-5% of adult-acquiredinfections

95% of infant-acquired infections

Chronic HBV infection

Chronic hepatitis

12-25% in 5 years

Cirrhosis

20-23% in 5 years

6-15% in 5 years

Hepatocellularcarcinoma

Liver failure

Liver transplant

Death

Death

chronic v iral hepatitis1
CHRONIC VIRALHEPATITIS
  • Hepatitis B virusandhepatitis C virusarethemajorcausesofchronichepatitisintheworld.
  • Approximately 80% ofindividualsinfectedwith HCV willbecomechroniccarriers, ofwhom a majoritywilldevelop a degreeofliverdamagerangingfromfattylivertocirrhosis.
  • Chronic HBV and HCV infectionpredisposepatientstodevelopinghepatocellularcarcinoma.
natural history of hep c

Only 20% will

show symptoms

Initially !

Natural History of Hep C

20%

Clear the

Virus

Chronic

Infection

Acute

Infection

Healthy

Liver

80% Virus

Continues

to Damage

Liver

Adapted from Lauer and Walker, NEJM 2001

natural history con t
Natural History Con’t

Liver

Cancer

1-4%/year

Cirrhosis

20-30%

Chronic

Hepatitis

Most symptoms begin to show only when liver is more severely damaged

autoimmune hepatitis
AUTOIMMUNE HEPATITIS
  • Patientswithseverediseasewhoare

treatedwithcorticosteroidshave a 10-year

survivalrateof 60% to 70%,

whereasuntreatedpatientshave a survivalrateoflessthan 30%.

autoimmune hepatitis histology
Autoimmune HepatitisHistology
  • Lymphoplasmacytic infiltrate
  • Interface hepatitis

Portal inflammation and invasion of limiting plate

autoimmune hepatitis histology1
Autoimmune HepatitisHistology
  • Prominent lobular infiltrate composed of mononuclear and plasma cells

Lobular infiltrate

autoimmune hepatitis histology2
Autoimmune HepatitisHistology
  • Prominent plasma cells appreciated in this specimen

Plasma cells

drug induced chronic hepatitis
DRUG-INDUCED CHRONIC HEPATITIS

Hepatotoxic drugs:

- Paracetamol

- Isoniazid

- Oestrogens

- Antibiotics

-Methotrexate

-others

slide37

DIVERSITY

> 1000 Hepatotoxic drugs

Diverse

mechanisms

Variety of liver diseases

slide38

METABOLIC ACTIVATION

Drug

CYP

Reactive metabolite

(High Amounts)

  • (Low Amounts)

Extensive

covalent

binding

 GSH

Protein

Immune reactions

Direct toxicity

slide39

MITOCHONDRIAL DYSFUNCTION

Drugs

 Beta-

oxidation

 Respi-

ration

Cell dysfunction

Cell death

Lactic acidosis

Steatosis

fatty liver
FATTY LIVER

Fatty Liver

  • Fat droplets appear in the cytoplasm ofhepatocytes;
  • they may appear a few daysafter an alcohol binge, but are almostalways present in heavy drinkers (> 80 gof alcohol per day for > 5 years).
  • Fattyliver may occur, however, with obesity,diabetes mellitus, starvation and chronichepatitis C virus infection
alcoholic h epatitis
ALCOHOLIC HEPATITIS
  • Alcohol abuse is a massive international problem which has huge resource implicationsboth 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 andfriends.
  • Alcohol damages not only the liver, but many other organs also.
slide43

Altered membrane proteins

Neoantigens formation

Impaired cytoskeletal transport

Stimulation of HSC

Immunological injury

Damage to cell

membranes

Alcoholic Hepatitis

Mechanisms of liver injury

Free radicals

Oxidative injury

Heat

Gut Permeability Endotoxaemia Kupfer cell activation

Gultathione

depletion

ROS &

Free radicals

TNFα

Alcohol dehydrogenase (ADH)

Peroxisomal Catalase

Genetics

Polymorphisms

Male vs Female

Race

Damage

Acetaldehyde

Ethanol

Miscrosomal ethanol-oxidising system (CYP 2E1)

Acetaldehyde

dehydrogenase

Downregulated in

chronic alcohol use

TNFα IL-1, IL-8

Acetate

alcoholic h epatitis1
ALCOHOLIC HEPATITIS
  • Alcoholicliverdiseasemaydevelopinwomenafterlessalcoholconsumptionthanisnecessarytocausehepatitis or cirrhosisinmen.
  • Dailyalcoholconsumptionofapproximately 50 g for 10 to 15 yearsisassociatedwithalcoholicliverdisease

inwomen, whereas

80 gisassociated

withalcoholiccirrhosis

inmen.

pathology of alcoholic hepatitis
Pathology of Alcoholic Hepatitis

Mallorys Hyaline

Centrilobular necrosis

Fatty change

Hepatocyte ballooning

PMN infiltrate

Pericellular fibrosis

alcoholic h epatitis2
ALCOHOLIC HEPATITIS
  • AlcoholichepatitisreferstothepathologicMallorystainfindingsofalcoholichyalinsurroundedbypolymorphonuclearcellinflammation
chronic hepatitis diagnosis
CHRONIC HEPATITISDIAGNOSIS

LABORATORY SYNDROMES:

  • Cytolitic syndrome (↑AST, ↑ALT, ↑GGT, ↑Bilirubin )
  • Cholestatic syndrome (↑conjugated Bilirubin, ↑Alkalinephosphatase, ↑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)
c hronic v iral h epatitis treatment
CHRONIC VIRAL HEPATITISTREATMENT
  • ANTIVIRAL THERAPY (Interferon therapy, Lamivudine therapy)
  • Corticosteroids are contraindicated, because viral replication is enhanced