Download chronic viral hepatitis

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
Walls of
scar
tissue
begin to
form
Healthy liver cells
become trapped
by a wall of scar
tissue
CYTOLYTIC SYNDROME
 alanine
aminotransferase increased,
 aspartate aminotransferase increased
 Increased LDH
 Increased ferritin
 Hyperbilirubiemia
Cholestasis

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







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
Hepatocellular Mesenchymal
insufficiency inflammation
 Albumin
 Transferrine
 Cholesterol
 protro,mbine
 Hyper-γ
globulinemia
 CRP
 ESR
 Cholinesterasa
 Α-lipoproteins
 Hyperbilirubinemia
Signs of CLD
CHRONIC HEPATITIS
CLASSIFICATION
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
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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
Grades of Inflammation
and Stages of Fibrosis on Liver
Biopsies
CHRONIC HEPATITIS
CLASSIFICATION
ACCORDING TO SEVERITY
(level of Aminotransferases)
A C T I V ITY
MILD
MODERATE
SEVERE
CHRONIC HEPATITIS
COMPLICATIONS
 HEPATIC
ENCEPHALOPATHY
 VARICEAL BLEEDING
 ASCITES
 GLOMERULONEPHRITIS
 OTHERS
General Concepts
 Hepatitis
= 'inflammation of the liver'.
 six medically important viruses are commonly
described as “hepatitis viruses”:
HAV,HBV,HCV,HDV,HEV,HGV.
Viral Hepatitis - Historical Perspectives
“Infectious”
Viral hepatitis
“Serum”
Enterically
E
transmitted
A
NANB
B D
Parenterally
C transmitted
F, G, TTV
? other
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.
HBV : Structure
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
Possible Outcomes of HBV Infection
Acute hepatitis B infection
3-5% of adultacquired infections
95% of infantacquired infections
Chronic HBV infection
Chronic hepatitis
12-25% in 5 years
6-15% in 5 years
Cirrhosis
Hepatocellular
carcinoma
Death
20-23% in 5 years
Liver failure
Liver transplant
Death
Laboratory Diagnosis
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.

Natural History of Hep C
Only 20% will
show symptoms
Initially !
Healthy
Liver
Acute
Infection
Adapted from Lauer and Walker, NEJM 2001
20%
Clear the
Virus
Chronic
Infection
80% Virus
Continues
to Damage
Liver
Natural History Con’t
Chronic
Hepatitis
Cirrhosis
20-30%
Liver
Cancer
1-4%/year
Most symptoms begin to show only when liver is more severely damaged
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%.
Autoimmune Hepatitis
Histology

Lymphoplasmacytic
infiltrate
 Interface hepatitis
Portal inflammation
and invasion of
limiting plate
Autoimmune Hepatitis
Histology

Prominent lobular
infiltrate composed of
mononuclear and
plasma cells
Lobular infiltrate
Autoimmune Hepatitis
Histology

Prominent plasma
cells appreciated in
this specimen
Plasma cells
DRUG-INDUCED CHRONIC
HEPATITIS
Hepatotoxic drugs:
- Paracetamol
- Isoniazid
- Oestrogens
- Antibiotics
-Methotrexate
-others
DIVERSITY
> 1000 Hepatotoxic drugs
Diverse
mechanisms
Variety of liver diseases
METABOLIC ACTIVATION
Drug
CYP
Reactive metabolite
(Low Amounts)
(High Amounts)
Protein
Immune reactions
Direct toxicity
Extensive
covalent
binding
 GSH
MITOCHONDRIAL DYSFUNCTION
Drugs
 Betaoxidation
Steatosis
 Respiration
Cell dysfunction
Cell death
Lactic acidosis
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
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.
Effects of
alcohol
abuse
Alcoholic Hepatitis
Mechanisms of liver injury
Free radicals
Oxidative injury
Heat
Gut Permeability
Endotoxaemia
Gultathione
depletion
Kupfer cell activation
TNFα
ROS &
Free radicals
Ethanol
Alcohol dehydrogenase (ADH)
Peroxisomal Catalase
Miscrosomal ethanol-oxidising
system (CYP 2E1)
Downregulated in
chronic alcohol use
Acetaldehyde
Acetaldehyde
dehydrogenase
Altered membrane proteins
Neoantigens
formation
Acetate
Impaired cytoskeletal transport
Stimulation of HSC
Genetics
Polymorphisms
Damage
Male vs Female
Race
TNFα
IL-1, IL-8
Immunological injury
Damage to cell
membranes
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.
Pathology of Alcoholic Hepatitis
Mallorys Hyaline
Centrilobular necrosis
Fatty change
Hepatocyte ballooning
PMN infiltrate
Pericellular fibrosis
ALCOHOLIC HEPATITIS
 Alcoholic
hepatitis
refers
to
the
pathologic Mallory
stain findings of
alcoholic
hyalin
surrounded
by
polymorphonuclea
r cell inflammation
CHRONIC HEPATITIS
DIAGNOSIS
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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)
CHRONIC VIRAL HEPATITIS
TREATMENT
 ANTIVIRAL
THERAPY (Interferon
therapy, Lamivudine therapy)
 Corticosteroids
are contraindicated,
because viral replication is enhanced
INTERFERON THERAPY
(Intron A, Velferon, Reaferon, Laferon)
CHRONIC VIRAL
HEPATITIS B:
5-10 million
Units 3 times a
week s/c or i/m
for 3- 4-12
months
CHRONIC VIRAL
HEPATITIS C:
3-5 million units
3 times a week
for 12-18 months
CHRONIC VIRAL
HEPATITIS D:
10 million units
3 times a week
for 12-18 months
Autoimmune Hepatitis
Week Monotherapy
Prednisolone,
mg
Prednisolone (mg) and
Azathioprine (mg/kg)
combination therapy
Prednisolone
Azathioprine
1
50
50
50-150
2
3
50
40
40
30
50-150
50-150
4
30
20
50-150
5
25
15
50-150
6
20
12,5
50-150
7,8
15
10
50-150
HEPATOPROTECTORS
Plant
Essential phospholipids
Carsil, Legalon,
Hepabene, Chofitol
Essentiale, Enerliv
Aminoacids
Glutargin, Citrarginin
α- lipoic acid
Berlithion
Ursodezoxycholic acid Ursofalc, Ursosan
Synthetic
Thiotriazolin, Antral
Animal
Vitohepat, Sirepar
Homeopathic
Halstena