Viral Hepatitis

Kartika Farahdilla
Lubna Qatrunada
M Ananta Winarto
Anatomy
Largest gland in the body, 1.5kg and 25% adult BW, lies in the RUQ, protected by thoracic cage and
diaphargm, lies ribs 7-11, crosses midline toward the left nipple.
• Surface: 1. Diaphragmatic surface

2. Visceral surface

• Lobes : 1. Anatomical lobes : falciform ligament separates Right and left lobes +
left sagital fissures.

2.acessory lobes : part of RL separated by tranverse porta hepatis,

Quadrate and caudate lobes

• Supply : 1. Blood Vessel : - dual blood supply:1) Vein: Nutrient 2) Artery(hepatic) : O2

-Hepatic portal vein formed by Superior Mesenteric

and splenic vein

2. Lymphatic : - Superficial lymphatic in the sub peritoneal fibrous

capsule of the liver

3. Nerves : -Hepatic plexus

• Portal tract : hepatic portal vein, hepatic artery, and hepatic bile duct.
Histology
• Hepatocytes and hepatic lobules

- Most functional cell, Large cuboidal,polyhedral with large and round nuclei and eosinophilic
cytoplasma rich in mitochondria.

- Function : synthesis plasma protein -> albumin.

Gluconeogenesis, Detoxification dan AA deamination.

Storage of glucose , triglyceride and Vit A dan Fe.

-Liver parenchyme is organized as hepatic lobules(functional unit of liver).

-Between hepatocytes = Vascular sinusoid ( thin,discontinous lining to allow plasma to fill the
perisinusoidal space(space of Disse)

-2 other cells:

Stellate machropage/kuppfer cells : APC, phagocyte aged erithrocyte

Hepatic stellate cell/ ito cell : Store vit A and lipid soluble vit, produce ECM becoming
myofibroblast after liver injury.
• Structure and function

-Rough ER : Synthesis plasma protein , meningkat di portal area.

-Smooth ER: Contain enzyme for detoxification and glucoronyl tranferase

-glycogen granules and lipid droplet in hepatocytes

-Peroxisomes : oxidation of excess FA, conversion purine to uric acid.

-Golgi Complexes: Involved in protein and bile synthesis.

-Mithocondria: Provide energy.

Physiology
• Regeneration: The liver possesses a remarkable ability to
restore itself after significant hepatic tissue loss from either
partial hepatectomy or acute liver injury, as long as the injury
is uncomplicated by viral infection or inflammation. hepatocyte
growth factor (HGF)
Function:
• Filtration of blood by kuppfer cell and storage of blood as
reservoir.
• Metabolism ( glicogen Storage and gluconeogenesis,
Conversion of galactose and fructose to glucose, AA
deamination, removal of ammonia to urea)
• Synthesis of large quantities of cholesterol, phospholipids, and
most lipoproteins
• Bile Formation, a mixture of bile acids (organic acids such as cholic acid), bile salts (the
deprotonated forms of bile acids), electrolytes, fatty acids, phospholipids, cholesterol, and
bilirubin. (Canalicular membrane-> release when duodenum digest meal digestion and storage
in gall bladder for fat absorption)

• Storage of vitamin and iron(Ferritin)

• Formation of coagulation factor( fibrinogen, prothrombin, factor VII)

• Formation of plasma protein

• Detoxification drugs, toxic, hormones and other substances (merubah xenobiotics (konjugasi
zat asing) dan dibuang lewat bile acid.

• Hormon secretion : thrombopetin, hepcidin, IGF-1, angiotensinogen

• Bilirubin metabolism
Viral Hepatitis
Viral hepatitis is a systemic infection affecting the liver predominantly

are caused by one of five viral agents:

• hepatitis A virus (HAV)

• hepatitis B virus (HBV)

• hepatitis C virus (HCV)，

• the HBV-associated delta agent or hepatitis D virus(HDV)

• hepatitis E virus (HEV)

Hepatitis A Virus (HAV)
HAV is a nonenveloped 27 -nm， heat-， acid-， and ether- resistant RNA virus in the
Hepatovirus genus of the picornavirus family

Inactivation of viral activity can be achieved by :

• Boiling for 1 min

• Contact with formaldehyde and chlorine

• By ultraviolet irradiation

Incubation period = ±4 weeks

Transmission = Fecal Oral Route

Hepatitis A Virus (HAV)
• Anti HAV IGM class = ±3 months, rarely
up to 6 – 12 months  Active Infection

• Anti HAV IGG class = protective antibody,

remains indefinitely
Hepatitis E Virus (HEV)
• genus Herpevirus, family Herpeviridae.

• Transmission = Fecal Oral Route

• Mostly through undercooked seafood & contaminated water

• Anti HEV IGM  Active infection

• HEV infection in pregnant women can be very serious

Hepatitis C Virus (HCV)
• RNA virus

• Genus Hepacivirus, Family Flaviviridae

• Transmission = via Blood (Childbirth, IV drugs, etc)

• Gold standard diagnosis using PCR (Early detection 1 – 2 weeks)

Detects Viral RNA in blood, if decreasing means recovery
Hepatitis B Virus (HBV)
• DNA Virus, Hepadnavirus type 1

• Transmission = via Blood (Childbirth, IV drugs, etc)

• Chronic happens in ±20% of all cases, most likely if infection occurs in children <6yo

• Have a compact genome structure ; S, C, P, and X genes

• Hepatitis B antigens and HBV DNA have been identified in extrahepatic site, including Iymph
nodes, bone marrow, circulating lymphocytes, spleen, and pancreas
 Hepatitis B Virus (HBV)

HBV antigens :

• HBsAg  Surface antigen

• HBcAg  Core antigen

• HBeAg  Secreted by infected cells, marker of active infection

Hepatitis B Virus (HBV)
• NK cells, Kupffer cells

• Presented by MHC class I  Bind to CD8 T cells  Apoptosis

• Presented by MHC class II  Bind to CD4 T cells 

Activate Th 1 & Th 2

• Th 2 converts B cell  Plasma cell  Antibody

Hepatitis D Virus
• Genus Deltavirus

• RNA virus that co-infects/superinfection with and requires the helper function of HBV for its
replication and expression

• HDV is a formalin-sensitive, 35- to 37-nm virus with a hybrid structure.

• Its nucleocapsid expresses HDV antigen (HDAg). Antigen expressed mainly in hepatocytes.

• If Anti-HDV IGM or IGG tests +  Active infection

• HDV antigen is expressed primarily in hepatocyte nuclei and is occasionally detectable in

serum
Serologic Markers
Serology
HBsAg
• Present in acute of chronic infection
• Detectable 1 to 2 weeks after infection

HBeAg
• Appears shortly after HBsAg
• Indicates viral Replication and Infectivity

HBsAB(Anti-HBS)
• Present after vaccination or clearance of HBsAg(Usually 1 to 3 months)
• Indicates immunity to HBV

Hb core Antibody (IgM anti-Hbc or IgG anti-HBc)

• Only Serological marker of HBV during "Window Period"
Clinical Progression
• Incubation Period
 Asymptomatic

• Prodromal phase
 Malaise, Fever, Nausea, Vomitting

• Icteric phase
 Tea colored urine, clay colored stool, Jaundice, Prodromal signs

• Convalescent phase
 Icteric
Diagnosis
• Serology

• Liver Chemistry tests

 AST, ALT, ALP, and total Bilirubin

• Histology--Immunoperoxidase staining

• HBV Viral DNA--Most accurate marker of viral

DNA and detected by PCR

• Liver Biopsy--to determine grade(Inflammation)

and stage(Fibrosis) in chronic Hepatitis
Progression
• Incubation Period: 30-180 days

• Acute HBV Infection: 90% resolve by themselves; less

than 1% develop fulminant hepatitic failure

• Chronic HBV Infection: 2-10% progress to chronic state

 90% in children less than five progress to chronic state
 Risk of Liver Cirrhosis: 5 year accumulation risk of 8% to 20%
 5% to 10% of people progress to HCC with or without preceding cirrhosis; less than
5% achieve a chronic carrier state
Treatment
1) Interferon therapy – First Line

• Method of action is the inhibition of viral replication of cells thus

assisting the immune system

• Interferon alpha: TX: SUB-Q 5 million units q D or 10 million

units 3x weekly Sub-Q

• Side effects: "Flulike Symptoms", alopecia, rash, diarrhea

 pINF-alpha(pegylated interferon-alpha): 180ug q weekly SUB-Q
 Better Choice than IFN-Alpha--Greater Bioavailability, Longer
half life, Better treatment schedule
Treatment cont.
2) Nucleoside Analogues -- Lamivudine, Entecavir, Telbivudine

Method of action is the inhibition of viral reverse transcriptase

• Lamivudine
 Dose : 100 mg PO q daily
 Good for reducing the risk of progression to hepatic decompensation in patients with cirrhosis or advanced
fibrosis
 Pregnancy category B--Not teratogenic in animal studies and successful use with pregnant women
 Problem: High rates of resistant mutations
 Side effect: lactic acidosis

• Entecavir – 1st line

 0.5 to 1mg PO
 very effective; low resistance and greater than 90% HBV DNA clearance rate in HBeAG positive Px's.
 more effective than lamivudine
 Side effect: lactic acidosis

• Telbivudine
 Dose: 600mg q daily
 Worse resistant profile than Entecavir
 Side effect: lactic acidosis
Treatment cont.
3) Nucleotide analogues
Method of action is the inhibition of viral reverse
transcriptase
• Tenovir (Indonesia)
 Dose: 300mg qd
 Highly effective with low resistance
 Well tolerated

• Adefovir – 1st line

 Dose: 10mg daily
 Resistance less than Tenovir
 Side effect: nephrotoxicity and lactic acid
Diagnosa Banding
• Penyakit karena virus  dilakukan tes diferensial heterofil dan tes
serologis

• Drug induced hepatitis  riwayat obat-obatan

• Hepatitis alkoholik  biasanya kadar serum aminotransferase tidak begitu

meningkat. Pada biopsi liver dapat ditemukan fatty infliltration, reaksi
inflamasi neutrofilik, dan alcoholic hyaline.

• Kolesistitis akut, batu empedu, atau ascending kolangitis  Untuk

menyingkirkan diagnosa ini dilakukan biopsi liver perkutan sebelum
dilakukan laparotomi.
• Extrahepatic manifestation of hepatitis

Clinical condition Associated comments

virus
Polyarteitis nodosea HBV 60 % have HBV

Glomeronephritis HCV & HBV Mainly mesengioproliferative –result in CRF

Porphyria cutnea tarda HCV Blistering lesion on back of hands
Cryoglobulinemia HCV Type 2 (mixed – essential)
Sjogren syndrom HCV Virus isolated from salivary tissue
Lichen planus HCV 60 % have HCV
Others associated with HCV Studies involve small number of patients
Erythema nodusm – erythema multiforme Impotance need evaluation
Polymyosistis – hachimoto’s thyroiditis
Diabetes mellitus – bahcet’s syndrome
Down syndrome – Aplastic anemia
Prophylaxis
HBV Vaccine

• Indicated for everyone and especially those in high risk groups

 IM injection at 0,1,6 months in infants and adults
 Response greater than 90% after 3rd dose

HBV Pregnant Mothers

• Give 1st dose of Hip B vaccine and Hip B Immunoglobulin(HBIG) o.5 ml within 12
hours of birth.
 2nd dose at 1 month, 3rd at 6 months
 Recheck at 12 months for active infection
 95% lifetime immunity
 Not Done---leads to 90% chronic HBV
 Transmitted through birth canal during birth or through umbilical cord.

Others i.e. those receiving a needle stick

• Should receive 0.04 to 0.7 ml/kg of HBIG and 1st dose vaccine within 48 and no later
than a week.
Terima Kasih