Prof. Dr. Asem Shehabi Faculty of Medicine University of Jordan Hepatitis viruses Prof. Dr. Asem Shehabi Faculty of Medicine University of Jordan

Hepatitis viruses Classification Hepatitis is inflammation of liver cells.. followed first by accumulation of bilirubin in liver & other body's tissues.. Jaundice/yellow colored Skin & Eye, Dark Urine, Pale stools, Fever, Weakness & Myalgia. Viral Hepatitis caused directly and mostly by five viruses : Hepatitis A (HAV), Hepatitis B (HBV) , Hepatitis C (HCV), Hepatitis D (HDV), Hepatitis E (HEV). Other viruses that may cause mild to severe form of Hepatitis as complication : Herpes simplex virus 1+2, Yellow fever virus, Cytomegalovirus, Epstein-Barr virus, & certain Enteroviruses.

Hepatitis A Virus Part of Picornavirus Group .. A small ss+ve RNA covered by a Protein shell.. Non-enveloped.. stable to Acid & Heat.. Survive at 0-25 C.. Few Days-Weeks in water & fresh food. It still highly Endemic in Most Developing Countries.. including All Arab Countries. Human Hepatitis virus (HAV) causes often Epidemic outbreaks ..One main serotype.. 4 genotypes . Transmission: Fecal-oral route.. Personal contact, Families.. Schools, Restaurants.. contamination water, Shellfish, Fresh vegetables with fecal sources. Often associated with Low Standard of Hygiene in Restaurants .

2/ Clinical Features: Incubation: 2-6 weeks. Virus multiplies first intestinal mesenteric Lymph nodes.. Spread to Blood causing mild viremia & Liver cells inflammation.. liver macrophages.. Return back from liver via bile duct to intestines.. large amount viruses particles excreted in feces, less in urine. HAV causes only acute infection.. mostly mild liver inflammation / Jaundice in Children (5%).. More severe Jaundice in adults ..Rarely Liver Cirrhosis/ Lever failure & Death. Hepatitis liver damage is due to immune response /hypersensitivity.. Increase amount Cytotoxic T-Cells & release of Cytokines..

Hepatitis A-2 There is no chronic infection cases nor healthy carriers.. Infected children may excrete virus up to 6 months. Most children recover from infection/Jaundice within 1- 4 week.. Adults 2-8 weeks. Lab diagnosis: Anti-HAV IgM indicates Acute infection.. IgG indicates Immunity .. Mostly Long-life immunity after natural infection. Inactivated HAV Vaccine is given intramuscularly 2- doses, Children 0-1-year .. Protection up to 95%.. AHV+HBV Vaccine is available..No effective drug treatment.

Hepatitis B-1 HBV has ds-DNA.. surrounded by capsid & envelop with complex structure ( Fig.-1) . Smallest human virus.. Replication in hepatocell nucleus.. Free virus DNA can be integrated as extrachromosomal nucleus. . other part host cells chromosomes. Three major HBV particles: HBsAg: Composed 3 surface antigens ( M, S,L-glycoproteins+ lipoprotein) embedded in outer Lipid envelope. HBsAg presence in blood indicates acute HBV infection .. produced in excess amount as small spheres and filaments in blood & liver cells..

Hepatitis B Virus

2/ HBcAg: composed protein core antigen nucleocapsid attached to viral DNA & DNA polymerase enzyme/ Dane particles are virus infectious part. in host plasma.. Associated with Acute Clinical features/chronic liver infection HBeAg: is derived from HBcAg during replication.. Present in blood during acute/chronic infection. HBV Classified in 8 major genotypes (A-H) & many subtypes.. According to the nucleotide sequences of each strain.. Each country has a specific number of genotype strains. HBV is heat-resistance up 20 minutes in boiling water, UV-Light.. Survive in blood droplets few days.. Killed by Autoclave/Formalin or 10% of hypochlorite solutions..24 hrs contact time..Survive few days.

HBV Antigens

2/ HBV is highly endemic in many countries.. About 300 millions chronic carriers worldwide.. One Million death occurs yearly worldwide. Jordan has about 2% chronic carriers. HBV is transmitted horizontally by blood transfusion.. vertically from infected mother through maternal fluid/blood to infant during delivery.. Less by transplacental route , Blood products, needle stick injures, saliva, semen or biting / scratching.. Intravenous drug use & sexual transmission is major infection source for adults in developed countries.

HBV Infection-3 HB Incub. period 2-6 months.. mean 3 months.. causes acute/ chronic hepatitis. Acute hepatitis B ranges from subclinical disease to fulminate hepatic failure in 2% of cases /death within few weeks-months according to the immunological response . Acute hepatitis begins with loss of appetite, nausea, vomiting, fever, abdominal pain, extreme fatigue.. Later few weeks Jaundice. This may indicates start of recovery or more severe disease. About 90% of infected neonates .. 50% of infected young children will become chronically infected. . only about 5%-10% of immune competent adults infected with HBV develop chronic hepatitis B.

4/ Adult acute infection: About 95% recover without complications.. Chronically infected.. especially Neonates/Children.. Their acute infection may not be clinically recognized. Immunity: Infection induce both B & T cell responses.. Chronic liver damage occurs with increased immune-mediated destruction of hepatocytes due to cytotoxic T cell reaction & autoimmune reaction.. causing Liver cirrhosis. Chronic hepatitis..with liver disease / serious liver cirrhosis.. May result later in Fulminant hepatitis or Hepatocellular carcinoma & death (1%) within 10-40 years.. Especially in association with other infectious agents..like Malaria, Bilharzias ,AIDS.

Interpretation of serologic Assays of HBV infection HBeAg Anti-HBe Anti-HBc Anti-HBS HBsAg No infection -ve Vaccination +ve Immunity after recent infection Acute /chronic infection + DNA

Laboratory Diagnosis The diagnosis of HBV infection is generally made on the basis of blood serology. Virtually all persons infected with HBV, either acutely or chronically, will have HBsAg, HBeAg , Anti-HBc , + HBV DNA Elevated transaminases/ alanine aminotransferase & Serum bilirubin for more than 2 weeks.. HBsAg is detectable several week after acute infection with/without the onset of clinical symptoms. Presence of HBeAg + HBV DNA indicates acute infection ..Patient is highly infectious . Persons who develop an immune response against HBV infection show mostly : 1) Anti-HBsAg 2) Anti-HBcAg 3) Anti- HBsAg within 6-12 months.

Treatment & Prevention Persistent HBeAg & HBV DNA have a generally worse prognosis .. A greater chance of developing Liver cirrhosis .. hepatocellular carcinoma. Accidental or acute HB infection can be treated with HB immune-globulin (HBIG) & lamivudine HBIG should be given within 24 hs and 48 hs after accidental infection & Plus HBV Vaccine Adults Vaccination – HBV: 2-3 doses.. Intramuscularly.. 95 % protection Vaccination newborn babies: 0, 1, 6 months about100% protection.. Protection is confirmed by presence high titers of Anti-ABsAg >100 IU

Hepatitis D HDV.. called Delta virus.. is a small circular RNA.. Its envelop composed of HBsAg ..Following attachment to HBsAg becomes infectious agent. HDV infection only occurs in the presence of HBV infection. First discovered in Italian patients infected with HBV.. Mostly found in elder patients & chronic cases. HDV infection is transmitted mostly by blood and blood products. The risk factors for infection are similar to those for HB infection.. HDV ..Commonly found intravenous drug users.

Hepatitis D-2 Co-infection (HBV+HDV) is associated more with liver cirrhosis , chronic disease & complications. Severe acute HB infection could suggest presence HD co-infection. Co-infection in a patient with HB is diagnosed by the presence of IgM HDV antibodies Treatment: Alpha Interferon+ Lamivudine is used to treat patients with chronic hepatitis B and hepatitis D infection.. HBV vaccine prevent infection with HDV.

Hepatitis C HCV : Part of Flavi virus group..small enveloped SS+ RNA covered by 2 envelop proteins (E1, E2), 6 Genotypes & many subtypes..Less Resistance to heat, dryness & disinfection solutions than HBV. HCV infection is more prevalent in developing countries than developed countries. Types 1 Worldwide , Type 4 Arab countries.. Mostly in Egypt (15 % population). Replication: Hepatocells, Lymphocytes, Stem cells Bone Marrow Incubation period: 6-8 weeks.. Mostly mild acute hepatitis or asymptomatic without Jaundice, Abnormal Liver Function tests .. Slowly progressive to Liver Chronic disease.. Cirrhosis or Hepatocellular Carcinoma (50%) after many years .

2/ Transmission: Blood transfusions, blood products, organ donation , intravenous drug abusers, needle-sticks injures , Haemodialysis patients, Rarely through sexual contact . Mother to child transmission occurs during delivery by maternal fluids, blood .. No vertical transmission. Diagnosis: Anti-HCV IgM indicates acute / chronic infection. Anti-HC V IgG alone indicates exposure ..Not Chronic case Combination therapy alpha-interferon & ribavirin for treatment acute /chronic cases..at least 12 months. There is no vaccine available due to continuous change of HCV envelop antigens.

Hepatitis E HEV ss(+)RNA.. It is still not well classified.. Heat and Acid stable.. Fecal-oral route. Transmission: Oral-fecal route through Water, Fresh Food, Close contact. Common in India, Mexico and North Africa..Few cases detected in Jordan Pathogenesis: Similar to HAV replicates in the gut initially, before invading the liver and return back to blood and Virus DNA shed in the stool before the onset of major clinical symptom Jaundice. Clinical Features: Incubation period 3-8 weeks Acute, self limiting hepatitis, no chronic carrier state ..most infections occur in young adults (15-40 )years. Complications: Severe cirrhosis in pregnant women & immunocompromised patients .. Mortality rate is high (up to 40%). Diagnosis: Anti-HEV IgG.. Detected only during Acute disease.. No vaccine or therapy is available.