Epidemiology: Hepatitis A Mode of transmission: Fecal Oral Hepatitis B Mode of transmission: HBV3 Ag in body Fluid of infected person Tears

Tears Saliva Seminal fluid CSF Ascitis fluid Brest milk Synovial fluid Gastric fluid Pleural fluid Urine Greatest impact: intimate (sexual contact) and perinatal transmission Hepatitis C (non A,non B) Mode of transmission: Blood donation

Hepatitis D Mode of transmission: Blood and blood products Drug addicts Haemophiliacs

Acute viral hepatitis 5 categories of viral agents: Hepatitis A virus (HAV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) subclinical persistent infection to rapidly progressive chronic liver Hepatitis D virus (HDV) disease with cirrhosis and hepatocellular carcinoma Hepatitis A - IP: 4 weeks - Virus present in liver, bile, stools, blood - Pre icteric phase- during late IP infectivity diminishes rapidly as jaundice appears

Clinical Features: Hepatitis A Hepatitis B and D Hepatitis C Hepatitis E Incubation period 15-45 days 30-180 days 15-60 days 14-60 days Mean 4 wks 4-12 wks 7 wks 5-6 wks

Prodromal: 1-2 wks Anorexia N/V Gen. Body malaise/fatigue Myo- arthralgia Head ache/photophobia Pharyngitis/coryza/cough Jaundice- prodromal symptoms diminish Temp. -38 to 39 C often in Hep. A and C Hep. B when heralded with Serum Sickness Syndrome: dark urine/ clay colored stools 1-5 days before jaundice, tender large liver, splenomegaly/cervical lymphadenopathy (10-20%) Recovery phase- post icteric (2-12 wks) -constitutional symptoms disappear -enlarged liver Complete recovery- 1 to 2 mos.

Hepatitis B Pathogenesis and natural course: Chronic HBV infection is a serious clinical problem 1. World wide distribution especially in the Asia-Pacific region, majority of cases acquired perinatally or in early childhood 2. Potential adverse sequelae -DNA plays a key role in the maintenance of chronic HBV infection -HBV is not usually cythopathogenic, but a state of interaction between virus, hepatocytes and host immune sys. HBV infection can be divided into 3 phases1. Immune Tolerance Phase- high HBV replication with little clinic-pathological changes 2. Immuno Clearance Phase- Hepatitis activity and hepatitis flares, increased serum ALT over symptoms upper limit of normal, + hepatitis decomposition Host immune response against HBV: -Hence, higher ALT levels reflect more vigorous immune esponse against HBV and more extensive hepatocyte damage -Hep Be Ag (HBeAg) and/or sero-conversion to antibody -(anti HBe) and/or undetectable HBV- DNA up to 85% of HBeAg sero-conversion assoc w/ clinical remission (inactive chronic HBV infection) - however, there can be reactivation or active hepatitis may occur due to: HBeAg reversion, or

 Occurrence of HBeAg negative HBV-DNA positive Chronic Hepatitis B Cirrhosis -Estimated Annual Incidence: 2.1% -HBeg Negative Hepatitis progress to cirrhosis (23%) -hepatocellular carcinoma (4.4%) with years follow up -even in asymptomatic chronic hep B,but sero(+) For HBeg and/or HBV- DNA are risk factors For cirrhosis and hepato cellular carcinoma -spontaneous HBsAg sero-clearance has excellent prognosis - HBV classified into 8 genotypes: A and D- Africa, Europe, India B and C- Asia E- West Africa G- France, Germany, USA H- France, Central America -Genotype B associated with spontaneous HBeg sero conversion at a younger age less active liver disease slower progression to cirrhosis less frequent development to hepeto cellular carcinoma -Management: Goals of treatment 1. sustained Viral Suppression- key to reduction or prevention of hepatic injury and disease progression, therefore,primary goal for treatment of Chronic Hepatitis B is to eliminate or permanently suppress HBv, thereby, decrease pathogenicity and infectivity stop or reduce hepatitis necro inflammation Short Term Goal 1) Ensure HBV- DNA sustained suppression 2) ALT normalization and prevent development of decompensatio reduce hepatic necro inflammation and fibrosis Ultimate long term goal 1) Interferon Alpha- Dual mode of action: Antiviral Immune modulatory Dose: 5mu daily 3x awk for 4-6mos. Result: HBEAg less in 33% of HBeAg positive 2) Lamivudin

3) Adefovir

Hepatitis Bx Antigen (HBxAg) - Antibodies in patients with severe chronic ative hepatitis and hepato cellular carcinoma - Encoding genes: S-genes C-genes P-genes X-genes - Transferases previously SGOT/SGPT - Alanine aminotransferase (ALT) - Aspartate serumtransferase (AST) - Pathogenesis:

not directly cytopathic to hepatocyte but rather cellular immune response of the host cytolytic T-cells recognize Hepatitis B viral Ag on liver cell surface and destroy HBV infected hepatocytes HBV may have direct cytopathic effect on liver cells, independent of immune system Hepatitis B Ags: 1) Hepatitis B surface Ag (HBVsAG)- protein in the outer surface of virus 2) Hepatitis B Core Ag (HBVcAg)- protein in nucleocapsid core, remains in hepatocyte for replication 3) Hepatitis B endoplasmic Ag (HBVeAg) -soluble non particulate nucleocapsid in the pre core region -bound to smooth endoplasmic reticulum and leads to its secretion into the circulation -qualitative marker of HBV replication and relative infectivity -persistent HBVeAG means ongoing viral replication and associated with continuing disease activity in chronic hepatitis -its disappearance means improvement and resolution of infection HBVsAg and serum containing HBVeAg is highly infectious and associated with presence of HB virus HBVsAg carrier mother who are HBVeAg+ transmits Hep B infection to offspring (>90%)