Hepatitis viruses

Virus Family Nucleic acid Capsid Envelope stable sensitive

properties

Hepatitis A (HAV) PICORNA

Hepatitis E (HEV) Unclassified (Hepevirus genus) Icosahedral

Hepatitis B (HBV) Hepadnavirus DNA (Partially DS circular)

Hepatitis D (HDV) Unclassified RNA (close circular SS ve sense) Spherical Enveloped Ether

Hepatitis C (HCV) Flaviviridae (Hepacivirus genus) RNA ( SS +ve sense) Icosahedral

RNA ( SS +ve sense) Naked (non enveloped) Ether heat(60 C for 1hr) acid Autoclave Boiling 5 min Chlorine

Genomic diversity & structure

One serotype known

Outer shell or envelop : host cell derived + HBV surface Ags Inner core (nucleocapsid) : core protein (HBc-Ag) + DNA + DNA polymerase Hbe-Ag: another protein not assembled within virion secreted in soluble form Chronic carriers are asymptomatic , lead to cirrhosis, liver failure and HCC Coinfection : same as B Superinfection of HBV carrier : over 70% Endemic area : among HBV patients by inapparent parentral route Non endemic : drug addicts -hemophilia Parentral Sexual Perinatal is infrequent 2-12 w (3months) Co-infection by HDV & HBV at same time is more severe than HBV alone-same chronocity Superinfection of HBV chronic carriers is more severe

6 genotypre - >100 subtypes According genes encode envelope glycoprotein Differ in : response to antiviral therapy & worldwide distribution (4a common in Egypt) Same : C/P As B lead to: cirrhosis, liver failure and HCC Usually per cutaneous & per mucosal by blood as HBV e.g. drug injection hemodyalysis Uncommon Sexual and mother to infant transmission ( e HIV ) No in Breast feeding 10-50 % no apparent risk factor 6-7 weeks (2 months) Asymptomatic or mild + non specific symptoms 70-90% progress to chronicity Cirrhosis - HCC Chronic liver disease Most common indication for liver transplantation A) early exposure Anti HCV Abs with in 2 5 m HCV RNA within 1-3 w ( diagnosis in sero-ve) B) Acute self limiting: Ab titre C) Resolution : no viremia normal AST ALT

chronicity

No chronicity Feceal-oral route

Epidemiology & Transmission

Poor sanitation children ( immune at 10 y) Good sanitation older

in serum - saliva-semen-vaginal secretion Endemic in tropical Parentral by blood transfusion or injections areas water brone Sexual epidemics Peri-natal from mother and Breast feeding (rare in utero Egypt : endemic & transmission) sporadic 40 d (1month) As HAV High mortality rate in pregnancy fulminant hepatitis 10-12 w (3 months) Asymptomatic or similar to A but more severe In adults: 90-95% recover In infants:80-95% become chronic carriers Chronicity lead to : Liver failure cirrhosis HCC ( HBV vaccine is 1st vaccine prevent human cancer ) A) acute infection HBV RNA & HBe-Ag viremic stage IP Anti HBe indicate resolution HBs-Ag late IP- symptomatic stage indicate active disease disappear after exposure by 6 months Anti HBs after window phase protective , neutralizing IgM specific anti HBc onset of clinical illness viral replication

IP C/P

Prognosis (outcome)

3- 4 w ( 1 month) Asymptomatic in children Severe in adults 99% Recover in 2-4 weeks No reinfection (long life immunity by IgG) No chronicity No carrier Prodromal phase Viremia (short duration-low titre) virus particles in stool

Serologic events

Acute phase ( jaundice - liver transaminases) virus particles in stool IgM Recovery phase IgG : long life immunity

Hepatitis viruses
D) Chronic : viremia + ALT increase intermittently

B) chronic infection HBs-Ag persist > 6 months in presense of HBe-ag or anti-HBe + Low titre of IgM anti-HBc

Anti HAV IgM :acute hepatitis A Anti HAV IgG :past infection or vaccination Lab diagnosis Antigen in stools by ELIZA HAV RNA in stools by PCR

HEV Antibodies & RNA in serum

AB detection by ELIZA acute window recovery +ve -ve -ve HBs-Ag -ve +ve Anti HBs -ve +ve +ve +ve anti HBc Vaccination by HBs-Ag Anti HBs only HBe-Ag high transmissibility anti HBe less transmiissability Viral DNA : infectious virions are present

chronic +ve -ve +ve

Detection of: HD Ag IgM, IgG anti HD HDV RNA

Antibodies ( by ELIZA ) -ve : early seronegative -ve in poor serologic response e.g. ( hemodyaliasis) confirmed by PCR +ve : not differenciate bet acute chronic resolved Fasle +ve : confirm by RIBA if +ve PCR HCV RNA by RT PCR Confirm active disaes Diagnose early sero ve Diagnose poor serologic response (-ve) resolution Quantative PCR : measure viral load monitor response to therapy

Active Formalin inactivated HAV vaccine Prepared in human cell culture Safe effective person > 1year 2 doses (initial & booster after 6-12 m) Immunization Passive : by gamma globulins 1-2 w after exposure to HAV make infection milder or subclinical

No vaccine

Active HBV vaccine (most effective) 1- plasma derived : HBs-Ag purified from +ve carrier treated e inactivating agents 2- recombinant DNA derived : HBs-Ag produced in yeast cell For : - 1- all infants 2- health care personnel 3- patients receive many transfusions or dialysis Passive immunization by HBv immune globulin ( HBIG) Immediate passive soon after exposure Both active & passive given at different sites to : 1infants to HBV +ve mothers 2- persons exposed HBV

No vaccine but HBV vaccine can prevent infection. however, it not protect carriers from superinfection

No vaccine

Hepatitis viruses
Control 1-Prevent fecal contamination 2-Good hygiene 3-Chorination of water 4-proper sewage disposal 1-virus inactivation in plasma pools products 2- screen all blood for transfusion & organ donors 3- sterilization of endoscopes surgical instruments 4-Use disposal needles syringes 5-health education of MOI 5-Prevent prevent percutaneous permucosal contact e blood or body fluids ( gloves, decontamination, ..)