Viral hepatitis a+e

VIRAL HEPATITIS Dr Kamran Afzal Classified Microbiologist

HEPATITIS Hepatitis is defined as a widespread damage to the liver hepatocytes with inflammatory changes In acute hepatitis liver damage is centrilobular or widespread and may either result in limited or massive necrosis of the liver parenchyma resulting in liver failure A: Infective B: Non-infective Direct cytotoxicity probably more important In chronic hepatitis there is long standing inflammation and replacement of liver parenchyma by fibrous tissue with loss of function ultimately leading to cirrhosis A: Infective B: Non-infective Immune response probably more important

A “ Infectious” “ Serum” Viral hepatitis Enterically transmitted Parenterally transmitted F, G, TTV ? other E NANB B D C Viral Hepatitis - Historical Perspectives

Classification of Hepatitis Viruses *linear, single strand; ** circular, double strand; *** circular, single strand Virus HAV HBV HCV HDV HEV DNA or RNA RNA* DNA** RNA* RNA*** RNA* Family Picornaviridae Hepadnaviridae Flaviviridae Deltavirus (genus) ? Envelope no yes yes yes no (Previously classified as a calicivirus)

Basic Features of Hepatitis Viruses Virus A B C D E Incubation Period* 4 (2-6) 8-12 (6-24) 6-9 (2-24) ? (2-10) 4-5 (2-9) Transmission fecal-oral parenteral parenteral parenteral fecal-oral * Weeks Chronic Infection No Yes Yes Yes No

CAUSES OF ACUTE HEPATITIS Viral Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus Hepatitis G virus Cytomegalo (CMV) Epstein-Barr (EBV) Herpes simplex (HSV) Yellow Fever viruses (YFV)

Non-Viral infections Bacterial: Typhoid fever, Q fever, RMSF, Leptospirosis, sepsis Parasitic: Amoebic, Toxocariasis, Liver flukes Drugs Acetaminophen, INH, rifampin, oral contraceptives, anti-seizure drugs, carbenicillin, sulfonamides Poisons Alcohol, Mushrooms, Carbon tetrachloride Metabolic Wilson’s disease, fatty change in pregnancy Autoimmune diseases Autoimmune hepatitis, SLE

CAUSES OF CHRONIC HEPATITIS Viral: B,C,D,G? Toxins: Alcohol, Drugs Biliary obstruction Primary biliary cirrhosis Secondary biliary cirrhosis: stricture, stone, neoplasms Primary sclerosing cholangitis Metabolic diseases Heamochromatosis: Primary and secondary Wilson’s disease Alpha-1 antitrypsin deficiency Hepatic congestion Initially congestion then inflammatory swelling and then cirrhosis Budd chiari syndrome, CCF, Venous congestion Unknown: Autoimmune, cryptogenic

LABORATORY FINDINGS IN AVH Laboratory indicators of liver pathology Elevated ALT (SGPT) and AST (SGOT) Elevated bilirubin Elevated alkaline phosphatase Laboratory indicators of infection Increased WBC Detection of IgM antibodies in acute infection Four fold rise in the antibody titer Isolation of the virus in cell culture Total immune globulin (Total Ig) Combination of IgM and IgG Early infection - primarily IgM Late infection - primarily IgG

NATURE OF HAV Enterovirus included in the family Picornaviridae HAV is a 27 – 30 nm spherical particle with cubic symmetry Contain linear ss-RNA genome Non-enveloped RNA virus Replicates in the cytoplasm of the cells Only one serotype

HAV CHARACTERS HAV are stable to treatment with 20% ether, acid and heat at 60 0 C for 1 hour The virus are destroyed by Autoclaving at 121 0 C for 20 minutes Boiling in water for 5 minutes Treatment with chlorine 1 ppm for 30 minutes Heating food > 85 0 C for 1 minute

EPIDEMIOLOGY A major communicable disease in the developing world Community hygiene is important in schools, hostels and jails, as overcrowding and poor sanitation favour the spread Well cooked food and sanitary water supply will protect Many cases occur in community-wide outbreaks highest attack rates in 5-14 year olds children serve as reservoir of infection Persons at increased risk of infection travelers homosexual men injecting drug users

TRANSMISSION Transmitted by fecal-oral route Ingestion of food or water contaminated, even in microscopic amounts Virus appears in the feces about 2 weeks before the appearance of symptoms Virus present in blood and feces 10-12 days after infection Level of viremia is low, chronic infection does not occur hence rarely transmitted through blood

Close personal contact Household contact, child day care centers Contaminated food or water with fecal matter Infected food handlers, raw shellfish Blood exposure (rare) Injecting drug use, transfusion Not transmitted by Transplacental route

PATHOGENESIS Entry from mouth The virus replicates in the gastrointestinal tract and spreads to the liver via blood, viral replication in the liver Hepatocytes are infected but no cytopathic effect on hepatocytes has been observed Cytotoxic T cells produced during the immunological reaction cause the damage which is repaired, infection clears and no chronicity develops In acute phase of the disease IgM antibodies appear- diagnostic, followed by the appearance of IgG antibodies – make the person immune to further infection

PATHOLOGY Microscopically there is spotty parenchymal cell degeneration, with necrosis of Hepatocytes and disruption of liver cell cords The parenchymal changes are accompanied by Reticuloendothelial (KUPFFER) cell hyperplasia, peri-portal infiltration by monoculear cells and cell degeneration Localised areas of necrosis are frequently observed Later, accumulation of macrophages near degenerating Hepatocytes

CLINICAL FINDINGS Incubation period is 2-4 weeks -> short incubation hepatitis Fever, anorexia, nausea, vomiting, jaundice, liver tenderness Dark urine, pale feces Most HAV infections are asymptomatic, detected only by the presence of antibodies No chronic carrier state, no chronic hepatitis, no predisposition to hepatocellular carcinoma Recovery in 4-6 weeks Complications Fulminant hepatitis, Cholestatic hepatitis, Relapsing hepatitis Mortality 0.1 – 1 %

LABORATORY DIAGNOSIS Acute infection is diagnosed by the detection of HAV-IgM in serum EIA Past Infection - immunity is determined by the detection of HAV-IgG EIA Cell culture Difficult and takes up to 4 weeks, not routinely performed Direct Detection EM, PCR of HAV in faeces Can detect illness earlier than serology but rarely performed

Fecal HAV Symptoms 0 1 2 3 4 5 6 12 24 Hepatitis A Infection Total anti-HAV Titer ALT IgM anti-HAV Months after exposure Typical Serological Course IgG anti-HAV

TREATMENT No antiviral therapy is available Bed rest During the period of anorexia, the patient should receive frequent small IV fluids with glucose Advise patient to avoid substances that may affect liver function Medication such as acetaminophen, herbs, illicit drugs and toxins Be very careful about personal hygiene to avoid fecal-oral transmission to other members of the household

PREVENTION Active immunization with vaccine containing inactivated HAV Passive immunization with immune serum globulin if given prior to infection or within 14 days after exposure to infection can prevent the disease

VACCINATION Hepatitis A vaccination is recommended for all children starting at age 1 year, travellers to certain countries, and others at risk A safe and effective formalin inactivated vaccine containing HAV grown in human diploid cell culture is available A full course containing two intramuscular injections of the vaccine 1 dose booster dose 6-18 months after first dose Protection starts after 4 weeks after injection and lasts for 10 – 20 years

Vaccine Recommendations International travelers Homosexual men IDUs Persons with occupational risk People with impaired immune systems or CLD People with blood-clotting disorders who receive clotting factors Healthcare workers Child care centers not routinely recommended Sewer workers or plumbers Food handlers: may be considered based on local circumstances

HEPATITIS E VIRUS Calicivirus-like viruses Non-enveloped RNA virus, 32-37nm in diameter Single stranded RNA genome Very labile and sensitive Can only be cultured recently

Most outbreaks and epidemics associated with fecally contaminated drinking water Several other large epidemics have occurred in the Indian subcontinent, the USSR, China, Africa and Mexico In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) has been found in healthy populations Minimal person-to-person transmission EPIDEMIOLOGY

TRANSMISSION HEV is found in the stool of persons with hepatitis E HEV is spread by eating or drinking contaminated food or water Transmission from person to person occurs less commonly than with hepatitis A virus Most outbreaks in developing countries have been associated with contaminated drinking water Pregnant women are more prone to develop HEV infection

Incubation period Average 40 days (Range 15-60 days) Case-fatality rate Overall 1-3% Pregnant women 15-25%, a high incidence of fetal wastage or perinatal morbidity and mortality Illness severity Increased with age Chronic sequelae None identified Jaundice, fatigue, abdominal pain, loss of appetite, nausea, vomiting, dark (tea colored) urine CLINICAL FEATURES

Symptoms ALT IgG anti-HEV IgM anti-HEV Virus in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Hepatitis E Virus Infection Typical Serologic Course Titer Weeks after Exposure

LABORATORY DIAGNOSIS Acute infection is diagnosed by the detection of HEV-IgM in serum EIA Four fold rise in antibodiy titer Past Infection - immunity is determined by the detection of HEV-IgG EIA Cell culture Difficult and takes up to 4 weeks, not routinely performed Direct Detection EM, PCR of HEV in faeces

No vaccine available for the HEV Unknown efficacy of IG prepared from donors in endemic areas Being a waterborne disease with feco-oral transmission, the steps and measures as discussed under HAV prevention are also useful for HEV prevention PREVENTION AND CONTROL MEASURES

HEALTH EDUCATION MESSAGES Always wash your hands with soap and water after using the bathroom, changing a diaper, and before preparing and eating food Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruits or vegetables that are not peeled or prepared properly Transmission from person to person occurs less commonly in Hepatitis E than with Hepatitis A virus As Hepatitis E is more severe among pregnant women, especially in third trimester, therefore special precautions, health education and hygienic measures are required in this group

All of the following can cause primary viral diarrhea EXCEPT: A. Rotavirus B. Norwalk virus C. Adenovirus D. Epstein-Barr virus E. Hepatitis A virus

All the following statements about viral hepatitis are true, EXCEPT: A. Hepatitis A and hepatitis E are transmitted primarily via the fecal-oral route B. Hepatitis B is no longer an important cause of post- transfusion hepatitis C. Hepatitis A virus produces acute but not chronic hepatitis D. Hepatitis D can only affect persons co-infected with hepatitis B E. An effective, killed vaccine is available for hepatitis C

The following viruses are associated with gastroenteritis A. Astroviruses B. Norwalk-like viruses C. Picornaviruses D. Adenoviruses E. Rotaviruses

The most likely infecting virus for an outbreak of diarrhea in a class of medical students A. Hantavirus B. Coxsackie virus C. Rota virus D. Hepatitis A virus E. Norwalk virus

Viral hepatitis a+e

More Related Content

Viral hepatitis a+e

Editor's Notes