Hepatitis A & E
Viral Hepatitis
• Viral infection of the liver by any of the 6 viruses, namely, HAV, HBV, C, D, E and G
• Other viruses which can infect the liver:
– CMV
– EBV
– Yellow fever
– Rubella
Hepatitis A
• Previously k/a
– Infectious Hepatitis
– Epidemic Jaundice
• Acute infection with Hepatitis A Virus (H.A.V)
• Heralded by nonspecific s/s like
– Nausea
– Vomiting
– Anorexia
• Numerous sub – clinical cases
• Benign – recovery takes several weeks
• Fatality-
– 0.1%, more in elderly
– Due to acute liver failure
Problem Statement- world
• Endemic in most developing countries and also frequent outbreaks
• Exact incidence very difficult to assess
– High % of sub clinical cases
• Incidence has reduced in the developed nations
• Geographical areas of the world can be categorized as with high, intermediate and low levels of Hepatitis A infection
1. Areas with high levels of infection
2. Areas with intermediate levels of infection:
3. Areas with low levels of infection
Areas with high levels of infection
• In developing countries
• Very poor sanitary conditions
• Most children (90%) have been infected before 10 yr.
• Childhood infection do not show noticeable symptoms
• Epidemics are uncommon as the older children and adults are mostly immune
• Symptomatic disease rates are low
Areas with intermediate levels of infection:
• Developing countries
• Counties with transitional economies
• Children often escape infection in early childhood
• Ironically this improved economic and sanitary conditions may lead to a higher susceptibility in older age groups and higher disease rates
• Infection occur in adolescents and adults
• Large outbreaks can occur
• Paradoxically, with transition from high to intermediate endemicity, the incidence of clinically significant disease increases
• Late childhood, early adulthood
Areas with low levels of infection
• Developed countries with good sanitary and hygienic condition
• Infection rates are low
• Disease may occur among adolescents and adults in high risk groups e.g.
-injection drug users,
-homosexual men,
-travel to high endemic area etc.
For lecture on Hepatitis A & E click link: http://www.ihatepsm.com/resource/hepatitis-e
Hepatitis A Problem Statement- India
• Exact incidence in India is not known
– High number of reports of outbreaks and sporadic cases in Indian cities, residential colonies and campuses are there
– Epidemics
• evolve slowly
• Involve wide geographic areas and
• Last many months
• Some common source epidemics may evolve explosively
Epidemiological Determinants:
Agent Factors
• Causative agent: Hepatitis A virus
– enterovirus of
– Picornaviridae family
– Multiplies only in hepatocytes
– Fecal shedding highest during late incubation period and early acute phase of illness
– Resistant to-
• Low pH
• Heat: Withstands heating up to 60⁰ C for one hour
• Chemicals: not affected by usual dose of chlorination
– Sensitive to-
• Formalin
• Ultraviolet rays
• Boiling for 5 minutes
• autoclaving
– Survives more than 10 weeks in well water
• Reservoir of infection:
– Human cases are the ONLY reservoir
– Cases range from asymptomatic (anicteric, usually in children) to severe ones
– No carrier state reported
• Period of infectivity:
– From 2 weeks before to 1 week after the onset of jaundice. Infectivity falls rapidly with the onset of jaundice
• Infective material: Mainly man’s feces
– Blood, serum and other body fluids are infective during the brief stage of viremia
• Virus excretion:
– HAV excreted in the feces for about 2 weeks before the onset of jaundice and up to 2 weeks thereafter
– No evidence for transmission by exposure to urine or naso-pharyngeal secretions
– Hemodialysis plays no role in the spread of hepatitis A to either patients or the staff
Host Factors
• Age:
– Infection more frequent among children than in adults
– Though all ages are susceptible if have not been infected or immunized
– Young children: infections tend to be mild or subclinical
• Ratio of anicteric to icteric cases is 12: 1
– Clinical severity increases with age
• Ratio of anicteric to icteric cases is 1: 3 in adults
– Fecal excretion of HAV antigen and RNA persists longer in young than in adults
– In India, by the age of 10 yr., 90% of healthy persons have serological evidence of HAV infection
• Sex: both sexes are equally susceptible
• Immunity:
– After attack: probably lasts for life
– Most people in endemic areas acquire immunity through subclinical infection
– IgM antibody appears early in illness and persists for over 90 days
– IgG appears more slowly and persists for many years
Environmental Factors
• Cases may occur throughout the year
• In India the disease tends to be associated with periods of heavy rainfall
• Poor sanitation
• Overcrowding
• Paradoxically, when standards of hygiene and sanitation are improved, morbidity from Hepatitis A virus infection may increase as also from other enteric viruses
Modes of Transmission
• Fecal – oral route is the major route of transmission
• Direct contact (person to person)
– Contaminated hands or objects such as eating utensils
• or indirect (contaminated water, food or milk)
• Water borne transmission more in developing countries
• In developed countries, food borne outbreaks have been reported e.g. salads and vegetables and raw or inadequately cooked shellfish and oysters cultivated in sewage polluted water
• Parenteral route
– Rarely transmitted by parenteral route (blood or skin penetration through contaminated needles)
– May occur during the stage of viremia
– Viremia stage occurs during prodromal phase
• Sexual transmission
– Mainly among homosexual men, because of oral – anal contact
– Health care personnel do not have an increased prevalence
• Nosocomial HAV transmission are rare
• Children play an important role in HAV transmission as they generally have asymptomatic or unrecognized illness
• Incubation period
– Ranges from 10 – 50 days
– Usually 14 – 28 days
– Length of IP is proportional to the dose of the virus ingested
• Clinical Spectrum
– Onset preceded by gastrointestinal symptoms such as
• Nausea
• Vomiting
• Anorexia and
– Mild fever
– Jaundice may appear within a few days of the prodromal period
• Anicteric hepatitis is more common
• Resolves completely in 98%
outcome children adults
In apparent (subclinical) infection 80 – 95% 10 – 20%
Icteric disease 5 – 20% 75 – 90%
Complete recovery > 98% > 98%
Chronic disease None None
Mortality rate 0.1% 0.3 – 2.1%
Diagnosis
• Liver function tests:
– Serum alanine aminotransferase
– Serum Bilirubin
• Specific laboratory diagnosis of Hepatitis A
– Demonstration of HAV particles or specific viral antigens in the feces, bile and blood
• HAV is detected in stool from appx. 2 weeks prior to onset of jaundice and up to 2 weeks later
– Anti HAV IgM- during acute phase, peaking about 2 weeks after liver enzymes elevation
• Decline to non-detectable levels within 3 – 6 months
• Hence detection of IgM specific Anti - HAV in the blood of an acutely infected patient confirms the diagnosis of hepatitis A
– Anti-HAV IgG appears soon after onset of disease and persists for decades
– ELISA is the method of choice for measuring HAV antibodies
Prevention and Control
• Control of reservoir - Difficult
– Fecal shedding of the virus is maximum during the incubation period and early phase of illness
– Occurrence of large number of subclinical cases
– Absence of specific treatment and
– Low socio-economic profile of the population usually involved
– Strict isolation of the case doesn’t help much as the maximal virus shedding has already occurred and subclinical cases keep spreading the virus
Still:
– Complete bed rest and
– Disinfection of feces and fomites is recommended
• 0.5% sodium hypochlorite is an effective disinfectant for the purpose
• Control of transmission: Best means of reducing the spread of infection
– Hand washing before eating and after toilet
– Sanitary disposal of excreta
– Purification of community water supplies by flocculation , filtration and adequate chlorination
• 1mg/L of free residual chlorine can cause destruction of the virus in 30 minutes at pH of 8.5 or less
• During epidemics, boiled water should be advocated for drinking
• Hence the effective long term control measures in communities comprise
– Safe drinking water
– Safe disposal of sewage
• Control of susceptible population:
• In areas of LOW endemicity, certain high-risk groups can be given targeted protection;
– Travellers to areas of intermediate or high endemicity
– Those requiring lifelong treatment with blood products
– Men having sex with men
– Workers in contact with non-human primates and
– Injection drug users
– Patients with chronic liver disease (as they are at increased risk for fulminant hepatitis A)
• Use of hepatitis A VACCINE is preferred over immune-globulin for both
– pre-exposure and also
– post-exposure prophylaxis
Vaccines
• Two types of vaccines
– Formaldehyde inactivated vaccines
• Produced in several countries
• Most commonly used worldwide
– Live attenuated vaccines
• Manufactured in China
• Available in several counties
• Inactivated hepatitis A vaccine
– Licensed for use in persons ≥12 months of age
– Schedule consists of 2 doses (first primary and second booster)
– I/M into deltoid muscle
– Interval between the primary and booster dose is 6 – 12 months, but is flexible to 18 to 36 months
– Can be administered simultaneously with other vaccines
– Protective efficacy: 94% after two doses
• Live attenuated vaccine
– Single dose
– Subcutaneous injection
• Both the vaccines
• Highly immunogenic and
• Long lasting immunity
• In both children and adults
Using hepatitis A vaccination in outbreak control:
Depends upon
• Epidemiologic features of the disease in the community and
• The feasibility of rapidly implementing a widespread vaccination programme
• The use of a single dose regimen of hepatitis A vaccine to control community-wide outbreaks has been most successful,
• When vaccination was started early in the course of the outbreak, and
• When high coverage of multiple age-cohorts was achieved.
• Vaccination efforts should be supplemented with health education and improved sanitation
• Combinations available:
• Hepatitis A and B vaccine
• Hepatitis A and Typhoid vaccine
• Mainly intended for use in adult travellers
WHO Recommendation Regarding Hepatitis-A Vaccine
• Low and very low endemicity area:
– Targeted vaccination of high-risk groups
• Countries moving from high to intermediate endemicity (Countries with improving socioeconomic status)
– WHO recommends that vaccination against HAV be integrated into the national immunization schedule for children aged ≥1 year
• because a relatively large proportion of the adult population is now susceptible to HAV and
• Hence large-scale hepatitis A vaccination is likely to be cost-effective
• Highly endemic countries
– In highly endemic countries almost all persons are asymptomatically infected with HAV in childhood, which effectively prevents clinical hepatitis A in adolescents and adults.
– In these countries, large-scale vaccination programmes are not recommended
Human Immunoglobulin (Ig)
• Protective efficacy against HAV infection is well documented
• Duration of protection is limited to approximately:
– 1 -2 months if dose is 0.02 ml/kg body weight
– 3 – 5 months if dose is 0.06 ml/kg
– Prophylaxis reached within hours of administration
• Efficacy high if administered in maximum 14 days of exposure
• Still the use of Ig declining world wide
– Insufficient concentration of anti-HAV IgG in nonspecific Ig
– Limited duration of protection
– Hepatitis A vaccines have been shown to induce rapid protection after the first dose
Hepatitis E
• Essentially a water borne disease
• Formerly termed:
– Enterically transmitted hepatitis non-A, non-B (HNANB)
• RNA virus- 4 genotypes (type 1, 2, 3 & 4)
– Genotype 1 usually seen in developing countries and causes community level outbreaks
– Genotype 3 is usually seen in developed countries and does not cause outbreaks
• Areas affected
– Those with limited access to essential water , sanitation, hygiene and health services
– Areas of conflict and humanitarian emergencies like war zones
– Camps for refugees
– Hepatitis E prevalence highest in east and south Asia with genotype 1 most commonly found in India
• Sero-prevalence rates of 25% have been reported in East and South Asia in some age groups
Transmission
• Mainly fecal - oral route
– Due to fecal contamination of drinking water
• Other routes may be involved
– Food borne transmission form products from infected animals
– Transfusion of infected blood products and
– Vertical transmission from pregnant women to her fetus
Clinical Picture
• I.P. ranges from 3 to 8 weeks
– Mean I.P. 40 days
• Period of communicability not known
• Symptoms:
– Though infection is frequent in children, it is mostly asymptomatic or very mild illness
– Symptoms more common in young adults (15 – 40 yr.)
• Jaundice
• Loss of appetite
• Abdominal pain and tenderness
• Nausea and vomiting
• Fever
• Enlarged and tender liver
• Illness lasts for 1 or 2 weeks
– Rarely fulminant hepatitis (acute liver failure) and death
• Fulminant hepatitis more frequent during pregnancy
• Pregnant women at greater risk of
– Obstetrical complications and
– Mortality which may be as high as 20% in third trimester
• Chronic hepatitis E infection and reactivation of infection has also been reported in immunocompromised
Diagnosis
• Clinically indistinguishable from other types of acute viral hepatitis
• Confirmation of diagnosis
– Detection of specific IgM and IgG antibodies
• Other test- RT-PCR to detect hepatitis E RNA in blood/stool
– Requires specialized laboratory facilities
Treatment
• Usually self-limiting
• Prevention most effective as no specific treatment
• Hospitalization required for
– fulminant cases and
– Symptomatic pregnant women
– Recovery nearly always complete
• No specific immunoglobulin prophylaxis available
Prevention
• Maintaining quality standards for public water supplies
• Establishing proper disposal systems for sanitary waste
• Individual level
– Hand washing (with safe water)before handling food
– Avoiding drinking water/ice of unknown purity and
– Adhering to WHO safe food practices
• First vaccine in 2011
– Registered in China
– Not available globally
For lecture on this topic click link: http://www.ihatepsm.com/resource/hepatitis-e
References
1. Viral Hepatitis, Park’s Textbook of Preventive and Social Medicine. 23rd ed;.editors: Dr Mrs Kumud Park, M/S Banarasidas Bhanot Publishers, Jabalpur, India
2. WHO (2012), Weekly Epidemiological Record, No. 28 – 29, 13th July 2012
3. CDC (1988); Epidemiologic Notes and Reports Hepatitis A Among Drug Abusers, Morbidity and Mortality Weekly Report (MMWR) Series; May 20, 1988 / 37(19);297-300,305.Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00000024.htm