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

Areas with high levels of infection
Areas with intermediate levels of infection:
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: Hepatitis A & 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: Hepatitis A & E
References

Viral Hepatitis, Park’s Textbook of Preventive and Social Medicine. 23rd ed;.editors: Dr Mrs Kumud Park, M/S Banarasidas Bhanot Publishers, Jabalpur, India
WHO (2012), Weekly Epidemiological Record, No. 28 – 29, 13th July 2012
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