Hepatitis B
Fact sheet
Updated July 2016
Key facts
- Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease.
- The virus is transmitted through contact with the blood or other body fluids of an infected person.
- An estimated 240 million people are chronically infected with
hepatitis B (defined as hepatitis B surface antigen positive for at
least 6 months).
- More than 686 000 people die every year due to complications of hepatitis B, including cirrhosis and liver cancer 1.
- Hepatitis B is an important occupational hazard for health workers.
- However, it can be prevented by currently available safe and effective vaccine.
Hepatitis B is a potentially life-threatening liver infection
caused by the hepatitis B virus. It is a major global health problem. It
can cause chronic infection and puts people at high risk of death from
cirrhosis and liver cancer.
A vaccine against hepatitis B has been available since 1982.
The vaccine is 95% effective in preventing infection and the development
of chronic disease and liver cancer due to hepatitis B.
Geographical distribution
Hepatitis B prevalence is highest in sub-Saharan Africa and
East Asia, where between 5–10% of the adult population is chronically
infected. High rates of chronic infections are also found in the Amazon
and the southern parts of eastern and central Europe. In the Middle
East and the Indian subcontinent, an estimated 2–5% of the general
population is chronically infected. Less than 1% of the population of
Western Europe and North America is chronically infected.
Transmission
The hepatitis B virus can survive outside the body for at
least 7 days. During this time, the virus can still cause infection if
it enters the body of a person who is not protected by the vaccine. The
incubation period of the hepatitis B virus is 75 days on average, but
can vary from 30 to 180 days. The virus may be detected within 30 to 60
days after infection and can persist and develop into chronic hepatitis
B.
In highly endemic areas, hepatitis B is most commonly spread
from mother to child at birth (perinatal transmission), or through
horizontal transmission (exposure to infected blood), especially from an
infected child to an uninfected child during the first 5 years of life.
The development of chronic infection is very common in infants infected
from their mothers or before the age of 5 years.
Hepatitis B is also spread by percutaneous or mucosal exposure
to infected blood and various body fluids, as well as through saliva,
menstrual, vaginal, and seminal fluids. Sexual transmission of hepatitis
B may occur, particularly in unvaccinated men who have sex with men and
heterosexual persons with multiple sex partners or contact with sex
workers. Infection in adulthood leads to chronic hepatitis in less than
5% of cases. Transmission of the virus may also occur through the reuse
of needles and syringes either in health-care settings or among persons
who inject drugs. In addition, infection can occur during medical,
surgical and dental procedures, through tattooing, or through the use of
razors and similar objects that are contaminated with infected blood.
Symptoms
Most people do not experience any symptoms during the acute
infection phase. However, some people have acute illness with symptoms
that last several weeks, including yellowing of the skin and eyes
(jaundice), dark urine, extreme fatigue, nausea, vomiting and abdominal
pain. A small subset of persons with acute hepatitis can develop acute
liver failure which can lead to death.
In some people, the hepatitis B virus can also cause a chronic
liver infection that can later develop into cirrhosis of the liver or
liver cancer.
Who is at risk for chronic disease?
The likelihood that infection becomes chronic depends upon the
age at which a person becomes infected. Children less than 6 years of
age who become infected with the hepatitis B virus are the most likely
to develop chronic infections.
In infants and children:
- 80–90% of infants infected during the first year of life develop chronic infections; and
- 30–50% of children infected before the age of 6 years develop chronic infections.
In adults:
- less than 5% of otherwise healthy persons who are infected as adults will develop chronic infection; and
- 20–30% of adults who are chronically infected will develop cirrhosis and/or liver cancer.
Diagnosis
It is not possible, on clinical grounds, to differentiate
hepatitis B from hepatitis caused by other viral agents and, hence,
laboratory confirmation of the diagnosis is essential. A number of blood
tests are available to diagnose and monitor people with hepatitis B.
They can be used to distinguish acute and chronic infections.
Laboratory diagnosis of hepatitis B infection focuses on the
detection of the hepatitis B surface antigen HBsAg. WHO recommends that
all blood donations be tested for hepatitis B to ensure blood safety and
avoid accidental transmission to people who receive blood products.
- Acute HBV infection is characterized by the presence of HBsAg and
immunoglobulin M (IgM) antibody to the core antigen, HBcAg. During the
initial phase of infection, patients are also seropositive for hepatitis
B e antigen (HBeAg). HBeAg is usually a marker of high levels of
replication of the virus. The presence of HBeAg indicates that the blood
and body fluids of the infected individual are highly contagious.
- Chronic infection is characterized by the persistence of HBsAg
for at least 6 months (with or without concurrent HBeAg). Persistence of
HBsAg is the principal marker of risk for developing chronic liver
disease and liver cancer (hepatocellular carcinoma) later in life.
Treatment
There is no specific treatment for
acute hepatitis B.
Therefore, care is aimed at maintaining comfort and adequate nutritional
balance, including replacement of fluids lost from vomiting and
diarrhoea.
Chronic hepatitis B infection can be treated with
drugs, including oral antiviral agents. Treatment can slow the
progression of cirrhosis, reduce incidence of liver cancer and improve
long term survival.
WHO recommends the use of oral treatments - tenofovir or
entecavir, because these are the most potent drugs to suppress hepatitis
B virus. They rarely lead to drug resistance as compared with other
drugs, are simple to take (1 pill a day), and have few side effects so
require only limited monitoring.
In most people, however, the treatment does not cure hepatitis
B infection, but only suppresses the replication of the virus.
Therefore, most people who start hepatitis B treatment must continue it
for life.
Treatment using interferon injections may be considered in
some people in certain high-income settings, as this may shorten
treatment duration, but its use is less feasible in low-resource
settings due to high cost and significant adverse effects requiring
careful monitoring.
There is still limited access to diagnosis and treatment of
hepatitis B in many resource-constrained settings, and many people are
diagnosed only when they already have advanced liver disease. Liver
cancer progresses rapidly, and since treatment options are limited, the
outcome is in general poor. In low-income settings, most people with
liver cancer die within months of diagnosis. In high-income countries,
surgery and chemotherapy can prolong life for up to a few years. Liver
transplantation is sometimes used in people with cirrhosis in high
income countries, with varying success.
Prevention
The hepatitis B vaccine is the mainstay of hepatitis B
prevention. WHO recommends that all infants receive the hepatitis B
vaccine as soon as possible after birth, preferably within 24 hours. The
birth dose should be followed by 2 or 3 doses to complete the primary
series. In most cases, 1 of the following 2 options is considered
appropriate:
- a 3-dose schedule of hepatitis B vaccine, with the first dose
(monovalent) being given at birth and the second and third (monovalent
or combined vaccine) given at the same time as the first and third doses
of diphtheria, pertussis (whooping cough), and tetanus – (DTP) vaccine;
or
- a 4-dose schedule, where a monovalent birth dose is followed by
three monovalent or combined vaccine doses, usually given with other
routine infant vaccines.
The complete vaccine series induces protective antibody levels
in more than 95% of infants, children and young adults. Protection
lasts at least 20 years and is probably lifelong. Thus, WHO does not
recommend booster vaccination for persons who have completed the 3 dose
vaccination schedule.
All children and adolescents younger than 18 years-old and not
previously vaccinated should receive the vaccine if they live in
countries where there is low or intermediate endemicity. In those
settings it is possible that more people in high-risk groups may acquire
the infection and they should also be vaccinated. They include:
- people who frequently require blood or blood products, dialysis patients, recipients of solid organ transplantations;
- people interned in prisons;
- persons who inject drugs;
- household and sexual contacts of people with chronic HBV infection;
- people with multiple sexual partners;
- health-care workers and others who may be exposed to blood and blood products through their work; and
- travellers who have not completed their hepatitis B vaccination
series, who should be offered the vaccine before leaving for endemic
areas.
The vaccine has an excellent record of safety and
effectiveness. Since 1982, over 1 billion doses of hepatitis B vaccine
have been used worldwide. In many countries where between 8–15% of
children used to become chronically infected with the hepatitis B virus,
vaccination has reduced the rate of chronic infection to less than 1%
among immunized children.
As of 2014, 184 Member States vaccinate infants against
hepatitis B as part of their vaccination schedules and 82% of children
in these states received the hepatitis B vaccine. This is a major
increase compared with 31 countries in 1992, the year that the World
Health Assembly passed a resolution to recommend global vaccination
against hepatitis B. Furthermore, as of 2014, 96 Member States have
introduced the hepatitis B birth dose vaccine.
In addition, implementing of blood safety strategies,
including quality-assured screening of all donated blood and blood
components used for transfusion, can prevent transmission of HBV. Safe
injection practices, eliminating unnecessary and unsafe injections, can
be effective strategies to protect against HBV transmission.
Furthermore, safer sex practices, including minimizing the number of
partners and using barrier protective measures (condoms), also protect
against transmission.
WHO response
In March 2015, WHO launched its first
"Guidelines for the prevention, care and treatment of persons living with chronic hepatitis B infection". The recommendations:
- promote the use of simple, non-invasive diagnostic tests to assess the stage of liver disease and eligibility for treatment;
- prioritize treatment for those with most advanced liver disease and at greatest risk of mortality; and
- recommend the preferred use of the nucleos(t)ide analogues with a
high barrier to drug resistance (tenofovir and entecavir, and entecavir
in children aged between 2–11 years) for first- and second-line
treatment.
These guidelines also recommend lifelong treatment in those
with cirrhosis; and regular monitoring for disease progression, toxicity
of drugs and early detection of liver cancer.
In May 2016, The World Health Assembly adopted the first “
Global Health Sector Strategy on Viral Hepatitis, 2016-2021”.
The strategy highlights the critical role of Universal Health Coverage
and the targets of the strategy are aligned with those of the
Sustainable Development Goals. The strategy has a vision of eliminating
viral hepatitis as a public health problem and this is encapsulated in
the global targets of reducing new viral hepatitis infections by 90% and
reducing deaths due to viral hepatitis by 65% by 2030. Actions to be
taken by countries and WHO Secretariat to reach these targets are
outlined in the strategy.
To support countries in moving towards achieving the global
hepatitis goals under the Sustainable Development Agenda 2030, WHO is
working in the following areas:
Hepatitis C virus (HCV) causes both acute and chronic
infection. Acute HCV infection is usually asymptomatic, and is only very
rarely associated with life-threatening disease. About 15–45% of
infected persons spontaneously clear the virus within 6 months of
infection without any treatment.
The remaining 55–85% of persons will develop chronic HCV
infection. Of those with chronic HCV infection, the risk of cirrhosis of
the liver is between 15–30% within 20 years.
Geographical distribution
Hepatitis C is found worldwide. The most affected regions are
Africa and Central and East Asia. Depending on the country, hepatitis C
infection can be concentrated in certain populations (for example, among
people who inject drugs) and/or in general populations. There are
multiple strains (or genotypes) of the HCV virus and their distribution
varies by region.
Transmission
The hepatitis C virus is a bloodborne virus. It is most commonly transmitted through:
- injecting drug use through the sharing of injection equipment;
- the reuse or inadequate sterilization of medical equipment, especially syringes and needles in healthcare settings; and
- the transfusion of unscreened blood and blood products.
HCV can also be transmitted sexually and can be passed from an
infected mother to her baby; however these modes of transmission are
much less common.
Hepatitis C is not spread through breast milk, food, water or
by casual contact such as hugging, kissing and sharing food or drinks
with an infected person.
Symptoms
The incubation period for hepatitis C is 2 weeks to 6 months.
Following initial infection, approximately 80% of people do not exhibit
any symptoms. Those who are acutely symptomatic may exhibit fever,
fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark
urine, grey-coloured faeces, joint pain and jaundice (yellowing of skin
and the whites of the eyes).
Screening and diagnosis
Due to the fact that acute HCV infection is usually
asymptomatic, few people are diagnosed during the acute phase. In those
people who go on to develop chronic HCV infection, the infection is also
often undiagnosed because the infection remains asymptomatic until
decades after infection when symptoms develop secondary to serious liver
damage.
HCV infection is diagnosed in 2 steps:
- Screening for anti-HCV antibodies with a serological test identifies people who have been infected with the virus.
- If the test is positive for anti-HCV antibodies, a nucleic acid
test for HCV ribonucleic acid (RNA) is needed to confirm chronic
infection because about 15–45% of people infected with HCV spontaneously
clear the infection by a strong immune response without the need for
treatment. Although no longer infected, they will still test positive
for anti-HCV antibodies.
After a person has been diagnosed with chronic hepatitis C
infection, they should have an assessment of the degree of liver damage
(fibrosis and cirrhosis). This can be done by liver biopsy or through a
variety of non-invasive tests.
In addition, these people should have a laboratory test to
identify the genotype of the hepatitis C strain. There are 6 genotypes
of the HCV and they respond differently to treatment. Furthermore, it is
possible for a person to be infected with more than 1 genotype. The
degree of liver damage and virus genotype are used to guide treatment
decisions and management of the disease.
Getting tested
Early diagnosis can prevent health problems that may result
from infection and prevent transmission of the virus. WHO recommends
screening for people who may be at increased risk of infection.
Populations at increased risk of HCV infection include:
- people who inject drugs;
- people who use intranasal drugs;
- recipients of infected blood products or invasive procedures in
health-care facilities with inadequate infection control practices ;
- children born to mothers infected with HCV ;
- people with sexual partners who are HCV-infected;
- people with HIV infection;
- prisoners or previously incarcerated persons; and
- people who have had tattoos or piercings.
Treatment
Hepatitis C does not always require treatment as the immune
response in some people will clear the infection, and some people with
chronic infection do not develop liver damage. When treatment is
necessary, the goal of hepatitis C treatment is cure. The cure rate
depends on several factors including the strain of the virus and the
type of treatment given.
The standard of care for hepatitis C is changing rapidly.
Until recently, hepatitis C treatment was based on therapy with
interferon and ribavirin, which required weekly injections for 48 weeks,
cured approximately half of treated patients, but caused frequent and
sometimes life-threatening adverse reactions.
Recently, new antiviral drugs have been developed. These
medicines, called direct antiviral agents (DAA) are much more effective,
safer and better-tolerated than the older therapies. Therapy with DAAs
can cure most persons with HCV infection and treatment is shorter
(usually 12 weeks) and safer. Although the production cost of DAAs is
low, these medicines remain very expensive in many high- and
middle-income countries. Prices have dropped dramatically in some
countries (primarily low-income) due to the introduction of generic
versions of these medicines.
Much needs to be done to ensure that these advances lead to greater access to treatment globally.
Prevention
Primary prevention
There is no vaccine for hepatitis C, therefore prevention of
HCV infection depends upon reducing the risk of exposure to the virus in
health-care settings and in higher risk populations, for example,
people who inject drugs, and through sexual contact.
The following list provides a limited example of primary prevention interventions recommended by WHO:
- hand hygiene: including surgical hand preparation, hand washing and use of gloves;
- safe handling and disposal of sharps and waste;
- provision of comprehensive harm-reduction services to people who inject drugs including sterile injecting equipment;
- testing of donated blood for hepatitis B and C (as well as HIV and syphilis);
- training of health personnel; and
- promotion of correct and consistent use of condoms.
Secondary and tertiary prevention
For people infected with the hepatitis C virus, WHO recommends:
- education and counselling on options for care and treatment;
- immunization with the hepatitis A and B vaccines to prevent
coinfection from these hepatitis viruses and to protect their liver;
- early and appropriate medical management including antiviral therapy if appropriate; and
- regular monitoring for early diagnosis of chronic liver disease.
Screening, care and treatment of persons with hepatitis C infection
In April 2016, WHO updated its "
Guidelines for the screening, care and treatment of persons with chronic hepatitis C". These guidelines complement existing WHO guidance on the prevention of transmission of bloodborne viruses, including HCV.
They are intended for policy-makers, government officials, and
others working in low- and middle-income countries who are developing
programmes for the screening, care and treatment of people with HCV
infection. These guidelines will help expand of treatment services to
patients with HCV infection, as they provide key recommendations in
these areas and discuss considerations for implementation.
Summary of key recommendations
Recommendations on screening for HCV infection
1. Screening to identify persons with HCV infection
It is recommended that HCV serology testing be offered to
individuals who are part of a population with high HCV prevalence or who
have a history of HCV risk exposure/ behaviour.
2. When to confirm the diagnosis of chronic HCV infection
It is suggested that following a positive HCV virus
serological test another test (NAT for the detection of HCV RNA) be
performed to diagnose chronic infection. NAT for HCV RNA should also be
performed to assess whether to start treatment for hepatitis C.
Recommendations on care of people infected with HCV
3. Screening for alcohol use and counselling to reduce moderate and high levels of alcohol intake
An alcohol intake assessment is recommended for all persons
with HCV virus infection followed by the offer of a behavioural alcohol
reduction intervention for persons with moderate-to-high alcohol intake.
4. Assessing degree of liver fibrosis and cirrhosis
In resource-limited settings, the aminotransferase/platelet
ratio index (APRI) or FIB4 tests should be used for the assessment of
hepatic fibrosis rather than other non-invasive tests that require more
resources such as elastography or Fibrotest.
Recommendations on hepatitis C treatment
5. Assessing for HCV treatment
All adults and children with chronic HCV infection should be assessed for antiviral treatment.
6. Treatment with direct-acting antivirals (DAAs)
WHO recommends that all patients with hepatitis C be treated
with DAA-based regimens, except for a few specific groups of people in
whom interferon-based regimens can still be used (as an alternative
regimen for patients with genotype 5 or 6 infection and those with
genotype 3 HCV infection who also have cirrhosis).
7. Telaprevir and boceprevir should no longer be used
These 2 first-generation DAAs, which are administered with
pegylated interferon and ribavirin, were recommended in the 2014
guidelines. Evidence now shows that they result in more frequent adverse
effects and less frequent cures compared with newer DAA-based regimens.
Thus, these 2 medicines are no longer recommended by WHO.
8. WHO recommends preferred and alternative DAA regimens based on genotype and cirrhosis status
The Guideline Development Group reviewed all the available
data (over 200 studies) to determine which regimens were most effective
and safest to treat each of the 6 different genotypes.
WHO response
In May 2016, The World Health Assembly adopted the first “
Global Health Sector Strategy on Viral Hepatitis, 2016-2021”.
The strategy highlights the critical role of Universal Health Coverage
and the targets of the strategy are aligned with those of the
Sustainable Development Goals. The strategy has a vision of eliminating
viral hepatitis as a public health problem and this is encapsulated in
the global targets of reducing new viral hepatitis infections by 90% and
reducing deaths due to viral hepatitis by 65% by 2030. Actions to be
taken by countries and WHO Secretariat to reach these targets are
outlined in the strategy.
WHO is working in the following areas to support countries in
moving towards achieving the global hepatitis goals under the
Sustainable Development Agenda 2030:
- raising awareness, promoting partnerships and mobilizing resources;
- formulating evidence-based policy and data for action;
- preventing transmission; and
- scaling up screening, care and treatment services.
Hepatitis D
Fact sheet
July 2016
Key facts
- Hepatitis D virus (HDV) is a ribonucleic acid (RNA) virus that
requires hepatitis B virus (HBV) for its replication. HDV infection
occurs only simultaneously or as super-infection with HBV.
- The virus is transmitted through contact with the blood or other body fluids of an infected person.
- Vertical transmission from mother to child is rare.
- Approximately 15 million people across the world are chronically coinfected with HDV and HBV 1.
- Currently there is no effective antiviral treatment for hepatitis D.
- Hepatitis D infection can be prevented by hepatitis B immunization.
Hepatitis D is a liver disease in both acute and chronic forms
caused by the hepatitis D virus (HDV) that requires HBV for its
replication. Hepatitis D infection cannot occur in the absence of
hepatitis B virus. The coinfection or super infection of HDV with HBV
causes a more severe disease than HBV monoinfection.
A vaccine against hepatitis B is the only method to prevent HDV infection.
Geographical distribution
It is estimated that globally, 5% of HBsAg positive people are
coinfected with HDV and the distribution is worldwide. High-prevalence
areas include the Mediterranean, Middle East, Pakistan, Central and
Northern Asia, Japan, Taiwan, Greenland and parts of Africa (mainly the
horn of Africa and West Africa), the Amazon Basin and certain areas of
the Pacific. Prevalence is low in North America and Northern Europe,
South Africa, and Eastern Asia.
Transmission
The routes of HDV transmission are the same as for HBV:
percutaneously or sexually through contact with infected blood or blood
products. Vertical transmission is possible but rare. Vaccination
against HBV prevents HDV coinfection, and hence expansion of childhood
HBV immunization programmes has resulted in a decline in hepatitis D
incidence worldwide. However, in some settings, the increase of
hepatitis D prevalence has been observed in people who inject drugs, or
as a result of migration from areas where HDV is endemic.
Symptoms
Acute hepatitis: simultaneous infection with HBV and HDV can
lead to a mild-to-severe or even fulminant hepatitis, but recovery is
usually complete and development of chronic hepatitis D is rare (less
than 5% of acute hepatitis).
Superinfection: HDV can infect a person already chronically
infected with HBV. The superinfection of HDV on chronic hepatitis B
accelerates progression to a more severe disease in all ages and in
70‒90% of persons. HDV superinfection accelerates progression to
cirrhosis almost a decade earlier than HBV monoinfected persons,
although HDV suppresses HBV replication. The mechanism in which HDV
causes more severe hepatitis and a faster progression of fibrosis than
HBV alone remains unclear.
Who is at risk?
Chronic HBV carriers are at risk for infection with HDV.
People who are not immune to HBV (either by natural disease or
immunization with the hepatitis B vaccine) are at risk of infection
with HBV which puts them at risk of HDV infection.
Screening and diagnosis
HDV infection is diagnosed by high titres of Immunoglobulin G
(IgG) and Immunoglobulin M (IgM) anti-HDV, and confirmed by detection of
HDV RNA in serum.
However, HDV diagnostics are not widely available and there is
no standardization for HDV RNA assays, which are used for monitoring
response to antiviral therapy.
Treatment
There is no specific treatment for acute or chronic HDV
infection. Persistent HDV replication is the most important predictor of
mortality and the need for antiviral therapy. Pegylated interferon
alpha is the only drug effective against HDV; antiviral nucleotide
analogues for HBV have no or limited effect on HDV replication. The
optimal duration of therapy is not well defined, nor how long patients
need to be HDV RNA negative after the end of therapy to achieve a
sustained virological response. More than 1 year of therapy may be
necessary.
The overall rate of sustained virological response remains
low, including in children, and most patients relapse after
discontinuation of therapy. Liver transplantation may be considered for
cases of fulminant hepatitis and end-stage liver disease. New
therapeutic agents and strategies are needed, and novel drugs, such as
prenylation inhibitor or HBV entry inhibitors, have shown early promise.
Prevention
Prevention and control of HDV infection requires prevention of
HBV transmission through hepatitis B immunization, blood safety,
injection safety, and harm reduction services. Hepatitis B immunization
does not provide protection against HDV for those already HBV infected.
WHO response
WHO does not have specific recommendation on hepatitis D,
however prevention of HBV transmission by hepatitis B immunization, safe
injection practices, blood safety, and harm reduction services with
clean needles and syringes, are effective in preventing HDV
transmission.
In May 2016, The World Health Assembly adopted the first “
Global Health Sector Strategy on Viral Hepatitis, 2016-2021”.
The strategy highlights the critical role of Universal Health Coverage
and the targets of the strategy are aligned with those of the
Sustainable Development Goals. The strategy has a vision of eliminating
viral hepatitis as a public health problem and this is encapsulated in
the global targets of reducing new viral hepatitis infections by 90% and
reducing deaths due to viral hepatitis by 65% by 2030. Actions to be
taken by countries and WHO Secretariat to reach these targets are
outlined in the strategy.
To support countries in moving towards achieving the global
hepatitis goals under the Sustainable Development Agenda 2030 WHO is
working in the following areas:
Hepatitis E is a liver disease caused by the hepatitis E virus
(HEV): a small virus, with a positive-sense, single-stranded
ribonucleic acid (RNA) genome. The virus has at least 4 different types:
genotypes 1, 2, 3 and 4. Genotypes 1 and 2 have been found only in
humans. Genotype 3 and 4 viruses circulate in several animals (including
pigs, wild boars, and deer) without causing any disease, and
occasionally infect humans.
The virus is shed in the stools of infected persons, and
enters the human body through the intestine. It is transmitted mainly
through contaminated drinking water. Usually the infection is
self-limiting and resolves within 2–6 weeks. Occasionally a serious
disease, known as fulminant hepatitis (acute liver failure) develops,
and a proportion of people with this disease can die.
Geographical distribution
Hepatitis E infection is found worldwide. Two different patterns are observed, where hepatitis E is found in:
- resource-poor areas with frequent water contamination; and
- areas with safe drinking water supplies.
The disease is common in resource-limited countries with
limited access to essential water, sanitation, hygiene and health
services. In these areas, the disease occurs both as outbreaks and as
sporadic cases. The outbreaks usually follow periods of faecal
contamination of drinking water supplies and may affect several hundred
to several thousand persons. Some of these outbreaks have occurred in
areas of conflict and humanitarian emergencies, such as war zones, and
in camps for refugees or internally displaced populations (IDP),
situations where sanitation and safe water supply pose special
challenges.
Sporadic cases are also believed to be related to
contamination of water or food, albeit at a smaller scale. In these
areas, an estimated 20 million infections and 3.3 million acute cases
occur annually worldwide
1 with an estimated 56 600 deaths
2. The cases in these areas are caused mostly by infection with genotype 1 virus, and much less frequently by genotype 2 virus.
In areas with better sanitation and water supply, hepatitis E
disease is infrequent with only occasional sporadic cases. Most of these
cases are caused by genotype 3 virus, and are caused by infection with
virus originating in animals, usually through ingestion of undercooked
animal meat (including animal liver) and are not related to
contamination of water or other foods.
Serological evidence of prior exposure to the virus has been
found in most areas, with higher seroprevalence rates (proportion of
people who test positive for IgG antibodies to HEV) in regions with
lower standards of sanitation and thus higher risk for transmission.
However, presence of these antibodies does not imply presence of or
increased risk of disease. The usefulness of such data for
epidemiological purposes may also be limited due to variable and
possible sub-optimal performance of available serological assays, and
possible disappearance of the antibody with the passage of time among
those exposed to the virus.
Transmission
The hepatitis E virus is transmitted mainly through the
faecal-oral route due to faecal contamination of drinking water. This
route accounts for a very large proportion of clinical cases with this
disease. The risk factors for hepatitis E are related to poor
sanitation, allowing virus excreted in the faeces of infected people to
reach drinking water supplies.
Other routes of transmission have been identified, but appear
to account for a much smaller number of clinical cases. These routes of
transmission include:
- ingestion of undercooked meat or meat products derived from infected animals;
- transfusion of infected blood products; and
- vertical transmission from a pregnant woman to her fetus.
The ingestion of raw or uncooked shellfish may be the source of sporadic cases in endemic areas.
Symptoms
The incubation period following exposure to the hepatitis E
virus ranges from 2 to 10 weeks, with an average of 5–6 weeks. The
infected persons are believed to excrete the virus beginning a few days
before to around 3-4 weeks after the onset of disease.
In areas with high disease endemicity, symptomatic infection
is most common in young adults aged 15–40 years. In these areas,
although infection does occur in children, they often have either no
symptoms or only a mild illness without jaundice that goes undiagnosed.
Typical signs and symptoms of hepatitis include:
- an initial phase of mild fever, reduced appetite (anorexia),
nausea and vomiting, lasting for a few days; some persons may also have
abdominal pain, itching (without skin lesions), skin rash, or joint
pain.
- jaundice (yellow discolouration of the skin and sclera of the eyes), with dark urine and pale stools; and
- a slightly enlarged, tender liver (hepatomegaly).
These symptoms are often indistinguishable from those
experienced during other liver illnesses and typically last between 1–6
weeks.
In rare cases, acute hepatitis E can be severe, and results in
fulminant hepatitis (acute liver failure); these patients are at risk
of death. Fulminant hepatitis occurs more frequently when hepatitis E
occurs during pregnancy. Pregnant women with hepatitis E, particularly
those in the second or third trimester, are at an increased risk of
acute liver failure, fetal loss and mortality. Case fatality rates as
high as 20–25% have been reported among pregnant women in their third
trimester.
Cases of chronic hepatitis E infection have been reported in
immunosuppressed people, particularly organ transplant recipients on
immunosuppressive drugs, with genotype 3 or 4 HEV infection.
Diagnosis
Cases of hepatitis E are not clinically distinguishable from
other types of acute viral hepatitis. Diagnosis can often be strongly
suspected in appropriate epidemiologic settings however, for example in
the occurrence of several cases in localities in known disease-endemic
areas, in settings with risk of water contamination, if the disease is
more severe in pregnant women, or if hepatitis A has been excluded.
Definitive diagnosis of hepatitis E infection is usually based
on the detection of specific IgM antibodies to the virus in a person’s
blood; this is usually adequate in areas where disease is common.
Additional tests include reverse transcriptase polymerase
chain reaction (RT-PCR) to detect the hepatitis E virus RNA in blood
and/or stool; this assay requires specialised laboratory facilities.
This test is particularly needed in areas where hepatitis E is
infrequent, and in cases with chronic HEV infection.
A test for viral antigen detection in serum has been
developed; its place in the diagnosis of hepatitis E is currently being
studied.
Treatment
There is no specific treatment capable of altering the course
of acute hepatitis E. As the disease is usually self-limiting,
hospitalization is generally not required. Hospitalization is required
for people with fulminant hepatitis, however, and should also be
considered for symptomatic pregnant women.
Immunosuppressed people with chronic hepatitis E benefit from
specific treatment using ribavirin, an antiviral drug. In some specific
situations, interferon has also been used successfully.
Prevention
Prevention is the most effective approach against the disease.
At the population level, transmission of HEV and hepatitis E disease
can be reduced by:
- maintaining quality standards for public water supplies;
- establishing proper disposal systems for human feces.
On an individual level, infection risk can be reduced by:
- maintaining hygienic practices such as hand-washing with safe water, particularly before handling food;
- avoiding consumption of water and/or ice of unknown purity; and
- adhering to WHO safe food practices.
In 2011, a recombinant subunit vaccine to prevent hepatitis E
virus infection was registered in China. It has not yet been approved in
other countries.
In 2015 the WHO’s Strategic Advisory Group of Experts (SAGE)
on Immunization reviewed the existing evidence on the burden of
hepatitis E and on the safety, immunogenicity, efficacy, and
cost-effectiveness of the licensed hepatitis E vaccine:
WHO has also written a position paper based on the SAGE review:
Recommendations from the position paper are summarized in the WHO response section below.
Guidelines for epidemic measures
WHO has published a manual on recognition, investigation and control of waterborne outbreaks of hepatitis E.
In brief, the following steps are recommended during a suspected outbreak of hepatitis E:
- verification of the diagnosis and confirmation of existence of an outbreak;
- determination of the mode of transmission, and identification of the population at increased risk of infection;
- improvement of sanitary and hygienic practices to eliminate faecal contamination of food and water; and
- elimination of the source of infection.
WHO response
WHO has issued a technical report “Waterborne Outbreaks of
Hepatitis E: recognition, investigation and control”. The manual gives
information about the epidemiology, clinical manifestations of the
disease, and diagnosis of hepatitis E. It also provides guidance to
public-health authorities on how to respond to outbreaks of hepatitis E
infection.
The WHO Strategic Advisory Group of Experts (SAGE) on
Immunization issued a position paper on hepatitis E in 2015 which
reviewed existing evidence on the burden of hepatitis E and on the
safety, immunogenicity, efficacy, and cost-effectiveness of the licensed
hepatitis E vaccine. Regarding the use of the hepatitis E vaccine, it
recommends the following:
- WHO recognizes the importance of hepatitis E as a public health
problem in many developing countries, particularly among special
populations such as pregnant women and individuals living in camps for
displaced persons and in outbreak situations.
- WHO does not make a recommendation on the introduction of the
vaccine for routine use in national programmes in populations where
epidemic and sporadic hepatitis E disease is common. However, national
authorities may decide to use the vaccine based on the local
epidemiology.
- Due to the lack of sufficient information on safety,
immunogenicity, and efficacy in the following population subgroups, WHO
does not recommend routine use of the vaccine in children aged under 16
years, pregnant women, people with chronic liver disease, people on
organ transplant waiting lists, and travellers.
- There may be special situations such as outbreaks where the risk
of hepatitis E or of its complications or mortality is particularly
high. The current WHO position concerning routine programmes should not
preclude the use of the vaccine in these specific situations. In
particular, the use of the vaccine to mitigate or prevent outbreaks of
hepatitis E should be considered as well as the use of the vaccine to
mitigate consequences in high risk groups such as pregnant women.
- As further data become available, the current WHO position on
hepatitis E vaccine will be reviewed and updated as necessary on the
basis of new information.
In May 2016, The World Health Assembly adopted the first
“Global Health Sector Strategy on Viral Hepatitis, 2016-2021”. The
strategy highlights the critical role of Universal Health Coverage and
the targets of the strategy are aligned with those of the Sustainable
Development Goals.
The strategy has a vision of eliminating viral hepatitis as a
public health problem and this is encapsulated in the global targets of
reducing new viral hepatitis infections by 90% and reducing deaths due
to viral hepatitis by 65% by 2030. Actions to be taken by countries and
WHO Secretariat to reach these targets are outlined in the strategy.
To support countries in moving towards achieving the global
hepatitis goals under the Sustainable Development Agenda 2030 WHO is
working in the following areas:
- raising awareness, promoting partnerships and mobilizing resources;
- formulating evidence-based policy and data for action;
- preventing transmission; and
- scaling up screening, care and treatment services.
WHO also organizes World Hepatitis Day on 28 July every year to increase awareness and understanding of viral hepatitis.
Source:
http://www.who.int/mediacentre/factsheets/fs280/en/
