Hepatitis A,B,C,D,and E,CAUSES,TRANSMISSION, EPIDEMIOLOGY AND TREATMENTS

Hepatitis A

Fact sheet

Key facts

Hepatitis A is a viral liver disease that can cause mild to severe illness.The hepatitis A virus (HAV) is transmitted through ingestion of contaminated food and water or through direct contact with an infectious person.Almost everyone recovers fully from hepatitis A with a lifelong immunity. However, a very small proportion of people infected with hepatitis A could die from fulminant hepatitis.The risk of hepatitis A infection is associated with a lack of safe water, and poor sanitation and hygiene (such as dirty hands).Epidemics can be explosive and cause substantial economic loss.A safe and effective vaccine is available to prevent hepatitis A.Safe water supply, food safety, improved sanitation, hand washing and the hepatitis A vaccine are the most effective ways to combat the disease.

Hepatitis A is a liver disease caused by the hepatitis A virus. The virus is primarily spread when an uninfected (and unvaccinated) person ingests food or water that is contaminated with the faeces of an infected person. The disease is closely associated with unsafe water or food, inadequate sanitation and poor personal hygiene.

Unlike hepatitis B and C, hepatitis A infection does not cause chronic liver disease and is rarely fatal, but it can cause debilitating symptoms and fulminant hepatitis (acute liver failure), which is often fatal.

Hepatitis A occurs sporadically and in epidemics worldwide, with a tendency for cyclic recurrences. The hepatitis A virus is one of the most frequent causes of foodborne infection. Epidemics related to contaminated food or water can erupt explosively, such as the epidemic in Shanghai in 1988 that affected about 300 000 people¹. Hepatitis A viruses persist in the environment and can withstand food-production processes routinely used to inactivate and/or control bacterial pathogens.

The disease can lead to significant economic and social consequences in communities. It can take weeks or months for people recovering from the illness to return to work, school, or daily life. The impact on food establishments identified with the virus, and local productivity in general, can be substantial.

Geographical distribution

Geographical distribution areas can be characterized as having high, intermediate or low levels of hepatitis A virus infection.

Areas with high levels of infection

In developing countries with poor sanitary conditions and hygienic practices, most children (90%) have been infected with the hepatitis A virus before the age of 10 years ². Those infected in childhood do not experience any noticeable symptoms. Epidemics are uncommon because older children and adults are generally immune. Symptomatic disease rates in these areas are low and outbreaks are rare.

Areas with intermediate levels of infection

In developing countries, countries with transitional economies, and regions where sanitary conditions are variable, children often escape infection in early childhood and reach adulthood without immunity. Ironically, these improved economic and sanitary conditions may lead to accumulation of adults who have never been infected and who have no immunity. This higher susceptibility in older age groups may lead to higher disease rates and large outbreaks can occur in these communities.

Areas with low levels of infection

In developed countries with good sanitary and hygienic conditions, infection rates are low. Disease may occur among adolescents and adults in high-risk groups, such as injecting-drug users, men who have sex with men, people travelling to areas of high endemicity, and in isolated populations, such as closed religious communities. However, when the virus gets introduced in such communities, high levels of hygiene stops person-to-person transmission and outbreaks die out rapidly.

Transmission

The hepatitis A virus is transmitted primarily by the faecal-oral route; that is when an uninfected person ingests food or water that has been contaminated with the faeces of an infected person. In families, this may happen though dirty hands when an infected person prepares food for family members. Waterborne outbreaks, though infrequent, are usually associated with sewage-contaminated or inadequately treated water.

The virus can also be transmitted through close physical contact with an infectious person, although casual contact among people does not spread the virus.

Symptoms

The incubation period of hepatitis A is usually 14–28 days.

Symptoms of hepatitis A range from mild to severe, and can include fever, malaise, loss of appetite, diarrhoea, nausea, abdominal discomfort, dark-coloured urine and jaundice (a yellowing of the skin and whites of the eyes). Not everyone who is infected will have all of the symptoms.

Adults have signs and symptoms of illness more often than children. The severity of disease and fatal outcomes are higher in older age groups. Infected children under 6 years of age do not usually experience noticeable symptoms, and only 10% develop jaundice. Among older children and adults, infection usually causes more severe symptoms, with jaundice occurring in more than 70% of cases. Hepatitis A sometimes relapses. The person who just recovered falls sick again with another acute episode. This is, however, followed by recovery.

Who is at risk?

Anyone who has not been vaccinated or previously infected can get infected with hepatitis A virus. In areas where the virus is widespread (high endemicity), most hepatitis A infections occur during early childhood. Risk factors in intermediate and high endemicity areas include:

poor sanitation;lack of safe water;use of recreational drugs;living in a household with an infected person;being a sexual partner of someone with acute hepatitis A infection; andtravelling to areas of high endemicity without being immunized.

Diagnosis

Cases of hepatitis A are not clinically distinguishable from other types of acute viral hepatitis. Specific diagnosis is made by the detection of HAV-specific Immunoglobulin G (IgM) antibodies in the blood. Additional tests include reverse transcriptase polymerase chain reaction (RT-PCR) to detect the hepatitis A virus RNA, and may require specialised laboratory facilities.

Treatment

There is no specific treatment for hepatitis A. Recovery from symptoms following infection may be slow and may take several weeks or months. Most important is the avoidance of unnecessary medications. Acetaminophen / Paracetamol and medication against vomiting should not be given.

Hospitalization is unnecessary in the absence of acute liver failure. Therapy is aimed at maintaining comfort and adequate nutritional balance, including replacement of fluids that are lost from vomiting and diarrhoea.

Prevention

Improved sanitation, food safety and immunization are the most effective ways to combat hepatitis A.

The spread of hepatitis A can be reduced by:

adequate supplies of safe drinking water;proper disposal of sewage within communities; andpersonal hygiene practices such as regular hand-washing with safe water.

Several injectable inactivated hepatitis A vaccines are available internationally. All are similar in terms of how well they protect people from the virus and their side-effects. No vaccine is licensed for children younger than 1 year of age. In China, a live oral vaccine is also available.

Nearly 100% of people develop protective levels of antibodies to the virus within 1 month after injection of a single dose of vaccine. Even after exposure to the virus, a single dose of the vaccine within 2 weeks of contact with the virus has protective effects. Still, manufacturers recommend 2 vaccine doses to ensure a longer-term protection of about 5 to 8 years after vaccination.

Millions of people have received injectable inactivated hepatitis A vaccine worldwide with no serious adverse events. The vaccine can be given as part of regular childhood immunizations programmes and also with other vaccines for travellers.

Immunization efforts

Vaccination against hepatitis A should be part of a comprehensive plan for the prevention and control of viral hepatitis. Planning for large-scale immunization programmes should involve careful economic evaluations and consider alternative or additional prevention methods, such as improved sanitation, and health education for improved hygiene practices.

Whether or not to include the vaccine in routine childhood immunizations depends on the local context. The proportion of susceptible people in the population and the level of exposure to the virus should be considered. Generally speaking, countries with intermediate endemicity will benefit the most from universal immunization of children. Countries with low endemicity may consider vaccinating high-risk adults. In countries with high endemicity, the use of vaccine is limited as most adults are naturally immune.

Countries with immunization schedules that include hepatitis A

As of June 2016, 16 countries used hepatitis A vaccine in routine immunization of children nationally (including 6 countries in the American region, 3 in the Eastern Mediterranean region , 4 in the European region and 3 in the Western Pacific region.

While the 2 dose regimen of inactivated hepatitis A vaccine is used in many countries, other countries may consider inclusion of a single-dose inactivated hepatitis A vaccine in their immunization schedules. Some countries also recommend the vaccine for people at increased risk of hepatitis A, including:

users of recreational drugs;travellers to countries where the virus is endemic;men who have sex with men; andpeople with chronic liver disease (because of their increased risk of serious complications if they acquire hepatitis A infection).

Regarding immunization for outbreak response, recommendations for hepatitis A vaccination should also be site-specific. The feasibility of rapidly implementing a widespread immunization campaign needs to be included.

Vaccination to control community-wide outbreaks is most successful in small communities, when the campaign is started early and when high coverage of multiple age groups is achieved. Vaccination efforts should be supplemented by health education to improve sanitation, hygiene practices and food safety.

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.

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; andscaling 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.

Hepatitis B

Fact sheet
Updated July 2016

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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.

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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:

• 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 July 28 every year to increase awareness and understanding of viral hepatitis.

Hepatitis C

Fact sheet
Updated July 2016

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Key facts

• Hepatitis C is a liver disease caused by the hepatitis C virus: the virus can cause both acute and chronic hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness.
• The hepatitis C virus is a bloodborne virus and the most common modes of infection are through unsafe injection practices, inadequate sterilization of medical equipment, and the transfusion of unscreened blood and blood products.
• Globally, between 130–150 million people globally have chronic hepatitis C infection.
• A significant number of those who are chronically infected will develop liver cirrhosis or liver cancer.
• Approximately 700 000 people die each year from hepatitis C-related liver diseases 1.
• Antiviral medicines can cure approximately 90% of persons with hepatitis C infection, thereby reducing the risk of death from liver cancer and cirrhosis, but access to diagnosis and treatment is low.
• There is currently no vaccine for hepatitis C; however research in this area is ongoing.

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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.

• Guidelines for the screening, care and treatment of persons with chronic hepatitis C

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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.

WHO also organizes World Hepatitis Day on 28 July every year to increase awareness and understanding of viral hepatitis.

Hepatitis D

Fact sheet
July 2016

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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.

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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:

• 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.

     Hepatitis E

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Key facts

• Hepatitis E is a liver disease caused by infection with a virus known as hepatitis E virus (HEV).
• Every year, there are an estimated 20 million HEV infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E1, and 56 600 hepatitis E-related deaths2.
• Hepatitis E is usually self-limiting but some cases may develop into fulminant hepatitis (acute liver failure).
• The virus is transmitted via the faecal-oral route, principally via contaminated water.
• Hepatitis E is found worldwide, but the prevalence is highest in East and South Asia.
• A vaccine to prevent hepatitis E virus infection has been developed and is licensed in China, but is not yet available elsewhere.

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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 worldwide1with an estimated 56 600 deaths2. 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:

• The global prevalence of hepatitis E virus infection and susceptibility: a systematic review.
• A systematic review on hepatitis E virus globally

WHO has also written a position paper based on the SAGE review:

• Hepatitis E position paper

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.

• Waterborne Outbreaks of Hepatitis E: recognition, investigation and control

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.

Guidelines & manuals

• Hepatitis C treatment
• Hepatitis B treatment
• Monitoring and evaluation of hepatitis B and C
• Hepatitis E waterborne outbreaks
• Development of national viral hepatitis plans

     Thanks