Liver disease: viral hepatitis - Amazon AWS

Clinical transmission and treatment, and some even being vaccine-preventable.

Module 1845

Liver disease: viral hepatitis From this pharmacy CPD module on viral hepatitis you will learn: • What can cause liver diseases • The different types of hepatitis that exist and how they are diagnosed and treated • Who is susceptible to the various types of hepatitis • The pharmacist’s role in helping patients manage hepatitis

ROSEMARY BLACKIE, PHARMACIST Liver disease is the fifth leading cause of death in the UK, killing more people than road accidents and diabetes combined. It is estimated that at any one time, there are around two million people with a liver problem. Liver disease can be the result of: • drug-use (illicit or prescribed) • infection • alcohol use • lifestyle factors • genetics. Signs and symptoms of liver disease occur at various stages. Some occur at the acute stage, while others do not appear until the liver has lost significant functionality. Many of the symptoms are non-specific, which makes diagnosis at an early stage difficult. Liver function and diagnostic tests are used to assess liver function, aid diagnosis and monitor disease. Other tests, such as antibodies for hepatitis infection and diagnostic markers for certain diseases, can be used to help determine the cause of liver disease.

This article focuses on viral hepatitis – a major cause of liver disease. There are five distinct types, with each having a different route of

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Hepatitis A virus (HAV) This viral infection is transmitted via the faecaloral route, and can be caused by eating food or drinking water contaminated with human faeces. Common examples include shellfish, and fruit and vegetables growing close to the ground. Infection can also be caused by close physical contact with an infected person, but not by casual contact. Food handlers can spread contamination if not observing good hygiene techniques. There are around 1.4 million HAV infections globally per year. High levels of infection are associated with areas of poor sanitary conditions and hygiene, including parts of the far east, Central America and north Africa. In endemic countries, infection is uncommon in adults as the vast majority have had HAV as a child – conferring lifelong immunity. Outbreaks do occur in developed countries – for example, an outbreak in Scotland in May 2017 was linked to a bakery.

In many cases, large numbers of people are affected quickly, such as in Shanghai in 1988, where 300,000 people were infected from a shellfish-borne outbreak. The infection’s spread has also been reported among men who have sex with men, as well as injecting drug users. Those traveling internationally are at an increased risk, especially when going to areas of poor sanitation and staying with the local population. In 2013, there were 283 confirmed laboratory cases of HAV infection in the UK, and there are estimates to show that between six and 30 cases occur per 100,000 international travellers per month. HAV is a ribonucleic acid (RNA) virus and has an incubation period of around 14-28 days. It may have non-specific symptoms, for example: • fever • diarrhoea • nausea • liver-related symptoms, such as jaundice and dark-coloured urine. Adults tend to experience symptoms more often than children, with severity increasing with age and with any existing chronic liver disease. HAV does not cause chronic liver disease, and acute liver failure is rare. Diagnosis is by detection of immunoglobulin M antibodies to the HAV in the blood. The presence of immunoglobulin G indicates previous infection, and therefore immunity. There is no specific treatment for HAV and recovery can take weeks or months. However, it is important to avoid medication that affects the liver, such as paracetamol. HAV is vaccine-preventable, with a primary course of two vaccines usually given 6-12 months apart. This confers at least 25 years’ protection and can be given from the age of one year. Good hygiene should be observed when travelling abroad, whether vaccinated or not.

Hepatitis B virus (HBV) HBV is spread via infected blood and bodily fluids (including saliva and vaginal fluids). It can also be passed from mother to child during childbirth Module 1845 | Liver disease: viral hepatitis | 1 of 4

– known as perinatal transmission – although it cannot pass through the placenta. It is estimated that 240 million people are chronically infected with HBV globally, and it is one of the most prevalent blood-borne viruses worldwide. Around 780,000 people die annually from HBV infection, mostly from cirrhosis and liver cancer. Approximately 90% of babies infected perinatally go on to develop chronic infection, but only 5% of those infected as adults develop chronic infection. Patients with chronic HBV infection develop progressive liver disease in 25% of cases. There is an incubation period of between 40160 days, and HBV can survive outside the body for at least seven days. Symptoms of infection in the acute phase may include nausea, anorexia and an ache in the right upper right of the abdominal, with jaundice occurring in up to 50% of adults. Diagnosis is by blood tests that detect virus antigens and antibodies. The presence of HBV antigens shows current infection, while their presence over a six month-period denotes chronic infection – which can develop into liver cancer or cirrhosis. Chronic infection can be treated, reducing the risk of detrimental consequences. Treatment suppresses virus replication, but does not clear it, meaning lifelong treatment may be required. The National Institute for Health and Care Excellence (Nice) guidelines for chronic HBV diagnosis and management recommend peginterferon alfa-2a, tenofovir disoproxil or entecavir as treatment options. HBV infection can be reactivated in those taking immunosuppressants or being treated for hepatitis C. Screening and appropriate prevention management is therefore advised. Vaccination is the mainstay of prevention and can be given from birth. The standard schedule is three injections – at birth, one and six months. Accelerated and super-accelerated regimens involve injections closer together, as well as a

fourth dose at 12 months. You should make patients who have HBV aware that they need to avoid unsafe sexual practices and cross-contact with blood or other bodily fluids. Medical and other devices (such as dental equipment, tattoo needles and razors) should not reused or shared. Vaccination is recommended for high-risk groups, which include: • frontline healthcare workers • injecting drug users • men who have sex with men • those changing sexual partners frequently. At least 20 years – and likely lifelong – protection is conferred in those who seroconvert (make antibodies) after receiving the three-dose primary immunisation course. Although not effective in treating acute cases of HVB, the vaccination can provide long-term protection against potential complications – such as liver cancer and cirrhosis – if given within the first 48 hours after infection. Hepatitis B immunoglobulin is used to give immediate – but temporary – protection after accidental contamination with infected blood, such as via needlestick injury. Children born to infected mothers should be given hepatitis B

immunoglobulin to provide immediate protection, and then vaccinated as soon as possible after birth.

Hepatitis C virus (HCV) It is estimated that 71 million people globally have chronic HCV infection, but many do not know that they are infected. Around 0.5% of the UK’s population have this infection. Injecting drug users have a higher prevalence of the infection – as high as 70% in the UK. About 20% of those infected will develop cirrhosis with alcoholism, while being male and over 40 years of age also increases the statistical risk of having HCV. HCV is a highly infectious blood-borne virus, requiring only a very tiny amount of virus to cause infection. There are six different types, known as genotypes, which have a similar genetic makeup. The virus itself can survive for up to two weeks in dried blood. Routes of infection include: • sharing injecting drug equipment and other paraphernalia • poor sterilisation • reuse of medical equipment • use of unscreened blood products

HBV vaccination is recommended for high-risk groups such as injecting drug users


• sexual transmission • via mother to baby during childbirth. HCV is not spread by bodily fluid contact – for example, during sexual intercourse – or by kissing or breast-feeding. However, risk is increased where there are cuts or other breaks in the skin barrier, resulting in blood-to-blood contact. It is not classed as a sexually transmitted infection. The incubation period of HCV is between two weeks and six months, with most people not experiencing any symptoms during initial infection. Those who do have symptoms have non-specific or general liver disease-type symptoms. This means few are diagnosed at the acute stage, which increases the risk of developing chronic infection and spreading the infection. Because the liver can remain fully functional until a large proportion has become damaged, HCV can remain hidden for decades, until symptoms secondary to the original infection occur. This explains why up to 50% of those infected do not know that they are. Symptoms associated with chronic HCV disease include: • fatigue • dry eyes • upper abdominal pain • aches and pains • poor concentration. It is important to note that symptom severity is not indicative of the amount of liver damage. Diagnosis is by blood test for antibodies to the HCV virus, which indicate whether there has been exposure to the virus, but not whether there is current infection. Antibodies are not usually detectable until three months after infection, but in some cases they may not be detectable for up to six months. HCV results in liver-cell death, thought to be caused by a combination of direct viral action and the body’s immune response to infection. Inflammation results in progression to fibrosis of the liver, and a cycle whereby inflammation and fibrosis stimulate each other to result in more

Module 1845 | Liver disease: viral hepatitis | 2 of 4

fibrosis. This happens at a faster rate than the liver can regenerate, so liver function declines. HCV is not vaccine-preventable, so the mainstay for prevention includes: • good hygiene • avoiding sharing injecting equipment • safe handling and disposal of sharps. Improved screening, as well as access to treatment and education, are all vital to help reduce the spread of HCV. You should encourage patients from at-risk groups to be tested, as early diagnosis increases treatment success and reduces the risk of complications and further transmission. The degree of liver damage is one of the factors involved in the decision to commence treatment, as if the liver is not too damaged, treatment can be delayed. Where there is already extensive fibrosis, treatment should ideally be commenced

much sooner. Factors which may increase the risk of treatment failing are: • being over 40 years of age at diagnosis • alcohol use • being male • co-infection with HIV or HBV. Treatment does not restore liver function, but the aim is to cure the disease. ‘Cure’ in this context is defined as when the virus can no longer be detected at 24 weeks after treatment completion. However, being cured does not prevent against reinfection. In 2011, direct-acting antivirals (DAAs) were launched and used in combination with ribavirin and interferon to treat HCV. Newly developed second-generation DAAs, which include sofosbuvir and simeprevir, do not need to be used with ribavirin, have fewer side-effects, shorter

treatment times and higher cure rates. However, these new DAAs are not yet available to everyone. Nice is currently reviewing treatment guidelines and most recently approved sofosbuvir-velpatasvir for use within the NHS, with a treatment time of 12 weeks. Monotherapy with any HCV treatment should be avoided to reduce resistance risk. Treatment regimens are specific to each patient, but the British National Formulary gives details of the drugs and combinations licensed for different genotypes. Sofosbuvir is the only one licensed for use in all six genotypes, in combination with other agents. In addition, screening for HVB should be carried out prior to commencing treatment with DAAs, as they can re-activate latent HVB infection. Stopping drinking alcohol and smoking, ceasing any illicit drug use, maintaining a healthy weight, and ensuring a balanced and healthy diet, will all help to reduce the risk of disease progression.

Hepatitis D virus (HDV) Hepatitis D can only occur when HBV is present. It is transmitted by blood-to-blood or bodily fluid contact. Around 15 million people globally are chronically coinfected with HDV and HBV. Chronic HVD development is rare, but coinfection with HDV increases the risk of cirrhosis and liver failure. There is no specific treatment. Although peginterferon alfa-2a is effective, most patients relapse after treatment is discontinued. Prevention is by vaccination against HBV and observing safe blood-to-blood transmissions. If already infected with HBV, the HBV vaccine will not prevent HDV infection.

Hepatitis E virus (HEV)

HCV is not vaccine-preventable, so a mainstay of prevention is the safe handling and disposal of sharps


It is estimated that worldwide there are 20 million HEV infections annually. It is spread by the faecaloral route – usually through contaminated food or water – but it is not spread by bodily fluid contact. It is also a zoonotic virus, meaning that it can exist in animals without causing disease, and can be passed onto humans by consuming poorly or

uncooked infected meat. The incubation period is three to eight weeks. It generally causes mild disease with non-specific symptoms – such as fatigue, abdominal pain, fever, and aches and pains – as well as those symptoms associated with liver disease, including jaundice, itching and change in urine colour. Diagnosis is by detection of antibodies in the blood, with most people experiencing mild disease and recovering in a month. However, HEV can cause severe disease, resulting in liver failure in up to 25% of pregnant women who contract it. Immunosuppressed patients are more likely to develop chronic disease (over six months) and cirrhosis. In some cases the nervous system is affected, which can result in severe arm and leg pains. There is no specific treatment for HEV. Good hygiene should be practised in endemic areas of the world, along with ensuring food is properly cooked to reduce the risk of contracting the infection.

The pharmacist’s role Those being treated for hepatitis will be under hospital direction. However, community pharmacy services still play an important role, as they will be a first port-of-call for requests for over-the-counter medication to treat any undiagnosed symptoms, as well as for support with the side-effects of treatment. To reduce the risk of disease progression, pharmacists are also in an ideal position to support patients through smoking cessation services, as well as diet and lifestyle advice. You can signpost patients to a number of sources of further information and help: • the British Liver Trust – at britishlivertrust.org.uk – has lots of information on all aspects of liver disease, as well as a helpline • the Hepatitis C Trust at – hepctrust.org.uk – has lots of specific information on all aspects of Hepatitis C, and a helpline. It also produces a booklet which is particularly useful for illicit drug users.


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Liver disease: viral hepatitis CPD Reflect How is hepatitis A transmitted? Which patient groups should be vaccinated against hepatitis B? What is the recommended treatment for hepatitis C? Plan This article contains information about hepatitis A, B, C, D and E infection, including about transmission, symptoms, diagnosis and treatment. Prevention, vaccination and the role of the pharmacist in supporting patients with hepatitis is also discussed. Act

• Read more about the different types of hepatitis on the World Health Organisation (WHO) website: hepatitis A at tinyurl.com/hepatitisa1; hepatitis B at tinyurl.com/hepatitisb1; hepatitis C at tinyurl.com/hepatitisc1; hepatitis D at tinyurl.com/hepatitisd1; and hepatitis E at tinyurl.com/hepatitise1. • Find out more about antiviral treatment for hepatitis from the BNF section 5.3.3 Viral hepatitis • Find out about reliable sources of information and support for patients with hepatitis, for example, the British Liver Trust at tinyurl.com/hepatitisa2 and the Hepatitis C Trust at tinyurl.com/hepatitisc2. Evaluate

1. The hepatitis A virus is transmitted via the faecal-oral route. True or false 2. Chronic liver disease does not occur with hepatitis A infection. True or false 3. The vaccine for hepatitis A can be given from birth and provides protection for up to 10 years. True or false 4. The hepatitis B virus is spread via infected blood and bodily fluids. True or false 5. The hepatitis B virus has an incubation period of around 14-28 days. True or false

Are you now confident in your knowledge of the different types of hepatitis and how they are managed? Could you give advice to patients about symptoms, treatment and prevention?

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6. Nice recommends sofosbuvir and simeprevir for the treatment of chronic hepatitis B infection. True or false 7. The hepatitis C virus can survive for up to two weeks in dried blood. True or false 8. Most people do not experience any symptoms during initial infection with hepatitis C. True or false 9. Peginterferon alfa-2a, tenofovir disoproxil and entecavir are recommended as monotherapy for the treatment of hepatitis C. True or false 10. Hepatitis D can only occur when hepatitis A is present. True or false

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