Viral hepatitis

There are five known hepatitis viruses: A, B, C, D, and E. All cause disease which primarily affect the liver.

Hepatitis A

Hepatitis A is an infectious disease caused by the hepatitis A virus (HAV). Hepatitis A is common in regions of the world with poor sanitation and inadequate safe water sources. Transmission routes are faecal-oral and blood. HAV infection is often asymptomatic, but when they do occur symptoms may include nausea, vomiting, diarrhoea, jaundice, fever, and abdominal pain.  Acute liver failure is a rare complication that is more common in the elderly.

Infection can be prevented by vaccination. Resistance is life-long following a single natural infection.

There is no specific treatment for HAV infection, other than maintaining adequate nutritional balance, and fluid replacement if vomiting and diarrhoea are severe.

Hepatitis B

Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV). It can cause both acute and chronic infections. Most cases of chronic disease are asymptomatic, however, cirrhosis and liver cancer may eventually develop. HBV is transmitted by exposure to infectious blood or body fluids. The infection can be diagnosed 30 to 60 days after exposure. HBV infection has been preventable by vaccination since 1982, with two or three doses required to achieve full protection. Natural life-long resistance develops following infection.

During initial infection, care is based on the patient’s symptoms. As an exception, early antiretroviral therapy may be indicated for cases of aggressive (fulminant) hepatitis or when the patient is immunocompromised. In those who develop chronic disease, antiviral medication such as tenofovir or interferon may be useful to reduce the risk of cirrhosis and liver cancer. The drugs available cannot clear the infection, rather they inhibit viral replication to limit liver damage. The World Health Organization recommended a combination of tenofovir and entecavir as first-line agents.

Drugs for HBV infections are discussed in more detail in the topic 'Viral hepatitis- HBV and HBC'

This review, published in The Lancet in Feb 2023 (doi.org/10.1016/S0140-6736(22)01468-4), contains a huge amount of detailed information about HBV, including synopses of current therapies, and of some new antiviral and immunomodulatory therapies that are in clinical development. It is hoped that some of these new agents will rid the body of HBV antigens and achieve a 'functional cure' of HBV infection.

Hepatitis C

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV). Few symptoms are evident during the initial period of infection, or even when disease has progressed to early chronic infection. Damage accumulates over time and can lead to liver disease, cirrhosis and liver cancer. HCV is spread primarily by blood-to-blood contact (e.g. associated with intravenous drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, blood transfusions, and mother-to-child transmission).

There is no vaccine against hepatitis C, however chronic HCV infection can be effectively managed about 95% of the time with antiviral medications. HCV treatment focusses on management rather than cure. Treatment aims are:

• eradication of virus
• decreasing morbidity and mortality
• normalization of biochemical markers
• improving clinical symptoms
• preventing spread of the disease
• preventing progression to cirrhosis and hepatocellular carcinoma
• preventing the development of end-stage liver disease and its manifestations

Drugs for HCV infections are discussed in more detail in the topic 'Viral hepatitis- HBV and HBC'

There are at least six genetically distinct HCV genotypes, or strains. Knowing the strain of the virus can help inform treatment recommendations. Treatment during the first six months is more effective than once chronic infection has established. In the US population, it is estimated that ~75% of HCV infections are genotype 1; 20-25% are genotypes 2 or 3; and the remaining small number of infections are genotypes 4, 5 or 6.

HCV genotypes

Hepatitis D

Hepatitis D is caused by the hepatitis D virus (HDV), a small spherical enveloped viroid, which can only replicate if co-infected with HBV. The presence of HDV+HBV results in more severe complications compared to infection with HBV alone, including greater risk of developing liver failure during acute infection, more rapid progression to cirrhosis and an increased risk of chronic infection progressing to liver cancer. HBV+HDV infection has a fatality rate of ~20%, the highest of all hepatitis infections. HDV infection is rare in developed countries, where it is mainly restricted to groups at high risk of hepatitis B infection, especially injecting drug users and to a lesser extent, patients receiving clotting factor concentrates.

Because of its reliance on HBV for replication, anti-HBV vaccination is HDV preventative. Pegylated interferon alpha is effective in reducing hepatitis D viral load, but it increases again when treatment is discontinued.

Hepatitis E

Hepatitis E is caused by the hepatitis E virus (HEV). HEV has a faecal-oral transmission route. Infection is usually acute and self-limiting, with low mortality in developed countries. However, immunocompromised patients (in particular organ transplant recipients taking immunosuppressive drugs) are at a greater risk of developing chronic HEV hepatitis, and these patients have a higher mortality rate. HEV infection is fatal in only ~2% of all cases. One other group with increased mortality (up to ~20%) is pregnant women who can develop a clinical syndrome called fulminant liver failure when infected with HEV.

Sanitation is the most important measure in prevention of HEV infection.  The HEV 239 vaccine is available in China, but the WHO does not make a recommendation regarding its routine use.

In terms of drug treatment, there is off-label experience for treating chronic hepatitis E infection with ribavirin, which indicates that low dose ribavirin for 3 months is associated with viral clearance in about two-thirds of chronic HEV infections. Virus can be cleared in organ transplant patients by temporarily reducing their level of immunosuppression.