Hepatitis B (HBV), the ‘Silent Epidemic’: Epidemiology, Vaccine, Symptoms, and Treatment

History

The earliest description of hepatitis-like symptoms, like jaundice, was by Hippocrates in the fifth century BCE [5]. However, it was not until 1883 that Lurmen recorded the first epidemic of serum hepatitis (as hepatitis B was previously known) in Germany. Shipyard workers in developed jaundice after receiving smallpox vaccines. The vaccines were derived from human lymph, and Lurmen observed that only workers who received certain batches of vaccines fell ill [5].

In 1943, Dr. Paul Beeson, an American physician, was the first to identify blood as one of the vehicles of transmission of the hepatitis B virus [5]. This was a landmark discovery in the history of viral infections. The next breakthrough came in 1965. Dr. Baruch Blumberg, an American physician, discovered the hepatitis B surface antigen (HBsAg), also called the ‘Australia antigen.’ 

Five years later, in 1970, a complete hepatitis B virion, known as the Dane particle, was identified [5,6]. This discovery led to the development of the first plasma-derived hepatitis B vaccine. It was licensed for use in the US in 1981. A recombinant hepatitis B vaccine soon replaced it in 1986 as people feared that the former could transmit live HBV and other blood-borne pathogens [5]. 

In 2016, the World Health Assembly made news with an action plan to eliminate viral hepatitis as a public health threat by 2030. The mission was to reduce the number of new chronic infections by 90% and the mortality rate by 65% [1]. 

There has been significant progress toward reaching these targets. 

From 2015 – 2020, there has been an increase in global coverage of the:

• Last dose of the HBV vaccine from 82% to 85% .
• Vaccines given at birth from 38% 43%. 

More regions have been following safe practices when performing blood transfusions and using syringes [7].

Epidemiology

All unvaccinated people are susceptible to HBV infection [8], especially:

• People who live with an infected person
• People with multiple sexual partners
• Healthcare workers
• People with kidney issues
• Drug addicts who use shared needles 
• Babies born to infected mothers [3]

Hepatitis B infections have a global footprint and are more prevalent in Asia, Africa, South America, and the Caribbean. They are reported throughout the year as the disease has no temporal pattern. But, the infection frequency and transmission pattern vary from region to region.

For instance, in Africa, Southeast Asia, and most parts of the Pacific Islands, childhood infections, including those acquired during birth, are more common. The incidence of adults being infected in the US, Western Europe, and Australia is higher. It explains why there are more chronic cases in the east compared to the west [5]. 

• In the United States, between 2009 and 2013, the number of cases of acute HBV infection in Kentucky, Tennessee, and West Virginia increased by 114%. Most of those infected were between 40 – 49 years of age. This trend was associated with increased use of shared needles. 
• By 2018, around 3,332 cases of acute illness were reported, but the CDC estimates the actual number of cases to be about 21,600. Statistics show that between 0.85 to 2.2 million people in the US have chronic hepatitis B [3]. 
• In 2020, European Center for Disease Prevention and Control (ECDC) data shows that around 14,428 cases of HBV infections were reported in EU/EEA member states. Of these cases, 43% of infected individuals were chronic, 7% were acute, and the rest were unknown. People between the age group of 35 – 44 years were the ones that were most affected by acute illness. The majority of those who had a chronic disease were aged 25 to 34 [9].

WHO estimates that the Western Pacific Region (including Cambodia, China, Laos, Mongolia, Vietnam, and a few other countries) accounts for around 45% of global HBV infections [10]. 

• In China, around 87 million people are currently living with chronic infections, accounting for almost one-third of HBV infections worldwide [11]. 
• Laos, a landlocked country in Southeast Asia, is considered to be highly endemic to HBV infection, with over 8% of the population infected by the virus. Also, it has one of the highest incidence rates in the world for liver cancer due to HBV infection or liver fluke (a parasitic infection). The incidence of liver cancer in Laos is around 35.7 and 14.2 cases per population of 100,000 [12]. 
• Vietnam is among the 20 countries that account for 75% of viral hepatitis cases worldwide. In 2017 alone,  there were over 7.5 million chronic HBV infections reported across the country. This number is over 8% of the population. Most chronic HBV infections here are acquired during childbirth [13]. 
• Among all the WHO regions, Cambodia is reported to have the highest prevalence of HBV infections, accounting for around 6.2% of the adult population. But, the country has put in tremendous effort in decreasing the prevalence of HBV infection among children aged between five and seven years. In 2017, the infection prevalence dropped to less than 1% [10].

The prevalence of HBV infections remains high in the WHO African Region (AFRO) despite immunization efforts. 

• Africans have a 60% lifetime risk of contracting HBV infection. Around 82 million people living in the sub-continent have chronic conditions. That is around one-fourth of all chronic cases worldwide. About 6.3 million children under five are seropositive for HBsAg – one of the serologic markers of the infection [14]. 
• The prevalence rate of HBV infections in the Sub-Saharan region of Africa is as high as 16.16%. 
• Mauritania is regarded as a hyper-endemic region for HBV. Nearly 25% of all infected adults die due to severe liver-related complications like liver cirrhosis or cancer. In particular, communities that are socially and economically challenged are the most affected [15].

How is it spread?

HBV infections spread from person to person mainly through direct contact with body fluids – including blood, breast milk, saliva, semen, sweat, tears, and urine. It does not spread through food or water. 

The following activities increase the risk of transmission:

• Having sexual intercourse with an infected person
• Kissing an infected person
• Using shared needles contaminated with the virus
• Using toothbrushes, razors, or other personal equipment of an infected person
• Mother-to-child transmission during delivery – infants who contract the virus have a high chance of developing chronic HBV infection
• Touching or licking the open sores of an infected person [3,5,16,17]

Biology of the disease

Once the virus enters the body, it multiplies in hepatocytes, cells that make up 80% of the liver mass. Eventually, the infected individual’s immune system is triggered, creating an immune response. Because of this immune response, the liver can get inflamed [8].

Symptoms

Symptoms can appear any time between two and five months (three months on average) following exposure to the virus. It can take several weeks or sometimes even months (usually six months) to fully recover. The concern is that many can be asymptomatic and still infect other people.

Symptoms vastly differ for acute (short-term) and chronic (long-term) infections. A person with an acute illness may experience:

• Fever
• Fatigue
• Abdominal pain
• Joint pain
• Loss of appetite
• Nausea
• Vomiting
• Dark colored urine
• Clay-colored bowel movements
• Jaundice

People who develop chronic hepatitis can remain asymptomatic for decades. If symptoms appear later in life, they can be similar to those experienced by a newly-infected person. This type of illness is more common in children. Adults who succumb to chronic disease are likely to develop chronic liver diseases such as liver cirrhosis or liver cancer [1,3].

Diagnosis

A laboratory diagnosis is needed to detect HBV infections. The HBV infection is diagnosed by detecting one of the serologic markers in the blood sample. They include HBsAg proteins, antibodies to HBsAg proteins, and IgM and IgG antibodies to core antigens HBV, IgM anti-HBc, and IgG anti-HBc, respectively. Since one of these serologic markers is present during different stages of infection, detecting their presence can confirm HBV [4]. 

Blood counts, liver enzymes, and liver histology are helpful in distinguishing between acute and chronic HBV infection [1,17].

Treatment

The CDC recommends people diagnosed with HBV take a hepatitis A shot and get tested for hepatitis C [3].

Acute HBV Infection

There is no treatment for acute hepatitis B. Around 95% of patients get cured without medical intervention [17]. Doctors recommend that patients rest well, have proper food, and drink more fluids [1,3]. Antiviral treatment is administered in severe cases to suppress virus replication, reduce liver inflammation, and prevent the disease from progressing to a chronic illness [17].

Chronic HBV Infection

There are several medications to treat chronic hepatitis B infections. While the treatment is not a cure, it can slow down the progression of liver-related complications such as cirrhosis. They can also reduce the incidence of liver cancer. But, these medications have to be taken indefinitely and can cause side effects. 

A silver lining is that not all patients need these medications. Lifestyle changes, like a nutritious diet, a healthy BMI, and avoiding alcohol and liver-damaging drugs, may help prevent complications [1,3]. In case of acute liver failure, doctors may consider performing liver transplantation surgery [17].

Prevention

Vaccination is the easiest way to protect against HBV infection. People of all age groups can take the HBV vaccine. They are safe, and the common side-effect that one can expect is soreness at the injection area [3].

WHO recommends that infants receive the first shot as early as possible – preferably within 24 hours. This is to be followed by two or three doses with a four weeks gap between each dose. Unlike the flu vaccine, which wanes off over time, HBV shots are effective for at least 20 years (even a lifetime) [1].

CDC recommends HBV screening as a preventive measure for:

• Children born to mothers with HBV infection
• People born in regions or countries endemic to HBV – this will help determine whether the person is living with chronic HBV infection
• Unvaccinated individuals born in the US to parents born in an HBV-endemic area
• People infected with Hepatitis C Virus (HCV)
• Pregnant women
• People who need immunosuppressive therapy 
• Men who have sexual intercourse with men
• People who had sexual intercourse with those infected or suspected to be infected with HBV
• People who are HIV positive
• People who are on dialysis
• Drugs addicts and people with elevated ALT levels [3]. 

Other preventive guidelines include:

• People who are pregnant taking antiviral drugs to protect their fetus from infection
• Using contraceptives during sexual intercourse and avoiding sexual relations with multiple partners
• Taking an HBV test before donating blood
• Avoiding receiving blood from those who had HBV in the past
• Older adults traveling to places that are endemic to HBV should consider receiving the vaccine
• Immediately cleaning and disinfecting surfaces with blood spills. Wearing gloves while doing the cleaning [1,3].

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