The Alphabets of Hepatitis: A to E Types and Their Complications

Did you know that 304 million people worldwide are living with Hepatitis B and C?

But what makes Hepatitis B different from Hepatitis C and the rest? What sets these forms apart?

Hepatitis is a liver inflammation caused by pathogens (i.e., viral and bacterial infections) and other metabolic factors (e.g., related diseases) [1, 2]. Viral Hepatitis is the most common with numerous cases estimated hundreds of millions of affected individuals worldwide. This refers to a group of hepatitis viruses A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) which primarily infect and replicate within the liver cells. However, although such types share the common host and target cells, they differ in various factors such as their origins, modes of transmission, and complications [3, 4].

Hepatitis A

Hepatitis A is caused by a non-enveloped RNA virus called picornavirus, also known as the Hepatitis A virus (HAV) [5, 6]. HAV Transmission is primarily via the fecal-oral route, where incidences of spreading often occur through physical contact with an infected individual, and in situations where poor sanitation and unhygienic conditions are present [5, 7].

HAV-infected patients suffer from an acute but self-limited infection. They may experience mild to severe symptoms such as fever, headache, jaundice, malaise, dark urine, clay-colored stools, and abdominal discomfort within 14 to 28 days of incubation. Adults with Hepatitis A display such symptoms, whereas infected children are usually asymptomatic [7, 8].

There is no specific treatment for Hepatitis A. Prevention through vaccination and improved sanitation is highly recommended to combat HAV [8, 9].

Hepatitis B

Hepatitis B is the most common type of hepatitis. It is caused by a DNA virus known as hepadnavirus (commonly called Hepatitis B virus or HBV). This double-stranded virus is typically transmitted through bodily fluids such as blood and semen [7, 10]. Transmission through the use of contaminated materials (e.g., syringes) also occurs in drug abuse-related cases [11, 12].

HBV can cause both acute and chronic infections. Acute infection involves symptoms such as anorexia, jaundice, joint pain, malaise, dark urine, clay-colored stools, fatigue, and abdominal pain [13]. When left untreated, it may develop into chronic hepatitis. Infants and neonates are the most susceptible to HBV chronic infection due to underdeveloped immune systems, whereas adult cases usually lead to liver cirrhosis or hepatocarcinoma. Patients are typically asymptomatic and vulnerable to Hepatitis D infection. Peak infectivity of HBV appears within 60-150 days of incubation [13, 14, 15].

Vaccines and health education are implemented to reduce the burden of HBV spreading. However, it remains one of the major health problems worldwide [13, 16].

Hepatitis C

Hepatitis C is caused by an RNA virus called flavivirus or the Hepatitis C virus (HCV). This causative agent is less contagious than HBV and is commonly transmitted through bodily fluids, particularly blood [17, 18, 19]. People infected with HCV typically suffer from an acute infection for six (6) months and may develop into chronic hepatitis if left untreated. While acute infections are considered self-limited, HCV infectivity often leads to chronic hepatitis as symptoms are not immediately present and patients are generally asymptomatic. The severity of chronic infections rapidly progresses into cirrhosis or liver cancer [18, 20].

HCV has been a significant problem affecting millions of people worldwide [21, 22]. Fortunately, specific treatments are already accessible for chronic HCV infections. Direct-acting antiviral regimens as well as interferon-based regimens are effectively used for treating HCV-infected patients. Strategic awareness is also implemented in reducing HCV cases [22, 23].

Hepatitis D

Hepatitis D is a viral hepatitis known to be the most severe among all types. It is mainly caused by a defective virus called delta virus, also known as Hepatitis D Virus (HDV), a unique pathogen among all viruses due to its structure and mechanism. HDV replicates and infects cells only with the presence of HBV infection [24, 25, 26].

Patients with chronic HBV infections are vulnerable to HDV. As it co-infects with HBV, it results in more rapid development of acute symptoms within 3-7 weeks of incubation. It can also lead to the progression of relative liver illnesses such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In rare cases, individuals with HDV may also develop fulminant hepatitis [24, 27]. HDV infects all ages, although cases are higher among men who have sex with men and commercial sex workers with existing hepatitis and Human Immunodeficiency Virus (HIV) [26, 27, 28].

Although dependent on HBV, HDV is substantially responsible for the overall burden caused by HBV. However, regardless of its significant contribution to the growing problem of HBV, there is yet no specific efficient treatment for hepatitis D [29]. The pegylated interferon alpha is generally recommended but limited to those with pre-existing conditions due to its side effects. Antiviral medications (i.e., Bulevirtide) and Hepatitis B immunization are also used to fight against HDV infections [28, 29].

Hepatitis E

Hepatitis E is caused by a single-stranded hepevirus, also known as Hepatitis E Virus (HEV). This RNA virus, originating from wild game products, is sometimes indistinguishable from hepatitis A due to its similar characteristics, symptoms, and progression. Comparably, HEV is also transmitted via the fecal-oral route and commonly ingested from contaminated water [30, 31].

People infected with HEV typically suffer from an acute infection that lasts for 1-4 weeks albeit immunosuppressed patients may develop chronic hepatitis within 4-5 weeks of incubation [30, 32, 33]. Pregnant women are also considered the most vulnerable group as HEV progresses severely, leading to liver dysfunctions, including liver fibrosis. No specific treatments are used for HEV as it is self-limited, although particular medicines are introduced for immunosuppressed patients (i.e., ribavirin) [34, 35].

The first hepatitis case was recorded in the 19th century. From then, seven types of viruses were identified until 1995. Among these, the A to E types are of greatest concern due to their rapid progression worldwide. On the other hand, Hepatitis F and G are still under evaluation with their existence not yet been proven. While the existing types have already infiltrated the health status of millions across the world, it is important to understand that their complications also vary depending on the genotypes of each form present in hepatitis cases: HAV has six (6); HBV has nine (9); HCV has six (6); HDV has eight (8); and HEV has four (4) [36, 37, 38].

While hepatitis may seem complex, an in-depth understanding of it is a first step toward effective prevention. Currently, strategic awareness through various campaigns, ongoing research, and clinical trials on hepatitis are continuously carried out. In 2016, the World Health Organization adopted the Global Health Sector Strategy (GHSS) to eliminate viral hepatitis by 2030, which has a goal of a major scale-down on the incidence and mortality rates. Easily accessible vaccines are also introduced worldwide, particularly for Hepatitis B [39, 40].

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