Childhood Hepatitis And Its Long-Term Effects

Childhood hepatitis is a common cause of concern among health experts all over the world. There has been an increasing health care burden of viral Hepatitis worldwide in recent years. Even though most of the viruses causing childhood hepatitis are self-limiting, Hepatitis B and Hepatitis C viruses can become chronic, leading to long-term complications. Health care experts now recognize the need for children with hepatitis b and hepatitis c to be monitored annually and for those with chronic infections to be given proper anti-viral therapy at the earliest stages. 

What Are The Types Of Childhood Hepatitis Infection?

Childhood Hepatitis can be caused by Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D and Hepatitis E viruses. However, due to the potential chronic nature of Hepatitis B and C viruses, these have been the most investigated in cases of Childhood Hepatitis. 

Childhood Hepatitis B Infection

The chances of an infection with Hepatitis B turning chronic can be evaluated on the bases of the age of the patient when they were first infected. Of the infants and babies less than one year of age who get infected with the Hepatitis B virus, 90% are found to have chronic infections. These infants are reported to be infected prenatally – which means a time before and after the female gives birth to the baby. Studies show the main source of infection of Hepatitis B virus in children is from mother to child (1). Data also shows that among those children who are infected with Hepatitis B before they turn five years of age, 25 to 50% are reported to have chronic hepatitis b infection with long-term effects. Compared to children, the risk of hepatitis B virus causing a chronic infection is much lower in adults. Studies found only 5 to 10% of adult hepatitis b viruses become chronic. (2) (3)

Childhood Hepatitis C Infection

A diagnosis of Hepatitis C and cirrhosis of the liver is rare in children. Studies which have been conducted with a long-term follow-up on those with childhood hepatitis show it to have very low prevalence rates all over the world. Data from Taiwan shows only 0.5% of children are affected with Hepatitis C, while the rates for liver cirrhosis are 0.2%. (4) Data from the United Kingdom shows the prevalence of Hepatitis C in children to be 0%, while liver cirrhosis may be found in 2.7% of the children. (5) 

Phases of Childhood Hepatitis Infection

• The first phase of the childhood hepatitis B virus is the immune tolerant phase. This is the phase where the child initially gets infected with the Hepatitis B virus, while their body’s immune system is tolerant to it. Hence, they are found to have high levels of Hepatitis B virus antigens and higher ALT levels. At this stage, there are no changes in the liver biopsy. However, children who are infected after their early infancy may have an unrecognized or much shorter first phase. 
• The second phase is known as the immune reactive phase and is characterized by lowering levels of Hepatitis B DNA, with an intermittent elevation of ALT levels. However, the ALT levels are seen to return back to normal after six months of infection. (6)
• The third phase of childhood hepatitis is also referred to as the low replicative phase. This phase is characterized by the seroconversion of Hepatitis B antigen to antibodies. The ALT levels have also further reduced or returned back to normal ranges. 
• The fourth phase is known as the reactivation phase or the HBeAg negative/ Anti HB positive chronic infection. This phase may be associated with liver injury. 

Symptoms of Childhood Hepatitis

The symptoms that may be commonly seen in children affected by childhood hepatitis include:

• Yellowish discolouration of the skin
• Yellowing of the eyes
• Fever
• Feeling Nauseous or vomiting
• A painful sensation in the abdomen
• General discomfort
• Runny nose and flu-like symptoms
• Soreness of the muscles
• Loss of appetite
• Diarrhoea and flatulence
• Itchiness on the skin
• Hives
• Darkening of the urine
• Clay-coloured stools

Long-Term Effects of Childhood Hepatitis

The long-term complications of Childhood hepatitis have often been hypothesized to include liver failure, liver cancer and even early mortality. This association has also been investigated in a number of studies over the past few years. 

One such retrospective study was conducted on children diagnosed with childhood hepatitis. The study concluded by showing none of the participants needed a liver transplant or undergoing severe complications. Among the total participants, 67 children with Hepatitis were not treated, and their symptoms were observed over ten years. From these untreated groups of children, 30 were found to become inactive carriers of the infection, while four had undergone seroconversion of their hepatitis B antigen to antibodies. Six of the children from the untreated group also achieved complete clearance from the infection. However, 16 children with hepatitis B continued to have a detectable antigen of Hepatitis B in their blood. This was accompanied by an elevated level of transaminase as well. 

The majority of the other studies conducted on childhood hepatitis showed the children to have a benign course of infection. (7) (8) (9) A high number of children may remain inactive carriers of the virus for many years, as seen in some Italian studies. (10)

The Bottom Line

Children may be at a higher risk for chronic hepatitis infection when exposed in infancy, as compared to getting infected as an adult. This is why it is important to understand the natural history of the hepatitis infection and its unique stages before a treatment decision is made. These children may require not only the correct anti-viral therapy but also lifestyle counselling that is appropriate for their age. For example, they may require to be instructed about the precautions of using toothbrushes and razors and how these personal items should never be shared with others. Paediatricians should also encourage parents to get their children vaccinated at the right milestones of their life. 

References

1. Livingston, S. E., Simonetti, J. P., Bulkow, L. R., Homan, C. E., Snowball, M. M., Cagle, H. H., Negus, S. E., & McMahon, B. J. (2007). Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology, 133(5), 1452–1457. https://doi.org/10.1053/j.gastro.2007.08.010
2. Jonas, M. M., Block, J. M., Haber, B. A., Karpen, S. J., London, W. T., Murray, K. F., Narkewicz, M. R., Rosenthal, P., Schwarz, K. B., McMahon, B. J., & Hepatitis B Foundation (2010). Treatment of children with chronic hepatitis B virus infection in the United States: patient selection and therapeutic options. Hepatology (Baltimore, Md.), 52(6), 2192–2205. https://doi.org/10.1002/hep.23934
3. Sokal, E. M., Paganelli, M., Wirth, S., Socha, P., Vajro, P., Lacaille, F., Kelly, D., Mieli-Vergani, G., & European Society of Pediatric Gastroenterology, Hepatology and Nutrition (2013). Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Journal of hepatology, 59(4), 814–829. https://doi.org/10.1016/j.jhep.2013.05.016
4. Wen, W. H., Chang, M. H., Hsu, H. Y., Ni, Y. H., & Chen, H. L. (2004). The development of hepatocellular carcinoma among prospectively followed children with chronic hepatitis B virus infection. The Journal of pediatrics, 144(3), 397–399. https://doi.org/10.1016/j.jpeds.2003.11.022
5. Boxall, E. H., Sira, J., Standish, R. A., Davies, P., Sleight, E., Dhillon, A. P., Scheuer, P. J., & Kelly, D. A. (2004). Natural history of hepatitis B in perinatally infected carriers. Archives of disease in childhood. Fetal and neonatal edition, 89(5), F456–F460. https://doi.org/10.1136/adc.2002.009837
6. Marx, G., Martin, S. R., Chicoine, J. F., & Alvarez, F. (2002). Long-term follow-up of chronic hepatitis B virus infection in children of different ethnic origins. The Journal of infectious diseases, 186(3), 295–301. https://doi.org/10.1086/341508
7. Bortolotti, F., Jara, P., Crivellaro, C., Hierro, L., Cadrobbi, P., Frauca, E., Camarena, C., De La Vega, A., Diaz, C., De Moliner, L., & Noventa, F. (1998). Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period. Journal of hepatology, 29(2), 184–190. https://doi.org/10.1016/s0168-8278(98)80002-0
8. Fujisawa, T., Komatsu, H., Inui, A., Sogo, T., Miyagawa, Y., Fujitsuka, S., Sekine, I., Kosugi, T., & Inui, M. (2000). Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood. Journal of pediatric gastroenterology and nutrition, 30(2), 201–206. https://doi.org/10.1097/00005176-200002000-00019
9. Bortolotti, F., Guido, M., Bartolacci, S., Cadrobbi, P., Crivellaro, C., Noventa, F., Morsica, G., Moriondo, M., & Gatta, A. (2006). Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study. Hepatology (Baltimore, Md.), 43(3), 556–562. https://doi.org/10.1002/hep.21077
10. Manno, M., Cammà, C., Schepis, F., Bassi, F., Gelmini, R., Giannini, F., Miselli, F., Grottola, A., Ferretti, I., Vecchi, C., De Palma, M., & Villa, E. (2004). Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years. Gastroenterology, 127(3), 756–763. https://doi.org/10.1053/j.gastro.2004.06.021