Hepatitis B is a vaccine preventable disease.
Hepatitis B is important and common cause of liver inflammatory disease that is hepatitis. Hepatitis B is widespread and found in world wide population. In India we have 4 crores people who are carrier of hepatitis B all over world 400 million are infected with hepatitis B virus. The proportion of population is infected is higher in rural and tribal areas. The areas of highest prevalence are sub-saharan Africa, China, pacific islands, Middle-east and Amazon basin. Considering a large number of carriers that is infected people it is a major health concern in our country and worldwide too. Typical of this infection is acute liver failure, chronic hepatitis, cirrhosis, and liver cancer. Nearly one in four who is carrier of Hepatitis B virus will develop Hepato-cellular carcinoma in their life time. Let’s discuss today in details about all these illnesses caused by hepatitis b virus.
What is hepatitis?
· Hepatitis is inflammation of liver.
· It may be caused by many non infectious as well as infectious agents affecting and injuring liver.
· When liver cells get injured by the infectious or non infectious agents it induces inflammation in the injury process or healing process leading various bad consequences even liver failure.
· If the injury is mild and repeated occurring for prolonged period it causes the dying cells of liver replaced by fibrous material in the process leading ultimately to cirrhosis.
· Hepatitis B virus is one of such causes leading to hepatitis.
· In addition to acute liver injury it is likely to cause chronic infection and inflammation leading to cirrhosis and liver cancer after many years.
· Even asymptomatic patients can also transmit the virus to other susceptible unvaccinated individuals.
About Hepatitis B virus:
· Hepatitis B is a virus and it belongs to hepadnaviridae family of virus.
· It’s a DNA virus, It has circular partially double stranded DNA genome.
· Important genes on this genome are S(surface), C(core), X and P(Polymer).
· The antigen on outer surface of this virus is coded by S gene and known as Hepatitis B surface antigen – HBsAg.
· Antigen in core of the virus is coded by C gene and is called as HBcAg also known as Hepatitis B core antigen.
· From HBcAg (Hepatitis B core antigen) another non structural and soluble antigen is derived it is called as Hepatitis B e antigen – HBeAg.
· Hepatitis B e antigen (HBeAg) is closely related to hepatitis B viral DNA snd indicates the replication of Hepatitis B viral DNA.
· Replication of virus takes place mainly in liver but kidney, spleen and pancreas, lymphocytes may get affected.
How is Hepatitis B virus transmitted?
· Hepatitis B virus is present in body fluids like blood, serum, saliva, vaginal fluids, and semen, in infected person.
· It mainly gets transmitted by blood exposure and sexual contact.
· Intravenous drugs and blood products are important cause of transmission in children and adolescents.
· Intravenous drug abuse is a leading cause of transmission of virus in drug abusers may be the important cause in adolescents.
· Sexual contact through child abuse can lead to the spread of the disease to children.
· Acupuncture, tattoos and sexual intimate contacts are also some causes which are important in causing disease spread.
· Mother to child transmission occurring perinatally is major cause and leads to chronic infections which may last for lifetimes. The risk is highest if mother is HBeAg positive and 90 percent of such infants may become chronic carriers if left untreated. Perinatal spread occurs by maternal blood and amniotic fluid and maternal feces. Immunoprophylaxis given with Hepatitis B immunoglobulin and also Hepatitis B given within 12 hours of birth protects 95% of infants of hepatitis B surface antigen positive mothers. All infants born to HBsAg positive mother should be tested for HBsAg and Anti-HBs to determine whether they are protected or infected.
· Hepatitis B doesn’t seem to be transmitted through breast milk so breast feeding is safe and should be promoted for babies of Hepatitis B positive mothers.
· When HBsAg remains positive for more than six months in blood the risk of getting chronic infection increases.
· Lesser the age at the time of the acquisition of the infection more are the chances of getting infected chronically and getting hepatocellular carcinoma after some years.
· If infant less than 1 year age gets infected there are 90 percent chances that it will get chronic infection for the lifetime.
· If child is 1-5 year of age at the time of the acquisition of the infection there are 30 percent chances that child will remain chronically infected for the entire life.
· In adults there are only 2 percent chances that if adult gets infection in adulthood he/she will remain infected for the entire life.
What happens when someone gets infected with Hepatitis B virus?
· The immediate response after getting infected with Hepatitis B is same for all other Hepatitis B virus.
· When this Hepatitis B virus goes to lever it replicates inside the liver cells.
· Replication of Hepatitis B virus in liver cell itself is injurious to liver cells.
· Also when there is ongoing replication of Hepatitis B virus inside the liver cells the HBcAg and HBeAg gets represented by cells as it sits on cell surface.
· When on cell surface these antigens are detected by the immunity as foreign particles and it takes action against these antigens.
· In this process the the cell surface and in turn the cells of liver get damaged.
· More sever the immune reaction more likely hood of getting cured of disease but that also means more extensive damage to the liver.
· Less the immunity less the chances of infection getting cured and more the likely hood getting infected chronically.
· Also if the immunity fails to recognize these antigen as foreign antigen that is immunity tolerates these antigen and does not fight against it the chances of getting chronic infection gets high. This is called as ‘immune tolerance phenomenon’. It is more likely in neonates and infants.
· So in infants getting chronic infection chances are more.
· Immune phenomenon is also cause of extra hepatic manifestations of Hepatitis B like polyarteritis nodosa, glomerulonephritis, polymyalgia rheumatic, leukocytoclastic vasculitis, GBS.
What are symptoms of Hepatitis B?
· If acquired in childhood many are likely to be asymptomatic in acute phase and more likely hood of getting chronic case.
· Usually acute infection symptoms are similar to that of Hepatitis A or Hepatitis C virus, and more likely to be more sever than HAV and HCV.
· Firstly before getting the symptoms of Hepatitis there are elevation of lever enzymes like ALT.
· Then patients develop prodromal symptoms like fatigue, anorexia and malaise.
· Sometimes the serum sickness like illness precedes that actual disease. This serum sickness like illness is marked by arthralgia and skin lesions in form of macules and papules that may look like urticarial rash.
· The symptoms of Hepatitis are nausea, vomiting, abdominal pain, loss of appetite, fever may be high grade.
· In some cases lose motion and diarrhea is also present.
· Jaundice is the significant finding that may be absent in some Hepatitis cases or may come later stages.
· Acute phase if resolving may last for 6-8 weeks if not resolving may lead to fulminent liver failure needing urgent liver transplant or may cause death.
· Chances of getting symptomatic disease in acute phase is much higher than Hepatitis a virus in Hepatitis B virus.
· Chances of liver failure in acute phase are also much higher than Hepatitis A in Hepatitis B.
· Many of those who got acute infection symptoms or acute infection asymptomatic are likely to develop chronic infection as they are called ‘chronic carriers’.
· These chronic carriers are likely get hepatitis chronic, Cirrhosis and Hepatocellular carcinoma.
· There are 3 types of chronic carriers, immune tolerant, immune active and inactive.
· Immune active means virus is replicating in the liver and immunity of the person is damaging the liver in process of fighting infection to the virus. This is presented by findings of hepatitis and increased liver enzymes. More likely of ongoing damage to liver if infection lasts the longet period, more likely hood of chronic hepatitis. Some of these develop antibodies to HBeAg and become negative to HBeAg this is called as inactive phase. But to get converted to inactive phase usually takes a lot of time and by that time usually liver damage has been already occurred. The available therapies are directed currently towards the Immune active phase.
· Unfortunately no therapy is effective for ‘immune tolerant’ that is ongoing replication of virus is there but immunity is not reacting against it. So infection is there but no biochemical or clinical markers of Hepatitis B are present. But still these children are in future likely hood of getting hepatocellular carcinoma or they can spread infection.
What are complications of Hepatitis B?
· As discussed earlier acute liver failure leading to coagulopathy, encephalopathy and cderebral edema leading to death is very possible.
· Also if the patient is simultaneously infected with Hepatitis D virus likely hood of death by acute liver failure is more than 30 percent. In such cases Liver transplant is the only life saving treatment thus early referral to lever transplant unit is needed if acute hepatitis symptoms are present.
· Also extra hepatic complications like poly arteritis nodosa and glomerulonephritis can be significant and life threatening.
How is Hepatitis B diagnosed?
· Many antigens and antibodies are used to diagnose Hepatitis B infection depending on stage.
· HBsAg is present nearly all cases and its presence generally occurs at the time of infection.
· Presence of HBsAg for more than 6 months indicates that it is a chronic infection.
· HBsAg level may fall before symptoms of acute infection wanes so HBcAg and anti HBc antibodies can be used.
· Anti HBc antibodies IgM type are present in acute infection and last for many months then replaced by IgG anti HBc.
· Anti HBs antibodies marked by development of immunity after vaccination.
· Thus after vaccination Anti HBs antibody are present while after disease recovery anti HBc antibody and anti HBs antibody both are present.
· HBeAg is marker of active infection in acute or chronic cases and development of Anti HBeAg is marked by improvement in clinical picture and is a goal of therapy.
What is treatment of Hepatitis B?
· Treatment of Hepatitis B is supportive and monitoring for liver failure and extra-hepatic complications is very important.
· Yet there is no treatment that can be considered definitive for chronic infection.
· The treatment needs to be individualized for each patients and especially children consider referral to experienced gastroenterologist.
· Treatment is directed to reducing viral replication detected by HBV DNA and formation of Anti HBe antibody and converting to inactive infection thus stopping liver injury and the infectivity reducing the spread of infection.
· Currently treatment is only indicated for patients that for under immune active category characterized by elevated AST and ALT and fibrosis on liver biopsy.
· Interferon-a2b is an interferon and it is immune-modulatory and antiviral effect having drug. If it used long term viral response rate is 25 percent only. The drawbacks are its high cost and subcut administration. Virus does not develops resistance to this agents. Flu like symptoms, bone marrow suppression, retinal changes, depression and auto immune diseases are possible side effects. Medicine is used when benefits are more than than the side effects.
· Lamivudin is also a drug antiviral used against Hepatitis B. It can be given orally and 33 percent patients show response turning to non detectable levels of HBeAg. 88 percent of those who show response remain so for 1 year at least. It inhibits enzyme reverse transcriptase. With this enzyme inhibited virus cannot multiply. It’s used for 52 weeks.
· Adefovir is also antiviral agent and interferes with multiplication of virus. Currently approved for use in children above age 12 years.
· Entecavir and tenofovir is approved currently for use in children above age 16 years old.
· Peg-interferon alfa 2 is a drug acts by same mechanism as that of interferon alfa 2b but currently not approved for use in children. It has additional benefit that it can be given once a week.
· Immune tolerant patients with HBeAg positive with high viral load with normal AST and ALT are currently not treated as no promising drug is present currently for the same.
How to prevent Hepatitis B?
· Preventive strategies for Hepatitis B include immunoglobulin injection and also effective vaccine.
· These strategies depend on whether the measure is taken before exposure or after child is exposed.
· Hepatitis B immunoglobulin are antibodies readymade prepared also called as HBIG is injected when child is exposed to virus.
· Most effective strategy is injecting immunoglobulin and vaccine together in neonates who are born to HBsAg positive mother within 12 hours of birth.
· Essentially effective strategies involve screening the mother for HBsAg during pregnancy. Those mother who are additionally HBeAg positive have 10 times more chance that neonate gets the chronic infection than those of HBeAg negative mothers.
· Use of antiviral medicines is considered in third trimester of pregnancy if mother with HBV DNA viral load more than 200000 iu/ml, and /or previous child developed chronic hepatitis B even after receiving HBIG and Hepatitis B vaccine. In such mothers drugs such as tenofovir, lamivudin and telbivudin is considered.
· Household, needle sharing and sexual contacts should be identified and vaccinated. The risk of transmission of virus perinataly should be explained. HBV id not spread by kissing, hugging, sharing water and utensils.
· The child who is HBsAg positive should not be discriminated and excluded from the school. The families should not be obligated to disclose the HBsAg positive status if they are likely to face discrimination.
· While administering HBIG it should be kept in mind that it only provides the protection for temporary period. It provides protection for only 3-4 months period.
About Hepatitis B vaccine:
· Hepatitis B vaccine is a single antigen vaccine. The antigen on surface of the virus is present in the vaccine when injected the immunity acts against it and also develops memory so that actual virus is identified and immune system fights with the virus.
· It is injectable vaccine given by injection into thigh muscle in children and can be given in shoulder muscle in adolescents and adults.
· It is a killed vaccine.
· It is to be stored at 2-8 degree Celsius.
· It provides active immunity against Hepatitis B.
· It is included in universal immunization schedule to be given at birth.
· Given this vaccine at birth along with HBIG prevents transmission of virus from HBsAg positive mother to neonate.
· It is generally given 3-4 doses. Generally 95 percent of those received vaccine 2 doses develop Anti HBs antibody that is they are protected for the virus. Additional 3rd or fourth dose maintains this immunity for prolonged period.
· All infants who are stable and who are born to HBsAg negative mother if weight is more than 2 kg at birth should be given Hepatitis B vaccine at birth or before discharge from hospital and additional doses are given at 1-4 months and 6-18 months. Or additional doses can be combined with DPT vaccination when patients visit OPD for DPT vaccination.
· All infants who are unstable or less than 2 kg at birth and born to HBsAg negative mother, the Hepatitis B vaccine should be postponed by 1 month or if given this dose should not be counted and the entire dosing schedule is repeated.
· Infants born to HBsAg positive mother should receive HBIG and Hepatitis B vaccine within 12 hours of birth. Even if infant is weighing less than 2 kg at birth and mother is HBsAg positive the infant should receive HBIG and Hepatitis B vaccine within 12 hours of birth.
· If mother’s HBsAg status is unknown the Hepatitis B vaccine is administered at birth and for infant weighing less than 2 kg even the HBIG is to be injected in such state.
· Post vaccination testing at 9-18 month of age needed for infants of HBsAg positive mother. In this testing HBsAg and anti HBs antibodies are tested. If anti HBs antibody are negative and HBsAg is positive child has got disease. If anti HBs antibody are positive child is immune to the virus, If child is negative for both HBsAg and anti HBs antibody again the entire vaccine schedule of Hepatitis B virus is repeated.
· Routine testing post vaccine testing is not recommended for infants of HBsAg negative mothers.
· So in short the Hepatitis B vaccine is given at birth then 3 more doses, along with DPT vaccination at 6, 10 and 14 weeks.
What are side effects of Hepatitis B vaccine?
· Pain at injection site: This is most common side effect of Hepatitis B vaccine Occurring in about 29 percent of those who have got the vaccine. Usually subsides in 2-3 days with simple measures such as cold compresses and oral paracetamol
· Fever may occur in 6 percent people of those who have got vaccine but this to usually subsides with oral fever medicine paracetamol.
· Sever life threatening anaphylactic reaction is very rare but may occur if the person is allergic to the contents of vaccine.
· The side effects are usually because of DPT in combination vaccine rather than Hepatitis B.
· But combination vaccine helps to reduce the number of pricks in children. So are more comfortable to use.
· When compared to Hepatitis B disease the side effects of vaccine are negligibly milder so it is very essential to vaccinate all children to stop the spread of the infection.
· Even adults and healthcare workers who aren’t vaccinated before and who are susceptible should be vaccinated in mass vaccination campaigns.
Dr Yatin Bhole MBBS DCh DNB
Bhole Children Clinic and vaccination center
Pediatrician in Ravet near punawale kiwale akurdi