HEPATITIS B : AN APPROACH
Family Physician, Matunga, Mumbai 400 019.
Wide prevalence of the hepatitis B brings it into the realms of Family Practice. Dr. Hemant Patel talks to Dr. Samir Shah and Dr. Suhas Prabhu to bring out salient features of the infection and approach for the Family Physicians.
Although many viruses can affect liver function and morphology indirectly, as a result of systemic infection, only a minority are truly hepatotropic i.e. primarily causing necro-inflammatory changes in the liver itself. Hepatitis B is one of such viruses and other being HAV, HCV, HDV and HEV.
HBV is a hardy virus unlike HIV, which resists boiling at 60o C for six hours and survives drying and storing at room temperature for a very long time. Again it is less infectious than HAV, but the persistent viremia in HBV infection makes it comparatively more infectious.
Epidemiologically, the prevalence rate of HBV infection in general population is 3-5%. 1.3 to 12.7% of children below 15 years are HBsAg +ve, while the figure in adult is 3.3 to 8.6%. There are 43 million estimated HBV carriers in India, of which 10% are highly infectious (HBeAg +ve).
Let us discuss this vital subject in different clinical case forms.
1st Sample Case
Mr. Subramanian, M/45, comes back from a business trip and his family wants to celebrate his home coming by throwing a party.
He c/o generalised weakness, poor appetite, nausea and high coloured urine.
Clinical Examination showed icterus, mild but tender hepatomegaly and biochemistry reveals : Urine = BS/BP +/+; S. Bilirubin (total) 4 mg%; SGPT 2000 IU, HBsAg +ve
As the patient is symptomatic and SGPT is 50 times normal with HBsAg +ve, this is a case of acute viral hepatitis B. Patient should be advised to take bed rest till jaundice comes down. If he looks clinically better, LFT may be repeated after 2-4 weeks which should show resolution. HBsAg should be repeated after 3 months and if +ve, again after six months to see whether the patient has cleared it or not.
Q. Should liver tonics and prednisolone be given in Hepatitis B?
Ans. No need to give liver tonics and prednisolone should not be given in Hepatitis B as it invariably leads to chronicity.
Q. Is Mr. Subramanian infectious to his family members?
Ans. All patients with HBsAg +ve are infectious and more so if HBeAg is +ve.
Q. What are the different Hepatitis B markers and their significance?
Ans. Australia Antigen or HBsAg appears first in the blood before the patient becomes symptomatic. During this period HBsAg and HBV-DNA also become +ve. HBsAg and HBV-DNA are markers for on-going viral replication and therefore positivity indicates highly infective state. Soon after this, pt becomes symptomatic and shows abnormal LFT. With good resolution, though LFT remains abnormal, HBsAg titre declines and disappears while Anti-HBe appears in the blood. HBsAg is not detected in the blood but Anti HBe-IgM comes first in acute phase followed by Anti HBe-IgG, which almost remains for life. Again with good resolution, patient clears HBsAg within 3-6 months and after a small gap of time, patient develops AntiHBs as a mark of recovery or immunity.
There are other markers like HBV-DNA, Antibodies to HBV-DNA polymerase HBxAg and Antibodies, Pre S-1 and Pre S-2. Antigens and Antibodies; but these are not done routinely and are cumbersome.
Q. What is ‘WINDOW PHASE’? And what does it signify?
Ans. During resolution of the disease, when the HBsAg is not detectable thus labelling the patient as HBsAg Negative Hepatitis. But at this time patient has antiHBc-IgM +ve and is infectious. Patient has not yet developed AntiHBs. If such blood is transfused to an HBsAg negative person, then he may develop post-transfusion Hepatitis B.
Q. Do all patients who are infected with hepatitis B virus, present like Mr. Subramanian?
Ans. In fact, a very few patients present like Mr. Subramanian, with obvious symptoms. Majority of them remain subclinical without any apparent signs or symptoms, they either recover completely or develop into a chronic state. 65% of Pts with HBV infection remain subclinical and all develop Anti-HBs; 25% of them present like Mr. Subramanian with acute signs and symptoms, of them 1% may develop fulminant course, which has poor prognosis. 10% of infected Pts develop chronicity! A very few lucky ones clear HBsAg after many years of chronicity, but majority of them develop chronic hepatitis and its complications like cirrhosis and hepatocellullar carcinoma, which is 300 times more common in HBsAg carriers than in general population.
Q. How does a child with hepatitis B infection present? Does the presentation differ from adult presentation?
Ans. There is no difference in presentation. The child may remain subclinical without any signs and symptoms or present as a case of acute hepatitis or accidentally found to be HBsAg +ve while investigating for some other disease.
Q. What are the other clinical manifestations, besides jaundice and hepatitis?
Ans. Extra hepatic manifestations due to circulating immuno complex (CIC) are seen more in females than males (though chronicity is more common in males than females), they are - urticaria - rash, arthralgia - arthritis, haematological-red cell aplasia, granulocytopenia. Bone marrow suppression, acute renal failure, glomerulonephritis, nephrotic syndrome, Neurological : Guillain-Barre-syndrome, peripheral neuritis. Pancreatitis.
Q. Do children also show extra hepatic manifestations?
Ans. Less commonly than Adults. But Rash and Arthralgia are occasionally seen.
2nd Sample Case
Mr. Abdul unmarried, young man of 25 years. During his pre-employment medical examination, he is found to be HBsAg +ve with normal LFT. He is asymptomatic.
Q. What could be the mode of acquiring HBsAg in this young unmarried man?
Ans. To find out the mode of transmission, one should try to find out whether there is any history suggestive of high risk behaviour like h/o sexual exposure, contact with commercial sex workers, homosexuality or drug abuse - viz by sharing same needles.
H/O Any surgical or dental procedure. Nowadays there is a fashion for ear piercing and tattoos.
H/O Any medical illness requiring frequent blood or blood product transfusion e.g. Haemophilia H/O Previous jobs like working in dispensary or laboratory or as police or fire personnel coming in contact with injured persons (infected with Hepatitis B).
H/O Jaundice in the past, in family or in close contact.
H/O Jaundice in mother during pregnancy.
So in mode of transmission we have,
Horizontal mode i.e. from infected person to another healthy person as in close contacts and vertical transmission (transplacental) from infected mother to infants.
The route of transmission could be parenteral either through IV or needle-stick injury or inapparent, which could be either sexual or non-sexual or non-sexual through other infected body fluids and oozing skin lesions.
Q. Both Mr. Subramanian and Mr. Abdul are HBsAg +ve. How do these two cases differ from each other?
Ans. Mr. Subramanian was a symptomatic HBsAg +ve case with abnormal LFT i.e. Acute Hepatitis B, while Mr. Abdul is a Chronic carrier.
Q. When do we label a case "CHRONIC"?
Ans. Persistence of HBsAg for more than six months with or without abnormal LFT.
Q. How do we know whether Mr. Abdul has acquired this infection recently or his infection is more than six months old?
Ans. To know this, in patients with HBsAg +ve, we must get Anti HBc-IgM done. If Anti HBc-IgM is also +ve, it means recent infection and if negative (i.e. indirectly IgG +ve) means old infection.
Q. Why majority of Pts clear HBsAg, while some do not?
Ans. Immunological status of the host is very important. If HBV and infected hepatocytes decide to remain in harmony, then patient does not develop abnormal liver function but may become a healthy chronic carrier. If hepatocytes fight and kill the HBV, initially there may be abnormal LFT but then patient recovers well and develops Anti HBs. If the viral load is more or hepatocytes get destroyed in the encounter, surviving viruses attack more hepatocytes and patient develops chronic hepatitis, cirrhosis of liver and hepato cellular carcinoma as a part of complications of chronic course.
It is very important to note that very few Pts with chronic state give H/O jaundice in the past, while a few pts with H/O acute hepatitis and jaundice develop chronic hepatitis.
3rd Sample Case
Miss. Karishma, F/22, comes with a smile and a box of sweets and introduces Mr. Sunil M/25 as her fiance! They are neighbours. She has comfortably walked into his heart and now next month she is planning to walk into his house. They are getting married. During counselling Mr. Sunil gave H/O jaundice one year back.
Q. What advice would you give to the couple who are to get married in a month?
Ans. Since we do not know what type of jaundice Mr. Sunil had, one should first ask for HBsAg. If it is -ve then everything is OK but if it comes +ve problems begin. Get his HBsAg to know infectivity, +ve indicates high infectivity and Miss should be warned against kissing. Considering that Miss Karishma is HBsAg negative, she should be properly vaccinated against HBV, and after confirming antibody status she should be advised about sexual relation with Mr. Sunil till then it is better to avoid sex or to practice safe-sex using a condom.
This is true for all married couples where one partner has or gets hepatitis B infection. They should be similarly advised as in Karishma and Sunil’s case.
Q. Many of our surgeon friends are HBsAg +ve and Pts do not know this fact about their operating surgeon, are these Pts at a risk of getting this infection from their surgeons?
Ans. If patients are HBsAg +ve then doctors are at risk and if the doctor is HBsAg +ve then his patients are at risk, though the risk is small.
Q. How can such a situation be prevented?
Ans. The best way is to educate our patients to get Hepatitis-B vaccine and protect themselves, irrespective of age, sex or presence of any illness or not, because you never know when would you need some surgery and land up on surgeons table.
Moral of the story here is do not leave safety of your life in someone’s hands. Protect yourself when effective vaccines are available. Strike the disease before it strikes you. As far as we doctors are concerned it protects us against accidental needle-stick injuries also.
4th Sample Case
Mrs. Juhi F/26 is 4 months pregnant and has come for ANC.
Q. What all investigations we should ask for as a part of ANC?
Ans. CBC, Blood group and Rh, PPBS, urine for sugar and protein, HBsAg, antibody for HIV 1 and 2.
Q. Why should we include HBsAg in routine ANC?
Ans. As we have seen in Mr. Abdul’s case, chronic carriers are often healthy and asymptomatic, unaware of their potentials to infect others. If this pregnant lady is also one of them, it will go unnoticed unless we do HBsAg as a routine investigation. HBsAg +ve mothers, particularly those who are HBeAg +ve, transmit this infection to their newborns. It is very important to note that 90% of these infected infants develop chronic Carrier State and many of them develop hepato cellular carcinoma at a very young age.
Q. This mode of transmission is called vertical transmission, is it not? Does this occur in intra uterine life or by some other way?
Ans. Yes, transmission of infection from mother to infant is vertical mode of transmission. Usually this infection occurs during the normal labour i.e., passage through the birth canal due to the inoculation from infected maternal blood and liquor, and not in IUL. Intra uterine transmission can occur in cases of threatened abortion and when mother gets acute hepatitis B infection in the last trimester.
Q. As the transmission is during normal passage of baby through the birth canal, should one consider the option of elective caesarean? Or as the rate of this infection in new-born is so high, should one consider for termination of pregnancy?
Ans. Though elective caesarean is recommended in HIV and Herpes Simplex Virus infection in mother, there is no such recommendation in Hepatitis B infection. As for the second question, mother is already infected and the new born can be protected by proper immunisation, MTP is not recommended.
Q. Breast milk is known to secrete HBsAg, should such mothers be allowed to breast feed their newborns?
Ans. No clear-cut guidelines are available in this direction but if the new-born has been vaccinated for both active and passive immunity then there is no risk of developing infection through breast-feeding.
Immunisation against Hepatitis B
Q. What are the different types of vaccines available, in India, to protect us against HEPATITIS B infection?
Ans. Two types of vaccines are available to us, one is called Recombinant DNA (r DNA) vaccine prepared from yeast and the second one is Plasma
derived prepared form the plasma of Hepatitis B carriers.
Q. What should be the criteria to select the vaccine?
Ans. Safety, Efficacy and Cost-Effectiveness.
We know the recommended schedule using either of the vaccines is to give 3 doses for primary immunisation, i.e. 0, 1 and 6 monthly interval followed by first Booster at 12 month interval, second at five year and third at 10 year. This schedule is recommended in babies born to HBsAg +ve mothers or in health care workers, immediately after needle-stick injury. HBIg given simultaneously with the first dose, is supposed to give early protection.
Q. The dose in children upto 10 years is 10 micro Gm and above that age is 20 micro Gm, do we have different dose in neonates?
Ans. The dose in the neonates is half of the usual paediatric dose.
Q. Are there any clinical conditions where we have to give more than usual adult dose?
Ans. Pts on dialysis and frequent blood transfusions or those who are immuno compromised, need double the adult dose and the frequent is decided after measuring antibody response.
Q. Why deltoid or anterolateral aspect of thigh is selected for vaccination? Can it be given intradermally or subcutaneously?
Ans. Antibody response is better when given 1 M. Injection in Deltoid due to less fat than in Gluteal region with more fat. Intradermal route has been tried to minimise the dose requirement and so also the cost but again antibody response is not long lasting. Subcutaneous route is usually not preferred as the Aluminium content of the vaccine may form nodule but it is the preferred route in patient with bleeding disorders like Haemophilia, where intramuscular route is to be avoided.
Q. If a person gets one dose of recombinant type vaccine and the next dose of plasma derived vaccine or vice-versa, will the antibody response get affected?
Ans. As the antigenic configuration remains the same, there should not be any difference in immune response.
Q. How should we deal with defaulters who do not come for proper timely vaccination?
Ans. Arbitrarily most experts would accept an interval of upto one year between first and the second dose. Thereafter it is better to vaccinate all over again. The interval between second and third is more flexible and probably acceptable upto 5 years. But we must educate our patients to come on time and not to delay vaccination.
Q. How dose one prevent transmission of infection from HBsAg +ve mother to infant?
Ans. If mother is HBsAg +ve at the time of delivery or she also has HBeAg then the baby should be given HB IG 0.05 ml/kg as soon as possible, ideally within 12 to 24 hrs with the first dose of vaccine at different site. Accelerated schedule may be adopted here. (Same approach in case of needle stick injury).
Q. After completing the primary course in time, when does the immunity develop?
Ans. In normal person with good immunology status it develops 1-3 months after the primary course is over.
Q. Does this hold true in children or do they develop immunity at different time?
Ans. There is no difference in children. But in premature babies less than 2000 Gms of birth weight, response may not be good and so either wait till baby is 2000 gms or give the first dose at 2 months with the first OPV and DPT. These vaccines can be given together at the same sitting but at different sites.
Q. DPT is a killed vaccine while OPV is live vaccine, can Measles and MMR which are live at tenuated vaccines also be given with HB vaccine?
Ans. Yes, no opportunity should be lost in giving Hepatitis B vaccine. Measles/MMR vaccine can be given along with Hepatitis vaccine but at a different site.
Q. What should be the ideal age for vaccination to start?
Ans. In babies, it should be started as soon as possible, ideally on the day one in the maternity home itself, but it can be given as late as with the first dose of DPT, provided HBsAg status of mother is negative.
Q. Is there any particular age limit in adults for starting the vaccination?
Ans. There is no age limit, because HBV infection can affect all age groups and without any sex discrimination. In adults with no h/o jaundice, primary course may be started, but patients with h/o jaundice it is better to get AntiHBc-IgG which is a better marker of previous infection with HBV than AntiHBs.
Q. Should we vaccinate HBsAg +ve cases?
Ans. As these patients are already infected they need not be vaccinated.
Q. Normally we do not ask for Anti HBs status before vaccination. Is there any harm if Anti HBs +ve person is vaccinated with vaccine?
Ans. There is no harm absolutely.
Q. Does a person become HBsAg +ve after vaccination?
Ans. HBsAg is a non-infectious subunit of HBV and so it is not infectious and without active infection, person can not become HBsAg +ve.
Q. Is it necessary to measure antibody level after HB vaccine?
Ans. No need to determine the antibody level in usual cases but may be required in immuno-compromised hosts, patients on dialysis or who receive frequent blood transfusion.
Q. What about adults? Do we need to determine antibody levels?
Ans. This is not necessary for individuals under 40 years but over 40 years and in circumstances such as CRF, monitoring is a good idea, if cost is not a problem.
Q. Vaccine is for prevention, but what can we offer to patients with chronic hepatitis?
Ans. Alpha-Interferon, 5 million Units daily, subcutaneously or 10 million Units 3 days in a wk. is given for 4 months in HBsAg +ve with HBeAg +ve or HBV DNA +ve patients where SGPT at least two times normal. Female patients with h/o acute hepatitis, low level of HBeAg/HBV DNA and without any major liver damage respond better. Recurrence is known. It has its own side effects, major being increased susceptibility to bacterial infection and bone marrow suppression.