| Abstract|| |
Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been infected; more than 350 million present with chronic HBV infection. A significant proportion (15-40%) of chronic HBV infected patients develop liver cirrhosis, liver failure, and primary hepatocellular carcinoma (HCC), making chronic hepatitis B one of the 10 major causes of death worldwide. The practice of preventive medicine involves three primary tasks: Screening, counseling, and immunization or chemoprophylaxis. Screening healthy individuals incurs an ethical obligation on the clinician. Persons who are most likely to be actively infected with HBV should be tested for chronic HBV infection. Testing should include a serologic assay for HBsAg offered as a part of routine care and be accompanied by appropriate counseling and referral for recommended clinical evaluation and care. To determine susceptibility among persons who are at ongoing risk for infection and recommended for vaccination, total anti-HBc or anti-HBs also should be tested at the time of serologic testing for chronic HBV infection. Recommendations related to screening for chronic HBV infection have been summarized in this article.
Keywords: HBsAg, Hepatitis B virus, ethical, preventive medicine, screening
|How to cite this article:|
Shenoy K T. Screening for chronic Hepatitis B. Hep B Annual 2010;7:5-15
| HBV: A Significant Cause of Worldwide Morbidity and Mortality|| |
Global distribution of HBV
Hepatitis B virus (HBV) infection is a major public health problem worldwide, as more than 2 billion people have been infected, whereas more than 350 million present with chronic HBV infection. It is estimated that a significant proportion (15-40%) of chronic HBV infected patients develop liver cirrhosis, liver failure, and primary hepatocellular carcinoma (HCC), making chronic hepatitis B one of the 10 major causes of death worldwide.  These individuals are typically hepatitis B surface antibody positive with or without core antibody positivity. Surface antibody indicates immunity, core antibody indicates exposure, and surface antigen indicates infection. There are approximately 400 million surface antigen-positive individuals worldwide, leading to approximately 1 million deaths per year. There are about 4 million acute cases per year; however, this number is probably an underestimate since many hepatitis B patients do not have symptoms and are not identified as true acute cases. Nearly 75% of chronic carriers worldwide are from the Asia-Pacific region [Figure 1]. Hepatitis B virus is the second most important carcinogen behind tobacco in this region and is the cause of 60% to 80% of all primary liver cancer there. Since HBV is a DNA virus, it is much more contagious than HIV because it can live outside the body for significant periods of time on different blood-contaminated articles and the HBV DNA in infected patients can be very high (10 8 to 10 11 IU/mL), whereas the HBV DNA in patients with HIV usually ranges from 50-10 5 copies/mL in untreated individuals.
India has intermediate endemicity of Hepatitis B, with Hepatitis B surface antigen (HBsAg) prevalence between 2% and 7% among populations studied with the average prevalence being 4%. It is estimated that there are 12.5 million HCV carriers in our country, and at least a quarter of them are likely to develop chronic liver disease in the next 10 to 15 years.  HBsAg prevalence among general population ranges from 0.1% to 11.7%, being between 2% to 8% in most studies. HBsAg prevalence rate among blood donors ranged from 1% to 4.7%. With the exception of higher HBsAg positivity in some North Eastern states (≈7%), no substantial geographical variation was apparent in other parts of India. Considering, on an average, HBsAg carrier rate of 5%, the total number of HBV carriers in the country was estimated to be about 50 million that forms nearly 15% of the entire pool of HBV carriers in the world and is the second largest pool of chronic HBV infections in the world. 
In a community prevalence study from Tamilnadu, the HBsAg prevalence was 5.7 per cent (CI: 4.6- 6.8) with 23.5 per cent (25/106) of these having positive HB e-antigen.  The lowest prevalence (0.97%) has been reported in Chandigarh in northern India. Anti-HBs antibody positivity, indicating past infection, follows the same epidemiological pattern as that of HBsAg carriage and about 14% of healthy volunteer blood donors are estimated to be anti-HBs positive.
A large study involving 8575 pregnant women from Northern India, documented HBsAg carrier rate in antenatal mothers to be 3.7%, HBeAg carrier rate 7.8% and vertical transmission was observed in 18.6%. A study from Eastern India demonstrated that HBsAg prevalence among antenatal mothers attending a maternity home in Calcutta is in conformity with national average of HBsAg prevalence (3-5%) in India [Table 1]. ,
|Table 1: Prevalence of HBeAg positivity in HBsAg positive women in India |
Click here to view
The HBsAg positivity in children below 15 years in India ranges from 1.3 - 12.7%. In a multicentric study Tandon et al have reported a positivity rate of 2.1% in the preschool age group. In this study the positivity in children less than 1 year age was 2.5%, in the 1-3 year age group it was 2.3%, and in the 4-5 years age group it was 1.6%. A population based study in Chennai revealed a higher prevalence of 12.5% in children less than one year, 9.4% in 1-5 years, 6.3% in 6-10 years and 7.8% in 11-15 years age group.  A similar prevalence was noted by Panda et al from Delhi who identified 12.2% HBsAg positivity in 1-5 years and 10% in 6-15 years age group. These studies highlight the fact that the prevalence varies in different regions in India and the overall positivity ranges from 1.3-12.7% [Table 1]. 
| Screening for Chronic Hepatitis B|| |
Persons who are most likely to be actively infected with HBV should be tested for chronic HBV infection. Testing should include a serologic assay for HBsAg offered as a part of routine care and be accompanied by appropriate counseling and referral for recommended clinical evaluation and care. Laboratories that provide HBsAg testing should use an FDA-licensed or FDA-approved HBsAg test and should perform testing according to the manufacturer's labelling, including testing of initially reactive specimens with a licensed, neutralizing confirmatory test.
Recommendations and federal mandates related to routine testing for chronic HBV infection have been summarized. To determine susceptibility among persons who are at ongoing risk for infection and recommended for vaccination, total anti-HBc or anti-HBs also should be tested at the time of serologic testing for chronic HBV infection. New populations recommended for testing are the following:
- Persons born in geographic regions with HBsAg prevalence of >2%: All persons born in geographic regions with HBsAg prevalence of >2% [Figure 1] and certain indigenous populations from countries with overall low HBV endemicity (<2%) should be tested for chronic HBV infection. Medical screening of applicants for lawful permanent residency in the United States represents an opportunity for education and voluntary HBsAg testing
- Persons with behavioral exposures to HBV: Men Who Have Sex with Men (MSM) and past or current Injection-Drug Users (IDUs) have higher prevalence of chronic HBV infection and should be tested for chronic HBV infection. Both of these populations are recommended for routine hepatitis B vaccination, and HBsAg testing is recommended as a component of prevaccination testing for these adults
- Persons receiving cytotoxic or immunosuppressive therapy: Persons receiving cytotoxic or immunosuppressive therapy should be tested for serologic markers of HBV infection. Prophylactic antiviral therapy can prevent reactivation in HBsAg-positive patients
- Persons with liver disease of unknown etiology: All persons with persistently elevated ALT or aspartate aminotransferase (AST) levels of unknown etiology should be tested for HBsAg as part of the medical evaluation of these abnormal laboratory values.
The practice of preventive medicine involves three primary tasks: screening, counseling, and immunization or chemoprophylaxis. Screening includes laboratory tests, physical examinations, and radiologic tests that are performed on asymptomatic individuals.
Early detection implies that a condition or disease is found before signs and symptoms have appeared. Diagnosis refers to confirming a disease process in symptomatic patients, which is therefore different from screening. Screening efforts can be classified as routine, mass or universal, and individualized. Routine screening is repetitive or automatic, based on age and gender. Mass screening entails a universal approach to screening in which no attempts to assess the risk profiles of individuals is made. Individualized screening, which often occurs in the context of the primary care visit, is based on many factors and includes counseling and a physician recommendation.
Criteria for use of a screening test
- The target condition must cause significant morbidity and mortality in the population. Rare diseases, even if lethal, are not good candidates for screening since the chances of benefiting the average screened individual are very low
- The preclinical stages must be detectable and have a high enough prevalence in the population to make early detection efforts worthwhile
- Early detection must improve cause-specific mortality, which is the true goal of screening programs
- Because screening tests are performed on a healthy population, they need to have acceptable accuracy and safety. They must also be relatively cost-effective, as determined by factors such as cost of the test, physician visit, follow-up diagnostic tests; lost wages or productivity; and any savings from avoided illness. Patient discomfort with screening tests affects compliance; the more invasive or distasteful a test, the less a healthy person will want to undergo the procedure
- Early detection is only useful if the natural history or outcome can be changed through appropriate treatment [Figure 2].
Characteristics of screening tests
Test effectiveness measured as
- Sensitivity: Ability to confirm disease
- Specificity: Ability to identify disease absence
Clinical importance related to predictive ability
- Positive Predictive Value: Proportion testing positive who actually have the disease
- Negative Predictive Value: Proportion testing negative who do not have the disease.
Application of screening to populations
The 2x2 Table describes screening test outcomes [Figure 3].
|Figure 3: The 2x2 Table describing the screening test outcomes elucidateGroup|
Click here to view
The 2 x 2 table is a grid that shows the four possible outcomes of a screening test.
- "a" = those persons with the disease who test positive for the disease (true positive)
- "b" = those persons without disease who test positive for the disease (false positive)
- "c" = those persons with disease who test negative for the disease (false negative)
- "d" = those without disease who test negative for the disease (true negative)
- The developers of a new test/procedure want to optimize the numbers of persons in Group (a) and Group (d). These are the two cells that denote a match between test results and the true disease condition of individuals.
How would people "move" between cells?
- Results from a test being newly developed are rarely "either/or"
- Need to define one or more "cutpoints" along a continuous measure
- Above = have the disease (ill); Below = do not have the disease
- Changing a cutpoint moves people from one cell to another and affects both columns of the 2x2 table.
(1) Sensitivity: Proportion of those with disease who test positive in the screened group [Figure 4]
Sensitivity can be expressed as
- As the proportion of diseased patients who have a positive screening test result, or
- As the ability of the test to detect disease when it is present (i.e., the true positive rate).
Sensitivity is viewed from the perspective in which the disease state of individuals is known with some certainty first, then the number of true positives is divided by the total number of screened individuals with the disease. The arrow shows this method of working vertically down the first column.
(2) Specificity: Proportion of those without disease who test negative in screened group [Figure 5]
Specificity is also defined as
- Ability of the test to correctly identify those without the disease who test negative in the screened population, and
- The true-negative rate of the screening test:
Specificity determines the number of false positives in the screened group. This value often determines the overall costs of any screening program, in terms of follow-up testing and physical and emotional distress to individuals.
The ideal situation-100% agreement [Figure 6]
Ideally, what a test developer wants to see is the 100% agreement that is shown in this slide.
- There are NO False Positives or False Negatives
- Presumably, if the new test/procedure is easier to do from a technical perspective, more acceptable to patients, less expensive, or has fewer risks, then the new option is going to be very attractive
- Of course, this degree of concordance is rarely achieved.
| Conclusion|| |
Screening healthy individuals incurs an ethical obligation on the clinician. Several authors suggest that since screening may cause harm to the patient, the principles that apply to gaining informed consent for risky procedures should apply. In this, as in all other instances, clinicians should respect patient autonomy and actively gain patient participation in the screening decision. Patient participation in the screening decision involves the expression of his/her own values, prior experiences with the health care system or with screening, and attitudes toward health and illness. Past medical experiences that the patient may remember with fear or embarrassment will color present perceptions about medical procedures. Understanding the barriers that an individual patient faces in daily life-like transportation, need for dependent care, work schedules-need to be resolved in the context of the clinician-patient interaction, or any decision that is made will be too difficult for the patient to act upon. Problem solving involves knowing the resources available to the community and having the motivation to follow up and track a patient's receipt of screening tests. Systems management is key to preventive health care. Adherence to a negotiated screening strategy is the goal of preventive medicine. The very low rates of patient participation in colorectal cancer screening prove that many factors affect adherence, which the clinician may or may not be aware of.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Konstantinos D. Pantazis, Ioannis S. Elefsiniotis, and Hero Brokalaki, "New Data concerning the Epidemiology of Hepatitis B Virus Infection in Greece," Gastroenterology Research and Practice, vol. 2008, Article ID 580341, 4 pages, 2008. doi:10.1155/2008/580341.
Datta S. An overview of molecular epidemiology of hepatitis B virus (HBV) in India. Virol J. 2008 Dec 19;5:156.
Kurien T , Thyagarajan SP, Jeyaseelan L, Peedicayil A, Rajendran P, Sivaram S, Hansdak S G. Community prevalence of hepatitis B infection and modes of transmission in Tamil Nadu, India. Indian J Med Res 121, May 2005, pp 670-675.
Sathiyasekaran M, Sankaranarayanan VS. Hepatitis B virus infection in children in India. Hep B Annual 2004;1:72-91.
Dr. K T Shenoy
Sr. Consultant, KIMS Hospital, Trivandrum, Kerala
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]