Screening of Hepatitis B, AASLD 2018 hepatitis B guidane

1A. SCREENING

HBsAg가 존재하면 hepatitis B로 진단하고, 만성 감염은 적어도 6개월 이상 HBsAg가 존재하는 경우입니다. 
The presence of HBsAg establishes the diagnosis of hepatitis B. Chronic versus acute infection is defined by the presence of HBsAg for at least 6 months. The prevalence of HBsAg varies greatly across countries, with high prevalence of HBsAg-positive persons defined as 8%, intermediate as 2% to 7%, and low as <2%.(21,22) In developed countries, the prevalence is higher among those who immigrated from high- or intermediate-prevalence countries and in those with high-risk behaviors. 

HBV는  perinatal, percutaneous, sexual exposure, close person-to-person contact를 통해서 전염됩니다.
HBV is transmitted by perinatal, percutaneous, and sexual exposure and by close person-to-person contact (presumably by open cuts and sores, especially among children in hyperendemic areas). In most countries where HBV is endemic, perinatal transmission remains the most important cause of chronic infection. Perinatal transmission also occurs in nonendemic countries (including the United States), mostly in children of HBV-infected mothers who do not receive appropriate HBV immunoprophylaxis at birth. The majority of children and adults with CHB in the United States are immigrants, have immigrant parents, or became exposed through other close household contacts.

Table 3은 HBV 감염에 대한 감시 검사와 음성인 경우 예방접종을 해야 하는 CHB  위험군을 나타냅니다. HBsAg과 anti-HBs는 감시 검사를 위해 사용되는 항목입니다. HBV 예방접종이 anti-HBc positivity를 만들지는 않습니다.
Table 3 displays those at risk for CHB who should be screened for HBV infection and immunized if seronegative. HBsAg and antibody to hepatitis B surface antigen (anti-HBs) should be used for screening (Table 4). Alternatively, antibody to hepatitis B core antigen (anti-HBc) can be utilized for screening as long as those who test positive are further tested for both HBsAg and anti-HBs to differentiate current infection from previous HBV exposure. HBV vaccination does not lead to anti-HBc positivity.

일부 사람들은 anti-HBc는 양성이지만 HBsAg가 음성인 경우가 있습니다. Anti-HBs가 양성 또는 음성일 수 있습니다. Isolated anti-HBc(anti-HBc positive but negative for HBsAg and antiHBs)는 다양한 이유로 생길 수 있습니다.
Some persons may test positive for anti-HBc, but not HBsAg; they may or may not also have anti-HBs, with the prevalence depending on local endemicity or the risk group. The finding of isolated anti-HBc (anti-HBc positive but negative for HBsAg and antiHBs) can occur for a variety of reasons.


i. Among intermediate- to high-risk populations, the most common reason is previous exposure to HBV infection; the majority of these persons recovered from acute HBV infection earlier in life and anti-HBs titers have waned to undetectable levels, but some had been chronically infected with HBV for decades before clearing HBsAg. In the former case, the risk of hepatocellular carcinoma (HCC) or cirrhosis attributed to HBV is minimal. In the latter, these persons are still at risk of developing HCC, with an incidence rate that appears to be similar to those with inactive chronic HBV with undetectable HBV-DNA levels. These individuals usually have low HBV-DNA levels (20-200 IU/mL, more commonly if they are anti-HBs negative than if they are anti-HBs positive) and are typically born in regions with high prevalence of HBV infection or have HIV or hepatitis C virus (HCV) infection.

ii. Much less commonly with new, more specific anti-HBc tests, anti-HBc may be a false-positive test result, particularly in persons from low prevalence areas with no risk factors for HBV infection. Earlier anti-HBc enzyme immunoassay and radioimmunoassay tests were less specific, more frequently yielding false-positive results.

iii. Anti-HBc may be the only marker of HBV infection during the window phase of acute hepatitis B; these persons should test positive for anti-HBc immunoglobulin M.

iv. Last, reports exist of HBsAg mutations leading to false-negative HBsAg results.

HIV 감염이나 HCV 또는 면역 억제 치료는 기존의 HBV가 있는 경우 잠재적 활성화 위험이 있으므로, anti-HBc에 대한 감시 검사를 해야 합니다. 
Because of the risk for HBV transmission, screening for anti-HBc occurs routinely in blood donors and, if feasible, in organ donors. Since the original anti-HBc studies, the specificity of anti-HBc tests has improved to 99.88% in blood donors and 96.85% in non-HBV medical conditions. Individuals with HIV infection or those about to undergo HCV or immunosuppressive therapy are at risk for potential reactivation if they have preexisting HBV and should be screened for anti-HBc.

The majority of individuals positive for anti-HBc alone do not have detectable HBV DNA, especially with older, less specific assays. For anti-HBc–positive individuals, additional tests to detect past or current infection include immunoglobulin M anti-HBc, antibody to hepatitis B e antigen (anti-HBe), and HBV DNA with a sensitive assay. Detectable HBV DNA documents infectivity, but a negative HBV DNA result does not rule out low levels of HBV DNA. Additionally repeat anti-HBc testing can be performed over time, particularly in blood donors in whom subsequent anti-HBc negativity suggests an initial false-positive result. Although reports vary depending on the sensitivity and specificity of the anti-HBc test used and HBV prevalence in the study population, the minority of patients have an anamnestic response to HBV vaccination, with the majority having a primary antibody response to hepatitis B vaccination similar to persons without any HBV seromarkers. Thus, vaccination could be considered reasonable for all screening indications in Table 3. Anti-HBc–positive HIV-infected individuals should receive HBV vaccination (ideally when CD4 counts exceed 200/lL) because most have primary responses to HBV vaccination, with 60% to 80% developing anti-HBs levels 10 mIU/mL after 3 or 4 vaccinations.Thus, limited data suggest that vaccination may be considered. When considering the benefit of using an anti-HBc–positive donor organ with possible occult HBV infection, the harm of hepatitis B transmission must be weighed against the clinical condition of the recipient patient. While persons who are positive for anti-HBc, but negative for HBsAg, are at very low risk of HBV reactivation, the risk can be substantial when chemotherapeutic or immunosuppressive drugs are administered singly or in combination (see Screening, Counseling, and Prevention of Hepatitis B, section 6D). Thus, all persons who are positive for anti-HBc (with or without anti-HBs) should be considered potentially at risk for HBV reactivation in this setting.

Guidance Statements on Screening for Hepatitis B Infection 
1. Screening should be performed using both HBsAg and anti-HBs. 

2. Screening is recommended in all persons born in countries with a HBsAg seroprevalence of 2%, U.S.-born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity (8%), pregnant women, persons needing immunosuppressive therapy, and the atrisk groups listed in Table 3. 

3. Anti-HBs–negative screened persons should be vaccinated. 

4. Screening for anti-HBc to determine prior exposure is not routinely recommended but is an important test in patients who have HIV infection, who are about to undergo HCV or anticancer and other immunosuppressive therapies or renal dialysis, and in donated blood (or, if feasible, organs) (see Screening, Counseling, and Prevention of Hepatitis B, section 6D).