HBsAg, anti-HBc, anti-HBs 검사

HBsAg (+)

중등도·고위험군¹⁾

예방적 항바이러스제
(ETV, TDF)
해당요법 시행동안 및 종료 후 6개월까지
(Rituximab 의 경우 12개월까지)³⁾

HBsAg (-)/Anti-HBc (+)

HBV DNA

설명

고위험군²⁾
(i.e. Rituximab),
조혈모세포이식³⁾

설명

중등도·저위험군

ALT, HBsAg,
HBV DNA 추적검사

설명

간이식 공여자가
이에 해당하는 경우

*밑줄을 클릭하면 자세한 약제 리스트를 확인할 수 있습니다.

1) HBsAg (+) or HBV DNA (+) 에서 중등도·고위험군에 해당하는 약제를 투여 받는 환자는 예방적 항바이러스제 사용시 급여 적용, 저위험군에 해당하는 약제를 투여받는 환자는 약값 전액을 환자가 부담토록 함
2) HBsAg(-)/Anti-HBc (+) 에서 고위험군 약제 투여나 조혈모세포이식을 받는 환자는 예방적 항바이러스제 사용시 급여 적용
3) 위에 명시된 투여기간 이후에는 약값 전액을 환자가 부담토록 함.
단, HBsAg(-)/anti-HBc(+), HBV DNA(-)에서 조혈모세포 이식을 받는 환자는 이식 후 18개월까지(총18개월 투여)인정

주의) 상기 약제들의 위험도 분류는 향후 문헌보고에 따라 변경 가능함

ETV, entecavir; TDF, tenofovir disoproxil fumarate

Made based on 2022 Korean Association for the Study of the Liver (KASL) Chronic Hepatitis B Clinical Practice Guideline

Table 9. Risk of hepatitis B reactivation associated with immune-related therapies

Risk of reactivation	Immune-related therapies
HBsAg positive
High risk (≥10%)	B-cell depleting agents (rituximab,ofatumumab, natalizumab, alemtuzumab, ibiritumomab and obinutuzumab) A human immunoglobulin G1 monoclonal antibody targeting CD38-expressing cells (daratumumab)*
	High-dose corticosteroids (prednosone ≥ 20 mg/day, ≥4-week)
	Anthracycline derivatives (doxorubicin, daunorubicin and epirubicin)
	More potent TNGa ingibitors (infliximab, adalimumab, certolizumab and golimumab)
	Local therapy for HCC (TACE) Chimeric Antigen Receptor (CAR) T cell therapy*
Moderate risk (1 - 10%)	Cytotoxic systemic chemotherapies other than anthracycline derivatives
	Moderate-dose corticosteroids (prednisone 10-20 mg/day, ≥4-week) Less potent TNF-a inhibitors (etanercept) Cytokine-based therapies (abatacept, ustekinumab, mogamulizumab, natalizumab, vedolizumab, secukinumab, tofacitinib baricitinib* and guselkumab*)
	Immunophilin inhibitors (cyclosporine)
	mTOR inhibitors (everolimus, temsirolimus) Tyrosine-kinase inhibitors (osimertinib, imatinib, nilotinib, gefitinib, dasatinib, erlotinib, afatinib, ibrutinib, idelalisib, palbocicib and ribociclib*) proteasome inhibitors (bortezomib) Histone deacetylase inhibitors Immune Checkpoint Inhibitors (ICIs) (pembrolizumab, nivolumab, atezolizumab, durvalumab)
Low risk (1 < 1%)	Antimetabolites, azathioprine, 6-mercaptopurine, methotrexate, mycophenolate mofetil, leflunomide, hydroxychloroquine, hydroxyurea, immunomodulatory drugs (thalidomide,lenalidomide and pomalidomide)
Low risk (1 < 1%)	Low-dose corticosteroids (prendnison < 10mg/day) intra-articular steroid injections (extermely low risk)

*For some immune-related therapies, the evidence for risk of HBV reactivation is insufficient.

고시 제2019-21호, B형간염 예방요법 급여기준 관련 질의 응답
http://www.hira.or.kr/bbsDummy.do?brdBltNo=7206&brdScnBltNo=4&pgmid=HIRAA020002000100#none
주의] 질의응답에서 제시한 B 형간염 재활성화 위험도 분류는 2019년에 이루어진 것으로, 2022년 대한간학회 만성 B 형 간염 진료 가이드라인에 제시된 Table 9를 참조해 주십시오.

2022 KASL clinical practice guidelines for management of chronic hepatitis B
Modified from Loomba and Liang (Gastroenterology 2017;152:1297-1309)

Table 9. Risk of hepatitis B reactivation associated with immune-related therapies

Risk of reactivation	Immune-related therapies
HBsAg-negative/anti-HBc-Positive
High risk (≥10%)	B-cell depleting agents (rituximab,ofatumumab, natalizumab, alemtuzumab, ibiritumomab and obinutuzumab)
Moderate risk (1 - 10%)	High-dose corticosterroids (prednisone ≥ 20 mg/day, ≥4-week)
	Anthracycline derivatives (doxorubicin, daunorubicin and epirubicin)
	More potent TNFa ingibitors (infliximab, adalimumab, certolizumab and golimumab)
	Cytotoxic systemic chemotherapies other than anthracycline derivatives Cytokine-based therapies (abatacept, ustekinumab, mogamulizumab, natalizumab, vedolizumab, secukinumab, tofacitinib baricitinib* and guselkumab*)
	Immunophilin inhibitors (cyclosporine)
	mTOR inhibitors (everolimus, temsirolimus) Tyrosine-kinase inhibitors (osimertinib, imatinib, nilotinib, gefitinib, dasatinib, erlotinib, afatinib, ibrutinib, idelalisib, palbociclib and ribociclib) Proteasome inhibitors (bortezomib) A human immunoglobulin G1 monoclonal antibody targeting CD38-expressing cells (daratumumab) Histone deacetylase inhibitors
Low risk (<1%)	Moderate-dose (prednisone 10-20mg/day), low-dose(prednisone < 10mg/day) corticosteroids
Low risk (<1%)	Antimetabolites, azathioprine, 6-mercaptopurine, methotrexate, mycophenolate mofetil, leflunomide, hydroxychloroauine, hydroxyurea* , immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide)* ICIs (pembrolizumab, nivolumab, atezolizumab, durvalumab) CAR T cell therapy*

2022 KASL clinical practice guidelines for management of chronic hepatitis B
Modified from Loomba and Liang (Gastroenterology 2017;152:1297-1309)

간이식 공여자가 이에 해당하는 경우

HBsAg 음성/anti-HBc 양성인 공여자로부터 간이식을 받는 HBsAg 음성인 환자의 경우, B형간염 바이러스에 대한 면역 상태에 따라 B형간염 발생률이 달라질 수 있으며(Figure 6), 이에 따라 경구용 항바이러스제 치료를 시행한다.(2022 대한간학회 만성B형 간염 진료 가이드라인)
anti-HBc(+)인 공여자로부터 간을 공여 받는 수혜자로서 human anti-hepatitis B immunoglobulin 제제를 투여하지 않는 환자에게 투여 시 : 면역억제 요법 시행 동안 및 요법 종료 후 6개월까지 투여인정

Anti-HNc (+) donors

HBsAg(+) recipients: NA + HBIG

HBsAg (-) recipients

Anti-HBc (-)
Anti-HBs (-)
47.8%
NA

Anti-HBc (+)
Anti-HBs (-)
13.1%
NA

Anti-HBc (-)
Anti-HBs (+)
9.7%
NA

Anti-HBc (+)
Anti-HBs (+)
1.4%
No treatment
or
NA

Reactivation rate of HBV
without antiviral prophylaxis* Treatment

Figure 6. Strategies after liver transplantation in patients receiving anti-HBc-positive liver graft.
Anti-HBc, antibody to HBcAg; HBsAg, hepatitis B surface antigen; NA, nucleos(t)ide analogue; HBIG, hepatitis B immunoglobulin; anti-HBs, antibody to HBsAg; HBV, hepatitis B virus.

*Pooled data from the study by Cholongitas et al.(J Hepatol 2010;52:272-279)

2022 KASL clinical practice guidelines for management of chronic hepatitis B