慢性乙型肝炎防治指南（2019年版）

doi:10.3877/cma.j.issn.1674-1358.2019.06.001

为了实现世界卫生组织提出的"2030年消除病毒性肝炎作为重大公共卫生威胁"的目标，中华医学会感染病学分会和肝病学分会于2019年组织国内有关专家，以国内外慢性乙型肝炎病毒感染的基础和临床研究进展为依据，结合现阶段我国的实际情况，更新形成了《慢性乙型肝炎防治指南（2019年版）》，为慢性乙型肝炎的预防、诊断和治疗提供重要依据。

关键词: 肝炎，乙型，慢性, 治疗, 预防, 指南

Key words: Hepatitis B, chronic, Treatment, Prevention, Guideline

表1 推荐意见的证据等级和推荐等级

级别		详细说明
证据等级		?
?	高质量（A）	进一步研究不大可能改变对该评估结果的信心
?	中等质量（B）	进一步研究有可能对该评估结果的信心产生重要影响
?	低质量（C）	进一步研究很有可能影响该评估结果，且该评估结果很可能改变
推荐等级		?
?	强推荐（1）	充分考虑到证据的质量、患者可能的预后及预防、诊断和治疗效果，有较高的成本效益比
?	弱推荐（2）	证据价值参差不齐，推荐意见存在不确定性，或推荐的意见可能会有较差的成本效益比等，更倾向于较低等级的推荐

表1 推荐意见的证据等级和推荐等级

级别		详细说明
证据等级		?
?	高质量（A）	进一步研究不大可能改变对该评估结果的信心
?	中等质量（B）	进一步研究有可能对该评估结果的信心产生重要影响
?	低质量（C）	进一步研究很有可能影响该评估结果，且该评估结果很可能改变
推荐等级		?
?	强推荐（1）	充分考虑到证据的质量、患者可能的预后及预防、诊断和治疗效果，有较高的成本效益比
?	弱推荐（2）	证据价值参差不齐，推荐意见存在不确定性，或推荐的意见可能会有较差的成本效益比等，更倾向于较低等级的推荐

表2 慢性HBV感染自然病程分期

项目		免疫耐受期（慢性HBV携带状态）	免疫清除期（HBeAg阳性CHB）	免疫控制期（非活动性HBsAg携带状态）	再活动期（HBeAg阴性CHB）
?	HBV血清学标志物	?	?	?	?
?	HBsAg（IU/ml）	> 1 × 10⁴	+	< 1 × 10³	+
?	抗-HBs	－	－	－	－
?	HBeAg	+	+	－	+/－
?	抗-HBe	－	－	+	+/－
?	抗-HBc	+	+	+	+
HBV DNA（IU/ml）		> 2 × 10⁷	> 2 × 10⁴	< 2 × 10³	≥ 2 × 10³
ALT		正常	持续或反复升高	正常	持续或反复升高
肝脏病理学		无明显炎症坏死和纤维化	有明显炎症坏死和（或）纤维化	无或仅有轻度炎症，可有不同程度的纤维化	有明显炎症坏死和（或）纤维化

表2 慢性HBV感染自然病程分期

项目		免疫耐受期（慢性HBV携带状态）	免疫清除期（HBeAg阳性CHB）	免疫控制期（非活动性HBsAg携带状态）	再活动期（HBeAg阴性CHB）
?	HBV血清学标志物	?	?	?	?
?	HBsAg（IU/ml）	> 1 × 10⁴	+	< 1 × 10³	+
?	抗-HBs	－	－	－	－
?	HBeAg	+	+	－	+/－
?	抗-HBe	－	－	+	+/－
?	抗-HBc	+	+	+	+
HBV DNA（IU/ml）		> 2 × 10⁷	> 2 × 10⁴	< 2 × 10³	≥ 2 × 10³
ALT		正常	持续或反复升高	正常	持续或反复升高
肝脏病理学		无明显炎症坏死和纤维化	有明显炎症坏死和（或）纤维化	无或仅有轻度炎症，可有不同程度的纤维化	有明显炎症坏死和（或）纤维化

表3 不同肝脏炎症分级标准对照表

Knodell评分系统				Scheuer评分系统			王泰龄评分系统			Ishak评分系统
评分	汇管区炎症伴或不伴桥接坏死	小叶内变性及灶性坏死	汇管区炎症	评分	汇管区及汇管区周围活动度	小叶内活动度	评分	汇管区及周围	小叶内	评分	汇管区炎症	汇管区周围及界面炎症	灶性坏死、凋亡或灶性炎症	融合性坏死
0	无	无	无	0	无或轻微	无	0	无炎症	无炎症	0	无	无	无	无
1	轻度PN	轻度（嗜酸小体、气球变和散在肝细胞坏死累及< 1/3小叶）	轻度（少量炎症细胞浸润< 1/3汇管区）	1	仅汇管区炎症	有炎症细胞浸润但无肝细胞损伤	1	汇管区炎症	变性及少数坏死灶	1	部分或所有汇管区轻度炎症	轻度（局部或少数汇管区）	每10倍镜视野下< 1个或没有	局灶性
3	中度PN（多数汇管区周围累及< 50%）	中度（1/3～2/3小叶被累及）	中度（炎症细胞增多在1/3～2/3汇管区）	2	轻度PN	灶性坏死或出现嗜酸小体	2	轻度PN	汇管区周围纤维化，纤维隔形成，小叶结构保留	2	部分或所有汇管区中度炎症	轻中度（局部或少数汇管区）	每10倍镜视野下2～4个	部分小叶内可见3带坏死
3	中度PN（多数汇管区周围累及< 50%）	中度（1/3～2/3小叶被累及）	中度（炎症细胞增多在1/3～2/3汇管区）	2	轻度PN	灶性坏死或出现嗜酸小体	2	轻度PN	汇管区周围纤维化，纤维隔形成，小叶结构保留	3	所有汇管区中重度炎症	中度（炎症范围< 50%汇管区或界板周围	每10倍镜视野下5～10个	大量小叶内可见3带坏死
4	重度PN（多数汇管区周围累及> 50%）	重度（累及> 2/3小叶）	重度（炎症细胞密集> 2/3汇管区）	3	中度PN	严重灶性肝细胞损伤	3	中度PN	纤维隔伴小叶结构紊乱，无肝硬化	4	所有汇管区重度炎症	重度（炎症范围> 50%汇管区或界板周围	每10倍视野下> 10个	3带坏死+偶见汇管区－中央区桥接坏死
5	中度PN并桥接坏死	—		4	重度PN	出现融合坏死	4	重度PN	早期肝硬化	5	—			3带坏死+严重汇管区－中央区桥接坏死
10	重度PN并桥接坏死或多小叶坏死	?		?	?	?	?	?	?	6	?			全小叶或多小叶坏死

表3 不同肝脏炎症分级标准对照表

Knodell评分系统				Scheuer评分系统			王泰龄评分系统			Ishak评分系统
评分	汇管区炎症伴或不伴桥接坏死	小叶内变性及灶性坏死	汇管区炎症	评分	汇管区及汇管区周围活动度	小叶内活动度	评分	汇管区及周围	小叶内	评分	汇管区炎症	汇管区周围及界面炎症	灶性坏死、凋亡或灶性炎症	融合性坏死
0	无	无	无	0	无或轻微	无	0	无炎症	无炎症	0	无	无	无	无
1	轻度PN	轻度（嗜酸小体、气球变和散在肝细胞坏死累及< 1/3小叶）	轻度（少量炎症细胞浸润< 1/3汇管区）	1	仅汇管区炎症	有炎症细胞浸润但无肝细胞损伤	1	汇管区炎症	变性及少数坏死灶	1	部分或所有汇管区轻度炎症	轻度（局部或少数汇管区）	每10倍镜视野下< 1个或没有	局灶性
3	中度PN（多数汇管区周围累及< 50%）	中度（1/3～2/3小叶被累及）	中度（炎症细胞增多在1/3～2/3汇管区）	2	轻度PN	灶性坏死或出现嗜酸小体	2	轻度PN	汇管区周围纤维化，纤维隔形成，小叶结构保留	2	部分或所有汇管区中度炎症	轻中度（局部或少数汇管区）	每10倍镜视野下2～4个	部分小叶内可见3带坏死
3	中度PN（多数汇管区周围累及< 50%）	中度（1/3～2/3小叶被累及）	中度（炎症细胞增多在1/3～2/3汇管区）	2	轻度PN	灶性坏死或出现嗜酸小体	2	轻度PN	汇管区周围纤维化，纤维隔形成，小叶结构保留	3	所有汇管区中重度炎症	中度（炎症范围< 50%汇管区或界板周围	每10倍镜视野下5～10个	大量小叶内可见3带坏死
4	重度PN（多数汇管区周围累及> 50%）	重度（累及> 2/3小叶）	重度（炎症细胞密集> 2/3汇管区）	3	中度PN	严重灶性肝细胞损伤	3	中度PN	纤维隔伴小叶结构紊乱，无肝硬化	4	所有汇管区重度炎症	重度（炎症范围> 50%汇管区或界板周围	每10倍视野下> 10个	3带坏死+偶见汇管区－中央区桥接坏死
5	中度PN并桥接坏死	—		4	重度PN	出现融合坏死	4	重度PN	早期肝硬化	5	—			3带坏死+严重汇管区－中央区桥接坏死
10	重度PN并桥接坏死或多小叶坏死	?		?	?	?	?	?	?	6	?			全小叶或多小叶坏死

表4 国内外肝纤维化分期标准对照表

Knodell评分系统		Scheuer评分系统		Metavir评分系统		王泰龄评分系统		Ishak评分系统
0分	无纤维化	0分	无纤维化	0分	无纤维化	0分	无纤维化	0分	无纤维化
1分	汇管区纤维性扩大	1分	汇管区纤维性扩大	1分	汇管区纤维性扩大，无间隔	1分	汇管区扩大，纤维化	1分	部分汇管区纤维性扩大伴或不伴短纤维间隔
1分	汇管区纤维性扩大	1分	汇管区纤维性扩大	1分	汇管区纤维性扩大，无间隔	1分	汇管区扩大，纤维化	2分	大部分汇管区纤维性扩大伴或不伴短纤维间隔
2分	—	2分	汇管区周围纤维化，汇管区-汇管区纤维间隔	2分	汇管区纤维扩大+少数间隔	2分	汇管区周围纤维化，纤维隔形成，小叶结构保留	3分	大部分汇管区纤维性扩大，偶见汇管区-汇管区纤维间隔
3分	出现桥接、汇管区-汇管区或汇管区-中央静脉纤维间隔	3分	桥接纤维化，伴小叶结构紊乱，无肝硬化	3分	大量间隔，伴结构紊乱，无肝硬化	3分	纤维隔伴小叶结构紊乱，无肝硬化	4分	大部分汇管区纤维性扩大，显著汇管区-汇管区或汇管区-中央静脉纤维间隔
4分	肝硬化	4分	可能/肯定肝硬化	4分	肝硬化	4分	早期肝硬化	5分	显著纤维化，偶见结节（不完全分割性肝硬化）
4分	肝硬化	4分	可能/肯定肝硬化	4分	肝硬化	4分	早期肝硬化	6分	肝硬化

表4 国内外肝纤维化分期标准对照表

Knodell评分系统		Scheuer评分系统		Metavir评分系统		王泰龄评分系统		Ishak评分系统
0分	无纤维化	0分	无纤维化	0分	无纤维化	0分	无纤维化	0分	无纤维化
1分	汇管区纤维性扩大	1分	汇管区纤维性扩大	1分	汇管区纤维性扩大，无间隔	1分	汇管区扩大，纤维化	1分	部分汇管区纤维性扩大伴或不伴短纤维间隔
1分	汇管区纤维性扩大	1分	汇管区纤维性扩大	1分	汇管区纤维性扩大，无间隔	1分	汇管区扩大，纤维化	2分	大部分汇管区纤维性扩大伴或不伴短纤维间隔
2分	—	2分	汇管区周围纤维化，汇管区-汇管区纤维间隔	2分	汇管区纤维扩大+少数间隔	2分	汇管区周围纤维化，纤维隔形成，小叶结构保留	3分	大部分汇管区纤维性扩大，偶见汇管区-汇管区纤维间隔
3分	出现桥接、汇管区-汇管区或汇管区-中央静脉纤维间隔	3分	桥接纤维化，伴小叶结构紊乱，无肝硬化	3分	大量间隔，伴结构紊乱，无肝硬化	3分	纤维隔伴小叶结构紊乱，无肝硬化	4分	大部分汇管区纤维性扩大，显著汇管区-汇管区或汇管区-中央静脉纤维间隔
4分	肝硬化	4分	可能/肯定肝硬化	4分	肝硬化	4分	早期肝硬化	5分	显著纤维化，偶见结节（不完全分割性肝硬化）
4分	肝硬化	4分	可能/肯定肝硬化	4分	肝硬化	4分	早期肝硬化	6分	肝硬化

图1 慢性HBV感染抗病毒治疗适应证的选择流程图

表5 核苷（酸）类似物耐药挽救治疗推荐

耐药种类	推荐药物
LAM或LdT耐药	换用TDF或TAF
ADV耐药，之前未使用LAM或LdT	换用ETV、TDF或TAF
ADV耐药，且对LAM/LdT耐药	换用TDF或TAF
ETV耐药	换用TDF或TAF
ETV和ADV耐药	ETV联合TDF，或ETV联合TAF

表5 核苷（酸）类似物耐药挽救治疗推荐

耐药种类	推荐药物
LAM或LdT耐药	换用TDF或TAF
ADV耐药，之前未使用LAM或LdT	换用ETV、TDF或TAF
ADV耐药，且对LAM/LdT耐药	换用TDF或TAF
ETV耐药	换用TDF或TAF
ETV和ADV耐药	ETV联合TDF，或ETV联合TAF

表6 儿童使用核苷（酸）类药的推荐剂量

药物	体质量（kg）	剂量（mg/d）
ETV	?	?
年龄≥ 2岁，且体质量≥ 10 kg；体质量> 30 kg，按成人剂量	10～11	0.15
	> 11～14	0.20
	> 14～17	0.25
	> 17～20	0.30
	> 20～23	0.35
	> 23～26	0.40
	> 26～30	0.45
	> 30	0.50
TDF	?	?
年龄≥ 2岁，且体质量≥ 17 kg，可口服片剂者	17～< 22	150
	22～< 28	200
	28～< 35	250
	≥ 35	300
年龄≥ 2岁，且体质量≥ 10 kg，不能口服片剂者，可使用粉剂，提供专用小勺，40 mg/勺	10～< 12	80（2勺）
	12～< 14	100（2.5勺）
	14～< 17	120（3勺）
	17～< 19	140（3.5勺）
	19～< 22	160（4勺）
	22～< 24	180（4.5勺）
	24～< 27	200（5勺）
	27～< 29	220（5.5勺）
	29～< 32	240（6.0勺）
	32～< 34	260（6.5勺）
	34～< 35	280（7.0勺）
	≥ 35	300（7.5勺）
TAF（年龄≥ 12岁）	≥ 35	25

表6 儿童使用核苷（酸）类药的推荐剂量

药物	体质量（kg）	剂量（mg/d）
ETV	?	?
年龄≥ 2岁，且体质量≥ 10 kg；体质量> 30 kg，按成人剂量	10～11	0.15
	> 11～14	0.20
	> 14～17	0.25
	> 17～20	0.30
	> 20～23	0.35
	> 23～26	0.40
	> 26～30	0.45
	> 30	0.50
TDF	?	?
年龄≥ 2岁，且体质量≥ 17 kg，可口服片剂者	17～< 22	150
	22～< 28	200
	28～< 35	250
	≥ 35	300
年龄≥ 2岁，且体质量≥ 10 kg，不能口服片剂者，可使用粉剂，提供专用小勺，40 mg/勺	10～< 12	80（2勺）
	12～< 14	100（2.5勺）
	14～< 17	120（3勺）
	17～< 19	140（3.5勺）
	19～< 22	160（4勺）
	22～< 24	180（4.5勺）
	24～< 27	200（5勺）
	27～< 29	220（5.5勺）
	29～< 32	240（6.0勺）
	32～< 34	260（6.5勺）
	34～< 35	280（7.0勺）
	≥ 35	300（7.5勺）
TAF（年龄≥ 12岁）	≥ 35	25

[1]	World Health Organization. Global hepatitis report 2017. Geneva[EB/OL]. [2019-11-06]. URL
[2]	Cui F, Shen L, Li L, et al. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China[J]. Emerg Infect Dis,2017,23(5):765-772.
[3]	Liu J, Liang W, Jing W, et al. Countdown to 2030: eliminating hepatitis B disease, China[J]. Bull World Health Organ,2019,97(3):230-238.
[4]	Xu Y, Liu H, Wang Y, et al. The next step in controlling HBV in China[J]. BMJ,2013,347:f4503.
[5]	Lu Y, Zhu FC, Liu JX, et al. The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China[J]. Vaccine,2017,35(48PtB):6627-6633.
[6]	Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology,2018,67(4):1560-1599.
[7]	Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices[J]. WMWR Recomm Rep,2018,67(1):1-31.
[8]	World Health Organization. Guidelines for the prevention, care and treatment of persons with chronc hepatitis B infection[M]. Geneva: World Health Organization,2015.
[9]	国家卫生计生委，国家发展改革委，教育部, 等. 中国病毒性肝炎防治规划(2017-2020年)[J]. 中国病毒病杂志,2018,8(1):1-7.
[10]	World Health Organization. Hepatitis B vaccines: WHO position paper, July 2017--Recommendations[J]. Vaccine,2019,37(2):223-225.
[11]	Bruce MG, Bruden D, Hurlburt D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 30-year follow-up study and response to a booster dose[J]. J Infect Dis,2016,214(1):16-22.
[12]	Levy M, Koren G. Hepatitis B vaccine in pregnancy: maternal and fetal safety[J]. Am J Perinatol,1991,8(3):227-232.
[13]	Moro PL, Zheteyeva Y, Barash F, et al. Assessing the safety of hepatitis B vaccination during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 1990-2016[J]. Vaccine,2018,36(1):50-54.
[14]	Sheffield JS, Hickman A, Tang J, et al. Efficacy of an accelerated hepatitis B vaccination program during pregnancy[J]. Obstet Gynecol,2011,117(5):1130-1135.
[15]	Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J]. Elife,2012,1:e00049.
[16]	Giersch K, Allweiss L, Volz T, et al. Serum HBV pgRNA as a clinical marker for cccDNA activity[J]. J Hepatol,2017,66(2):460-462.
[17]	鲁凤民，王杰，庄辉. HBV RNA病毒样颗粒的潜在临床意义[J]. 中华肝脏病杂志,2016,24(9):641-642.
[18]	鲁凤民，窦晓光，张文宏, 等. 慢性乙型肝炎患者血清HBV RNA检测的临床意义[J]. 临床肝胆病杂志,2018,34(5):934-938.
[19]	McNaughton AL, D’Arienzo V, Ansari MA, et al. Insights from deep sequencing of the HBV genome-unique, tiny, and misunderstood[J]. Gastroenterology,2019,156(2):384-399.
[20]	Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: Recent advances[J]. J Gastroenterol Hepatol,2011,26 (Suppl 1):123-130.
[21]	Livingston SE, Simonetti JP, Bulkow LR, et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F[J]. Gastroenterology,2007,133(5):1452-1457.
[22]	Yu MW, Yeh SH, Chen PJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men [J]. J Natl Cancer Inst,2005,97(4):265-272.
[23]	Tang LSY, Covert E, Wilson E, et al. Chronic hepatitis B infection: a review[J]. JAMA,2018,319(17):1802-1813.
[24]	Indolfi G, Easterbrook P, Dusheiko G, et al. Hepatitis B virus infection in children and adolescents[J]. Lancet Gastroenterol Hepatol,2019,4(6):466-476.
[25]	Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination of hepatitis B: a modelling study[J]. Lancet Infect Dis, 2016,16(12):1399-1408.
[26]	Liu JF, Yao NJ, Chen TY, et al. Prevalence of mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis[J]. J Hepatol,2019,70:e123-e124.
[27]	中华医学会感染病学分会，GRADE中国中心. 中国乙型肝炎病毒母婴传播防治指南(2019年版)[J]. 中华传染病杂志,2019,37(7):388-396.
[28]	Liaw YF. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment[J]. Liver Int,2009,29(Suppl 1):100-107.
[29]	Fanning GC, Zoulim F, Hou J, et al. Therapeutic strategies for hepatitis B virus infection: towards a cure[J]. Nat Rev Drug Discov,2019,18(11):827-844.
[30]	Hui CK, Leung N, Yuen ST, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase[J]. Hepatology,2007,46(2):395-401.
[31]	Liaw YF. Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy[J]. J Gastroenterol Hepatol,2003,18(3):246-252.
[32]	Chu CM, Hung SJ, Lin J, et al. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels[J]. Am J Med,2004,116(12):829-834.
[33]	Chu CM, Liaw YF. Prevalence of and risk factors for hepatitis B viremia after spontaneous hepatitis B surface antigen seroclearance in hepatitis B carriers[J]. Clin Infect Dis,2012,54(1):88-90.
[34]	Chu CM, Liaw YF. Hepatitis B surface antigen seroclearance during chronic HBV infection[J]. Antivir Ther,2010,15(2):133-143.
[35]	Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors[J]. J Hepatol,2008,48(2):335-352.
[36]	Chen YC, Chu CM, Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B[J]. Hepatology,2010,51(2):435-444.
[37]	Park BK, Park YN, Ahn SH, et al. Long-term outcome of chronic hepatitis B based on histological grade and stage[J]. J Gastroenterol Hepatol,2007,22(3):383-388.
[38]	Lin SM, Yu ML, Lee CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma[J]. J Hepatol,2007,46(1):45-52.
[39]	Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: natural history and treatment[J]. Semin Liver Dis,2006,26(2):142-152.
[40]	Chen YC, Chu CM, Yeh CT, et al. Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study[J]. Hepatol Int,2007,1(1):267-273.
[41]	Hsu YS, Chien RN, Yeh CT, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B[J]. Hepatology,2002,35(6):1522-1527.
[42]	McMahon BJ, Holck P, Bulkow L, et al. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus[J]. Ann Intern Med,2001,135(9):759-768.
[43]	Fattovich G, Giustina G, Schalm SW, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis[J]. Hepatology,1995,21(1):77-82.
[44]	Fattovich G. Natural history and prognosis of hepatitis B[J]. Semin Liver Dis,2003,23(1):47-58.
[45]	Tseng TC, Liu CJ, Yang HC, et al. Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads[J]. Hepatology,2013,57(2):441-450.
[46]	Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load[J]. Gastroenterology,2012,142(5):1140-1149.
[47]	Zhang Z, Zhang JY, Wang LF, et al. Immunopathogenesis and prognostic immune markers of chronic hepatitis B virus infection[J]. J Gastroenterol Hepatol,2012,27(2):223-230.
[48]	Dandri M, Locarnini S. New insight in the pathobiology of hepatitis B virus infection[J]. Gut,2012,61(Suppl 1):i6-17.
[49]	Isogawa M, Tanaka Y. Immunobiology of hepatitis B virus infection[J]. Hepatol Res,2015,45(2):179-189.
[50]	Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response[J]. Annu Rev Immunol,2001,19:65-91.
[51]	Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection[J]. Gut,2012,61(12):1754-1764.
[52]	Cornberg M, Wong VW, Locarnini S, et al. The role of quantitative hepatitis B surface antigen revisited[J]. J Hepatol,2017,66(2):398-411.
[53]	Hou JL, Zhao W, Lee C, et al. Outcomes of long-term treatment of chronic HBV infection with entecavir or other agents from a randomized trial in 24 countries[J]. Clin Gastroenterol Hepatol,2019. [Epub ahead of print].
[54]	Kim JH, Sinn DH, Kang W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J]. Hepatology,2017,66(2):335-343.
[55]	Wiegand J, Hasenclever D, Tillmann HL. Should treatment of hepatitis B depend on hepatitis B virus genotypes? A hypothesis generated from an explorative analysis of published evidence[J]. Antivir Ther,2008,13(2):211-220.
[56]	Ni YH, Chang MH, Wang KJ, et al. Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma[J]. Gastroenterology,2004,127(6):1733-1738.
[57]	Chu CJ, Hussain M, Lok AS. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C[J]. Gastroenterology,2002,122(7):1756-1762.
[58]	Watanabe K, Takahashi T, Takahashi S, et al. Comparative study of genotype B and C hepatitis B virus-induced chronic hepatitis in relation to the basic core promoter and precore mutations[J]. J Gastroenterol Hepatol,2005,20(3):441-449.
[59]	Rajoriya N, Combet C, Zoulim F, et al. How viral genetic variants and genotypes influence disease and treatment outcome of chronic hepatitis B. Time for an individualised approach?[J]. J Hepatol,2017,67(6):1281-1297.
[60]	Jia W, Song LW, Fang YQ, et al. Antibody to hepatitis B core antigen levels in the natural history of chronic hepatitis B: a prospective observational study[J]. Medicine (Baltimore),2014,93(29):e322.
[61]	Song LW, Liu PG, Liu CJ, et al. Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection[J]. Clin Microbiol Infect,2015,21(2):197-203.
[62]	Fan R, Sun J, Yuan Q, et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues[J]. Gut,2016,65(2):313-320.
[63]	Hou FQ, Song LW, Yuan Q, et al. Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBeAg-positive chronic hepatitis B patients receiving peginterferon[J]. Theranostics,2015,5(3):218-226.
[64]	Zhou J, Song L, Zhao H, et al. Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase[J]. Sci Rep,2017,7(1):2747.
[65]	Wang J, Shen T, Huang X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound[J]. J Hepatol,2016,65(4):700-710.
[66]	Fan R, Zhou B, Xu M, et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of nucles(t)ide analogue therapy[J]. Clin Gastroenterol Hepatol,2019,pii:S1542-3565(19)30790-6.
[67]	Wong DK, Seto WK, Cheung KS, et al. Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA[J]. Liver Int,2017,37(7):995-1001.
[68]	Martinot-Peignoux M, Lapalus M, Maylin S, et al. Baseline HBsAg and HBcrAg titres allow peginterferon-based 'precision medicine’ in HBeAg-negative chronic hepatitis B patients[J]. J Viral Hepat,2016,23(11):905-911
[69]	Honda M, Shirasaki T, Terashima T, et al. Hepatitis B virus (HBV) core-related antigen during nucleos(t)ide analog therapy is related to intra-hepatic HBV replication and development of hepatocellular carcinoma[J]. J Infect Dis,2016,213(7):1096-1106.
[70]	Chuaypen N, Posuwan N, Payungporn S, et al. Serum hepatitis B core-related antigen as a treatment predictor of pegylated interferon in patients with HBeAg-positive chronic hepatitis B[J]. Liver Int,2016,36(6):827-836.
[71]	Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries[J]. Am J Gastroenterol,2017,112(1):18-35.
[72]	Wang K, Lin W, Kuang Z, et al. Longitudinal change of body mass index is associated with alanine aminotransferase elevation after complete viral suppression in chronic hepatitis B patients[J]. J Infect Dis,2019,220(9):1469-1476.
[73]	Amaddeo G, Cao Q, Ladeiro Y, et al. Integration of tumour and viral genomic characterizations in HBV-related hepatocellular carcinomas[J]. Gut,2015,64(5):820-829.
[74]	Seo SI, Kim HS, Kim WJ, et al. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma[J]. World J Gastroenterol,2015,21(13):3928-3935.
[75]	Wai CT, Cheng CL, Wee A, et al. Non-invasive models for predicting histology in patients with chronic hepatitis B[J]. Liver Int,2006,26(6):666-672.
[76]	Kim WR, Berg T, Asselah T, et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients[J]. J Hepatol,2016,64(4):773-780.
[77]	Dong XQ, Wu Z, Zhao H, et al. Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients[J]. J Viral Hepat,2019,26(2):297-307.
[78]	Sonneveld MJ, Brouwer WP, Chan HL, et al. Optimisation of the use of APRI and FIB-4 to rule out cirrhosis in patients with chronic hepatitis B: results from the SONIC-B study[J]. Lancet Gastroenterol Hepatol,2019,4(7):538-544.
[79]	Lemoine M, Shimakawa Y, Nayagam S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa[J]. Gut,2016,65(8):1369-1376.
[80]	Chen YP, Hu XM, Liang XE, et al. Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection[J]. J Gastroenterol Hepatol,2018,33(1):256-263.
[81]	Yao M, Wang L, You H, et al. Serum GP73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B[J]. Clin Chim Acta,2019,493:92-97.
[82]	Wang L, Liu T, Zhou J, et al. Changes in serum chitinase 3-like 1 levels correlate with changes in liver fibrosis measured by two established quantitative methods in chronic hepatitis B patients following antiviral therapy[J]. Hepatol Res,2018,48(3):E283-E290.
[83]	Yan L, Deng Y, Zhou J, et al. Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT [J]. Infection,2018,46(3):385-393.
[84]	European Association for Study of Liver, Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH clinical practice guidelines: non-invasive tests for evaluation of liver disease severity and prognosis[J]. J Hepatol,2015,63(1):237-264.
[85]	中国肝炎防治基金会，中华医学会感染病学分会，中华医学会肝病学分会和中国研究型医院学会肝病专业委员会. 瞬时弹性成像技术诊断肝纤维化专家共识(2018年更新版)[J]. 中华肝脏病杂志,2019,27(3):182-191.
[86]	Chen YP, Liang XE, Dai L, et al. Improving transient elastography performance for detecting hepatitis B cirrhosis [J]. Dig Liver Dis,2012,44(1):61-66.
[87]	Chen YP, Liang XE, Zhang Q, et al. Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B[J]. J Gastroenterol Hepatol,2012,27(7):1219-1226.
[88]	Chan HL, Wong GL, Choi PC, et al. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B[J]. J Viral Hepat,2009,16(1):36-44.
[89]	Liang XE, Zhong C, Huang L, et al. Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers[J]. J Gastroenterol Hepatol,2017,32(2):459-465.
[90]	Scott DR, Levy MT. Liver transient elastography (Fibroscan): a place in the management algorithms of chronic viral hepatitis[J]. Antivir Ther,2010,15(1):1-11.
[91]	Wu Z, Dong X, Wang G, et al. Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal[J]. J Viral Hepat,2019,26(2):287-296.
[92]	Jia J, Hou J, Ding H, et al. Transient elastography compared to serum markers to predict liver fibrosis in a cohort of Chinese patients with chronic hepatitis B[J]. J Gastroenterol Hepatol,2015,30(4):756-762.
[93]	Fetzer DT, Rodgers SK, Seow JH, et al. Ultrasound evaluation in patients at risk for hepatocellular carcinoma[J]. Radiol Clin North Am,2019,57(3):563-583.
[94]	Elsayes KM, Kielar AZ, Chernyak V, et al. LI-RADS: a conceptual and historical review from its beginning to its recent integration into AASLD clinical practice guidance[J]. J Hepatocell Carcinoma,2019,6:49-69.
[95]	Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis[J]. Hepatology,1981,1(5):431-435.
[96]	Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment[J]. J Hepatol,1991,13(3):372-374.
[97]	Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group[J]. Hepatology,1996,24(2):289-293.
[98]	Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis[J]. J Hepatol,1995,22(6):696-699.
[99]	Kim SU, Oh HJ, Wanless IR, et al. The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis [J]. J Hepatol,2012,57(3):556-563.
[100]	王泰龄，刘霞，周元平, 等. 慢性肝炎炎症活动度及纤维化程度计分方案[J]. 中华肝脏病杂志,1998,6(4):195.
[101]	Xu S, Wang Y, Tai DCS, et al. qFibrosis: a fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients[J]. J Hepatol,2014,61(2):260-269.
[102]	Sun Y, Zhou J, Wang L, et al. New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment[J]. Hepatology,2017,65(5):1438-1450.
[103]	Wong GL. Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend[J]. Clin Mol Hepatol,2018,24(2):108-113.
[104]	Martin P. Immune-tolerant hepatitis B: maybe a misnomer but still hard to treat[J]. Hepatology,2019,69(6):2315-2317.
[105]	Maimone S, Caccamo G, Squadrito G, et al. A combination of different diagnostic tools allows identification of inactive hepatitis B virus carriers at a single time point evaluation[J]. Liver Int,2017,37(3):362-368.
[106]	Liu J, Yang HI, Lee MH, et al. Serum levels of hepatitis B surface antigen and DNA can predict inactive carriers with low risk of disease progression[J]. Hepatology,2016,64(2):381-389.
[107]	Raimondo G, Locarnini S, Pollicino T, et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection[J]. J Hepatol,2019,71(2):397-408.
[108]	Wu X, Zhou J, Xie W, et al. Entecavir monotherapy versus de novo combination of lamivudine and adefovir for compensated hepatitis B virus-related cirrhosis: a real-world prospective multicenter cohort study[J]. Infect Drug Resist,2019,12:745-757.
[109]	Suk KT, Baik SK, Yoon JH, et al. Revision and update on clinical practice guideline for liver cirrhosis[J]. Korean J Hepatol,2012,18(1):1-21.
[110]	D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies[J]. J Hepatol,2006,44(1):217-231.
[111]	D’Amico G, Morabito A, D’Amico M, et al. New concepts on the clinical course and stratification of compensated and decompensated cirrhosis[J]. Hepatol Int,2018.12(Suppl 1):34-43.
[112]	European Association for the Study of the Liver, European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol,2017,67(2):370-398.
[113]	中华医学会肝病学分会，中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015更新版)[J]. 中国肝脏病杂志(电子版),2015,7(3):1-18.
[114]	Mak LY, Seto WK, Fung J, et al. Novel developments of hepatitis B: treatment goals, agents and monitoring tools[J]. Expert Rev Clin Pharmacol,2019,12(2):109-120.
[115]	Seto WK, Lo YR, Pawlotsky JM, et al. Chronic hepatitis B virus infection[J]. Lancet,2018,392(10161):2313-2324.
[116]	Ning Q, Wu D, Wang GQ, et al. Roadmap to functional cure of chronic hepatitis B: An expert consensus[J]. J Viral Hepat,2019,26(10):1146-1155.
[117]	Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B[J]. N Engl J Med,2006,354(10):1001-1010.
[118]	Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B[J]. N Engl J Med,2006,354(10):1011-1020.
[119]	Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B[J]. Hepatology,2010,51(2):422-430.
[120]	Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B[J]. Hepatology,2010,52(3):886-893.
[121]	Xu Y, Zhang YG, Wang X, et al. Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis[J]. World J Gastroenterol,2015,21(25):7869-7876.
[122]	Su TH, Hu TH, Chen CY, et al. Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients[J]. Liver Int,2016,36(12):1755-1764.
[123]	Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy[J]. Hepatology,2009,49(5):1503-1514.
[124]	Hou JL, Gao ZL, Xie Q, et al. Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks: a randomized controlled trial[J]. J Viral Hepat,2015,22(2):85-93.
[125]	Liang X, Gao Z, Xie Q, et al. Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results[J]. Hepatol Int,2019,13(3):260-269.
[126]	Liu Y, Corsa AC, Buti M, et al. No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg-patients with chronic hepatitis B after 8 years of treatment[J]. J Viral Hepat,2017,24(1):68-74.
[127]	Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study[J]. Lancet,2013,381(9865):468-475.
[128]	Kim WR, Loomba R, Berg T, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B[J]. Cancer,2015,121(20):3631-3638.
[129]	Lim YS, Byun KS, Yoo BC, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial[J]. Gut,2016,65(5):852-860.
[130]	Kim HJ, Cho JY, Kim YJ, et al. Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple nucleos(t)ide analogue failure in chronic hepatitis B patients[J]. Korean J Intern Med,2015,30(1):32-41.
[131]	Suzuki F, Suzuki Y, Hosaka T, et al. Efficacy of long-term tenofovir-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs[J]. J Gastroenterol,2017,52(5):641-651.
[132]	Zhou J, Liu YY, Lian JS, et al. Efficacy and safety of tenofovir disoproxil treatment for chronic hepatitis B patients with genotypic resistance to other nucleoside analogues: A prospective study[J]. Chin Med J (Engl),2017,130(8):914-919.
[133]	Fasano M, Maggi P, Leone A, et al. Long-term efficacy and safety of switching from lamivudine + adefovir to tenofovir disoproxil fumarate in virologically suppressed patients[J]. Dig Liver Dis,2017,49(5):530-534.
[134]	Rodriguez M, Pascasio JM, Fraga E, et al. Tenofovir vs lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study[J]. World J Gastroenterol,2017,23(41):7459-7469.
[135]	Fung S, Kwan P, Fabri M, et al. Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study[J]. J Hepatol,2017,66(1):11-18.
[136]	Lim YS, Lee YS, Gwak GY, et al. Monotherapy with tenofovir disoproxil fumarate for multiple drug-resistant chronic hepatitis B: 3-year trial[J]. Hepatology,2017,66(3):772-783.
[137]	Lim YS, Gwak GY, Choi J, et al. Monotherapy with tenofovir disoproxil fumarate for adefovir-resistant vs. entecavir-resistant chronic hepatitis B: A 5-year clinical trial[J]. J Hepatol,2019,71(1): 35-44.
[138]	Lee HW, Park JY, Lee JW, et al. Long-term efficacy of tenofovir disoproxil fumarate monotherapy for multidrug-resistant chronic HBV infection[J]. Clin Gastroenterol Hepatol,2019,17(7):1348-1355. e2.
[139]	Lim YS, Yoo BC, Byun KS, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial[J]. Gut,2016,65(6):1042-1051.
[140]	Chan HL, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial[J]. Lancet Gastroenterol Hepatol,2016,1(3):185-195.
[141]	Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial[J]. Lancet Gastroenterol Hepatol,2016,1(3):196-206.
[142]	Agarwal K, Brunetto M, Seto WK, et al. 96weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection[J]. J Hepatol,2018,68(4):672-681.
[143]	中华医学会肝病学分会肝炎学组，中华肝脏病杂志. 非一线核苷(酸)类似物经治慢性乙型肝炎患者治疗策略调整专家共识[J]. 中华肝脏病杂志,2019,27(5):343-346.
[144]	Hsu CW, Su WW, Lee CM, et al. Phase Ⅳ randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B[J]. J Formos Med Assoc,2018,117(7):588-597.
[145]	侯凤琴，尹亚琳，曾玲英, 等. 聚乙二醇干扰素α-2b(Y型, 40 kD)注射液治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性分析[J]. 中华肝脏病杂志,2017,25(8):589-596.
[146]	张文宏，张大志，窦晓光，等. 聚乙二醇干扰素α治疗慢性乙型肝炎专家共识[J]. 中华肝脏病杂志,2017,25(9):678-686.
[147]	Wu D, Wang P, Han M, et al. Sequential combination therapy with interferon, interleukin-2 and therapeutic vaccine in entecavir-suppressed chronic hepatitis B patients: the Endeavor study[J]. Hepatol Int,2019,13(5):573-586.
[148]	Ning Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial)[J]. J Hepatol,2014,61(4):777-784.
[149]	Han M, Jiang J, Hou J, et al. Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-alpha 2a: 1 year follow-up of the OSST study[J]. Antivir Ther,2016,21(4):337-344.
[150]	Hu P, Shang J, Zhang W, et al. HBsAg loss with Peg-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)ide analog: New Switch study[J]. J Clin Transl Hepatol,2018,6(1):25-34.
[151]	Chan HLY, Chan FWS, Hui AJ, et al. Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir--A prospective study[J]. J Viral Hepat,2019,26(1):126-135.
[152]	Li SY, Li H, Xiong YL, et al. Peginterferon is preferable to entecavir for prevention of unfavourable events in patients with HBeAg-positive chronic hepatitis B: A five-year observational cohort study[J]. J Viral Hepat,2017,24(Suppl 1):12-20.
[153]	Ren P, Cao Z, Mo R, et al. Interferon-based treatment is superior to nucleos(t)ide analog in reducing HBV-related hepatocellular carcinoma for chronic hepatitis B patients at high risk[J]. Expert Opin Biol Ther,2018,18(10):1085-1094.
[154]	Lampertico P, Messinger D, Cornberg M, et al. A genotype-specific baseline score predicts post-treatment response to peginterferon alfa-2a in hepatitis B e antigen-negative chronic hepatitis B[J]. Ann Gastroenterol,2018,31(6):712-721.
[155]	Chan HLY, Messinger D, Papatheodoridis GV, et al. A baseline tool for predicting response to peginterferon alfa-2a in HBeAg-positive patients with chronic hepatitis B[J]. Aliment Pharmacol Ther,2018,48(5):547-555.
[156]	Chen H, Sun J, Zhou B, et al. Variants in STAT4 associated with cure of chronic HBV infection in HBeAg-positive patients treated with pegylated interferon-alpha[J]. Clin Gastroenterol Hepatol,2019. [Epub ahead of print].
[157]	蒋永芳，马静，贺波, 等. 阿德福韦酯联合安络化纤丸治疗慢性乙型肝炎的疗效[J]. 中华肝脏病杂志,2012,20(5):344-347.
[158]	王林，卢玮，高玉华, 等. 安络化纤丸对肝纤维化大鼠肝组织基质金属蛋白酶及其抑制物表达的影响[J]. 中华肝脏病杂志,2019,27(4):267-273.
[159]	苗亮，杨婉娜，董晓琴, 等. 安络化纤丸联合恩替卡韦治疗可显著提高慢性乙型肝炎病毒感染者肝纤维化的改善率[J]. 中华肝脏病杂志,2019,27(7):521-526.
[160]	杨年欢，袁国盛，周宇辰, 等. 恩替卡韦联合复方鳖甲软肝片治疗慢性乙型肝炎肝纤维化96周的临床疗效[J]. 南方医科大学学报,2016,36(6):775-779.
[161]	杨瑞华，李芹，陈玮. 扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化疗效的Meta分析[J]. 中华肝脏病杂志,2015,23(4):295-296.
[162]	Chen J, Zhao SS, Liu XX, et al. Comparison of the efficacy of tenofovir versus tenofovir plus entecavir in the treatment of chronic hepatitis B in patients with poor efficacy of entecavir: A systematic review and meta-analysis[J]. Clin Ther,2017,39(9):1870-1880.
[163]	Chaung KT, O’Brien C, Ha NB, et al. Alternative therapies for chronic hepatitis B patients with partial virological response to standard entecavir monotherapy[J]. J Clin Gastroenterol,2016,50(4):338-344.
[164]	Bozza C, Cinausero M, Iacono D, et al. Hepatitis B and cancer: A practical guide for the oncologist[J]. Crit Rev Oncol Hematol,2016,98:137-146.
[165]	Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B[J]. J Clin Oncol,2013,31(22):2765-2772.
[166]	Liu CJ, Chen PJ, Chen DS, et al. Hepatitis B virus reactivation in patients receiving cancer chemotherapy: natural history, pathogenesis, and management[J]. Hepatol Int,2013,7(2):316-326.
[167]	Choi J, Lim YS. Characteristics, prevention, and management of hepatitis B virus (HBV) reactivation in HBV-infected patients who require immunosuppressive therapy[J]. J Infect Dis,2017,216(Suppl 8):S778-S784.
[168]	Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy [J]. Gastroenterology, 2015,148(1):215-219.
[169]	Sarmati L, Andreoni M, Antonelli G, et al. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper[J]. Clin Microbiol Infect,2017,23(12):935-940.
[170]	Gentile G, Andreoni M, Antonelli G, et al. Screening, monitoring, prevention, prophylaxis and therapy for hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation: a systematic review[J]. Clin Microbiol Infect,2017,23(12):916-923.
[171]	Zhang MY, Zhu GQ, Shi KQ, et al. Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation[J]. Oncotarget,2016,7(21):30642-30658.
[172]	Yang C, Qin B, Yuan Z, et al. Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation[J]. Ann Hepatol,2016,15(4):501-511.
[173]	Liu WP, Xiao XB, Xue M, et al. Prophylactic use of entecavir for lymphoma patients with past hepatitis B virus infection: A randomized controlled trial[J]. Clin Lymphoma Myeloma Leuk,2019,19(2):103-108.
[174]	Seto WK, Chan TS, Hwang YY, et al. Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study[J]. J Clin Oncol,2014,32(33):3736-3743.
[175]	Kusumoto S, Tanaka Y, Suzuki R, et al. Monitoring of hepatitis B virus (HBV) DNA and risk of HBV reactivation in B-cell lymphoma: A prospective observational study[J]. Clin Infect Dis,2015,61(5):719-729.
[176]	Buti M, Manzano ML, Morillas RM, et al. Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study[J]. PLoS One,2017,12(9):e0184550.
[177]	Kusumoto S, Arcaini L, Hong X, et al. Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy[J]. Blood,2019,133(2):137-146.
[178]	Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update[J]. Hepatol Int,2016,10(1):1-98.
[179]	Liu WP, Wang XP, Zheng W, et al. Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma[J]. Leuk Lymphoma,2016,57(6):1355-1362.
[180]	Nakaya A, Fujita S, Satake A, et al. Delayed HBV reactivation in rituximab-containing chemotherapy: How long should we continue anti-virus prophylaxis or monitoring HBV-DNA?[J]. Leuk Res,2016,50:46-49.
[181]	中华医学会肝病学分会. 感染乙型肝炎病毒的育龄女性临床管理共识[J]. 中华肝脏病杂志,2018,26(3):204-208.
[182]	Zou H, Chen Y, Duan Z, et al. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers[J]. J Viral Hepat,2012,19(2):e18-25.
[183]	Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load[J]. N Engl J Med,2016,374(24):2324-2334.
[184]	Shang J, Wen Q, Wang CC, et al. Safety and efficacy of telbivudine for chronic hepatitis B during the entire pregnancy: Long-term follow-up[J]. J Viral Hepat,2017,24(Suppl 1):43-48.
[185]	Corbett AH, Kayira D, White NR, et al. Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study[J]. Antivir Ther,2014,19(6):587-595.
[186]	Benaboud S, Pruvost A, Coffie PA, et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d’Ivoire, in the ANRS 12109 TEmAA Study, Step 2[J]. Antimicrob Agents Chemother,2011,55(3):1315-1317.
[187]	Chang CY, Aziz N, Poongkunran M, et al. Serum aminotransferase flares in pregnant and postpartum women with current or prior treatment for chronic hepatitis B[J]. J Clin Gastroenterol,2018,52(3):255-261.
[188]	Nguyen V, Tan PK, Greenup AJ, et al. Anti-viral therapy for prevention of perinatal HBV transmission: extending therapy beyond birth does not protect against post-partum flare[J]. Aliment Pharmacol Ther,2014,39(10):1225-1234.
[189]	ter Borg MJ, Leemans WF, de Man RA, et al. Exacerbation of chronic hepatitis B infection after delivery[J]. J Viral Hepat,2008,15(1):37-41.
[190]	Jonas MM, Lok AS, McMahon BJ, et al. Antiviral therapy in management of chronic hepatitis B viral infection in children: A systematic review and meta-analysis[J]. Hepatology,2016,63(1):307-318.
[191]	Sokal EM, Paganelli M, Wirth S, et al. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition[J]. J Hepatol,2013,59(4):814-829.
[192]	World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[S]. Contributed by Libraries Australia. Geneva: 2015.
[193]	Komatsu H, Inui A, Fujisawa T. Pediatric hepatitis B treatment[J]. Ann Transl Med,2017,5(3):37.
[194]	Wirth S, Zhang H, Hardikar W, et al. Efficacy and safety of peginterferon alfa-2a (40 kD) in children with chronic hepatitis B: The PEG-B-ACTIVE Study[J]. Hepatology,2018,68(5):1681-1694.
[195]	Lampertico P, Chan HL, Janssen HL, et al. Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients[J]. Aliment Pharmacol Ther,2016,44(1):16-34.
[196]	Han Y, Zeng A, Liao H, et al. The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis[J]. Int Immunopharmacol,2017,42:168-175.
[197]	Grossi G, Loglio A, Facchetti F, et al. Tenofovir alafenamide as a rescue therapy in a patient with HBV-cirrhosis with a history of Fanconi syndrome and multidrug resistance[J]. J Hepatol,2018,68(1):195-198.
[198]	Shah AS, Amarapurkar DN. Spectrum of hepatitis B and renal involvement[J]. Liver Int,2018,38(1):23-32.
[199]	中华医学会感染病学分会艾滋病丙型肝炎学组，中国疾病预防控制中心. 中国艾滋病诊疗指南(2018年版)[J]. 中华内科杂志,2018,57(12):867-884.
[200]	Li Y, Xie J, Han Y, et al. Lamivudine monotherapy-based cART is efficacious for HBV treatment in HIV/HBV coinfection when baseline HBV DNA < 20,000 IU/ml[J]. J Acquir Immune Defic Syndr,2016,72(1):39-45.
[201]	李航，张福杰，卢洪洲, 等. HIV感染合并慢性肾脏病患者管理专家共识[J]. 中国艾滋病性病,2017,23(6):578-581.
[202]	Yuen MF. Anti-viral therapy in hepatitis B virus reactivation with acute-on-chronic liver failure[J]. Hepatol Int,2015,9(3):373-377.
[203]	姜立胜，李用国，陈姝, 等. 抗病毒治疗对乙型肝炎相关慢加急性肝衰竭近期及远期疗效的影响[J]. 临床肝胆病杂志,2013,29(2):110-113.
[204]	Sun LJ, Yu JW, Zhao YH, et al. Influential factors of prognosis in lamivudine treatment for patients with acute-on-chronic hepatitis B liver failure[J]. J Gastroenterol Hepatol,2010,25(3):583-590.
[205]	Zhang Y, Hu XY, Zhong S, et al. Entecavir vs lamivudine therapy for naive patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure[J]. World J Gastroenterol,2014,20(16):4745-4752.
[206]	Huang KW, Tam KW, Luo JC, et al. Efficacy and safety of lamivudine versus entecavir for treating chronic hepatitis B virus-related acute exacerbation and acute-on-chronic liver failure: A systematic review and Meta-analysis[J]. J Clin Gastroenterol,2017,51(6):539-547.
[207]	Garg H, Sarin SK, Kumar M, et al. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure[J]. Hepatology,2011,53(3):774-780.
[208]	郑玉山，孙凤兰，刘现红. 替比夫定与恩替卡韦治疗慢加急性肝衰竭的疗效分析[J]. 临床肝胆病杂志,2011,27(6):641-642, 646.
[209]	中华医学会感染病学分会肝衰竭与人工肝学组，中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 中华肝脏病杂志,2019,27(1):18-26.
[210]	Sun P, Dong X, Cheng X, et al. Nucleot(s)ide analogues for hepatitis B virus-related hepatocellular carcinoma after curative treatment: a systematic review and meta-analysis[J]. PLoS One,2014,9(7):e102761.
[211]	Yin J, Li N, Han Y, et al. Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study[J]. J Clin Oncol,2013,31(29):3647-3655.
[212]	Huang G, Lau WY, Wang ZG, et al. Antiviral therapy improves postoperative survival in patients with hepatocellular carcinoma: a randomized controlled trial[J]. Ann Surg,2015,261(1):56-66.
[213]	Wong JS, Wong GL, Tsoi KK, et al. Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma[J]. Aliment Pharmacol Ther,2011,33(10):1104-1112.
[214]	Wu CY, Chen YJ, Ho HJ, et al. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection[J]. JAMA,2012,308(18):1906-1914.
[215]	Jang JW, Choi JY, Bae SH, et al. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization[J]. Hepatology,2006,43(2):233-240.
[216]	Sun HC, Tang ZY, Wang L, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial[J]. J Cancer Res Clin Oncol,2006,132(7):458-465.
[217]	Lao XM, Luo G, Ye LT, et al. Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma[J]. Liver Int,2013,33(4):595-604.
[218]	Jang JW, Choi JY, Bae SH, et al. Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma[J]. J Hepatol,2004,41(3):427-435.
[219]	Peng JW, Lin GN, Xiao JJ, et al. Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy[J]. Asia Pac J Clin Oncol,2012,8(4):356-361.
[220]	Kim JH, Park JW, Kim TH, et al. Hepatitis B virus reactivation after three-dimensional conformal radiotherapy in patients with hepatitis B virus-related hepatocellular carcinoma[J]. Int J Radiat Oncol Biol Phys,2007,69(3):813-819.
[221]	Yeo W, Lam KC, Zee B, et al. Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy[J]. Ann Oncol,2004,15(11):1661-1666.
[222]	Maiwall R, Kumar M. Prevention and treatment of recurrent hepatitis B after liver transplantation[J]. J Clin Transl Hepatol,2016,4(1):54-65.
[223]	Cholongitas E, Papatheodoridis GV. High genetic barrier nucleos(t)ide analogue(s) for prophylaxis from hepatitis B virus recurrence after liver transplantation: a systematic review[J]. Am J Transplant,2013,13(2):353-362.
[224]	Yi NJ, Choi JY, Suh KS, et al. Post-transplantation sequential entecavir monotherapy following 1-year combination therapy with hepatitis B immunoglobulin[J]. J Gastroenterol,2013,48(12):1401-1410.
[225]	Teperman LW, Poordad F, Bzowej N, et al. Randomized trial of emtricitabine/tenofovir disoproxil fumarate after hepatitis B immunoglobulin withdrawal after liver transplantation[J]. Liver Transpl,2013,19(6):594-601.
[226]	Chen G, Liu H, Hu ZQ, et al. A new scheme with infusion of hepatitis B immunoglobulin combined with entecavir for prophylaxis of hepatitis B virus recurrence among liver transplant recipients[J]. Eur J Gastroenterol Hepatol,2015,27(8):901-906.
[227]	中国医师协会器官移植医师分会，中华医学会器官移植学分会. 中国肝癌肝移植临床实践指南(2018版)[J]. 中华消化外科杂志,2019,18(1):1-7.

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The guideline of prevention and treatment for chronic hepatitis B: a 2019 update

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The guideline of prevention and treatment for chronic hepatitis B: a 2019 update