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我国部分地区慢性HBV感染者HDV感染情况调查
DOI: 10.3969/j.issn.1001-5256.2023.04.009
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：刘玉梅完成实验和数据分析，撰写论文；郭小平、张慧敏、白洪霞、王春梅、任姗、蒋永芳、杨胜、彭锋、王晓忠、于雷、廖柏明、宁玲、何英利、杨霞、黄亮参与收集样本和临床数据；刘学恩、庄辉负责课题设计，指导撰写文章并最后定稿。
An investigation of hepatitis D virus infection among patients with chronic hepatitis B virus infection in some regions of China
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摘要:
目的 了解目前我国部分地区慢性HBV感染者丁型肝炎病毒(HDV) 感染流行情况。 方法 2021年3月—2022年6月从全国10个省市自治区收集3 131例慢性HBV感染者血清，用抗-HDV IgG酶联免疫试剂检测全部血清标本。对抗-HDV IgG阳性标本用巢式逆转录聚合酶链式反应(nRT-PCR) 法检测HDV RNA。对HDV RNA阳性标本的nRT-PCR扩增产物测序后进行序列分析，确定HDV基因型。分析抗-HDV IgG阳性患者的临床特征。计量资料两组间比较采用Mann-Whitney U秩和检验。计数资料两组间比较采用χ2检验或Fisher精确检验。 结果 3 131例慢性HBV感染者的抗-HDV IgG阳性率为0.70%(22/3 131)，内蒙古自治区、新疆维吾尔自治区、北京市和湖南省慢性HBV感染者的抗-HDV IgG阳性率分别为1.81%(16/886)、0.88%(2/226)、0.28%(2/708) 和1.00%(2/200)，其中内蒙古自治区慢性HBV感染者抗-HDV IgG阳性率显著高于北京市(P=0.004)，其余地区间比较差异均无统计学意义(P值均＞0.05)。对内蒙古自治区慢性HBV感染者临床特征分析发现，抗-HDV IgG阳性组蒙古族患者(P=0.001)、ALT异常患者(P=0.007) 和抗病毒治疗患者(P=0.029) 的比例显著高于抗-HDV IgG阴性组，而中位HBV DNA水平明显较低(P=0.030)。共检出19例HDV RNA阳性标本，均为HDV基因1型。 结论 我国不同地区HDV流行率差异较大，内蒙古自治区慢性HBV感染者中HDV流行率较高。我国北方部分省市的HDV流行基因型主要为1型。 Abstract:Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing (P=0.004), and there was no significant difference between the other regions (P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality (P=0.001), abnormal alanine aminotransferase (P=0.007), or antiviral treatment (P=0.029), as well as a significantly lower median HBV DNA level (P=0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China. -
Key words:
- Hepatitis B Virus /
- Hepatitis Delta Virus /
- Anti-HDV IgG /
- Genotype
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图 1 我国部分地区慢性HBV感染者HDV感染流行率
Figure 1. Prevalence rates of HDV infection among patients with chronic HBV infection in some areas of China
图 2 内蒙古地区抗-HDV IgG阳性和阴性慢性HBV感染者临床特征比较
Figure 2. Clinical characteristics of anti-HDV IgG positive and negative patients with chronic HBV infection in Inner Mongolia
表 1 内蒙古地区有明确诊断的720例各类慢性HBV感染者抗-HDV IgG阳性率
Table 1. The positive rate of anti-HDV IgG in 720 patients with chronic HBV infection with definite diagnosis in Inner Mongolia
临床诊断 例数 抗-HDV IgG阳性
[例(%)]HBsAg携带者 160 1(0.63) 慢性乙型肝炎 525 9(1.71) 乙型肝炎肝硬化 33 2(6.06) 肝癌 2 0(0.00) 合计 720 12(1.67) 
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表 2 抗-HDV IgG阳性和阴性慢性HBV感染者临床特征
Table 2. Clinical characteristics of anti-HDV IgG positive and negative patients with chronic HBV infection
临床特征 慢性HBV感染者 抗-HDV IgG阴性 抗-HDV IgG阳性 统计值 P值 男/女(例) 1 842/1 160
(n=3 002)1 830/1 150
(n=2 980)12/10
(n=22)χ2=0.434 0.510 年龄(岁) 47.00(37.00~56.00)
(n=2 996)47.00(37.00~56.00)
(n=2 974)46.00(40.75~54.00)
(n=22)Z=0.382 0.702 民族(汉/蒙古族/其他, 例) 2 037/134/135
(n=2 306)2 027/125/135
(n=2 287)10/9/0
(n=19)χ2=27.535 ＜0.001 临床诊断(慢性乙型肝炎合并肝硬化/肝癌, 例) 470/214
(n=2 826)467/214
(n=2 809)3/0
(n=17)χ2=1.203 0.719 抗病毒治疗史(有/无, 例) 1 212/490
(n=1 702)1 202/489
(n=1 691)10/1
(n=11)0.194 HBV DNA(log10 IU/mL) 2.00(1.30~3.43)
(n=2 762)2.00(1.30~3.43)
(n=2 740)1.48(1.48~2.95)
(n=22)Z=0.821 0.412 HBsAg阳性[例(%)] 2 741(97.79)
(n=2 803)2 721(97.77)
(n=2 783)20(100.00)
(n=20)＞0.05 HBeAg阳性[例(%)] 927(37.62)
(n=2 464)921(37.64)
(n=2 447)6(35.29)
(n=17)χ2=0.040 0.842 抗-HBc阳性[例(%)] 2 196(83.69)
(n=2 624)2 178(83.64)
(n=2 604)18(90.00)
(n=20)0.759 抗HCV阳性[例(%)] 19(1.03)
(n=1 842)19(1.04)
(n=1 826)0(0.00)
(n=16)＞0.05 抗HIV阳性[例(%)] 9(0.50)
(n=1 797)9(0.51)
(n=1 782)0(0.00)
(n=15)＞0.05 ALT(U/L) 25.08(17.00~39.20)
(n=2 851)25.00(17.00~39.00)
(n=2 831)26.04(14.98~50.63)
(n=20)Z=0.335 0.738 ALT＞40 U/L[例(%)] 686(24.06)
(n=2 851)678(23.95)
(n=2 831)8(40.00)
(n=20)0.113 AST(U/L) 26.00(20.00~38.00)
(n=2 838)26.00(20.00~38.00)
(n=2 818)24.69(20.83~36.50)
(n=20)Z=0.206 0.837 AST＞40 U/L[例(%)] 623(21.95)
(n=2 838)620(22.00)
(n=2 818)3(15.00)
(n=20)0.593 ALP(U/L) 78.00(63.0~99.00)
(n=2 573)78.00(63.00~99.00)
(n=2 555)75.05(64.00~94.58)
(n=18)Z=0.342 0.733 GGT(U/L) 26.00(16.00~44.00)
(n=2 577)26.00(16.00~44.00)
(n=2 559)24.63(12.75~50.50)
(n=18)Z=0.161 0.872 PLT(×109/L) 183.00(123.00~231.80)
(n=2 523)182.50(123.53~231.80)
(n=2 506)190.00(92.50~237.00)
(n=17)Z=0.348 0.728 TBil(μmol/L) 16.30(12.16~23.20)
(n=2 833)16.30(12.20~23.20)
(n=2 815)12.50(10.18~19.35)
(n=18)Z=1.753 0.080 AFP(ng/mL) 2.85(1.92~4.88)
(n=2 380)2.86(1.92 ~4.90)
(n=2 368)2.24(1.76 ~2.79)
(n=12)Z=1.959 0.050 注：n表示有数据患者的例数。
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