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[图瓦共和国作为地方性流行区慢性丁型病毒性肝炎患者的临床病程及结局]

[Clinical course and outcomes of chronic viral hepatitis D in patients from Republic of Tuva as endemic region].

作者信息

Isaeva O V, Il'chenko L Yu, Saryglar A A, Karlsen A A, Kyuregyan K K, Mikhailov M I

机构信息

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBEI FPE Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia.

FSBSI I.I. Mechnikov Research Institute of Vaccines and Sera; FSBSI M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences; FSAEI HE N.I. Pirogov Russian Research Medical University of the Ministry of Health of Russia.

出版信息

Vopr Virusol. 2021 Mar 7;66(1):74-83. doi: 10.36233/0507-4088-29.

DOI:10.36233/0507-4088-29
PMID:33683068
Abstract

INTRODUCTION

Hepatitis D (delta, 5) is caused by an RNA virus (hepatitis D virus, HDV) from genus Deltavirus, and is the most severe and difficult to treat disease among both viral hepatitis and infectious diseases in general. The development of HDV infection in the host organism is possible only in the presence of hepatitis B virus (HBV). Coinfection with HBV and HDV is associated with a more rapid progression of chronic viral hepatitis (CVH) to liver cirrhosis (LC) and an unfavorable outcome in comparison with HBV monoinfection. Data on the influence of clinical, biochemical and virological factors on the infectious process in patients with hepatitis D are limited due to the insufficient amount of research on this theme.The study aimed to determine demographic, clinical, biochemical, and virological factors influencing the course and progression of CVH D in patients followed during 10 years, residing in the territory of the Tuva Republic, one of the endemic regions of the Russian Federation.

MATERIAL AND METHODS

Changes in clinical and laboratory parameters were analyzed in dynamics in 121 HDV infected patients with a different course of the disease, who were under observation from 2009 to 2019. Three groups of patients were identified: group 1 - 61 patients with disease progression of chronic hepatitis to LC (Child-Pugh class B-C), group 2 - 49 patients with non-progressive chronic hepatitis, and group 3 - 11 patients with slowly progressive LC (class A). Demographic data, the presence of detectable HBV DNA, indicators of the functional state of the liver: alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total bilirubin content were analyzed. The severity of hepatic encephalopathy was assessed by the duration of the numbers connection test (NCT).

RESULTS

All patients belonged to the same ethnic group (Tuvinians), were infected with HDV genotype 1 and were positive for HDV RNA throughout the entire follow-up period. There were no significant differences in sex ratio and mean age at the time of inclusion in the study between the groups. In group 1, the average number of years from inclusion in the study to the formation of LC was 3.65 ± 2.3 years, years to the lethal outcome: 4.5 ± 3 years. Significantly higher levels of AST/GOT, ALP, GGT, total bilirubin (TB) and NCT grade were found in group 1 compared to group 2. ALT/GPT levels did not differ significantly in these groups. When comparing groups with disease progression and slowly progressive LC (groups 1 and 3), no significant differences were found in any of the clinical and biochemical parameters. ALT/GPT, GGT, TB and NCT values were significantly higher in patients with slowly progressive LC (group 3) compared to group 2. No differences in AST/GOT and ALP levels were found between these groups. Detectable HBV DNA was significantly more frequent in patients with progressive disease and with chronic viral hepatitis than in patients with slowly progressive LC. There were no significant differences in the frequency of HBV DNA detection in patients from groups 1 and 2.

CONCLUSION

The results obtained on a relatively homogeneous cohort demonstrated that age and gender are not the factors influencing the progression of chronic viral hepatitis D to cirrhosis. The lack of detectable HBV DNA is associated with the slow progression of LC. The revealed differences in clinical and biochemical parameters reflect the degree of functional liver damage in chronic viral hepatitis D and HDV-associated cirrhosis.

摘要

引言

丁型肝炎(δ型肝炎,5型肝炎)由丁型肝炎病毒(HDV)引起,HDV属于δ病毒属,是病毒性肝炎乃至所有传染病中最严重且最难治疗的疾病。HDV感染在宿主体内的发展只有在乙型肝炎病毒(HBV)存在的情况下才有可能。与单纯HBV感染相比,HBV和HDV合并感染会使慢性病毒性肝炎(CVH)更快发展为肝硬化(LC),且预后不良。由于关于这一主题的研究数量不足,临床、生化和病毒学因素对丁型肝炎患者感染过程影响的数据有限。本研究旨在确定居住在俄罗斯联邦地方性流行地区之一图瓦共和国境内、随访10年的CVH D患者中,影响疾病进程和进展的人口统计学、临床、生化和病毒学因素。

材料与方法

对2009年至2019年期间接受观察的121例病情不同的HDV感染患者的临床和实验室参数变化进行动态分析。确定了三组患者:第1组 - 61例慢性肝炎进展为LC(Child-Pugh B - C级)的患者,第2组 - 49例非进展性慢性肝炎患者,第3组 - 11例缓慢进展性LC(A级)患者。分析了人口统计学数据、可检测到的HBV DNA的存在情况、肝脏功能状态指标:丙氨酸氨基转移酶(ALT/GPT)、天冬氨酸氨基转移酶(AST/GOT)、碱性磷酸酶(ALP)、γ-谷氨酰转移酶(GGT)以及总胆红素含量。通过数字连接试验(NCT)的持续时间评估肝性脑病的严重程度。

结果

所有患者属于同一民族(图瓦人),感染HDV 1基因型,且在整个随访期间HDV RNA均呈阳性。各组之间纳入研究时的性别比例和平均年龄无显著差异。在第1组中,从纳入研究到形成LC的平均年数为3.65±2.3年,至死亡结局的年数为4.5±3年。与第2组相比,第1组中AST/GOT、ALP、GGT、总胆红素(TB)水平和NCT分级显著更高。这些组中的ALT/GPT水平无显著差异。在比较疾病进展组和缓慢进展性LC组(第1组和第3组)时,任何临床和生化参数均未发现显著差异。与第2组相比,缓慢进展性LC患者(第3组)的ALT/GPT、GGT、TB和NCT值显著更高。这些组之间在AST/GOT和ALP水平上未发现差异。进展性疾病和慢性病毒性肝炎患者中可检测到的HBV DNA明显比缓慢进展性LC患者更常见。第1组和第2组患者中HBV DNA检测频率无显著差异。

结论

在相对同质的队列中获得的结果表明,年龄和性别不是影响慢性丁型病毒性肝炎发展为肝硬化的因素。未检测到HBV DNA与LC的缓慢进展相关。所揭示的临床和生化参数差异反映了慢性丁型病毒性肝炎和HDV相关肝硬化中肝脏功能损害的程度。

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