Micas Florence, Suin Vanessa, Péron Jean-Marie, Scholtes Caroline, Tuaillon Edouard, Vanwolleghem Thomas, Bocket Laurence, Lhomme Sébastien, Dimeglio Chloé, Izopet Jacques, Abravanel Florence
Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France.
National Reference Centre of Hepatitis Viruses, Sciensano, Brussels, Belgium.
Front Microbiol. 2021 Apr 14;12:645020. doi: 10.3389/fmicb.2021.645020. eCollection 2021.
Hepatitis E virus (HEV) genotypes 3 and 4 are the major causes of acute hepatitis in industrialized countries. Genotype 3 is mainly found in Europe and America, while genotype 4 is predominant in Asia. Several Japanese studies have suggested that genotype 4 is more virulent than genotype 3. We investigated this aspect by analyzing the clinical and biological data for 27 French and Belgian immunocompetent patients infected with HEV genotype 4. Their infections were probably acquired locally, since none of these patients reported traveling outside France or Belgium during the 2-8 weeks before symptoms onset. Each patient was matched for age (±5 years) and gender with two patients infected with HEV genotype 3. Bivariate analysis indicated that the HEV genotype 4-infected patients had significantly higher alanine aminotransferase (ALT) (2067 IU/L) and aspartate aminotransferase (AST) (1581 IU/L) activities and total bilirubin concentrations (92.4 μmol/L) than did those infected with HEV genotype 3 (1566 IU/L, = 0.016; 657 IU/L, = 0.003 and 47 μmol/L, = 0.046) at diagnosis. In contrast, more patients infected with HEV genotype 3 reported dark urine (71% vs. 39%, = 0.02) and experienced asthenia (89% vs. 58%, < 0.01) than did those infected with HEV genotype 4. Two HEV genotype 4-infected patients died of multi-organ failure, while none of the genotype 3-infected patients died ( = 0.035). Finally, stepwise regression analysis retained only a greater increase in ALT (odds-ratio: 1.0005, 95% confidence interval: 1.00012-1.00084) and less frequent fever (odds-ratio = 0.1244; 95% confidence interval: 0.01887-0.82020) for patients infected with HEV genotype 4. We conclude that HEV-4 infections are likely to be associated with higher ALT activity than HEV-3 infections. Additional immunological and virological studies are required to confirm these findings and better understand the influence, if any, of genotype on HEV pathophysiology.
戊型肝炎病毒（HEV）3型和4型是工业化国家急性肝炎的主要病因。3型主要在欧美发现，而4型在亚洲占主导。多项日本研究表明，4型比3型的毒性更强。我们通过分析27例感染HEV 4型的法国和比利时免疫功能正常患者的临床和生物学数据来研究这一方面。他们的感染可能是在当地获得的，因为这些患者在症状出现前的2 - 8周内均未报告有法国或比利时境外旅行史。将每位感染HEV 4型的患者按年龄（±5岁）和性别与两名感染HEV 3型的患者进行匹配。双变量分析表明，感染HEV 4型的患者在诊断时的丙氨酸转氨酶（ALT）（2067 IU/L）、天冬氨酸转氨酶（AST）（1581 IU/L）活性和总胆红素浓度（92.4 μmol/L）显著高于感染HEV 3型的患者（分别为1566 IU/L，P = 0.016；657 IU/L，P = 0.003；47 μmol/L，P = 0.046）。相比之下，感染HEV 3型的患者中报告尿色深的更多（71% 对39%，P = 0.02），且出现乏力的更多（89% 对58%，P < 0.01）。两名感染HEV 4型的患者死于多器官功能衰竭，而感染3型的患者均未死亡（P = 0.035）。最后，逐步回归分析仅保留了感染HEV 4型患者ALT升高幅度更大（优势比：1.0005，95%置信区间：1.00012 - 1.00084）和发热频率更低（优势比 = 0.1244；95%置信区间：0.01887 - 0.82020）这两个因素。我们得出结论，HEV - 4感染可能比HEV - 3感染与更高的ALT活性相关。需要进一步的免疫学和病毒学研究来证实这些发现，并更好地理解基因型对HEV病理生理学的影响（如果有影响的话）。
