BACKGROUND AIMS Acute infection of hepatitis E virus (HEV) causes varying degrees of liver damage. Although liver-related death due strictly to HEV infection is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic hepatitis B virus (HBV) infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC). METHODS Serum and data were collected from two independent retrospective cohorts of patients with chronic HBV infection, comprising 2123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrollment and HEV superinfection was defined by the presence of HEV-IgG seroconversion. RESULTS In the non-cirrhotic cohort, 46 of 2123 patients developed HEV superinfection. Though HEV superinfection was associated with increased incidence of liver-related death only in the overall cohort, it was a risk factor for all three endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than those without (50% vs. 2.8%, P=0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n=414) were further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, P< 0.001). CONCLUSIONS In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in cirrhosis patients.

中文翻译：

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HEV重复感染加速慢性HBV感染患者的疾病进展并增加肝硬化患者的死亡率

背景 目的 戊型肝炎病毒 (HEV) 的急性感染会导致不同程度的肝损伤。尽管严格由 HEV 感染导致的肝脏相关死亡在健康个体中很少见，但尚不清楚 HEV 重复感染是否与慢性乙型肝炎病毒 (HBV) 感染患者的较差结局相关。因此，我们探讨了 HEV 重复感染是否与肝脏相关死亡、肝硬化和肝细胞癌 (HCC) 的发生率增加有关。方法 从慢性 HBV 感染患者的两个独立回顾性队列中收集血清和数据，分别包括 2123 名无肝硬化患者和 414 名基线肝硬化患者。所有患者在入组时 HEV-IgG 均呈阴性，HEV 重复感染定义为存在 HEV-IgG 血清学转换。结果 在非肝硬化队列中，2123 名患者中有 46 名发生 HEV 双重感染。尽管 HEV 重复感染仅在整个队列中与肝脏相关死亡的发生率增加有关，但在 723 名 HBeAg 阴性慢性乙型肝炎患者亚组中，它是所有三个终点（肝脏相关死亡、肝硬化和 HCC）的危险因素。乙肝病毒感染。此外，在随访期间发生肝硬化的 4 名患者在 HEV 双重感染后的 1 年死亡率高于未发生肝硬化的患者（50% vs. 2.8%，P=0.001）。为了阐明 HEV 双重感染与死亡风险之间的感知关系，进一步分析了一个独立的肝硬化患者队列（n=414），以控制因肝硬化而导致的死亡风险的固有增加。10 例 HEV 重复感染的肝硬化患者的 1 年死亡率高于未感染的肝硬化患者（30% vs. 0%，P<0.001）。结论 在两个慢性 HBV 感染患者队列中，急性 HEV 重复感染增加了肝脏相关死亡的风险，尤其是在肝硬化患者中。