A Report on the Death of Mixed Infection of HEV and HBV

Mixed infection with hepatitis E virus (HEV) in patients with chronic hepatitis B virus (HBV) infection is frequent. HEV mixed infection often leads to activation of hepatic pathological changes and worsens the inflammatory activity. However, it is not known clearly how these two types of virus influence each other in human body. Intensive investigation has revealed that HEV mixed infection inhibits HBV replication. We have just encountered a relative rare case. The patient who was a HBV carrier and was infected by HEV. Before he was infected by the HEV, the measurement of his HBV DNA fixed quantity examination on fluorescence was <103 copies/ml; his routine biochemistry was normal; and his anti HEV-IgM and anti-HEV-IgG appeared to be negative reaction. After he was infected by HEV, his routine biochemistry increased, and the measurement of his HBV DNA fixed quantity examination on fluorescence was 8.51 × 105 copies/ml. It indicated that the replication of HBV was activated after the patient infected HEV. Finally, he was dead. This case revealed that HEV mixed infection may activate the replication of HBV, not inhibit HBV replication, and demonstrated the needs for further studies about the mechanism of the interaction of the two viruses.


Introduction
Mixed infection with hepatitis E virus (HEV) occurred in patients with chronic hepatitis B virus (HBV) infection is frequent [1]- [18].It often leads to activation of hepatic pathological changes and worsens the inflammatory activity [1] [2], causes severe liver decompensation, which is frequently complicated with hepatic encephalopathy and renal failure.Acute hepatitis E in these patients has a protracted course with high morbidity and mortality [3].However, it is not known clearly how these two types of virus influence each other in human body.Intensive investigation has revealed that HEV mixed infection inhibits HBV replication [1] [4]- [6].
Whereas, we encountered a relatively rare case.The patient had a acute HEV infection, who has been a HBV carrier for 20 years.The replication of HBV was activated remarkably after the patient infected HEV.

Case Report
The patient was 46 years old.20 years ago, his HBsAg, HBeAb and HBcAb all appeared to be positive reaction without any relevant symptoms.He was diagnosed by the local physician as "hepatitis B" and was occasionally treated with the help of some liver-protecting medicine.He had no record of drinking, injury, operation, blood transfusion, or other infectious diseases, but had a 20-year-smoking history.Before he was infected by the HEV, the measurement of his HBV DNA fixed quantity examination on fluorescence was <10 3 copies/ml; his routine biochemistry was normal; and his anti HEV-IgM and anti-HEV-IgG appeared to be negative reaction.
On the 29th of December, the patient had the symptoms of sudden weakness, anorexia, fever and icterus.Physical examination on admission results are as following: body temperature 38.1˚C; pulse 72/minute; blood pressure 120/80 mmHg; no abnormal evidence shown in neck artery and vein; soft abdomen; no pressed pain and no rebounding pain of the upper part of the side; touched appendix ensiformis to 3.0 cm with slippery surface, side parts and slight pressed pain; Murphy's sign appeared negative reaction; throbbing pain in liver area.
He was diagnosed as acute HEV infection based on the symptom and the laboratory test results.
It showed a large-area necrosis on the liver of the patient through transoesophageal echocardiography (Figure 1).Since the patient experienced the attack, we carried out the examination of HEV RNA in blood serum and excrement, and found that the HEV RNA appeared to be positive reaction.Subsequently, we sequenced the partial HEV gene, and analysised it by alignment and phylogenetic analysis.It showed that the HEV in blood serum and excrement of the patient belonged to the genotype IV.The homology with JYI-ChiSai01C, which is a HEV genotype IV strain, was 92.5%.The homology with the other genotype IV strains was above 85% (Figure 2 and Figure 3).The nucleotide homology analysed by Clustal W. The homology with JYI-ChiSai01C, which is a HEV genotype IV strain, was 92.5%.The homology with the other genotype IV strains was above 85.0%.The homology with the other genotype was below 80.0%.After the patient was hospitalized, we took the anti-viral, decreasing ferment and jaundice measures.However, there was no significant improvement, so the patient was transferred to another hospital and received continuous treatment there with still no improvement.The patient died on the 11th day after he was transferred.

Discussion
Mixed infection with hepatitis E virus (HEV) occurred in patients with chronic hepatitis B virus (HBV) infection is frequent [1]- [18].It often leads to patients has a protracted course with high morbidity and mortality [3].
Nowadays, Intensive investigation has revealed that HEV mixed infection inhibits HBV replication [1] [4]- [6].At the same time, some researchers think that HEV infection may activate the replication of HBV [8].However these finding mainly based on the epidemiology.
As we reported, the patient's HBV DNA was <10 3 copies/ml before he was infected by HEV, but after the infection, his HBV DNA reached 8.51 × 10 5 copies/ml along with other biochemical higher quota.It suggested that the patient died as a result of the HBV in his body being activated after he acquired HEV, which caused the large-area necrosis in his liver.This case revealed that HEV mixed infection may activate the replication of HBV, not inhibits HBV replication.However, the questions are required to be further studied, such as how HEV activates HBV, and what the vital mechanism is between the superinfection of HEV and HBV.

Figure 1 .
Figure 1.Transoesophageal echocardiography of the liver of the patient.It showed a large-area necrosis.

Figure 3 .
Figure 3.Nucleotide homology analysis between the HEV isolated from the patient and the other HEV.The nucleotide homology analysed by Clustal W. The homology with JYI-ChiSai01C, which is a HEV genotype IV strain, was 92.5%.The homology with the other genotype IV strains was above 85.0%.The homology with the other genotype was below 80.0%.

Table 1 .
Laboratory results of the 46-year-old man.

Table 2 .
Blood clotting system test.