title: Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit.
abstract: Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%-2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: YiMin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton L8S 4L8 ON, Canada.|Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: JiMin
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: ShuFa
authors.initials: S
authors.lastname: Zheng
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Shi
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: LanJuan
authors.initials: L
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015687:Cell Hypoxia; D005260:Female; D006505:Hepatitis / Q000150:complications* / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000472:pathogenicity; D007251:Influenza, Human / Q000150:complications* / Q000401:mortality / Q000628:therapy / Q000821:virology; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008099:Liver / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase