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.

Acute Liver Failure Associated with Influenza A Virus Infection: an Autopsy Case Report

“…However, drug involvement was less likely in this case, as the proportion of eosinophils was not elevated and no typical histologic al findings of a druginduced liver injury, such as cholestasis, were observed. The typical histological characteristic of hypoxic hepatitis is centrilobular hepatocyte necrosis without prominent inflammation (3,8), which is consistent with the findings in this case.…”

Influenza A virus infection induces liver injury in mice

“…Further study found that Kupffer cells and apoptotic hepatocytes mediated inflammatory injury [18]. Hypoxic hepatitis was a clinical characteristic in the H7N9 infection [9]. Recent data further confirmed that hypoxic hepatitis can be an important causative factor for acute liver failure associated with influenza virus infection instead of virus related hepatitis [19].…”

“…A novel pandemic 2009 influenza A ⁄ H1N1 different from the seasonal influenza infection induced hepatocellular injury with increased serum aminotransaminase levels [6,7]. When humans are infected with H7N9, hypoxic and fatty changes in the liver tissue have been observed [8,9]. Moreover, in advanced chronic liver disease, diseases caused by the common bacteria Streptococcus pneumoniae or influenza virus increased the risk for serious health complications and death [10].…”

Impacts of age and gender at the risk of underlying medical conditions and death in patients with avian influenza A (H7N9): a meta-analysis study

“… 2 Although previous studies have shown that H7N9 infection is often accompanied by multiple chronic conditions (hypertension, diabetes, chronic bronchitis, etc. ), 3 – 6 the most recent H7N9 epidemic seems to reveal a different increased risk of death in elderly patients with particular chronic underlying medical conditions (UMCs). 3 , 6 , 7 …”

“…), 3 – 6 the most recent H7N9 epidemic seems to reveal a different increased risk of death in elderly patients with particular chronic underlying medical conditions (UMCs). 3 , 6 , 7 …”