5.2  MERS-CoV-liver injury
The patients infected by MERS-CoV were also presented with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels above normal. Besides the elevated liver enzymes, the albumin levels were decreased, which serves as an indicator of the severity of the disease [[67], [68], [69]]. The MERS-CoV enters the host cell through the DPP-4 receptor and spreads the infection [70]. The liver is the main organ that expresses high levels of Dipeptidyl peptidase 4 (DPP-4) [71]. This was experimentally proved by infecting the transgenic mice expressing hDPP4 with MERS-CoV which indicated that the liver injury had taken place on the 5th day of the infection as evidenced by the pathological manifestations such as disintegrated death of hepatocytes in the hepatic sinus, penetration of large amounts of activated macrophages and Kupffer cells. The changes related to fat metabolism were observed on the 9th day of infection, and the liver cell necrosis was quite less [72] (represented in Table 1).
The histopathological findings of the hepatic tissue during MERS-CoV infection include infiltration of lobular lymphocytes, mild cellular hydropic degeneration in hepatic parenchyma, and mild portal tract [73,74]. During the acute phase of infection, the levels of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-17, and IL-15 were significantly elevated [75]. But the question of whether liver injury initiated is due to the viral-mediated pathogenesis or due to the drugs that have been used during the viral infection remains elusive [37].