SARS‐associated viral hepatitis caused by a novel coronavirus: Report of three cases

Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of...

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Published in:	Hepatology (Baltimore, Md.) Md.), 2004-02, Vol.39 (2), p.302-310
Main Authors:	Chau, Tai‐Nin, Lee, Kam‐Cheong, Yao, Hung, Tsang, Tak‐Yin, Chow, Tat‐Chong, Yeung, Yiu‐Cheong, Choi, Kin‐Wing, Tso, Yuk‐Keung, Lau, Terence, Lai, Sik‐To, Lai, Ching‐Lung
Format:	Article
Language:	eng
Subjects:	Adult Anti-Inflammatory Agents - therapeutic use Apoptosis Biological and medical sciences Biopsy Coronavirus - genetics Coronavirus - isolation & purification DNA, Viral - analysis Drug Combinations Female Gastroenterology. Liver. Pancreas. Abdomen Hepatitis, Viral, Human - drug therapy Hepatitis, Viral, Human - pathology Hepatitis, Viral, Human - virology HIV Protease Inhibitors - therapeutic use Human viral diseases Humans Infectious diseases Liver - pathology Liver - virology Lopinavir Medical sciences Methylprednisolone - therapeutic use Middle Aged Mitosis Pyrimidinones - therapeutic use Ritonavir - therapeutic use Severe Acute Respiratory Syndrome - complications Severe Acute Respiratory Syndrome - drug therapy Severe Acute Respiratory Syndrome - pathology Viral diseases Viral diseases of the respiratory system and ent viral diseases Viral Hepatitis
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Summary:	Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) using enhanced real‐time PCR was applied to look for evidence of SARS‐associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki‐67. RT‐PCR showed evidence of SARS‐associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro‐ or macro‐vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS‐associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course. (HEPATOLOGY 2004;39:302–310.)
ISSN:	0270-9139 1527-3350