Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 2000; 6(6): 805-811
Published online Dec 15, 2000. doi: 10.3748/wjg.v6.i6.805
Hepatitis C virus may infect extrahepatic tissues in patients with hepatitis C
Fu Ming Yan, An Shen Chen, Fei Hao, Xi Ping Zhao, Chang Hai Gu, Li Bin Zhao, Dong Liang Yang, Lian Jie Hao
Fu Ming Yan, An Shen Chen, Li Bin Zhao, Department of Infectious Diseases, the 161st Central Hospital of Chinese PLA, Wuhan 430010, Hubei Province, China
Fei Hao, Chang Hai Gu, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
Xi Ping Zhao, Dong Liang Yang, Lian Jie Hao, Division of Clinical Immunology, Tongji Hospital, Tongji Medical University, Wuhan, Hubei Province, China
Fu Ming Yan, graduated from Hubei Medical University in 1983 and got master degree from Third Military Medical University in 1997, now an associate chief physician, specialized research on the pantropism of HCV infection, having more than 10 papers published.
Author contributions: All authors contributed equally to the work.
Supported by the Medical and Health Sciences Foundation of Chinese PLA, No.98D066
Correspondence to: Dr. Fu Ming Yan, Department of Infectious Diseases, the 161st Central Hospital of Chinese PLA, Wuhan 430010, Hubei Province, China. Email: ljhao@tjh.tjmu.edu.cn
Telephone: +86-27-82903100 Ext.2424
Received: February 24, 2000
Revised: July 19, 2000
Accepted: July 31, 2000
Published online: December 15, 2000

AIM: To explore the status of extrahepatic hepatitis C virus (HCV) infection and replication in hepatitis C patients, and its potential implication in HCV infection and pathogenicity.

METHODS: By reverse-transcriptase poly-merase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry, HCV RNA, HCV replicative intermediate (minus-strand of HCV RNA), and HCV antigens were detected in 38 autopsy extrahepatic tissue specimens (including 9 kidneys, 9 hearts, 9 pancreas, 5 intestines, 2 adrenal glands, 2 spleens, 1 lymph node, and 1 gallbladder) from 9 hepatitis C patients, respectively; and the status of HCV replication in extrahepatic tissues was studied.

RESULTS: By RT-PCR, all 9 patients were positive for HCV RNA in kidney, heart, pancreas, and intestine, but only 6 (66.7%) patients were positive for HCV replicative intermediate. HCV RNA and HCV antigens were detected in kidney, heart, pancreas, intestine, adrenal gland, lymph node, and gallbladder in 5 (55.6%) and 6 (66.7%) patients by ISH and immunohistochemistry, respectively. HCV RNA and HCV antigens were not detected in these extrahepatic organs in 3 (33.3%) patients, although their livers were positive for HCV. HCV replicative intermediate detected by RT-PCR was consistent with HCV RNA and HCV antigens detected by ISH and immunohistochemistry (Kappa = 0.42-0.75). HCV RNA and HCV antigens were detected in myocardial cells, epithelial cells of intestinal gladular, interstitial cells of kidney, epithelial cells of tubules and glomerulus, pancreas acinar cells and epithelial cells of pancreatic duct, epithelial cells of mucous membrane sinus of gallbladder, cortex and medulla cells in adrenal gland, and mononuclear cells in lymph node. HCV RNA was also detected in bile duct epithelial cells, sinusoidal cells, and mononuclear cells in liver tissues by ISH.

CONCLUSION: HCV can infect extrahepatic tissues, and many various tissue cells may support HCV replication; extrahepatic HCV infection and replication may be of “concomitant state” in most of patients with hepati tis C. The infected extrahepatic tissues might act as a reservoir for HCV, and play a role in both HCV persistence and reactivation of infection. HCV as an etiologic agent replicating and expressing viral proteins in extrahepatic tissues itself contributes to extrahepatic syndrome associated-HCV infection in a few patients with chronic HCV infection.

Keywords: hepatitis C virus, hepatitis C antigens, in situ hybridization, immunohistochemistry, RNA, polymerase chain reaction, antibodies, monoclonal, digoxigenin