Researchers at the University of Pennsylvania have demonstrated that morphine withdrawal complicates hepatitis C by suppressing IFN-alpha-mediated immunity and enhancing virus replication.
The paper by Wang et al., “Morphine withdrawal enhances hepatitis C virus (HCV) replicon expression,” appears in the November issue of The American Journal of Pathology and is accompanied by a commentary.
Hepatitis C virus (HCV) is common among intravenous drug users, with 70 to 80% of abusers infected in the United States. This high association has peaked interest in determining the effects of drug abuse, specifically opiates, on progression of the disease. The discovery of such an association would impact treatment of both HCV infection and drug abuse.
Dr. Wen-Zhe Ho has been interested in such interplay for some time. His laboratory has previously shown using cell culture that morphine enhances virus replication and inhibits IFN-alpha (a natural anti-viral factor produced by immune, as well as host cells, and the only one approved in recombinant form for treating HCV infection). To further these results, his lab has used a cell model system to determine the consequences of morphine withdrawal, which is a common recurring event in opioid users.
Chuan-Qing Wang and colleagues examined the effects of morphine withdrawal (MW) on HCV-infected cultured liver cells by exposing cells to the drug for four days followed by its removal. They also assessed the effects of using naloxone, to block the opioid receptors, in conjunction with drug removal, i.e. precipitated morphine withdrawal (PW). To measure HCV replication, they used a virus-like “replicon” that mimics the events that occur in liver cells and expression of viral RNA and proteins that HCV uses. Although the replicon does not produce the infectious virus, the HCV replicon system represents the best available system for examining the impact of opiates on HCV at the time of their research study.
Similar to their previous results, the authors found that MW and PW increased levels of HCV replicon RNA and protein expression. In addition, both withdrawal scenarios inhibited IFN-alpha expression in liver cells in the presence or absence of HCV replicon. Since IFN-alpha is a critical self-defense mechanism utilized by liver cells to fight off viral infection, including HIV, this study suggests that morphine withdrawal weakens host cell immunity and provides a favorable environment for HCV growth in the liver.