免疫抑制对HBV and HCV的影响

Impact of Immunosuppression on Viral Hepatitis B and C

W. Ray Kim*. Mayo Clinic College of Medicine， Rochester， MN，USA

Competent immune function is an important determinant of thenatural history of viral hepatitis as well as treatment response.Hepatitis B virus (HBV) is， in general， thought not to be cytopathic and the hepatic injury in patients with HBV infection is predominantly immune-related. However， it is well established that suppression of humoral and/or cellular immune function is detrimental in patients with chronic HBV infection. Although the pathogenesis of liver inflammation from hepatitis C virus (CV) infection is incompletely understood， abundant T cells aggregated in lymphoid infiltrates in portal areas are involved in the cytolysis of infected hepatocytes and fibrogenesis.

Common clinical circumstances in which immunosuppression affects viral hepatitis B and C include (1) chemotherapy for malignancies， (2) solid organ and bone marrow transplantation， and (3) human immunodeficiency virus (HIV) infection.

Reactivation of HBV in the setting of chemotherapy is best described in patients with lymphoma. Approximately 50% of HBsAg-positive patients develop a flare of hepatitis during or shortly after chemotherapy. In a number of studies， the fatality rate of HBV reactivation is reported to be higher than 10%. The frequency and severity of HBV reactivation may be influenced by the level and duration of immunosuppression as well as the host HBV factors， such as HBeAg status or serum HBV DNA levels. Because of these significant risks of reactivation， antiviral therapy is usually recommended in patients with HBV undergoing chemotherapy for malignancies. In a meta-analysis that investigated the role of lamivudine prophylaxis， patients who received lamivudine was at a much lower risk of developing HBV-related hepatic failure and dying from HBV-related causes. The impact of cancer chemotherapy on HCV is much less dramatic than on HBV.

For example， chemotherapy for breast cancer was found to be safe in women with HCV infection. Although HCV RNA level may increase in patients receiving rituximab therapy， adverse events related to HCV are much less frequent compared to HBV and no formal recommendation is made for screening or treatment for HCV prior to chemotherapy.

Liver transplantation has been a model with which to study the impact of immunosuppression in patients with viral hepatitis. In the absence of prophylaxis against HBV， reinfection of the graft is almost universal after liver transplantation in patients who are HBsAg-positive. It is now well established that reinfection of the graft can be effectively prevented by hepatitis B immune globulin and oral antiviral agents. Unfortunately， prevention of graft reinfection is not possible with HCV and the vast majority of liver transplant recipients do develop recurrent HCV infection.

Subsequently， progression of disease progression is more rapid in these patients receiving immunosuppression than in immune competent patients. Response to anti-HCV therapy is also reduced in liver transplant recipients. For other solid organ transplants， HBsAg-positive recipients face a high rate of reactivation of HBV. While some believe that HBV reactivation in these patients is not as detrimental as in liver transplant recipients， antiviral prophylaxis is usually recommended. Since interferon-based anti-HCV therapy is contraindicated in patients with renal or heart transplantation， careful selection of HCV-positive candidates is necessary including consideration of combined liver transplantation in patients with advanced liver disease.

HIV infection significantly affects the natural history of HBV and HCV. HIV coinfection increases the risk of cirrhosis in patients with HBV， although these patients tend to have lower ALT levels. More importantly， HIV-HBV co-infection increases liver-related mortality 17 times compared to HBV mono-infection. Similarly， the risk of cirrhosis is two fold increased in patients with HIV-HCV co-infection. Since the introduction of highly active antiretroviral therapy， HCV-related liver disease has become a major cause of morbidity and mortality in HIV infected patients. In the US， screening for HIV is recommended for all patients with HCV infection and HBV patients with risk factors. Individualized treatment decisions are necessary for optimal outcome in these patients.