AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was assoc...AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P<0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.展开更多
Chronic hepatitis C virus(HCV) infection can cause liver cirrhosis and hepatocellular carcinoma(HCC). Several studies have demonstrated that the eradication of HCV reduces the occurrence of HCC. In Japan, as many peop...Chronic hepatitis C virus(HCV) infection can cause liver cirrhosis and hepatocellular carcinoma(HCC). Several studies have demonstrated that the eradication of HCV reduces the occurrence of HCC. In Japan, as many people live to an advanced age, HCV-infected patients are also getting older, and the age at HCC diagnosis has also increased. Although older HCV-infected patients have a risk of developing HCC, the treatment response to peginterferon-alpha plus ribavirin therapy is relatively poor in these patients because of drop-out or discontinuation of this treatment due to adverse events. It is established that the mechanism of action between interferon-alpha and interferon-beta is slightly different. Short-term natural interferon-beta monotherapy is effective for patients with acute hepatitis C and patients infected with HCV genotype 2 and low viral loads. Natural interferon-beta plus ribavirin for 48 wk or for 24 wk are also effective for some patients with HCV genotype 1 or HCV genotype 2. Natural interferon-beta plus ribavirin has been used for certain "difficult-totreat" HCV-infected patients. In the era of direct-acting anti-virals, natural interferon-beta plus ribavirin may be one of the therapeutic options for special groups of HCV-infected patients. In the near future, signal transduction pathways of interferon-beta will inform further directions.展开更多
文摘AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P<0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.
文摘Chronic hepatitis C virus(HCV) infection can cause liver cirrhosis and hepatocellular carcinoma(HCC). Several studies have demonstrated that the eradication of HCV reduces the occurrence of HCC. In Japan, as many people live to an advanced age, HCV-infected patients are also getting older, and the age at HCC diagnosis has also increased. Although older HCV-infected patients have a risk of developing HCC, the treatment response to peginterferon-alpha plus ribavirin therapy is relatively poor in these patients because of drop-out or discontinuation of this treatment due to adverse events. It is established that the mechanism of action between interferon-alpha and interferon-beta is slightly different. Short-term natural interferon-beta monotherapy is effective for patients with acute hepatitis C and patients infected with HCV genotype 2 and low viral loads. Natural interferon-beta plus ribavirin for 48 wk or for 24 wk are also effective for some patients with HCV genotype 1 or HCV genotype 2. Natural interferon-beta plus ribavirin has been used for certain "difficult-totreat" HCV-infected patients. In the era of direct-acting anti-virals, natural interferon-beta plus ribavirin may be one of the therapeutic options for special groups of HCV-infected patients. In the near future, signal transduction pathways of interferon-beta will inform further directions.
