AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepa...AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation （OLT） before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-γ and TNF-α in culture supematants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS： The levels of INF-γ and TNF-α in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns （INF-γ 155.52±72.32 ng/L vs 14.76±9.88 ng/L vs 13.22±10.35 ng/L, F= 6.946, P= 0.027〈0.05; TNF-α 80.839±46.75 ng/L vs18.59±17.29 ng/L vs9.758±7.96 ng/L, F= 22.61, P = 0.0001〈0.05）. The levels of INF-γ and TNF-α were higher in groups with phytohemagglutinin （PHA） than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-γ and TNF-α could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated （HBV detected rate： 51.4%, 13.3%, 50% respectively; HBV DNA： 3.55±0.674 log（10） copies/mL vs 3.00±0.329 log（10） copies/mL vs 4.608±1.344 log（10） copies/mL, F= 7.582, P= 0.002〈0.05）. HBV DNA in serum was 4.48±1.463 log（10） copies/mL before surgery and 〈 10^3 copies/mL after OLT except for one with 5.72×10^6 copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-γ and TNF-α were lower in patients with a high HBV load than in those with a low HBV load （HBV DNA detected/undetected in PBMCs： IFN-γ 138.08±72.44 ng/L vs 164.24±72.07 ng/L, t = 1.065, P= 0.297〉0.05, TNF-α 80.75±47.30 ng/L vs 74.10±49.70 ng/L, t= 0.407, P= 0.686〉 0.05; HBV DNA positive/negative： IFN-γ 136.77±70.04 ng/L vs 175.27±71.50 ng/L, t= 1.702, P= 0.097〉0.05; TNF-α 75.37±43.02 ng/L vs 81.53±52.46 ng/L, t = 0.402, P = 0.690〉0.05）. CONCLUSION： The yielding of INF-γ and TNF-α from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.展开更多
Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response....Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus （HCV） infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome.展开更多
AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B ...AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0.0002 and P = 0.001, respectively), but no association with IL28 B haplotype was observed.CONCLUSION IL28 B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.展开更多
AIM: To evaluate the efficacy of amantadine plus interferonalpha and ribavirin in non-responder patients with chronic hepatitis C.METHODS: Twenty-six non-responder patients received the regimen of IFN-α-2a at a dose ...AIM: To evaluate the efficacy of amantadine plus interferonalpha and ribavirin in non-responder patients with chronic hepatitis C.METHODS: Twenty-six non-responder patients received the regimen of IFN-α-2a at a dose of 6 million units three times a week, 1 000-1 200 mg of ribavirin daily, and 200 mg of amantadine daily in divided doses over 48 wk. After the end of treatment, at the 72nd wk, a sustained viral response rate was determined.RESULTS: An early (after 12 wk of therapy) response was seen in 34.6% (9/26) of patients. Response rate at the 24th wk was 42.3% (11/26). End of treatment response (ETR) was 53.8% (14/26). Sustained viral response (SVR) was 42.3% (11/26). There was a statistically significant difference between 0 and 12 wk (P = 0.04), 0 and 24 wk (P = 0.01), 0 and 48 wk (P = 0.00), and 0 and 72 wk (P = 0.001). No patient had severe adverse effects during the treatment.CONCLUSION: Combination regimen of interferon-α,ribavirin and amantadine can enhance sustained viral response on IFN-α and ribavirin non-responder patients with HCV. Triple therapy with amantadine should be evaluated in further studies.展开更多
基金Supported by the Technology Program of Guangdong Province, No. 2004B35001001
文摘AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation （OLT） before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-γ and TNF-α in culture supematants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS： The levels of INF-γ and TNF-α in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns （INF-γ 155.52±72.32 ng/L vs 14.76±9.88 ng/L vs 13.22±10.35 ng/L, F= 6.946, P= 0.027〈0.05; TNF-α 80.839±46.75 ng/L vs18.59±17.29 ng/L vs9.758±7.96 ng/L, F= 22.61, P = 0.0001〈0.05）. The levels of INF-γ and TNF-α were higher in groups with phytohemagglutinin （PHA） than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-γ and TNF-α could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated （HBV detected rate： 51.4%, 13.3%, 50% respectively; HBV DNA： 3.55±0.674 log（10） copies/mL vs 3.00±0.329 log（10） copies/mL vs 4.608±1.344 log（10） copies/mL, F= 7.582, P= 0.002〈0.05）. HBV DNA in serum was 4.48±1.463 log（10） copies/mL before surgery and 〈 10^3 copies/mL after OLT except for one with 5.72×10^6 copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-γ and TNF-α were lower in patients with a high HBV load than in those with a low HBV load （HBV DNA detected/undetected in PBMCs： IFN-γ 138.08±72.44 ng/L vs 164.24±72.07 ng/L, t = 1.065, P= 0.297〉0.05, TNF-α 80.75±47.30 ng/L vs 74.10±49.70 ng/L, t= 0.407, P= 0.686〉 0.05; HBV DNA positive/negative： IFN-γ 136.77±70.04 ng/L vs 175.27±71.50 ng/L, t= 1.702, P= 0.097〉0.05; TNF-α 75.37±43.02 ng/L vs 81.53±52.46 ng/L, t = 0.402, P = 0.690〉0.05）. CONCLUSION： The yielding of INF-γ and TNF-α from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.
文摘Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus （HCV） infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome.
文摘AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0.0002 and P = 0.001, respectively), but no association with IL28 B haplotype was observed.CONCLUSION IL28 B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.
文摘AIM: To evaluate the efficacy of amantadine plus interferonalpha and ribavirin in non-responder patients with chronic hepatitis C.METHODS: Twenty-six non-responder patients received the regimen of IFN-α-2a at a dose of 6 million units three times a week, 1 000-1 200 mg of ribavirin daily, and 200 mg of amantadine daily in divided doses over 48 wk. After the end of treatment, at the 72nd wk, a sustained viral response rate was determined.RESULTS: An early (after 12 wk of therapy) response was seen in 34.6% (9/26) of patients. Response rate at the 24th wk was 42.3% (11/26). End of treatment response (ETR) was 53.8% (14/26). Sustained viral response (SVR) was 42.3% (11/26). There was a statistically significant difference between 0 and 12 wk (P = 0.04), 0 and 24 wk (P = 0.01), 0 and 48 wk (P = 0.00), and 0 and 72 wk (P = 0.001). No patient had severe adverse effects during the treatment.CONCLUSION: Combination regimen of interferon-α,ribavirin and amantadine can enhance sustained viral response on IFN-α and ribavirin non-responder patients with HCV. Triple therapy with amantadine should be evaluated in further studies.
