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@#Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.
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Objective@#To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B.@*Methods@#Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation.@*Results@#Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response.@*Conclusions@#The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.
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Background @#Low triglycerides and cholesterol was associated with hepatitis C virus (HCV) infection. Chronic HCV infection is the main cause of liver injury and it may influence to serum lipid levels. We aimed to evaluate the effect of antiviral treatment on the change of lipid profiles during interferon-based anti-HCV treatment. @*Material and Methods @#Totally 863 patients who completed the interferon-based antiviral therapy in Kaohsiung Medical University Hospital were included in this present study. The lipid profile measured and assessed in the baseline of the treatment and after 6 months of completion of the treatment. @*Results @#The most of the patients (81.2%) were achieved sustained virological response (SVR) by antiviral therapy. There was no significant difference between baseline triglycerides (TG) levels in the SVR group and non SVR groups. The TG levels at 6 months after completion of the treatment was significantly elevated in SVR group (102.9±57.0 mg/dL, p=0.0001) but did not elevated in non SVR group (94.5±45.6 mg/dL, p=0.690) compared with baseline TG levels. </br> After adjusting patients by four indexes for fibrosis (FIB4) in cut-off point 3.25, serum TG levels significantly increased in low FIB4 group (103.2±57.9 mg/dL, p=0.0001) but not in high FIB4 group (98.1±49.6 mg/dL, p=0.095) after 6 months end of the treatment. Serum TG level was increased greater in patients who had low FIB4 score and patients who achieved SVR (baseline 89.1±34.8 mg/dL; 6 months after treatment 104.3±59.3 mg/dL, paired T test p=0.0001). @*Conclusion@#The eradication of HCV is the main cause of the increase of lipids after Pegylated Interferon and Ribavirin treatment. </br> However advanced fibrosis also has an effect in increase of TG after the treatment.
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Objective To investigate the predictive value of on-treatment hepatitis B surface antigens (HBsAg)levels for HBsAg loss/seroconversion in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB)patients treated with pegylated interferon (peg-IFN)-α-2a.Methods HBeAg-negative CHB naive patients were collected from 2008 May to 2011 August in Beijing Ditan Hospital affiliated to Capital Medical University.Eligible patients had been HBsAg-positive,HBeAg-negative and with detectable hepatitis B virus (HBV)DNA for>6 months,had elevated alanine aminotransferase for>3 months,had no other liver diseases,and had been treated with peg-IFN-α-2a>3 months or had finished the treatment.All the enrolled patients were administered with peg-IFN-α-2a 180 μg/week.Serum HBV DNA,HBsAg,and anti-HBs levels were measured at baseline and every 3 months during peg-IFN-α-2a treatment.The primary efficacy of response to the treatment was HBsAg loss.Comparison between groups was conducted by chi-square test.The absolute levels of HBsAg and the decline rate of HBsAg at week 12 and week 24 were assessed using receiver operating characteristic (ROC)curve for predicting HBsAg loss at week 96 and week 120.Results A total of 81 patients were included into the data analysis. According to on-treatment HBsAg decline,patients were divided into completed response group (12 cases, 14.8%),partial response group (20 cases,24.7%),and poor response group (49 cases,60.5 %).On week 12 of treatment,mean HBsAg decline levels in completed response and partial response groups were 0.62(0.06,0.91)lg IU/mL and 0.19 (-0.01 ,0.48)lg IU/mL,respectively,which was not statistical different (Z =1 .581 ,P =0.209 ).Adjusting for differences of baseline factors (calculation of the mean decline of HBsAg),completed response group and partial response group had much more pronounced decline than poor response group 0.00 (-0.01 ,0.14)lg IU/mL,χ2 =9.00,P <0.01 ].On week 24, difference of HBsAg decline among the 3 groups was statistically significant (χ2 =27.72,P <0.01).The predictive ability of HBsAg cut-off level at week 24 was better than week 12 for HBsAg loss at either 96 or 120 weeks,and the differences of the area under the ROC curve were both significantly different (χ2 =3.880,P =0.049 and χ2 =4.412,P =0.036,respectively).Conclusion Dynamics of HBsAg level in early treatment of peg-IFN-α-2a can predict the therapeutic effect of patients with HBeAg-negative CHB.
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Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.
Subject(s)
Female , Humans , Middle Aged , Antifungal Agents/therapeutic use , Antiviral Agents/adverse effects , Cryptococcus neoformans/immunology , Drug Therapy, Combination , Hepatitis C, Chronic/diagnosis , Immunocompromised Host , Interferon-alpha/adverse effects , Meningitis, Cryptococcal/drug therapy , Opportunistic Infections/diagnosis , Polyethylene Glycols/adverse effects , Recombinant Proteins/adverse effects , Ribavirin/adverse effects , Time Factors , Treatment OutcomeABSTRACT
Objective To investigate the efficacy of polyethylene glycol (PEG)-interferon α (PEG-IFNα) in treating HBeAg-positive chronic hepatitis B (CHB) and explore the relationship between hepatitis B virus (HBV) genotypes and the effect of interferon α (IFNα) therapy.Methods A total of 199 CHB patients with known genotypes were given subcutaneous injection of PEG-IFNα-2a or PEG-IFNαt-2b once a week for 48 weeks,with another 24 weeks follow up.The seroconversion of HBeAg influenced by HBV genotypes were analyzed after discontinuation of treatment.Results In local area,genotype C was the major genotype[64.32％ (128/199)].Except serum ALT and AST level,the differences in gender,age,liver inflammation,degree of liver fibrosis,HBeAg level and HBV DNA level between genotype B and C were not statistically significant(all P ＞0.05).The seroconversion rate of HBeAg in patients with genotype B at early stage of therapy (3 months) was significantly higher than that of patients with genotype C [26.76％ (19/71) vs 10.16％ (13/128),x2 =9.330,P =0.002].While at the end of follow-up,seroconversion rate of HBeAg in patients with genotype B (followed up for 6 months) was higher than that of patients with genotype C [39.44％ (28/71) vs 30.47％ (39/128)],but the difference was not statistically significant(x2 =1.645,P =0.200).By univariate analysis based on log-rank test,the time of HBeAg seroconversion in patients with genotype B was much earlier than that of genotype C [(13.99 ± 0.67) months vs (15.47 ± 0.41)months],but the difference was not statistically significant (P =0.150).Conclusions The seroconversion rate of HBeAg in patients with genotype B treated with PEG-IFNα was significantly higher than that of genotype C in early stage of therapy (3 months),while similar at the end of therapy.
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Objective To investigate the effect of Peg-Interferon α-2a therapy on the quality of life (QOL) of patients with chronic hepatitis C,and to evaluate the effect of healthcare insurance policy in Guangzhou city on these patients.Methods Totally 102 patients with chronic hepatitis C were enrolled.Forty-two patients (group A) were treated with Peg-Interferon α-2a plus ribavirin whose medical expenses were covered by medical insurance; 30 patients (group B ) received the same therapy but at their own expenses ; and the other 30 patients ( group C) were not treated with Peg-Interferon α-2a.QOL of patients in three groups were investigated using the general quality of life inventory questionnaire (GQOLI-74) before and after Peg-Interferon α-2a treatment.Wilcoxon test was used to compare on all scales and total scores before and after treatment in each group,and Kruskal-Wallis test was performed to compare on all scales and total scores among three groups.Results Before treatment,the physical function,psychological function,social function,material life and total score of group A were 55.3,58.8,61.9,60.6 and 58.5 ; those of group B were 57.5,60.4,61.1,55.2 and 58.3; those of group C were 58.6,60.3,57.5,54.8 and 56.4.There was no statistic difference on all scales and total scores among three groups (Z =- 1.177,- 0.846,- 1.062,-0.377 and - 1.085,P ＞ 0.05).After treatment,group A had higher QOL on all scales (67.1,76.4,68.1,70.1) and total score (72.6) than group C (54.6,54.0,53.3,57.5 and 54.6,P ＜0.01) ; group B had higher QOL (P ＜0.05) on three scales (65.1,65.0 and 69.6) and total score ( 64.3 ) except material life ( 56.3 ) than group C ; group A had higher QOL on psychological function,material life and total score than group B ( P ＜ 0.05 ).Conclusions QOLs of chronic hepatitis C patients treated with Peg-Interferon α-2a are higher than those without Peg-Interferon α-2a treatment.Patients whose medical expenses are covered by medical insurance may have higher QOLs than those at their own expenses.
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The current best treatment for HCV infection is combination therapy with PEG-interferon and ribavirin. This combination therapy has markedly increased the number of sustained virologic responders but is associated with various side effects, especially hematological abnormalities. We recently experienced a 45-year-old man who developed PEG-interferon induced autoimmune hemolytic anemia (AIHA) and retinal premacular hemorrhage. The worsening hemolysis after ribavirin withdrawal and exclusion of other causes implicated PEG-interferon as the cause of the AIHA. To the best of our knowledge, this is the first case reported from Korea. Treatment with PEG-interferon requires careful follow-up, as it can induce or exacerbate autoimmune diseases.
Subject(s)
Humans , Middle Aged , Anemia, Hemolytic, Autoimmune , Autoimmune Diseases , Follow-Up Studies , Hemolysis , Hemorrhage , Hepatitis , Hepatitis C , Hepatitis C, Chronic , Korea , Retinal Hemorrhage , Retinaldehyde , RibavirinABSTRACT
According to estimations there are corresponds approximately 380000 carriers of HCV in Mongolia, this is approximately 15,4% of the population. Standard therapy of the HCV infection is the donation of PEG-Interferonalfa plus Ribavirin. The therapy successes dependents on the viral genotype. Diagnostic and therapy of the HCV are very expensive and complicated. But accurate diagnosis and therapy are always our main goal in order to clarify to elucidate. Therefore, I would like to propose the foundation of a specialized laboratory in Ulaanbaatar with the help of the German government and develop health programs for the education of the population. German clinics are prepared to support this project of the HCV.
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Peg-interferon is the main therapeutic agent in patients infected with the hepatitis C virus. It is rather safe, but it is known to induce production of autoantibodies and it can lead to the occurrence of autoimmune disease. Interferon induced thyroiditis is considered a major clinical problem for patients who receive interferon therapy. We recently experienced a 36 year-old woman who developed peg-interferon induced thyroiditis. To the best of our knowledge, this is a rare case report in Korea. We report here on this casea long with a review of the literature.