A simple-to-use score system for predicting HBsAg clearance to peginterferon alfa-2b in nucleoside analogs-experienced chronic hepatitis B patients.

Objective: Patients with chronic hepatitis B (CHB) often fail to achieve clearance of the hepatitis B surface antigen (HBsAg) with peginterferon treatment. Our study aimed to develop a simple-to-use scoring system to predict the likelihood of HBsAg clearance following treatment with peginterferon alfa-2b(PEG-IFN-α2b) in patients with CHB. Methods: A total of 231 patients were enrolled and divided into HBsAg clearance (n = 37) and non-HBsAg clearance (n = 194) groups. Multifactor logistic models were constructed using univariate and multiple logistic regression analyses. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis were used to evaluate the discrimination, calibration, and clinical applicability of the predictive scoring system. Results: Four clinical variables (age, baseline HBsAg level, HBsAg level decline at week 12, and alanine aminotransferase ratio at week 12) were independently associated with HBsAg clearance after PEG-IFN-α2b treatment and, therefore, were used to develop a predictive scoring system ranging from 0 to 13. The optimal cut-off value was >4, with a sensitivity of 86.49%, specificity of 72.16%, positive predictive value of 37.2%, negative predictive value of 96.6%, and an AUC of 0.872. This model exhibited good discrimination, calibration, and clinical applicability. Among patients with scores <4, 4, or > 4 HBsAg clearance was achieved in 0.85, 14.29, and 37.21% of the patients, respectively. Conclusion: The scoring system could effectively predict the predominance of HBsAg clearance after PEG-IFN-α2b treatment in the early stage. This may be helpful when making clinical decisions for the treatment of patients with CHB.

Predictive factors for functional cure after sequential therapy with nucleos(t)ide analogues and pegylated interferon alfa-2b in treatment of chronic hepatitis B / 临床肝胆病杂志

Objective To investigate the independent predictive factors for functional cure after long-term nucleos(t)ide analogue (NUC) antiviral therapy followed by pegylated interferon α-2b therapy in chronic hepatitis B (CHB) patients. Methods A total of 162 CHB patients who were admitted to several hospitals in Qingdao, China, from 2018 to 2021 were enrolled as subjects, and all patients received pegylated interferon α-2b for at least 48 weeks after NUC therapy for one year or longer. According to whether HBsAg clearance was achieved at week 48 of pegylated interferon α-2b treatment, the patients were divided into functional cure group with 79 patients and non-cure group with 83 patients, and related clinical indices were compared between the two groups. The two-independent-samples t test and the Mann-Whitney U rank sum test were used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was performed, and the univariate and multivariate logistic regression analyses were used to investigate the independent predictive factors for functional cure. The receiver operating characteristic (ROC) curve was plotted for related variables, and the area under the ROC curve (AUC) was used to evaluate the prediction accuracy of the variables. Results Compared with the non-cure group, the functional cure group had a significantly lower HBsAg level at baseline [21.63 (3.33-157.60) IU/mL vs 794.70 (336.10-1 185.34) IU/mL, Z =-8.869, P 1000 IU/mL (0 vs 8.4%, χ 2 =5.073, P =0.024), a significantly lower level of total bilirubin at baseline [12.60 (10.12-15.93) μmol/L vs 15.50 (11.80-24.10) μmol/L, Z =-3.611, P 2×upper limit of normal (16.5% vs 4.8%, χ 2 =5.835, P =0.016). The multivariate logistic regression analysis showed that baseline HBsAg (odds ratio [ OR ]=0.996, 95% confidence interval [ CI ]: 0.995-0.997, P < 0.001), HBsAg at week 12 of pegylated interferon α-2b treatment ( OR =0.990, 95% CI : 0.986-0.994, P < 0.001), HBsAg at week 24 of pegylated interferon α-2b treatment ( OR =0.983, 95% CI : 0.975-0.991, P < 0.001), and baseline total bilirubin ( OR =0.885, 95% CI : 0.826-0.949, P =0.001) were independent predictive factors for functional cure. The ROC curve of baseline HBsAg showed an AUC of 0.904 and the optimal cut-off value of 118.24 IU/mL; the ROC curve of HBsAg at week 12 of pegylated interferon α-2b treatment showed an AUC of 0.948 and the optimal cut-off value of 73.74 IU/mL; the ROC curve of HBsAg at week 24 of pegylated interferon α-2b treatment showed an AUC of 0.975 and the optimal cut-off value of 11.01 IU/mL; the ROC curve of baseline total bilirubin showed an AUC of 0.664 and the optimal cut-off value of 19.9 μmol/L. Conclusion Baseline HBsAg, HBsAg at week 12 of pegylated interferon α-2b treatment, HBsAg at week 24 of pegylated interferon α-2b, and baseline total bilirubin are independent predictive factors for functional cure at week 48 of pegylated interferon α-2b treatment in CHB patients receiving sequential therapy with NUC and pegylated interferon α-2b.

Effect of Lyophilization on Stability of PEG-Protein Conjugate: A Case Study with Peginterferon alfa-2b

Abstract The purpose of the present study was to develop stable lyophilized formulation of peginterferon alfa-2b which is acquiescent to the short lyophilization process. The present study evaluates the effect of buffering components and cryoprotectant(s) on depegylation of the peginterferon alfa-2b in combination with lyophilization process. Finally, a short lyophilization process was identified which can produce a stable pharmaceutical form of peginterferon alfa-2b without any depegylation during long-term storage. Formulations were analyzed mainly for depegylation by HP-size exclusion chromatography and in-vitro antiviral activity. Residual moisture content in the lyophilized product was also used as a key indicating parameter to check its role with respect to depegylation upon storage under various temperature conditions. It was observed that the peginterferon alfa-2b when formulated in presence of cryoprotectant like sucrose requires longer lyophilization process of about 5 days, irrespective of the buffering components used, to reduce the level of residual moisture content and thereby to produce the stable formulation without depegylation. A stable formulation in presence of high concentration of lactose as a cryoprotectant was developed which can withstand stresses exerted to protein-polymer conjugate during lyophilization phases without any significant depegylation. A short lyophilization process of about 48 hours can be utilized for peginterferon alfa-2b when formulated in presence of lactose as a cryoprotectant through which a stable lyophilized formulation can be produced as against longer process required when sucrose is used a cryoprotectant, which is essential from commercial point of view as lyophilization is a costly process.

Influence of some methylated hepatocarcinogenesis-related genes on the response to antiviral therapy and development of fibrosis in chronic hepatitis C patients.

Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis.

Pegylated interferon therapy during early pregnancy for hepatitis B infection: does it prevent vertical transmission?

In general, interferon (IFN) is avoided during pregnancy due to the possibility of fetal side effects. We, herein, reported two child-bearing women with chronic hepatitis B (HB) infection who used pegylated interferon alfa 2b (PEG IFNα 2b) in first trimester unintentionally. We compared HB contracting rates of gestations in which IFN was used and not used. The cases are unique in that they could highlight the importance of IFN use in early gestation for preventing vertical transmission particularly if combined with antiviral therapy for the rest of pregnancy.

Development of bronchiolitis obliterans organizing pneumonia during standard treatment of hepatitis C with Peg-IFNα2b

No abstract available.

A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma.

BACKGROUND: Ipilimumab and peginterferon alfa-2b are established systemic treatment options for melanoma that have distinct mechanisms of action. Given the need for improved therapies for advanced melanoma, we conducted an open-label, single institution, phase Ib study to assess the safety and tolerability of using these two agents in combination. METHODS: Study treatment consisted of ipilimumab given every 3 weeks, for a total of four infusions, concurrent with peginterferon alfa-2b administered subcutaneous weekly for a total of 12 weeks. This was followed by maintenance therapy with peginterferon alfa-2b administered subcutaneously weekly for up to 144 additional weeks. The study was designed as a two-stage dose escalation scheme with continuous dose-limiting toxicity monitoring during the induction phase. RESULTS: Thirty one patients received at least 1 dose of study treatment and 30 were assessable for efficacy endpoints. We found that ipilimumab at 3 mg/kg dosing with peginterfeon alfa-2b at 2 µg/kg/week was the maximum tolerated dose of this combination. The incidence of grade 3 drug-related adverse events (AEs) was 45.2%. There were no grade 4/5 AEs. The overall response rate was 40% by immune-related response criteria. Median progression-free survival was 5.9 months. The median overall survival was not reached with at a median follow-up of 35.8 months. CONCLUSIONS: We report that the combination of ipilimumab at 3 mg/kg dosing combined with peginterfeon alfa-2b at 2 µg/kg/week demonstrated an acceptable toxicity profile and a promising efficacy signal. Further study of this combination is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01496807, Registered December 19th, 2011.

HBsAg and HBeAg in the prediction of a clinical response to peginterferon α-2b therapy in Chinese HBeAg-positive patients.

BACKGROUND: This study aimed to evaluate the predictive values of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels in 171 Chinese patients with chronic hepatitis B who received a 48-week course of pegylated interferon alfa-2b therapy at 1.5 mcg/kg. METHODS: HBsAg, HBeAg, and hepatitis B virus (HBV) DNA levels were measured at baseline and weeks 12, 24, 48, and 72. Clinical responses were defined as a combined response (CR, HBeAg seroconversion [sustained response, SR] combined with HBV DNA level <2,000 IU/mL at week 72). The positive predictive value and negative predictive value were calculated for HBsAg alone and/or combined with HBeAg and HBV DNA at weeks 12 and 24. RESULTS: Of 171 patients included, 58 (33.9 %) achieved a SR. Of patients who achieved a SR, 33 (56.9 %) achieved a CR. Totally 19.3 % (33/171) patients achieved CR and 80.7 % (138/171) patients did not. Patients with HBsAg <1500 IU/mL at week 12 had a 47.4 % chance of achieving an off-treatment SR and patients with a HBsAg decrease >1.5 logIU/mL at week 12 had a 54.5 % chance. Patients with HBsAg >20,000 IU/mL at weeks 12 and 24 had a 93.8 and 100.0 % chance, respectively, of not achieving a CR. An HBsAg level or changes at weeks 12 and 24, combined with HBeAg or HBV DNA, increased the chance for a SR and CR. CONCLUSIONS: On-treatment HBsAg quantification, alone or in combination with HBeAg or HBV DNA, predicted off-treatment SR and CR after 48 weeks of PEG-IFNα-2b therapy, and thus, may guide clinicians in making a therapeutic decision to continue or terminate the therapy.

Efficacy and Tolerability of Peginterferon alpha-2a and Peginterferon alpha-2b in Iranian Patients With Chronic Hepatitis C.

BACKGROUND: Nearly 0.5% of Iranians are infected with HCV. Peginterferon-alpha-2a and Peginterferon-alpha-2b are the two available types of interferon for the treatment of hepatitis C. Comparing the results of these two treatments is still a challenge. OBJECTIVES: The aim of this study was to compare the results of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients with chronic hepatitis C. PATIENTS AND METHODS: 289 patients with chronic hepatitis C attending Tehran Hepatitis Center (THC) and Hepatitis Clinic of Tehran Blood Transfusion Organization (TBTO) from January 2008 to April 2013 and treated with combination of Peginterferon-alpha-2a or Peginterferon-alpha-2b plus Ribavirin were enrolled in this retrospective cross-sectional study. Treatment response and side effects were compared. RESULTS: Among all naive patients, 82.0% achieved SVR, 5.4% were resistant to therapy and 11.0% withdrew the treatment. Relapse was seen in 12.2% of naive patients who finished the course of treatment. RVR and EVR were seen in 67.7% and 90.6% of naive patients, respectively. Patients divided into two groups. Group A consists of 247 patients treated with Peginterferon-alpha-2a and group B 42 patients treated with Peginterferon-alpha-2b. No significant difference in treatment response was observed between naive patients of the two groups. The rates of arthralgia/myalgia, alopecia, pruritus, insomnia, dyspnea and anorexia were higher in group A and the rates of dermal problems, coryza and bleeding were higher in group B. In a subgroup analysis, the two kinds of Peginterferon-alpha-2a available in Iran were compared. Rapid and early viral responses and relapse rates were lower in the one made in Iran and the long-term responses were not different. The rates of arthralgia/myalgia, fever, alopecia, pruritus, insomnia, dyspnea, anorexia, cough, headache and abdominal pain were higher and the rates of irritability and coryza were lower in the one made in Iran. CONCLUSIONS: There was no significant difference in the efficacy of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients. Physicians might choose the treatment regimen for every individual concerning the differences in side effects of Peginterferons.

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C.

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus (HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 µg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin (800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed. RESULTS: Eighty-two patients (35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response (RVR): while the figures were 74.1% for early virologic response (EVR) and 44.4% for sustained virologic response (SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events (SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication. CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.

Predicting the outcomes of combination therapy in patients with chronic hepatitis C using artificial neural network.

BACKGROUND: Treatment with Peginterferon Alpha-2b plus Ribavirin is the current standard therapy for chronic hepatitis C (CHC). However, many host related and viral parameters are associated with different outcomes of combination therapy. OBJECTIVES: The aim of this study was to develop an artificial neural network (ANN) model to predetermine individual responses to therapy based on patient's demographics and laboratory data. PATIENTS AND METHODS: This case-control study was conducted in Tehran, Iran, on 139 patients divided into sustained virologic response (SVR) (n = 50), relapse (n = 50) and non-response (n = 39) groups according to their response to combination therapy for 48 weeks. The ANN was trained 300 times (epochs) using clinical data. To test the ANN performance, the part of data that was selected randomly and not used in training process was entered to the ANN and the outputs were compared with real data. RESULTS: Hemoglobin (P < 0.001), cholesterol (P = 0.001) and IL-28b genotype (P = 0.002) values had significant differences between the three groups. Significant predictive factor(s) for each group were hemoglobin for SVR (OR: 1.517; 95% CI: 1.233-1.868; P < 0.001), IL-28b genotype for relapse (OR: 0.577; 95% CI: 0.339-0.981; P = 0.041) and hemoglobin (OR: 0.824; 95% CI: 0.693-0.980; P = 0.017) and IL-28b genotype (OR: 2.584; 95% CI: 1.430-4.668;P = 0.001) for non-response. The accuracy of ANN to predict SVR, relapse and non-response were 93%, 90%, and 90%, respectively. CONCLUSIONS: Using baseline laboratory data and host characteristics, ANN has been shown as an accurate model to predict treatment outcome, which can lead to appropriate decision making and decrease the frequency of ineffective treatment in patients with chronic hepatitis C virus (HCV) infection.

Prediction of a null response to pegylated interferon α-2b plus ribavirin in patients with high viral load genotype 1b hepatitis C.

BACKGROUND/AIMS: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon α-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, α-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

Combination immunotherapy for high-risk resected and metastatic melanoma patients.

BACKGROUND: Patients with advanced melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment for patients with high-risk, resected stage 3, recurrent, refractory, or stage 4 melanoma. METHODS: We conducted a phase 2 clinical trial of HyperAcute Melanoma (HAM) vaccine (NLG-12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design consisted of a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM plus Sylatron (subcutaneously, 6 µg/kg). Trial endpoint outcomes include clinical response, overall safety, and correlative findings for observed antitumor effect. RESULTS: Our cohort consisted of 25 patients with a median age of 60. Twenty-one patients completed the trial and 4 stopped because of progressive disease (PD). According to the Response Evaluation Criteria in Solid Tumors, of the 16 stage 4 patients, 2 had a complete response (CR), 1 had stable disease, and 4 had no evidence of disease (NED) after resection. For stage 2/3 patients, 3 of 9 remained NED, and the 1 stage 2C patient had slow PD with a single site resected and is currently NED. The median overall survival time was 29 months, with 60% of the patients surviving for >1 year. Of the 25 patients, 12 (48%) are still alive. All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Four of 25 patients developed vitiligo, correlating with 2 CR patients and 2 NED patients. CONCLUSION: Combination immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and therapeutic efficacy should be further explored to enhance the benefit of this promising immunotherapeutic approach.

Hepatitis C virus treatment in the 'real-world': how well do 'real' patients respond?

BACKGROUND: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. OBJECTIVES: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. METHODS: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. RESULTS: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). CONCLUSIONS: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials.

Prediction of a Null Response to Pegylated Interferon alpha-2b Plus Ribavirin in Patients with High Viral Load Genotype 1b Hepatitis C

BACKGROUND/AIMS: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon alpha-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, alpha-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

Serum proteins in chronic hepatitis B patients treated with peginterferon alfa-2b.

AIM: To study the differential protein profile in serum of hepatitis B patients. METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b. The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis (2-DE). Differentially expressed protein spots were identified by electrospray ionization-quadrupole time-of-flight mass spectrometry. Alpha-2-HS-glycoprotein, complement component C3c and CD5 antigen were further analyzed by an enzyme-linked immunosorbent assay and immunonephelometry. RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B (CHB) were studied. These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders (n = 9) and non-responders (n = 10). 2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa-2b. From the quantitative analysis of the 2-D gel, 7 proteins were detected between the two groups at different levels before treatment. Among these potential candidates, serum levels of alpha-2-HS-glycoprotein, complement component C3c and CD5 antigen-like precursor were further analyzed. In the validation phase, 23 subjects, 9 sustained responders and 14 non-responders, were recruited. Interestingly, the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders. CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.

Resultados del tratamiento de la hepatitis crónica por virus C en un hospital público, en Chile / Results of chronic hepatitis C treatment in a public hospital

Background: Chronic hepatitis C is an important health problem in Chile. In 2005, the Ministry of Health started a pilot treatment program with peg interferon and ribavirin, to be developed in public hospitals all over the country. Aim: To report the results ofhepatitis C treatment obtained at our institution. Patients and Methods: Between 2005 and 2009, 63 patients were referred for treatment. In all, the viral load and genotype were determined. Peg interferon alpha-2a or alpha-2b plus ribavirin were used for therapy for up to 48 weeks in genotypes (G) 1 or 4 or 24 weeks in genotypes 2 or 3. If at the end oftreatment, viral load measured by polymerase chain reaction (PCR) was negative, it was repeated 6 months later. A negative viral load at that time was considered a sustained viral response (SVR). Results: Among the 51 patients who started treatment, 42 (80.4%) were G1,1 was G2,1 was G4 and 7 were G3. A SVR was reached in 51.1% ofG 1 and 4 and in 87.5% in G 3 and 2. In a univariate analysis, the variables significantly associated with a positive viral response were the degree offibrosis and body mass index. Conclusions: These results are similar to those obtained in other international series, demonstrating that Hispanic ethnicity does not influence the response to treatment. Our good results could be explained by the excellent compliance of the patients to the treatment. A higher degree offibrosis and a higher BMI were associated with a poor response.

The Combination Therapy with Peg-interferon Alfa and Ribavirin for Chronic Hepatitis C in Korea as an Initial Treatment / 고신대학교의과대학학술지

OBJECTIVES: The combination therapy with peginterferon and ribavirin has been used to treat chronic hepatitis C for several years in Korea but there is a few report about the results of the treatment. We evaluated safety and efficacy of the combination therapy with Peg-interferon and ribavirin and analyzed factors that may affect treatment. METHODS: Total 72 untreated chronic hepatitis C patients were administered pegylated interferon alfa-2a (180microg/week) or alfa-2b (1.5microg/kg/week) and ribavirin (800 mg/day in genotype 2, 1000-1200 mg/day in genotype 1). Duration of the treatment was 24 weeks in genotype 2 and 48 weeks in genotype 1. Response of the treatment was evaluated by rapid virologic response (RVR), early virologic response (EVR), end treatment virologic response (ETR), sustained virologic response (SVR) and adverse event. RESULTS: The RVR, EVR, ETR, SVR were 61.8%, 82.5%, 88.9% and 80.5% retrospectively. The SVR of genotype 1 was 63.4% and non-genotype 1 was 96.7%. Genotype (Odds ratio: 14.92) was an independent predictor of the SVR. Leukocytopenia, flu-like symptoms, itching, rash and anemia were common adverse events of the combination therapy and if then we reduced dose and there was one case of cessation. CONCLUSIONS: The combination therapy with Peg-interferon and ribavirin shows efficacy to the Korean patients with chronic hepatitis C as an initial treatment. Genotypes 2 and 3 were more likely to have a sustained virologic response.