Predictive Factors For Sustained Response Research Articles

P636 Changes in peripheral helper T-cell was associated with sustained response to a 12-week EEN therapy in active Crohn’s disease: A pilot study

Abstract Background Exclusive enteral nutrition (EEN) is an effective solution in inducing remission in patients with active Crohn’s disease (CD). However, the underlying mechanism is not completely clear. Evidence is accumulating that potential beneficial in regulating the inflammatory immune response of CD, a chronic inflammation dominated by pathogenic TH1 and TH17 cells. We investigated the relationship between changes of circulating helper T cell and clinical response in CD during treatment with EEN. Methods Sixty-eight adults with active CD treated successfully with EEN were prospectively study. Peripheral helper T cell (Th1, Th2, Th17 and Treg) were evaluated using flow cytometry from baseline to Weeks 4 and 12. We also determine the prognostic value of the ratio of delta Th cell at Weeks 4 to baseline (△Th w4-w0) in patients receiving EEN. Mucosal healing was assessed with endoscopy at baseline and Week 12. Results Treatment with EEN significantly improved disease activity scores and laboratory biochemical markers measured at Weeks 4 and 12 compared with baseline (p < 0.05 and p < 0.001). After the initiate of EEN, we observe early modulating effects of EEN on helper T-cell percentages, especially in Treg cell. Furthermore, we found a long-term increase in Treg cell percentages in patients who sustained response to EEN during follow-up. Mean increases of Treg cell from baseline in patients sustained response were significantly larger in a patient who loss of response (p < 0.01). Receiver operating characteristic (ROC) analysis to predict sustained response at 12 weeks showed area under the curve (95% confidence interval) of Treg cell at 4 weeks (Treg w4) and change in Treg cell from baseline to 4 weeks (△Treg w4-w0) to be 0.75 (0.56–0.87) and 0.84 (0.63–0.92), respectively. Logistic regression analysis confirmed that △Treg w4-w0 (31.8%) after the EEN was significant independent predictive factors for sustained response. Mucosal healing at Week 12 was achieved by 97.1% of patients who long-term increase of Treg cell compared with 51.5% of those temporary raise (p < 0.001). Conclusion EEN resulted in rapid improvements in laboratory markers and early increase in Th subsets percentages. Early increase of Treg cell predicts a sustained response to EEN and mucosal healing. Monitoring of Treg cell may help predicts the sustained clinical response and course.

PF690 PREDICTORS OF THERAPY FREE RESPONSES IN ITP PATIENTS RECEIVING TPO‐RA. RESULTS FROM A SPANISH MULTICENTER STUDY

Background:Thrombopoietin receptor agonists (TPO‐RA) are a well‐established treatment in patients with primary immune thrombocytopenia (ITP). Sustained treatment‐free responses (TFR) after TPO‐RA discontinuation in adult ITP have been reported; yet, to date there are no predictors to identify in which patients this approach is likely to be successful.Aims:To evaluate clinical predictors of TFR in a real world cohort of ITP patients treated with TPO‐RA.Methods:Patients aged >18 years with primary ITP who had initiated TPO‐RA (eltrombopag [EPG] or romiplostim [ROM]) treatment between January 2012 and December 2014 were included in this retrospective, multicenter study from 19 secondary and tertiary Spanish hospitals. Data on patient characteristics, history of disease and previous therapies, TPO‐RA administration, response and discontinuation were collected from medical records.Results:A total of 121 patients with a median age of 63 years (range 19–96 years), 59% females initiated TPO‐RA as long‐term therapy (ROM 54; EPG 67). Sixty‐eight percent of the patients treated with TPO‐RA met criteria for chronic, 16% for newly diagnosed and 16% for persistent ITP. The median time on TPO‐RA treatment was 35.2 months (1 to 67.3 months), and the median follow‐up from start of TPO‐RA until collection of data was 44.9 months (23.8 to 67.5 months). A total of 39 patients (32.2%) switched TPO‐RA during follow‐up. The most frequent cause for switching was lack of efficacy (48.7% of cases ‐in 89.5% the initial TPO‐RA was EPG‐). Due to switching the exposure to both TPO‐RAs was similar during follow‐up; 80 patients received ROM and a similar number was treated with EPG, with total exposure (years) of 161.0, and 168.3, respectively.During follow‐up almost one half of the patients (46.3%, n = 56) tapered‐off the TPO‐RA; 10 out of the 37 cases that discontinued ROM had previously received EPG, and 4 out of the 19 that stopped EPG had switched from ROM. After a median of 432 days (29–1344) under TPO‐RA treatment, 35 patients (28.9%) maintained TFR defined as platelet counts >50x109/l for more than 6 months. In 4 of these 35 cases, TPO‐RAs were reintroduced due to loss of response after a median TFR of 20.5 months. Potential predictors of TFR in the remaining 31 patients (25.6%) with sustained platelet counts in the absence of any agent meant to increase platelet count (median 32 months, 8–217) were analyzed. No specific patient feature (e.g. age, comorbidities, ITP duration, previous treatments), bleeding, previous therapies nor phase of disease seemed to consistently predict for sustained response off therapy. However, univariate analysis (Chi‐square) did identify statistically significant predictors of TFR. Interestingly, while the specific TPO‐RA that was discontinued did not influence the probability to achieve TFR, receiving ROM as first TPO‐RA was positively associated with TFR (P = 0.010), while switching TPO‐RA negatively predicted sustained platelet responses (P = 0.002). In multivariate analysis with logistic regression both variables predicted significantly higher odds of TFR (Table 1).Summary/Conclusion:Platelet response following TPO‐RA cessation is sustained in 25.6% of adult patients with primary ITP. Although published studies have not identified a predictive factor of sustained response after TPO‐RA discontinuation, in this long‐term follow up analysis, ROM as first TPO‐RA being administered, and no need of TPO‐RA switching are factors that positively correlate with the probability to achieve TFR.image

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.

Successful Discontinuation of Eltrombopag after Complete Remission in Patients with Primary Immune Thrombocytopenia

Background: Eltrombopag is effective and safe for treating chronic immune thrombocytopenia (ITP) patients who have not responded to previous therapy. Interestingly, some patients in whom hemostatic platelet counts are achieved with eltrombopag may sustain the platelet response when eltrombopag ceases to be administered. However, the frequency of sustained responses after discontinuing eltrombopag without additional therapy for ITP is largely unknown.Methods: A total of 260 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry were retrospectively evaluated. The study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee.Results: The median age was 62 [range, 18–93] years. There were 165 women and 95 men. According to the standard definition, patients were allocated to newly diagnosed (n=29), persistent (n=36) and chronic (n=195) ITP groups. The median time from diagnosis to eltrombopag initiation was 24 [range, 1–480] months. The median number of previous therapies was 3 [range, 0–10], including splenectomy (22%), rituximab (23%) and romiplostim (19%). The initial response rate to eltrombopag was 231/260 (89%), including 77% (n=201) cases of complete remission (platelet count ≥100 x 109/L). The median duration of eltrombopag treatment was 6 [range, 1–54] months.Eltrombopag was discontinued in 80 out of 201 (39.8%) patients who achieved CR. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=33), platelet count >400x109/L (n=29), patient’s request (n=5), aspartate aminotransferase elevation (n=3), diarrhea (n=3), thrombosis (n=3) and other reasons (n=4). For analysis of discontinuation, patients with follow-up < 6 months (n=15), newly diagnosed ITP (n=11) or patients who received concomitant or previous (6 months before) treatments at the start of eltrombopag use (n=5) were excluded. Of the 49 evaluable patients, 22 (45%) had an immediate relapse after stopping eltrombopag. One patient with sustained response after stopping treatment relapsed at 10 months. A total of 26 patients (53%) showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 [range, 6–25] months. These patients were characterized by a median time since ITP diagnosis of 46.5±114.1 months, with 4/26 having ITP <1 year. Eleven patients (42%) were male and their median age was 59 [range, 18-88] years. They had received a median of four previous treatment lines [range: 0–9 lines] and 11 (42%) were splenectomized. The median platelet count before starting eltrombopag was 22 x 109/L and that before eltrombopag withdrawal was 269 x 109/L.The main characteristics (age, gender, duration of ITP, prior anti-ITP lines, prior splenectomy, prior rituximab, prior romiplostim, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 26 patients with sustained response after stopping eltrombopag were compared with those of the 23 patients relapsing after eltrombopag withdrawal. No predictive factors of sustained response after eltrombopag withdrawal could be identified.Conclusion: Platelet response following eltrombopag cessation may be sustained in nearly half of adult patients with primary ITP after CR with eltrombopag. However, reliable markers for predicting which patients will have this response are lacking. DisclosuresNo relevant conflicts of interest to declare.

Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients

AbstractWe conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m2 and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician’s preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 109/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.

The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study.

Thrombopoietin-receptor agonists (Tpo-RAs) are highly effective in immune thrombocytopenia (ITP). Recently, cases of durable remission after Tpo-RA discontinuation in adult ITP have been reported. We aimed to describe the subset of patients in whom transient Tpo-RA therapy may induce a durable response. We studied all adults with primary ITP treated with at least one Tpo-RA over a 5-year period (n=54) and seen at one of three participating referral centres in France. Tpo-RAs were discontinued in 20 of 28 patients who achieved a complete response. We excluded six patients because a previous treatment at the start of Tpo-RA treatment may have interfered with the response. Overall, eight patients with chronic ITP showed a sustained response [median follow-up: 13·5months (range 5-27months)]. We could not identify a predictive factor of sustained response. In conclusion, a substantial proportion of ITP patients receiving Tpo-RAs can maintain a durable response after treatment discontinuation.

Prolonged Remission After TPO-Receptor Agonist Discontinuation In Adults With Chronic ITP. Results Of a French Observational Study

▪ IntroductionRomiplostim and eltrombopag, the two TPO-receptors agonists (TPO-RAs), that have been approved in adult's ITP show a great clinical efficacy, with a 70 to 80% lasting response-rate in long-term studies. Due to their mechanism of action, the platelet count decreases back to its baseline level within 10 days after TPO-RA withdrawal in the large majority of the cases. However, recent unexpected cases of durable remission after TPO-RAs discontinuation have been reported. The aim of this study was first to look at the proportion of patients in whom TPO-RAs are able to induce a durable response and secondly to describe the characteristics of such patients. Patients and methodsAll adults with primary ITP treated by at least one TPO-RA over a 5–year period, seen in one of the 3 participating referral centers, have been included. All patients were consecutively captured through a database, and no one excluded. A complete response (CR) was defined as a platelet count >100 x 109/L, and a response (R) by a platelet count over 30 x 109/L with a least a doubling of the baseline value. Last follow-up was obtained by contacting the physician in care of the patient. ResultsFifty four patients (35 females) were recruited, including 35 patients (65%) with chronic, 11 (20%) with persistent and 8 (15%) with newly-diagnosed ITP. After a median of 4 treatment-lines (including rituximab in 59% and splenectomy in 33%), 18 received eltrombopag, 22 romiplostim and 14 received both TPO-RAs sequentially for an overall median time of 10 months (range: 1-70 months). The initial overall response rate on TPO-RA was 44/54 (81.5%) with 28/54 patients achieving a CR (51.8%) and 16/54 a R (29.6%). In 20 out of 28 patients achieving a CR, TPO-RA was discontinued. Among them, 6 patients were excluded from the analysis as concomitant or previous treatment at the initiation of TPO-R therapy may have interfered with the response after stopping TPO-RA. Three patients received rituximab either concomitantly (n=2) or 6 months before TPO-RA (n=1); 2 patients were splenectomized either concomitantly (n=1) or 2 months before TPO-RA administration (n=2). In one patient, TPO-RA was stopped while the patient has a newly diagnosed ITP. Among the 14 evaluable patients, 6 (30%) relapsed within 10 days after stopping TPO-RA, requiring a rescue therapy. In 8 patients (70%), a durable CR was observed after TPO-RA discontinuation with a median follow-up period of 13.5 months (range: 5-27 months). All of them had a previous history of chronic ITP (median ITP duration before TPO-RAs: 103 months (13-297)), and have received a median of 5 lines of treatment (2-12). Interestingly, three out of 8 patients received short course (<1 months) of TPO-RA. In this study including a relatively low number of patients, we did not found predictive factor of sustained response (age, gender, duration of ITP, previous number of therapies before TPO-RA). ConclusionOur study suggests that almost 15 % of patients treated for chronic ITP with TPO-RA achieve a durable response after treatment discontinuation. A prospective trial is needed to confirm this unexpected rate of response in a larger series of patients and to identify predicting factors of lasting remission. Disclosures:Off Label Use: Romiplostin, eltrombopag.

Efficacy of Infliximab in Intestinal Behçet’s Disease

Although infliximab is widely accepted as a therapeutic option for inflammatory bowel disease, its therapeutic efficacy for the treatment of intestinal Behçet's disease (BD) is unknown. We investigated the short-term and long-term response rates to infliximab in intestinal BD and predictive factors of sustained treatment response following infliximab treatment. This study was conducted using a retrospective noncontrolled review of medical records from 8 tertiary hospitals in Korea. We collected clinical, demographic, and laboratory data for patients with 28 patients with intestinal BD who received at least 1 dose of infliximab. Response rates of infliximab at 2, 4, 30, and 54 weeks for each patient and factors predictive of sustained response were investigated. Adverse events were also identified. The median duration of follow-up after initial infliximab infusion was of 29.5 months. The clinical response rates at 2, 4, 30, and 54 weeks were 75%, 64.3%, 50%, and 39.1%, respectively, with clinical remission rates of 32.1%, 28.6%, 46.2%, and 39.1%, respectively. After multivariate analysis, older age at diagnosis (≥40 yr), female sex, a longer disease duration (≥5 yr), concomitant immunomodulator use, and achievement of remission at week 4 were found to be predictive factors of sustained response. There was 1 serious infection but no malignancies or deaths in this study. Infliximab was a well-tolerated and effective therapy for patients with moderate-to-severe intestinal BD. Moreover, we found 5 predictive factors associated with sustained response, which might assist in optimal patient selection for infliximab treatment.

Management of hepatitis C/HIV coinfection

One third of HIV-infected individuals in Europe and the USA have a hepatitis C coinfection. With the introduction of highly active antiretroviral therapy for treatment of HIV, liver disease caused by chronic hepatitis C virus infection has now become an increasingly important cause of morbidity and mortality among HIV-infected patients. Therefore, treatment strategies for management of hepatitis C coinfection in HIV-infected individuals are urgently needed. With the introduction of pegylated interferon/ribavirin combination therapy significantly improved treatment options for HIV/hepatitis C virus-coinfected patients have become available, leading to sustained virological response rates of over 40%. Increasing knowledge on the management of adverse events under hepatitis C therapy and optimized selection of antiretrovirals in HIV/hepatitis C virus-coinfected patients has helped to reduce complications and improve overall treatment outcome. Treatment with pegylated interferon plus ribavirin is safe and effective in HIV/hepatitis C virus-coinfected patients. Longer treatment durations of 48 weeks are recommended for genotype 2 or 3. Positive predictive factors for sustained response are hepatitis C virus genotype 2 or 3 and early treatment response.

Percentage of Hepatitis C Virus-Infected Hepatocytes Is a Better Predictor of Response Than Serum Viremia Levels

Pegylated alpha-interferon plus ribavirin is the current therapy for chronic hepatitis C virus (HCV) infection. Serum HCV-RNA concentration before treatment has been identified as an independent predictive factor of response. We have compared the percentage of HCV-infected hepatocytes with the concentration of serum HCV-RNA in baseline samples as predictors of response. We included 97 patients with chronic HCV infection (genotype 1), treated with pegylated-interferon-alpha2b plus ribavirin. Of these 97, 38 (39%) were sustained responders and 59 (61%) were not. Statistical differences between responders and nonresponders were found regarding the percentage of infected hepatocytes (6.83+/-4.50% versus 13.44+/-10.05%; P=0.00003) but not in serum HCV-RNA concentration [1.71+/-2.70 (x10(6) IU/L) versus 1.32+/-1.86 (x10(6) IU/L); P=0.40694]. Other factors associated with response were age, gamma-glutamyl transpeptidase level, and absence of previous therapy. Logistic regression demonstrated that percentage of infected hepatocytes (odds ratio, 1.160; 95% confidence interval, 1.065-1.264) and previous therapy (odds ratio, 0.294; 95% confidence interval, 0.109-0.795) were significant predictive factors for response. Therefore, the percentage of infected hepatocytes in liver biopsy before treatment is a better predictive factor of sustained response to 48 weeks of therapy with pegylated alpha-interferon plus ribavirin than serum HCV-RNA concentration in baseline serum sample.

Traitement curatif de courte durée de l’hépatite chronique virale C

Chronic viral C hepatitis can be cured by shorter treatment than recommended. It is illustrated by our two case reports. We report two cases of chronic viral C hepatitis cured by short therapy with interferon standard alone in one case and the combination of pegylated-interferon and ribavirin in the second case. Genotype was undetermined for one patient and 3a for the other. Excepted genotyping and early testing of viral load decrease during treatment (12th week), we lack early predictive factors of sustained response that could help avoid prolonged, poorly tolerated therapy in future non-responders. These observations show that the treatment duration of chronic viral C hepatitis can be shortened in selected patients, who should be identified as soon as possible after the beginning of the treatment.

Predictors of response to infliximab in luminal Crohn's disease

To identify predictive factors of response to infliximab in luminal Crohn's disease (CD). All consecutive patients with luminal CD treated with infliximab between October 1999 and March 2003 in Bordeaux's referral centers were included. All had at least 3 months follow-up post infliximab infusion and no prior treatment with infliximab. Response rates were determined 2 and 8 weeks after infusion according to Crohn's Disease Activity Index (CDAI) (remission=CDAI<150 and response=CDAI decrease more than 100). Among 44 patients (33 female; mean age 35 +/- 14 yr.), 39 (88%) had a clinical response 2 weeks after infusion (79% in remission). At week 8, the rate of response was 61.4% and exclusive colonic involvement predicted sustained response to treatment (P=0.03). The probability of remission at 56 weeks was 21.4%. Multivariate analysis demonstrated that the only factor associated with response duration was initiating immunosuppressive (IS) therapy in women (RR=3.61 95%CI[1.25-10.41], P=0.017). Exclusive colonic involvement is the only predictive factor of sustained response to infliximab in luminal CD. At the time of infliximab infusion, initiation or modification of IS therapy may favor sustained response, at least in women.

Interferon beta induction/interferon alpha therapy in patients with interferon-resistant chronic hepatitis C

The treatment of chronic hepatitis C with a standard regimen of therapy with interferon (IFN) alpha for 6 months results in a sustained response (SR) in a minority of patients with high levels of HCV-RNA. The aim of this study was to assess whether a high dose of IFN and IFN beta induction/IFN alpha therapy increase efficacy, and to identify the determinants or predictive factors of SR in patients with IFN resistant chronic hepatitis C. In 99 patients with high levels of HCV-RNA (>1 Meq/ml), we compared the efficacy of IFN beta induction/IFN alpha therapy ( n=50) and IFN alpha monotherapy ( n=49). HCV-RNA clearence was observed in 22 patients (44%) in IFN beta induction/IFN alpha group and 11 (22.4%) in IFN alpha monotherapy group at 7 days after the start of treatment, there were significant difference between these two groups ( P=0.0327); in 26 (52%) and 13 (26.5%) at the end of treatment, there were significant difference between these two groups ( P=0.0134); in 9 (18%) and 3 (6.1%) at 6 months after the end of treatment, there was no difference between these two groups ( P=0.1212), respectively. SR was observed in 9 (18%) and non-response in 41 (82%) with the IFN beta induction/IFN alpha therapy, and in 3 (6.1%) and 46 (93.9%) with IFN alpha monotherapy, respectively. IFN beta induction/IFN alpha therapy was better than IFN alpha monotherapy by HCV-RNA clearance at 7 days after the start of treatment and at the end of treatment, but there was no significant difference between these two groups at 6 months after the end of treatment. IFN beta induction/IFN alpha therapy was superior to IFN alpha monotherapy in the treatment of chronic hepatitis C, and this therapy may be recommended for patients with high levels of HCV-RNA of chronic hepatitis C.

Interferon-alpha treatment of chronic hepatitis C in children with hemophilia.

In children with hemophilia, hepatitis C virus (HCV) is the major cause of chronic liver disease. In this study, long-term efficacy of interferon-alpha was studied to determine the factors that predict a sustained response to interferon therapy in young children with hemophilia who have chronic hepatitis C. Seventeen Korean children with hemophilia and chronic hepatitis C were treated with 3.7 million units/m2 of interferon-alpha2a three times weekly for 6 months. Liver biopsy, pretreatment serum HCV RNA quantitation with competitive reverse transcription assay, and HCV genotyping with reverse hybridization assay were performed. Hepatitis C virus genotypes 1a, 1b, and 2a were found in three (18%), five (29%), and six (35%) patients, respectively. Interferon-alpha was well tolerated, and the frequency of bleeding did not increase. Of the 17 patients, 7 (41%) had a sustained response for 3 years after the end of therapy. Patients with a sustained response had lower pretreatment serum HCV RNA levels. One (13%) of eight patients with genotype 1 and five (83%) of six with genotype 2 had a sustained response (P < 0.05). Interferon-alpha treatment of chronic hepatitis C in children with hemophilia was safe and effective in producing sustained responses. The pretreatment serum HCV RNA level and viral genotype may be predictive factors for sustained response to interferon therapy.

Interferon‐α Treatment of Chronic Hepatitis C in Children with Hemophilia

ABSTRACTBackgroundIn children with hemophilia, hepatitis C virus (HCV) is the major cause of chronic liver disease. In this study, long‐term efficacy of interferon‐α was studied to determine the factors that predict a sustained response to interferon therapy in young children with hemophilia who have chronic hepatitis C.MethodsSeventeen Korean children with hemophilia and chronic hepatitis C were treated with 3.7 million units/m2 of interferon‐α2a three times weekly for 6 months. Liver biopsy, pretreatment serum HCV RNA quantitation with competitive reverse transcription assay, and HCV genotyping with reverse hybridization assay were performed.ResultsHepatitis C virus genotypes 1a, 1b, and 2a were found in three (18%), five (29%), and six (35%) patients, respectively. Interferon‐α was well tolerated, and the frequency of bleeding did not increase. Of the 17 patients, 7 (41%) had a sustained response for 3 years after the end of therapy. Patients with a sustained response had lower pretreatment serum HCV RNA levels. One (13%) of eight patients with genotype 1 and five (83%) of six with genotype 2 had a sustained response (P &lt; 0.05).ConclusionsInterferon‐α treatment of chronic hepatitis C in children with hemophilia was safe and effective in producing sustained responses. The pretreatment serum HCV RNA level and viral genotype may be predictive factors for sustained response to interferon therapy.

Utility of early testing for HCV viremia as predictive factor of sustained response during interferon or interferon plus ribavirin treatment

Background/Aim: To evaluate the utility of early testing for hepatitis C viremia as a predictor of treatment outcome during interferon or combination therapy. Methods: We studied 184 patients with chronic hepatitis C who received interferon and were monitored for HCV RNA. Sixty-two patients received interferon alone for 12 months and 122 patients, who were still HCV RNA positive at 2 months, received an additional 12-month course of interferon and ribavirin combination therapy. Results: Using this strategy, sustained response occurred in a total of 34 patients (18.5%). Independent variables associated with sustained response were HCV genotype ( p=0.06), viral load ≤5.1 logs/ml ( p= 0.005) and negative HCV RNA at 1 month ( p<0.0001) in the interferon group, and female sex ( p=0.04), genotype ( p=0.03), viral load ≤5.5 logs/ml ( p=0.01), normal ALT ( p=0.001) and decline in viral load ≥1.2 logs/ml after 2 months of interferon monotherapy ( p<0.001) and negative viremia at 5 months of ribavirin onset ( p<0.0001) in the combination therapy group. Persistence of viremia at 1 month of interferon monotherapy and at 5 months of combination therapy were the strongest predictors of non-response (negative predictive value of 100% and 99%, respectively). Conclusions: Qualitative assessment of HCV RNA during treatment is the strongest predictor of sustained response during interferon or combination therapy for chronic hepatitis C.

Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C

Background & Aims: In patients with chronic hepatitis C treated with interferon alfa, sustained normalization of alanine aminotransferase was observed in about 20%, and no predictive factor of response could be clearly identified. The aims of this study were to assess the efficacy of an escalating dose of interferon and to determine the predictive factors of response. Methods: Seventy-five patients were randomly assigned to two groups. Twenty-five patients received a dosage of 3 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, and 50 patients received a dose that was increased to 5 million units at 8 weeks in nonresponders and to 10 million units 8 weeks later in persistent nonresponders. Multivariate analysis was performed to determine the features associated with response. Results: A sustained response was observed in 17% of the patients with constant dosage and in 19% of patients with an escalating dosage. Low pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype were found to be independent predictive factors of sustained response. Conclusions: In patients with chronic hepatitis C, an escalating dosage of interferon did not improve the overall rate of response. Low pretreatment serum hepatitis C virus RNA levels and genotype other than 1b were the only predictive factors of sustained response.

Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients.(ABSTRACT TRUNCATED AT 250 WORDS)