Recalcitrant giant orf recurrence after amputation: A case report and review of the literature.

Orf is caused by a parapoxvirus. We present a recurrent, giant digital orf case in a female patient with a history of hairy cell leukemia. In spite of shave excision, the lesion progressed and recurred after digital amputation. Treatment with topical imiquimod cream and systemic subcutaneous interferon alfa-2a was successful.

A Case of Acquired von Willebrand Disease Secondary to Myeloproliferative Neoplasm.

Acquired von Willebrand Disease (AVWD) is a rare disorder in which qualitative or quantitative defects in von Willebrand factor (VWF) occur secondary to other conditions. AVWD occurs in patients with myeloproliferative disorders due to formation of autoantibodies against VWF and development of excessive shear stress causing disruption of VWF multimers. AVWD is different from congenital VWD in its acute onset and absence of family history. We report a 42-year-old gentleman with essential thrombocythemia, who was on cytoreductive therapy with hydroxyurea, and presented with an acute history of gum bleeding with hemoptysis, without any antecedent trauma or infections. His platelet count was very high, and prothrombin time and activated partial thromboplastin time were prolonged. The VWF ristocetin cofactor assay (VWF: RCo) was low, but VWF antigen level (VWF: Ag) was normal. Their ratio (VWF: RCo/VWF: Ag) was much lower than the acceptable lower limit. Treatment in AVWD is focused on addressing the underlying disorder. Early recognition of AVWD and its primary cause is mandatory in providing adequate therapy and achieving a cure.

Treatment of severe pneumonia due to COVID-19 with peginterferon alfa 2a.

The outbreak of the new coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Until now, no definite effective treatment has been identified. We reported 3 patients with severe COVID-19 treated with pegylated interferon alfa 2a with satisfactory recovery. Based on these observations, randomized studies with interferons should be considered in deteriorating patients infected with COVID-19.

Treatment of transfusion-dependent congenital dyserythropoietic anemia Type I patients with pegylated interferon alpha-2a.

OBJECTIVE: Pegylated IFN-α2a has been reported in two case reports as being efficacious in treating CDA-I patients. This study aims to assess its efficacy on a series of CDA-I patients. METHODS: Study sample consisted of seven CDA type 1 transfusion-dependent patients. They received pegylated interferon alpha-2a at an initial dose of 90-180 µg once a week, tapered according to clinical response and side effects. Good response was defined as Hb ≥ 10 g/dL for ≥3 months, partial response was defined as 7 ≤ Hb<10 g/dL for ≥3 months, and no response was defined as HB < 7 g/dL for over 3 months on treatment. Time to response was defined as the time needed to achieve hemoglobin levels ≥ 10 g/dL without transfusion. Patients were evaluated periodically by abdominal ultrasounds to rule out liver adenomas. RESULTS: Five patients (71%) had a good response to treatment. One patient stopped treatment due to side effects. One patient had partial response. One patient, with more severe phenotype and poor compliance, had poor response to treatment. No abnormal findings were found in ultrasound examination. No effect on serum ferritin level could be established. CONCLUSION: Pegylated interferon α2a therapy is efficacious in CDA-I patients with a reasonable safety profile.

Pegylated-interferon consolidation treatment versus nucleos(t)ide analogue consolidation treatment in non-cirrhotic hepatitis B patients with hepatitis B e antigen seroconversion: an open-label pilot trial.

BACKGROUND: The safety of nucleos(t)ide analogue (NA) treatment cessation remains one of the most controversial topics in the management of chronic hepatitis B (CHB) patients. This study investigated the efficiency of 48-week pegylated-interferon (peg-IFN) alfa-2a consolidation therapy on viral relapse after discontinued NA treatment in CHB patients who achieved hepatitis B e antigen (HBeAg) seroconversion for > 1 year. METHODS: NA-treated HBeAg-positive patients who achieved the standard of discontinued NA treatment (i.e. time of HBeAg seroconversion > 1 year) were randomly assigned to receive peg-IFN consolidation (n = 24) treatment or continue original NA therapy (n = 24) for 48 weeks. The treatments were then discontinued, and the patients were observed up to 144 weeks. The primary endpoint was the proportion of patients with viral relapse at week 144 among those who received at least one dose of study drug or had at least one study visit [modified intention-to-treat population (mITT)]. RESULTS: Of the 24 patients who received peg-IFN treatment, 6 (25%) experienced viral relapse and 8 (36.3%) showed HBsAg loss during 96 weeks of treatment-free follow-up. Of the patients who underwent NA consolidation treatment, only 1 (4.3%) of 23 patients showed HBsAg loss and 14 (58.3%) of 24 patients experienced viral relapse during follow-up. HBsAg level decline < 0.25 log10 IU/mL at week 96 was significantly associated with viral relapse. CONCLUSION: A 48-week peg-IFN alfa-2a consolidation therapy increased the rate of HBsAg loss and sustained viral replication suppression in HBeAg-positive patients who achieved HBeAg seroconversion for > 1 year after NA treatment discontinuation.

Patient characteristics associated with peglyated interferon alfa-2a induced neutropenia in chronic hepatitis C patients.

Neutropenia is a haematologic disorder commonly reported in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa-2a (PEG-IFN α-2a). The objective of the present project is to identify patient characteristics associated with neutropenia in hepatitis C patients. Demographic, clinical, and genetic data from 715 patients with chronic HCV infection treated with PEG-IFN α-2a and ribavirin. The outcome variable was the development of grade 3 or 4 neutropenia, defined as the decrease in neutrophil counts below 1 109 /L anytime during study. Predictors of neutropenia were identified using a 2-stage approach. First, univariate analysis was performed to identify possible predictors of neutropenia. T test was used for continuous variables and Fisher's exact test was used for categorical variables. Second, multiple logistic regression with stepwise addition was then performed using predictors identified in the univariate analysis step to produce final model containing independent predictors at P < .05. Logistic regression identified female gender, absolute neutrophils counts, and cholesterol level as the main predictors of neutropenia. Female gender increases the odds of experiencing neutropenia by 86% compared to male gender. A 1 unit (mmol/L) increase in cholesterol level decreases the odds of developing neutropenia by 13%. A 55% reduction in the likelihood of developing neutropenia for a 1 unit (109 /L) increase in the absolute neutrophils counts. Patients with high risk of developing neutropenia can be identified. Identification of this cohort allows early intervention to prevent neutropenia. Possible intervention is to administer drugs that raise neutrophil count such as filgrastim before neutropenia occurs.

Cepeginterferon alfa-2b in the treatment of chronic myeloproliferative diseases.

AIM: A comparative evaluation of the effectiveness of different therapeutic strategies in patients with polycythemia vera (PV) and essential thrombocythemia (ET). MATERIALS AND METHODS: Patients with PV or ET, diagnosed according to the criteria WHO 2016 were included in the study. The primary endpoint - 6 months of therapy (clinical-hematological and molecular responses). The secondary endpoint - 12 months of therapy (clinico-hematologic, molecular, histological responses). Sixty three patients were included in the analysis: the first group consisted of 33 patients who received the therapy with ce-pegiterferone alpha-2b (ce-pegalpha-INF-α-2b), 10 of them received previous treatment; the second group - 23 patients btained hydroxycarbamide; the third group - 7 patients were treated with recombinant interferon alpha therapy (rINFα). In comparison groups, differences in age were revealed: patients receiving hydroxycarbamide therapy were older. Phlebotomy occurred in 36% of patients in the first group, 9% in the second group, and 14% in the third group. RESULTS: By the 6th month of therapy, 43% of the patients receiving the ce-pegalpha-INF-α-2b had complete clinical-hematologic response, 36% had partial clinical-hematologic remission and stabilization of the disease was established in 21% cases. No disease progression occured. By the 12th month of therapy, statistically significant differences in terms of efficacy between the different therapeutic groups (p = 0.2462, Fisher's exact test). In all three groups, the allelic load of JAK2V617F decreased: from 50 to 19%, from 22.3 to 15.8%, from 50 to 7.19%, respectively. The lower the allele load positively correlated with better response to therapy, which was observed in all analyzed groups. Hematologic adverse events (AEs) were more frequently observed in patients receiving ce-pegalpha-INF-α-2b therapy. Local reactions developed on 3-7 days of therapy as a hyperemic macula at the injection site. Both these reactions and hair loss did not influence on patient's condition. In the second group (patients with hydroxycarbamide therapy) there were changes in the skin and mucous membranes: dry skin, stomatitis, and in older patients new keratomas appeared. The flu-like syndrome was the most common adverse event associated with the therapy of ce-pegalpha-INF-α-2b, which fully relived during the first month of therapy. There was only one case with the flu-like syndrome we observed at the 11th month of therapy. As a rule, the biochemical blood test changes did not influence on patient's condition, were mostly associated with dietary violations, had a tendency to self-resolution and did not require medical interventions. Serious AEs were reported in one case - pulmonary embolism in a patient treated with rINFα. The reasons for the therapy discontinue in group 1: toxic hepatitis, intolerance, by the request of the patient, inadequate efficacy of therapy; in group 2: skin toxicity, in group 3: thromboses. CONCLUSION: Treatment of ce-pegalpha-INF-α-2b in patients with PV and ET is highly effective - the most patients pbtained clinical and hematological responses. There were no statistically significant differences in these parameters in comparison with hydroxycarbamide and rINFα. The use of the ce-pegalpha-INF-α-2b had an acceptable safety profile. The estimated therapeutic dose should be calculated according to body weight. To reduce the frequency of hematologic AE, titration of the drug dose is required.

Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV).

BACKGROUND: Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. METHODS: Among 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6-24 months while on therapy in all patients, and after therapy discontinuation in some patients. RESULTS: The median age of analyzed 58 patients was 52 years, and 29% were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69% patients, respectively. Twenty-nine patients (50%) had a BM response, including 13 (22%) with a complete BM response (BM-CR). Moreover, 13 patients (22%) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69%), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous. CONCLUSIONS: Our results show the ability of PEG-IFN-α-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation. Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.

Interferon alpha-2a as alternative treatment for conjunctival squamous cell carcinoma. / Interferón alfa-2a como tratamiento alternativo para el carcinoma conjuntival de células escamosas.

CASE REPORT: A 35 year-old male patient with a history of HIV infection characterized by progressive tumour growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a. DISCUSSION: Interferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma.

Correlation between serum ferritin level and antiviral effect of pegylated interferon in chronic hepatitis C patients with genotype 1b / 临床肝胆病杂志

Objective To investigate the correlation between serum ferritin (SF) level and antiviral effect of pegylated interferon-α-2a (Peg-IFNα-2a) in chronic hepatitis C (CHC) patients.Methods A total of 85 CHC patients who were admitted to The First People's Hospital of Zigong from November 2013 to July 2014 were enrolled and treated with subcutaneous injection of Peg-IFNc-2a 180 μμg once a week combined with oral ribavirin 10-15 mg · kg-1 · d-1.The course of treatment was 48 weeks and the patients were followed up for 24 weeks after the treatment ended.SF was measured at week 0,and HCV RNA was measured at weeks 0,4,12,24,48,and 72 to evaluate therapeutic outcome.According to the therapeutic outcome,the patients were divided into rapid virologic response (RVR) group,early virologic response (EVR) group,sustained virologic response (SVR) group,no response group (NR group),and recurrence group;according to the SF level,the patients were divided into high-SF group (≥400 ng/ml) and low-SF group (＜400 ng/ml).An analysis of variance was used for comparison of continuous data between groups,and SNK-q test was used for comparison between any two groups;the chi-square test was used for comparison of categorical data between groups,and Spearman rank correlation was used for correlation analysis.Results Of all patients,36 (42.35％) achieved RVR,70(82.35％) achieved EVR,68 (80.00％) achieved SVR,15 (17.65％) had no response,and 2 (2.35％) experienced recurrence.The NR group and recurrence group had a significant increase in SF level,and the NR group had a significantly higher SF level than RVR group (1489.15 ± 278.21 ng/ml vs 398.12 ±-252.45 ng/ml,q =10.826,P ＜0.01),EVR group (1489.15 ± 278.21 ng/ml vs 514.85-± 275.64 ng/ml,q =10.151,P ＜ 0.01),and SVR group (1489.15 ± 278.21 ng/ml vs 486.45 ± 251.60 ng/ml,q =10.614,P ＜0.01).SF level was negatively correlated with the therapeutic effect of PEG-IFN (rs =-0.688,P ＜0.001).Compared with the high-SF group,the low-SF group had a significantly higher proportion of patients who achieved RVR (85.29％ vs 13.73％,P ＜0.001),EVR (100％ vs 70.59％,P ＜ 0.001),or SVR (100％ vs 66.67％,P ＜ 0.001) and a significantly lower proportion of patients who had no response (0 vs 29.41％,P ＜ 0.001).Conclusion In CHC patients,SF level before treatment is correlated with the antiviral effect of PEG-IFN,suggesting that SF level can predict the antiviral effect of PEG-IFN in CHC patients.

Correlation between serum ferritin level and antiviral effect of pegylated interferon in chronic hepatitis C patients with genotype 1b / 临床肝胆病杂志

Objective To investigate the correlation between serum ferritin (SF) level and antiviral effect of pegylated interferon-α-2a (Peg-IFNα-2a) in chronic hepatitis C (CHC) patients.Methods A total of 85 CHC patients who were admitted to The First People's Hospital of Zigong from November 2013 to July 2014 were enrolled and treated with subcutaneous injection of Peg-IFNc-2a 180 μμg once a week combined with oral ribavirin 10-15 mg · kg-1 · d-1.The course of treatment was 48 weeks and the patients were followed up for 24 weeks after the treatment ended.SF was measured at week 0,and HCV RNA was measured at weeks 0,4,12,24,48,and 72 to evaluate therapeutic outcome.According to the therapeutic outcome,the patients were divided into rapid virologic response (RVR) group,early virologic response (EVR) group,sustained virologic response (SVR) group,no response group (NR group),and recurrence group;according to the SF level,the patients were divided into high-SF group (≥400 ng/ml) and low-SF group (＜400 ng/ml).An analysis of variance was used for comparison of continuous data between groups,and SNK-q test was used for comparison between any two groups;the chi-square test was used for comparison of categorical data between groups,and Spearman rank correlation was used for correlation analysis.Results Of all patients,36 (42.35％) achieved RVR,70(82.35％) achieved EVR,68 (80.00％) achieved SVR,15 (17.65％) had no response,and 2 (2.35％) experienced recurrence.The NR group and recurrence group had a significant increase in SF level,and the NR group had a significantly higher SF level than RVR group (1489.15 ± 278.21 ng/ml vs 398.12 ±-252.45 ng/ml,q =10.826,P ＜0.01),EVR group (1489.15 ± 278.21 ng/ml vs 514.85-± 275.64 ng/ml,q =10.151,P ＜ 0.01),and SVR group (1489.15 ± 278.21 ng/ml vs 486.45 ± 251.60 ng/ml,q =10.614,P ＜0.01).SF level was negatively correlated with the therapeutic effect of PEG-IFN (rs =-0.688,P ＜0.001).Compared with the high-SF group,the low-SF group had a significantly higher proportion of patients who achieved RVR (85.29％ vs 13.73％,P ＜0.001),EVR (100％ vs 70.59％,P ＜ 0.001),or SVR (100％ vs 66.67％,P ＜ 0.001) and a significantly lower proportion of patients who had no response (0 vs 29.41％,P ＜ 0.001).Conclusion In CHC patients,SF level before treatment is correlated with the antiviral effect of PEG-IFN,suggesting that SF level can predict the antiviral effect of PEG-IFN in CHC patients.

Treatment intensification with boceprevir in HIV-positive patients with acute HCV-genotype 1 infection at high risk for treatment failure.

BACKGROUND: According to current guidelines, the universal use of direct-acting antiviral agents in HIV-positive patients with acute hepatitis C (AHC) is not recommended. We aimed to evaluate the concept of treatment intensification with boceprevir (BOC) in HIV-positive patients with HCV-genotype 1 AHC (HIV/AHC-GT1) at high risk for failure to pegylated interferon/ribavirin therapy (PEGIFN/RBV). METHODS: Nineteen consecutive HIV-positive patients with HIV/AHC-GT1 who underwent antiviral therapy were studied retrospectively. Patients were treated with PEGIFN/RBV for 24 or 48 weeks, depending on rapid virologic response (RVR; undetectable HCV-RNA at treatment week [W] 4). Patients without complete early virologic response (cEVR; undetectable HCV-RNA at W 12) were offered treatment intensification with BOC at W 12, resulting in 36 weeks of BOC/PEGIFN/RBV triple therapy (total treatment duration: 48 weeks). RESULTS: Thirty-seven percent (7/19) of patients had an RVR and 74 % (14/19) of patients had a cEVR. BOC was used in four out of five patients who did not achieve cEVR and one patient elected to proceed with PEGIFN/RBV. Sustained virologic response (SVR; undetectable HCV-RNA 24 weeks after the end of treatment) rates were 100 % (14/14) among patients with cEVR treated with PEGIFN/RBV and 75 % (3/4) among patients without cEVR receiving BOC add-on. The patient without cEVR who preferred to continue with PEGIFN/RBV did not achieve SVR. Thus, the overall SVR rate was 89 % (17/19) in intention to treat analysis. CONCLUSIONS: BOC add-on in selected HIV/AHC-GT1 resulted in a high overall SVR rate. If 2nd generation direct-acting antiviral agents (DAAs) are not available, treatment intensification with BOC can be considered in HIV/AHC-GT1 at high risk for failure to PEGIFN/RBV.

Efficacy of peginterferon α-2a in treatment of chronic hepatitis B resistant to multiple nucleos(t)ide analogues / 临床肝胆病杂志

ObjectiveTo investigate the efficacy of peginterferon alfa-2a (PEG-IFN α-2a) in the treatment of HBeAg-positive chronic hepatitis B (CHB) resistant to multiple nucleos(t)ide analogues (NAs). MethodsA total of 120 patients with HBeAg-positive CHB resistant to multiple nucleos(t)ide analogues who were hospitalized or treated in the outpatient department in our hospital from August 2009 to February 2014 were randomly divided into two groups, with 60 patients in each group. The patients in the treatment group stopped NAs and were given PEG-IFNα-2a for 48 weeks, and those in the control group received PEG-IFNα-2a for 48 weeks in addition to the original therapeutic regimen with NAs. The changes in the serological markers of hepatitis B and HBV DNA were observed at weeks 24 and 48 of treatment and at 24 weeks after drug discontinuation. The chi-square test was used for comparison of categorical data between groups, while comporison of continuous data was mode by t test. ResultsThe patients in both groups achieved a satisfactory outcome. The serum HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, and HBsAg clearance rate showed no significant differences between the two groups at weeks 24 and 48 of treatment and at 24 weeks after treatment (all P＞0.05). The adverse events that occurred during PEG-IFNα-2a treatment were pyrexia, headache, inflammation at the injection site, diarrhea, neutropenia, anemia, and depression, and the disease is not serious. ConclusionPEG-IFNα-2a is safe and effective in the treatment of CHB resistant to multiple NAs, and the patients can convert to PEG-IFNα-2a directly as their antiviral therapy.

The influence factor analysis of nutritional risk in treatment of pegylated interferon and ribavirin in patients with chronic hepatitis C / 天津医药

Objective To explore the nutritional risk factors in patients with chronic hepatitis C (CHC), who have been accepted pegylated interferon (IFN) and ribavirin (RVB) therapy (PR). Methods A total of 175 CHC patients treated with PR were included in this study. Data of heights, body weights, and calculated body mass index (BMI) were recorded in patients. At the same time, patients were evaluated nutritional risk with Nutritional Risk Screen 2002 (NRS 2002), and divided into risk group (n=35) and non-risk group (n=140). Results There were significant differences in age, HCV genotype (1b type and not 1b), clinical type (CHC/cirrhosis), the length of treatment time and the tolerance degree for PR therapy between two groups (P<0.05). Logistic regression analysis showed that age (OR=16.068,β=2.777), IFN dosage (OR=3.096, β=1.130), RVB dosage (OR=3.382, β=1.219) and clinical type (OR=5.092, β=1.628) were nutritional risk factors. The HCV genotype (OR=0.384; β=-0.957) was protective factors for nutritional risk. Conclusion There is higher occurrence rate of nutritional risk for CHC patients accepted PR therapy. The dependant nutritional risk factors are advanced age, intolerance for PR therapy and cirrhosis associated CHC. HCV without genotypes 1b is not a nutritional risk factor.

Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.

Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

Efficacy of 24-week pegylated interferon alpha and ribavirin combination therapy in highly selected patients infected with hepatitis C virus genotype 1.

BACKGROUND: Previous studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate. OBJECTIVES: The current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR. PATIENTS AND METHODS: In this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group. RESULTS: The majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99). CONCLUSIONS: The current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.

Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behcet's Disease

Behcet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behcet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behcet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders.

BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection and prior null response (<2 log HCV RNA decline after ⩾ 12 weeks of PegIFN/RBV) have limited options. We evaluated daclatasvir plus once- or twice-daily asunaprevir in non-cirrhotic genotype 1 null responders. METHODS: In this randomized, phase 2a, open-label, 24-week treatment study, 101 patients received daclatasvir (60 mg) once-daily. In addition, 38 genotype 1b patients received asunaprevir (200mg) twice- (DUAL A1) or once-daily (DUAL A2); 36 genotype 1a and 5 genotype 1b patients received asunaprevir twice- (QUAD B1) or once-daily (QUAD B2) plus PegIFN/RBV; and 18 genotype 1a and 4 genotype 1b patients received asunaprevir twice-daily plus ribavirin (TRIPLE B3). The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (sustained virologic response, SVR12). RESULTS: Across all groups, mean HCV RNA was ⩾ 6 log IU/ml, and 99% of patients had a non-CC IL28B genotype. SVR12 rates were 78% (A1), 65% (A2), 95% (B1), and 95% (B2). In B3, most genotype 1a patients experienced virologic breakthrough. The most common adverse events were headache, diarrhea, and asthenia. Grade 3-4 aminotransferase elevations were infrequent and not treatment-limiting. CONCLUSIONS: In genotype 1 null responders, daclatasvir plus twice-daily asunaprevir DUAL therapy is effective for most genotype 1b patients, and daclatasvir, asunaprevir, and PegIFN/RBV QUAD therapy is effective for nearly all genotype 1a and 1b patients; but neither DUAL nor TRIPLE therapy is effective for genotype 1a patients. Interferon-free regimens including daclatasvir and twice-daily asunaprevir for genotype 1 null responders should be tailored to subtype.

Baseline high viral load and unfavorable patterns of alanine aminotransferase change predict virological relapse in patients with chronic hepatitis C genotype 1 or 2 obtaining rapid virological response during antiviral therapy.

BACKGROUND: Rapid virological response (RVR) strongly predicts sustained virological response (SVR) in patients with chronic hepatitis C (CHC), and abbreviates antiviral therapy in some patients. OBJECTIVES: To identify factors predicting virological relapse (VR) in CHC patients who attained RVR. PATIENTS AND METHODS: Medical records of 133 CHC patients with an RVR after completing 24 weeks of antiviral therapy (a combination of pegylated interferon-α and ribavirin) were analyzed. Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR. Patients with normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end-of-treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels were classified as having favorable patterns of ALT change. A trend of increasing ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV RNA ≥ 600000 IU/mL. RESULTS: In total, 116 (87.2%) patients had a SVR and 14 (10.5%) had VR. The VR rates were comparable between patients with genotype-1 (13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis revealed that HVL (P = 0.015; odds ratio [OR] = 14.754; 95% confidence interval (CI) = 1.671-130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95% CI = 1.078-17.930) independently predicted VR. In subgroup analysis, low viral load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%). Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005). CONCLUSIONS: In southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in patients with CHC attaining RVR, except in the subgroup of patients treated with peg-IFN-α-2b with HVL and on-treatment unfavorable ALT patterns.