Efficacy Of Interferon Therapy Research Articles

Re-Evaluating the Use of IFN-β and Relapsing Multiple Sclerosis: Safety, Efficacy and Place in Therapy.

The advent of interferon therapy for the treatment of multiple sclerosis (MS) was a massive advancement in the field and changed the course of the disease. While the exact mechanism of interferon therapy in MS is unknown, disease control is likely mediated by reducing Th1 and Th17 cells while increasing regulatory T cells and altering the cytokine profile. Interferon therapy not only gave physicians and patients an evidence-based treatment option to treat MS by decreasing relapses and the accrual of disability but it also provided valuable insight into disease pathophysiology that allowed for the development of further treatments. Currently, there are 18 disease-modifying therapies available for the treatment of MS with varying efficacies, routes of administration, and mechanisms. As treatment options in the field have evolved, interferon therapy is less commonly prescribed as first-line therapy, because the newer therapies are more effective and better tolerated. That being said, interferons still have a place in the field in both clinical practice and clinical trial research. In this review, we will summarize the safety and efficacy of interferon therapy and discuss its current place in MS care.

FeLV-infection: problems and prospects of vaccine prevention and interferon-therapy of feline leukemia

Here, we review an overall effectiveness of interferon-based preparations and interferon biosynthesis inducers for treatment of feline leukemia, as well as development of methodological approaches to improve efficacy of interferon therapy. Feline leukemia is a systemic hematopoietic malignancy caused by a single-stranded RNA retrovirus called Feline Leukemia Virus (FeLV) that leads to lethal outcome within about 3 years after the onset. FelV is widely distributed in population of domestic cats worldwide, being often detected in the blood of wild cats, including those of rare and endangered species. In some regions, FeLV prevalence may be high not only among domestic cats, but among wild as well. Currently, there are several commercially available vaccines to protect cats from FeLV infection (e.g., inactivated whole-virion vaccines such as Nobivac adjuvanted Feline 2-FeLV, two-adjuvant subunit vaccine FeLV-derived protein antigens as well as non-adjuvanted vector DNA vaccine). However, none of such vaccines provides durable protection. In addition, vaccination of cats against FeLV is often associated with development of diverse inflammatory, allergic and shock complications, and highly serious side effects such as developing vaccine-associated sarcoma at the injection site that some researchers connect with use of adjuvants like aluminum salts etc. We briefly describe FeLV virus, pathogenetic parametersassociated with FeLV infection as well as current technologies for preventing and treating feline leukemia. A historic background and current state of interferon therapy for FeLV infection as well as associated neoplastic processes in domestic cats and some wild species are evaluated. Possible interventions aimed at improving efficiency of interferon therapy of feline leukemia based on using new recombinant interferon preparations of various types and subtypes, as well as interferon inducers are discussed. In conclusion, it is noted that another interesting and potentially highly promising option in defining strategy of biotherapy associated with modulating IFN system in FeLV-infected animals might be to use of synthetic inducers triggering endogenous IFN production.

Efficacy of interferon therapy in patients with hepatitis B virus‐related primary hepatic carcinoma after transcatheter arterial chemoembolization

AbstractObjectiveIntrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). There are few reports of adjuvant interferon (IFN) therapy for HBV‐related HCC after TACE. The aim of the present study was to evaluate the effect of IFN therapy in patients with HBV‐related primary HCC after TACE.MethodsThe study included 138 patients with HBV‐related unresectable HCC recruited from May 2014 to October 2015. Patients were randomly assigned to the control (n = 68, TACE) or observation group (n = 70, TACE + IFN), and were followed up for more than 24 months. Clinical indexes (cellular immune function, hepatic function, HBV DNA levels, hepatitis B e‐antigen seroconversion and conversion rate, and hepatic fibrosis) before and after treatment, as well as the short‐term curative effect and recurrence, were compared between the groups. To assess the effect of treatment based on the Modified Response Evaluation Criteria in Solid Tumors, progression‐free survival, overall survival, and adverse events were recorded and compared.ResultsAfter treatment, the percentages of CD3+, CD4+, CD4+/CD8+, and natural killer cells were significantly increased in the observation group (TACE + IFN group; P < 0.001) and significantly decreased in the control group (TACE group; P < 0.001). After 4 weeks, the levels of these cells in the observation group were significantly higher than in the control group (P < 0.001). Alanine aminotransferase improved significantly during the follow‐up period in both the control and observation groups (P < 0.001), but was significantly lower in the observation group at 24 and 48 weeks (P < 0.001). At 48 weeks, the HBV DNA undetectable rate was 59.8% in the observation group, whereas HBV DNA levels increased after treatment in the control group; in fact, in 14 patients, HBV DNA levels increased >10‐fold compared with baseline, and the activation rate was 20.6%. There was a significant difference in HBV DNA levels after treatment between the groups (P < 0.001). In the observation group, the hepatitis B e‐antigen seroconversion rate was 45.0%, and the hepatitis B e‐antigen conversion rate was 35.0%; there was no hepatitis B e‐antigen seroconversion or conversion in the control group (χ2 = 9.258, P = 0.001). Hyaluronidase, the layer of mucin, type III collagen, and type IV peptide were decreased in the observation group (P < 0.05), and increased in the control group, and the difference between the groups was statistically significant (P < 0.05). There were statistically significant differences in both the disease control rate and objective response rate between the two groups (χ2 = 4.199, P = 0.040 and χ2 = 9.932, P = 0.001, respectively). At 24‐month follow up, compared with the rates in the control group, the intrahepatic tumor recurrence rate (55.7% vs 69.1%, χ2 = 4.503, P = 0.034) and death rate (38.6% vs 64.7%, χ2 = 9.431, P = 0.002) in the observation group were significantly lower. Both the median progression‐free survival (23.6, 95% [CI 21.4–25.8] months vs 20.3 [95% CI 15.8–24.8] months, χ2 = 4.58, P = 0.026) and overall survival (29.0 [95% CI 27.5–32.1] months vs 26.0 [95% CI 20.1–31.9] months, χ2 = 8.96, P = 0.003] were significantly longer in the observation group than in the control group. Multivariate analysis showed that the number of tumor nodules (P = 0.012) and TACE‐IFN treatment (P = 0.008) were independent factors for overall survival.ConclusionsIFN therapy can effectively enhance cellular immune function, inhibit HBV replication, improve hepatic function, reduce recurrence, and improve survival in patients with HBV‐related HCC after TACE treatment. The side‐effects of IFN are controllable, and the treatment is safe and effective.

Natural history of chronic hepatitis B virus infection in childhood and efficacy of interferon therapy

Objectives. In short-term observations, interferon (IFN) therapy has been shown to be effective in producing both biochemical and virological responses in children with chronic hepatitis B virus (HBV) infection. However, in long-term follow up, no studies have shown a clear advantage of IFN therapy during childhood. We conducted a retrospective study on the sustained effect of IFN therapy among a Japanese pediatric population. Methods and subjects. A retrospective study was performed on 155 children with chronic HBV infection who were followed in two affiliated hospitals during the period from 1986 to 2013. Results. The 155 patients comprised 97 males and 58 female. Infection route was maternal transmission in 96/155 patients. HBV genotype was A in 17, B in 6, and C in 51 patients. IFN therapy was performed in 48 patients. One year after the completion of IFN therapy, normalization of alanine aminotransferase (ALT) and lower viral levels (<104 copies/ml) was observed in 43 and 29 patients, respectively. The sustained effects of IFN therapy were evaluated by comparison between 43 hepatitis B e-antigen (HBeAg)-positive patients treated with IFN and 67 patients with chronic hepatitis B observed without IFN therapy. A Cox’s proportional hazard analysis showed a higher seroconversion rate in the IFN group than in the untreated group (p = 0.003). Similarly, there were higher rates of ALT normalization and lower viral levels in the IFN group than in the untreated group (p = 0.001 for both). Conclusion. IFN therapy showed sustained effects for achieving ALT normalization and HBeAg seroconversion and for reducing the viral load in children with chronic hepatitis B.

Role of Neopterin in Determining the Efficacy of Interferon Therapy in Chronic Hepatitis B and C

Neopterin (NP) is a pteridine derivative that is secreted as a response to gamma interferon stimulation. The purpose in this study was to investigate the relationship between the NP levels and the disease and determining the efficacy of an interferon (IFN) therapy in patients with chronic hepatitis B (CHB) and C (CHC). The study was conducted on 49 cases with CHB, 30 cases with CHC and 72 healthy individuals. Serum samples were taken from the patients receiving treatment at the beginning and at the end of the treatment and only once from the healthy individuals in the control group. The NP levels were found significantly higher in the patients with CHB and CHC than those in the control group. When the pre and post-treatment serum NP levels of the patients who received an interferon therapy were compared, the post-treatment NP levels of the patients who responded to the treatment were significantly higher. When a comparison was made before and after treatment, a decrease was seen in the NP levels in most of the infections due to decreased activation of the immune system. However, when the disease was treated with an IFN therapy, which is a treatment stimulating the immune system, the post-treatment NP level remained high.

Prognostic effect of response to interferon therapy after laparoscopic splenectomy among patients with marked thrombocytopenia and hepatitis C virus-related cirrhosis.

Laparoscopic splenectomy enables patients with marked thrombocytopenia and hepatitis C virus (HCV)-related cirrhosis to receive sufficient interferon-based therapy. The purpose of this study was to evaluate whether the response to interferon after laparoscopic splenectomy contributes to the survival of cirrhotic patients with marked thrombocytopenia. Eighty-seven patients with marked thrombocytopenia and HCV-related cirrhosis who met the inclusion criteria were enrolled. Of the 87 patients, 65 underwent laparoscopic splenectomy for IFN therapy, and 22 patients declined laparoscopic splenectomy and IFN therapy. Finally, 61 patients received IFN therapy after splenectomy, and 26 patients did not receive IFN therapy. The numbers of patients in the sustained virological response (SVR) group, the transient response (TR) group, the no response (NR) group, and the no interferon (IFN) group were 25, 12, 24, and 26, respectively. Seven-year survival in the SVR group, the TR group, NR group, and the no IFN group was 86, 76, 44, and 42%, respectively. When the response group was defined as the SVR or TR group, survival was significantly higher for the response group than for the other groups. However, there was no significant difference between survival in the NR and no IFN groups. On multivariate analysis, independent factors related to survival were the response to interferon, the presence of esophageal varices, and a history of treatment for hepatocellular carcinoma. A good response to interferon after splenectomy was associated with a favorable prognosis. Therefore, prediction of the efficacy of IFN therapy is crucial before splenectomy.

Intact dendritic cell pathogen-recognition receptor functions associate with chronic hepatitis C treatment-induced viral clearance.

Although studies have addressed the exhaustion of the host's immune response to HCV and its role in treatment, there is little information about the possible contribution of innate immunity to treatment-induced clearance. We hypothesized that because intact myeloid dendritic cell (MDC) pathogen sensing functions are associated with improved HCV-specific CD8+ T cell functionality in some chronically infected patients, it might enhance HCV clearance rate under standard interferon therapy. To investigate this hypothesis, TLR-induced MDC activation and HCV-specific CD8+ T cell response quality were monitored longitudinally at the single-cell level using polychromatic flow cytometry in chronically infected patients undergoing interferon therapy. We correlated the immunological, biochemical and virological data with response to treatment. We demonstrate that the clinical efficacy of interferon-induced viral clearance is influenced by the extent to which HCV inhibits MDC functions before treatment, rather than solely on a breakdown of the extrinsic T cell immunosuppressive environment. Thus, viral inhibition of MDC functions before treatment emerges as a co-determining factor in the clinical efficacy of interferon therapy during chronic HCV infection.

Impact of virus clearance for the development of hemorrhagic stroke in chronic hepatitis C

The aim of this retrospective cohort study was to assess the cumulative incidence and predictive factors for intracerebral hemorrhagic stroke after the termination of interferon (IFN) therapy in Japanese patients with hepatitis C virus (HCV). A total of 4,649 HCV-positive patients treated with IFN were enrolled. The primary goal is the first onset of intracerebral hemorrhagic stroke. The mean observation period was 8.0 years. Evaluation was performed using the Kaplan-Meier method and the Cox proportional hazard model. A P-value of less than 0.05 was considered statistically significant. A total of 28 developed intracerebral hemorrhagic stroke. The cumulative incidence of intracerebral hemorrhagic stroke was 0.3% at 5 years, 0.8% at 10 years, and 1.7% at 15 years. Intracerebral hemorrhagic stroke occurred when patients had age increments of 10 years (hazard ratio: 2.77; 95% confidence interval (CI) 1.48-5.18; P = 0.001), hypertension (hazard ratio: 2.30; 95% CI 1.09-4.83; P = 0.021), liver cirrhosis (hazard ratio: 4.50; 95% CI 2.07-9.78; P < 0.001), and HCV non-clearance (hazard ratio: 3.22; 95% CI 1.22-8.53; P = 0.018). On the intracerebral hemorrhagic stroke based on the difference of liver fibrosis and efficacy of IFN therapy, HCV clearance reduced to 24.3% (1/4.11) compared to HCV non-clearance in cirrhotic patients (P = 0.040). In conclusion, HCV clearance reduced the development of intracerebral hemorrhagic stroke. In particular, HCV clearance reduced intracerebral hemorrhagic stroke to about one-fourth in cirrhotic patients.

Эффективность интерферонотерапии для профилактики развития и прогрессирования катаракты после хирургического лечения первичной глаукомы

<p style="text-align: justify;"><span style="color: #800000;"><span style="color: #800000;">https://doi.org/10.31288/oftalmolzh201321518</span></span> <p style="text-align: justify;"><span style="color: #800000;"><strong>Efficacy of interferon-therapy for prevention of developing and progressing cataract after surgical treatment of primary glaucoma</strong></span> <p style="text-align: justify;"><strong>K. P. Pavlyuchenko, S. Yu. Mogilevskyy, V. O. Pentchyuk</strong>

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon-based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa-2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real-time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide -155, -443 and -1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at -443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide -443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment.

Interferon Impedes an Early Step of Hepatitis Delta Virus Infection

Hepatitis delta virus (HDV) infects hepatocytes, the major cell type of the liver. Infection of the liver may be either transient or chronic. The prognosis for patients with chronic HDV infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. The best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. This efficacy of interferon therapy has been puzzling in that HDV replication in transfected cell lines is reported as insensitive to administration of interferon alpha or gamma. Similarly, this study shows that even when an interferon response was induced by transfection of poly(IC) into a cell line, HDV RNA accumulation was only modestly inhibited. However, when the HDV replication was initiated by infection of primary human hepatocytes, simultaneous addition of interferons alpha or gamma at 600 units/ml, a concentration comparable to that achieved in treated patients, the subsequent HDV RNA accumulation was inhibited by at least 80%. These interferon treatments were shown to produce significant time-dependent increases of host response proteins such as for Stat-1, phosphoStat-1, Mx1/2/3 and PKR, and yet interferon pretreatment of hepatocytes did not confer an increased inhibition of HDV replication over interferon treatment at the time of (or after) infection. These and other data support the interpretation that interferon action against HDV replication can occur and is largely mediated at the level of entry into primary human hepatocytes. Thus in vivo, the success of long-term interferon therapy for chronic HDV, may likewise involve blocking HDV spread by interfering with the initiation of productive infection of naïve hepatocytes.

Clinical features of biochemical cholestasis in patients with recurrent hepatitis C after living-donor liver transplantation

Recurrent hepatitis C after liver transplantation (HepC-LT) progresses faster than hepatitis C in non-transplant settings. Cholestasis has been suggested to be one characteristic of HepC-LT related to the rapid progression. We investigated the clinical features of biochemical cholestasis, which we defined as high serum concentrations of alkaline phosphatase and gamma-glutamyl transpeptidase, in patients with recurrent hepatitis C after living-donor liver transplantation. Eighty patients were diagnosed with post-transplant recurrent hepatitis C after exclusion of other aetiologies of cholestasis by liver biopsy and imaging. The clinical features of biochemical cholestasis in the patients with HepC-LT, including histological changes, the efficacy of interferon therapy and helper T-cell (Th) subsets in the peripheral blood, were analysed. Fifty-five of the 80 patients with HepC-LT (69%) had evidence of biochemical cholestasis. Progression of liver fibrosis to stage F3 or F4 was significantly accelerated in patients with biochemical cholestasis compared with patients without cholestasis. The biochemical cholestasis in patients with HepC-LT improved after interferon therapy in 22 of 39 patients (56%) who showed a virological response to the therapy, suggesting that hepatitis C virus (HCV) caused the biochemical cholestasis in these patients. Patients with biochemical cholestasis who had a biochemical response to interferon therapy showed an increased Th1 responses in peripheral blood. In conclusion, biochemical cholestasis is the characteristic feature of HepC-LT and is related to progression of liver fibrosis. An increased Th1 response is associated with cholestasis caused by HCV after liver transplantation.

Effects of Immunosuppressants on the Progression of Hepatitis C in Hepatitis C Virus-Positive Renal Transplantation and the Usefulness of Interferon Therapy

Objective The purpose of this study was to analyze the effects of immunosuppressants on hepatitis C virus (HCV) replication to establish optimal immunosuppressive therapy in HCV-positive renal transplantation. Materials and Methods Cyclosporine (CsA), tacrolimus (Tac), mycophenolate acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and methylprednisolone (MP) were administered to HCV replicon cells alone or in combination with interferon (IFN). HCV RNA was quantitatively determined. Of our 2064 recipients of renal transplantations between 1980 and 2005, 153 were HCV-positive. We analyzed changes in hepatic function and the efficacy of IFN therapy in these patients. Results Only CsA strongly inhibited the growth of HCV RNA (13.1% at 1.0 μg/mL). MPA enhanced the inhibition of the growth of HCV RNA in the presence of IFN. Tac and MP reduced, rather than enhanced, the efficacy of IFN. Progression to chronic hepatitis occurred in a significantly smaller number of patients in the CsA than the Tac group (6 vs 19; P = .04). Serum alanine aminotransferase (ALT) levels were comparable pretransplantation and posttransplantation in the CsA group (24.8 ± 20.5 vs 28.9 ± 28.3 IU/L, respectively, while a significant elevation was noted in the Tac group (22.2 ± 21.5 vs 32.6 ± 30.8 IU/L, respectively; P = .024). Two of 4 patients who underwent combination therapy with IFN and ribavirin during treatment with CsA and MMF obtained an HCV-negative status for over 24 weeks. Conclusions CsA effectively prevents the progression of chronic hepatitis in HCV-positive renal transplant patients. A greater response rate can be expected by concurrent administration of CsA and MMF under IFN therapy.

Retrospective analysis of chronic hepatitis C in untreated patients with nonlinear mixed effects model

It is well known that viral load of the hepatitis C virus (HCV) is related to the efficacy of interferon therapy. The complex biological parameters that impact on viral load are essentially unknown. The current knowledge of the hepatitis C virus does not provide a mathematical model for viral load dynamics within untreated patients. We car-ried out an empirical modelling to investigate whether different fluctuation patterns exist and how these patterns (if exist) are related to host-specific factors. Data was prospectively col-lected from 147 untreated patients chronically infected with hepatitis C, each contributing be-tween 2 to 10 years of measurements. We pro-pose to use a three parameter logistic model to describe the overall pattern of viral load fluctua-tion based on an exploratory analysis of the data. To incorporate the correlation feature of longitu-dinal data and patient to patient variation, we introduced random effects components into the model. On the basis of this nonlinear mixed ef-fects modelling, we investigated effects of host-specific factors on viral load fluctuation by in-corporating covariates into the model. The pro-posed model provided a good fit for describing fluctuations of viral load measured with varying frequency over different time intervals. The aver-age viral load growth time was significantly dif-ferent between infection sources. There was a large patient to patient variation in viral load as-ymptote.

Efficacy of Interferon Therapy in Elderly Patients with Chronic Hepatitis C

Objective: We assessed the efficacy and safety of interferon (IFN) monotherapy in 84 elderly patients aged ≧65 years with chronic hepatitis C in a retrospective cohort study. Methods:Twenty-two of the 84 elderly patients were treated with IFN at a dose of 6 million units daily for 6–8 weeks, 18 patients were treated 2–3 times a week for 24 weeks and 44 patients were treated daily for 2–8 weeks and 2–3 times a week for 16–24 weeks. Results: A sustained virological response (SVR) occurred in 35.7% (30/84) of the patients by intention-to-treat analysis. Multivariate analysis showed that patients achieved a significant SVR when: (1) serum HCV-RNA level before IFN therapy was <100 KIU/ml (p < 0.0001) and (2) staging of liver fibrosis was mild (p = 0.040). Eleven (13.1%) patients discontinued the IFN regimen due to adverse events. Regarding factors predicting discontinuation of IFN, univariate analysis showed that patients aged >70 years were prone to drop out of therapy due to adverse events in IFN therapy (p = 0.009). Conclusion: Our results suggest that IFN administration is suitable for 65- to 70-year-old patients with chronic hepatitis C without genotype 1b and high virus load.

Swimming in cloudy waters: Efforts to prevent HCV-related HCC

Swimming in cloudy waters: Efforts to prevent HCV-related HCC

Split-dosing of subcutaneous alpha and beta interferon reduces local cutaneous complications

RATIONALE: Interferon (IFN) therapy for multiple sclerosis (MS) and hepatitis C (HepC) is associated with severe local adverse effects.METHODS: We studied the efficacy of a split-dosing regimen for subcutaneous interferons. A MS patient receiving recombinant IFN1β 9×106 units on alternate days and a HepC patient receiving pegylated IFNα2a 180mcg weekly were referred for evaluation. Erythematous lesions evolving into necrotic ulcers presented 6 weeks after IFN1β injection. Pruritic hive-like lesions developed 2 hours after IFNα2a injection. No improvement occurred with alternate injection sites. Therapy was discontinued. Prick/intradermal skin tests and incremental challenge were performed in the HepC patient due to rapid onset of reaction. Prick tests were done with undiluted IFNα2A (180mcg/1cc), histamine (6mg/ml) and saline controls. Intradermal skin testing was performed with IFNα2A diluted in saline (1:100 concentration), histamine and saline controls. Subcutaneous incremental challenge began with undiluted IFNα2A 18mcg. Trials of split-dosing, half the standard dose given at two separate sites, were initiated in both patients. The patients were followed for site reactions over subsequent weeks after therapy re-initiation.RESULTS: No immediate or delayed hypersensitivity or irritant reaction was observed after skin testing and challenge with IFNα2a. Split dosing of interferons significantly reduced the severity of reactions and permitted the continued use of these drugs.CONCLUSION: Given the efficacy of interferon therapy and the frequency of cutaneous side-effects, an alternative dosing regimen in patients with severe local complications should be considered. RATIONALE: Interferon (IFN) therapy for multiple sclerosis (MS) and hepatitis C (HepC) is associated with severe local adverse effects. METHODS: We studied the efficacy of a split-dosing regimen for subcutaneous interferons. A MS patient receiving recombinant IFN1β 9×106 units on alternate days and a HepC patient receiving pegylated IFNα2a 180mcg weekly were referred for evaluation. Erythematous lesions evolving into necrotic ulcers presented 6 weeks after IFN1β injection. Pruritic hive-like lesions developed 2 hours after IFNα2a injection. No improvement occurred with alternate injection sites. Therapy was discontinued. Prick/intradermal skin tests and incremental challenge were performed in the HepC patient due to rapid onset of reaction. Prick tests were done with undiluted IFNα2A (180mcg/1cc), histamine (6mg/ml) and saline controls. Intradermal skin testing was performed with IFNα2A diluted in saline (1:100 concentration), histamine and saline controls. Subcutaneous incremental challenge began with undiluted IFNα2A 18mcg. Trials of split-dosing, half the standard dose given at two separate sites, were initiated in both patients. The patients were followed for site reactions over subsequent weeks after therapy re-initiation. RESULTS: No immediate or delayed hypersensitivity or irritant reaction was observed after skin testing and challenge with IFNα2a. Split dosing of interferons significantly reduced the severity of reactions and permitted the continued use of these drugs. CONCLUSION: Given the efficacy of interferon therapy and the frequency of cutaneous side-effects, an alternative dosing regimen in patients with severe local complications should be considered.

Decreased risk of hepatocellular carcinoma in patients with chronic hepatitis C whose serum alanine aminotransferase levels became less than twice the upper limit of normal following interferon therapy

The incidence of hepatocellular carcinoma (HCC) in C-viral chronic hepatitis (CH) and liver cirrhosis (LC) patients after interferon (IFN) therapy was evaluated according to alanine aminotransferase (ALT) levels. Two hundred sixty-nine patients with C-viral CH and LC were treated with natural IFN-alpha. The efficacy of IFN therapy was evaluated based on virologic response and ALT levels using the following groups: virologic-sustained responders (VSR); biochemical-sustained responders (BSR); partial responders (PR), which consisted of BSR patients whose serum ALT levels later relapsed; non-responders (NR)1, which included patients with serum ALT levels that were usually less than 80 IU/l; and NR2, NR with ALT levels persistently more than 80 IU/l. Of the 269 patients, 22 (8.2%) developed HCC after IFN therapy. The incidence of HCC (%/patient/year) was 0.78%, 0%, 0%, 0.17%, 4.68% in VSR, BR, PR, NR1, NR2, respectively. Multivariate analysis revealed that an increase in ALT levels to more than 80 IU/l is an important risk factor for the occurrence of HCC. We concluded that the patients with ALT levels less than twice the upper limit of normal after IFN therapy have a reduced risk of progression to HCC from C-viral chronic liver disease.

Efficacy of interferon therapy for aged patients with chronic hepatitis C

Efficacy of interferon therapy for aged patients with chronic hepatitis C

PSORIASIS SHOULD NOT BE A CONTRAINDICATION TO INTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C

Purpose: The purpose of the study was to determine the safety and efficacy of interferon therapy on psoriasis in hepatitis C patients treated with interferon. Psoriasis, as an autoimmune condition, has been considered a contraindication to interferon therapy in chronic hepatitis C. Methods: A retrospective review of 100 charts of patients with Hepatitis C at an outpatient tertiary liver clinic was performed. 6 patients were identified who had psoriasis and received interferon therapy. A systematic chart review was performed; age, sex, and biopsy results were obtained. The type and duration of therapy was also reviewed including the response to treatment and psoriatic flares during treatment. Results: Of the 6 patients, 4 were male and 2 were females. The majority of patients had advanced liver disease, either bridging fibrosis (2) or cirrhosis (3). Treatment duration ranged from 24 to 96 weeks with either conventional interferon 3/week or pegylated interferon, or both. 3/6 patients had a sustained virologic response (SVR) with therapy. While 2 patients had a worsening of their psoriasis, it had little impact on their treatment since they were able to complete a full course of treatment. One patient who had a SVR has actually had complete resolution of his psoriasis while on treatment that has still not reappeared 6 months after stopping treatment. Conclusions: Interferon therapy for Hepatitis C patients did not have a clinically significant impact on their psoriasis. Patients were able to tolerate the standard duration of therapy and obtain a SVR in 33% of those treated. Patients with psoriasis and Hepatitis C, especially those with advanced his-tologic liver disease, should be considered for interferon therapy in order to prevent progression to cirrhosis and its deadly consequences. Psoriasis should not be considered a contraindication to interferon therapy in patients with hepatitis C.Table 1