Use of Pegylated Interferon Alpha-2a in Cutaneous T-cell Lymphoma: A Retrospective Case Collection.

Mycosis fungoides and Sézary syndrome are rare and largely incurable types of cutaneous T-cell lymphoma with limited therapeutic options. In 1984 Bunn et al. reported that interferon alpha is an efficient monotherapy in cutaneous T-cell lymphoma and 14 years later it was shown in a prospective, randomized trial that a combination of interferon alpha and psoralen plus ultraviolet A therapy (PUVA) is most efficient in the treatment of cutaneous T-cell lymphoma. Since then interferon alpha as single agent or, most often, in combination with phototherapy and/or retinoids has been integrated as standard of care in cutaneous T-cell lymphoma guidelines worldwide. However, production of interferon alpha was discontinued recently worldwide and pegylated interferon alpha-2a (PEG-IFNα) has been used as an alternative therapy. In contrast to numerous interferon alpha studies, only a few studies focusing on PEG-IFNα are available. Therefore, the aim of this study was to conduct a retrospective data collection to report on the efficacy, adverse events and therapy regimens of PEG-IFNα in cutaneous T-cell lymphoma. In 28 patients with cutaneous T-cell lymphoma treated in Germany and in the Netherlands, 36% of patients achieved complete remission, 36% partial remission and 29% stable disease. Eighteen percent of patients developed adverse events during therapy, which led to the discontinuation of PEG-IFNα therapy in 2 patients. The most common concomittant therapies were oral PUVA phototherapy and local radiotherapy. In conclusion, PEG-IFNα, especially in combination with skin-directed therapies, is an effective treatment option for cutaneous T-cell lymphoma in clinical practice.

Efficacy and safety of topical 5-fluorouracil in conjunctival intraepithelial neoplasia refractory to interferon alpha-2b.

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Aprepitant exerts anti-fibrotic effect via inhibition of TGF-ß/Smad3 pathway in bleomycin-induced pulmonary fibrosis in rats.

Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-ß) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-ß, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway.

Clinical Trial of High-Dose Pegylated-Interferon-Alfa-2b Combined With Phototherapy in Advanced Stage Mycosis Fungoides.

The combination of Interferon-α-2b (IFN-α-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.

Celecoxib, ibuprofen, and indomethacin alleviate depression-like behavior induced by interferon-alfa in mice.

Background Interferon-α (IFNα) therapy causes psychiatric side effects, including depression that may result in poor compliance of therapy. It is important to find alternative therapies for the prevention of IFNα induced depression. Non-steroidal anti-inflammatory drugs (NSAIDs) have been useful in depressive disorder. Therefore the effects of celecoxib, ibuprofen, and indomethacin were evaluated following IFNα-induced depression in mice. Methods Male albino mice weighing 26 ± 2 g were used. Depression was induced by IFNα (16 × 105 IU/kg, SC) for six consecutive days. Animals were first subject to the locomotor test, then the splash test and finally the forced swimming test (FST) on the 7th day. The NSAIDs were administered (IP) either one single dose before the test, or simultaneously with IFNα. Results locomotor activity was only impaired by ibuprofen high dose (75 mg/kg), thus it was not further evaluated. Following IFNα therapy depression-like behaviors were observed; significant changes during the splash test (grooming time 24 ± 7 sec vs. control 63 ± 7 sec), the FST (immobility time 166  ± 15 sec vs. control 128  ± 6 sec), and sucrose preference reduced to 64 ± 0.8%. The NSAIDs noticeably reduced the immobility time in FST, while grooming time was increased. Celecoxib and indomethacin single doses were effective while ibuprofen showed better antidepressant effects when it was administered along with IFNα. Conclusions The NSAIDs were able to prevent IFNα induced depression in mice. NSAIDs administration with IFNα does not interfere with clinical benefit effects of IFNα and they could also be useful to prevent IFNα psychiatric side effects, thus further clinical trials are suggested.

Important Group Differences on the Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: The Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC). OBJECTIVES: To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data. METHODS: Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N = 750) in first-line mRCC, and axitinib versus sorafenib (N = 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item "I am bothered by side effects of treatment," EuroQol five-dimensional questionnaire utility score, and adverse events. RESULTS: When the "I am bothered by side effects of treatment" score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol five-dimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points. CONCLUSIONS: Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.

Alternative treatment in Hepatitis B by using polyherbal formulation.

The hepatitis B is most prevalent diseases (along with morbidities) in Asian countries. This research study has been conducted to provide an alternative treatment which is safe, effective and cost-effective to comprehend relations of disease, symptoms, patients response and the clinical response via better management of hepatitis B. The goal of this research is to evaluate efficacy and safety of herbal medicine as compared to allopathic medicine in patients suffering from hepatitis B. This was a single blind, randomized controlled clinical trial conducted at Shifa-ul-Mulk Memorial Hospital Hamdard University, Karachi and Dar ul Shifa Unani Dawakhana Karachi, Pakistan. The patients of both genders ranging from 25 to 50 years with symptoms and diagnosed for hepatitis B that fulfilled the criteria for membership, and consented for participation were registered. Ethical committee clearance and permission was obtained from the concerned committee at Faculty of Eastern Medicine, Hamdard University, Karachi, Pakistan. No significant difference was identified after treatment and it was found that the efficacy of Alpha (Control drug) is same as Safoof akseer e jigar (Test drug). The data offered support to the null hypothesis and therefore research hypothesis was rejected. According to the statistical analysis by chi square, hepatitis B was recorded as negative in 26 patients (57.77%) out of 45 patients by the use of Interferon Alpha (control therapy) and in 27 patients (64.28%) out of 42 patients by the use of Safoof akseer e jigar (test drug). Comparison of the data recorded of the patients was determined as both drugs showed significant improvement and p value>0.05. The efficacy response is equal in both drugs while test drug showed more safety response. It is concluded that Safoof akseer e jigar possesses as effective a therapeutic value in treating hepatitis B as allopathic medicine.

Eficacia y seguridad del uso de bexaroteno en el tratamiento de micosis fungoide con progresión o persistencia de enfermedad cutánea, luego de tratamiento local y progresión a más de dos terapias sistémicas previas / Efficacy and safety of the use of bexarotene in the treatment of mycosis fungoides with progression or persistence of skin disease, after local treatment and progression to more than two previous systemic therapies

INTRODUCCIÓN: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad del uso de bexaroteno, para el tratamiento de micosis fungoide con progresión o persistencia de enfermedad cutánea, luego de tratamiento local y progresión a más de dos terapias sistémicas previas. La micosis fungoide (MF) es uno de los tipos de linfoma cutáneo de células T (LCCT) más comunes y representa aproximadamente el 5% de todos los linfomas. La MF se presenta en la piel en forma de placas, parches, pápulas, tumores, y eritrodermias. Además, la MF también puede involucrar enfermedad linfática, visceral y en médula ósea. La MF, usualmente es una neoplasia indolente; sin embargo, en algunos casos se puede comportar de forma agresiva e incluso producir la muerte. En el Perú si bien no se conoce la frecuencia de MF con exactitud, se estima que esta representa el 44% del total de linfomas cutáneos primarios. El tratamiento para la MF dependerá del estadío de la enfermedad y del antecedente de tratamiento previo. En la actualidad, en el Petitorio Farmacológico de EsSalud, dentro de las terapias sistémicas, para la población de interés, se encuentra la quimioterapia basada en gemcitabina. Sin embargo, existen otras alternativas de terapias sistémicas como el bexaroteno el cual suele ser considerado como tratamiento para refractariedad previo a gemcitabina, sobre todo en enfermedad temprana, tal como se detalla más adelante en la GPS internacionales incluidas en el presente documento. Por lo tanto, el objetivo de este dictamen es evaluar la eficacia y seguridad del uso de bexaroteno, para el tratamiento de micosis fungoide con progresión o persistencia a enfermedad cutánea, luego de tratamiento local y progresión a más de dos terapias sistémicas previas. METODOLOGIA: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del uso de bexaroteno, para el tratamiento de micosis fungoide con progresión o persistencia a enfermedad cutánea, luego de tratamiento local y progresión a más de una terapia sistémica previa. Esta búsqueda se realizó utilizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE) y National Library of Medicine (PubMed -Medline). Adicionalmente, se realizó una búsqueda manual del listado de referencias bibliográficas de los estudios seleccionados a fin de identificar otros estudios que pudieran ser útiles para la presente evaluación. Por otro lado, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como la Cochrane Group, The National Institute for Health and Care Excellence (NICE), The Agency for Health Care Research and Quality (AHRQ), y The Scottish Medicines Consortium (SMC). Esta búsqueda se completó revisando publicaciones de grupos dedicados a la educación, investigación y mejora de la práctica clínica oncológica dentro de América y Europa, como The National Comprehensive Cancer Network (NCCN), The American Society of Clinical Oncology (ASCO) y The European Society of Medical Oncology (ESMO). Por último, se completó la búsqueda ingresando a la página web www.clinicaltrials.gov, para así poder identificar ensayos clínicos en elaboración o que no hayan sido publicados aún, y así disminuir el riesgo de sesgo de publicación. RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica hasta la fecha para el sustento del uso de bexaroteno en el tratamiento de micosis fungoide con progresión o persistencia de enfermedad cutánea, luego de tratamiento local y progresión a más de una terapia sistémica previa. Así, se presenta la evidencia disponible según el tipo de publicación priorizada en los criterios de inclusión (i.e., GP, ETS, RS y ECA fase III). CONCLUSIONES: En el presente dictamen se evaluó la evidencia científica publicada hasta la fecha en relación al uso bexaroteno para el tratamiento de LCCT (de tipo micosis fungoide) temprana (i.e., estadios IA a IIA) con progresión de enfermedad cutánea o persistencia de enfermedad cutánea luego de tratamiento local y más de una terapia sistémica previa. − En la actualidad en el Petitorio Farmacológico de EsSalud, dentro de las terapias sistémicas para la población de interés, se encuentra la opción de quimioterapia basada en gemcitabina. Sin embargo, existen otras alternativas de terapias sistémicas como el bexaroteno el cual suele ser considerado como tratamiento para refractariedad previo a gemcitabina, sobre todo en enfermedad temprana, tal como se indica en la GPC de NCCN. Por lo tanto, surge la necesidad de evaluar bexaroteno como posible tratamiento para población con enfermedad temprana refractaria a tratamientos local y sistémico previo. A la fecha, toda la evidencia existente en torno al uso de bexaroteno como monoterapia en pacientes con micosis fungoide temprana y refractaria recae en los resultados publicados por Duvic et al., 2001, los cuales proviene de un ensayo de fase II-III, que presenta varias limitaciones y una baja calidad metodológica con alto riesgo de sesgo en varios puntos evaluados. Adicionalmente, lo grupos comparados son en relación a la dosis de uso de bexaroteno y no frente a placebo, o un tratamiento distinto; más aún no se presenta pruebas estadísticas que analicen las diferencias entre dichos grupos de dosis distintas. Por lo tanto, no es claro en qué se traducen los resultados obtenidos en dicho ensayo, tanto para la respuesta global como para calidad de vida del paciente. Por último, a pesar de que los eventos adversos serios son poco frecuentes, existe una proporción elevada de eventos adversos en general. Adicionalmente, dentro del Petitorio Farmacológico de EsSalud se encuentra gemcitabina como opción de tratamiento para MF. La GPC de NCCN 2017, con igual grado de recomendación que bexaroteno, menciona el uso de gemcitabina como una opción de tratamiento para pacientes con enfermedad temprana que han progresado a otras terapias previas. Específicamente, se menciona el uso de gemcitabina para pacientes con enfermedad temprana que han progresado a tratamientos sistémicos como metotrexato e interferón alfa, lo cual se ajusta a la población de la pregunta PICO de interés. Por lo expuesto, el Instituto de Evaluación de Tecnologías Sanitarias-IETSI, no aprueba el uso de bexaroteno como tratamiento para LCCT (de tipo micosis fungoide) temprana (i.e., estadios IA a IIA) con progresión de enfermedad cutánea o persistencia de enfermedad cutánea luego de tratamiento local y más de dos terapias sistémicas previas.

The Clinical Efficacy and Adverse Effects of Interferon Combined with Matrine in Chronic hepatitis B: A Systematic Review and Meta-Analysis.

Currently, many studies have demonstrated certain beneficial effects of interferon (IFN) combined with matrine (Mat) for chronic hepatitis B (CHB) in China. However, the evidence from these randomized control trials is still controversial. Therefore, the aim of this meta-analysis was to explore the efficacy and safety of Mat combined with IFN for CHB. We performed a systematic search of seven databases to identify all randomized controlled trials that treated CHB with IFN or IFN plus Mat from their start date to September 30, 2015. The clinical efficacy and adverse effects were evaluated. Nine studies involving 1089 participants were included. Compared with IFN monotherapy, IFN 5 MU combined with Mat 150 mg augmented the hepatitis B e-antigen negative conversion rate after 3-month treatment [relative ratio (RR) = 1.41; 95% confidence interval (CI) (1.18, 1.69), p = 0.0002] and after 12-month treatment [RR = 1.96; 95% CI (1.21, 3.19), p = 0.006], hepatitis B virus DNA negative conversion rate after 3-month treatment [RR = 1.37; 95% CI (1.16, 1.62), p = 0.0002] and after 12-month treatment [RR = 1.96; 95% CI (1.21, 3.19), p = 0.006], hepatitis B virus e antibody (anti-HBe) conversion rate after 3-month treatment [RR = 1.47; 95% CI (1.19, 1.81), p = 0.0003], and AST level after 3-week treatment [weighted mean difference = -22; 95% CI (-40.41, -3.59), p = 0.02]. Furthermore, IFN 3 MU 3 months combined with Mat 150 mg after 2-month treatment reduced the risk of leucopenia and thrombocytopenia [RR = 0.55; 95% CI (0.36, 0.85), p = 0.007]. Unfortunately, all of the included trials were not in favor of hepatitis B surface antigen (HBsAg) negative conversion rate or influenza-like symptoms. Combination therapy with IFN plus Mat exhibited better clinical efficacy and fewer adverse effects than did IFN monotherapy in patients with CHB, except in the improvement of HBsAg negative conversion rate and influenza-like symptoms. Given the poor methodological quality of the evidence currently available, future high-quality, three-blinded randomized control trials are necessary to confirm these results. Copyright © 2017 John Wiley & Sons, Ltd.

Interferon-based chemoradiation followed by gemcitabine for resected pancreatic adenocarcinoma: long-term follow-up.

To report long-term follow up of a phase II, single-arm trial of resectable pancreatic ductal adenocarcinoma (PDAC) treated with adjuvant interferon-based chemoradiation followed by gemcitabine to determine survival, recurrence, and complications. METHODS: From 2002 to 2005, 53 patients with PDAC underwent pancreaticoduodenectomy and received adjuvant interferon-based chemoradiation consisting of external-beam irradiation and simultaneous 3-drug chemotherapy of continuous daily 5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous interferon-α, followed by two months of weekly intravenous gemcitabine. RESULTS: Actual overall survival for the 5- and 10-year periods were 26% and 10%, respectively, with a median overall survival of 25 months (95% CI: 16.4-38.5). Adverse prognostic factors on multivariate analysis were positive tumor margin (p < 0.035), lymphovascular invasion (p < 0.015), and perineural invasion (p < 0.026). Median time to recurrence was 11 months. Positive tumor margin was associated with lymph node involvement (p < 0.005), portal vein resection (p < 0.038), and metastases (p < 0.018). Late complications were frequent and predominated by gastrointestinal and infectious complications. CONCLUSIONS: Adjuvant interferon-based chemoradiation for PDAC improves long-term survival compared to standard therapy. However, recurrence rates and long-term complications remain high, thus further studies are indicated to assess patient characteristics that indicate a favorable treatment profile.

Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review.

BACKGROUND: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. METHODS: Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint. RESULTS: Eight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression. LIMITATIONS: A meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence. CONCLUSIONS: This systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear.

Noninvasive markers of liver fibrosis: on-treatment changes of serum markers predict the outcome of antifibrotic therapy.

AIM: The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established. METHODS: A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study. RESULTS: At 24 months, absolute changes in Ishak fibrosis stage and ELF ranged from -4 to +4 and from -2.41 to +2.68, respectively. Absolute changes in ELF at 12 months were significantly associated with changes in both ELF and histology at 24 months. A model combining both baseline ELF and change of ELF at 12 months could predict the 24-month ELF (R=0.609, P<1×10), a decrease in ELF at 24 months [area under the curve (AUC): 0.80-0.85] and an increase in ELF at 24 months (AUC: 0.81-0.85). Furthermore, a model combining both baseline histologic stage and ELF together with the change of ELF at 12 months could predict 24-month histology (R=0.601, P<1×10, AUC: 0.88-0.92), histologic fibrosis regression (AUC: 0.81-0.84) and progression (AUC: 0.86-0.91). CONCLUSION: Our observations suggest that a change in the serum marker ELF predicts changes in liver fibrosis over a longer period. These data support the use of ELF as a surrogate marker of liver fibrosis evolution in monitoring antifibrotic treatments, thus permitting 'response-guided' therapy by the early identification of patients who will benefit from prolonged treatment.

Polyunsaturated fatty acids levels and initial presentation of somatic symptoms induced by interferon-alpha therapy in patients with chronic hepatitis C viral infection.

OBJECTIVES: Somatic symptoms are common in depressive disorder and are similar to sickness behaviors due to inflammatory activation after cytokine administration. Omega-3 polyunsaturated fatty acids (PUFAs) are natural anti-inflammatory agents and may reduce inflammation-induced behavioral changes. The aim of this study was to investigate the role of PUFAs on the development of somatic symptoms and depression in patients of hepatitis C virus infection (HCV) receiving interferon-alpha therapy (IFN-α) in a prospective manner. METHODS: In this 24-week, prospective cohort study, 43 patients with chronic HCV ongoing IFN-α therapy were assessed with the mini-international neuropsychiatric interview for major depressive episodes and neurotoxicity rating scale (NRS) for somatic symptoms. RESULTS: One-third later developed IFN-α-induced depression (depression (DEP) group). As compared to subjects without depression, DEP group had higher NRS scores (P < 0.001), lower eicosapentaenoic acid (EPA) levels (P = 0.038) at week 2. Somatic symptoms, regardless of painful/non-painful characteristics, had positive association with arachidonic acid (P < 0.05), and negative association with EPA (P < 0.05). CONCLUSION: This study implies that early intervention with omega-3 PUFAs might be a promising strategy to prevent depression and somatic symptoms in patients receiving cytokine therapy.

Ways to manage hepatitis C without cirrhosis: Treatment by comparison of coded eastern medicine hepcinal with interferon alpha 2b and ribavirin.

Hepatitis C virus (HCV) infection is a serious and significant global health problem in the Pakistan and elsewhere. In majority of cases HCV infection remains asymptomatic but in advance cases it may progress to fibrosis of liver, shrinkage of liver cells or failure of liver. The hepatitis C may progress to cause liver cirrhosis that mostly develop in 20% of the affected patients in 20 years with an increased risk in male, alcoholic drink, immune-compromised and who acquire HCV infection after the age of 40 years. This was an open-label prospective study conducted on 66 clinically and immunologically diagnosed cases of HCV infection. In Hepcinal treated group, there were significant improvement in HCV associated symptoms compared to control group (p<0.05). While Interferon therapy resulted in significant improvement in serological response (55.88%) compared to Hepcinal treated patients (46.88%). It was concluded that Hepcinal has shown better clinical response but no significant serological response (p=0.3244) and it might be an alternative therapy to treat hepatitis C infection and to prevent its progression into chronic ailment.

First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials.

In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon α (IFNα) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFNα monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFNα (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFNα; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFNα monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine kinase inhibitors.

Effects of preventive versus "on-demand" nutritional support on paid labour productivity, physical exercise and performance status during PEG-interferon-containing treatment for hepatitis C.

BACKGROUND AND OBJECTIVE: Deterioration of nutritional status during PEG-interferon containing therapy for chronic hepatitis C can be ameliorated by preventive nutritional support. We aimed to explore whether such support also affects paid labour productivity, physical exercise and performance status. METHODS: In this prospective randomized controlled trial (J Hepatol 2012;57:1069-75), 53 patients with chronic hepatitis C had been allocated to "on demand" support (n=26: nutritional intervention if weight loss>5%) or preventive support (n=27: regular dietary advice plus energy- and protein-rich evening snack) during PEG-interferon-containing therapy. Paid labour productivity, physical exercise and performance status were evaluated at baseline, after 24 and (if applicable) after 48 weeks of treatment. RESULTS: At baseline, 46% of patients performed paid labour and 62% performed some kind of physical exercise. Furthermore, most patients were able to carry out normal activity with only minor symptoms of disease (mean Karnofsky performance score: 94). Decreases of paid labour productivity (-21% vs. -70%, P=0.003), physical exercise activity (-43% vs. -87%, P=0.005) and Karnofsky performance scores (-12% vs. -24%, P<0.001) were less in the preventive than in "on demand" group after 24 weeks of treatment. Effects of preventive nutritional support were even more pronounced after 48 weeks. CONCLUSIONS: Preventive nutritional support markedly ameliorates decreases of paid labour productivity, physical exercise and performance status during PEG-interferon-containing treatment for chronic hepatitis C.

Combined etiology for bilateral and simultaneous optic neuropathy in a patient with ciancobalamin deficit and hepatitis C treated with peg-interferon and ribavirin.

We report the case of a 53-year-old female patient who developed bilateral sudden visual acuity loss after 15 weeks from the initiation of Peg-Interferon and Ribavirin treatment for hepatitis C. Debut was simultaneous and asymmetric, reported in the morning, at awakening. No pain or other symptom was reported by the patient. Results. At presentation, visual acuity was 0.2 in RE and 3/ 50 in LE. Pupillary reflexes were sluggish and severe dyschromatopsia was documented in both eyes (Ishihara plates). Fundus examination revealed bilateral pale optic disc edema, more prominent in LE, with splinter hemorrhages in the RNFL around the optic disk. Visual field exam demonstrated severe defects in 3 quadrants of the RE, whereas in the LE, it was impossible to perform the investigation due to VA<0.1. Neurologic evaluation was normal; other possible causes of systemic vasculitis were excluded by negative lab tests. Acute inflammatory markers (fibrinogen and ESR) and mild pancytopenia were the only documented laboratory changes in this patient. Anamnesis cleared the traditional risk factors for conventional AION (hypertension, diabetes, ischemic heart disease, and hypercholesterolemia). Cranial and orbital CT scan and MRI findings were normal. Patient was withdrawn from the Interferon and Ribavirin treatment and was administered methyl prednisolone pulse therapy (1g/ day) for 3 days, continued with oral Prednisone (60 mg/ day) tapered slowly for over 12 weeks. VA increased to 0.8 during treatment in the RE, but visual recovery in the LE was not as spectacular (0.16) as in the fellow eye. Modified latencies and amplitudes in evoked visual potentials examination during 4 months time emphasized bilateral optic atrophy. Optic nerve sufferance was amplified by a low level of vitamin B12, detected by chance at the last eye visit. Due to the general condition, dietary supplementation was not possible. Conclusion. A case of a patient with bilateral and simultaneous NAION caused by IFN and Ribavirin treatment for hepatitis C, who was also vitamin B12 deficient, was analyzed. Therefore, a combined etiology for optic atrophy was explained.

The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome.

Factors Associated with Failure to Achieve SVR in Hepatitis C Genotype 3 Patients Within an Integrated Care Delivery System.

BACKGROUND: Achievement of sustained virologic response (SVR) and factors associated with treatment failure in hepatitis C virus (HCV) genotype 3 have been described in tertiary and referral care settings, with rates of SVR reported to range between 72% and 89%. Fewer data exist on SVR outside of these settings. OBJECTIVE: To describe rates of SVR and characterize factors associated with achievement of SVR within an integrated health care delivery system. METHODS: A retrospective cohort study of genotype 3 HCV patients treated with dual therapy (pegylated interferon-alpha plus ribavirin) was conducted at Kaiser Permanente Southern California. Adult patients diagnosed with HCV and testing positive for HCV-RNA genotype 3 were identified from electronic medical records. Data were collected on patient demographics, baseline health status, and comorbid conditions. A multivariate logistic regression model was used to determine the association between baseline patient factors and SVR. RESULTS: A total of 484 HCV genotype 3 patients met the eligibility criteria. The median age was 49 years, and 65.7% were male. Overall, 252 (52.1%) achieved SVR. Aged ≥ 45 years and male gender were associated with lower rates of SVR; cirrhosis and chronic diseases (diabetes and chronic obstructive pulmonary disease) were also associated with lower rates of SVR. CONCLUSIONS: SVR was lower in patients within an integrated care delivery system than in those in tertiary and referral centers. Males and older patients had lower rates of SVR, as well as patients with cirrhosis, diabetes, and chronic obstructive pulmonary disease.

THE ABSENCE OF THYROID DISEASE IN AN AUSTRALIAN HEPATITIS C COHORT TREATED WITH TRIPLE COMBINATION THERAPY: A PARADIGM SHIFT.

OBJECTIVE: To assess the prevalence of thyroid disease in triple combination therapy with interferon (IFN)-α, ribavirin (RBV), and protease inhibitors (boceprevir and telaprevir) for the treatment of chronic hepatitis C virus (HCV) infection in an Australian hepatitis C cohort. Also, to compare with those who received dual RBV and IFN in the past. METHODS: A preliminary, retrospective, and nested case control study of thyroid disease in patients who underwent triple combination therapy for chronic HCV infection compared with dual therapy at a major tertiary referral hospital center. Fifty-nine patients were treated with such therapy at the Hunter New England Area Hepatitis C Treatment Center. Of these, 38 were treated with boceprevir and 21 with telaprevir. All had genotype 1 HCV infection. The main outcome measures included (1) the prevalence of thyroid disease (TD), including hyperthyroidism and hypothyroidism, and (2) thyroid outcome comparison with patients who had received dual therapy. RESULTS: There was no case of TD detected for the entire duration of therapy with triple anti-HCV therapy. There was a significant absence of TD in the protease inhibitor-treated group. CONCLUSION: No case of TD was detected during the treatment of HCV patients with protease inhibitor-based triple therapy. The reasons for this are unclear. Larger studies are necessary to confirm this finding.