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  1. Lai JY, Ho JX, Kow ASF, Liang G, Tham CL, Ho YC, et al.
    Front Immunol, 2023;14:1048592.
    PMID: 36911685 DOI: 10.3389/fimmu.2023.1048592
    Interferons (IFNs) are important in controlling the innate immune response to viral infections. Besides that, studies have found that IFNs also have antimicrobial, antiproliferative/antitumor and immunomodulatory effects. IFNs are divided into Type I, II and III. Type I IFNs, in particular IFN-α, is an approved treatment for hepatitis C. However, patients developed neuropsychological disorders during treatment. IFN-α induces proinflammatory cytokines, indoleamine 2,3-dioxygenase (IDO), oxidative and nitrative stress that intensifies the body's inflammatory response in the treatment of chronic inflammatory disease. The severity of the immune response is related to behavioral changes in both animal models and humans. Reactive oxygen species (ROS) is important for synaptic plasticity and long-term potentiation (LTP) in the hippocampus. However, excess ROS will generate highly reactive free radicals which may lead to neuronal damage and neurodegeneration. The limbic system regulates memory and emotional response, damage of neurons in this region is correlated with mood disorders. Due to the drawbacks of the treatment, often patients will not complete the treatment sessions, and this affects their recovery process. However, with proper management, this could be avoided. This review briefly describes the different types of IFNs and its pharmacological and clinical usages and a focus on IFN-α and its implications on depression.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  2. Hui BSM, Zhi LR, Retinasamy T, Arulsamy A, Law CSW, Shaikh MF, et al.
    J Alzheimers Dis, 2023;94(s1):S45-S66.
    PMID: 36776068 DOI: 10.3233/JAD-221081
    BACKGROUND: Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-α, which governs various pathological pathways in different NDs.

    OBJECTIVE: This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-α in neurodegeneration/NDs.

    METHODS: Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search.

    RESULTS: A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production.

    CONCLUSION: The exact role IFN-α in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.

    Matched MeSH terms: Interferon-alpha/therapeutic use
  3. Gill H, Leung GMK, Ooi MGM, Teo WZY, Wong CL, Choi CW, et al.
    Clin Exp Med, 2023 Dec;23(8):4199-4217.
    PMID: 37747591 DOI: 10.1007/s10238-023-01189-9
    Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).
    Matched MeSH terms: Interferon-alpha/therapeutic use
  4. Choon SE, Khoo JJ
    Med J Malaysia, 1997 Dec;52(4):437-40.
    PMID: 10968124
    Kaposi's sarcoma is an uncommon cutaneous neoplasm seen classically in elderly males of East European or Jewish extract. It has been known to be endemic in sub-Saharan Africa for many years. Numerous cases had been described in patients on long-term immunosuppressive therapy and in patients living with acquired immunodeficiency syndrome (AIDS). In spite of the increasing number of organ transplant recipients and people living with AIDS. Kaposi's sarcoma remains rare in Asia. We report two cases seen in Johor, Malaysia.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  5. Guan R
    Med J Malaysia, 2005 Jul;60 Suppl B:28-33.
    PMID: 16108170
    Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
    Matched MeSH terms: Interferon-alpha/therapeutic use*
  6. Shahidah KN, Merican I
    Med J Malaysia, 2005 Jul;60 Suppl B:35-8.
    PMID: 16108171
    Matched MeSH terms: Interferon-alpha/therapeutic use
  7. Gan GG, Pasagna JF, Eow GI, Nadarajan VS
    Singapore Med J, 2007 Mar;48(3):e74-6.
    PMID: 17342275
    Chronic neutrophilic leukaemia is a rare myeloproliferative disease characterised by splenomegaly, sustained neutrophilia, raised vitamin B12 level and absence of the Philadelphia chromosome. We report a 74-year-old man who presented first with Sweet's syndrome and subsequently leukocytosis. He had splenomegaly, a raised vitamin B12 level, serum uric acid and neutrophil alkaline phosphatase score. Cytogenetic study of the marrow was normal and peripheral blood for BCR-ABL gene transcript was not detectable. He subsequently passed away with bronchopneumonia.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  8. Hamidah A, Thambidorai CR, Jamal R
    Med J Malaysia, 2005 Oct;60(4):517-9.
    PMID: 16570722
    We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.
    Matched MeSH terms: Interferon-alpha/therapeutic use*
  9. Hamidah A, Yong JF, Zulkifli HI, Jamal R
    Med J Malaysia, 2002 Sep;57(3):353-6.
    PMID: 12440276
    We describe two cases of transfusion dependent thalassaemics with chronic hepatitis C virus infection whom were treated successfully with interferon and ribavirin, following failure of response or relapse after an initial response to interferon monotherapy. They had sustained virological response for more than twelve months after completing therapy. Transfusion requirements were significantly increased during the combination therapy, probably due to ribavirin-induced haemolysis. Serum ferritin level decreased significantly during the treatment. Combination therapy with interferon alfa and ribavirin may be a feasible treatment option for some nonresponders to prior interferon monotherapy.
    Matched MeSH terms: Interferon-alpha/therapeutic use*
  10. Wong RR, Abd-Aziz N, Affendi S, Poh CL
    J Biomed Sci, 2020 Jan 03;27(1):4.
    PMID: 31898495 DOI: 10.1186/s12929-019-0614-x
    Dengue virus (DENV) is the etiological agent of dengue fever. Severe dengue could be fatal and there is currently no effective antiviral agent or vaccine. The only licensed vaccine, Dengvaxia, has low efficacy against serotypes 1 and 2. Cellular miRNAs are post-transcriptional regulators that could play a role in direct regulation of viral genes. Host miRNA expressions could either promote or repress viral replications. Induction of some cellular miRNAs could help the virus to evade the host immune response by suppressing the IFN-α/β signaling pathway while others could upregulate IFN-α/β production and inhibit the viral infection. Understanding miRNA expressions and functions during dengue infections would provide insights into the development of miRNA-based therapeutics which could be strategized to act either as miRNA antagonists or miRNA mimics. The known mechanisms of how miRNAs impact DENV replication are diverse. They could suppress DENV multiplication by directly binding to the viral genome, resulting in translational repression. Other miRNA actions include modulation of host factors. In addition, miRNAs that could modulate immunopathogenesis are discussed. Major hurdles lie in the development of chemical modifications and delivery systems for in vivo delivery. Nevertheless, advancement in miRNA formulations and delivery systems hold great promise for the therapeutic potential of miRNA-based therapy, as supported by Miravirsen for treatment of Hepatitis C infection which has successfully completed phase II clinical trial.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  11. Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, et al.
    J Clin Virol, 2014 Dec;61(4):509-16.
    PMID: 25200354 DOI: 10.1016/j.jcv.2014.08.008
    In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.
    Matched MeSH terms: Interferon-alpha/therapeutic use*
  12. Abdullah JM, Mutum SS, Nasuha NA, Biswal BM, Ariff AR
    Neurol. Med. Chir. (Tokyo), 2002 Jun;42(6):259-63.
    PMID: 12116532
    A 28-year-old Malay man presented with progressive paraparesis over a period of 6 months. Magnetic resonance imaging of the spine revealed a thoracic intramedullary spinal cord tumor at the T-7 level with homogeneous enhancement following intravenous gadolinium administration. Laminectomy and partial decompression of the tumor was performed. Histological examination of the tumor revealed features of spindle cell hemangioendothelioma. The patient was managed with limited field radiotherapy followed by systemic interferon therapy. Good neurological improvement was seen subsequently. The patient has survived 48 months with growth restraint at the primary site, although residual neurological deficit persists. Immunotherapy should be considered as a treatment modality for intramedullary hemangioendothelioma of the spinal cord after surgery and radiotherapy.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  13. Solomon T
    Curr. Opin. Neurol., 2003 Jun;16(3):411-8.
    PMID: 12858080
    The exotic and emerging viral encephalitides are caused by animal or human viruses and characterised by sudden unexpected outbreaks of neurological disease, usually in tropical and sub-tropical regions, but sometimes spreading to temperate areas. Although a wide range of viruses come within this label, as this review highlights, there are common research questions as to the origin and spread of the viruses, the contribution of viral and host factors to the clinical presentations and outcome, and the possibilities for treatment and vaccination.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  14. Abd El-Maksoud E, Salem AM, Maher AM, Hegazy MGA
    Trop Biomed, 2020 Dec 01;37(4):1083-1092.
    PMID: 33612760 DOI: 10.47665/tb.37.4.1083
    HCV genotype 4 dominates the HCV epidemic in Egypt. Drug resistance was the most serious side effect that reflects bad clinical outcome. Several studies had demonstrated that baseline serum interferon-γ-inducible-protein 10 (IP-10) levels and interleukin 28B polymorphisms were associated with the resistance to the standard of care pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy and development of post-treatment relapse. Our purpose was to assess the predictive value of combining IP-10 levels and IL28B genotypes to PEG-IFNα/RBV therapy response in Egyptian chronic HCV infection patients with genotype 4. Ninety Egyptian patients chronically infected by HCV genotype-4 treated with pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy were enrolled. Serum IP-10 levels were determined by enzyme linked immunosorbent assay pre- and post- treatment. IL-28B (rs12979860 and rs8099917) polymorphisms were performed by PCR-RFLP in all patients. Overall, 38 patients (42.2%) achieved sustained virologic response (SVR) and 52 (57.8%) patients have non-viral response (NVR). Pretreatment serum IP-10 mean levels were significantly lower in patients who achieved SVR than in NVR (P<0.05). CC genotype in IL28B polymorphism (rs12979860) was the favorable genotype as 65.8% achieved SVR, while TT genotype in IL-28B polymorphism (rs8099917) was the favorable genotype as 81.5% achieved SVR. Baseline IP-10 was significantly correlated to genotypes CC in rs12979860 and TT in rs8099917. Combined use of serum baseline IP-10 levels with IL-28B polymorphisms could improve the prediction of SVR to PEG-IFNα/RBV therapy in Egyptian chronic HCV infection patients with genotype 4.
    Matched MeSH terms: Interferon-alpha/therapeutic use
  15. Tan SS, Adlin Nadia Z
    Med J Malaysia, 2017 06;72(3):165-174.
    PMID: 28733564 MyJurnal
    AIM: To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice.

    METHODS: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012.

    RESULTS: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57.1% of patients. The predominant HCV genotype (GT) was 3 at 60.6%, second was GT1 at 36.1% and other GTs were uncommon at about 1% or less. About half of our patients have high baseline viral load (>800,000 iu/ml), 18.3% had liver cirrhosis and 22.3% had HIV co-infection. Co-morbid illness was found in 42.9%, hypertension and type 2 diabetes were the two most common. The overall sustained virological response (SVR) by intention-to-treat analysis were 54.9% (n=150/273), 41.2% (40/97) for GT1, 100% (5/5) for GT2 and 62% (101/163) for GT3. Subgroup analysis for HCV monoinfected, treatment naïve showed SVR of 49.2% (31/63) for GT1, 100% (5/5) for GT2 and 67% (69/103) for GT3. In HCV mono-infected and treatment experienced (n=29), the SVR was 28.6% (4/14) for GT1, 21.4% (69/103) for GT3. In the HIV/HCV co-infected, treatment naïve (n=56), the SVR was 28.6% (4/14) for GT1 and 64.3% (27/42) for GT3. Treatment naïve GT3 mono-infected patients had a statistically significant higher SVR compared to treatment experienced patients (P=0.001). In GT3 patients who achieved rapid virological response, the SVR was significantly higher at 85.2% (P< 0.001). The SVR for cirrhotics were low especially for GT1 at 21% (4/19) and 31% (4/13) based on all patients and treatment naïve HCV monoinfected respectively. In GT3 cirrhotics the corresponding SVR were 57.1% (16/28) and 60.9% (14/23). Premature discontinuation rate was 21.2% with the majority due to intolerable adverse events at 12.1%.

    CONCLUSIONS: In our routine clinical practice, the HCV patients we treated were young, predominantly of GT3 and many had difficult-to-treat clinical characteristics. The SVR of our patients were below those reported in Asian clinical trials but in keeping with some "real world" data.

    Matched MeSH terms: Interferon-alpha/therapeutic use*
  16. Manns M, Zeuzem S, Sood A, Lurie Y, Cornberg M, Klinker H, et al.
    J Hepatol, 2011 Sep;55(3):554-563.
    PMID: 21237227 DOI: 10.1016/j.jhep.2010.12.024
    BACKGROUND & AIMS: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy.

    METHODS: Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5μg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0μg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5μg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800-1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR).

    RESULTS: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms.

    CONCLUSIONS: For patients with chronic hepatitis C genotype 2/3 infection, 24weeks of peginterferon alfa-2b (1.5μg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment.

    Matched MeSH terms: Interferon-alpha/therapeutic use
  17. Sukeepaisarnjaroen W, Pham T, Tanwandee T, Nazareth S, Galhenage S, Mollison L, et al.
    World J Gastroenterol, 2015 Jul 28;21(28):8660-9.
    PMID: 26229408 DOI: 10.3748/wjg.v21.i28.8660
    To examined the efficacy and safety of treatment with boceprevir, PEGylated-interferon and ribavirin (PR) in hepatitis C virus genotype 1 (HCVGT1) PR treatment-failures in Asia.
    Matched MeSH terms: Interferon-alpha/therapeutic use
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