Interferon Combination Therapy Research Articles

The Role of PD-1/PD-L1 Inhibitors in the Treatment of Nasopharyngeal Carcinoma in the Epstein-barr Virus Microenvironment

This article offers an extensive examination of nasopharyngeal carcinoma (NPC), with a particular emphasis on its epidemiological features, relationship with Epstein-Barr virus (EBV) infection, classification system, and current immunotherapy approaches. NPC is notably prevalent in East and Southeast Asia, displaying a robust association with EBV infection, particularly in the non-keratinized subtype. Considering the successful implementation of PD-1/PD-L1 immune checkpoint substance across various cancer, their potential therapeutic benefits in NPC have attracted considerable attention. Although PD-1/PD-L1 inhibitors have exhibited effectualness in NPC patients, the response rate remains inconsistent, suggesting a requirement for deeper investigation into the regulatory mechanisms that govern PD-L1 expression. Furthermore, the approach of combined interferon therapy, designed to augment anti-tumor immunity, has demonstrated potential in enhancing therapeutic outcomes and extending patient survival when administered concomitantly with PD-1/PD-L1 inhibitors. However, several obstacles remain, including drug resistance and the substantial heterogeneity observed in NPC tumors. Tumors from different patients display variations in gene expression patterns, immune microenvironment composition, and other factors, which may lead to divergent patient responses to the combined treatment regimen of PD-1/PD-L1 inhibitors and interferon. This article highlights the research significance of PD-1/PD-L1 combined with interferon in NPC treatment and anticipates its extensive clinical application in the future. Nonetheless, to achieve this goal, several challenges must be tackled through persistent and rigorous research and exploration.

Salmonella immunotherapy engineered with highly efficient tumor antigen coating establishes antigen-specific CD8+ T cell immunity and increases in antitumor efficacy with type I interferon combination therapy

ABSTRACT Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity. In addition, pairing Sal-9RE7 with adjuvant Albumin-IFNβ (Alb-IFNβ), a protein cytokine fusion, the combination significantly increased the antitumor efficacy and enhanced immunogenicity in the tumor microenvironment (TME). Our study made a significant contribution to personalized bacterial immunotherapy via TAA delivery and demonstrated the advantage of combination therapy.

Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

Neurocognitive Changes in Chronic Hepatitis C Patients Receiving Combination Therapy of Interferon and Ribavirin: A Systematic Review

Background: Approximately 3% of the world’s total population is affected by the Hepatitis C virus (HCV). The treatment for HCV differs widely across countries, and one of the therapies used is the combination of interferon (INF) and ribavirin (RBV). Few studies have shown that this combination increases the rate of sustained virological response in HCV patients, resulting in beneficial effects on cognition, while other studies report that it leads to cognitive decline. Thus, this systematic review aims to assess the effects of INF+RBV therapy on neurocognitive changes in HCV patients. Methods: Studies reporting the effect of INF+RBV on neurocognitive changes were searched using Scopus, PubMed, Academia, Google Scholar, Science Direct, and Cochrane. The studies were retrieved till August 23, 2021. The quality assessment of the included studies was done using Cochrane’s bias assessment tool. Results: A total of 6380 articles were found in the initial search. After removing the duplicates, 619 articles were screened on the basis of titles. Further, after the screening, 54 articles were screened on the basis of abstract, and finally, 16 articles were included in this study. Nine studies reported a decline in cognitive function post-INF+RBV therapy, while 7 articles reported improvement in cognitive functions. Conclusion: In conclusion, the combination therapy of INF and RBV may result in cognitive decline in HCV patients.

Combination Therapy of ReciGen Interferon, Methylprednisolone, and Sovodak as a Candidate for Treatment of Patients With Severe COVID-19 in Iran: A Case Series

Introduction: During the current worldwide pandemic of coronavirus disease 2019 (CPVID-19), this disease was first identified in Iran at the end of February. This study was conducted to examine patients with severe COVID-19 disease, who were treated with three medications, namely ReciGen, methylprednisolone, and Sovodak. Case Presentation: We identified 10 patients (3 males and 7 females) with the mean (±SD) age of 55.70±21.48 years, who were admitted to the only referral hospital in Rafsanjan County (Iran) from March to July 2020 with confirmed infections with severe COVID-19. They were treated with the combination therapy of subcutaneous ReciGen interferon every other day, methylprednisolone at a dose of 250 mg every 6 hours for 5 days, and one tablet of Sovodak daily. Conclusion: In the series of cases investigated in this study, the general conditions of all patients improved in terms of their clinical parameters after receiving the combination therapy, and all patients were discharged with a blood oxygen level of≥93% and in good general conditions.

Efficacy and Safety of Interferon in the Treatment of Patients with COVID-19: A Systematic Review and Meta-analysis

Introduction. Interferons (IFNs) modulate the response of the immune system to viruses and decrease vascular leakage. IFNs have shown in-vitro activity against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). It may improve acute respiratory distress syndrome (ARDS) complications in COVID-19. It is currently under investigation as a potential treatment for COVID-19. Objective. This review assessed the efficacy and safety of interferon and interferon combination therapy in patients with COVID-19. Methods. A systematic review and meta-analysis were performed. A search was conducted from December 1, 2019, until March 30, 2021, in MEDLINE, Cochrane CENTRAL, clinicaltrials.gov, medRxiv, ChinaXiv, and bioRxiv databases for studies and preprints. The search was conducted using the keywords “interferon” and “COVID-19” with no restrictions on language. Reference lists of selected articles were also reviewed. Randomized controlled trials on the use of interferon or interferon combination therapy compared with standard of care were included. Two reviewers independently screened, appraised, and extracted data. The risk of bias was appraised using the Evaluation of Articles on Therapy. Certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Data were analyzed using RevMan 5.4. Results. Three RCTs with low certainty of evidence involving 4,279 hospitalized COVID 19 adult patients were included. IFN-β with or without lopinavir did not significantly reduce mortality (RR 1.12, 95% CI 0.83-1.51 and RR 1.16, 95% CI 0.96-1.39, respectively) compared with standard of care. IFN-β showed clinical response on day 14 (aOR 4.05 (95% CI, 1.42-11.55) and reduction in mortality (aOR 6.65, 95% 1.67-26.45) after adjustment for co-administration of glucocorticoid and IVIg. It also showed increased odds of recovery on day 16 (OR 3.19, 95% CI 1.24-8.24), but it did not significantly reduce the odds of developing severe disease or death (OR 0.28, 95% CI 0.07-1.08), intubation, or death (OR 0.42, 95% CI 0.09-1.83) and hospital discharge on day 16 (OR 1.63, 95% CI 0.61-4.35). Serious adverse events in patients receiving IFN-β did not differ from those receiving standard of care. Conclusion. IFN-β or combined with lopinavir did not reduce mortality and progression to severe disease when added to standard of care but showed clinical response on day 16. It demonstrated a reduction in mortality in one study with small sample size. Adverse and serious adverse events were not statistically significant between groups. Its efficacy and safety should further be assessed in randomized controlled trials with higher sample sizes, without co-interventions, and during the earlier stages of COVID-19. Current use of interferon is limited only in clinical trials and compassionate use in severe to critical COVID-19.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Frequency of Erectile Dysfunction in Patients Receiving Pegylated Interferon and Ribavirin for the Treatment of Chronic Hepatitis C

Objective: The purpose behind this study was to determine the frequency of erectile dysfunction in patients receiving pegylated interferon and ribavirin for the treatment of chronic hepatitis C.
 Study Design: Prospective observational study.
 Setting: Department of Gastroenterology and Hepatology, Medical Unit III, Services Hospital, Lahore.
 Period: Six months from 10st July 2017 to 9th January 2018.
 Materials and Methods: We have evaluated a total of 130 patients through a consecutive sampling technique who were admitted or visited Out-Patient-Department (OPD) with an underlying diagnosis of hepatitis C virus infection and advise to take anti viral regime (Pegylated interferon and ribavirin combination therapy) for HCV treatment and followed after 12 weeks and 24 weeks for erectile dysfunction.
 Results: A total of 130 patients with HCV infection were included. The overall mean age of the patients was 37.4±9.6 years. The overall frequency of erectile dysfunction was 83.07%. Among them, equal percentage of patients at 12 and at week 24 did not have erectile dysfunction (N = 76, 58.5%). While severe erectile dysfunction was surprisingly more common at week 12 (14.61%, N = 19) than at week 24 (13.07%, N = 17) of treatment. Significant association of severe erectile dysfunction was only observed at week 12 in age group 40 – 60 years (p <0.05).
 Conclusion: Erectile dysfunction is more common and potential side effect of patients being treated with pegylated interferon and ribavirin but duration of therapy did not affect the prevalence of sexual impairment although with increasing age, the prevalence of sexual dysfunction is significantly increased.

Peginterferon and Entecavir Combination Therapy Improves Outcome of Non-Early Response Hepatitis B e Antigen-Positive Patients.

BackgroundThe efficacy of nucleot(s)ide analogs (NAs) and pegylated interferon (PegIFN) combination therapy for hepatitis B e antigen–positive (HBeAg+) patients is still controversial. Whether PegIFN and entecavir (ETV) combination therapy could provide a greater benefit for HBeAg+ patients was assessed.MethodsTreatment-naïve HBeAg+ patients initiated on PegIFN alfa-2a (PegIFNα-2a) for 24 weeks without early response (early response: HBsAg <1500 IU/mL and hepatitis B virus [HBV] DNA <105 copies/mL) were recruited in the current study. Among total of 94 patients, 51 were continued on PegIFNα-2a monotherapy, and 43 were offered PegIFNα-2a and ETV combined therapy.ResultsBetter outcomes in response to the combined therapy, compared with that of the monotherapy, were demonstrated, including more HBsAg decline and loss and HBV DNA decline and HBeAg clearance. Importantly, the patients with HBsAg levels between 1500 and 20 000 IU/mL initially or between 5000 and 20 000 IU/mL after 24 weeks of PegIFNα-2a benefitted more from the combined therapy, compared with those on monotherapy.ConclusionsCombined therapy of PegIFNα-2a and ETV is more efficacious for HBeAg+ patients without early response to PegIFN monotherapy, and HBsAg levels are a good predictor of treatment outcomes.

Lopinavir/ritonavir and interferon combination therapy may help shorten the duration of viral shedding in patients with COVID-19: A retrospective study in two designated hospitals in Anhui, China.

Prolonged viral shedding may pose a threat to the control of coronavirus disease‐2019 (COVID‐19), and data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) shedding are still limited, with the associated factors being unknown. All adult patients with laboratory‐confirmed COVID‐19 were included in this retrospective cross‐sectional study in two designated hospitals during 21 January 2020 to 16 March 2020 in Anhui, China. In all patients, data on the duration of SARS‐CoV‐2 RNA shedding were analyzed by reviewing all RNA detection results during hospitalization. In addition, demographic, clinical, treatment, laboratory, and outcome data were also collected from electronic medical records. Factors associated with prolonged viral shedding were analyzed with the Cox proportional hazards model. Among 181 patients, the mean age was 44.3 ± 13.2 years, and 55.2% were male. The median duration of viral shedding from illness onset was 18.0 days (interquartile range [IQR], 15.0‐24.0). Prolonged viral shedding was associated with longer hospital stays (P < .001) and higher medical costs (P < .001). The severity of COVID‐19 had nothing to do with prolonged shedding. Moreover, the median time from onset to antiviral treatment initiation was 5.0 days (IQR, 3.0‐7.0). Delayed antiviral treatment (hazard ratio [HR], 0.976; 95% confidence interval [CI], 0.962‐0.990]) and lopinavir/ritonavir + interferon‐α (IFN‐α) combination therapy as the initial antiviral treatment (HR 1.649; 95% CI, 1.162‐2.339) were independent factors associated with prolonged SARS‐CoV‐2 RNA shedding. SARS‐CoV‐2 showed prolonged viral shedding, causing increased hospital stays and medical costs. Early initiation of lopinavir/ritonavir + IFN‐α combination therapy may help shorten the duration of SARS‐CoV‐2 shedding.

Thyroid disturbances in children treated with combined pegylated interferon-alpha and ribavirin for chronic hepatitis C.

BackgroundImmunomodulatory properties of interferon (IFN) have been documented. It may induce autoimmune diseases such as autoimmune thyroiditis with hypo- or hyperthyroidism. In addition, it may impair thyroid hormone synthesis through affecting iodide organification in thyroid gland.PurposeThe aim of this study was to describe thyroid function tests disturbances in children with chronic hepatitis C (CHC) receiving pegylated interferon-alpha (PEG IFN-α) plus ribavirin.MethodsFifty children with CHC virus infection who received combined pegylated interferon-alpha with ribavirin were selected. Other 50 apparently healthy children of matched age and sex (considered as control group) were selected. All children (100) were subject to liver function tests, virological studies, and follow-up of thyroid function test during and after the treatment course.ResultsOur study showed that 28% of children received combined PEG IFN-α plus ribavirin showed subclinical hypothyroidism. After 24 weeks treatment with combined therapy of IFN plus ribavirin, the mean level of thyroid stimulating hormone (TSH) was 3.23±88 mU/mL, while TSH was 1.16± 0.77 mU/mL before starting treatment. On the other hand, mean TSH was 1.09±0.92 mU/mL in normal control group.ConclusionThis study revealed an association between subclinical thyroid dysfunction and treatment with IFN-alpha and ribavirin in children. Further studies on larger number of patients and longer follow-up duration are recommended for further confirmation.

Retinal Changes In Patients with Hepatitis C Virus under treatment with interferon and ribavirin.

Background: Chronic Hepatitis C is common problem worldwide treated by combination of interferon alpha and ribavirin. Retinopathy is one of the side effects of interferon therapy. Aim: determine the frequency and risk factors of retinopathy in patients with chronic hepatitis C treated by interferon and ribavirin combination therapy in Egypt. Methods and Results: Total 100 patients were enrolled among which, 16 (16%) developed retinopathy in the form of cotton wool spots and 14(14%) developed atypical complications. Conclusion: Retinopathy may occur in patients with chronic hepatitis C receiving interferon alpha and ribavirin.

Ribavirin Induced Anemia among Patients with Hepatitis-C at Tertiary Care Hospital.

Introduction: Hepatitis C is among one of the major global health issues; which may cause chronic liver disease, end stage liver disease, and hepatocellular carcinoma; subsequently requiring liver transplant. For HCV, standard treatment is a combination therapy of ribavirin and interferon for six months. Ribavirin fostered hemolysis is a major treatment-associated adverse effect.Objective: To assess ribavirin induced anemia among Hepatitis C patients visiting Civil Hospital, Karachi (CHK).Methodology: This hospital-based cross-sectional study was conducted from October 2017 to January 2018. 106 Hepatitis C patients; through non-probability convenient sampling technique; visiting CHK, a public sector tertiary care hospital were enrolled. Results: Among106 patients, 53 (50.0%) were males and 53 (50.0%) were females. Mean ±SD age was 37.05 ±10.793. Mean ±SD duration of ribavirin use was 3.03 ±1.523 months. Around 16.0% had ribavirin dose reduction. All of them experienced weakness, fatigue and light-headedness, 59.4% developed microcytic hypochromic anemia, 23.6% had severe anemia. Mean ±SD hemoglobin (g/dL) level before the onset of treatment was 12.78 ±1.555. Mean hemoglobin level during treatment was 10.72g/dL. Mean reduction in hemoglobin levels was 2.07g/dL. The reduction in hemoglobin levels and the duration of therapy were correlated (p-value &lt;0.05). The severity of anemia was related to age of the patients (p-value &lt;0.05) but not with gender and morphology of red blood cell.Conclusion: Ribavirin induces anemia, its severity is related to the duration of ribavirin therapy and initial hemoglobin levels. It is sometime severe enough to warrant dose reduction and consequently suboptimal dose of ribavirin affect efficacy.&#x0D; Key Words: Hepatitis C, Ribavirin, Microcytic Hypochromic Anemia.

Meta-analysis of the clinical value of oxymatrine on sustained virological response in chronic hepatitis B

Introduction. Oxymatrine (OMTR) is widely used for the treatment of chronic hepatitis B (CHB) in China. Several recent reports revealed that OMTR together with interferon yielded a higher sustained virological response (SVR) than interferon alone.Aim. To elucidate this topic using meta-analysis of data from published randomized controlled trials (RCTs).Material and methods. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated SVR to interferon therapies and interferon plus OMTR therapies in CHB patients.Results. The literature search yielded 238 studies, and 11 RCTs comprising 968 patients matched the selection criteria. Overall, SVR was significantly higher in patients treated with interferon plus OMTR than in patients treated with interferon alone (SVR: 60.7 vs. 39.8%; relative risk: 1.56; 95% confidence interval: 1.37-1.77; p < 0.05). Combined therapy of interferon plus OMTR were also superior to interferon therapies alone in achieving the end-of-treatment viral response, alaninetransaminase normalization, HBeAg loss, and HBeAg seroconversion.Conclusions. Combined therapy of interferon plus OMTR may yield a higher SVR than interferon therapies. The exact outcome needs to perform rigorously designed, multicenter, and large randomized controlled trials.

Comparison of pegylated interferon monotherapy and de novo pegylated interferon plus tenofovir combination therapy in patients with chronic hepatitis B.

Background and aim: We aimed to evaluate the effectiveness of pegylated interferon (Peg-IFN) monotherapy (IFN group) and combination therapy with tenofovir (TDF) and Peg-IFN (IFN+TDF group) in chronic hepatitis B (CHB) patients.Patients and methods: Data of 143 CHB patients were analyzed in this study. All patients enrolled received liver biopsy. Virologic responses were defined as hepatitis B virus (HBV) DNA <100 IU/mL, biochemical responses were defined as normalization of alanine aminotransferse (ALT) levels, and HBeAg serological response was defined as HBeAg loss or HBeAg seroconversion to HBeAb. HBsAg serological response was defined as HBsAg loss or HBsAg seroconversion to HBsAb.Results: We observed that a total of 16.7% (11/66) and 33.8% (26/77) patients in IFN and IFN+TDF group achieved complete viral suppression after 48 weeks treatment (P=0.02). Although HBeAg levels in CHB patients in the IFN+TDF group decreased more rapidly during the 48-week treatment, we did not observe significant differences in HBeAg serological loss or seroconversion rates between the two groups at 24 and 48 weeks. HBsAg loss was observed in 13.0% (10/77) of CHB patients in the IFN+TDF group at 48 weeks, compared with only 3% (2/66) patients in the IFN group (P=0.032). No significant difference was observed in HBsAg seroconversion rate between the two groups during 48-week treatment. The biochemical response rate was also significantly higher in the IFN+TDF group than that in the IFN group at week 48 (P=0.015). Multivariate logistic analysis showed that IFN+TDF treatment (OR=4.41, P=0.003), severe baseline hepatic inflammation (OR=4.16, P<0.001), and lower baseline serum HBV DNA levels (OR=0.98, P=0.03) were strong predictors for the virological response. Younger age (OR=0.89, P=0.01), higher baseline ALT level (OR=1.01, P=0.038), and lower baseline HBeAg level (OR=0.99, P=0.008) were independent predictors for HBeAg sero-response after 48 weeks treatment. While only severe liver fibrosis (OR=1.69, P=0.028) and lower baseline HBsAg level (OR=0.22, P=0.005) were independent factors associated with HBsAg sero-response after 48 weeks treatment.Conclusion: Peg-IFN combined with TDF may increase the virological response rate, biochemical response rate, and HBsAg loss rate in patients with CHB infection. The combination treatment is more suitable for those patients who are likely to respond to the treatment.

RIBAVIRIN INDUCED ANEMIA: A CROSS SECTIONAL STUDY AMONG PATIENTS WITH HEPATITIS C, VISITING OUT PATIENT DEPARTMENT OF A MAJOR PUBLIC SECTOR TERTIARY CARE HOSPITAL, KARACHI, PAKISTAN.

Background: Hepatitis C is among one of the major global health issues; which may cause chronic liver disease, end stage liver disease, and hepatocellular carcinoma; subsequently requiring liver transplant. For HCV, standard treatment is a combination therapy of ribavirin and interferon for six months. Ribavirin fostered hemolysis is a major treatment-associated adverse effect. Our study aimed to assess ribavirin induced anemia among Hepatitis C patients visiting Civil Hospital, Karachi. Methods: A hospital-based cross-sectional study which included 106 Hepatitis C patients, of 15-60 years' age, visiting CHK, a public sector tertiary care hospital, from October 2017 to January 2018 by using non-probability convenient sampling technique. Results: Total 106 patients participated, 53 (50.0%) were males and 53 (50.0%) were females. Mean (±SD) age was 37.05 (±10.793). Mean (±SD) duration of ribavirin use was 3.03 (±1.523) months. Around 16.0% had ribavirin dose reduction. All of them experienced weakness, fatigue and light-headedness, 59.4% developed microcytic hypochromic anemia, 23.6% had severe anemia. Mean (±SD) hemoglobin level before the onset of treatment was 12.78 (±1.555). Mean hemoglobin level during treatment was 10.72g/dL. Mean reduction in hemoglobin levels was 2.07g/dL. The reduction in hemoglobin levels and the duration of therapy were correlated (p-value &lt;0.05). The severity of anemia was related to age of the patients (p-value &lt;0.05) but not with gender and RBC morphology. Conclusion: Ribavirin induces anemia. The duration of ribavirin therapy and initial hemoglobin levels were related to the severity of anemia, significant enough to cause dose modification and subsequently suboptimal levels affecting efficacy. In return hemoglobin reduction, dose modification and age of the patient were also related.

Impact of human cytomegalovirus on the response of chronic hepatitis C virus-infected patients to pegylated interferone and ribavirin combination therapy

Objective The aim of this study was to study the impact of human cytomegalovirus infection in response rates of patients with chronic hepatitis C virus infection to pegylated interferon and ribavirin combination therapy. Background Cytomegalovirus affects the liver and overall immunological status of the host body. In chronic hepatitis C virus patients, co-infection with Cytomegalovirus could be an additional threat to the host and may contribute to the complexity of disease outcome. Patients and Methods This study was conducted on 40 patients with chronic hepatitis C virus infection candidates for pegylated interferon and ribavirin combination therapy. They were classified into two groups according to response to therapy. Group I (non-responders): included 20 chronic hepatitis C virus patients with any form of non response to therapy. They were 12 males (60%) and 8 females (40%). Group II (responders): included 20 patients with adequate response to therapy at the end of treatment (48 weeks). They were 9 males (45 %) and 11 females (55 %). Results There were significant increases in the number of patients with positive polymerase chain reaction for Human cytomegalovirus DNA in non-responders when compared with responders (14 out of 20 patients versus 5 out of 20 patients respectively). Conclusion Human cytomegalovirus is one of the independent factors that may significantly affect response of chronic hepatitis C virus patients to pegylated interferon and ribavirin combination therapy.

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia.

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. In this latter population, while the course of hepatitis C was accelerated as a consequence of immunodeficiency, the advent of highly active antiretroviral therapy led acquired immunodeficiency syndrome (AIDS) to decline and hepatitis C to progressively emerge as a dominant cause of mortality, in parallel. In patients with thalassemia, transfusion-related transmission of HCV was efficiently interrupted in 1992 with the advent of sensitive screening tests for testing donors for HCV, whereas treatment with interferon and ribavirin of infected thalassemics was constrained by an increased risk of anemia due to the hemolytic properties of ribavirin coupled with interferon-induced bone marrow suppression. The advent of safe and potent regimens based on the oral administration of direct antiviral agents has revolutionized therapy of HCV in patients with congenital blood diseases, providing substantial clinical benefits and making elimination of infection in these populations, possible.

Ocular effects of hepatitis c virus antiviral drugs

Purpose The goal of this research is to find out the incidence of any ophthalmic adverse effects associated with sofosbuvir − ribavirin combination therapy in comparison with sofosbuvir − ribavirin − interferon combination therapy in patients having chronic hepatitis C. Patients and methods A prospective nonrandomized comparative study was carried on 80 eyes of 40 patients with a documented diagnosis of chronic hepatitis C referred by the Internal Medicine and Hepatogastroenterology Department. Study group 1 (20 patients; 40 eyes) patients enrolled in the dual-therapy delineation (a 24-week regimen of 400 mg/day sofosbuvir and a 600 mg/day ribavirin) and study group 2 (20 patients; 40 eyes) patients registered in the triple-therapy planning (12-week regimen of sofosbuvir and ribavirin plus 180-µg peginterferon α-2a subcutaneously weekly). All recorded patients were subjected to entire ophthalmic examination before the medicaments strategy inauguration with periodic examination at 3 and 6 months during the treatment plan using Schirmer test and tear film breakup time test. Results Retinopathy has been evidenced at 3 months after treatment onset in 15% of group 2 candidates and receded at 6 months, which dates 3 months after treatment termination, with no cases of retinopathy in group 1 patients; the difference was statistically insignificant. Schirmer test and tear film breakup time results changed significantly over the 6-month study period. In study group 1, values of both tests decreased at 3 months after the start of sofosbuvir antiviral drug therapy and continued to dwindle throughout the period of follow-up. On the contrary, in study group 2, they decreased at 3 months after treatment onset but came to the common standard values 3 months after treatment discontinuation. Conclusion In our research, both study groups show that the drug-induced dry eye effects were in any event reasonably mild and had trivial effect on one’s daily performance. The retinal lesions in our patients were peacefully asymptomatic, as there were no effects on the best corrected visual acuity (BCVA) in all patients throughout the 6-month study period.

Hepatitis C Genotypes in Libya: Correlation with Patients' Characteristics, Level of Viremia, and Degree of Liver Fibrosis.

Our study sought to determine the distribution of hepatitis C virus (HCV)-genotypes among patients attending two tertiary care hospitals in Benghazi and Tripoli, Libya, and correlate this with patient's characteristics, viral load, and degree of fibrosis. We conducted a retrospective study of 286 HCV-RNA positive Libyan patients referred from different health care facilities in east and west Libya for specific HCV treatment. HCV genotyping was carried out by gene amplification. Liver histology was graded by Metavir score according to the stage of fibrosis. HCV genotypes 1, 2, 3, and 4 were found in 24.1%, 10.8%, 3.4%, and 61.5% of the patients, respectively. Genotype 4 was detected more frequently in patients from east Libya (Benghazi) compared to west Libya (Tripoli) (75.9% vs. 41.6%, p = 0.245). Genotype 1 was more frequent in patients from west Libya compared to east Libya (34.1% vs. 16.8%, p = 0.657). There was a significant correlation between HCV genotype distribution and viral load. Patients with genotype 4 exhibited a higher degree of liver fibrosis (p < 0.001). HCV genotype 4 is the predominant genotype in Libya followed by genotype 1. However, as we go from the east to the west of the country, genotype 1 increases. Genotype 4 was associated with higher level of viremia and higher stage of liver fibrosis. It is important to note that both genotypes 1 and 4 are associated with a poor response to pegylated interferon and ribavirin combination therapy. The findings emphasize the need to develop improved strategies in Libya for the successful treatment of HCV infection with novel newly available antiviral drugs.