Treatment of hepatitis C virus infection with direct-acting antiviral agent-based regimens in Iranian patients with hereditary bleeding disorders.

BACKGROUND: Chronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD. PATIENTS AND METHODS: The present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment. RESULTS: A total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2-100%). CONCLUSION: Hepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.

Acute changes in cardiac function by direct acting antiviral therapy for hepatitis C-infected patients with thalassemia.

BACKGROUND: Patients with thalassemia may also have cardiac abnormalities due to congenital problems, anemia, and increased burden of iron in their myocardium. This study was designed to evaluate the effects of direct acting antiviral (DAA) therapy on the cardiac function of hepatitis C virus (HCV)-infected patients with thalassemia. METHOD: HCV-infected thalassemia patients were enrolled to this prospective evaluation. Daily tablets of 90 mg Ledipasvir (or 60 mg Daclatasvir) plus 400 mg Sofosbuvir (±ribavirin) were prescribed for the patients according to the Iran Hepatitis Network's guidelines. An echocardiography fellow collected the echocardiography findings before and after the treatment of all the patients. The patients were followed up for any cardiac events within 12 weeks after finishing the treatment. RESULTS: Thirty-two patients with the mean age of 24.2 ± 6.4 years were evaluated. All patients showed a sustained virological response at the 12th week after finishing the treatment. The patients' left ventricular end systolic diameter (3.0 vs 3.24; P = 0.003) and volume (33.8 vs 43.6; P = 0.001), global longitudinal strain of the left ventricle (-22.0 vs -20.6, P = 0.046), and average (-21.4 vs -20.3; P = 0.048), and the right ventricle size (3.12 vs 3.31; P = 0.012) were significantly increased after finishing the treatment. Changes in the abovementioned parameters were not correlated with the patients' myocardium iron load. There were no significant differences in other echocardiographic parameters ( P > 0.05) before and after the treatment. CONCLUSION: Sofosbuvir-based regimens for HCV treatment were safe for our HCV-infected patients with thalassemia. Our patients' ejection fraction remained unchanged. Hence, more specialized echocardiographic evaluations were recommended for those with a history of cardiac abnormalities, cardiac iron overload, and in case of any cardiac adverse event during DAA therapy in patients with thalassemia.

A facile PCR-RFLP method for genotyping of ITPA rs1127354 and rs7270101 polymorphisms.

BACKGROUND: Inosine triphosphate pyrophosphatase (ITPA) gene single nucleotide polymorphisms (SNPs), rs1127354 and rs7270101, may cause a functional impairment in ITPase enzyme, resulting anemia protection in patients with chronic hepatitis C virus (HCV) infection undergoing ribavirin (RBV)-dependent regimens. The main purpose of this study was to provide and validate a simple, rapid, and inexpensive polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for genotyping of ITPA rs1127354 and rs7270101 polymorphisms in chronic HCV-infected patients. METHODS: In the current study, 100 Iranian patients with chronic hepatitis C were examined and genotyped for ITPA rs1127354 and rs7270101 gene polymorphisms. To genotype rs1127354 and rs7270101 polymorphisms, PCR-RFLP technique and sequencing technique were performed on these samples. To validate the PCR-RFLP method, the PCR-RFLP genotyping results should be 100% concordant with the PCR-sequencing results. RESULTS: The rs1127354 and rs7270101 polymorphisms of ITPA gene were genotyped by PCR-RFLP technique and sequencing simultaneously, and the results of both techniques were 100% concordant in all 100 patients. Both PCR-RFLP and sequencing techniques indicated that the genotypic frequency of rs7270101 was 80% AA, 19% AC and 1% CC, and for rs1127354 was 79% CC, 20% CA and 1% AA, respectively. CONCLUSION: We developed and validated a rapid and inexpensive PCR-RFLP technique for the detection of ITPA rs1127354 and rs7270101 gene polymorphisms.

Impact of IFNL4 rs12979860 and rs8099917 polymorphisms on response to Peg-Interferon-α and Ribavirin in patients with congenital bleeding disorder and chronic hepatitis C.

BACKGROUND: The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC). METHODS: This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV). Baseline patient and viral parameters were measured and analyzed statistically to assess their combined and individual contributions to SVR prediction. RESULTS: The most prevalent variants of rs12979860 and rs8099917 identified among the study patients were CT (45.9%) and TT (57.6%), respectively. Overall, SVR was achieved in 69% of the study patients. The rate of SVR was lower in patients with HCV genotype-1 than in those with HCV genotype-3 (62% vs 88%; P<.001; OR=0.23). Multivariate analysis of SVR predictors in patients with HCV genotype-1 infection included age (<24 years), BMI (<25), absence of cirrhosis, HCV RNA level (<400 000 IU/mL), rs8099917 TT and rs12979860 CC, all of which were associated with a higher SVR rate. In HCV genotype-3 infection, only rs12979860 CC was significantly associated with SVR. CONCLUSION: These results demonstrate that polymorphisms of the IFNL4 gene are highly associated with SVR to PegIFN and RBV combination therapy in patients with a congenital bleeding disorder and CHC. Assessment of rs12979860 and rs8099917 genotypes can guide physicians in choosing an optimal treatment regimen, including less expensive therapies that may only be available in many geographic locales.

The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C.

BACKGROUND: A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC). MATERIALS AND METHODS: In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated. Single-nucleotide polymorphisms (SNPs) in IFNL genomic region including rs368234815, rs12979860, and rs8099917 were analyzed by DNA sequencing. RESULTS: Of the 92 patients, 63 (68.5%) achieved sustained virological response (SVR). Of the 43 patients with rs368234815 TT/TT genotype, 36 (83.7%) achieved SVR, while in 49 patients with non-TT/TT genotypes, 27 (55.1%) achieved SVR. Other pretreatment parameters predicted SVR were patients' body mass index, HCV genotype, rs12979860, and rs8099917 SNPs. In multivariate analysis, all above-mentioned parameters except rs8099917 remained as predictors of SVR. IFNL4 rs368234815 was a strong predictor of SVR; however, the prediction power of this SNP was the same as that of rs12979860 SNP in the patients of the current study. CONCLUSION: IFNL4 rs368234815 SNP can be considered for decision-making in the treatment of HCV-infected patients.

High Response Rate to Pegylated Interferon Alpha and Ribavirin Combination Therapy in Hemophilic Children with Chronic Hepatitis C; A Case-Control Study.

Scarce data is available on the efficacy of Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) combination therapy in hemophilic children with chronic hepatitis C. The aim of this study was to evaluate the efficacy of Peg-IFN and RBV combination therapy for hemophilic children infected with hepatitis C virus (HCV) in comparison with adult hemophilic patients with chronic hepatitis C. A case-control study comprised 31 pediatric hemophilic patients ages under 16 years with previously untreated HCV genotype-1 or -3 infection as the case group and 62 treatment naive adult hemophilic patients with chronic HCV infection as the control group. Case and control groups were matched case by case according to HCV genotype, HCV RNA level and rs12979860 polymorphism. All patients in the case and control groups were treated with Peg-IFN and RBV for 24-48 weeks according to HCV genotype. Sustained virological response (SVR) was achieved in 26 (83.9%) pediatric patients and in 39 (62.9%) of adult patients (P = 0.05, OR = 3.07, 95%CI = 1.03-9.09). The rate of SVR was not different according to HCV genotype, HCV RNA level, and rs12979860 polymorphism in both studied groups whereas achieving early virological response was associated with achievement of SVR in both groups. The efficacy of Peg-IFN and RBV combination therapy in hemophilic children with chronic hepatitis C is higher than that of adult hemophilic patients.

Standard and pegylated interferon therapy of HDV infection: A systematic review and meta- analysis.

BACKGROUND: Hepatitis D virus (HDV) infection is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Although interferon is the only approved anti-HDV therapy, evidence regarding the efficacy and safety of its various regimens is either old or scattered. MATERIALS AND METHODS: We searched systematically Medline, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, and ISI. The studies that evaluated treatment of chronic HDV infection with standard or pegylated interferon for at least 48 weeks were identified. Our inclusion criteria were positive anti-HDV antibody for 6 months and positive HDV-PCR at the start of study. We performed a meta-analysis for proportions using the arcsine transformation in random effects model. Sustained virological response (SVR) rate (negative Polymerase chain reaction (PCR) 6 months after cessation of therapy) was the end point of interest. RESULTS: Data were abstracted from 14 studies containing 227 chronic HDV-infected patients who received standard or pegylated interferon alpha-2a or -2b. Twenty-one and 30 patients of 71 and 156 who received standard or peginterferon, respectively, beyond 48 weeks achieved SVR. Pooled SVR rates were 29% [95% confidence interval (CI) 19; 41] and 19% (95% CI 10; 29), respectively. The rates of treatment withdrawal were similar. CONCLUSION: Our systematic review indicates that the literature lacks sufficient evidence to establish precise recommendations for treatment of HDV infection. Meta-analysis of these studies shows that standard dose of peginterferon is more effective than high dose of standard interferon as anti-HDV therapy.

WITHDRAWN: Low dose ribavirin for treatment of HCV infected thalassemia major patients: New indications for combination therapy.

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Peginterferon alpha-2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single-centre study of 367 cases.

BACKGROUND/AIMS: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV therapy but there is little information about safety and efficacy of peginterferon alpha-2a and ribavirin combination therapy in these patients. MATERIAL AND METHODS: In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 microg of Pegasys and 800-1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). RESULTS: Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56-66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1-3.1), genotype non-1 OR=1.8 (95% CI 1.1-3.2), BMI<25 OR=2.1 (95% CI 1.3-3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1-3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation. CONCLUSIONS: Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.

Comparative efficacy and overall safety of different doses of consensus interferon for treatment of chronic HCV infection: a systematic review and meta-analysis.

BACKGROUND: About one-half of patients with hepatitis C genotype 1 and one-third with genotype 2/3 have treatment failure with peginterferon alpha and ribavirin. Consensus interferon (CIFN) is an option for retreatment of these patients. OBJECTIVE: To summarize comparative safety and efficacy of different regimens of CIFN for the treatment of patients with chronic hepatitis C infection. DATA SOURCE: Medline, Scopus, ISI, and Cochran Central Register of Clinical Trials were used. STUDY ELIGIBILITY CRITERIA: Randomized clinical trials (RCTs) were eligible for inclusion in the study. PARTICIPANTS: HIV and HBV seronegative patients with positive HCV-RNA during the 6 months before the start of the study were eligible for inclusion. INTERVENTIONS: Different regimens of CIFN were studied. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were appraised based on methods of random sequence generation, allocation concealment, and blinding. The random effects model of DerSimonian and Laird was employed to run the meta-analysis. The end-point was sustained virological response (SVR). RESULTS: Data of 10 RCTs including 1,600 subjects were extracted. High daily induction dose regimen of CIFN did not yield a higher rate of SVR than low daily induction dose treatment regimen, RR = 0.83 (95% CI 0.58-1.17). A dose of 9 µg thrice weekly (tiw) was associated with a significantly higher rate of SVR compared with 3 µg [RR = 3.14 (95% CI 1.68-5.58)][Symbol: see text]. Withdrawal rate was similar [RR = 1.28 (95% CI 0.65-2.50)] but dose modification was higher in 9 µg [RR = 3.22 (95% CI 1.08-9.60)]. A dose of 18/15 µg tiw was not more effective than 9 µg over a similar treatment duration [RR = 1.02 (95% CI 0. 87-1.19)]. LIMITATIONS: Limitations include inadequate reporting of methodological information and side effects, lack of publication bias assessment due to the small number of studies in each analysis. CONCLUSIONS: High dose daily induction therapy with CIFN is not superior to low dose therapy in terms of SVR. It seems that 9 µg tiw is the optimal treatment dose of CIFN for treatment of HCV infection. Optimal duration and safety profile of CIFN therapy have yet been elucidated.

Real-life efficacy of generic sofosbuvir/ledipasvir for treatment of Iranian patients with chronic hepatitis C: A cohort study.

BACKGROUND: Treatment of hepatitis C virus (HCV) infection with recently introduced direct-acting antiviral agents (DAA) is effective and safe, however there is little known regarding safety and efficacy of generic DAAs in the real-life clinical setting. This study aimed to evaluate the efficacy and safety of generic sofosbuvir/ledipasvir (SOF/LDV) in a real-life clinical experience. METHODS: In this prospective cohort study, patients with chronic HCV infection who referred to Middle East Liver Diseases (MELD) Center were included. Based on the patients' condition, they were treated with SOF/LDV fixed-dose combination with or without ribavirin (RBV) for 12 or 24 weeks. RESULTS: A total of 30 (M/F: 19/11) patients with chronic HCV genotype 1 infection with a mean age of 49.8 years were treated with generic SOF/LDV with (9 patients) or without (11 patients) RBV for 12 (27 patients) or 24 (3 patients) weeks. Ten (33.3%) had cirrhosis and 13 (43.3%) with a previous history of treatment with interferon (IFN)-based regimens. Among the 30 patients, 26 (86.7%, 95% CI=70.3%-94.7%) achieved a rapid virologic response, 30 (100%, 95% CI=88.7%-100%) achieved the end of treatment response and 30 (100%, 95% CI=88.7%-100%) achieved a sustained virologic response. No severe treatment adverse event was observed however, 6 (20%) patients experienced mild to moderate adverse events. CONCLUSION: The treatment of HCV genotype 1 infection with generic SOF/LDV found to be safe and effective even in patients with cirrhosis and previous history of treatment with IFN-based treatments.

Distribution of hepatitis C virus genotype in Iranian multiply transfused patients with thalassemia.

BACKGROUND: Hepatitis C virus (HCV) infection is the most common transfusion-transmitted disease in multiply transfused patients worldwide. In this study, the aim was to investigate distribution of HCV genotypes in Iranian patients with thalassemia. STUDY DESIGN AND METHODS: Blood samples were received from 280 multiply transfused patients with thalassemia with chronic hepatitis C who were referred to us to start pegylated interferon-alpha plus ribavirin for duration of 48 weeks. HCV RNA viral load was detected using Amplicor test (Version 2, Roche Molecular Systems). Genotyping was performed by genotype-specific primers. RESULTS: HCV genotype distribution was 1 in 57%, 3 in 35%, 2 in 1%, and mixed in 4% (1 + 3 in 2.8%, 3 + 4 in 0.4%, mixed subtypes in 0.8%) cases. A total of 2.5% of isolates were nontypable. Genotype 1 was associated with higher rate of splenectomy and greater serum ferritin. CONCLUSION: Genotype 1 is the most frequently detected HCV genotype in Iranian patients with thalassemia and might cause more need for splenectomy and more severe iron overloading. Higher HCV viral load could be regarded as another risk factor for greater iron overloading.

First Report of Prevalence of Blood-Borne Viruses (HBV, HCV, HIV, HTLV-1 and Parvovirus B19) Among Hemophilia Patients in Afghanistan.

Blood-borne viruses including Hepatitis B and C, HIV, HTLV-1 and parvovirus B19 are still a factor of concern, especially for hemophilia patients. Although the safety of the blood supply continues to improve worldwide, the blood supply system in Afghanistan was damaged by many years of conflict and political instability. To date, there are few studies focused on the prevalence of blood-borne viruses in hemophilia patients. This study is first to investigate the prevalence of five blood-borne viruses in Afghanistan hemophilia patients in four cities including Kabul, Herat, Mazar-i-Sharif and Jalal Abad. A total of 80 hemophilia male patients were screening for the presence of five transfusion-transmitted viruses using ELISA and PCR. Data obtained showed 2.5% seropositivity for HBV, 8.75% seropositivity for HCV, and 91.25% seropositivity for parvovirus B19. None of the patients were positive for HIV and HTLV-1 and the prevalence of HCV was higher in older patients rather than younger patients. This finding, the first to report in Afghanistan, shows a high prevalence of parvovirus B19 in Afghanistan hemophilia patients and implementation of highly sensitive screening is necessary.

A Simple PCR-RFLP Method for Genotyping of IFNL4 rs368234815 Polymorphism in Patients With Chronic Hepatitis C.

BACKGROUND: The IFNL4 rs368234815 polymorphism plays a prominent role in spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. This study aimed to develop a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for assessment of rs368234815 polymorphism. METHODS: We genotyped the rs368234815 polymorphism in 87 patients with chronic HCV by PCR sequencing and PCR-RFLP methods, simultaneously. RESULTS: Genotyping of IFNL4 rs368234815 via PCR-RFLP was concordant with PCR sequencing in all 87 individuals (100%). The analytical sensitivity and specificity of the developed PCR-RFLP method for genotyping of rs368234815 polymorphism were each 100%. Among these patients with chronic HCV, the frequency of rs368234815 TT/TT, TT/ΔG, and ΔG/ΔG were 44.8%, 37.9%, and 17.3%, respectively. CONCLUSIONS: The PCR-RFLP method that we developed is accurate, rapid, inexpensive, and easy to perform for genotyping of the IFNL4 rs368234815 polymorphism. This method can be used for clinical and research work.

Combination of sofosbuvir, pegylated-interferon and ribavirin for treatment of hepatitis C virus genotype 1 infection: a systematic review and meta-analysis.

BACKGROUND: Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding Sofosbuvir (SOF), an HCV polymerase inhibitor to the conventional therapy of Pegylated-interferon (PegIFN) plus Ribavirin (RBV) can increase the rate of sustained virologic response (SVR) among HCV-infected patients. This study was conducted to determine the effect of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using systematic review with meta-analysis. METHODS: In this study, electronic databases including PubMed, Scopus, Science Direct, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the efficacy of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection were included in the meta-analysis. RESULTS: After screening of 757 records, we included five articles with total sample size of 411 to the meta-analysis. Based on the fixed-effect model (χ 2 = 5.29, P = 0.26 and I2 = 24.4%), pooled SVR rate for treatment regimen of PegIFN and RBV plus SOF was calculated as 88.54% (95% CI = 85.77%-91.32%). CONCLUSIONS: Combination therapy with PegIFN and RBV plus SOF results in high treatment response in patients with HCV genotype 1 infection.

The ITPA and C20orf194 Polymorphisms and Hematological Changes During Treatment With Pegylated-Interferon Plus Ribavirin in Patients With Chronic Hepatitis C.

BACKGROUND: It has been found that ITPase deficiency is caused by ITPA gene polymorphisms. It was observed that ITPA polymorphisms have impact on hematological changes, including hemoglobin (Hb)-decline during treatment of chronic hepatitis C (CHC) patients with pegylated-interferon (PEG-IFN) plus ribavirin (RBV). OBJECTIVES: This study aimed to assess the effect of ITPA and C20orf194 polymorphisms on hematological changes at week 4 of treatment with PEG-IFN plus RBV in patients with CHC. PATIENTS AND METHODS: In this retrospective study, 168 patients with CHC (56% HCV genotype-1 and 44% HCV genotype-3) under the treatment of PEG-IFN plus RBV were genotyped for rs1127354, rs7270101 and rs6051702 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism. Hematological changes including Hb-, platelet (Plt)- and white blood cell-decline at week 4 of the treatment were assessed. RESULTS: In univariate analysis, rs1127354 and HCV genotypes were found to influence the Hb-decline at week 4 of the treatment. In multivariate analysis, rs1127354 CA + AA and HCV genotype-3 were found to have a great role on prevention of Hb-decline. Furthermore, rs1127354 and HCV RNA levels were found to influence the Plt-decline at week 4 of the treatment in the univariate analysis. In multivariate analysis, rs1127354 CA + AA and HCV RNA levels less than 600,000 IU/mL were found to be associated with a higher level of Plt-decline. CONCLUSIONS: In patients with CHC, who were treated with PEG-IFN plus RBV, Hb-decline was affected by rs1127354 and HCV genotypes. However, Plt-decline may be altered by rs1127354 and baseline HCV RNA levels.

Safety and Efficacy of Adding Ribavirin to Interferon or Peginterferon in Treatment of Hepatitis C Infection in Patients With Thalassemia: A Systematic Review on Randomized Controlled Trials.

CONTEXT: Hepatitis C virus (HCV) infection is a major cause of liver-morbidity and mortality among patients with thalassemia. Peginterferon plus ribavirin is currently the recommended therapy for hepatitis C infection in patients do not have thalassemia, but using ribavirin in patients with thalassemia is restricted due to its hemolytic effect. To evaluate the efficacy and safety of adding ribavirin to peginterferon or interferon, authors performed a systematic review on the available literatures. EVIDENCE ACQUISITION: Trials were identified through electronic database, manual searches of journals and bibliographies and approaching authors of trials. Randomized trials that enrolled patients with a diagnosis of thalassemia and chronic hepatitis C infection treated with interferon or peginterferon with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcomes were sustained virological response (SVR), liver-related morbidity, mortality and adverse events. The odds ratios from each trial were calculated individually and in the subgroup analysis of trials. Data were analyzed with fixed-effect model. RESULTS: Three randomized clinical trials with 92 patients were included. All three trials had unclear risk of bias. Compared with peginterferon monotherapy, adding ribavirin to peginterferon had significant beneficial effect on sustained virological response (OR = 3.44, 95% CI: 1.18 - 10.06). There was no significant difference between combination therapy and monotherapy in the end of treatment achievement response. Other than about 30% increase in blood transfusion due to anemia that returned to normal level 2 - 3 months after treatment, there was no significant increase in side effects followed by adding ribavirin to pegylated interferon (Peg-IFN). Data were insufficient to determine the impact of genotype, viral load and age on the response to treatment. CONCLUSIONS: Compared with monotherapy, adding ribavirin to treatment is more effective in removing hepatitis C virus from the bloodstream in patients with thalassemia, it is also more effective in reducing the relapse rate after treatment. Except the increase in blood transfusion, there was no significant increase in side effects followed by adding ribavirin.

Next Steps Toward Eradication of Hepatitis C in the Era of Direct Acting Antivirals.

CONTEXT: After the introduction of safe and highly effective hepatitis C virus (HCV) treatments, eradication of HCV in the next 20 years is the ultimate goal. Since 2011, the advent of first generation direct acting antivirals (DAAs) were started and followed by the introduction of a new wave of DAAs in 2013 which exhibit outstanding efficacy. It is obvious that the eradication of hepatitis C is not restricted to development of DAAs. EVIDENCE ACQUISITION: An electronic search of available literature published was conducted in all peer-reviewed journal indexed in PubMed, Scopus and Google scholar. The literature search was done among articles related treatment of hepatitis C with DAAs in different patient groups with mass screening of the patients and cost benefit of new treatments as main key words. RESULTS: There are major steps that should be taken to eradicate HCV, including (1) the development of screening strategies, particularly for groups such as intravenous drug users and recipients of blood or blood products before the introduction of HCV screening in donors; (2) the development of strategies to overcome issues with the high cost of recently introduced treatments; (3) special attention to special patient groups, such as HIV/HCV co-infection, hemophilia, thalassemia, hemodialysis, and liver-transplant patients; and (4) development of preventive strategies, such as the development of an efficient HCV vaccine, special attention to harm reduction in high-risk groups, and promotion of mass awareness of HCV. CONCLUSIONS: The eradication of HCV will require significant governmental financial investment for screening, prevention, and treatment of infected patients. Although, we have a long way to eradication of HCV, the next steps could be including proper planning to patient finding, availability of new treatments to all patients and development of HCV prevention strategies such as vaccines.

The Prevalence of Hepatitis C Virus Core Amino Acid 70 Substitution and Genotypes of Polymorphisms Near the IFNL3 Gene in Iranian Patients With Chronic Hepatitis C.

BACKGROUND: Molecular studies have demonstrated that the hepatitis C virus (HCV) genotype and host genetics play predictive roles in the management of patients infected with HCV. OBJECTIVES: This study aimed to investigate the HCV genotype, core amino acid (aa) 70 substitution, and polymorphisms near the IFNL3 gene (including rs12979860 and rs8099917) among Iranian patients with chronic hepatitis C (CHC). PATIENTS AND METHODS: In this cross-sectional study, the molecular profiles of the HCV genotype, core aa 70 substitution, and rs12979860 and rs8099917 polymorphisms and plasma HCV RNA levels were determined in 429 CHC patients including 141 hemophilic, 84 thalassemic, and 204 non-hemophilic, non-thalassemic patients. RESULTS: The hepatitis C virus subtype 1a was the most common subtype in the study population. Core aa substitution Arg70Gln was strongly associated with cirrhosis (OR = 2.49; 95% CI = 1.13 - 5.50; P = 0.020). Core aa 70 substitutions were more frequently observed in patients with the HCV subtype 1b than in patients with any other HCV subtypes (P < 0.001). Core aa 70 substitutions were also more common in patients with the rs12979860 TT genotype than in patients with non-TT genotypes (17.3% vs. 8.5%, P = 0.022) and also in rs8099917 non-TT genotypes than in the TT genotype (14.0% vs. 7.0%, P = 0.026). The HCV genotypes and rs8099917 polymorphisms were correlated in which HCV subtype 1b was in favor of rs8099917 GG and HCV subtype 3a favored rs8099917 TT (P = 0.021). Furthermore, the rs12979860 TT and rs8099917 GG genotypes showed significantly lower HCV RNA levels than the other genotypes (P < 0.001). CONCLUSIONS: There is an as yet unexplained association between HCV and host parameters with unknown mechanisms in patients with chronic HCV infection. The assessments of core aa 70 substitution and polymorphisms near the IFNL3 gene could offer promising steps to improve the management of patients with HCV.