The interactive effects of different exercises and hawthorn consumption on the pain threshold of TMT-induced Alzheimer male rats.

Exercise increases the pain threshold in healthy people. However, the pain threshold modulation effect of exercise and hawthorn is unclear because of its potential benefits in people with persistent pain, including those with Alzheimer's disease. Accordingly, after the induction of Alzheimer's disease by trimethyl chloride, male rats with Alzheimer's disease were subjected to a 12-week training regimen consisting of resistance training, swimming endurance exercises, and combined exercises. In addition, hawthorn extract was orally administered to the rats. Then, their pain threshold was evaluated using three Tail-flick, Hot-plate, and Formalin tests. Our results showed that Alzheimer's decreased the pain threshold in all three behavioral tests. Combined exercise with hawthorn consumption had the most statistically significant effect on Alzheimer's male rats' pain threshold in all three experiments. A combination of swimming endurance and resistance exercises with hawthorn consumption may modulate hyperalgesia in Alzheimer's rats. Future studies need to determine the effects of these factors on the treatment and/or management of painful conditions.

Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention.

Aims: This study was designed to investigate the effects of resistance training (RT) and hawthorn extract (Ha) on Glypican-4 (GPC-4) and Insulin-regulated glycosylphosphatidylinositol-specific phospholipase D (GPLD1) serum levels in T2DM and to examine the relationship of these variables with glycemic indexes. Method: 40 male Wistar rats were divided into five equal groups: Healthy Control (H-C), Diabetes Control (D-C), Diabetes Resistance training (D-RT), Diabetes Hawthorn (D-Ha), and Diabetes Resistance training Hawthorn (D-RT-Ha). T2DM was induced with a 4-week high-fat diet (HFD) and one dose of STZ intraperitoneal injection (35 mg/kg). 1-week after the injection, RT (with a range of 50%-100%1RM/3 day/week) and gavage of Ha extract (100 mg/kg/day) was performed for 12 weeks. Results: The glycemic indices improvement (reducing blood glucose and increasing serum insulin level) caused by RT and/or Ha increased GPC-4 and decreased GPLD1 in the T2DM rats, but these positive changes were more effective in the combination of RT + Ha. A strong correlation was also observed between GPC-4 and GPLD1 with blood glucose and insulin. Conclusion: The increase in serum GPC-4 levels was probably due to the direct effect of RT + Ha, and the improvement of glycemic indexes after RT and Ha. The double effect of RT + Ha can be a regulatory mechanism for GPC-4 and its related factors in controlling T2DM complications.

Trends in the Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV Infections in Iranian Patients with Hereditary Bleeding Disorders.

BACKGROUND: Patients with hereditary bleeding disorders (HBDs) have always been vulnerable to transfusion-transmitted infections (TTIs) such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections due to being regular recipients of blood and blood products. This study aimed to detect the trends in the prevalence of HBV, HCV, and HIV infections by birthyear in Iranian patients with HBDs to show the efficacy of national interventions implemented to administrate control and to prevent these infections, i.e., blood safety, newborn HBV vaccination, and safe replacement treatments. METHODS: In this retrospective study, the trends in the prevalence of hepatitis B core antibody (HBcAb), HCV antibody (HCV-Ab), and HIV antibody (HIV-Ab) in Iranian patients with HBDs born before 2012 were assessed using patients' clinical archives. The determinants of HBV, HCV, and HIV infections were investigated in bivariable and multivariable logistic regression analyses. RESULTS: Out of 1475 patients with HBDs, most were male (87.7%) and diagnosed with hemophilia A (52.1%) and severe bleeding disorder (63.7%). The prevalence of HBcAb, HCV-Ab, and confirmed HIV-Ab was 22.9%, 59.8%, and 1.2%, respectively. The trends in HBcAb, HCV-Ab, and HIV-Ab were all decreasing by birthyear and reached a stable level of 0% for patients with birthyears in 1999, 2000, and 1984, respectively. In multivariable analysis, birthyear was significantly associated with HBcAb prevalence. In the multivariable analysis, type of HBD; birthyear; bleeding severity; histories of receiving packed cells, fresh frozen plasma, and cryoprecipitate before 1996; and history of receiving factor concentrate before 1997 were highly associated with the prevalence of HCV-Ab. Moreover, in the bivariable analysis, birthyear and type of HBD were associated with HIV-Ab prevalence. CONCLUSION: This study demonstrated the decreasing trends in HBV, HCV, and HIV seroprevalence in Iranian patients with HBDs following preventive interventions such as HBV vaccination, blood safety measures, and the provision of safe replacement treatments.

The effectiveness of community ageing in place, advancing better living for elders as a biobehavioural environmental approach for disability among low-income older adults: a systematic review and meta-analysis.

BACKGROUND: community ageing in place, advancing better living for elders (CAPABLE), which is a biobehavioural environmental approach by addressing individual capacities and the home environment, aims to reduce the impact of disability among low-income older adults. OBJECTIVE: this meta-analysis aims to elucidate the efficacy of the CAPABLE program on related outcomes in low-income older adults. METHODS: a systematic search of MEDLINE/PubMed, CINAHL and EMBASE was conducted for articles published up to August 2022. A systematic review and meta-analysis were performed to calculate the pooled effect sizes of the efficacy of the CAPABLE program on home safety hazards, activities of daily living (ADLs), instrumental ADLs (IADLs), depression, falls efficacy, pain and quality of life. RESULTS: seven studies involving 2,921 low-income older adults (1,117 as the CAPABLE group and 1,804 served as a control) with an average age ranging from 65 to 79 were included in the present meta-analysis. Pre-post effect analyses showed that CAPABLE was significantly associated with lower home safety hazards, ADLs, IADLs, depression, falls efficacy, pain and quality of life. Additionally, there were statistically significant associations between the CAPABLE program with improvements in ADLs, IADLs and quality of life compared with controls. CONCLUSION: CAPABLE intervention may be a promising strategy to reduce health disparities, and disability limitations, and improve the quality of life in low-income community-dwelling older adults who suffer from disabilities by addressing both the person and the environment.

The global impact of COVID-19 pandemic on the incidence of pediatric new-onset type 1 diabetes and ketoacidosis: A systematic review and meta-analysis.

Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the incidence of pediatric T1D and/or diabetic ketoacidosis (DKA). Therefore, this meta-analysis aims to estimate the risk of global pediatric new-onset T1D, DKA, and severe DKA before and after the COVID-19 pandemic. A systematic search of MEDLINE/PubMed, CINAHL, Scopus, and EMBASE was conducted for articles published up to March 2022. A random-effects meta-analysis was performed to compare the relative risk of T1D and DKA among pediatric patients with T1D between the COVID-19 pre-pandemic and pandemic periods. We also compared glucose and HbA1c values in children who were newly diagnosed with T1D before and after the COVID-19 pandemic. The global incidence rate of T1D in the 2019 period was 19.73 per 100 000 children and 32.39 per 100 000 in the 2020 period. Compared with pre-COVID-19 pandemic, the number of worldwide pediatric new-onset T1D, DKA, and severe DKA during the first year of the COVID-19 pandemic increased by 9.5%, 25%, and 19.5%, respectively. Compared with pre-COVID-19 pandemic levels, the median glucose, and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic increased by 6.43% and 6.42%, respectively. The COVID-19 pandemic has significantly increased the risk of global pediatric new-onset T1D, DKA, and severe DKA. Moreover, higher glucose and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic mandates targeted measures to raise public and physician awareness.

Resistance training and Urtica dioica increase neurotrophin levels and improve cognitive function by increasing age in the hippocampus of rats.

INTRODUCTION: Inflammation and oxidative stress are two major factors in accelerating brain aging. Consumption of some traditional herbs with antioxidant and anti-inflammatory properties such as Urtica dioica extract (Ud) and resistance training (RT) may be effective in controlling premature aging and memory impairment. Therefore, we hypothesized that the combined effect of RT and Ud might play an essential role in preventing memory disorders and hippocampal tissue changes caused by increasing age in rats. METHODS: 28 male Wistar rats (24-week) were divided into 4-groups (n = 7): control (C), Ud, RT, and Ud+RT. RT groups were trained for five weeks, and Ud extract in the 0.0166 w/v concentration (50 mg/kg, oral/daily) was administered. We also examined the effects of RT and Ud on the behavioral (memory and learning), histological (the morphological changes in the dentate gyrus), and transcript aspects of hippocampal tissue. RESULTS: Aging led to karyopyknosis in the hippocampal tissue, which was alleviated by RT and Ud supplementation. RT and Ud were accompanied by increased GPx, GSH, GAP-43, and decreased CAP-1 levels in the hippocampus. Moreover, RT and Ud led to increased NGF, BDNF, and GAP-43 levels, decreased MDA, and protection of hippocampal tissue from karyopyknosis, which was associated with cognitive improvement. However, these interventions had no significant effect on the hippocampal levels of IL-1ß, SOD, and CAT. CONCLUSIONS: These findings suggest that increasing age decreases hippocampal NGF, BDNF, and GAP-43 levels and impairs cognition, which may be reversed by regular RT and Ud extract.

Exercise training and de-training effects on serum leptin and TNF-α in high fat induced diabetic rats.

BACKGROUND: Adipocytokines, which are secreted by the adipose tissue, contribute to the pathogenesis of obesity-related complications. To evaluate this assumption, we investigated the effects of aerobic exercise training (AET), resistance exercise training (RET), and 4 weeks of de-training on serum leptin and TNF-α levels in diabetic rats. METHOD: 36 Wistar rats were divided into normal diet (ND) (control, RET, AET) and high-fat diet (HFD) + STZ (control, RET, AET) groups. Serum insulin, leptin, and TNF-α levels were assessed by commercial ELISA kits. Also fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) levels were measured by the colorimetric kits. RESULTS: Diabetes induction increased body weight (BW) and FBG, and decreased insulin compared to the ND rats' groups (p < 0.001). 12-weeks of AET and RET programs in the trained diabetic rats led to a decrease in TG, LDL-C, leptin, TNF-α, and FBG, and an increase in insulin compared to the HFD + STZ-C group (p < 0.001). Besides, there was no difference between AET and RET in improving the variables studied (p > 0.05). Also, de-training led to increased BW, TG, leptin, and TNF-α compared to the end of the exercise training (p < 0.05). The correlation between the variables studied was established at different stages of the study (p < 0.05), and only BW was not correlated with insulin during exercise training and de-training (p > 0.05). CONCLUSION: These findings indicate that both AET and RET are useful in reducing levels of serum adipocytokines (TNF-α, leptin) in diabetic and non-diabetic rats. At the same time, 4 weeks of de-training was sufficient to lose the metabolic adaptations.

Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats.

INTRODUCTION: Diabetes mellitus is related to cognitive impairments and molecular abnormalities of the hippocampus. A growing body of evidence suggests that Urtica dioica (Ud) and exercise training (ET) have potential therapeutic effects on diabetes and its related complications. Therefore, we hypothesized that the combined effect of exercise training (ET) and Ud might play an important role in insulin signaling pathway, oxidative stress, neuroinflammation, and cognitive impairment in diabetic rats. METHODS: Forty animals were divided into five groups (N = 8): healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-exercise training (D-ET), diabetes-Urtica dioica (D-Ud), diabetes-exercise training-Urtica dioica (D-ET-Ud). Streptozotocin (STZ) (Single dosage; 45 mg/kg, i.p.) was used to induce diabetes. Then, ET (moderate intensity/5day/week) and Ud extract (50 mg/kg, oral/daily) were administered for six weeks. We also investigated the effects of ET and Ud on cognitive performance (assessed through Morris Water Maze tests), antioxidant capacity, and lipid peroxidation markers in hippocampus. Furthermore, we measured levels of insulin sensitivity and signaling factors (insulin-Ins, insulin receptor-IR and insulin-like growth factor-1 receptor-IGF-1R), and neuroinflammatory markers (IL-1 ß, TNF-α). This was followed by TUNEL assessment of the apoptosis rate in all regions of the hippocampus. RESULTS: D-sed rats compared to H-sed animals showed significant impairments (P < 0.001) in hippocampal insulin sensitivity and signaling, oxidative stress, neuroinflammation, and apoptosis, which resulted in cognitive dysfunction. Ud extract and ET treatment effectively improved these impairments in D-ET (P < 0.001), D-Ud (P < 0.05), and D-ET-Ud (P < 0.001) groups compared to D-sed rats. Moreover, diabetes mediated hippocampal oxidative stress, neuroinflammation, insulin signaling deficits, apoptosis, and cognitive dysfunction was further reversed by chronic Ud+ET administration in D-ET-Ud rats (P < 0.001) compared to D-sed animals. CONCLUSIONS: Ud extract and ET ameliorate cognitive dysfunction via improvement in hippocampal oxidative stress, neuroinflammation, insulin signaling pathway, and apoptosis in STZ-induced diabetic rats. The results of this study provide new experimental evidence for using Ud+ET in the treatment of hippocampal complications and cognitive dysfunction caused by diabetes.

Ameliorative effects of endurance training and Matricaria chamomilla flowers hydroethanolic extract on cognitive deficit in type 2 diabetes rats.

Diabetes mellitus is mainly associated with degeneration of the central nervous system, which eventually leads to cognitive deficit. Although some studies suggest that exercise can improve the cognitive decline associated with diabetes, the potential effects of endurance training (ET) accompanied by Matricaria chamomilla (M.ch) flowers extract on cognitive impairment in type 2 diabetes has been poorly understood. Forty male Wistar rats were randomized into 5 equal groups of 8: healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-endurance training (D-ET), diabetes-Matricaria chamomilla. (D-M.ch), and diabetes-endurance training-Matricaria chamomilla. (D-ET-M.ch). Nicotinamide (110 mg/kg, i.p.) and Streptozotocin (65 mg/kg, i.p.) were utilized to initiate type 2 diabetes. Then, ET (5 days/week) and M.ch (200 mg/kg body weight/daily) were administered for 12 weeks. After 12 weeks of the experiment, cognitive functions were assessed using the Morris Water Maze (MWM) test and a passive avoidance paradigm using a shuttle box device. Subsequently, using crystal violet staining, neuron necrosis was examined in the CA3 area of the hippocampus. Diabetic rats showed cognitive impairment following an increase in the number of necrotic cells in region CA3 of the hippocampal tissue. Also, diabetes increased serum levels of lipid peroxidation and decreased total antioxidant capacity in serum and hippocampal tissue. ET + M.ch treatment prevented the necrosis of neurons in the hippocampal tissue. Following positive changes in hippocampal tissue and serum antioxidant enzyme levels, an improvement was observed in the cognitive impairment of the diabetic rats receiving ET + M.ch. Therefore the results showed that treatment with ET + M.ch could ameliorate memory and inactive avoidance in diabetic rats. Hence, the use of ET + M.ch interventions is proposed as a new therapeutic perspective on the death of hippocampal neurons and cognitive deficit caused by diabetes.

Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-Induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Many body systems and organs, including the hippocampus, are affected by diabetes, and undergo changes that may increase the risk of cognitive decline. Urtica dioica (UD) has long been recognized as a medicinal plant with beneficial effects on blood glucose control in diabetes. AIM OF THE STUDY: The present study aimed to investigate the effect of endurance exercise (Ex), along with Urtica dioica (UD) hydro-alcoholic extract on some functional, histological, and molecular aspects of the hippocampus in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: 60 male Wistar rats were divided into five groups (N = 12): healthy control (H-C), diabetes control (D-C), diabetes exercise (D-Ex), diabetes Urtica dioica (D-UD), and diabetes exercise Urtica dioica (D-Ex-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the injection by STZ, Ex (moderate intensity/5day/week) and gavage of UD extract (50mg/kg/day) was performed for six weeks. Cognitive functions were evaluated by the Morris Water Maze test, routine histological examination, and molecular studies were done via Hematoxylin & Eosin stain, and Western blot. RESULTS: Diabetic rats showed spatial learning and memory deficits, as well as negatively affects to the tissue and structure of the hippocampus in the dentate gyrus (DG) and cornu ammonis (CA) areas. Ex + UD treatment caused a decrease of neural disorganization, an increase of neural-microglial density, and thickness of the pyramidal-molecular layer in the hippocampus. In addition, Ex + UD caused a rise of GAP-43 protein levels, a reduction of CAP-1 protein levels, improved hippocampal structure, and improved learning and memory function. CONCLUSIONS: These results show that Ex, along with the UD extract, may decrease levels of the central neural complications of diabetes. Given the importance of recognizing non-pharmacological complementary therapies in this field, future studies are warranted.

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.

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.

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.

A Cost-Utility and Cost-Effectiveness Analysis of Different Oral Antiviral Medications in Patients With HBeAg-Negative Chronic Hepatitis B in Iran: An Economic Microsimulation Decision Model.

BACKGROUND: Although hepatitis B infection is the major cause of chronic liver disease in Iran, no studies have employed economic evaluations of the medications used to treat Iranian patients with chronic hepatitis B (CHB). Therefore, the cost-effectiveness of the different treatment options for this disease in Iran is unknown. OBJECTIVES: The aim of this study was to compare the cost utility and cost-effectiveness of medication strategies tailored to local conditions in patients with HB e antigen (HBeAg)-negative CHB infection in Iran. METHODS: An economic evaluation of the cost utility of the following five oral medication strategies was conducted: adefovir (ADV), lamivudine (LAM), ADV + LAM, entecavir (ETV), and tenofovir (TDF). A Markov microsimulation model was used to estimate the clinical and economic outcomes over the course of the patient's lifetime and based on a societal perspective. Medical and nonmedical direct costs and indirect costs were included in the study and life-years gained (LYG) and quality-adjusted life-years (QALY) were determined as measures of effectiveness. The results are presented in terms of the incremental cost-effectiveness ratio (ICER) per QALY or LYG. The model consisted of nine stages of the disease. The transition probabilities for the movement between the different stages were based on clinical evidence and international expert opinion. A probabilistic sensitivity analysis (PSA) was used to measure the effects of uncertainty in the model parameters. RESULTS: The results revealed that the TDF treatment strategy was more effective and less costly than the other options. In addition, TDF had the highest QALY and LYG in the HBeAg-negative CHB patients, with 13.58 and 21.26 (discounted) in all comparisons. The PSA proved the robustness of the model results. The cost-effectiveness acceptability curves showed that TDF was the most cost-effective treatment in 59% - 78% of the simulations of HBeAg-negative patients, with WTP thresholds less than $14010 (maximum WTP per QALY). CONCLUSIONS: The use of TDF in patients with HBeAg-negative CHB seemed to be a highly cost-effective strategy. Compared with the other available medication options, TDF was the most cost-saving strategy. Thus, TDF may be the best option as a first-line medication. Patients can also be switched from other medications to TDF.

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.

Epidemic History of Hepatitis C Virus among Patients with Inherited Bleeding Disorders in Iran.

The high rate of hepatitis C virus (HCV) infection among transfusion related risk groups such as patients with inherited bleeding disorders highlighting the investigation on prevalent subtypes and their epidemic history among this group. In this study, 166 new HCV NS5B sequences isolated from patients with inherited bleeding disorders together with 29 sequences related to hemophiliacs obtained from a previous study on diversity of HCV in Iran were analyzed. The most prevalent subtype was 1a (65%), followed by 3a (18.7%),1b (14.5%),4(1.2%) and 2k (0.6%). Subtypes 1a and 3a showed exponential expansion during the 20th century. Whereas expansion of 3a started around 20 years earlier than 1a among the study patients, the epidemic growth of 1a revealed a delay of about 10 years compared with that found for this subtype in developed countries. Our results supported the view that the spread of 3a reached the plateau 10 years prior to the screening of blood donors for HCV. Rather, 1a reached the plateau when screening program was implemented. The differences observed in the epidemic behavior of HCV-1a and 3a may be associated with different transmission routes of two subtypes. Indeed, expansion of 1a was more commonly linked to blood transfusion, while 3a was more strongly associated to drug use and specially IDU after 1960. Our findings also showed HCV transmission through blood products has effectively been controlled from late 1990s. In conclusion, the implementation of strategies such as standard surveillance programs and subsiding antiviral treatments seems to be essential to both prevent new HCV infections and to decline the current and future HCV disease among Iranian patients with inherited bleeding disorders.

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.

Hepatitis A Virus and Hepatitis E Virus Seroprevalence Among Blood Donors in Tehran, Iran.

BACKGROUND: Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are both transmitted by the fecal-oral route and are known as the leading causes of acute viral hepatitis in the world, especially in developing countries. There is a lack of updated data on HAV and HEV seroprevalence in Iran. OBJECTIVES: The aim of this study was to determine the seroprevalence of HAV and HEV among a group of blood donors in Tehran, Iran. MATERIALS AND METHODS: A cross-sectional study was performed from July 2014 to December 2014, on a total of 559 blood donors referred to the Tehran blood transfusion center. The serum samples were tested for antibodies to HAV and HEV, using the enzyme-linked immunosorbent assay. RESULTS: In the present study, 536 (95.9%) cases were male and 23 (4.1%) female with mean age of 38 years. Out of 559 blood donors, 107 (19.1%) were first-time donors, 163 (29.2%) lapsed donors and 289 (51.7%) regular donors. Anti-HAV was found in 395 (70.7%) and anti-HEV in 45 (8.1%) of the blood donors. The HAV and HEV seroprevalence increased by age. There was no significant difference between genders in terms of anti-HAV and anti-HEV status. The HAV and HEV seroprevalence was significantly related to the level of education, where the donors with higher level of education had lower rate of HAV and HEV seroprevalence. The HAV and HEV seroprevalence was significantly higher in regular and lapsed donors than in first-time donors. CONCLUSIONS: The present study showed that both HAV and HEV infections are still endemic in Iran.

The Role of Polymorphisms Near the IL28B Gene on Response to Peg-Interferon and Ribavirin in Thalassemic Patients With Hepatitis C.

BACKGROUND: Hepatitis C Virus (HCV) is the major cause of liver failure in thalassemic patients. In these patients, iron overload and their comorbidities make difficulties during Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy. OBJECTIVES: We aimed to assess the impact of polymorphisms near the IL28B gene on virological response in HCV - infected thalassemic patients, who were treated with PEG-IFN and RBV. PATIENTS AND METHODS: This cross - sectional study was conducted on 143 thalassemic patients with chronic hepatitis C, who were treated with a combination of PEG-IFN and RBV regimen. The rs12979860 and rs8099917 polymorphisms were assessed as the most common polymorphisms near the IL28B gene by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The rate of sustained virological response (SVR) was significantly lower in thalassemic patients with HCV genotype-1 infection compared to patients with HCV genotype-3 infection. Among baseline predictors, rs12979860 and rs8099917 polymorphisms were found to be the only parameters associated with achievement of SVR in thalassemic patients with HCV genotype-1 infection however, there was no association between these polymorphisms and the rate of SVR in thalassemic patients with HCV genotype-3 infection. CONCLUSIONS: In HCV genotype-1- infected thalassemic patients with rs12979860 CC genotype and without severe comorbidities, PEG-IFN and RBV combination therapy can be tried yet in those with rs12979860 CT/TT it may be reasonable to treat cases with new direct-acting antivirals.