bita behnava

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.

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.

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.

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.

Direct-acting antiviral agents (DAAs) have changed the treatment landscape of hepatitis C virus (HCV) infection. Sofosbuvir (SOF), as a DAA inhibiting HCV NS5B polymerase, has found a remarkable contribution to the treatment regimens of HCV genotype-2 (HCV-2) and -3 infections. In this meta-analysis, we aimed to evaluate the efficacy of the combination of SOF and Ribavirin (RBV) with or without pegylated-interferon (PegIFN) in the treatment of HCV-2 and -3 infections. In this meta-analysis, we searched electronic databases including PubMed, Scopus, ScienceDirect, and Web of Science using appropriate and relevant keywords. Based on the results of the heterogeneity test (chi-squared and I-squared), fixed- or random-effects models were used to calculate the pooled sustained virological response (SVR) rates. After removing duplicates and screening of 1408 articles, 16 studies were included in the quantitative synthesis. The pooled SVR rates calculated for the treatment of patients suffering HCV-2 infection were 91.2% (95% CI: 86.6% - 95.8%) using the SOF + RBV regimen for 12 weeks and 92.6% (95% CI: 87.1% - 98.1%) using the SOF + RBV + PegIFN regimen for 12 weeks. The pooled SVR calculated for the treatment of patients suffering HCV-3 infection was 53.1% (95% CI: 41% - 65.1%) using the SOF + RBV regimen for 12 weeks, 81.6% (95% CI: 74.4% - 88.7%) using the SOF + RBV regimen for 24 weeks, and 93.8% (95% CI: 86.9% - 100%) using the SOF + RBV + PegIFN regimen for 12 weeks. The combination of SOF and BV with or without PegIFN for 12 weeks is highly efficacious (> 90%) for the treatment of patients with HCV-2 infection. However, for the treatment of patients with HCV-3 infection only would 12 weeks of SOF + PegIFN + RBV result in > 90% treatment success.

One of the challenges to treat hepatitis C virus (HCV) infection is the activation of hepatitis B virus (HBV) that occurs during treatment of HCV infection with direct-acting antivirals (DAAs) in some patients. The detection of serum or liver HBV DNA in the absence of serum HBsAg (HBV surface antigen) is described as occult HBV infection (OBI). The current study aimed at determining the prevalence of OBI in Iranian DAA-naïve HCV-infected patients with hemophilia. The current study was conducted on 100 patients with hemophilia receiving DAAs. The sera obtained from these patients were tested for the presence of HBsAg. Then, the presence of the HBV DNA was detected in peripheral blood mononuclear cell (PBMC) and also plasma samples using nested polymerase chain reaction (PCR). Among the 100 study subjects, 81 (81%) were male and 19 (19%) female. The mean age of the patients was 37 ± 10.50 years. All patients had previously received HBV vaccine. In the current study, HBV DNA was observed in 1% of plasma and in 3% of PBMC samples. In addition, none of the patients who had positive result for HBV detection test previously had markers of HBV infection (anti-HBc (HB core antigen) antibodies, anti-HBs antigens, and positive result of DNA PCR) and all had negative results for HCV RNA after treatment. Generally, the prevalence of OBI was low, but however, HBsAg negativity was not sufficient to completely exclude the presence of HBV DNA. Thus, the serological markers of HBV infection should be confirmed by molecular tests for the presence of possible occult infection.

Hepatitis C virus (HCV), as a global health concern, has infected around 1.6% of the world population. Introduction of direct-acting antiviral regimens such as sofosbuvir/ledipasvir (SOF/LDV) made the treatment of HCV infection superior to previous HCV antiviral therapies in terms of efficacy and feasibility. The current study aimed at assessing the efficacy and safety of generic SOF/LDV in the Iranian patients with HCV infection.
The current prospective, cohort study was conducted on patients with HCV infection referred to Middle East Liver Diseases Center in 2016. Patients without cirrhosis were treated with daily fixed-dose combination of SOF/LDV (Sobopasvir) for 12 weeks. In cases with compensated cirrhosis, patients were treated with SOF/LDV plus daily weight adjusted ribavirin (RBV) for 12 weeks. If the patient with cirrhosis was RBV-intolerant, he/she was treated with daily fixed-dose combination of SOF/LDV for 24 weeks.
In the current study, 30 patients with the mean age of 52.9 years were enrolled and treated with SOF/LDV. Most of the patients were male (73.3%), had cirrhosis (53.3%), infected with HCV-1a (46.7%), and had previous history of HCV antiviral therapy (62.1%). All the patients completed the course of treatment. Rapid virologic and sustained virologic responses were observed in 29 (96.7%, 95%CI = 83.3% - 99.4%) and also 29 (96.7%, 95%CI = 83.3% - 99.4%) cases, respectively. The only case of treatment failure was a relapse. No serious adverse-event was observed during the treatment course.
The generic SOF/LDV was efficacious and safe to treat Iranian patients with chronic HCV infection.

Sustained virologic response (SVR) to pegylated-interferon (PegIFN) and ribavirin (RBV) in hepatitis C virus (HCV)-infected patients could be predicted by detection of serum HCV RNA whereas detection of HCV RNA in other reservoirs such as peripheral blood mononuclear cells (PBMCs) for prediction of treatment response is still a mystery.
This study aimed at assessing the prediction of SVR by detection of HCV RNA in PBMCs or serum in patients during treatment.
In a cohort study (2011 to 2014), 100 chronic HCV patients at Tehran Hepatitis Center were treated with PegIFN and RBV. Serum HCV RNA level was measured at baseline, 4, 12, and 24 weeks during treatment and at 24 weeks after termination of treatment. Meanwhile, HCV RNA was evaluated in PBMCs at weeks 4, 12, and 24 during the treatment.
Out of 100 patients treated in this study, 91 completed the course of treatment. Most patients were young males infected with HCV genotype 1. Cirrhosis and previous history of treatment was found in 16.5% and 26.5% of patients. Sustained virologic response was achieved in 65 (71.4%) patients. Among baseline parameters, only female gender was significantly associated with SVR. Undetectable serum HCV RNA at week 4 (OR = 4.74) and week 12 (OR = 11.63) of treatment predicted SVR rate while the same was not true for detection of serum HCV RNA at week 24 of treatment. Moreover, detection of HCV RNA in PBMCs at weeks 4 and 12 of treatment was not associated with the rate of SVR, while absence of HCV RNA in PBMCs at week 24 of treatment was associated with SVR (OR = 4.55).
Detection of HCV RNA in PBMCs, especially at week 24 of treatment with PegIFN and RBV, could be considered as an additional marker for prediction of treatment response. It is recommended to assess HCV on-treatment kinetic in PBMCs of patients treated with direct-acting antiviral agents for prediction of treatment response.

The presence of the hepatitis C virus (HCV) in cells of extrahepatic organs like peripheral blood mononuclear cells (PBMCs) have important implications for transmission, disease progression, and effective treatment of HCV-infected patients. The impact of host genetics such as polymorphisms near Interferon lambda 3 (IFNL3) on clearance of HCV RNA from buffy coat (BC) following successful clearance of HCV from plasma using Pegylated-IFN (PegIFN) and Ribavirin (RBV) treatment was evaluated in our study.
For detection of residual HCV RNA in BC samples, blood samples of 69 patients with sustained virologic response (SVR) after treatment with PegIFN and RBV were evaluated. Polymorphisms near IFNL3 gene including rs12979860 and rs8099917 were assessed using PCR-RFLP method.
The most prevalent rs12979860 and rs8099917 genotypes were CT (49.3%) and TT (62.3%), respectively. Nine (13.04%, 95%CI: 7.01% - 22.96%) patients had HCV RNA in their BC samples. The favorable genotypes of the 2 polymorphisms (rs12979860 CC and rs8099917 TT) were more frequently observed in patients with undetectable HCV RNA in their BC samples than those with HCV RNA in their BC samples (rs12979860 CC, 45% vs. 22.2%, P = 0.016 and rs8099917 TT, 66.7% vs. 33.3%, P = 0.01).
The polymorphisms of IFNL3 could play a crucial role not only in spontaneous clearance of HCV and SVR rate after PegIFN and RBV therapy, but also in the clearance of HCV from BC after PegIFN and RBV therapy.

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 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.
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.
IFNL4 rs368234815 SNP can be considered for decision‑making in the treatment of HCV‑infected patients.

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.
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 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.
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 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.

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.
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.
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.

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.
Three randomized clinical trials with 92 patients were included. All three trials hadunclear 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 wasnosignificant 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.
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.

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). 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 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. 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. 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 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. 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 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. 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. 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.

Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).. To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB..Patients and The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.. In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.. The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF..

Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.. In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.. Patients and In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.. For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P = 0.03) and undetectable HCV RNA level at week 12 (P < 0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.. The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen..

Hepatitis B virus (HBV) has been classified into ten genotypes (A-J) based on genome sequence divergence, which is very important for etiological and clinical investigations. HBV genotypes have distinct geographical distributions worldwide.. The aim of this study was to investigate the distribution of HBV genotypes among Azerbaijani patients with chronic hepatitis B, came from the Republic of Azerbaijan country to Iran to receive medical care..Patients and One hundred and three patients with chronic HBV infection, referred to hospitals related to Iran University of Medical Sciences and Tehran Hepatitis Center from August 2011 to July 2014, were enrolled in this cross sectional study. About 3-milliliter of peripheral blood was taken from each patient. After viral DNA extraction, HBV genotypes were tested using the INNO-LiPA™ HBV kit (Innogenetics, Ghent, Belgium). HBV genotyping was confirmed using sequencing of hepatitis B surface antigen (HBsAg) and polymerase (pol) regions of HBV.. The mean age of patients was 35.9 ± 11.7 years (19-66). Of 103 patients, 72 (69.9%) were male. In the present study, the predominant HBV genotype was D (93.2%) followed by genotype A (5.8%) and concurrent infection with A and D genotypes (0.97%).. The main and frequent HBV genotype among Azerbaijani patients with chronic hepatitis B virus infection was genotype D followed by genotype A..

About 30% of individuals with hepatitis C virus (HCV) infection are able to clear HCV spontaneously. Differences in host genetics affect the outcome of HCV infection. Single nucleotide polymorphisms (SNPs) of the Interferon lambda (IFNL) genes were associated with spontaneous and treatment-induced clearance of HCV infection.. The aim of this study was to evaluate the association between the IFNL4 rs12979860 SNP and spontaneous clearance of HCV infection in Iranian population.. A case-control study was designed on 91 cases with spontaneous HCV infection clearance and 259 patients with persistent HCV infection as the control group. The rs12979860 SNP was assessed as the most common IFNL polymorphism by PCR-RFLP method.. Distribution of rs12979860 CC genotype in the spontaneous clearance group was around two folds of its distribution in chronic hepatitis C group (P < 0.001, OR = 4.09, 95% CI = 2.44-6.86).. The rs12979860 SNP was observed as a strong host genetic factor associated with spontaneous clearance of hepatitis C infection..

Recent genome wide association studies (GWAS) have shown important roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28 (IL28B) gene in spontaneous and drug-induced clearance of hepatitis C virus (HCV) in genotype 1 HCV infection.. This meta-analysis was designed to determine the world-wide distribution patterns of IL28B genotypes and alleles, and to find possible linkages between IL28B and HCV genotypes..Patients and Manual and electronic databases were searched. Critical appraisal was performed. According to the results of heterogeneity tests, we used fix/random model for the analysis. The data concerning patients’ ethnicity and HCV genotypes were analyzed by using statistical analysis software.. A total of 255 articles were found. After article review and quality assessment, 50 studies, including 18662 patients and 1313 healthy subjects, were analyzed. Presence of HCV genotype 3 versus genotype 1 was significantly associated with a higher frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI: 1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV infected patients. Prevalence of rs12979860 TT genotype in the African-American genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)], and significantly different compared to all other ethnicities.. There were significant linkages between HCV genotypes and IL28B genotypes/alleles. Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a better chance to clear HCV in the acute phase..

Chronic hepatitis B is one of the most common causes of cirrhosis and hepatocellular toxicity in many countries, including Iran. Cytotoxic T lymphocyte (CTL) and Natural killer (NK) cells are the two of main cell populations considered as cytotoxic cells. One of the distinct pathways CTL and NK cells exert cytotoxicity is perforin/granzyme. After the cytotoxic cell/target cell junction, perforin is released from granules by exocytosis. Once it is anchored, perforin forms cylindrical pores through which granzymes and granulysin enter and induce apoptosis.. Large controlled trials have demonstrated the efficacy of PEG-IFN-α-2a in treatment of chronic hepatitis B. This study was aimed to examine whether the enhancement of cytotoxicity by PEG-IFN-α-2a is mainly due to the perforin pathway..Patients and This research work was performed on 50 patients and five healthy people. Patients with chronic hepatitis B were further subdivided into two groups: patients with inactive chronic hepatitis B (carriers, n = 30), and those with active chronic hepatitis B who were under treatment with PEG-IFN-alfa-2a (n = 20) for minimum six and maximum 12 months. Serum perforin level was measured using ELISA method (CUSABIO Company), HBV viral load was assessed using COBAS Taq-man, and we used Elecsys hepatitis B surface antigen (HBs Ag) II quantitative assay method for HBs Ag determination. HBeAg was evaluated by ELISA method, and AST and ALT were measured by routine laboratorymethods.. Based on the results obtained serum perforin level in healthy group was 0.64 ng/mL, the mean of serum perforin level in inactive HBs Ag carriers was 2.63ng/mL, and 4.63 ng/mL in patients with active chronic hepatitis B under treatment with PEG-IFN-α-2a. The mean of serum perforin level in patients with and without virologic response to treatment were 5.45 ng/mL,and 3.4 ng/mL respectively. Finally in patients with virologic response and seroconverted serum perforin level was 7.23 ng/mL.. Based on our results higher perforin level in patients under treatment with PEG-IFN-α-2a, could be an indication of elevated cytotoxicity via perforin/granzyme pathway..

Hepatitis A and E virus (HAV and HEV) infections are acute and self-limited diseases that usually spread through oral-fecal route. Also, blood transfusion as a possible route of entrically transmitted hepatitis has been suggested. Hemophilia and thalassemia patients are highly at risk of transfusion-transmissible viruses (HBV, HCV, and HIV). Any superimposed infection with other viral hepatitis (in particular hepatitis A) cause active liver failure in hemophilia and thalassemia patients.. The aim of this study is to consider seroprevalence of anti HAV and HEV antibodies (Ab) in thalassemia and hemophilia patients with chronic hepatitis C in Iran..Patients and In a cross-sectional study and under general census sampling, sera of 219 thalassemia and hemophilia patients infected with HCV were examined in Tehran Hepatitis Center (THC) between 2009 and 2010. Enzyme-linked immunisorbentassey (ELISA) was done to observe anti HAV and HEV IgG Ab. Patients were chosen from all provinces of Iran.. Anti-HAV IgG antibodies were observed more frequently in thalassemia patients (60/64; 93.8%) than in hemophilia patients (104/155; 67.1%, P < 0.001). The seroprevalence of both antibodies increased with age. Among thalassemia patients, there was no significant association between HAV seropositivity and other variables, but in hemophilia group, seropositive patients were significantly older than seronegative group (P < 0.05). Totally, anti HEV Ab (1/64; 1.6% thalassemia and 5/155; 3.2% hemophilia) was seropositive in six patients. There was no significant association between HEV infection and other variables in thalassemia patients, however, in hemophilia patients, HEV positive ones were significantly older than HEV negative group (P=0.01).. Vaccination of non-immune individuals against HAV infection in high risk groups especially hemophilia and thalassemia patients is recommended. Results did not show any differences about seroprevalence of HEV among Iranian general population..

The prevalence of hepatitis C in Iran is 1% and 18% in general population and thalassemia patients respectively. The cost effectiveness analysis of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination treatment strategy of chronic hepatitis C in thalassemia patients in comparison with monotherapy could help clinicians and policy makers to provide the best treatment for the patients.. In this study we aimed to assess whether adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different genotypes and different subgroups of 280 patients with chronic hepatitis C infection from the perspective of society in Iranian setting..Patients and A cost effectiveness analysis including all costs and outcomes of treatments for chronic hepatitis C infected thalassemia major patients was conducted. We constructed a decision tree of treatment course in which a hypothetical cohort of 100 patients received “PEG IFN alfa-2a” or “Peg IFN alfa-2a plus Ribavirin.” The cost analysis was based on cost data for 2008 and we used 9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a strategy is cost effective, one time and three times of GDP per capita were used as threshold based on recommendation of the World Health Organization.. The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD) per one Sustain Virological Response (SVR), respectively. In low viral load and high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR, respectively. The calculated ICER for combination therapy in subgroup of patients with previously resistant to monotherapy was 13,006 USD per SVR. Combination therapy in previously resistant patients to combination therapy was a dominant strategy.. Adding low dose of Ribavirin to PEG IFN alfa-2a for treatment of chronic hepatitis C patients with genotype-1 was “highly cost effective” and in patients with low viral load and in previous monotherapy resistant patients was “cost effective.”.

Zinc deficiency has been reported frequently in hepatitis C patients in the literature. Furthermore, a decrease in zinc level has been shown in beta thalassemia major as well. Iranians consume a large amount of phytate in their regimens which can bind with zinc and decrease its gastrointestinal absorption.. This study was designed to determine plasma zinc level in an Iranian sample with the diagnosis of hepatitis C with or without concomitant beta thalassemia major..Patients and Between April 2011 and April 2012, plasma zinc level was determined via atomic absorption method, in 130 hepatitis C patients with or without beta thalassemia major in a known referral center of hepatic diseases in Tehran, Iran.. Mean ± standard deviation (SD) of plasma zinc levels was determined as 0.78 ± 0.22 mg/L. Also zinc level was 0.76 ± 0.19 mg/L and 0.80 ± 0.24 mg/L in thalassemic and non thalassemic patients, respectively. T-test analysis showed that there is no significant difference between these two groups regarding plasma zinc level (P = 0.235).. It is concluded that zinc level of studied patients is less than which is reported in normal Iranian population. Moreover, there is not a significant difference in plasma zinc levels between thalassemic and non thalassemic patients and it seems to be a common problem in both ones. Addition of zinc supplement may be recommended in both groups in order to optimize the nutritional support and probably improve the treatment response..

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. 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. 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. 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.

IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon. The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C.Patients and In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46). It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.

Despite significant advances in the treatment of chronic hepatitis C in the past decades, factors which can affect response rates to combination therapy; peginterferon and ribavirin, are still under study and reaching sustained virological response (SVR) is affected by several different factors.. To investigate predictor factors contributing to SVR in Iranian patients..Patients and The present non-randomized, clinical trial was conducted on 100 patients referred to the Tehran Hepatitis Center in 2009-2011. The patients were administered combined peginterferon α-2a-ribavirin treatment, based on the standard protocol of the Iranian Ministry of Health. At the end of the treatment, the SVR rate and predictors were evaluated.. The mean age of the patients was 42 and 78% were male. Genotype 1a was the most common (70%) and 55% of patients were treatment naïve. The outcomes showed that 12%, 16% and 22% patients were; non-responders, breakthroughs and relapsers, respectively, while 50% of the patients reached SVR. Patients reaching SVR were aged 40 years or lower, they were less likely to have been a non-responder in prior treatments, more likely to have a non-1a genotype and a higher number had an HCV RNA of less than 600 000 IU/ml. The multivariate analysis showed that an age of 40 or lower (OR = 3.74, CI95% = 1.52-9.22), a non-1a genotype (OR = 3.71, CI 95% = 1.40-9.81) and an HCV RNA less than 600 000 IU/ml (OR = 2.52, CI 95% = 1.03-6.15) may be useful SVR predictors.. The findings of the present study showed that half of the patients reached SVR through combined peginterferon α-2a and ribavirin treatment, the majority of whom had genotype 3a and a minority had genotype 1a. In addition, an age of 40 or lower, non-1a genotype and a viral load less than 600 000 IU/ml were strong SVR predictors.

Nucleos(t)ide analogues, such as lamivudine and adefovir, are effective drugs for treatment of hepatitis B patients. However, long-term treatment with these drugs leads to the emergence of the nucleos(t)ide analogue resistant strains. The impact of nucleos(t)ide analogues on the emergence of HBsAg escape mutations is not clarified. Hence, the aim of this study was to determine HBsAg escape mutations in chronic hepatitis B patients treated with nucleos(t)ide analogues. A cross-sectional study was performed on 50 patients with chronic hepatitis B under treatment with nucleos(t)ide analogues (lamivudine and/or adefovir) and 50 naive chronic hepatitis B patients. HBV DNA was extracted from plasma and S gene of virus was amplified by Nested-PCR followed by direct sequencing. HBsAg gene sequence of the samples was evaluated for detection of HBsAg escape mutations. Among the 100 patients, the following HBsAg escape mutations were identified: sQ101H, sG119R, sP120S, sP127S, sA128V, sG130N, sG130R, sT131I, sM133I, and sY134N. The frequency of HBsAg escape mutations in patients under treatment of nucleos(t)ide analogues was 16% and in naïve patients was 6% (p=0.2, OR=2.98). According to the obtained results, there seems to be no association between using nucleos(t)ide analogues and emergence of HBsAg escape mutations.