amirhoushang sharifi

Hepatitis C virus (HCV) causes one of the major chronic liver diseases (CLD). Hepatitis C virus- core encoding sequence possesses an overlapping open reading frame (ORF) that expresses a protein called F or core.
The current study aimed at assessing the presence and titer of anti-core antibody (Ab) in 70 Iranian patients infected with HCV-1a, responder and non-responder groups, under combination therapy with pegylated interferon-α (PegIFN-α) plus ribavirin (RBV) using an enzyme-linked immunosorbent assay (ELISA).
In the current cohort study, HCV-1a core gene was amplified and cloned into vector followed by expressing in Escherichia coli and then, purified by ion exchange chromatography. The antibody titer of patients was evaluated before, during (12, 24, and 48 weeks), and 6 months after the end of therapy (ETR).
The seroprevalence of anti-core Ab was 75.7% in pretreatment sera. The combination therapy could induce a decline in the level of anti-core Ab in both groups of responders and non-responders. These changes were significant only in the responders (P = 0.003). The seroprevalence of anti-core Ab had no correlation with the outcome of treatment.
According to the current study results, HCV core protein elicit a specific antibody response other than the anti-core protein antibodies. The current study data also suggested that the level of anti-core antibody might be affected by the combination therapy and associated with sustained virological response (SVR). The data implied that the declining trend of anti-core Abs during the treatment might be an alternative representation of the therapeutic response in Iranian population infected with HCV.

One of the most important global public health concerns is chronic hepatitis C virus (HCV) infection, causing liver-related morbidity and mortality with a significant prevalence rate. Cirrhosis caused by hepatitis C is one of the most common causes of liver transplantation. Therefore, determining the prevalence of HCV infection and its geographical distribution is essential..
The aim of this study was to estimate the point prevalence of HCV infection among Iranian general population..
Published studies reporting the prevalence of HCV infection in the Iranian general population were identified by a comprehensive literature search. Studies assessing and reporting HCV Ab positivity were evaluated in this review. Furthermore, an additional grey-literature search was performed to obtain other relevant studies..
Twelve studies were eligible for inclusion in this review. The overall seroprevalence of HCV was 0.6% (95% CI: 0.4% to 0.8%). The seroprevalence of HCV infection varied considerably among different provinces ranging from 0.08% to 1.6%. Hormozgan province was reported to have the highest HCV Ab seropositivity rate while Mazandaran province had the lowest rate. The overall prevalence of actual viremia was 0.4% (range = 0.05 - 0.87), based on the results of five studies using PCR for confirmation of HCV diagnosis..
Our results demonstrated that the seroprevalence of HCV among Iranian general population is lower compared to other countries in the middle-east. However, the significant heterogeneity across included studies limits this conclusion. Therefore, to reduce the existing heterogeneity in the literature and strengthen the current evidence on the prevalence of HCV infection among Iranian general population, further high quality studies are required..

The combination of sofosbuvir and daclatasvir can be used to treat all genotypes of hepatitis C. Current guidelines for treating hepatitis C cirrhosis do not clarify weather 12 weeks or 24 weeks of treatment is appropriate..
In the present study, we aimed at evaluating the efficacy of sofosbuvir, daclatasvir, and ribavirin given for 12 weeks in treating cirrhotic patients with hepatitis C genotypes 1 and 3 infections..
One hundred patients with hepatitis C and cirrhosis infected with Genotypes 1 and 3 were included in the present study. They were treated with 1 tablet of a combination pill of 400 mg sofosbuvir and 60 mg daclatasvir daily and weight-based ribavirin for 12 weeks. Response to treatment was assessed 12 weeks after the end of the treatment with a sensitive assay (SVR12). This study was registered with ClinicalTrials.gov, ID: NCT02596880..
One patient developed increased creatinine level following severe diarrhea and gastroenteritis and was excluded, 1 patient died due to unrelated reasons and 4 others were lost to follow-up. Among the 94 patients who finished the study, 92 achieved SVR12 (98%, per-protocol, 92% intention-to-treat). None of the patients reported any side effects. Of the 100 original patients, 56 were Genotype 1 and 44 were Genotype 3. One of the two patients not achieving SVR12 was Genotype 1, and the other two were Genotype 3..
The fixed-dose combination drug of sofosbuvir and daclatasvir given together with weight-base ribavirin for 12 weeks is extremely effective and safe in treating HCV patients with Genotypes 1 and 3 and cirrhosis..

Interferon-free treatments for hepatitis C have been recently available. They can cure over 95% of patients within 12 weeks without significant side effects. A combination of daclatasvir and sofosbuvir has been particularly useful as it is effective against all genotypes of hepatitis C virus (HCV). The combination of sofosbuvir and daclatasvir in a single pill has been recently manufactured in Iran (Sovodak®). The current paper is a preliminary report on the first patients treated with Sovodak.
100 patients with cirrhosis due to hepatitis C were included. All genotypes of HCV were eligible. All the patients received treatment with daclatasvir and sofosbuvir (Sovodak) in combination with ribavirin for 12 weeks and were evaluated for effectiveness of the treatment 12 weeks after termination of the treatment (SVR12, sustained virological response at 12 week). The results of the first 50 patients are presented here.
Of the first 50 patients enrolled in the study, 47 reached the endpoints. Of them, 17 were infected with HCV genotype 3 and showed 100% response to the treatment (17/17). The remaining 30 patients were infected with genotype 1 and 97% responded (29/30) to the treatment. No adverse effects were reported.
According to international guidelines, the combination of sofosbuvir and daclatasvir is the first line of treatment for all genotypes of HCV infection. For patients with cirrhosis, ribavirin is also added. In our study the efficacy of this combination in patients with cirrhosis was 97% and 100% for genotypes 1 and 3, respectively. Due to its high efficacy and ease of use, we recommend Sovodak for the treatment of all genotypes of HCV in Iran.

Information regarding solid pseudopapillary neoplasm (SPN) of the pancreas is limited in Iran. We aimed to review the clinicocytopathological features and follow-up of patients with SPN of pancreas who were diagnosed in a single center in Iran.
Seven patients with SPN of the pancreas were diagnosed during January 2010 to March 2015 at the Digestive Disease Research Institute of Tehran University of Medical Sciences. The patients were reviewed prospectively.
Six out of the 7 patients were female and the mean age of all the patients was 29.4 years ranging from 15 to 61 years. The most common clinical presentation was nonspecific abdominal pain (N=6). The tumors were located mostly in head and neck of the pancreas. SPN was diagnosed in all patients by fine needle aspiration through endosonography (EUS-FNA). All patients underwent surgery. Histological findings of surgical tissues were consistent with EUS-FNA. The postoperative follow-up period of about 14 months was uneventful.
SPN of the pancreas is a rare pancreatic tumor which affects primarily young women. EUS-guided FNA could play an important role in preoperative diagnosis of SPN of the pancreas.

Evidence indicates that insulin resistance results in poor sustained viral response (SVR) in patients with chronic hepatitis C (CHC). Metformin is an oral hypoglycemic agent which improves insulin resistance. We sought to determine if the addition of metformin to the treatment regimen could improve SVR in treatment-naïve CHC patients in a randomized, double-blind, placebo-controlled trial. We randomized 140 consecutive CHC patients to receive either metformin 500 mg three times a day or placebo in addition to pegylated interferon (PEG-IFN) and ribavirin (RBV). Only treatment-naïve subjects aged between 15 and 65 years of age were included. SVR was defined as no detectable HCV RNA six months after the end of treatment. Subjects who received at least one dose of PEG-IFN were included in the final analysis. The SVR rate in the metformin group was 75% versus 79% in controls (intention-to-treat) which was not significantly different. Also, the difference between the placebo and metformin group was not significant in subsets of different genotypes or those with homeostasis model assessment of insulin resistance (HOMA-IR) levels greater than 2 or body mass index greater than 25. The most common complaint was gastrointestinal discomfort (13% in metformin group versus 4% in controls; p=0.002) that lead to discontinuation of metformin in 8 participants. Although triple therapy with metformin, PEG-IFN and RBV is relatively well tolerated, the addition of metformin did not significantly improve viral response in CHC patients.

Due to a lack of clear criteria for recognizing subjects at risk of progression to gastric cancer (GC), this cohort study seeks to identify predictors of GC death in a high-risk population. During 2000–2001, 1011 randomly selected residents of Ardabil, Iran without a history of gastrointestinal diseases, underwent upper endoscopy with targeted biopsy sampling. Until 2013, cancer mortality data were obtained using cancer and death registry data and verbal autopsy reports. Cox regression was used to estimate hazard ratios (HR). A total of 3.95% of the participants [mean age: 53.1 ± 9.9 years, 49.8% males, and 88.2% Helicobacter pylori (H. pylori-positive)] died of GC. In the multivariate model, precancerous lesions at the beginning of follow-up were associated with increased GC mortality. The HR [95% confidence interval (CI)] was 7.4 (1.6–33.8) for atrophic gastritis (AG) and 23.6 (5.5–102.3) for intestinal metaplasia (IM). Age over 50 (HR = 4.4; 1.3–14.2), family history of GC (HR = 6.8; 3.3–13.8), smoking (HR = 7.4; 3.2–17.3), and endoscopically confirmed gastric ulcer (GU, HR = 6.5; 2.5–16.4) were independently associated with GC mortality. The concomitant presence of a precancerous lesion increased the HR to 46.5 (10.8–198.6) for a family history of GC, 27.6 (6.5–116.4) for smoking, and 25.1 (6.3–105.3) for age >50 years. In this population with a high rate of H. pylori infection, age over 50 years, smoking, family history of GC, IM, AG, and in particular, an undiagnosed GU were significant independent risk factors for mortality due to GC. The assessment of a combination of these risk factors might identify individuals at risk of GC who could possibly benefit from regular surveillance.

Oral cavity has been proposed as an important reservoir of H.pylori, being implicated in bacterial transmission through oral-oral route. However, some investigators believe that the newborn acquires H.pylori from mother through vaginal delivery. In this study, oral and vaginal yeasts were examined for the intracellular occurrence of H.pylori and their possible role in bacterial transmission. Sixty nine oral and vaginal yeasts from expecting mothers (39 oral and 30 vaginal) and seven oral yeasts from neonates(6/46 vaginal delivery, 1/43 cesarean) were identified and studied by light and fluorescent microscopy for observing the intracellular bacterium-like bodies(BLBs). Whole DNAs of yeasts were recruited for detection of H.pylori-specific genes. Urea breath test (UBT) was performed for detection of H.pylori infection in mothers. Stool antigen test (SAT) was used for detection of H.pylori antigens in infants’ stool at birth and six months of age. Oral yeasts were isolated more frequently from normally-delivered neonates. The frequency of H.pylori genes in mothers'' vaginal yeasts was significantly higher than in mothers'' oral yeasts. A significant correlation was found between the occurrence of H.pylori genes in vaginal yeasts and that in neonates'' oral yeasts, occurrence of H.pylori genes in mothers'' vaginal yeasts or neonates'' oral yeasts, and UBT+ results in mothers. C.albicans which colonizes the oral cavity of neonates through vaginal delivery or contact with environment or healthcare workers could be an important reservoir of H.pylori. Vaginal yeasts are more potent in accommodating H.pylori than oral yeasts. Accordingly, vaginal yeast is proposed as the primary reservoir of H.pylori which facilitates H.pylori transmission to neonates.

Chronic hepatitis C might lead to several immunological dysfunctions. Studies have shown a positive association between hepatitis C virus (HCV) infection and psoriasis. These results suggest that the infection may be one of the triggering factors for the development or exacerbation of psoriasis. Here, we present a case of chronic HCV infection with psoriasis who developed exacerbation of skin lesions during therapy with peginterferon alpha-2a plus ribavirin. We discuss the management, course and results of HCV treatment in this patient

Throughout the world, many migrant and mobile populations are at elevated risk for HIV. Iran has a large immigrant population from neighboring Afghanistan; however, few data exist on the prevalence of HIV in this community. In 2008, we conducted a study to assess the presence of HIV infection among 477 immigrants in a town to the northeast of Tehran using a rapid test in the field. HIV prevalence was 0.2% (95% CI 0.005-1.2) with one person HIV-positive. We recommend periodic HIV sero-surveillance with detailed behavioral measures for this population in the future.

Chronic hepatitis C (CHC) is a major contributor to cirrhosis and hepatocellular carcinoma and major global public health problem that causes mortality in both developed and developing countries.For the past decade, treatment with pegylated interferon (peg interferon α) and ribavirin (RBV) has been associated with rates of sustained virologic response of ≤ 66% among patients with hepatitis C virus (HCV) infec­tion. In this study, we report the response rate of Iranian treatment-naïve CHC patients to Pegaferon, a locally developed pegylated inter­feron-α2a (PEG-IFNα2a). Patients diagnosed with CHC who referred to two university based outpatient clinics in Tehran from December 2007 to May 2011 were enrolled in a single-group, open-labeled experimental design. Eligible patients were above 15 years of age and had HCV infection with evi­dence of chronic hepatitis. Exclusion criteria included the presence of a debilitating disease, decompensated cirrhosis or refusal to participate in the study. Patients were treated with 180μg Pegaferon weekly in addition to 800-1200 mg daily, weight-based RBV for 24 or 48 weeks depending on genotype. Viral response and adverse effects were recorded. A total of 216 patients were enrolled in the study of which 83.3% were male and 16.7% were female. In 93 (43.1%) patients, the HCV RNA viral load was ≥ 800,000 IU/ml before starting treatment. “As-treated analysis” indicated that a total of 168 (77.8%) patients achieved sustained viral response (SVR, undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment). This study, with a larger number of participants, confirms the results of a previous study by the authors that Pegaferon, a PEG-IFNα 2a locally produced in Iran, is effective in treatment-naïve CHC patients.

Neuropsychiatric side effects of peg interferon- (PEG-IFN-) therapy consist of a large spectrum of symptoms. Organic personality syndrome, organic affective syndrome, psychotic manifestations and seizures are more common side effects of PEG-IFN- whereas cranial neuropathy and movement disorders are less common. Bell’s palsy is often idiopathic, but has been linked to some viral infections, particularly with herpes viruses. Other infections, such as human immunodeficiency virus infection and Lyme disease, may also lead to idiopathic facial paralysis. Neither acute nor chronic Hepatitis C infection has been implicated previously in Bell’s palsy, but PEG-IFN- may play a role. Two patients with CHC who developed Bell’s palsy before and during treatment with PEG-IFN- and Ribavirin are presented here.

Regulatory T cells (Tregs) have been involved in impaired immunityand may have a pivotal role in persistence of viral infections. To develop a simple and reliable in-house three color flow cytometery of peripheral blood to understand the role of HCV infection in the increase of Tregs. The level of naturally occurring CD4+CD25+FoxP3+ regulatory T cells (nTregs) in 20 chronically infected with hepatitis C virus (HCV) patients was compared to those of 15 healthy individuals by flowcytometry. In a different approach we performed permeabilization and intracellular staining before surface staining which allows the preservation of the surface molecules in the combined detection process and results in the normal frequency of nTregs in blood. Using the optimized method, it was shown that a significantly higher proportion of nTregs in the total CD4+ T cell population was seen in the peripheral blood of chronic HCV patients (0.83 ± 0.21%, p=0.05) as compared to controls (0.26 ± 0.1, p=0.05). In accordance with other studies, we showed that HCV infection induces a dramatic increase in Tregs, which might contribute to the immune response failure during HCV infection.

To evaluate the safety and effectiveness of locally produced pegylated interferon-α2a in treatment-naïve patients with chronic hepatitis C. All treatment-naïve patients diagnosed with chronic hepatitis C who referred to two university based outpatient clinics in Tehran from December 2007 to May 2008 were enrolled. Exclusion criteria included the presence of a debilitating disease, decompensated cirrhosis, or refusal to participate in the study. Patients were treated with 180 μg pegylated interferon-α2a (Pegaferon) weekly and 800 – 1200 mg ribavirin daily for 24 or 48 weeks depending on genotype and weight. Viral and biochemical response and adverse drug reactions were recorded. A total of 108 patients were enrolled; 63 with genotype 1 and 45 with genotypes 2 and 3. The mean age of the patients was 39 years (range: 19 – 65). Ninety-seven patients completed the study and 76 achieved sustained viral response. The sustained viral response among patients completing the study was 67% for genotype 1 and 95% for genotypes 2 and 3. Adverse events were well tolerated and none led to discontinuation of treatment, however dose adjustment was necessitated in 16 patients. The most common adverse events were fatigue (73.5%), poor appetite (66.2%), and feverishness (57.4%). The mean hemoglobin drop was 2.9 g/dL. Locally produced PEG-IFN in Iran is safe and effective in treatment-naïve chronic hepatitis C. ClinicalTrials.gov identifier: NCT01137383