arghavan haj

Chronic hepatitis C virus (HCV) is associated with extra hepatic autoimmune disorders, while peg-IFNa-2a/RBV combination therapy may exacerbate these conditions. Autoantibodies to cytoplasmic structures, called rod and ring particles (RR), have strong associations with these patients and are identified by HEp-2 cells..
Our purpose was to study the correlation of autoantibodies to cytoplasmic rod and ring particles in the serum of patients with chronic HCV infection with their response to standard therapy..
Serum samples were gathered from 120 patients with HCV infection (40 naive treatments, 40 with sustained virological response (SVR), and 40 with relapse response) during peg-IFNa-2a/RBV combination therapy and analyzed for the presence of RR antibodies by IIF on commercially available HEp-2 cell substrate slides from Euroimmun (Lu beck, Germany)..
Anti-rod and ring (anti-RR) autoantibodies were detected in only the serum of 1 out of 120 patients (0.8%), which belonged to a patient (out of 40) with relapse response (2.5%). No correlation was found between the types of response to peg-IFNa-2a/RBV combination therapy and the presence of anti-RR autoantibodies..
The only HCV patient with RR autoantibodies previously had received IFN/ribavirin antiviral therapy. The presence of these autoantibodies is extremely rare in Iranian HCV patients. Further studies are warranted to determine the role of genetic background and geographical pattern in the prevalence of these novel autoantibodies worldwide..

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.

Serum pepsinogen I and II are considered as indicators of changes in gastric morphology. Important publications from the last decades are reviewed with regard to the serum level of these biomarkers for the diagnosis of normal gastric mucosa, diffuse gastritis and its change to atrophic gastritis and intestinal metaplasia as well as gastric cancer. Due to the low sensitivity of serum biomarkers for diagnosis of gastric cancer, especially at its early stage and the poor prognosis of the tumor at the time of diagnosis, its prevention by eradication of H. pylori remains the mandatory strategy. On the other hand, the severity of regression and non-reversibility of precancerous lesions and intestinal metaplasia in gastric mucosa through eradication of H. pylori make it necessary to diagnose diffuse gastritis at its early stage. Increased serum pepsinogen II compared to normal serum pepsinogen I seems to indicate the presence of diffuse gastritis without precancerous lesions suitable for eradication of H. pylori infection, when it is serologically positive. A diagram illustrates the strategy of this therapeutic measure depending on the age of people and the level of serum biomarkers in areas with high gastric cancer prevalence.

The role of different viral proteins in the progression of the disease to cirrhosis is not completely understood. The ARFP/F protein is a newly described protein synthesized from the +1 or -2 reading frames of the core protein gene, which its function remains unknown. The purpose of this study is to detect specific antibodies to HCV-ARF/Core+1 protein in cirrhotic and non-cirrhotic patients with HCV and investigate any possible association. ARF/Core+1 recombinant proteins from HCV genotype 1a were expressed in Escherichia coli, and purified. Using an enzyme-linked immunosorbent assay, we assessed the prevalence of anti-ARF/Core+1 antibodies in 50 cirrhotic and 50 non-cirrhotic hepatitis C patients. All 50 cirrhotic patients were positive for anti-ARF/Core+1 antibody, while only 80% positive samples among non-cirrhotic patients were detected. The titer of anti-ARF/Core+1 antibody was also significantly higher in patients with cirrhosis than in non-cirrhotic patients. Compared to 80% positive samples among non-cirrhotic patients all 50 cirrhotic patients were positive for anti-ARF/Core+1 antibody and titer of anti-ARF/Core+1 antibody was significantly higher in patients with cirrhosis than in non-cirrhotic. These results suggest that ARF/Core+1 protein is associated with cirrhosis. A possible causative association between ARF/Core+1 and cirrhosis as well as the mechanism of this association needs to be further investigated.

The mechanism behind the apparent lack of effective antiviral immune esponse in patients with chronic hepatitis C irus (HCV) infection is poorly understood. Although multiple levels of abnormalities have been dentified in innate and daptive immunity, it is postulated that production of specific cytokines such as IL-10 aycontribute to the induction and maintenance of HCV persistence. Production of IL-10 by CD4+,CD25+,IL-10+ regulatory T cells with regulatory capacity (Tregs) appears to be one of the viral mechanisms that alter the antiviral immune response. As the first report, that attempts to mimic physiological forces that can occur during HCV infection, in this study we evaluate the ability of HCV-core antigens in increasing the frequency of CD4+,CD25+,IL-10+ regulatory T cells. We analyzed peripheral blood mononuclear cells (PBMCs) from chronic HCV-infected patients (n and normal controls (n=6) to determine the effect of the HCV-core antigen in the frequency of HCV-specific IL 10 production. PBMCs of different groups were isolated, cultured and stimulated with core antigen. Then, an in house triple-stain flow cytometric method was used to investigate the frequency of CD4+,CD25+,IL-10 producing cells. Following incubation of PBMCs with HCV-core antigen, a population of CD4+,CD25+,IL-10+ cells (regulatory T cells) increased. However we observed no increase in Tregs in the negative controls. The study supports the view that specific CD4+,CD25+,IL-10+ T cells may be implicated in host immune tolerance during an HCV infection. It is likely that HCV vaccine candidates avoid epitopes that lead to strong IL-10 production.

Northern Iran (Ardabil) is characterized by a high gastric cancer (GC) rate, whereas Southern Iran (Kerman and Yazd) has a low GC rate. The aim of this study is to verify the potential for pepsinogen I and II to detect atrophic gastritis (AG) in both high and low risk populations for GC. Sera of blood donors and patients with GC from Ardebil, Kerman and Yazd were used to measure levels of pepsinogen I, II and H. pylori IgG antibody. GC rates in these cities were determined according to the Cancer Registry and upper gastrointestinal (GI) endoscopy results. There were 449 subjects with an average age of 45 ± 15 years. The GC rate in the endoscopy units of the hospital in Ardabil was four times higher than Kerman or Yazd. The mean serum pepsinogen I levels did not differ between Ardabil (102 ± 42.6 µg/mL), Kerman (103.3 ± 49.8 µg/mL), and Yazd (111.7 ± 39 µg/mL). Pepsinogen II levels were: 8.1 ± 4.7 µg/mL (Ardabil), 7.5 ± 5.3 µg/mL (Kerman), and 7.6 ± 4.4 µg/mL (Yazd), which were not different. The H. pylori infection rates were: Ardabil (61%), Kerman (55%), and Yazd (73%). A low ratio of pepsinogen I to II (≤3) was seen in Ardabil (1.3%), Kerman (1.9%), and Yazd (0.0%), which was not significant. A total of 51.9% of GC patients from Ardabil had normal pepsinogen I (≥70 µg/mL) levels and pepsinogen I/II ratios that were >5. Serum biomarkers pepsinogen I and II and their ratios are probably not sensitive predictors of AG in areas that have either a high or low GC prevalence. This finding is likely related to the lack of an association between GC and advanced AG.

Regression of precancerous lesions after H. pylori eradication remains controversial. This study evaluates the change and topography in first degree relatives (FDR) of gastric cancer (GC) patients following H. pylori eradication. Participants underwent endoscopy with antrum and corpus histological examinations. Subjects with pangastritis were randomly allocated to placebo or eradication therapy and followed over 4½ years. Among 989 evaluated FDR, we excluded 468 patients as follows: 108 had macroscopic lesions, 243 had no evidence of any H. pylori infection, and 117 were excluded for other reasons. The remaining subjects (n = 521) were allocated to therapy (group A, n = 261) or placebo (group B, n = 260) groups. Interim analysis of 403 subjects (201 placebo, 202 therapy) showed regression of atrophy (60 out of 97 in the antrum and 37 out of 104 in the corpus) in H.pylori-eradicated versus regression of atrophy (57 out of 184 in the antrum and 23 out of 173 in the corpus) in non-H.pylori-eradicated cases over 2½ years (P<0.0001). No regression of intestinal metaplasia (IM) occurred in the antrum and corpus of treated subjects over 4½ years. However, progression of IM occurred in the antrum in 17 out of 90 patients in the non-H. pylori-eradicated versus 4 out of 68 H. pylori-eradicated subjects after 4½ years (P<0.05). Eradication of H. pylori is associated with regression of gastric atrophy but not IM, even in its early stages. Gastric atrophy and IM in the antrum have shown more rapid progression in cases not treated for H. pylori infection (over 4½ years follow-up) compared to H. pylori-eradicated cases.