فهرست مطالب
Hepatitis Monthly
Volume:13 Issue: 9, Sep 2013
- تاریخ انتشار: 1392/07/13
- تعداد عناوین: 9
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Page 1BackgroundDetermination of the Hepatitis C virus (HCV) genotype distributed in a particular area has an important role on public health throughout the world..ObjectivesThe aim of this study was to determine the frequency of HCV genotypes in Azerbaijani patients..Patients andMethodsFrom March 2010 until March 2012, 235 Azerbaijani patients with established chronic hepatitis C, referred to Hospitals related to Iran University of Medical Sciences and Tehran Hepatitis Center, Clinical department of Baqiyatallah Research Center for Gastroeneterology and Liver Disease, were enrolled in this cross sectional study. About 5 mL of peripheral blood was collected from patients and after separation of plasma, viral RNA extracted. HCV-RNA were amplified by RT-nested PCR using primers from the 5´-UTR and genotyped by RFLP assay, and then HCV genotypes were confirmed using sequencing of cloned PCR products into pJET1.2/blunt cloning vector..ResultsHCV genotyping of positive plasma samples demonstrated that predominant HCV subtype was noted for 1b (71.1%) followed by subtype 3a (17.0%), genotype 2 (6.8%), 1a (1.7%), and mixed infection (3.4%). The mean ± SD age of patients was 37.3 ± 11.8 (range: 2-63) years. Out of 235 patients, 139 (59.1%) were male. The frequency of HCV subtype 3a was higher in patients under 40 years old (3a: 18.1% vs. 15.0%), and subtype 3a was higher in male patients (3a: 18.7% vs. 14.6%)..ConclusionsThe current study shows that the predominant HCV genotype among Azerbaijani patients with established chronic hepatitis C is subtype 1b (71.1%) followed by subtype 3a (17.0%)..Keywords: Hepatitis C, Infection, Genotype
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Page 6BackgroundThe 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..ObjectivesIn 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 andMethodsA 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..ResultsThe 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..ConclusionsAdding 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.”.Keywords: Hepatitis C, PEG, Interferon Alfa, 2a, Ribavirin, Cost, Benefit Analysis, Decision Support Techniques, Iran
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Page 14IntroductionSorafenib, an oral multikinase inhibitor, is the only systemic agent proven to be effective in patients with hepatocellular carcinoma (HCC). There are no approved second line systemic therapies in patients who have had disease progression on or are not eligible to sorafenib..Case PresentationWe describe two cases of unresectable HCC that were treated with low, «metronomic» doses of capecitabine. In the first patient, capecitabine was used after sorafenib failure. In the second case, treatment with capecitabine was attempted since the patient was considered not eligible for sorafenib due to spontaneous hepatic bleeding of a large HCC lesion. Treatment was effective and well tolerated in both patients with long-lasting objective responses..ConclusionsLacking established second-line therapy, metronomic capecitabine may be a valid alternative in the treatment of HCC patients who are judged not eligible for sorafenib or those having progression disease on sorafenib..Keywords: Hepatocellular Carcinoma, Capecitabine, Sorafenib
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Page 18BackgroundBesides the great importance of the issue in terms of public health, there is a lack of studies evaluating the performance of several of the currently used point of care tests (POCTs) for the detection of anti-HCV..ObjectivesTo investigate the performance of two POCTs for anti-HCV detection and to assess the impact of the reading time on diagnostic performance..Patients andMethodsA total of 307 subjects were divided into three groups (1- HCV infected; 2- other chronic liver diseases; and 3- controls). The POCTs HCV Rapid Test Bioeasy® and Imuno-Rapido HCV® were read at 3, 5, 10, 15, 20 and 30 minutes. The sensitivity and specificity of the POCTs were calculated in relation to anti-HCV detection by chemiluminescence..ResultsValid results were obtained for all tests. When compared to the chemiluminescence, both tests showed sensitivity of 97.1% and specificity of 100%. No changes in the sensitivity or specificity of the tests were observed at different reading times and when patients with other chronic liver diseases were evaluated as a control group..ConclusionsThe POCTs evaluated in this study showed high sensitivity and specificity, with no change in the performance after the third minute of reading..Keywords: Point, of, Care Systems, Hepatitis C, Diagnosis
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Page 23BackgroundThe mutations of LHBs in pre-S, especially in pre-S2, are definitive in hepatocellular carcinoma (HCC) associated with HBV. However, the mechanisms of the N-glycosylation modification in LHBs are unclear. The N-glycosylation modification of LHBs affects Endoplasmic Reticulum stress, cell proliferation and its secretion which was further studied..ObjectivesThe objectives of our studies was to indentified that modification of LHBs by N glycosylation modulate their secretion, affect ER stress or expression of cycling, cell cycle and proliferation..Materials And MethodsThe LHBs was mutated; then expression of proteins related to endoplasmic reticulum stress and EAED path of L02 cells affected by LHBs and its mutations was evaluated. LHBs proteins bound to multiubiquitin chains and its glycosylation motif were studied. The subcellular localization and secretion of LHBs and its mutations were identified. The effect on cell cycle and proliferation by LHBs and its mutations were detected..ResultsThese data demonstrated that the N-glycosylation motifs of LHBs were associated with ER stress. The N15S, N123S, and N177S mutated LHBs proteins could induce overexpression of EDEM in L02 cells. LHBs and its mutated proteins contained p62-derived UBA domain, which could affect expression of cyclins. The subcellular localization of LHBs in endoplasmic reticulum was similar to its mutations. The secretion of LHBs was blocked by N320K mutation, which could induce an increase in G1 phase and inhibition of S phase, and inhibited mitotic entry..ConclusionsIn conclusion, our studies powerfully demonstrated that modification of LHBs by N glycosylation could modulate their secretion, affect ER stress or expression of cycling, cell cycle and proliferation. The N320K may be the key sites N-linked glycosylation modification of LHBs. It may be a mechanism of HBV-induced HCC..Keywords: Glycosylation_Hepatitis B Virus_Endoplasmic Reticulum Stress_Cell Proliferation
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Page 31BackgroundAs most HBV-related acute-on-chronic liver failure (ACLF) have concurrent cirrhosis, it is important to clarify the association of viral factors with ACLF with or without cirrhosis..ObjectivesThe aim of this study was to analyze the association of HBV genotypes and mutations with ACLF development underlying different chronic liver diseases..Patients andMethodsEighty-seven ACLF patients including 29 patients with chronic hepatitis (ACLF-CHB) and 58 patients with liver cirrhosis (ACLF-LC) were enrolled. Age and sex matched patients with chronic hepatitis (CHB) and liver cirrhosis (LC) were enrolled as controls. The genotypes and mutations at HBV basic core promoter (BCP), precore (PC), and partial C regions were determined by nested PCR and direct sequencing..ResultsOur results revealed significantly higher incidences (P < 0.05) of genotype B with C1913A/G or A1846T in patients with ACLF-CHB than those with CHB; genotype C with C1913A/G or A1846T in patients with ACLF-CHB and ACLF-LC than those with CHB and LC, respectively. Multivariable analysis indicated that A1846T and C1913A/G mutations were independent factors for ACLF (OR = 2.86 and 5.93, respectively), suggesting an association between the mutations and development of ACLF. In addition, there were no significant differences in mutations at T1753V, A1762T, G1764A, G1896A, and G1899A which were found between either CHB and ACLF-CHB or LC and ACLF-LC patients, suggesting no associations of these mutations with ACLF development..ConclusionsOur findings suggest that CHB or LC patients infected with HBV A1846T and C1913A/G mutants are more susceptible to develop ACLF..Keywords: Liver Failure_Hepatitis B Virus_Mutation_Risk Factors
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Page 39BackgroundMaintenance of the adequate intraoperative renal perfusion is very important during Orthotopic Liver Transplantation (OLT) to prevent acute renal failure..ObjectivesFor the first time, this study was designed to survey the effects of octreotide on urine output during anesthesia for OLT and early postoperative renal function..Patients andMethodsIn this randomized double-blind placebo controlled clinical trial, 79 of 89 patients who underwent OLT and fulfilled the study requirement were randomly allocated into two groups. In the octreotide group, the patients received octreotide infusion from the start of the operation. On the other hand, the control group patients received physiologic saline infusion instead of octreotide. The Mean Arterial Pressure (MAP), heart rate, urine output, norepinephrine usage, and dosage during the three stages of OLT, and baseline and postoperative creatinine were recorded and compared between the two groups..ResultsNo significant differences were found between the two groups regarding the demographic characteristics and graft factors (P > 0.05). However, urine output and MAP during the three stages of OLT were significantly higher in the octreotide group compared to the control group (P < 0.05). Moreover, no significant difference was observed between the two groups regarding baseline as well as postoperative creatinine (P > 0.05)..ConclusionsThe results demonstrated that octreotide infusion during anesthesia for OLT not only augmented the vasoconstriction effect of norepinephrine to increase MAP, but also maintained better renal perfusion and urine output during the operation..Keywords: Liver Transplantation, Octreotide, Urine
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Page 46BackgroundThere is still no suitable mice model that can completely mimic the human fulminant hepatitis, which sets a block for drug effect evaluation and mechanism researching of human fulminant hepatitis..ObjectivesThe aim of this study was to establish an animal model able to mimic the main features of human fulminant hepatitis..Materials And MethodsDimethylnitrosamine (DMN) was peritoneally injected to mice for liver injury induction. Serum biochemicals, and Prothrombin Time were tested, and Prothrombin activity was calculated, the liver tissue pathological changes were evaluated via macroscopic view observation, HE staining, immunochemical staining, and electron microscopy observation. The mRNA levels of TNF-a, Fas, and IL-1beta were tested with quantitative PCR assay..ResultsThe serum levels of both ALT and AST were elevated significantly and showed a high plateau. Liver pathological changes were progressed before 48 hours post DMN injection and then started to restore. The mRNA and protein expression levels of TNF-α and IL-1β were significantly elevated. The PT started to extend from 36 hours and PTA was lower than 40% from then on..ConclusionsThis kind of DMN induced mice liver injury is similar to human fulminant hepatitis in main features. This work provided a mice model which could mimic human fulminant hepatitis, and could be valuable for fulminant hepatitis mechanism research and liver protection drug evaluation..Keywords: Liver, Mice, Dimethylnitrosamine, Hepatitis