فهرست مطالب
Hepatitis Monthly
Volume:17 Issue: 2, Feb 2017
- تاریخ انتشار: 1395/12/15
- تعداد عناوین: 8
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Page 1BackgroundOne 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..ObjectivesThe aim of this study was to estimate the point prevalence of HCV infection among Iranian general population..MethodsPublished 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..ResultsTwelve 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..ConclusionsOur 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..Keywords: Hepatitis C, Iran, General Population, Systematic Review
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Page 2Context: Hepatitis A virus (HAV) infection is the most common type of acute viral hepatitis that has been proposed as an important public health issue. Most of the countries in WHO Eastern Mediterranean region (EMR) and Middle East (ME) have a high endemicity of HAV infection. To provide a comprehensive estimation of the epidemiology of HAV in this region, we carried out a systematic review on the literature reporting the prevalence of HAV infection in the EMR and ME..
Evidence Acquisition: We conducted a systematic search in the databases including PubMed, Scopus, Science Direct, and Web of science using appropriate search strategies. Observational studies published between January 1990 and July 2016 with clearly stated data regarding HAV Ab (IgG) in non-high-risk groups from countries of EMR and ME were examined. We estimated the prevalence of HAV infection and 95% confidence interval based on the pooled data from all included studies for each country, and the regions were weighted according to the population size of each country in that region..ResultsThe HAV prevalence in ME, WHO EMR, and in total was 61.60 (61.31 - 61.89), 65.74 (65.39 - 66.09), and 62.60 (62.32 - 62.89), respectively. We found no eligible study for Bahrain, Djibouti, Libya, Oman, Qatar, and Sudan. Cyprus had the lowest prevalence rate of HAV (2.61% (1.53 - 4.17)) that along with UAE and Kuwait, it had a prevalence rate below 50%. The most HAV prevalence rates were related to Afghanistan (99.01 (95.51 - 99.89)), Iraq (96.35 (95.97 - 96.70)), Somalia (96.00 (94.16 - 97.33)), and Palestine (93.70 (90.96 - 95.77)), in sequence..ConclusionsThe countries of EMR and ME need more and constant programs for prevention and control of HAV infection. Also, further primary original epidemiological studies are needed in some countries of the region..Keywords: Hepatitis A, Prevalence, Middle East, Systematic Review -
Page 3BackgroundRecapitulating the native cell niche and extracellular matrix (ECM) architecture in vitro helps reconstruct injured tissues. Collagen I and heparin are two important constituents of the ECMs, which play crucial roles in regulating cell behaviors. Specifically in the liver, these components can affect the differentiation and functionality of the cells..ObjectivesThe aims of this study were to first fabricate and characterize a heparin/collagen scaffold and then investigate the scaffolds efficiency in directing the differentiation of Whartons jelly-derived mesenchymal stem cells (WJ-MSCs) towards hepatocyte..MethodsAfter fabricating the rat tail collagen I sponge-shaped scaffolds, heparin was chemically immobilized on the scaffolds using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The scaffold chemical characteristics and architecture were evaluated by Fourier-transformed infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), respectively. In the next step, Whartons jelly-derived mesenchymal stem cells were seeded on the scaffolds and cell viability and morphology were assessed using MTT assay and SEM, respectively. Moreover, followed by exposing the WJ-MSCs to the hepatogenic media for 3 weeks, liver-specific marker expression and indocyanine green (ICG) clearance tests were performed..ResultsThe data showed that 0.25 mg/mL heparin had no detrimental effects on the cell viability and proliferation compared to the observed effects in non-heparinized conditions. SEM micrographs showed that while immobilizing heparin had no considerable effect on the porosity of the scaffolds, the mean value of the pore sizes of heparinized sponges was higher than that of non-heparinized ones. The hepatocyte differentiation appeared to be enhanced in the cells cultured in heparinized sponges as indicated by higher percentage of the cells expressing cytokeratin 19 and albumin as well as improved indocyanine green clearance levels..ConclusionsHeparin/collagen scaffold serves as a good platform for promoting differentiation into hepatocytes and therefore, it has the potential to be considered for drug discovery and liver regenerative medicine..Keywords: Wharton's Jelly-Derived Mesenchymal Stem Cells, Hepatocytes, Collagen, Heparin, Tissue Engineering, Scaffold
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Page 4BackgroundOne of the deadliest types of liver cancer is hepatocellular carcinoma (HCC). The current treatment methods show poor tolerance and low efficacy. Phallusia nigra (P. nigra) is a kind of sea squirt or marine tunicate that lives in tropical seas around the world. As a marine animal, it contains natural bioactive products. It has been shown that P. nigra has some biological properties, including anti-inflammatory property..ObjectivesIn this study, we examined the selective toxicity of methanolic extracts obtained from body and wall of Persian Gulf P. nigra on isolated mitochondria obtained from liver hepatocytes of hepatocellular carcinoma-induced rats..MethodsFor induction of HCC, the rats were injected with a single dose of diethyl nitrosamine (DEN) at 200 mg/kg, followed by dietary administration of 2-acetylaminofluorene (2-AAF) (0.02%) for 14 days. Then, the HCC induction was approved by histopathological evaluations, liver function markers (ALT, AST, and ALP), and determination of blood levels of liver cancer specific marker, i.e. alpha-fetoprotein (AFP). At the end, mitochondria isolated from cancerous and normal hepatocytes were applied for subsequent investigations..ResultsOur results showed that different concentrations (250, 500, and 1000 μg/mL) of both extracts (from body and wall) significantly induced reactive oxygen species (ROS) formation, promoted mitochondrial swelling, decreased mitochondrial membrane potential (MMP), and increased cytochrome c release only in HCC hepatocyte mitochondria in a time and concentration dependent manner. No significant change in the above mentioned parameters was observed in the control hepatocyte mitochondria..ConclusionsOur results suggest that bioactive compounds of P. nigra could be promising anti-HCC molecules. However, further studies are needed including molecular identification tests, confirmatory in vivo experiments, and clinical trials..Keywords: Hepatocellular Carcinoma, Mitochondrial Targeting, Selective Toxicity, Phallusia nigra
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Page 5BackgroundProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of hepatic disorders that can progress rapidly, leading to cirrhosis and death due to liver failure. Mutations and variations in three genes, including ATP8B1, ABCB11, and ABCB4, have been reported to be the main genetic cause of three subtypes of this disorder including PFIC1, PFIC2, and PFIC3, respectively..ObjectivesTherefore, the aim of this study was to investigate more common mutations and variations associated with PFIC considering clinical and Para-clinical features of the disease..MethodsThirty-five unrelated patients with PFIC from the south of Iran were selected randomly among all PFIC patients referring to Namazi hospital, affiliated to Shiraz University of Medical Sciences. Genomic DNA was extracted from the peripheral blood lymphocytes. Sequences related to these variations were then amplified by PCR in the 35 cholestasis patients and analyzed by Sanger® sequencing..ResultsThe results showed that there was no variation in interest exon of ABCB4. Moreover, in ATP8B1, there was no prevalent mutation and only an unknown significant variation (c.*1101 366G > A) was found. However, in the ABCB11 gene, different variations were found including c.1434 174G > A, c.1434 70C > T, c.1331T > C (p.Val444Ala, a common variant proposed to be associated with cholestasis), c.1309-93G > A, c.1309-165C > T. Also, 11 and 13 cases showed heterozygote and homozygote, respectively, for V444A variation of the ABCB11 gene..ConclusionsThe allele frequency of V444A in this study was 52.8%. This variation has been previously implicated with higher frequencies in ICP and DIC than normal subjects, suggesting that this variation may become disease-relevant in certain conditions..Keywords: Intrahepatic Cholestasis, Mutation, ABCB4, ATP8B1, ABCB11
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Page 6BackgroundThis study aimed to retrospectively assess the safety and usefulness of hepatic arterial infusion chemotherapy (HAIC) with cisplatin in patients with hepatocellular carcinoma (HCC) and Child-Pugh (C-P) score ≥ 8, who were refractory to or ineligible for transcatheter arterial chemoembolization (TACE)..MethodsIn this study, 28 cisplatin-naïve patients with HCC, C-P score ≥ 8, and no evidence of extrahepatic lesions were treated using HAIC with cisplatin between July 2004 and July 2013..ResultsOf 28 patients, 10 were refractory to TACE and 18 ineligible for TACE. In terms of C-P score, 17 patients had a score of 8, 6 a score of 9, and 5 a score of 10. The injected dose of cisplatin was reduced in 64.3% of cases. The overall response rate was 10.7%, with a disease control rate of 35.7%. Overall, median survival time (MST) and progression-free survival were 186 and 80 days, respectively. In patients with macroscopic vascular invasion (MVI-positive; n = 9), these values decreased to 161 and 72 days, respectively; while they increased to 341 and 87 days, respectively, in MVI-negative patients (n = 19). Patients achieving partial response (PR) and stable disease (SD) status as well as those achieving SD status showed significantly better survival than patients with progressive disease (PD status): PR SD vs. PD: MST = 447 vs. 123 days, PConclusionsHAIC with cisplatin can be safely administered in patients with HCC and C-P score ≥ 8, who are TACE-refractory or -ineligible. An extended survival time is expected when the treatment outcome is either SD or more favorable..Keywords: Chemotherapy, Cisplatin, Intraarterial, Liver Cancer
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Page 7BackgroundA major risk during blood transfusion is the transmission of infectious agents such as Hepatitis B virus (HBV). Screening for anti-HBc antibodies has long been used to test HBV infection and thus, blood safety. However, the development of advanced tools enabling HBV-DNA detection rendered the diagnostic benefit of anti-HBc test uncertain..ObjectivesIn this study, we aimed to evaluate the relationship between HBV-DNA, anti-HBs, and anti-HBc loads..MethodsSera of 7200 blood donors were first screened for HBs antigen (HBsAg) and anti-HBc antibody. Samples that were found to be HBsAg-negative but anti-HBc-positive were further tested for anti-HBs and HBV-DNA..ResultsOf the 7200 tested samples, 7143 (99.2%) were HBsAg-negative, while the remaining 57 (0.8%) samples were HBsAg-positive. Among the HBsAg-negative samples, 490 (6.8%) were anti-HBc-positive. Of the anti-HBc positive samples, 397 (81%) were anti-HBs-positive, while the remaining 93 (19%) samples were anti-HBs-negative. Interestingly, all of the anti-HBc positive samples, which also were positive for anti-HBs, exhibited negative HBV-DNA results. On the other hand, the anti-HBc positive samples, which were negative for anti-HBs, showed both negative and positive HBV-DNA results..ConclusionsBlood samples which are positive for both anti-HBc and anti-HBs are characterized by negative HBV load..Keywords: Hepatitis B Virus (HBV)_Anti-HBc_Anti-HBs_Blood Safety
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Page 8BackgroundPumilio/fem-3 mRNA binding factor (PUF) proteins can bind RNA in a sequence-specific manner. The deciphered RNA-recognition code of these proteins has enabled researchers to design engineered PUF proteins, capable of binding to any desired target in order to modify its ultimate fate. In this study, a modified Homo sapiens Pumilio 1-homology domain (HsPUM1-HD) was engineered to bind to the internal ribosome entry site (IRES) of hepatitis C virus (HCV) genome to potentially inhibit viral translation..MethodsBased on the RNA-recognition code, required modifications were applied to HsPUM1-HD in order to change its natural recognition sequence to a sequence in the stem-loop III of HCV IRES. RNA protein pull-down assay was performed to assess the sequence specificity of the modified HsPUM1-HD (mHsPUM1-HD). Translational inhibitory effect of mHsPUM1-HD was evaluated in a dual-luciferase reporter assay..ResultsThe mHsPUM1-HD was found to bind to its cognate RNA in a sequence-specific manner, as a biotinylated target RNA captured mHsPUM1-HD through binding to streptavidin magnetic beads. This protein also reduced HCV IRES-dependent firefly luciferase translation by 40% in HEK293 cells..ConclusionsThe present study is the first report of an engineered HsPUM1-HD with potential anti-HCV activity. These findings suggest that PUM-HDs can be engineered to target desired RNAs of infectious agents in order to specifically interrupt protein translation, as an essential step of their life cycle..Keywords: Hepatitis C Virus_Pumilio Protein_Internal Ribosome Entry Sites