فهرست مطالب
Hepatitis Monthly
Volume:13 Issue: 5, May 2013
- تاریخ انتشار: 1392/04/14
- تعداد عناوین: 27
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Page 1Background
Wilson disease is a rare disorder of copper metabolism due to mutation in ATP7B gene. Proper counseling of patients with Wilson disease, and their families necessitates finding mutation in ATP7B gene. Finding mutations in ATP7B gene with 21 exons, and more than 500 mutations is expensive and time-consuming..
ObjectivesThe aim of this study was to provide a simple multiplex amplification refractory mutation system PCR (M-ARMS-PCR) for screening eight common mutations in ATP7B gene..Patients and
MethodsTwo sets of ARMS mutant and normal specific primer pairs were designed for genotyping of p.R778L, p.R969Q, p.H1069Q, and p.3400delC mutations as Set 1 and p.W779G, c.3061-1G > A, p.I1102T, and p.N1270S mutations as Set 2. The Multiplex ARMS assay was then subsequently tested in 65 patients with Wilson disease with known and unknown ATP7B mutations..
ResultsUsing these two sets, we identified H1069Q mutation in four patients, c.2335T > G mutation in three, c.3061-1G > A splice site mutation in five, c.3305T > C mutation in one, and c.3809A > G mutation in two patients..
ConclusionsThe Multiplex ARMS assay used in this study can be an efficient, reliable, and cost effective method as a primary screen for patients with Wilson disease..
Keywords: Multiplex Polymerase Chain Reaction, Hepatolenticular Degeneration, Iran -
Page 2Background
HCV virus (HCV) is a significant global problem with wide-ranging socio-economic impacts. Because of the high morbidity and mortality associated with end-stage liver disease, cirrhosis, and hepatocellular carcinoma (HCC), the economic burden of HCV infection is substantial..
ObjectivesThis study aimed to estimate the direct medical care costs of chronic HCV infection..Patients and
MethodsFor this cross-sectional study, 365 courses of HCV treatment were extracted from medical records of 284 patients being referred to Tehran HCV clinic, a clinical clinic of Baqiyatallah Research Center for Gastroenterology and Liver diseases, from 2005 to 2010. All the patients had been diagnosed with HCV. Direct medical care costs for each course of HCV treatment have been calculated based on Purchasing Power Parity Dollar (PPP$)..
ResultsAverage direct medical costs for the courses treated with conventional interferon plus ribavirin (INF-RBV) were 4,403 PPP$, and 20,010 PPP$ for peg-interferon plus ribavirin (PEG-RBV) courses. There was an increase of the direct costs in both courses of treatment to achieve Sustain Viral Response (SVR). The costs amounted to 10,072 PPP$ in (INF-RBV) treatment and 34,035 PPP$ in (PEG-RBV). The significant difference between the costs of these two courses of treatment is attributable to high cost of Peg-interferon. This indicates that the medication costs are the dominant costs..
ConclusionsAccording to the results, total direct medical costs for HCV patients in Iran exceeded 12 billion PPP$ in (INF-RBV) treatment and 55 billion PPP$ in (PEG-RBV)..
Keywords: Hepatitis C, Chronic, Health Care Costs, Peginterferon Alfa, 2a -
Page 3Background
Single nucleotide polymorphisms (SNP) in the promoter region of the interleukin (IL)-10 genes have a role in determining hepatitis B virus (HBV) outcome..
ObjectivesThis study evaluates the correlation between HBV infection and SNP in IL-10 gene promoter..Patients and
MethodsNinety-six HBV-infected patients (32 chronic hepatitis B infection patients, 34 healthy carriers, 30 spontaneously recovered cases) and 31 healthy controls were enrolled. Three biallelic (-819,-592,-1082) regions in the IL-10 gene promoter were sequenced for all patients..
ResultsGenotypes and haplotypes of IL-10 gene promoter region at position -1082, -819 and -592 were not significantly different among controls, HBV recovered cases, carriers and chronic HBV patients. Nevertheless, A/A genotype at position -592 and T/T genotype at position -819 were more frequently seen in the HBV clearance group, while frequency of G/G genotype at position -1082 was more prevalent in the persistence group. GCC/GCC and GCC/ACC haplotypes were significantly observed in anti-HBe positive individuals..
ConclusionsOur findings showed that IL-10 promoter polymorphisms were not correlated with HBV infection prognosis. Nevertheless, individuals carrying high and intermediate producer of IL-10 haplotypes had a better ability to develop anti-HBe than low producer carriers..
Keywords: Hepatitis B virus, Genotype, Interleukin, 10, Haplotypes -
Page 4Background
Liver biopsy has remained the gold standard for the diagnosis of chronic hepatitis C; even though, it has a low but non-negligible rate of both false negative and complications. Several authors have proposed noninvasive tools to diagnose cirrhosis. But none of them showed complete concordance with liver biopsy..
ObjectivesTo devise a score based on noninvasive routine parameters that discriminate between patients with a high risk, and those with a low risk of cirrhosis among patients with chronic hepatitis C without performing liver biopsy, and to compare this score with other ones using routine parameters devoted to this aim..Patients and
MethodsWe reviewed the charts of patients with chronic hepatitis C who performed a liver biopsy between 2000 and 2004. Multivariate analysis was used to identify independent predictors of cirrhosis. An independent group of patients with chronic hepatitis C admitted for a liver biopsy between 2007 and 2012 constituted the validation set..
ResultsWe enrolled 249 patients who had complete laboratoristic data, and sufficient liver tissue for fibrosis staging. Age, AST, prothrombin activity, and platelets were identified as independent predictors of histological cirrhosis. We categorized these variables, and devised a novel score called CISCUN (Cirrhosis Score University of Naples), giving one point to each of the following predictors: age > 40 years; AST > 2 upper normal values; platelet count < 160.000/mmc; prothrombin activity < 100%. Cirrhosis rate was 2.9% for the 103 patients with a CISCUN = 0 or 1, 23.4% for the 124 patients with a CISCUN of 2 or 3, and 86.4% for the 22 patients with a CISCUN = 4. These results were confirmed in the independent validation group of 285 patients with similar characteristics..
ConclusionsPatients with chronic hepatitis C and with a CISCUN ≤ 1 had a very low rate of cirrhosis while those with a CISCUN = 4 had a high risk of cirrhosis. Patients with CISCUN = 2 or 3 had an intermediate rate of cirrhosis, and therefore needed to perform a liver biopsy to receive a reliable diagnosis..
Keywords: Liver Cirrhosis, Fibrosis, Biopsy, Noninvasive Ventilation -
Page 5Background
There are insufficient data available on utilization and health care costs of non-alcoholic fatty liver disease. The cost data for different health conditions and services is a major gap in Iranian health system. So this study is the primary or first step towards filling this gap..
ObjectivesThis study aims to estimate the diagnosis and treatment costs of Non-alcoholic Fatty Liver..Patients and
MethodsThis cross-sectional study was conducted on 528 subjects. The subjects had been diagnosed with non-alcoholic fatty liver. All the subjects had been referred to the Tehran Fatty Liver Clinic, a clinic of the Baqiyatallah Research Center for Gastroenterology and Liver Diseases, in 2009 and they had been observed for 2 years to determine the frequency of health care utilization (physician visit, laboratory tests, medication and cost of sonography). The costs of diagnosis and treatment for each person were estimated in Purchasing Power Parity dollars (PPP$)..
ResultsThe average total cost was 5,043 PPP$ per person in the 2 years of observation. Majority of these 528 patients (87.9%) had a BMI ≥ 25 (kg/m2). Also, 33.9% were diagnosed with comorbid diseases such as Diabetes Mellitus (DM), Coronary Artery Disease (CAD), hypertension (HTN) and hypothyroidism (HYPO)..
ConclusionsThe results confirmed that the total costs for non-alcoholic fatty liver among the Iranian adult urban population alone exceeded 1 billion PPP$ per year. These costs can be saved or reduced by effective disease management and early prevention..
Keywords: Non, alcoholic Fatty Liver Disease, Costs, Cost Analysis, Delivery of Health Care, Utilization -
Page 6Background
Hepatitis C virus (HCV) is the cause of high morbidity and mortality worldwide, inflicting around one million people in Pakistan alone. The HCV genomic RNA harbors conserved structural elements that are indispensable for its replication. The 3’ untranslated region (UTR) contains several of these elements essentially involved in regulating the major steps of the viral life cycle..
ObjectivesDifferences in regulatory elements of HCV may contribute towards differential infectivity of local isolates. The present study explicates sequence analysis and secondary structure prediction of HCV 3''UTR region of subtype 3a from Pakistan to characterize this particular region..Patients and
MethodsHCV 3''UTR region was amplified, cloned and sequenced from five different patients. Sequence and structural analysis was performed and phylogenetic analysis was carried out using the 3''UTR sequence reported in NCBI nucleotide data base (http://www.ncbi.nlm.nih.gov/nuccore) by other studies..
ResultsSequence analysis of the amplified fragment from five patients indicated that the 3''UTR is composed of 214-235 nts. Its sequence contains a type-specific variable region followed by a poly U/UC region and a highly conserved X-tail of 98 nts. The variable region reported here has 26 nts and one stem loop at the secondary structure that differentiate it from HCV genotype 1a (GT1a) 3''UTR which contains additional 14 nts and two stem loops. The poly U/UC region varied in length (100-79 nts) and nucleotide sequence within the Pakistani isolates, and among different genotypes. Some substitutions found in the X-tail do not affect secondary structure of this element suggesting that this region might play an important role in replication, stabilization and packaging of HCV genome. Additionally, U residues are not present at the end of the X-tail in Pakistani 3a isolates as otherwise reported for the variants of genotype 1b..
ConclusionsSequence and structural diversity of the 3''UTR variable region and Poly U/UC region found in the local isolates indicate specificity in the regulating elements of 3''UTR that might be associated with differential replication efficacy of the HCV Pakistani isolates. The study necessitates functional characterization of these regulating elements to elucidate variable viral efficiency and pathogenicity associated with inter-geographical isolates..
Keywords: Hepacivirus, Phylogeny, Untranslated Regions, Multilocus Sequence Typing -
Page 7Background
Hepatitis D virus (HDV) is a defective virus dependent on hepatitis B virus (HBV) for its replication. Due to HDV transmission routes, patients undergoing hemodialysis and those with HIV infection are at risk of acquiring HDV..
ObjectivesThis study was aimed to determine the frequency and genotype of HDV infection among patients with HIV infection and those undergoing hemodialysis..Patients and
Methods720 cases including 120 patients undergoing hemodialysis, and 600 patients with HIV infection were studied. All cases with positive results for HBsAg were evaluated for the presence of anti-HDV antibodies. Samples with Anti-HDV positive results were subjected to nested PCR for HDV-RNA confirmation, and sequenced for HDV genotype determination..
ResultsHBsAg was found in 9 (7.5%) of 120 patients undergoing hemodialysis, and 9 (1.5%) of 600 patients with HIV infection. 3 (33.3%) of patients undergoing hemodialysis with positive results for HBsAg, and 5 (55.5%) of cases with HIV infection and positive results for HBsAg, had positive findings for anti-HDV which were then subjected to nested PCR. The amplification results confirmed that in 3 (37.5%) samples HDV-RNA was detected. Overall 2.5% of patients undergoing hemodialysis, and 0.8% of cases infected with HIV had positive results for anti-HDV and 1.7% and 0.2% of cases undergoing hemodialysis and patients infected with HIV had positive findings for HDV-RNA respectively. All of the HDV isolates were clustered in clade 1..
ConclusionsThe survey showed that overall HDV frequency was not high in our high risk cases. Therefore, practitioners and health care managers should become aware of the risk of dual infection with HBV and HDV especially in high risk patients..
Keywords: Hepatitis Delta Virus, HIV, Hemodialysis, Genotype -
Page 8Background
Hepatocellular carcinoma (HCC) is one of the leading causes of death in Saudi male patients. Local clinical and demographic data of this disease are scarce..
ObjectivesWe sought to describe the clinical characteristics and outcomes of patients from two tertiary care centers in Saudi Arabia..Patients and
MethodsData were collected for all patients diagnosed to have hepatocellular carcinoma between June 2003 and July 2008 who had been registered in a special research database (the Saudi Observatory Liver Disease Registry (SOLID)). Data were extracted from SOLID for clinical, biochemical, radiologic parameters and outcome..
ResultsData was available for 363 patients, the mean age of diagnosis was 66 years, 74% of patients were males, and Hepatitis C was the underlying cause of liver disease in 48%, while Hepatitis B in 29%. Most of the patients were diagnosed at an advanced stage, 53 % of patients had a CLIP score of 4 to 6 (advanced stage), 55% had large multi-nodular tumors and 16% had vascular invasion or extra-hepatic spread at the time of diagnosis. Most of the patients had decompensated cirrhosis; with child-pogh score B in 44% and C in 26% with presence of portal hypertension in 55%. Forty eight percent died during the study period. Predictors of poor survival in the univariate analysis were; presence of portal vein thrombosis (P = 0.03), portal hypertension (P < 0.0001), presence of ascites (P = 0.022), hepatic encephalopathy (P < 0.0001), advanced child-pough score (P < 0.0001), bilirubin > 22 (P < 0.0001) and INR > 1.2 (P = 0.02). On multivariate analysis, only the presence of portal hypertension, bilirubin > 22 and severe hepatic encephalopathy were significant with adjusted hazard ratio of 1.6 (95% CI; 1.04-2.47), 1.76 (95% CI; 1.12-2.8), and 3.18 (95% CI; 1.42-7.14) respectively..
ConclusionsThe data from this cohort indicates that most of patients diagnosed with HCC present at late tumor and liver disease stages, when prognosis is usually dismal. Regular cancer surveillance in cirrhotic patients might change the outcomes. Further studies with results of treatment outcomes in this community are needed..
Keywords: Carcinoma, Hepatocellular, Alpha, Fetoproteins, Hepatitis B, Hepatitis C, Saudi Arabia -
Page 9Background
Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy..
ObjectivesMeasuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting..Patients and
MethodsWe evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4)..
ResultsTE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD: 18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS..
ConclusionLong term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance..
Keywords: Liver Cirrhosis, Elasticity Imaging Techniques, Insulin Resistance -
Page 10Background
Given the long term exposure to risk factors, it is likely that older adults exhibit the highest proportions of HBV serological markers. Nevertheless, there are few methodologically adequate studies in Brazil evaluating the prevalence and risk factors for HBV infection in individuals aged 60 years or more..
ObjectivesTo estimate the prevalence and factors associated with HBV infection in elderly residents in the city of Tubarão/SC..Patients and
MethodsThis cross-sectional study included 820 individuals (≥ 60 years) selected by simple random sampling. The variables were compared by chi-square test or Fisher''s exact test and those with P < 0.200 were included in the regression model..
ResultsThe mean age of patients was 68.6 ± 7.0 years, 39% were men and 92% Caucasian. Five subjects (0.6%) presented with positive HBsAg and 124 (15.1%) were anti-HBc reactive. Bivariate analysis showed that the presence of anti-HBc was associated with age ≥ 67 years, ≤ 4 years of schooling, acupuncture therapy and lower proportion of subjects exposed to invasive procedures. In multivariate analysis, the following variables remained independently associated with HBV infection: male gender, marital status, ≤ 4 years of schooling and acupuncture..
ConclusionsThe prevalence of anti-HBc among the elderly in the city of Tubarão was higher than in previous studies evaluating blood donors in the same region. Despite the association of previous HBV infection and factors indirectly related to sexual risk behaviors, the results suggest the involvement of invasive therapeutic procedures in the HBV transmission chain..
Keywords: Hepatitis B, Epidemiology, Infectious Disease Transmission, Prevalence, Risk Factors -
Page 11Background
Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of insulin resistance (IR) syndrome. The effect of insulin sensitizers on liver function tests and metabolic indices in NAFLD patients is a matter of debate..
ObjectivesThe aim of study was to compare the effects of two different insulin sensitizers, pioglitazone, and metformin, on liver function tests (LFT), lipid profile, homeostasis model assessment-IR (HOMA-IR) index, and liver fat content (LFC) in NAFLD patients..
Materials And MethodsThis double blind clinical trial was performed on patients who were referred to a gastroenterology clinic with evidence of fatty liver in ultrasonography. After excluding other causes, participants with persistent elevated alanine aminotransferase (ALT) levels and “NAFLD liver fat score” greater than -0.64 were presumed to have NAFLD and were enrolled. They were randomly assigned to take metformin (1 g/day) or pioglitazone (30 mg/day) for four months. Fasting serum glucose (FSG), ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, cholesterol (CHOL), high and low density lipoprotein (HDL, LDL), HOMA-IR, and LFC were checked at the baseline, two and four months post-treatment. LFC was measured by a validated formula..
ResultsEighty patients (68 males) with mean age of 35.27 (± 7.98) were included. After 2 months, LFT was improved significantly in the pioglitazone group and did not change in the metformin group. After four months, both medications significantly decreased serum levels of LFT, FSG, CHOL, LDL, HOMA-IR, and LFC, and increased serum level of HDL. No statistically significant differences were seen between the two treatment groups with regard to the changes of laboratory parameters and LFC from baseline to four months post-treatment..
ConclusionsDuring the four months, the use of metformin (1 g/day) and pioglitazone (30 mg/day) were safe and might have equally affected LFT, HOMA-IR, lipid profile, and LFC in NAFLD patients..
Keywords: Fatty Liver, Insulin Resistance, Metformin, Pioglitazone -
Page 12Background
Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway..
ObjectivesThe present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD..Patients and
MethodsEighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms..
ResultsA significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697)..
Conclusionsadiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations..
Keywords: Fatty Liver, Adiponectin, Polymorphism -
Page 13Background
Hepatitis C virus (HCV) is the major cause of chronic liver disease. HCV is a single stranded positive sense RNA of approximately 9.6 Kb. Because of high conservativeness of 5΄untranslated region of HCV genome, it is widely used for virus genotyping. Different methods are used for the virus genotyping, but all involve some difficulties..
ObjectivesThe aim of the present study was to develop an in-house reverse hybridization method as a line probe assay, for HCV genotyping..
Materials And MethodsSixty serum samples were collected with newly diagnosis of HCV infection. Genotyping process had already been performed for the samples using RT-PCR RFLP method. After total RNA extraction from the samples and cDNA synthesis, nested PCR method was applied for amplification of the target sequence on the 5΄UTR. In the nested PCR, biotinylated oligonucleotides were used as inner primers. Optimized concentrations of the biotinylated inner primers (as positive control), two universal and seven specific probes were spotted onto nylon membrane stripes in a defined pattern. Hybridization process was conducted between the probes and the denaturized biotin labeled PCR products. Finally, the stripes were developed by using streptavidin conjugated alkaline phosphate as a signal generating agent. To determine the diagnostic sensitivity and specificity of the home made LiPA, a panel containing 60 confirmed sera with positive results for HCV (and PCR-RFLP genotyped) was subjected to evaluate..
ResultsAgarose gel electrophoresis of the nested PCR products using the outer and inner primers showed 305 and 234 bp fragments respectively. After performing hybridization and detection processes on the prepared strips, the colored bands were formed for the positive control, universal probes and the corresponding genotypes. HCV genotype results were found to be in 100% concordance through studying 60 sera that were successfully typed by the two methods. P-value of 0.045 conveys that the two methods were the same and had no significant difference..
ConclusionsThe most common genotyping method in Iran is RT-PCR RFLP. Given the results and advantages of this homemade technique, such as high specificity and sensitivity, ability for detection of most genotypes, it provides possibility of evaluating much of the isolates without needing electrophoresis stage..
Keywords: Hepatitis C Virus, Genotyping, LIPA Protein, Human -
Page 14Background
Population based studies on prevalence and risk factors of NAFLD in Iranian population are few. The prevalence of NAFLD and non alcoholic steatohepatitis (NASH) in Iranians varies from 2.9% to 7.1% in general population and 55.8% in patients with type 2 diabetes mellitus..
ObjectivesTo determine the prevalence and determinants of non alcoholic fatty liver disease (NAFLD) in a sample of adult Iranian general population..Patients and
MethodsThis was a cross-sectional study being performed in Shiraz, southern Iran during a 10-month period from November 2010 to September 2011 through cluster random sampling of Iranian general population in Shiraz region. All individuals undergone anthropometric, blood pressure measurements, thorough medical history and physical examinations. Laboratory measurements included fasting blood glucose (FBS), lipid profile, complete blood count (CBC) and liver function tests. NAFLD was diagnosed by transabdominal ultrasonography..
Results819 subjects were included in this study among which were 340 males (41.5%) and 479 females (58.5%) with the mean age of 43.1 ± 14.1 years. NAFLD was diagnosed in 176 (21.5%) subjects. Patients with NAFLD were significantly older (P < 0.001), had higher proportion of male gender (P = 0.004) and had higher BMI (P < 0.001). They also had higher prevalence of hypertension (P < 0.001), high FBS (P < 0.001), high cholesterol (P = 0.026), high triglyceride (P < 0.001) and high waist circumference (P < 0.001). Taking all these together, patients with NAFLD had significantly higher prevalence of metabolic syndrome when compared to healthy subjects (P < 0.001)..
ConclusionThe prevalence of NAFLD in this group of Iranian adult general population is 21.5%. NAFLD in Iranian population is associated with male gender, old age, obesity, and features of metabolic syndrome..
Keywords: Non alcoholic Fatty Liver Disease, Prevalence, Risk Factors, Metabolic Syndrome, Iran -
Page 15Background
The presence of an infected family member significantly increases the risk of HBV transmission, but many socio-demographic and viral characteristics of family members affect the transmission rate..
ObjectivesIn this study, we have used data mining techniques to investigate the impact of different variables in intrafamilial transmission of HBV infection..Patients and
Methodsdemographic information, viral markers, and medical history of 330 patients with chronic hepatitis B and their offspring attending a referral center in Tehran were collected. Data-mining techniques were administered to detect patterns..
ResultsThe overall transmission rate was 15.7% (5.4% and 27.3% for male and female index cases respectively). In female patients, HBe Ag positively affected the transmission rate (49% vs. 23.4%). There was a dominant change in transmission rate of female patients with negative results for Hbe Ag with HDV coinfection, where the transmission rate changed from 25% in patients with negative results for HDV Ab to 5% in those with positive results. In Hbe Ag negative male index cases, the transmission rate was 1.3% in cases with positive results for HDV Ab compared to 7% in those with negative findings. The overall transmission rate was statistically different between patients with positive and negative results for HDV Ab (P = 0.016)..
ConclusionsThere is a minor but consistent pattern change in the presence of HDV infection which reduces familial transmission of HBV, especially in female patients with negative results for HBe Ag..
Keywords: Data Mining, Hepatitis B Virus, Hepatitis D, Machine Learning -
Page 16Background
The hepatitis B virus X (HBx) protein has long been recognized as an important transcriptional transactivator of several genes. Human aldo-keto reductase family 1, member C1 (AKR1C1), a member of the family of AKR1CS, is significantly increased in HBx-expressed cells..
ObjectivesThis study aimed to investigate the possible mechanism of HBx in regulating AKR1C1 expression in HepG2.2.15 cells and the role of AKR1C1 for HBV-induced HCC..
Materials And MethodsRT-PCR was performed to detect AKR1C1 expression on mRNA level in HepG2 and HepG2.2.15 cell. The promoter activity of AKR1C1 was assayed by transient transfection and Dual-luciferase reporter assay system. The AKR1C1 promoter sequence was screened using the TFSEARCH database and the ALIBABA 2.0 software. The potential transcription factors binding sites were identified using 5’ functional deletion analysis and site-directed mutagenesis..
ResultsIn this study, we found that HBx promoted AKR1C1 expression in HepG2.2.15 cells. Knockdown of HBx inhibited AKR1C1 activation. The role of HBx expression in regulating the promoter activity of human AKR1C1 gene was analyzed. The 5’functional deletion analysis identified that the region between -128 and -88 was the minimal promoter region of HBx to activate AKR1C1 gene expression. Site-directed mutagenesis studies suggested that nuclear factor-Y (NF-Y) plays an important role in this HBx-induced AKR1C1 activation..
ConclusionsIn HepG2.2.1.5 cell, HBx can promote AKR1C1 promoter activity and thus activates the basal transcription of AKR1C1 gene. This process is mediated by the transcription factor NF-Y. This study explored the mechanism for the regulation of HBV on AKR1C1 expression and has provided a new understanding of HBV-induced HCC..
Keywords: Hepatitis B Virus X Protein, HepG2 Cells, 3 alpha, beta, 20 beta, hydroxysteroid dehydrogenase -
Page 17Background
Abnormal serum lipid profiles have been noted in patients with chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b infection who have an unfavorable response to pegylated interferon (peg-IFN) plus ribavirin (RBV) combination therapy. However, after the discovery of single nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent predictive factors affecting the response to peg-IFN plus RBV, lipid factors are thought to be confounding factors..
ObjectivesTo re-examine the significance of lipoprotein profiles on virological response to peg-IFN plus RBV combination therapy in patients with chronic HCV G1b infection, we examined cholesterol and triglyceride concentrations in each lipoprotein fraction separated by high performance liquid chromatography..Patients and
MethodsLipoprotein profiles were examined using fasting sera from 108 patients infected with HCV G1b who had chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles and clinical data, including IL28B genotype and amino acid substitution at aa70 of HCV G1b, were compared between patients with a sustained virological response (SVR) and non-SVR or a non-virological response (NVR) and virological responses other than NVR (non-NVR). In addition, significant predictive factors independently associated with virological response to peg-IFNα-2b plus RBV were determined by logistic regression analysis..
ResultsAn increased ratio of cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917 (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In contrast, lipid factors were not elucidated as independent predictive factors for NVR..
ConclusionsExamination of the fasting lipid profile has clinical importance in predicting the efficacy of peg-IFNα-2b plus RBV combination therapy for patients with HCV G1b even after the discovery of the IL28 genotype as a potent predictive factor..
Keywords: Hepatitis C, Ribavirin, Lipoproteins, Lipoproteins VLDL, Chromatography, High Pressure Liquid -
Page 18Background
Worldwide, hepatitis A is a common infection during childhood especially in developing countries. It can cause severe complications in adults and patients with underlying diseases..
ObjectivesThis study was performed to determine the seroprevalence of hepatitis A in 1 - 15 year-old children of Kashan..Patients and
MethodsThis cross-sectional study was performed on 666 one to fifteen year-old children from health-care centers in Kashan city during 2012. Total antibodies against hepatitis A were measured in sera by enzyme-linked immunosorbent assay (ELISA)..
ResultsTotally, 3.9% of children were seropositive. Mean number of family members was 3.92 ± 0.89. There was no difference in seroprevalence of hepatitis A relative to sex, family size, mean age and age groups..
ConclusionsIn this city, a great proportion of children are susceptible to hepatitis A and it’s complications at an older age. This decrease in seropositivity may be caused by elevated hygien level. According to our results hepatitis A vaccination is recommended at early childhood such as that of other regions where low prevalence of hepatitis A infection is found..
Keywords: Epidemiology, Hepatitis A, Antibody -
Page 19Background
Egypt has one of the highest (16-8%) prevalence rates of HCV infection in the world. Approximately 90% of Egyptian HCV isolates belong to a single subtype (4a), which responds less successfully to interferon therapy than other subtypes. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naive HCV-infected patients have shown conflicting results..
Objectivesassessing the effects of Peginterferon alpha-2a versus Peginterferon alpha-2b on the sustained virological response in naive chronic HCV genotype-4 Egyptian patients..Patients and
Methodsthis retrospective study cohort consists of 3718 chronic HCV patients admitted to a large, Egyptian medical center. 1985 patients had been treated with PEG-IFN alfa-2a plus RBV and 1733 patients with PEG-IFN alfa-2b plus RBV between years 2007-2011. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects..
ResultsThe ETR & SVR in patients treated with PEGIFN alfa-2a was 64.1% and 59.6% as compared to treatment with PEGIFN alfa-2b where these parameters were 58.2% and 53.9% respectively (P < 0.05). Treatment discontinuation rates, were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Significant dose reduction was evident with peginterferon alfa-2b (35.3%) than peginterferon alpha-2a (27.3 %) (P < 0.01). Patients with lower base line AFP and ALT were most likely to achieve SVR using INF alpha 2-a..
ConclusionsPeginterferon alpha-2a has a higher efficacy regarding ETR and SVR as compared to Peginterferon alfa-2b in treatment of naive chronic HCV genotype-4 patients..
Keywords: Chronic Hepatitis C, Peginterferon, Alpha, 2a, 2b -
Page 20Background
Occult hepatitis B virus (HBV) infection (OBI) is frequently reported in patients with chronic hepatitis C virus (HCV) infection. An association between OBI and more liver damage, cirrhosis, hepatocellular carcinoma, and reduced response to interferon therapy in patients with HCV infection is suggested..
ObjectivesThe aim of this study was to determine the prevalence of occult HBV, and evaluate its clinical influence on patients with chronic HCV..Patients and
MethodsA cohort study including50 patients with positive results for HCV, and negative results for HBsAg tests was performed. The patients were divided into two groups: one group had positive results for both HCV and occult HBV tests (n = 18), and the other had positive results for HCV, but negative findings for occult HBV (n = 32). All were treated with PEG-IFN alpha-2a and Ribavirin. Presence of HCV RNA was followed in these patients..
ResultsHBV-DNA was detected using nested-PCR in 20% of plasma and 32.6% of peripheral blood mononuclear cell (PBMC) compartments. No significant differences were observed between patients with and without occult HBV for sex, age, duration of HCV infection, histological markers, presence of anti-HBc, HCV viral load, and HCV genotype. The response rate was significantly higher in patients with positive results for HBV-DNA test compared to those with negative findings (100% vs. 71.9 %, P < 0.05)..
ConclusionsIn conclusion, occult HBV was found in 36% of patients with negative results for HBsAg, but positive results for HCV. Detection of HBV-DNA in both PBMCs and plasma together in comparison with plasma alone provided more true identification of OBI.The SVR rate was significantly higher in coinfected patients than mono-infected ones..
Keywords: Hepatitis B, Hepatitis C Virus, Peripheral Blood Mononuclear Cell -
Page 21Background
Homocysteine is a sulfur-containing amino acid which formed (mainly in the liver) during the metabolism of methionine. Prior studies indicated the important role of hyperhomocysteinemia in pathogenesis and progression of alcoholic liver disease, liver steatosis and cirrhosis. One of the most important mechanisms by which homocysteine promote the development of hepatic injury is oxidative stress. Transcription factor Nrf2-mediated antioxidant response, represents critical cellular defense mechanism that serves to maintain intracellular redox homeostasis and limit oxidative stress. Glutamate cysteine ligase catalytic (GCLc) is rate limiting enzyme in the synthesis of glutathione, an important endogenous antioxidant..
ObjectivesThis study was conducted to investigate whether homocysteine induces the Nrf2 dependent expression of GCLc in hepatoma cell line (HepG2) and whether this induction is mediated by antioxidant response element (ARE) which present within its promoter..
Materials And MethodsGlutathione (GSH) content was measured by flow cytometry. Using electro mobility shift assay (EMSA) and western blotting, ARE-binding activity of Nrf2 for GCLc was demonstrated. Real time RT-PCR and western blotting were performed to evaluate whether homocysteine was able to induce mRNA and protein expression of GCL..
ResultsExposure of HepG2 cells to 50 µMD/L homocysteine and western blotting of nuclear extracts revealed that Nrf2 is strongly stabilized and became detectable in nuclear extracts. EMSA demonstrated increased binding of Nrf2 to oligomers containing GCL promoter - specific ARE -binding site.A time- dependent increase in the gene and protein expression of GCL was observed. Additionally, GSH, which is prime scavenger of free radicals in cells, decreased initially. Elevation of GSH, following the initial decline, closely correlated with gene expression profile of GCLc, which is a rate-limiting enzyme in GSH synthesis..
ConclusionsAltogether, we provide direct evidence that homocysteine activates Nrf2-mediated antioxidant response, which protects HepG2 cells from oxidative damage..
Keywords: HepG2 Cells, Oxidative Stress, Homocysteine -
Page 22Introduction
Recipients of liver transplantation are prone to different types of infections such as tuberculosis (TB)..
Case PresentationHerein we report a 59-year-old man with liver transplantation due to HBV cirrhosis who developed isolated hepatic TB, 18 months after OLT (orthotropic liver transplantation). He has been successfully treated with anti-TB regimen and now after 12 months he is completely symptom-free..
ConclusionsOrgan transplantation and treatment of transplanted patients with immunosuppressive drugs would prone them to various unusual infections. One of these is unusual primary involvement of liver by tuberculosis which has been extremely rare in the previous reports..
Keywords: Liver Transplantation, Tuberculosis, Liver