Hepatitis Monthly
Volume:14 Issue: 11, Nov 2014

Iron overload is frequently observed in patients with chronic hepatitis C (CHC) and is associated with the increased risk of liver fibrosis and carcinogenesis. Hepcidin is a regulator of iron homeostasis and a component of innate immunity. Based on experimental studies, iron overload might be a result of low hepcidin synthesis in CHC. The aim of this case-control study was to assess hepcidin mRNA expression in liver tissue of patients with CHC in terms of iron metabolism parameters, hemochromatosis (HFE) gene mutations, disease activity, and efficacy of antiviral treatment with pegylated interferon and ribavirin.Patients and A total of 31 patients with CHC, who were qualified for antiviral therapy, were compared with 19 patients with chronic hepatitis B (CHB). In both groups, liver function tests and serum iron parameters were assayed and hepcidin mRNA expression was measured in liver specimens using real time PCR with normalization to reference genes mRNA of stable expression. Patients with CHC had lower hepcidin mRNA expression and more frequently iron deposits in hepatocytes than subjects with CHB did. In CHC group, hepcidin mRNA expression was positively correlated with alanine aminotransferase activity and serum iron concentration. Low expression of hepcidin had no correlation with tissue iron overload in those with CHC. In univariate analysis, HCV viral load and efficacy of antiviral treatment were not significantly associated with hepcidin mRNA expression. Further studies on the role of hepcidin in pathogenesis of CHC are needed to assess the potency of its use in antiviral treatment.

Context: Insulin resistance is a hallmark of metabolic syndrome (MS). It has been proposed that both polycystic ovarian syndrome (PCOS) and nonalcoholic fatty liver disease (NAFLD) are correlated with Insulin resistance. Therefore, PCOS and NAFLD can be attributed with insulin resistance and therefore MS. The aim of this meta-analysis was to determine whether PCOS patients are at a high risk of NAFLD.Evidence Acquisition: Google scholar, Scopus, ISI Web of Science, Embase, MEDLINE, and some Iranian databases such as scientific information database (SID), IranMedex, and MagIran were searched to identify relevant studies. We included all papers regardless of their language from January 1985 to June 2013. By using data on prevalence of NAFLD in patients with and without PCOS, odds ratio (OR) with 95% confidence intervals (CIs) were calculated in each study. Chi-squared test was used to assess heterogeneity between studies. We finally included seven eligible studies. According to chi-squared test, there was a significant heterogeneity (73.6%) between studies (P = 0.001). NAFLD prevalence was significantly higher in patients with PCOS compared to healthy control, with an overall OR of 3.93 (95% CI: 2.17, 7.11).There was no significant publication bias based on Begg's and Egger's tests. According to the results of this meta-analysis, there was a high risk of NAFLD in women with PCOS. We suggest evaluating patients with PCOS regarding NAFLD.

Nucleoside analogues are recommended as antiviral treatments for patients with hepatitis B virus (HBV)-associated liver failure. Clinical data comparing entecavir (ETV) and lamivudine (LAM) are inconsistent in this setting. To compare the efficacy and safety of ETV and LAM in patients with chronic hepatitis B (CHB)-associated liver failure.Patients and A literature search was performed on articles published until January 2014 on therapy with ETV and LAM for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was the primary efficacy measure, while total bilirubin (TBIL), prothrombin activity (PTA) changes and HBV DNA negative change rates were secondary efficacy measures. A quantitative meta-analysis was performed to compare the efficacy of the two drugs. Safety of ETV and LAM was observed. Four randomized controlled trials and nine retrospective cohort studies comprising a total of 1549 patients were selected. Overall analysis revealed comparable survival rates between patients received ETV and those received LAM (4 weeks: RR = 1.03, 95%CI [0.89, 1.18], P = 0.73; 8 weeks: RR = 0.98, 95% CI [0.85, 1.14], P = 0.84; 12 weeks: RR = 0.98, 95% CI [0.90, 1.08], P = 0.70; 24 weeks: RR = 1.02, 95% CI [0.94, 1.10], P = 0.66). After 24 weeks of treatment, patients treated with ETV had a significantly lower TBIL levels (MD = -37.34, 95% CI [-63.57, -11.11], P = 0.005), higher PTA levels (MD = 11.10, 95% CI [2.47, 19.73], P = 0.01) and higher HBV DNA negative rates (RR = 2.76, 95% CI [1.69, 4.51], P < 0.0001) than those treated with LAM. In addition, no drug related adverse effects were observed in the two treatment groups. ETV and LAM treatments had similar effects to improve 24 weeks survival rate of patients with CHB-associated liver failure, but ETV was associated with greater clinical improvement. Both drugs were tolerated well during the treatment. It is suggested to perform further studies to verify the results.

Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. While both E1 and E2 are hypervariable in nature, it is difficult to design vaccines or therapeutic drugs against them. The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors.Patients and This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common.

There are limited data on the prevalence of the hepatitis B virus (HBV) infection in the agricultural population worldwide. This study aimed to determine the prevalence of HBV infection and associated risk factors in the reproductive-age female farmworker. This cross-sectional study was conducted between January and April 2013 in southeastern region (SAR) of Turkey. A community-based representative agricultural sample (n = 705) from the agricultural areas of nine provinces of SAR was randomly determined by clustering method using Epi Info software. Questionnaires including demographic information and risk factors of HBV were administered to participants. The presence of HBsAg, anti-HBs, anti-HBc, and anti-HBe antibodies in blood samples were measured by ELISA. The prevalence of the HBsAg, anti-HBs, anti-HBc, anti-HBe antibodies, and seropositivity were 5.7%, 25.9%, 28.9%, 16.4%, and 36.7%, respectively. There was no association between the HBsAg and the size of the household, age, education level, parity, and place of birth while the prevalence of HBsAg was higher in seasonal migratory farmworkers and people living in urban areas and the prevalence of anti-HBs antibody was significantly higher in women ≥ 35 years of age, those with a high parity, and those who gave birth without the assistance of health professionals (P < 0.05). The risk for HBV infection in the seasonal migratory group was 4.3 times higher in comparison to local workers (P = 0.00; OR = 4.3; 95% CI, 2.2-8.4), with a prevalence rate of 11%. The monitoring of at-risk groups like seasonal migratory farmworkers is necessary to strengthen the healthcare service provided to this population.

Hepatitis C virus (HCV) infection rates in drug users vary among different regions of China. Drug users who are unaware of their HCV serostatus tend to engage in more risky behaviors. This prospective study aimed to assess risk factors of HCV infection in drug users among 11 methadone maintenance treatment (MMT) clinics in Xi’an, China.Patients and Baseline characteristics and drug use information of patients were collected upon enrollment in the study and anti-HCV tests were performed within one month after the enrollment. Data on daily medication, monthly random urine morphine test results, illicit drug use and MMT retention time were recorded during a 5-year follow-up. Of 10243 patients, 58.0% had positive results for anti-HCV. Injection drug use, longer duration of drug abuse, older age, female gender, unmarried status and unemployment were independent risk factors of HCV infection. Urine test positivity rate was lower (14.8% vs. 16.7%, χ2 = 100.235, P < 0.05), but MMT retention rate was higher (log-rank χ2 = 4.397, P < 0.05) in the anti-HCV positive group than anti-HCV negative one. However, multivariate regression revealed no significant association between anti-HCV serostatus and either MMT retention time or illicit drug use. The major risk factor of HCV infection was injection drug use. The patient’s awareness of his or her HCV status had a minor effect in reduction of illicit drug use and improvement in MMT retention. Therefore, adequate counseling is necessary for drug users in MMT clinics in Xi’an.

Hepatitis C virus (HCV) is major cause of liver cirrhosis in humans. HCV capsid (core) protein (HCVcp) is a highly demanded antigen for various diagnostic, immunization and pathogenesis studies. Plants are considered as an expression system for producing safe and inexpensive biopharmaceutical proteins. Although invention of transgenic (stable) tobacco plants expressing HCVcp with proper antigenic properties was recently reported, no data for “transient-expression” that is currently the method of choice for rapid, simple and lower-priced protein expression in plants is available for HCVcp. The purpose of this study was to design a highly codon-optimized HCVcp gene for construction of an efficient transient-plant expression system for production of HCVcp with proper antigenic properties in a regional tobacco plant (Iranian Jafarabadi-cultivar) by evaluation of different classes of vectors and suppression of gene-silencing in tobacco. A codon-optimized gene encoding the Kozak sequence, 6xHis-tag, HCVcp (1-122) and KDEL peptide in tandem (from N- to C-terminal) was designed and inserted into potato virus-X (PVX) and classic pBI121 binary vectors in separate cloning reactions. The resulted recombinant plasmids were transferred into Agrobacterium tumefaciens and vacuum infiltrated into tobacco leaves. The effect of gene silencing suppressor P19 protein derived from tomato bushy stunt virus on the expression yield of HCVcp by each construct was also evaluated by co-infiltration in separate groups. The expressed HCVcp was evaluated by dot and western blotting and ELISA assays. The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of “GGTAAG” splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). The plant-derived HCVcp (pHCVcp) could properly identify the HCVcp antibody in HCV-infected human sera compared to Escherichia coli-derived HCVcp (eHCVcp), indicating its potential for diagnostic/immunization applications. By employment of gene optimization strategies, use of viral-based vectors and suppression of plant-derived gene silencing effect, efficient transient expression of HCVcp in tobacco with proper antigenic properties could be possible.