Hepatitis Monthly
Volume:14 Issue: 6, Jun 2014

Context: Portal Hypertension (PH) is a progressive complication due to chronic liver disease. In addition to pathophysiologic changes in the micro-circulation, in PH are established fibrous tissue (periportal fibrous septal) and regenerative hyperplastic nodules (from micro- to macro-nodules) promoting hepatic architectural distortion.Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1981 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the keywords: "portal hypertension, children, immune system, endocrine system, liver fibrosis". It is believed that PH results from three “phenotype”: ischemia-reperfusion, involving nervous system (NS); edema and oxidative damage, involving immune system; inflammation and angiogenesis, involving endocrine system. However, its exact cause still underdiagnosed and unknown. PH is a dynamic and potentially reversible process. Researchers have tried to demonstrate mechanisms underlying PH and its related-complications. This review focuses on the current knowledge regarding the pathogenesis, and immune, endocrine-metabolic factors of disease. The strong positive association between immune system and development of PH could be efficient to identify non-invasive markers of disease, to modify prognosis of PH, and to development and application of specific and individual anti-inflammatory therapy.

Hepatitis C virus (HCV) infection is a significant health concern in patients with end-stage renal disease under dialysis. Epidemiological studies have reported a prevalence rate of 5.5-55.9% for this condition in Iran. We evaluated the risk factors for HCV infection and seroconversion in hemodialysis patients.Patients and A retrospective analysis was performed on 455 hemodialysis patients from each of the five dialysis units in Tabriz, northwest Iran. Possible risk factors for HCV infection and seroconversion were evaluated. A total of 37 patients were HCV positive (8.1% of the study population) and seroconversion occurred in 18 of them during the dialysis treatment (3.95% of the study population). History of renal transplantation (44.4%, P < 0.0001), surgical intervention (except for renal transplantation and AV fistula placement) (94.4%, P = 0.03), and mean duration of dialysis (106.06 ± 55.519, P < 0.0001) had strong statistically significant associations with the seroconversion. The current study indicates increased risk for HCV infection in patients under dialysis and its relation with the mean duration of hemodialysis, history of renal transplantation and surgical intervention. Considering the immune deficiency in these patients, intense education to both patients and medical staff will be beneficial.

Hepatitis C virus (HCV) is known for the eminent global disease burden responsible for encumbering public health. Development of an effective vaccine is the major need of the day; however, several obstacles loom ahead of this objective. One of the major barriers is that as a RNA virus, it mutates rapidly resulting in high sequence divergence and several viral isolates in the world. Theglycoprotein 2 (gpE2) is the primary component of HCV envelope with direct interaction with the host cell surface receptors; it is an indispensable target of neutralizing antibodies and hence, should be a fundamental component of vaccine design. This study focused on B-cells and T-cells epitopes prediction in HCV gpE2, particularly in 3a genotype, in Pakistan and identification of the conserved epitopes among various 3a isolates at global level, principally conserved across HCV major genotypes. Epitope finding was done by using online available bioinformatics tools including Immune Epitope Database (IEDB), ProPred-I, and ProPred. Conservation of these epitopes was found by aligning selected gpE2 sequences using MultAlin online software and conservancy analysis tool available at IEDB. Many B-cell and T-cell epitopes predicted in gpE2 were found conserved among HCV 3a genotypes whereas few were conserved in other genotypes anticipating these epitopes as potential candidates of producing strong B-cell and T-cell response against HCV 3a and other genotypes. HCV gpE2 is an ideal target for HCV vaccine. Prediction of epitope immunogenicity and characterization on the basis of peptide sequences will be significantly helpful for development of a heterologous vaccine against HCV variants.

Hepatitis C virus (HCV) is able to down-regulate innate immune response. It is important to know the immune pathways that this virus interacts with. HCV non-structural protein 3 (NS3) plays an important role in this viral feature. HCV NS3 protein could affect the expression of antiviral protein such as viperin, and interleukin 28whichare important proteins in antiviral response. HCV has developed different mechanisms to maintain a persistent infection, especially by disrupting type I interferon response and subsequent suppression of expression of Interferon stimulatory genes (ISGs). Viperin, a member of ISGs, is considered as a host antiviral protein, which interferes with viral replication. Since it is a good target for some viruses to evade host responses, it is interesting to study if HCV has evolved a mechanism to interfere with this member of ISGs. We evaluated the impact of NS3, NS3/4A and a mutated nonfunctional NS3 on ISGs expression such as viperin and IL-28 after the induction of IFN signaling Jak-STAT pathway using IFN-. NS3 protein disrupted the expressions of viperin gene and IL-28, an inducer for the expression of ISGs and viperin itself. By comparing the roles of NS3 and NS3/4A protease activities in suppressing the innate immune responses, we also showed that NS3 (without NS4A) has the ability to down-regulate ISGs expression, similar to that of NS3/4A. ISGs expression is impeded by NS3 protease activity and its interaction with Jak-STAT pathway proteins. In addition, the NS3/4A substrates spectrum seems to be similar to those of NS3.

The seroepidemiology of hepatitis E virus (HEV) infection in rural areas in Mexico has been poorly studied. The aim of the study was to determine the seroprevalence and correlates of anti-HEV IgG antibodies in adults in rural areas in Durango, Mexico. We performed a cross-sectional study to determine the frequency of anti-HEV IgG antibodies in 273 adults living in rural Durango, Mexico using an enzyme-linked immunoassay. In addition, we searched for an association of HEV exposure with the socio-demographic and behavioral characteristics of the subjects studied. One hundred (36.6%) of the 273 rural adults (mean age: 39.85 ± 17.15 years) had anti-HEV IgG antibodies. Multivariate analysis of socio-demographic and behavioral characteristics of the participants showed that HEV exposure was associated with increasing age (OR = 1.04; 95% CI: 1.04-1.05; P < 0.001), consumption of untreated water (OR = 1.92; 95% CI: 1.06-3.46; P = 0.03), and availability of water at home (OR = 1.87; 95% CI: 1.07-3.27; P = 0.02). In contrast, other socio-demographic and behavioral characteristics including educational level, occupation, socio-economic status, foreign travel, consumption of unwashed raw fruits, consumption of raw or undercooked meat and raising animals did not show associations with HEV exposure. The seroprevalence of HEV infection found in rural Durango is higher than those reported in other Mexican populations. Consumption of untreated water is an important factor for HEV exposure in rural areas in Durango. The correlates of HEV seropositivity found in the present study can be used for an optimal planning of preventive measures against HEV infection.

Immune cells and molecules play a vital role in initiating, maintaining, and regulating immunological homeostasis and inflammation in many pathological and physiological processes; however, the changes on expressions and functions of these cells and molecules in hepatitis B virus (HBV) infection has not been elucidated well. The current study aimed to determine the expression pattern of different cytokines, chemokines, and immune cells in HBV infection and their association with disease progression. Sixty-nine patients with chronic HBV infection were enrolled. Five immune cell subsets and 46 cytokines and chemokines were analyzed by flow cytometry and Luminex 200. In comparison to healthy individuals and asymptomatic HBV carriers, expression of CXCL9, CXCL10, CXCL11, and IL-10 were elevated in patients with chronic active HBV and had positive correlation with ALT levels. In contrast, G-CSF, MCP-3, and IFN-γ levels were significantly decreased in patients with chronic active HBV infection in contrast to carriers and healthy individuals; however, these down regulations did not show any correlation with either virological findings or liver inflammation. Although the proportion of CD4+ CD25high regulatory T cells (Tregs) was higher in patients with HBV infection than in healthy controls, no correlations were found between Tregs and other cytokines or chemokines. CXCR3-associated chemokines might contribute to liver inflammation in chronic hepatitis B, while MCP-3 and G-CSF were inhibited by HBV infection. Host immune response was suppressed as manifested by an increase in CD4+ CD25high Tregs and IL-10 as well as a decrease in IFN-γ. Exploiting the expression pattern of cytokine and chemokine may help to develop a better understanding of chronic HBV infection pathogenesis.

Treatment with Peginterferon Alpha-2b plus Ribavirin is the current standard therapy for chronic hepatitis C (CHC). However, many host related and viral parameters are associated with different outcomes of combination therapy. The aim of this study was to develop an artificial neural network (ANN) model to predetermine individual responses to therapy based on patient’s demographics and laboratory data.Patients and This case-control study was conducted in Tehran, Iran, on 139 patients divided into sustained virologic response (SVR) (n = 50), relapse (n = 50) and non-response (n = 39) groups according to their response to combination therapy for 48 weeks. The ANN was trained 300 times (epochs) using clinical data. To test the ANN performance, the part of data that was selected randomly and not used in training process was entered to the ANN and the outputs were compared with real data. Hemoglobin (P < 0.001), cholesterol (P = 0.001) and IL-28b genotype (P = 0.002) values had significant differences between the three groups. Significant predictive factor(s) for each group were hemoglobin for SVR (OR: 1.517; 95% CI: 1.233-1.868; P < 0.001), IL-28b genotype for relapse (OR: 0.577; 95% CI: 0.339-0.981; P = 0.041) and hemoglobin (OR: 0.824; 95% CI: 0.693-0.980; P = 0.017) and IL-28b genotype (OR: 2.584; 95% CI: 1.430-4.668;P = 0.001) for non-response. The accuracy of ANN to predict SVR, relapse and non-response were 93%, 90%, and 90%, respectively. Using baseline laboratory data and host characteristics, ANN has been shown as an accurate model to predict treatment outcome, which can lead to appropriate decision making and decrease the frequency of ineffective treatment in patients with chronic hepatitis C virus (HCV) infection.

Controlling parenchymal hemorrhage especially in liver parenchyma, despite all the progress in surgical science, is still one of the challenges surgeons face saving patients’ lives and there is a research challenge among researchers in this field to introduce a more effective method. This study attempts to determine the haemostatic effect of ferric chloride and compare it with that of the standard method (suturing technique) in controlling bleeding from liver parenchymal tissue. In this animal model study 60 male Wistar rats were used. An incision, two centimeters (cm) long and half a cm deep, was made on each rat’s liver and the hemostasis time was measured once using ferric chloride with different concentrations (5%, 10%, 15%, 25% and 50%) and then using the control method (i.e. controlling bleeding by suturing). The liver tissue was examined for pathological changes. The hemostasis time of ferric chloride concentration groups was significantly less than that of the control group (P value < 0.001). The pathologic examination showed the highest frequency of low grade inflammation based on the defined pathological grading. Ferric chloride is an effective haemostatic agent in controlling liver parenchymal tissue hemorrhage in an animal model.