فهرست مطالب
Hepatitis Monthly
Volume:14 Issue: 2, Feb 2014
- تاریخ انتشار: 1392/12/14
- تعداد عناوین: 8
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Page 9036Background
Liver enzymes elevations (LEE) can be observed after kidney transplantation due to multifactorial causes..
ObjectivesWe performed a retrospective study on 1589 kidney transplants, 971 male and 618 female, who were hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab) negative, and had no other liver diseases, to detect the prevalence of LEE and its risk factors in these patients between May 2008 and May 2010..Patients and
MethodsLiver enzymes and other biochemical parameters were measured in all recipients. Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4 - 12 months after transplantation, and Group III, more than one year post-transplantation..
ResultsThe highest LEE was more frequent in older patients (P < 0.001) and male individuals (P < 0.001). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in patients who received kidneys from deceased donors (10.4% and 23.8%, respectively) as compared to living donor transplants (5.6% and 14.8%, respectively) (P < 0.001). The elevation of ALT was the liver enzyme abnormality after kidney transplantation with the highest prevalence (34.3%). The levels of ALT and AST were significantly elevated within the first 3 months after transplantation, followed by the 4-12 months period (P < 0.001). There was a reverse correlation between liver enzyme levels and renal allograft function in both univariate and linear regression analyses. This correlation increased over time. There was also a significant relation between cyclosporine blood levels and liver enzyme values in the univariate analysis. However, this relationship was attenuated over time. Elevated liver enzymes also correlated with anemia..
ConclusionsThe LEE is a common finding among kidney transplant recipients. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation..
Keywords: Kidney, Transplantation, Cyclosporine, Aspartate aminotransferase, Alanine aminotransferase -
Page 10939Context: Non-alcoholic fatty liver disease (NAFLD) is a growing health problem in both developed and developing countries. Metabolic abnormalities, specially insulin resistance and hyperglycemia are highly correlated with NAFLD. Lifestyle modifications including physical activity and promoting nutrient intakes are critical in prevention and treatment of NAFLD. Hence, in this article we aimed to review the evidence regarding the effects of various macronutrients on fat accumulation in hepatic cells as well as the level of liver enzymes..Evidence Acquisitions: The relevant English and non-English published papers were searched using online databases of PubMed, ISI Web of Science, SCOPUS, Science Direct and EMBASE from January 2000 to January 2013. We summarized the findings of 40 relevant studies in this review..ResultsAlthough a hypocaloric diet could prevent the progression of fat accumulation in liver, the diet composition is another aspect which should be considered in diet therapy of patients with NAFLD..ConclusionsSeveral studies assessed the effects of dietary composition on fat storage in liver; however, their findings are inconsistent. Most studies focused on the quantity of carbohydrate and dietary fat; whilst there is very limited information regarding the role of protein intake..Keywords: Non, alcoholic Fatty Liver Disease, Food, Intra, Abdominal Fat, Carbohydrates, Proteins
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Page 14228BackgroundAn exact histologic staging of liver fibrosis is essential for identifying the best therapeutic strategy and determining the disease prognosis in patients with chronic hepatitis B (CHB). While liver biopsy has a vital role in the management of liver diseases, it also sustains some limitations hampering its widespread use..ObjectivesIn this study, we evaluated and compared several available indices of the severity of liver diseases in patients with hepatitis..Patients andMethodsExclusion criteria were as follows: decompensated liver disease, alcoholic liver disease or alcohol intake of 40 g or more per week; co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus..ResultsResults showed that AST to platelet ratio index (APRI) (odds ratio = 2.35, P = 0.01) and age (odds ratio = 1.04, P = 0.007) were independently predictive of the presence of significant liver necrosis and inflammation. On the other hand, AARPRI (odds ratio = 3.8, P = 0.07), age (odds ratio = 1.04, P = 0.02), and ALT levels (odds ratio = 1.01, P = 0.007) were predictive of a significant liver fibrosis. Further analysis with receiver-operating curve showed that none of these predictors had a fair diagnostic value (area under the curve < 70)..ConclusionsThe APRI had the highest sensitivity and specificity (64% and 71%, respectively) for prediction of the presence of liver disease. We suggest that APRI may be applicable for the detection of a severe liver disease..Keywords: Chronic Hepatitis B, Liver Cirrhosis, Liver Disease
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Page 15124Introduction
Patients with Hepatitis C are commonly treated with combination of Pegylated Interferon alfa-2a and Ribavirin. Less than 1% of patients receiving this treatment experience very uncommon ophthalmological side effects such as optic neuropathy and vision disorder, which are usually subclinical, mild and reversible, not requiring the withdrawal of the treatment. Retinopathy is the most commonly reported ocular side effect of interferon use, usually presenting with cotton wool spots and retinal hemorrhages..
Case PresentationWe represent a case of severe retinopathy and optic neuropathy in a patient with chronic hepatitis C genotype 3a infection, treated with the combination of PEG-IFN alfa-2a (180 mkg once weekly) and Ribavirin (1200 mg daily). Bilateral visual loss of both eyes developed at 11th week of therapy and changes in retina and optic nerve were observed. Fluorescein angiography and optical coherence tomography showed bilateral anterior ischemic optic neuropathy and macular edema. Visual acuity improved 1 month and fundoscopic changes were no longer present 6 months after the urgent permanent discontinuation of PEG-IFN treatment and the pulse steroid therapy followed by a 2 week course of oral prednisone..
DiscussionIn case of interferon-associated retinopathy discontinuation of the therapy and treatment with high dose steroids can be beneficial. The prognosis of interferon-associated opthalmological side effects remains uncertain: in some patients visual acuity improves, other continues with poor visual outcome. Considering that, all patients should undergo ophthalmologic examination before treatment with interferon and their ophthalmological status should be monitored regularly while receiving this therapy..
Keywords: Hepatitis C, Chronic, Peginterferon alfa, 2a, Optic Nerve Diseases, Pulse Therapy, Drug -
Page 15285BackgroundHBeAg negative hepatitis B infection exerts both inactive carrier state and chronic active hepatitis, which are sometimes difficult to differentiate. Serial hepatitis B virus (HBV) DNA quantification, alanine transaminase (ALT) measurement, and liver histology assessment can help to differentiate these forms of hepatitis B infection..ObjectivesWe aimed to clarify the clinical and laboratory characteristics of HBeAg negative hepatitis B patients..Patients andMethodsPatients with hepatitis B, referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2013, were included and followed for one year. Laboratory assessments including liver function tests, HBV DNA quantification, and liver biopsy (for some cases) were performed..ResultsTwo hundred forty-three HBeAg negative hepatitis B patients were stratified into three groups based on to their HBV DNA level including group 1 (G1) with HBV DNA level < 2000 IU/mL, group 2 (G2) with HBV DNA level 2000-20000 IU/mL, and group 3 (G3) with HBV DNA level > 20000 IU/mL. The G2 had more similarity to G1 than G3 regarding their clinical characteristics..ConclusionsIt is concluded that most HBeAg negative hepatitis B patients with serum HBV DNA level of 2000-20000 IU/mL, persistent normal ALT concentration, and no or mild liver damage on biopsy can be clinically managed as HBV inactive carriers..Keywords: Hepatitis B, Liver Cirrhosis, Viral Load
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Page 15900BackgroundThe hepatitis B virus (HBV) antigen-induced cellular immune response plays an important role in HBV clearance. Changes in the diversity of complementarity determining region 3 (CDR3) and T-cell receptor (TCR) sequences are used to monitor the response of T cells to antigens..ObjectivesThe aim of the present study was to determine whether the TCR Vβ repertoire of patients with chronic severe hepatitis B (CSHB) undergoes increased stimulation, and to identify conserved motifs in specific TCR Vβ families..Patients andMethodsPeripheral blood mononuclear cells (PBMCs) from 18 patients with CSHB were sorted into CD4+ and CD8+ T subsets, using monoclonal antibody-coated magnetic beads. The TCR Vβ CDR3 was subsequently characterized using immune spectratyping. The TCR Vβ families exhibiting a CDR3 spectratype that underwent monoclonal expansion were sequenced..ResultsThe number of oligoclonal or monoclonal expansion TCR Vβ families detected in the analyzed CD8+ T cells was significantly higher than the number detected in CD4+ T cells. The CDR3 spectratype analysis showed predominant usage of TCR Vβ5, Vβ7, Vβ9, Vβ12, and Vβ18 families in CD8+ T cell subsets of CSHB patients. Furthermore, conserved amino acid motifs were found to be associated with the monoclonal expansion of CD8+ TCR Vβ families. In addition, JB1S1 and JB2S7 region genes were present at a high frequency..ConclusionsThe CD4+ and CD8+ TCR Vβ gene families undergo clonal expansion in CSHB patients, and CD8+ T cells play a major role in the pathogenesis of CSHB. Moreover, the conserved motifs and limited use of joining region genes observed in the CSHB patients of this cohort indicated that similar antigenic epitopes are recognized..Keywords: Hepatitis B, Genes, T, Cell Receptor, CD8, Positive T, Lymphocytes, Complementarity Determining Regions, Clonal expansion, Immunity, Cellular
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Page 16161Background
HBV-specific cytotoxic T lymphocyte (CTL) activity is believed to play a critical role in controlling HBV infection. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway manipulates cell fate decisions in many different cell types by regulating the activity of downstream effectors. We have previously testified that the fusion protein of CTP-HBcAg18-27--Tapasin could enter the cytoplasm of dendritic cells and efficiently induce robust specific CTL response in vitro..
ObjectivesIn the present study, we evaluated specific CTL response and the level of apoptosis of CD8+ T cells induced by CTP-HBcAg18-27-Tapasin in HLA-A2 transgenic mice (H-2Kb). Meanwhile, we preliminary investigated PI3K, phosphorylation level of Akt, and mammalian target of rapamycin (mTOR) as positive regulator of the magnitude and effector function of the hepatitis B virus-specific cytotoxic T lymphocytes in HLA-A2 transgenic mice..
Materials And MethodsHLA-A2 transgenic mice were immunized by intramuscular injection in the hind legs three times at one-week intervals with PBS, CTP-HBcAg18-27-Tapasin (50 μg), CTP-HBcAg18-27 (50 μg), HBcAg18-27-Tapasin (50 μg), and HBcAg18-27 (50 μg). One week after the last immunization, mice were sacrificed and splenocytes were harvested in strile condition. The specific CTL response was analyzed by flow cytometry and enzyme linked immunosorbent assay (ELISA); the expression of (PI3K)/Akt signaling was detected by RT-PCR and western blot..
ResultsThe results showed that CTP-HBcAg18-27-Tapasin significantly increased the percentages of IFN-γ+ CD8α+ T cells, the numbers of these polyfunctional triple-cytokine-producing (IFN-γ, TNF-α, and IL-2) CD8+T cells, the secretion of cytokine IFN-γ, IL-2, and TNF-α, while in comparison to control group, it significantly decreased the percentage of apoptotic CD8+ T cells in HLA-A2 transgenic mice. Moreover, the expression of PI3K, P-Akt, and P-mTOR was significantly upregulated in CTP-HBcAg18-27-Tapasin group compared with control groups..
ConclusionsIn conclusion, CTP-HBcAg18-27-Tapasin could reduce apoptosis of CD8+ T cells, increase the percentages of IFN-γ+ CD8α+ T cells, and elicit cell-mediated immunity in HLA-A2 transgenic mice; these processes were associated with activation of the PI3K/Akt signaling pathway..
Keywords: Tapasin, Mice, Transgenic, T, Lymphocytes, Cytotoxic, PI3K, Akt -
Page 16214BackgroundAssociation of hepatitis B virus (HBV) genotype C with hepatocellular carcinoma (HCC) development remains controversial. HBV basal core promoter (BCP) double mutations (T1762A1764) are very strong confounding factors of genotypes B and C in HCC development..ObjectivesTo investigate the association of HBV genotype C with HCC development after controlling for BCP double mutations..Materials And MethodsFour hundred and two serum samples from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH) and also from asymptomatic HBsAg carriers were analyzed..ResultsGenotypes B (31.1%), C (62.8%), and I (6.1%) were detected. With the severity of liver disease the prevalence of genotype B decreased, but genotype C increased. No trend was found for genotype I. The prevalence of BCP double mutations in genotypes C and I viruses was significantly higher than genotype B. BCP double mutations are risk factors for CH, LC and HCC. Genotype C was not identified as a particular risk factor for HCC prior to the stratification analysis but after that genotype C viruses with BCP double mutations were found to be a particular risk factor for HCC (P = 0.008, OR = 17.19 [95% CI: 2.10 - 140.41]), but those with the wild-type BCP were not. In the interaction analysis, genotype C and BCP double mutations were found to have a synergistic effect on HCC development (P < 0.0001, OR = 52.56 [95% CI: 11.49-240.52])..ConclusionsThe effect of HBV genotype C on the development of HCC differs between wild-type viruses and those with BCP double mutations, suggesting that not all individuals infected with genotype C HBV are at increased risk of HCC..Keywords: Hepatitis B Virus_Genotypes_Basal Core Promoter Double Mutations_Hepatocellular Carcinoma