Impact of weight reduction program on serum alanine aminotransferase activity and immunologic response in obese hepatitis B patients.

Background: Globally, chronic B viral hepatitis (HBV) is a major health problem. Obesity is a common problem among patients with HBV. Several studies have reported that obesity is an important risk factor that alters immune system response in individuals with no underlying cause of liver disease. However, there is a strong association between BMI and the human immune system among HBV patients. Objective: This study was to examine the correlation between body mass index, serum alanine aminotransferase activity (ALT) and immunologic response in obese hepatitis B patients. Material and methods: One hundred fifty male patients with chronic hepatitis B virus, their age ranged from 30 to 45 (38.64 ± 7.12) years and their BMI ranged from 30-35 kg/m2. All Subjects were included in two groups: The first group received weight reduction program in the form of treadmill aerobic exercises in addition to diet control whereas the second group received no therapeutic intervention. Parameters of serum alanine aminotransferase (ALT), CD3, CD4 and CD8 were quantified; Leukocyte, differential counts and body mass index (BMI) were measured before and after 3 months at the end of the study. Results: There was a 24.7%, 36.8%, 30.8%, 40.7%, 28.6%, 25.9%, 33.3% and 14.3 % reduction in mean values of alanine aminotransferase (ALT), white blood cells, total neutrophil count, monocytes, CD3, CD4 ,CD8 and BMI respectively in group (A) at the end of the study. In addition, there were significant differences between mean levels of the investigated parameters in groups. Conclusion: Based on our findings, weight loss modulates serum alanine aminotransferase and immune system parameters of patients with hepatitis B virus infection.

Efficacy of entecavir and tenofovir in chronic hepatitis B under treatment in the public health system in southern Brazil

There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.

Ebola virus disease 2014

Ebola virus disease was irst described in 1976 originating from the Ebola River in the Democratic Republic of Congo. Since then, Ebola virus has become an important public health threat in Africa, and now it is of great concern worldwide due to the recent outbreaks (9216 cases with 4555 deaths up to October 20th, 2014), and it is so far the largest and deadliest recorded in history. Five Ebola virus species have been identiied (including Zaire, Sudan, Ivory Coast, Reston, and Bundibugyo Ebola virus), and four of them have proved to be highly pathogenic for both human and non-human primates, causing viral hemorrhagic fever with case fatality rates of up to 90%, for which no approved therapeutics or vaccines are currently available. Ebola virus infections are characterized by immune suppression and a systemic inlammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. The major affected countries, Sierra Leone, Guinea, Liberia, and Nigeria, have been struggling to contain and to mitigate the outbreak. Gene sequencing of the 2014 virus (2014WA) outbreak has demonstrated 98% homology with the Zaire Ebola virus, with a 49% case fatality ratio across the affected countries. In this review the characteristics of the viruses, pathogenesis, diagnosis, treatment, and the cases reported in health care workers (HCW) are described, as well as a summary of outbreaks of the virus since its discovery, including these last two outbreaks in Africa.

The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma

Background: There are a few published studies about prognostic markers of Epstein-B virus (EBV) related to outcomes in pediatric Hodgkin Lymphoma (HL). Objectives: We aimed to investigate the prognostic value and effect of EBV on survival by using biopsy materials in children and adolescents diagnosed with HL. Patients and Methods: EBV LMP-1 expression was examined using immunohistochemical methods in 58 tumor samples. Clinical features, overall survival (OS) and failure free survival time (FFS) were compared between EBV LMP-1 positive and negative patients. Results: In 20 (35%) patients tumors were LMP-1 positive. When compared with patients above 10 years old, EBV LMP-1 was often positive in patients under 10 years old (30% vs. 70%, P = 0.02). In our most cases having B symptoms and advanced stage, EBV positiveness in Hodgkin Reed-Stenberg cells (H-RS) was not a significant determinant for survival (P = 0.78). Half of the past clinical trials in childhood HL reported longer survival rates in EBV LMP-1 positive patients. In some trials similar to our results there was no significant relationship between EBV and prognosis. Conclusions: The reason of diminished EBV positiviness may be related to technical methods such as not using immunohistochemical and in situ hybridization for EBER antigen but in laboratory conditions painting of control tissues with EBV impair this probability. In addition, cases enrolled to our study were living in Istanbul where social and economical factors are improved rather than generally.

Original Research Article Humoral and cellular immune responses to modified hepatitis B plasmid DNA vaccine in mice

Purpose: To evaluate the immunogenicity and types of immune response of a quality-controlled modified recombinant hepatitis B surface antigen (HBsAg) plasmid encoding HBsAg in mice. Methods: The characterized plasmid DNA was used in the immunization of Balb/c mice. Three groups of mice were intramuscularly injected with three different concentrations (50, 25 and 10 μg/100 μL) of the modified plasmid. Humoral immune response was monitored by enzyme-linked immunosorbent assay (ELISA), while cellular immune response was investigated by analysis of spleen cytokine profile (TNFα, IFN γ and IL2) as well as CD69 expression level in CD4 and CD8 positive cells. Results: In general, the activated CD4 cells showing intracellular cytokines were higher than CD8 positive population of cells (p < 0.05). These findings indicate that the vaccine induced both a humoral and cellular immunity. Cytokine profile also showed high levels of TNFα, IFN γ and IL2 and CD69 expression in the group of animals immunized at a dose of 10 μg when compared to control group (p < 0.05). Conclusion: A 10 μg dose intramuscular injection of the modified DNA-based vaccine encoding HBsAg in mice induces both high humoral and cellular immune responses.

Detection of Brucella ovis in ovine from Paraíba State, in the Northeast region of Brazil

To determine the presence of Brucella ovis in ovine from Paraíba State, in the Northeast region of Brazil, 80 animals slaughtered in the public slaughterhouse of Patos city were used. Before slaughter, blood samples were collected by jugular venopuncture from each animal, and after slaughter, testicles, epidydimus and uterus were aseptically collected. For the serological diagnosis of B. ovis and B. abortus infections, the agar gel immunodiffusion (AGID) and Rose Bengal (RBT) tests were carried out, respectively. In addition, microbiological culture and polymerase chain reaction (PCR) were performed on testicle, epidydimus and uterus samples. Six animals (7.5%) tested positive for the presence of B. ovis antibodies and all animals tested negative for the presence of B. abortus antibodies. One AGID-positive animal tested positive at uterine swab culture. PCR was able to amplify DNA of Brucella spp. from the pool of testicle, epidydimus and uterus samples from AGID-positive animals. This is the first report of isolation and detection of B. ovis DNA by PCR in ovine from the Northeast region of Brazil.

Management of Bell's Palsy: A Report of 2 Cases

Bell's palsy is a neuropathy of the peripheral seventh cranial nerve, resulting from traumatic, compressive, infective, inflammatory or metabolic abnormalities or it can be idiopathic. HIV, Epstein-Barr virus and hepatitis B virus have been suspected as initiating organisms, but herpes simplex virus is the most frequently implicated. This report describes 2 cases of Bell's palsy in children that were managed with antiviral agents. Both patients experienced complete recovery within 28 days; after 1 year follow-up, no recurrence was observed and both patients have normal facial movement. Differential diagnosis is essential to guide the treatment plan in Bell's palsy. Special attention should be given to children with respect to prescription of medications that can cause important side effects.

Hepatocellular carcinoma

Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation, A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis, Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma, However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen, In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma, Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C, These studies generally are not randomized, and a randomized prospective study is required to address this issue. (C) 1999 Lippincott Williams & Wilkins, Inc.

Review of genetic and epigenetic alterations in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is associated with multiple risk factors and is believed to arise from pre-neoplastic lesions, usually in the background of cirrhosis. However, the genetic and epigenetic events of hepatocarcinogenesis are relatively poorly understood. HCC display gross genomic alterations, including chromosomal instability (CIN), CpG island methylation, DNA rearrangements associated with hepatitis B virus (HBV) DNA integration, DNA hypomethylation and, to a lesser degree, microsatellite instability. Various studies have reported CIN at chromosomal regions, 1p, 4q, 5q, 6q, 8p, 10q, 11p, 16p, 16q, 17p and 22q. Frequent promoter hypermethylation and subsequent loss of protein expression has also been demonstrated in HCC at tumor suppressor gene (TSG), p16, p14, p15, SOCS1, RIZ1, E-cadherin and 14-3-3 sigma. An interesting observation emerging from these studies is the presence of a methylator phenotype in hepatocarcinogenesis, although it does not seem advantageous to have high levels of microsatellite instability. Methylation also appears to be an early event, suggesting that this may precede cirrhosis. However, these genes have been studied in isolation and global studies of methylator phenotype are required to assess the significance of epigenetic silencing in hepatocarcinogenesis. Based on previous data there are obvious fundamental differences in the mechanisms of hepatic carcinogenesis, with at least two distinct mechanisms of malignant transformation in the liver, related to CIN and CpG island methylation. The reason for these differences and the relative importance of these mechanisms are not clear but likely relate to the etiopathogenesis of HCC. Defining these broad mechanisms is a necessary prelude to determine the timing of events in malignant transformation of the liver and to investigate the role of known risk factors for HCC.

Efficacy and safety of entecavir for chronic HBV in HIV/HBV coinfected patients receiving lamivudine as part of antiretroviral therapy

Background: Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining Suppression of plasma HIV RNA less than 400 copies/ml. Methods: Sixty-eight patients were randomized to entecavir 1 mg (n = 51) or placebo (n = 17) once daily for 24 weeks; 65 patients continued the study with entecavir for an additional 24 weeks. Lamivudine-containing HAART was continued throughout. Results: At week 24, the mean HBV DNA in entecavir-treated patients was 5.52 log(10) - copies/ml versus 9.27 log(10) copies/ml for placebo, and at week 48, it was 4.79log(10) copies/ml versus 5.63log(10) copies/ml, respectively. The mean HBV DNA change from baseline for entecavir was -3.65 log(10) copies/ml (versus + 0.11 for placebo, P < 0.0001) and alanine aminotransferase normalization in 34%. of patients (versus 8% for placebo, P=0.08)At 48 weeks, mean change in HBV DNA reached -4.20log(10) copies/ml inpatients who received entecavir for the entire 48 weeks. The frequency of adverse events with entecavir and placebo was comparable. Through 48 weeks, no clinically relevant changes in HIV viremia or CD4 cell Counts were identified. Conclusion: In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Mini-microabscess syndrome in liver transplant recipients

Cytomegalovirus (CMV) is a significant cause of morbidity in immunosuppressed patients. It is characterized in the liver by parenchymal microabscesses, usually containing CMV-infected cells. However, not all hepatic microabscesses are due to CMV infection. In 1992, we described ''mini'' microabscess (MMA) syndrome, a distinct clinical syndrome that occurs in transplanted livers. This report analyzes the clinical and laboratory features of 57 cases of MMA syndrome occurring in 52 patients and compares these with 19 biopsy-proven cases of CMV infection. The diagnosis of MMA syndrome can only be made histologically. The microabscesses are smaller and more numerous than in CMV infection, and there are no viral inclusions present. CMV DNA could not be detected in liver biopsy specimens with MMAs by using ''nested'' polymerase chain reaction (PCR), indicating that MMA syndrome is not caused by CMV infection. The pattern of liver enzyme and bilirubin elevation is predominantly hepatocellular, with transaminase levels elevated, on average, six to eight times the upper limit of normal. The clinical features of MMA syndrome are that it predominantly affects female (40 of 52 patients) orthotopic liver transplant (OLT) recipients of all ages (range, 11 months to 66.9 years). MMA syndrome is unrelated to the indication for initial OLT and tends to occur later after transplantation than CMV infection (median, 91 days post-OLT vs. 32 days for CMV hepatitis). Although the etiology of MMA syndrome is not clear, it does not appear to adversely affect graft or patient survival.

A Neuropsychological Study Comparing Patients Infected With HCV and HBV Without Psychiatric Comorbidities

Hepatitis C is one of the most common chronic infectious diseases worldwide, with well-documented extra-hepatic manifestations, such as a broad number of cognitive deficits. These impairments may be explained by psychiatric comorbidities, which have not been investigated properly in the literature. In order to elucidate a specific hepatitis C virus (HCV) induced cognitive impairment not related to mental disorders, neuropsychological performance of patients infected with HCV was compared with that of patients infected with hepatitis B virus cognitive impairment, especially psychiatric comorbidities. A total of 33 patients infected with HCV and 22 patients infected with HBV were included in the study. There were no significant differences between the two groups with regard to age or years of education. The group of patients infected with HCV performed significantly worse on visuo-spatial memory tasks after adjusting for years of education and age. There were no significant differences between patients infected with HCV and patients infected with HBV with regards to other neuropsychological functions. The data indicate that patients infected with HCV patients have poorer visuo-spacial memory performance than patients infected with HBV, suggesting that the cognitive deficit may be specific to HCV infection and not to secondary comorbid psychiatric disorders. J. Med. Virol. 81: 1184-1188, 2009. (C) 2009 Wiley-Liss, Inc.

Dengue and dengue hemorrhagic fever among adults: Clinical outcomes related to viremia, serotypes, and antibody response

Background. Clinical manifestations of dengue vary in different areas of endemicity and between specific age groups, whereas predictors of outcome have remained controversial. In Brazil, the disease burden predominantly affects adults, with an increasing trend toward progression to dengue hemorrhagic fever (DHF) noted. Methods. A cohort of adults with confirmed cases of dengue was recruited in central Brazil in 2005. Patients were classified according to the severity of their disease. Associations of antibody responses, viremia levels (as determined by real-time polymerase chain reaction [PCR]), and serotypes (as determined by multiplex PCR) with disease severity were evaluated. Results. Of the 185 symptomatic patients > 14 years of age who had a confirmed case of dengue, 26.5% and 23.2% were classified as having intermediate dengue fever (DF)/ DHF (defined as internal hemorrhage, plasma leakage, manifested signs of shock, and/ or thrombocytopenia [platelet count, <= 50,000 platelets/mm(3)]) and DHF, respectively. The onset of intermediate DF/ DHF and DHF occurred at a late stage of disease, around the period of defervescence. Patients with DHF had abnormal liver enzyme levels, with a > 3-fold increase in aspartate aminotransferase level, compared with the range of values considered to be normal. Overall, 65% of patients presented with secondary infections with dengue virus, with such infection occurring in similar proportions of patients in each of the 3 disease category groups. Dengue virus serotype 3 (DV3) was the predominant serotype, and viremia was detected during and after defervescence among patients with DHF or intermediate DF/ DHF. Conclusions. Viremia was detected after defervescence in adult patients classified as having DHF or intermediate DF/ DHF. Secondary infection was not a predictor of severe clinical manifestation in adults with infected with the DV3 serotype.

Liver transplantation at a University Hospital, Faculty of the Medicine of Ribeirao Preto, University of Sao Paulo: Results for the first 60 recipients

The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAR Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5 % among FAP and Child A patients (P <.05) and 16.6% for period B among 11. 1 % Child B patients and 5.5 % FAP patients; 3.3 % of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.

Silencing of HTLV-1 gag and env genes by small interfering RNAs in HEK 293 cells

Since the discovery of RNAi technology, several functional genomic and disease therapy studies have been conducted using this technique in the field of oncology and virology. RNAi-based antiviral therapies are being studied for the treatment of retroviruses such as HIV-1. These studies include the silencing of regulatory, infectivity and structural genes. The HTLV-1 structural genes are responsible for the synthesis of proteins involved in the entry, assembly and release of particles during viral infection. To examine the possibility of silencing HTLV-1 genes gag and env by RNA interference technology, these genes were cloned into reporter plasmids. These vectors expressed the target mRNAs fused to EGFP reporter genes. Three small interference RNAs (siRNAs) corresponding to gag and three corresponding to env were designed to analyze the effect of silencing by RNAi technology. The plasmids and siRNAs were co-transfected into HEK 293 cells. The results demonstrated that the expression of the HTLV-1 gag and env genes decreased significantly in vitro. Thus, siRNAs can be used to inhibit HTLV-1 structural genes in transformed cells, which could provide a tool for clarifying the roles of HTLV-1 structural genes, as well as a therapy for this infection. (C) 2011 Elsevier B.V. All rights reserved.