On behalf of the Organizing Committee, we are pleased to welcome you in Paris for the fourth Dominique Dormont International Conference. This annual conference is in memory of the spirit of Dominique Dormont and his dedication to research on pathogenesis and treatment of chronic infectious diseases.
From May 2009 to April 2013, a cross-sectional study of CHC patients was performed at a public university-based outpatient clinic for infectious diseases (Centro de Treinamento e Referências em Doenças Infecciosas e Parasitárias Orestes Diniz - Secretaria Municipal de Saúde de Belo Horizonte e Universidade Federal de Minas Gerais/CTR DIP Orestes Diniz- SMSA-BH/UFMG) in Belo Horizonte, Brazil. All of the patients in this study were older than 18 years of age, displayed anti-HCV antibody positivity for more than six months according to a third-generation enzyme-linked immunosorbent assay (ELISA) and expressed hepatitisCvirus (HCV) ribonucleic acid (RNA) as detected by polymerase chain reaction (PCR) (AMPLICOR, Roche Molecular Systems). Patients were excluded from the study if they exhibited co-infectionwith the hepatitis B virus or human immunodeﬁ ciency virus (HIV) or a low score on the Mini- Mental Status Examination, which was suggestive of a cognitive deﬁ cit. This report is a component of a major project investigating the psychopathological characteristics of CHC patients and the clinicaland laboratorial correlates of these characteristics 16,17 .
The objective of this study was to evaluate the prevalence and risk factors associated with HCV infection in a group ofHIV seropositive patients. We analyzed the medical records of 1,457 patients. All patients were tested for HCV infection by third generation ELISA. Whenever possible, a sample of the positive patients was also tested for HCV by PCR. HCV positive patients were analyzed according to their risk factors for both infections. The prevalence of anti-HCV positive patients was 17.7% (258 patients). Eighty-two (82) of these patients were also tested by PCR and 81 were positive for HCV virus (98%). One hundred fifty-one (58.5%) were intravenous drug users (IDU); 42 (16.3%) were sexual partners ofHIV patients; 23 (8.9%) were homosexual males; 12 (4.7%) had received blood transfusion; 61 (17.5%) had promiscuous sexual habits; 14 (5.4%) denied any risk factor; 12 (4.7%) were sexual partners of IDU. Two hundred four patients mentioned only one risk factor. Among them, 28 (10.9%) were sexual partners ofHIV- positive patients. Although intravenous drug use was the most important risk factor for co-infection, sexual transmission seemed to contribute to the high HCV seroprevalence in this group of patients.
Abstract: HepatitisCvirus (HCV) patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL) 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitisCinfection. Our study included 15 patients with chronic HCV infectionand newly diagnosed isolated autoimmune thrombocytopenia (Group I) and 15 patients with chronic HCV infectionand normal platelet count as controls (Group II). All patients were examined for personal history andclinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR), abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001) while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001) in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I), r = 0.038, p = 0.89 (Group II)] or IL-12 [r = 0.497, p = 0.06 (Group I), r = 0.499, p = 0.058 (Group II)]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033) or IL-12 (r = 0.967, p = 0.001), while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = –0.08 and p = 0.851 for IL-12). Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.
HBV infectionand its clinical complications (CID 2012). Regarding the HAV, Mexico is a region of high ende- micity for this infection because 80% ofchildren below the age of 10 and 90% of adults in general are positive for anti-HAV IgG antibodies (Panduro et al. 2011). Thus, it is not surprising that in this study, 54% of the HBV DNA+ children, with most being OBI, had anti-HAV IgM antibodies. This fact also coincides with the finding that none of them had been vaccinated. Therefore, HAV- HBV co-infections among OBI cases may be more com- mon than expected; moreover, they are not easily dis- criminated from each other by clinical evaluation only. The high prevalence of OBI found in this study suggests that nucleic acid testing for HBV may be a more objec- tive diagnostic tool due to the misconception among most physicians that HAV is the only virus responsible for hepatitis in children. Both HAV and HAV-HBV co- infections can lead to ALF with high mortality (Squires et al. 2006); hence, vaccination against hepatitis A in children should be reinforced (AAP/CID 2007).
Because of its various forms of transmission, he- patitis remains circulating in the population. The most common forms ofinfection are sexual, pa- renteral and vertical . However, other forms of transmission such as use of manicure tools, crack pipe and tools to inhale cocaine have been associa- ted withhepatitis . The incidence may be even higher than those reported in various regions of the country as often hepatitis is only diagnosed after clinical suspicion. The delay in diagnosis may con- tribute to a poor prognosis, with the presence of complications such as liver cirrhosis, hepatocellular carcinoma cell and even death.
HepatitisCvirus (HCV) is essentially hepatotropic but its manifesta- tions can extend beyond the liver. It can be associated with autoim- mune diseases, such as mixed cryoglobulinemia, membranoprolifera- tive glomerulonephritis, autoimmune thyroiditis, and lymphoprolif- erative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon- α (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.
Abstract: In Mato Grosso do Sul state, Brazil, the number of prisoners has increased in the recent years and the control ofhepatitisCvirus (HCV) has become more complex. The aim of the present study was to estimate the prevalence and identify the genotypes of HCV in prisoners as well as the factors associated with this infectious disease. Thereby, 443 men and 243 women from prisons were interviewed and subjected to blood collection. Anti-HCV reactive samples were analyzed by RT-PCR and genotyped. The overall seroprevalence of HCV infection was 4.8% (95%CI: 3.4 to 6.8%). Furthermore, the prevalence was higher in: men, injecting drug users, tattooed persons, those who were more than 50 years old, individuals who have been arrested multiple times, people with previous history of sexually transmitted disease (STD), persons who received blood transfusions or those withHIV/AIDS. The prevalence of RNA HCV by PCR was 3.0% (95%CI: 1.7 to 4.2%). Moreover, the coinfection ofHIVand HCV was 33.3%. In addition, genotype 1 was the most frequent (85%) followed by genotype 3 (15%). The screening strategy for HCV and other infectious diseases in inmates is important as it establishes an early diagnosis, opportunity for treatment and allows the breaking of the transmission chain.
Background: Occult hepatitis B virus (HBV) infection is defined by the presence of HBV-DNA by PCR in serum or liver tissue samples from HBsAg-negative individuals. Recent reports suggest that hepatitisCvirus (HCV) carriers who also harbor this silent infection have more advanced liver fibrosis, reduced response to interferon, and increased risk of developing hepatocellular carcinoma. Similar findings have been described among chronic hepatitisC patients with serological markers of prior HBV infection (anti-HBc positive, with or without anti-HBs), irrespective of HBV-DNA detection. However, these studies have failed to appropriately control for factors known to impact HCV-related fibrogenesis including duration ofinfection, alcohol abuse, and age at infection. Aims: To assess the prevalence and impact of occult and previous HBV infection on clinical, biochemical, virological and histological features in patients with chronic hepatitisC from a liver clinic cohort. Methods: This case-control study included non-alcoholic subjects whose sera tested negative for HBsAg and anti-HIV, and positive for HCV-RNA. All patients had prior parenteral exposure as the probable source of HCV infection (blood transfusions or IV drug use). Serum samples were collected within 6 months of liver biopsy and were tested for HBV-DNA using a commercial PCR assay with sensitivity of 10 3 copies/mL (Amplicor HBV MONITOR®
The existence of a quasispecies popula- tion appears to hamper the development of vaccines for HCV and to favor the perpetua- tion of the virus in the human organism. In a study of 12 patients with acute hepatitisC, Farci et al. (31) observed that individuals who developed chronic infection had a sig- nificantly greater HVR1 genetic diversity after 8 to 11 weeks compared to patients who eliminated the virus during the acute phase. The influence of HCV quasispecies on the response to therapy with alpha interferon has been analyzed by many investigators (32-36). Although the results were not uni- form, a higher HVR1 complexity and diver- sity before treatment appeared to be more frequently observed among non-responders. The role of HCV quasispecies in the severity of recurrent hepatitisC after liver transplantation has been evaluated in several studies.
In order to estimate the prevalence of human immunodeficiency virus type 1 (HIV-1) andhepatitisCvirus (HCV) co-infection in hard-to-reach intravenous drug users, 199 subjects from high-risk inner-city locales, the so called “shooting galleries”, were consented, interviewed, and tested in Miami, FL, US. Positive HIV-1 status was based on repeatedly reactive ELISA and confirmatory Western Blot. Positive HCV status was based on reactive ELISA and confirmatory polymerase chain reaction techniques. Overall, 50 (25%) were not infected with either virus, 61 (31%) were HIV-1/HCV co-infected, 17 (8%) infected by HIV-1 only, and 71 (36%) infected by HCV only. The results of the multivariable analyses showed that more years using heroin was the only significant risk factor for HCV only infection (odds ratio = 1.15; 95% confidence interval = 1.07, 1.24) and for HIV-1/HCV co-infection (odds ratio = 1.17; 95% confidence interval = 1.09, 1.26). This paper demonstrates that HIV-1/HCV co-infection is highly preva- lent among so called “shooting galleries”.
Group A – Sixty-nine patients co-infected by HIVand HCV Group B – Sixty-four patients mono-infected by HCV. At baseline, the following data were collected from patients: age, gender, risk group for HIV-HCV infection, use of medications, occurrence of symptoms-signs related to hepatic disease, liver enzymes profile, qualitative RNA-HCV with viral genotyping, HIV viral load, CD 4 and CD 8 counts. Intensity of liver disease was assessed using the Child- Turcotte-Pugh 5-15 score: < 7 Child A (compensated liver disease), between 7 and 9, Child B (significant liver dysfunction) and >9, Child C (decompensated liver disease). All patients were subjected to abdominal ultrasound, with description of the liver, spleen, and portal vein and a search for findings consistent with chronic liver disease. Patients with increased alanine aminotransferase (ALT) levels had a liver biopsy to assess necroinflamatory activity and fibrosis, unless there was decompensated liver disease with a prolonged prothrombin time. The METAVIR score system was used to determine hepatic histology according to necroinflamatory activity and fibrosis stage. Specimens were graded for the degree of activity using a four-level grading system based on the presence and severity of piecemeal necrosis, lobular necrosis and portal inflammation. Fibrosis stage was assessed through a four-level staging system, based on the presence of portal fibrosis, with or without septa and cirrhosis.
One reason the model equations can be solved analytically is that the assumption T = constant is made, linearizing the mass- action infection term bTV . The assumption of constant T has typically been made when short-term (2 week or less) clinical trials are examined. However, the obtained solution may be more general, particularly for direct-acting antivirals. When therapy is very potent so the viral load rapidly decays many logs during the first days of therapy, as seen for example with daclatasvir, where V decays 3 logs in the first 12 hrs of therapy , the term bTV no longer significantly influences the dynamics. Thus, after a very brief transient, whether T is constant or not may have no practical effect on the underlying viral dynamics. Guedj et al  showed this to be the case for daclatasvir by finding an extremely accurate approximate solution to the viral dynamic model they used by assuming there were no new infections after therapy started, i.e. that bTV = 0.
assay (AUSAB EIA, Abbott Laboratories, North Chicago, IL, USA). Anti-HCV antibodies were detected with a commercially available third-generation enzyme-linked immunosorbent assay kit (Abbott Laboratories). HCV RNA viral loads were quantified by means of a real-time polymerase chain reaction assay (RealTime HCV; Abbott Molecular, Des Plaines IL, USA; detection limit: 12 IU/mL) . Anti-HIV antibody assays (SERODIA-HIV, Fujirebio, Tokyo, Japan) were performed according to the manufacturer’s instructions. HIV RNA viral loads were quantified by means of reverse-transcription polymerase chain reaction (Roche Amplicor, ver. 1.5, Roche Diagnostics, Branchburg, NJ, USA). CD4 counts were determined by flow cytometry (FACFlow, BD FACSCalibur, Becton Dickinson, San Jose, CA, USA). HCV genotype was determined by using a VERSANT HCV Genotype 2.0 Assay (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA), according to the manufacturer’s strict instructions.
T cell count associated with vaccination, a control group of 31 HIV-infected, non–HAV-vaccinated children (mean age, 5.8 years), divided into similar clinicaland immunologic categories, was included. Two intramuscular doses ofhepatitis A vaccine (Havrix; Glaxo SmithKline Beecham) were administered with a 6-month interval between doses. Blood samples were obtained before and 4–8 weeks after the first and second doses. Serum samples were stored at ⫺80C until tested for antibody levels.
At the moment, patients with HCV genotype 3 infections are considered a special population and have become one of the most challenging subpopulations to treat. Studies have shown that genotype 3 is associated with faster progression to cirrhosis and, thus, has a higher likelihood of hepatocellular carcinoma in comparison to the other genotypes (3,4). In addition, few effective treatment options are available and the use of some therapeutic options is not yet supported by clinical trial data in this subset of patients. Finally, patients with HCV genotype 3 infectionand cirrhosis, especially those who are treatment-experienced, have the lowest SVRs in the DAA era.
The present study has limitations, the most relevant of which is possibly related to the model used to calculate the FPR in HCV-infected and in HCV/HIV-co-infected patients. Ideally, in the calculation of fibrosis progression, consecu- tive biopsies should be performed with a long interval be- tween them in patients untreated for HCV, which would be ethically unacceptable. The present model, described else- where (3), permits the evaluation of the cumulative effect of fibrosis progression according to the duration ofinfection. Although previously validated, this model may be criticized since it considers the patient to have no fibrosis at the time of HCV infection. The accuracy of the calculation of the esti- mated length ofinfection can also be criticized, as it is based on patient history. In order to adequately analyze the dura- tion of HCV infection, the population evaluated here in- cluded only patients with a history of blood transfusion or intravenous drug users, since in this population contamina- tion generally occurs during the first transfusion or in the first year of intravenous drug use in as many as 90% of cases (38). Although not an ideal method, this estimate using a single biopsy remains a useful tool in the study of the natural history of chronic hepatitisC. Besides, the groups presented some differences related to epidemiological aspects that possibly influenced the results when comparative analyses were performed.
A extracção de DNA plasmídico foi executada através da lise alcalina de suspensões bacterianas. As colónias identificadas como possíveis clones recombinantes, obtidos pela inserção de DNA alvo nos vectores utilizados, foram repicadas, com um palito estéril, para tubos com 2ml contendo meio LB lí quido suplementado com ampicilina (100μg/ml). Estes foram mantidos durante a noite a 37°C, com agitação, até à obtenção de uma cultura bacteriana saturada. Posteriormente, centrifugou-se 1,5ml da mesma a 16000g durante 2min, tendo o sedimento celular sido recuperado, após decantação do sobrenadante. As células foram, posteriormente, ressuspendidas em 200μl de TEG (25mM Tris-HCl pH 8,0, 1mM EDTA, 1% glucose) frio, e as suspensões assim obtidas adicionadas de 250μl de solução de lise (0,2M NaOH, 1,5% SDS). As suspensões bacterianas foram agitadas suavemente, por inversão, para estimular o efeito de lise, e em seguida adicionadas de 250μl de acetato de potássio 3M (pH 5,4). De imediato, procedeu- se, novamente, à sua agitação por inversões sucessivas. Os tubos contendo o lisado celular foram, então, centrifugados a 16000g durante 15min, à temperatura ambiente. O sobrenadante foi transferido para novos microtubos contendo igual volume de isopropanol (aproximadamente 700μl), e o seu conteúdo homogeneizado por inversão suave. Os ácidos nucleicos precipitados foram, em seguida, colhidos por centrifugação nas mesmas condições descritas anteriormente. O sedimento de ácidos nucleicos foi lavado com 250μl de etanol e em seguida seco sob vácuo (Concentrator 5301 - Eppendorf, EUA). Por fim, o sedimento seco foi ressuspendido em 30μl de TE (1M Tris-HCl pH 8,0, 0,5M EDTA) com 100μg/ml RNase e incubado a 37°C, em banho- maria, durante 30minutos (para permitir uma eficiente degradação do RNA presente).
A cross-sectional study was conducted in a convenience sample drawn from patients attending all charitable, private and public drug treatment centers in the munici- palities of Goiânia and Campo Grande, central-western Brazil, between August 2005 and July 2006. There were selected 851 users, 542 from 18 centers (ten to 70 patients per center) in Goiânia and 309 from eight centers (ten to 76 patients per center) in Campo Grande. All subjects were informed on the study objectives and procedures and invited to participate. The following inclusion criteria were applied: 18 years of age or more; injecting and/or non-injecting drug use; and enroll- ment in a drug treatment center. All patients agreed to participate in the study. Injecting drug users (IDU) were defi ned as those patients reporting intravenous drug use; and non-injecting drug users (NIDU) were defi ned as those patients who reported never using intravenous drugs and reported lifetime use of marijuana, cocaine (powder, crack, and “merla”), heroin, LSD, and ecstasy through other routes (sniffi ng, smoking, and ingestion). Of 851 users, 691 (81.2%) were eligible to participate in the study, of which were 102 IDU and 589 NIDU. A standardized questionnaire based on the World Health Organization (WHO) recommendations 8 was applied to