Case report: hepatitis in a child infected with SARS-CoV-2 presenting toll-like receptor 7 Gln11Leu single nucleotide polymorphism.

BACKGROUND: Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2'-5'-oligoadenylate synthase-3, oas-3). CASE PRESENTATION: We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein-Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out. CONCLUSION: To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.

[Interaction between HIV-1 and GB virus type-C during coinfection status]. / Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección.

The human immunodeficiency virus (HIV) infection is one of the most important problems in public health. It is estimated that 3 3 million people are infected around the world. HIV and GBV-C share the same transmission route, being frequent the co-infection. Since both viruses replicate in CD4+ lymphocytes, recent studies have described an interaction. Decreasing of HIV viral load and higher CD4 counts have been observed in co-infected patients, leading a better clinical outcome. Nevertheless, some epidemiological studies have shown contradictory results. Additionally, in vitro models report inhibition of HIV by E1, E2, NS3 and NS5A GBV-C proteins, resulting in a decreasing of p24 antigen. This review summarizes the principal findings about co-infection and mechanisms that have been proposed for HIV-1 inhibition.

Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección / Interaction between HIV-1 and GB virus type-C during coinfection status

The human immunodeficiency virus (HIV) infection is one of the most important problems in public health. It is estimated that 3 3 million people are infected around the world. HIV and GBV-C share the same transmission route, being frequent the co-infection. Since both viruses replicate in CD4+ lymphocytes, recent studies have described an interaction. Decreasing of HIV viral load and higher CD4 counts have been observed in co-infected patients, leading a better clinical outcome. Nevertheless, some epidemiological studies have shown contradictory results. Additionally, in vitro models report inhibition of HIV by E1, E2, NS3 and NS5A GBV-C proteins, resulting in a decreasing of p24 antigen. This review summarizes the principal findings about co-infection and mechanisms that have been proposed for HIV-1 inhibition.

La infección por el virus de la inmunodeficiencia humana (VIH) continúa siendo uno de los principales problemas en salud pública; se estima que existen actualmente más de 33 millones de personas infectadas en el mundo. El VIH y el virus GB tipo C (GBV-C) comparten la misma vía de transmisión, por lo que es frecuente encontrar individuos co-infectados. Estudios recientes han descrito un efecto inhibitorio asociado a disminución en la carga viral de VIH, altos recuentos de CD4 y mayor tiempo de sobrevida en pacientes co-infectados, resultando en un mejor pronóstico y menor progreso a SIDA; adicionalmente, estudios in vitro indican que las proteínas virales E1, E2, NS3 y NS5A del GBV-C estarían implicadas en la inhibición del VIH-1. En el presente artículo se revisan los principales aspectos de la co-infección, y se describen los mecanismos propuestos para la inhibición de la replicación del VIH-1 mediada por las proteínas virales del GBV-C.

Autoimmune hepatitis type-2 and Epstein-Barr virus infection in a toddler: art of facts or an artifact?

Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) with prolonged cholestasis, elevated serum transaminases, EBV serology compatible with recent EBV infection and positive anti liver kidney microsomal antibody type 1 which is characteristic of new-onset autoimmune hepatitis type 2. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation with predominant T-lymphocytes and plasma cells and interface hepatitis. Persistent EBV-related hepatitis was excluded by the absence of viral inclusions and steatosis on liver specimens and negative liver EBV-PCR. In conclusion, our case strongly suggests that in children with prolonged cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, liver biopsy seems mandatory in an attempt to achieve a correct and timely diagnosis of a potentially catastrophic disease as autoimmune hepatitis. Although some cases of autoimmune hepatitis type 1 following EBV infection have been reported in adults, to the best of our knowledge, the present case of autoimmune hepatitis type 2 after EBV infection represents the first case in children ever reported in the English literature.

Short communication: Evaluation of GB virus C/hepatitis G viral load among HIV type 1-coinfected patients in São Paulo, Brazil.

Recent studies suggest that GB virus C/hepatitis G virus (GBV-C/HGV) infection in HIV-positive individuals is associated with a slower progression to AIDS, leading to a lower HIV viral load and higher counts of CD4(+) T cells, although many studies have failed to demonstrate these beneficial effects. We developed a Real-Time PCR (TaqMan RT qPCR) to quantify the viral load of GBV-C/HGV in 102 HIV-1-infected patients, who were also evaluated for the presence of anti-E2. The prevalence of GBV-C/HGV infection was 21% among infected patients and the mean plasma viral load was 3.62 ± 0.64 log(10) copies/ml. Despite the high prevalence, there was no statistical difference when we compared the mean viral load (p≤0.46) and the average count of CD4(+) (p≤0.29) and CD8(+) (p≤0.64) among patients infected by GBV-C/HGV and HIV and patients infected only by HIV. This fact can be explained by the number of patients included in the study. Nevertheless, compared to other studies, we observed a discrete number of patients with undetectable HIV load and lower median viral load in the group presenting GBV-C/HGV RNA. Our study suggests that there may be an impact on HIV viral load in GBV-C/HGV-coinfected patients. However, further studies are needed to elucidate the molecular and cellular mechanisms involved in this viral interaction, previously reported in other studies, with the aim of contributing to the development of new targets for drugs against HIV.

Prevalence of non-organ-specific autoantibodies in a rural community from northeastern Brazil: a population-based study.

Non-organ-specific autoantibodies (NOSA) are well-recognized diagnostic markers of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but can also be observed in patients with viral hepatitis as well as in healthy subjects. The aim of this study was to evaluate the prevalence of NOSA in subjects living in a rural community in Brazil and to correlate their occurrence with the presence of liver disease. Seven hundred twenty-five apparently healthy subjects were randomly selected for assessment of antinuclear (ANA), anti-smooth muscle (SMA), antimitochondrial (AMA), anti-liver/kidney microsome type 1, and anti-liver cytosol type 1 antibodies. Subjects with those NOSA were evaluated for the presence of AIH, PBC, and viral hepatitis. Reactivities for all NOSA, SMA, ANA, and AMA were detected, respectively, in 14, 10, 4, and 0.1% of subjects, with a mean titer of 1:40. NOSA-positive subjects were significantly older and more frequently females. No correlation was observed between the occurrence of NOSA and PBC, AIH, or viral hepatitis. The prevalence of NOSA in Brazilians was 14%. They were usually low titer. NOSA were more frequently observed in females and older subjects and their presence was not correlated with the presence of AIH, PBC, or viral hepatitis.

Adenosin deaminasa como molécula coestimuladora y marcador de inmunidad celular / Adenosine deaminase as costimulatory molecule and marker of cellular immunity

La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interés debido a que el defecto congénito de esta enzima causa el síndrome de inmunodeficiencia combinada severa. Una de las tres isoformas de la enzima (ecto-ADA) es capaz de unirse a la glicoproteína CD26 y a los receptores de adenosina A1 y A2B. La interacción ADA-CD26 produce una señal coestimuladora en los eventos de activación de las células T y en la secreción de IFN-g, TNF-a e IL-6. Durante dicha activación la actividad de la enzima está regulada de manera positiva por IL-2 e IL-12 y negativamente por IL-4, basado en un mecanismo de translocación. Diversos estudios señalan que los niveles séricos y plasmáticos de ADA se elevan en algunas enfermedades causadas por microorganismos que infectan principalmente a los macrófagos; así como en trastornos hipertensivos, lo cual podría representar un mecanismo compensatorio como consecuencia de la elevación de los niveles de adenosina y la liberación de mediadores hormonales e inflamatorios estimulados por la hipoxia.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-g, TNF-a and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

[Immune tolerance at 50 years from the Nobel Prize in Medicine and Physiology: a perspective as a mechanism of immune response against pathogens]. / La tolerancia inmunológica a 50 años del Premio Nobel en Medicina y Fisiología: una perspectiva como mecanismo de respuesta inmune frente a patógenos.

The immune system has the capability of protection against infectious disease which is accomplished by an enormous repertoire of receptors specifically reactive to foreign antigens, but it is tolerant to self-antigens, establishing biological identity. The ability to discriminate between self and non-self is a central property of the immune system, by using complex network of cellular and molecular mechanisms in order to prevent autoimmunity; this function is called immune tolerance. Thus, the Interaction between immune system and antigens is required for the generation of tolerance and it is critical in different physiological and pathological conditions in order to limit the damage to self tissues. Since Medawar description, who showed that the tolerance is an acquired property playing a central role in the homeostasis, several mechanism has been proposed to explain it. It is accepted today that an important group of antigen specific cells called regulatory T cell, both natural and induced, are critical as a unifying mechanism to maintain self-tolerance. These suppressor lymphocyte subpopulations had shown to play an important role not only by controlling autoimmune disease but also in the pathogenesis of many chronic infectious diseases, either manipulated by the microorganism to escape from the immune system, or induced by the host to reduce inflammatory damage. This review has the intention of updating about modern concepts in immune tolerance mechanisms, with special emphasis played by Treg cell in the tolerance which is unquestionable induced during the course of chronic infections diseases.

[Adenosine deaminase as costimulatory molecule and marker of cellular immunity]. / Adenosin deaminasa como molécula coestimuladora y marcador de inmunidad celular.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-gamma, TNF-alpha and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

GB virus type C infection modulates T-cell activation independently of HIV-1 viral load.

BACKGROUND: Many clinical studies have suggested a beneficial effect of GB virus type C (GBV-C) on the course of HIV-1 infection, but the mechanisms involved in such amelioration are not clear. As recent evidence has implicated cellular activation in HIV-1 pathogenesis, we investigated the effect of GBV-C viremia on T-cell activation in early HIV-1 infection. METHODS: Forty-eight recently infected HIV-1 patients (23 GBV-C viremic) were evaluated for T-cell counts, expanded immunophenotyping GBV-C RNA detection, and HIV-1 viral load. Nonparametric univariate and multivariate analyses were carried out to identify variables associated with cellular activation, including GBV-C status, HIV-1 viral load, T lymphocyte counts, and CD38 and chemokine (C-C motif) receptor 5 (CCR5) surface expression. FINDING: We not only confirmed the positive correlation between HIV-1 viral load and the percentage of T cells positive for CD38(+)CD8(+) but also observed that GBV-C viremic patients had a lower percentage of T cells positive for CD38(+)CD4(+), CD38(+)CD8(+), CCR5(+)CD4(+), and CCR5(+)CD8(+) compared with HIV-1-infected patients who were not GBV-C viremic. In regression models, GBV-C RNA(+) status was associated with a reduction in the CD38 on CD4(+) or CD8(+) T cells and CCR5(+) on CD8(+) T cells, independent of the HIV-1 viral load or CD4(+) and CD8(+) T-cell counts. These results were also supported by the lower expression of CD69 and CD25 in GBV-C viremic patients. INTERPRETATION: The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients.

Estudo de prevalência de auto-anticorpos não órgão específicos em população rural do nordeste brasileiro (Cavunge-Ba) / Study of the prevalence of autoantibodies not specific national rural population of Northeast Brazil (Cavunge-Ba)

Os auto-anticorpos hepáticos (AAH), incluindo os anticorpos antinúcleo (ANA), antimúsculo liso (SMA), antimicrossoma de fígado e rim do tipo 1 (anti-M1), anticitosol hepático do tipo 1 (anti-LC1) e antimitocôndria (AMA), podem ser encontrados em 1 por cento a 43 por cento dos indivíduos saudáveis, sendo considerados auto-anticorpos naturais. Por outro lado, são também considerados marcadores de enfermidades auto-imunes, particularmente hepatite auto-imune (HAI) e cirrose biliar primária (CBP), duas doenças auto-imunes do fígado de prevalência ainda desconhecida na população brasileira. Com o intuito de avaliar a freqüência de AAH na população normal e sua correlação com estado de doença e de investigar a prevalência de HAI e CBP no Brasil, foram coletadas amostras de soro de 725 indivíduos, aleatoriamente selecionados, residentes no povoado de Cavunge para realização de AAH por imunofluorescência indireta (IFI), empregando cortes de roedores, fibroblastos e células Hep-2. Os resultados foram comparados com dados demográficos e marcadores sorológicos de infecção por vírus A, B e C. Positividade para AAH foi considerada na presença de titulação igualou superior a 1:40, sendo considerada clinicamente relevante titulação igualou superior a 1:80. Cento e um indivíduos (14 por cento) apresentaram reatividade para AAH, a maioria com títulos de 1:40, sendo observada positividade para SMA, ANA e AMA em respectivamente 10 por cento, 4 por cento e 0,1 por cento dos indivíduos. Não foi encontrada reatividade para anti-LKM 1 e anti-LC 1. Os principais padrões de IFI para SMA e ANA foram, respectivamente, vaso e glomérulo I e nuclear pontilhado grosso. Apenas um indivíduo com SMA exibiu reatividade para anti-microfilamento em baixo título, não sendo observado...

Fulminant hepatic failure in northern Brazil: morphological, immunohistochemical and pathogenic aspects of Lábrea hepatitis and yellow fever.

A morphological evaluation of histopathological liver samples from 42 fulminant hepatic failure cases from the Amazon Basin was undertaken in order to differentiate yellow fever (YF) from Lábrea hepatitis (LH) and other entities. The pattern and distribution of liver cell death as well as ballooning degeneration and midzonal apoptotic bodies were the most distinctive features of YF, whereas morula cells were the major finding for LH. Nineteen well characterised cases were further submitted to immunohistochemical studies for expression of YF antigen, hepatitis B surface antigen (HBsAg) and delta virus antigen. In both diseases, but particularly in LH, portal vein branch phlebitis was evident and might have played a role in the pathogenesis of hepatic injury, leading to hepatic extinction and portal tract approximation. The regeneration pattern was remarkable: a high proliferative index was detected in YF, whereas in LH multinucleation and pseudoacinar transformation, associated with portal type I collagen deposition and portal elastic fibre proliferation, was seen. In conclusion, midzonal apoptosis, portal phlebitis and a high proliferative index in patients without evidence of previous liver injury was the dominant picture in YF. On the other hand, LH cases showed extensive, predominantly lytic hepatocytic necrosis, portal and hepatic vein phlebitis and morula cells in patients with a morphological background of chronic liver disease.

[The changing epidemiology of viral hepatitis in Chile]. / Cambios en la epidemiología de las hepatitis virales en Chile y consideraciones en estrategias de prevención.

The social and sanitary changes that Chile is experiencing will change the epidemiologic profile of viral hepatitis. Virus A hepatitis will displace to older ages, and immunization plans with specific vaccines should be considered. The real prevalence of hepatitis B may be higher, due to an underreporting of the disease. The education and vaccination of high risk groups should be reinforced. E virus hepatitis requires more research in risk groups and in certain animal species consumed by humans. C virus hepatitis is the greatest challenge as it causes chronic liver disease and is the main cause for liver transplantation.

Cambios en la epidemiología de las hepatitis virales en Chile y consideraciones en estrategias de prevención / The changing epidemiology of viral hepatitis in Chile

The social and sanitary changes that Chile is experiencing will change the epidemiologic profile of viral hepatitis. Virus A hepatitis will displace to older ages, and immunization plans with specific vaccines should be considered. The real prevalence of hepatitis B may be higher, due to an underreporting of the disease. The education and vaccination of high risk groups should be reinforced. E virus hepatitis requires more research in risk groups and in certain animal species consumed by humans. C virus hepatitis is the greatest challenge as it causes chronic liver disease and is the main cause for liver transplantation.

[Cytomegalovirus infection with hepatic involvement in immunocompetent adults]. / Infección por citomegalovirus con compromiso hepático en adultos inmunocompetentes.

We retrospectively evaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic between March 1999 and March 2004 who presented fever and asthenia, mild to moderate increase of transaminases and serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history of transfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV) and Epstein-Barr virus (EBV). The laboratory diagnosis of recent cytomegalovirus infection was made by especific IgM detection (ELISA) or a significant increase of specific IgG. The most frequent symptoms were fever (85%) and asthenia (83%), followed by cephalea (25%), splenomegaly (20%), adenomegalies (22%), pharyngitis (25%), myalgias (25%) and hepatomegaly (19%). All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73). In average, ALT was increased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosis of CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice, the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgM against CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infection should be investigated.

Infeccion por citomegalovirus con compromiso hepatico en adultos inmunocompetentes / Cytomegalovirus infection with hepatic involvement in immunocompetent adults

Evaluamos retrospectivamente a 73 adultos inmunocompetentes que consultaron entre marzo de 1999 y marzo de 2004 a un centro infectológico ambulatorio por fiebre y astenia, con elevación discreta de las transaminasas y serología compatible con infección reciente por citomegalovirus (CMV). Excluimos a pacientes con antecedentes de transfusiones, adicciones e inmunodeficiencias, así como aquellos con alteraciones hepáticas preexistentes o con serología compatible con infección aguda por hepatitis A, B, C (VHA, VHB, VHC) o virus Epstein Barr (VEB). El diagnóstico de infección reciente por citomegalovirus se efectuó mediante la detección de IgM específica (ELISA de captura), seroconversión o aumento cuádruple del título de IgG específica, en presencia de un cuadro clínico compatible. Los síntomas más frecuentes fueron: fiebre (85%) y astenia (83%), cefalea (25%), esplenomegalia (20%), adenomegalia (22%), faringitis (25%), mialgia (25%) y hepatomegalia (19 %). Se encontró elevación discreta de transaminasas y linfomonocitosis en todos los pacientes (73/73). La elevación promedio de GPT fue de 6 veces y la de GOT fue de 3.5 veces su valor límite. Las características clínicas que diferencian la infección por CMV de la infección por VEB son la menor frecuencia de poliadenopatías y faringitis en la primera. El diagnóstico diferencial de la infección por CMV con compromise hepático con las hepatitis A y B agudas se basa en la ausencia de ictericia, la menor elevación de las transaminasas, la linfomonocitosis intensa y la presencia de IgM específica que caracterizan a la infección por CMV. En conclusión, ante un paciente joven, previamente sano, con fiebre, astenia intensa, linfomonocitosis y elevación discreta de transaminasas, es importante investigar infección por citomegalovirus.(AU)

We retrospectivelyevaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic betweenMarch 1999 and March 2004 who presented fever and asthenia, mild to moderate increase of transaminasesand serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history oftransfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV) and Epstein Barr virus (EBV). The laboratory diagnosis ofrecent cytomegalovirus infection was made by especific IgM detection (ELISA) or a significant increase of specific IgG. The most frequent symptoms were fever (85%) and asthenia (83%), followed by cephalea (25%), splenomegaly (20%), adenomegalies (22%), pharyngitis (25%), myalgias (25%) and hepatomegaly (19%). All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73). In average, ALT wasincreased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosisof CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice,the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgMagainst CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infectionshould be investigated.(AU)

Infeccion por citomegalovirus con compromiso hepatico en adultos inmunocompetentes / Cytomegalovirus infection with hepatic involvement in immunocompetent adults

Evaluamos retrospectivamente a 73 adultos inmunocompetentes que consultaron entre marzo de 1999 y marzo de 2004 a un centro infectológico ambulatorio por fiebre y astenia, con elevación discreta de las transaminasas y serología compatible con infección reciente por citomegalovirus (CMV). Excluimos a pacientes con antecedentes de transfusiones, adicciones e inmunodeficiencias, así como aquellos con alteraciones hepáticas preexistentes o con serología compatible con infección aguda por hepatitis A, B, C (VHA, VHB, VHC) o virus Epstein Barr (VEB). El diagnóstico de infección reciente por citomegalovirus se efectuó mediante la detección de IgM específica (ELISA de captura), seroconversión o aumento cuádruple del título de IgG específica, en presencia de un cuadro clínico compatible. Los síntomas más frecuentes fueron: fiebre (85%) y astenia (83%), cefalea (25%), esplenomegalia (20%), adenomegalia (22%), faringitis (25%), mialgia (25%) y hepatomegalia (19 %). Se encontró elevación discreta de transaminasas y linfomonocitosis en todos los pacientes (73/73). La elevación promedio de GPT fue de 6 veces y la de GOT fue de 3.5 veces su valor límite. Las características clínicas que diferencian la infección por CMV de la infección por VEB son la menor frecuencia de poliadenopatías y faringitis en la primera. El diagnóstico diferencial de la infección por CMV con compromise hepático con las hepatitis A y B agudas se basa en la ausencia de ictericia, la menor elevación de las transaminasas, la linfomonocitosis intensa y la presencia de IgM específica que caracterizan a la infección por CMV. En conclusión, ante un paciente joven, previamente sano, con fiebre, astenia intensa, linfomonocitosis y elevación discreta de transaminasas, es importante investigar infección por citomegalovirus.(AU)

We retrospectivelyevaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic betweenMarch 1999 and March 2004 who presented fever and asthenia, mild to moderate increase of transaminasesand serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history oftransfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV) and Epstein Barr virus (EBV). The laboratory diagnosis ofrecent cytomegalovirus infection was made by especific IgM detection (ELISA) or a significant increase of specific IgG. The most frequent symptoms were fever (85%) and asthenia (83%), followed by cephalea (25%), splenomegaly (20%), adenomegalies (22%), pharyngitis (25%), myalgias (25%) and hepatomegaly (19%). All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73). In average, ALT wasincreased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosisof CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice,the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgMagainst CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infectionshould be investigated.(AU)

Infeccion por citomegalovirus con compromiso hepatico en adultos inmunocompetentes / Cytomegalovirus infection with hepatic involvement in immunocompetent adults

Evaluamos retrospectivamente a 73 adultos inmunocompetentes que consultaron entre marzo de 1999 y marzo de 2004 a un centro infectológico ambulatorio por fiebre y astenia, con elevación discreta de las transaminasas y serología compatible con infección reciente por citomegalovirus (CMV). Excluimos a pacientes con antecedentes de transfusiones, adicciones e inmunodeficiencias, así como aquellos con alteraciones hepáticas preexistentes o con serología compatible con infección aguda por hepatitis A, B, C (VHA, VHB, VHC) o virus Epstein Barr (VEB). El diagnóstico de infección reciente por citomegalovirus se efectuó mediante la detección de IgM específica (ELISA de captura), seroconversión o aumento cuádruple del título de IgG específica, en presencia de un cuadro clínico compatible. Los síntomas más frecuentes fueron: fiebre (85%) y astenia (83%), cefalea (25%), esplenomegalia (20%), adenomegalia (22%), faringitis (25%), mialgia (25%) y hepatomegalia (19 %). Se encontró elevación discreta de transaminasas y linfomonocitosis en todos los pacientes (73/73). La elevación promedio de GPT fue de 6 veces y la de GOT fue de 3.5 veces su valor límite. Las características clínicas que diferencian la infección por CMV de la infección por VEB son la menor frecuencia de poliadenopatías y faringitis en la primera. El diagnóstico diferencial de la infección por CMV con compromise hepático con las hepatitis A y B agudas se basa en la ausencia de ictericia, la menor elevación de las transaminasas, la linfomonocitosis intensa y la presencia de IgM específica que caracterizan a la infección por CMV. En conclusión, ante un paciente joven, previamente sano, con fiebre, astenia intensa, linfomonocitosis y elevación discreta de transaminasas, es importante investigar infección por citomegalovirus.

We retrospectivelyevaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic betweenMarch 1999 and March 2004 who presented fever and asthenia, mild to moderate increase of transaminasesand serological findings compatible with recent cytomegalovirus infection. We excluded patients with a history oftransfusions, drug abuse, immunodeficiencies, preexistent hepatic impairment or serological findings compatible with acute hepatitis A, B and C (HAV, HBV, HCV) and Epstein Barr virus (EBV). The laboratory diagnosis ofrecent cytomegalovirus infection was made by especific IgM detection (ELISA) or a significant increase of specific IgG. The most frequent symptoms were fever (85%) and asthenia (83%), followed by cephalea (25%), splenomegaly (20%), adenomegalies (22%), pharyngitis (25%), myalgias (25%) and hepatomegaly (19%). All the patients showed moderate increase of transaminases and lymphomonocytosis (73/73). In average, ALT wasincreased by 6 fold and AST by 3.5 fold. The clinical characteristics that differentiate CMV infection from Epstein-Barr infection are the lesser frequency of adenomegalies and pharyngitis in the former. The differential diagnosisof CMV infection with hepatic involvement from acute hepatitis A and B, is based on the absence of jaundice,the lower elevation of transaminases, the intense lymphomonocytosis and the presence of specific IgMagainst CMV that are characteristic of CMV infection. In conclusion, in previously healthy young adults with fever, intense asthenia, lymphomonocytosis and moderate increase in transaminases levels, cytomegalovirus infectionshould be investigated.

Importancia del pesquisaje de hepatitis virales en el diseño de estrategias de vacunación / Importance of the investigations of viral hepatitis for designing vaccination strategies

Se analiza de forma longitudinal la incidencia de hepatitis virales, así como las tasas deportadores del antígeno de superficie del virus de la hepatitis B (HBsAg) y de anticuerposcontra el virus de la hepatitis C, detectados en los programas de pesquisaje basados en elSistema Ultramicroanalítico (SUMA). Se demuestra la disminución de la incidencia de hepatitis B a tan sólo 1,2 x 100000 habitantes en el año 2002, así como de las tasas de portadores del HBsAg, en correspondencia con la vacunación. La hepatitis C también ha disminuido, probablemente como consecuencia de medidas de control epidemiológico. La hepatitis A es diagnosticada con un ELISA desarrollado por el Instituto de Medicina Tropical “Pedro Kourí”, y se ha mantenido muy elevada en los últimos años, de forma sostenida sobre 100 x 100000 habitantes a partir de 1991, por lo que debe valorarse laintroducción de la vacunación para su control(AU)

GBV-C/HGV and HIV-1 coinfection.

An interesting interaction pattern has been found between HIV-1 and GBV-C/HGV, resulting in protection against progression to AIDS. The mechanisms involved in this interaction remain to be clarified. We examined the current knowledge concerning this coinfection and developed hypotheses to explain its effects. A better understanding of this interaction could result in new concepts, which may lead to new strategies to control HIV-1 replication and progression to AIDS.