ABSTRACT
This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.
Subject(s)
Male , Hepatitis A virus , Hepatitis A/complications , Liver Failure, Acute/virology , Macaca fascicularis/virology , Parvoviridae Infections/complications , Parvovirus B19, Human , Antibodies, Viral/blood , Coinfection/virology , Disease Models, Animal , Hepatitis A virus/immunology , Hepatitis A/immunology , Parvoviridae Infections/immunology , Parvovirus B19, Human/immunology , ViremiaABSTRACT
OBJECTIVE: To describe the clinical manifestations and outcome of acute liver failure (ALF) associated with dengue viral infection, a rare but severe complication. METHODS: One hundred and fifty five consecutive patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described. RESULTS: All patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum) age was 33.5 (17, 47) years with 50% female. The median (minimum, maximum) duration from the onset of fever to development of ALF was 7.5 (5, 13) days and the maximum hepatic encephalopathy (HE) grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS) on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase [median admission 1140.5 u/L (639, 4161); median peak 2487 u/L (998, 5181)], serum bilirubin [median admission 29 µmol/L (23, 291); median peak 127 µmol/L (72, 592)], and prothrombin time [median admission 16.8 s (15.3, 26.2); median peak 22 s (15.3, 40.7)]. The survival rate with standard medical therapy alone was 100%. CONCLUSIONS: Dengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Dengue/complications , Hepatitis, Viral, Human/virology , Liver Failure, Acute/virology , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness IndexABSTRACT
The human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection is a common problem in the world, with an estimated prevalence of up to 8 percent. We report a 27-year-old man admitted to the intensive care unit with an acute liver failure by HBV. During hospital stay, a co-infection with HIV virus was detected. Treatment with early antiviral therapy was started with emtricitabine, tenofovir and raltegravir, to cover both HBV and HIV. Despite therapy, the patient died two weeks after admission.
Subject(s)
Adult , Humans , Male , HIV Infections/complications , Hepatitis B/complications , Liver Failure, Acute/virology , Coinfection/virology , Fatal Outcome , Hepatitis B virusABSTRACT
Fulminant hepatic failure (FHF) is characterized by massive hepatocellular injury, whose physiopathology is still unclear. Hepatitis B (HBV) is probably the most common viral cause of FHF, while hepatitis A (HAV) virus seem occurs less frequently. However, the host and viral factors that determine the outcome of these infections are poorly understood. In the present study, viral load and genotyping determining regions of HAV and HBV genomes were sequenced. Eight FHF patients and one patient with severe acute hepatitis (SAH) were included. Liver and blood samples were collected during liver transplantation or necropsy procedures. HAV-RNA and HBV-DNA were extracted from serum, biopsy and paraffin liver. Nucleotide sequencing of HAV-RNA was performed from VP1/2A and HBV-DNA from PreS/S region. The amplified samples were quantified by Real-Time PCR. The cases of HAV infection were due to subgenotype IA. The cases of HBV infection were due to genotype A2 and D4. The case of HAV/HBV coinfection was infected by genotype IA and D3. Hepatitis A and B infection were associated with genotypes most prevalent in Brazil. In hepatitis A infection the mean of period evolution was 13 days. In hepatitis B, FHF patients infected by genotype D have a shorter period of evolution than FHF patients infected by genotype A (mean 15 v. 53 days). There was no association with genotype-determining region with the severity of hepatitis, however nucleotide differences and high viral load could be observed among FHF.
Subject(s)
Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Hepatitis A Virus, Human/genetics , Hepatitis A/virology , Hepatitis B virus/genetics , Hepatitis B/virology , Liver Failure, Acute/virology , Acute Disease , Base Sequence , Brazil , DNA, Viral/analysis , Genotype , Hepatitis A Virus, Human/immunology , Hepatitis A/complications , Hepatitis B virus/immunology , Hepatitis B/complications , Molecular Sequence Data , Mutation , Phylogeny , Polymerase Chain Reaction , RNA, Viral/analysis , Viral LoadABSTRACT
Fulminant hepatic failure [FHF] is a devastating complication of acute viral hepatitis, leading to death in most cases. The etiology and predictors of outcome differ according to the geographical region. This study was conducted with the aim of evaluating the etiology, complications, and outcome of FHF in Bangladesh. In this prospective study, we included 67 consecutive cases of FHF presenting to the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, between November 2003 and May 2008. Thirty-nine of the patients were male and 28 were female. Data was analyzed using SPSS, version 13.0. The mean age of the subjects was 31.9 +/- 11 .7 years. Hepatitis E virus [HEV] was the commonest etiological factor for FHF [50 cases, 74.6%]; of the 50 cases with HEV infection, 43 [64.2%] were not coinfected with any other virus, four cases were Hepatitis B virus [HBV] carriers, and three had coinfection with hepatitis A virus [HAV]. HBV was the cause of FHF in nine [13.4%] patients. HCV, paracetamol, and alcohol were not responsible for any of the cases. Most of the patients [57 patients, 85%] developed FHF within 2 weeks of the onset of jaundice. Of the 67 patients, 49 [73.1%] died. Cerebral edema was the single most common cause of death [48 patients, 71.6%]. Other complications were renal failure [23 patients, 34.3%], sepsis [15 patients, 22.4%], electrolyte imbalance [12 patients 17.9%], and bleeding tendency [7 patients, 10.4%]. Occurrence of cerebral edema, longer prothrombin time, higher grade of encephalopathy, and longer jaundice-to-encephalopathy interval had significant negative influence on outcome. The etiology of FHF in Bangladesh is different from that in the West. Prolongation of prothrombin time and occurrence of cerebral edema are predictors of the worst prognosis
Subject(s)
Humans , Male , Female , Liver Failure, Acute/therapy , Liver Failure, Acute/virology , Developing Countries , Treatment Outcome , PrognosisABSTRACT
La infección por el virus de hepatitis A (HAV) es endémica en Argentina. El uso de técnicas moleculares permitió extender la detección del RNA del HAV en sueroy heces en pacientes con diferentes presentaciones clínicas. Comparamos la sensibilidad del protocolo de RT-PCR que usamos con cebadores dirigidos a distintas regiones del genoma, resultando la detección de la región VP3 C terminal la más sensible. Se obtuvieron prospectivamente muestras de suero y materia fecal de 20 niños con hepatitis aguda autolimitada por HAV. El RNA del HAV fue detectado en 18/20 niños en muestras basales y en 19/20 sumando una muestra posterior. El RNA del HAV fue detectable en 9/20 acientes hasta 30 días en suero; en materia fecal en 2/20 hasta 60 días y en 1/20 hasta 90 días. La secuencia genómica para la región VP1/2A en 8 muestras demostró que todas pertenecían al subgenotipo IA, aunque eran diferentes entre sí. Solo en 1/11 niños con falla hepatica fulminante fue posible la detección del RNA del HAV utilizando la región VP3 C terminal y el genotipo fue I. La reciente introducción de la vacunación universal en niños de 1 año de edad en Argentina podría disminuir drásticamente la circulación del virus, emergiendo nuevas fuentes de infección y permitiendo la introducción de nuevos genotipos. Las técnicas moleculares aplicadas al estudio de la historia natural de la infección y a la vigilancia epidemiológica contribuyenal control y la toma de decisiones eficientes en políticas de Salud Pública.
Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liverfailure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentinaand it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologicsurveillance may contribute to efficient control and lead to rational decisions in public health policies.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Feces/virology , Hepatitis A/diagnosis , Hepatovirus/isolation & purification , Viremia/virology , Virus Shedding , Acute Disease , Hepatitis A/complications , Hepatitis A/virology , Hepatovirus/genetics , Liver Failure, Acute/blood , Liver Failure, Acute/virology , Molecular Sequence Data , Oligonucleotide Probes , Prospective Studies , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Time FactorsABSTRACT
Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de na vacuna para HEV, actualmente en fase III.
Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples from 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys from Buenos Aires province and the third was a 3- year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains from sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEV in children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALF. Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV, presently in phase III trials.
Subject(s)
Humans , Animals , Male , Female , Infant , Child, Preschool , Child , Adolescent , Hepatitis E virus/genetics , Hepatitis E/genetics , Liver Failure, Acute/virology , Argentina , DNA Primers/genetics , Feces/virology , Genome, Viral , Genotype , Hepatitis E virus/isolation & purification , Hepatitis E/diagnosis , Liver Failure, Acute/diagnosis , Liver Failure, Acute/genetics , Pedigree , RNA, Viral/blood , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis , SwineABSTRACT
In this communication we report 46 cases of acute liver failure in children diagnosed at the Hospital Infantil Nossa Senhora da Glória in Vitória, E Santo. Serology for IgM anti-HAV, IgM anti-HBc, HbsAg, anti-HCV and biochemical tests were performed in all cases in a routine laboratory. The M/F ratio was 1.1:1 and the mean age was 4.7±3.2 years, without gender difference. Anti-HAV IgM+ in 38 (82.6 percent) cases, anti-HbcIgM+ in two (4.3 percent) cases and 6 (13.1 percent) cases were negative for all viral markers investigated. Anti- HCV+ in one anti-HAV IgM+ case. HbsAg+ in two anti-HbcIgM+ and in two HAVIgM+ cases. Among the six A, B and C negative cases, four (8.6 percent) did not have the suspected exogenous intoxication. Mortality was 50 percent, without gender or age differences. These results demonstrate that HAV infection is the main etiology of acute liver failure in children in Brazil, confirming that, although it is a self limited, relatively mild illness, it can cause serious and even fatal disease. The observation of four cases without A, B and C viral markers and no history of exogenous intoxication, agree with the observation of non A-E acute sporadic hepatitis in Northeastern Brazil