Hepatitis B virus depicts a high degree of conservation during the immune-tolerant phase in familiarly transmitted chronic hepatitis B infection: deep-sequencing and phylogenetic analysis.

When intrafamilial transmission of hepatitis B virus (HBV) occurs, a virus with the same characteristics interacts with diverse hosts' immune systems and may thus result in different mutations to escape immune pressure. In this study, the HBV genomic characterization was assessed longitudinally after intrafamilial transmission using nucleotide sequence data of phylogenetic and mutational analyses, including those obtained by deep-sequencing for the first time. Furthermore, HBeAg-anti-HBe profile and variability of HBV core-derived epitopes were also evaluated. Strong evidence was obtained from intrafamilial transmission of HBV genotype D1 by phylogenetic inferences. HBV isolates exhibited high degree (~99%) of genomic conservation for almost 20 years, when patients were persistently HBeAg positive with normal amino transferase levels. This identity remained high among immune-tolerant siblings. In contrast, it diminished significantly (P = 0.02) when the mother cleared HBeAg (immune clearance phase). By deep-sequencing, the quantitative analysis of the dynamics of basal core promoter (BCP) (A1762T, G1764A; A1766C; T1773C; 8-bp deletion; and other) and precore (G1896A) variants among HBV isolates from family members exhibited differences during the follow-up. However, only those from the mother showed amino acid variations at core protein that would impair their MHC-II binding. Hence, when intrafamilial transmission occurs, HBV was highly conserved under the immune-tolerant phase, but it exhibited mutations more frequently during the immune clearance phase. The analysis of the HBV BCP and precore mutants after intrafamilial HBV transmission contributes to a better understanding of how they evolve over time.

Molecular diagnosis of polycystic echinococcosis due to Echinococcus vogeli in a Paraguayan immigrant in Argentina.

Polycystic echinococcosis due to Echinococcus vogeli is a rare parasitic infection that occurs in rural areas of Central and South America. Only molecular identification performed on formalin-fixed paraffin-embedded liver tissue samples gave an unequivocal diagnosis of this disease in a Paraguayan immigrant in Argentina.

Genotypes B and C hepatocellular carcinoma-associated hepatitis B virus pre-S mutants: their detection among F1b and A2 - but not F4 - isolates from Argentina.

Prevalence rates of hepatocellular carcinoma (HCC)-associated hepatitis B virus (HBV) pre-S mutants among most genotypes are still lacking. In this study, viral (sub)genotypes of 70 Argentine nucleotide sequences (33 newly obtained) were determined by phylogenetic analysis, and the presence of such mutants was assessed in the American continent for the first time. Nucleotide substitutions of the pre-S2 start codon were observed in 10% of the HBV/A2 sequences. Ten per cent of the HBV/A2 and 12.5% of the HBV/F1b - but none of HBV/F4 - exhibited a deletion in the pre-S1/pre-S2 region. The contribution of these variants to liver cirrhosis (LC) and/or HCC development among HBV/F and HBV/A isolates deserves further prospective clinical studies.

Hipertensión pulmonar asociada a Lupus eritematoso sistémico y embarazo / Pulmonary hypertension with systemic lupus erythematosus and pregnancy

La hipertensión pulmonar asociada es un padecimiento poco frecuente en los pacientes con lupus (LES), que por su morbimortalidad conlleva un pronóstico grave en el embarazo y posparto inmediato. El aumento de la resistencia arterial pulmonar asociado a los cambios fisiológicos cardiovasculares del fin del embarazo y del trabajo de parto generan una situación clínica de dificultoso manejo...Nuestro objetivo es presentar el caso de una paciente con LES previamente diagnosticado, en la que se desarrolla hipertensión pulmonar asociada (HPA)al final del segundo trimestre de un embarazo gemelar, que responde adecuadamente a sildenafil y evoluciona favorablemente (ella y sus dos niños) luego de realizarse cesárea programada en la semana 32.

Hipertensión pulmonar asociada a Lupus eritematoso sistémico y embarazo / Pulmonary hypertension with systemic lupus erythematosus and pregnancy

La hipertensión pulmonar asociada es un padecimiento poco frecuente en los pacientes con lupus (LES), que por su morbimortalidad conlleva un pronóstico grave en el embarazo y posparto inmediato. El aumento de la resistencia arterial pulmonar asociado a los cambios fisiológicos cardiovasculares del fin del embarazo y del trabajo de parto generan una situación clínica de dificultoso manejo...Nuestro objetivo es presentar el caso de una paciente con LES previamente diagnosticado, en la que se desarrolla hipertensión pulmonar asociada (HPA)al final del segundo trimestre de un embarazo gemelar, que responde adecuadamente a sildenafil y evoluciona favorablemente (ella y sus dos niños) luego de realizarse cesárea programada en la semana 32.(AU)

Application of ultrasound in diagnosis, treatment, epidemiology, public health and control of Echinococcus granulosus and E. multilocularis.

The last 30 years have seen an impressive use of ultrasonography (US) in many fields of veterinary and clinical medicine and the technique is being increasingly applied to a wide variety of parasitic infections including the cestode zoonoses Echinococcus granulosus and E. multilocularis. US provides real-time results which are permanently recordable with a high resolution and diagnostic accuracy. These properties, coupled with the clinical value of the images obtained and the non-invasive nature of the test which is safe, require no special patient preparation time; it is easy to operate and this has resulted in the establishment of US as the diagnostic technique of choice for cystic (CE) and alveolar (AE) echinococcosis. The lack of ionizing radiation and side-effects mean that examination times are not restricted. The hand-held probes facilitate what amounts to a rapid, bloodless non-invasive laparotomy, enabling a search from an infinite number of angles for lesions producing information on their number, size and type of cysts, their location and clinical implications. Such clinical information has facilitated the development of treatment protocols for different cyst types. Less invasive surgical techniques, such as US guidance for PAIR (Puncture, Aspiration, Injection, Re-aspiration), PAIRD (PAIR plus Drainage) or PPDC (Percutaneous Puncture with Drainage and Curettage) are also possible. Longitudinal US studies have facilitated monitoring the effects of the outcome of treatment and chemotherapy. Portable ultrasound scanners which today weigh as little as a few pounds, powered by battery or generators have facilitated the use of the technique in mass community-based screening studies. The majority of these studies have been conducted in remote, low socio-economic areas where there were few, if any, hospitals, veterinary facilities, schools or trained personnel. The surveys led to the discovery of unexpectedly high prevalences of CE and AE in asymptomatic individuals of endemic areas and especially amongst transhumant or nomadic pastoralists living in various parts of the world. Screening for CE and AE is justified as an early diagnosis leads to a better prognosis following treatment. The application of US in field and clinical settings has led to a better understanding of the natural history of CE and AE and to the development of a WHO standardized classification of cyst types for CE. This classification can be used in helping define the treatment options for the different cysts found during the surveys, which in turn can also be used to calculate the public health cost of treating the disease in an endemic community. The case mix revealed can also influence the specificity (particularly proportions of cyst types CE4 and CE5 and cystic lesions--CL) of US as a diagnostic test in a particular setting. Community based US surveys have provided new insights into the public health importance of CE and AE in different endemic settings. By screening whole populations they disclose the true extent of the disease and reveal particular age and sex risk factors. Through the treatment and follow-up of all infected cases found during the mass screening surveys a drastic reduction in the public health impact of the disease in endemic communities can be achieved. Educational impacts of such surveys at the national, community and individual levels for both professional and lay people are beginning to be appreciated. The translation of the information gained into active control programmes remains to be realized. In areas where intermediate hosts, such as sheep and goats, are not slaughtered in large numbers mass US screening surveys to determine the prevalence of CE in livestock has proved possible. Longitudinal studies in such intermediate hosts would reveal changes in prevalence over time, which has been used as a marker for control success in other programmes. Mass US screening surveys in an ongoing control programme in Argentina has demonstrated the early impact of control in the human population and identified breakthroughs in that control programme. Mass US screening surveys must adhere to the highest ethical standards and the outcome of surveys should result in the application of appropriate WHO recommended treatment options for different cyst types. Follow-up strategies have to be in place prior to the implementation of such surveys for all infected individuals who do not require treatment and for all suspected, but not confirmed, cases found during the surveys. The use of US in community screening surveys has revealed the complexity of ethical issues (informed consent, confidentiality, follow-up, detection of lesions that are not the focus of the study etc) and also provided real solutions to providing the most ethical guidelines for the early detection and treatment of CE and AE.

Epidemiological surveillance of human hydatidosis by means of ultrasonography: its contribution to the evaluation of control programs.

Epidemiological surveillance for hydatidosis is based on initial determination and follow-up of the infestation rate in man, sheep and dogs. The use of ultrasonography (US) as a screening method has demonstrated its usefulness in detecting asymptomatic human carriers of abdominal hydatidosis. To evaluate the contribution of US to epidemiological surveillance within the framework of disease control programs, we performed 719 US studies in school children from 7 to 13 years of age, in rural areas of Río Negro, Argentina, subjected to canine deparasitization during 1984/1986 and 1997/1998. In the first period, 15/268 (5.6%), while in the second, 5/451 (1.1%) carriers were detected (P < 0.0004). The average diameter of the cysts was 4.71 cm in 1984/1986 and 2.14 in 1997/1998. US as a mass screening method allows evaluation of early changes in human prevalence rates, closely related to infestation rates in sheeps and dogs, thus providing a sensitive indicator of the evaluation of control programs.

Combined therapy with interferon and ribavirin in chronic hepatitis C does not affect serum quasispecies diversity.

Our aim was to investigate if interferon plus ribavirin has any effect on serum HCV quasispecies distribution and the relationship between diversity of HCV quasispecies and treatment response. In all, 21 patients were treated with interferon plus ribavirin for 48 weeks. The presence of HCV quasispecies was determined in serum samples at baseline and at the fourth week of treatment by SSCP analysis of the hypervariable region. SSCP pattern was defined as single or multiple band. A single band was found in six patients and multiple bands in nine. No significant difference was found between SSCP pattern in pretreatment samples and response to the therapy. In none of the patients were observed changes in number of SSCP bands between samples taken at baseline and in the fourth week of the therapy. In conclusion, the complexity of HCV quasispecies before the therapy was not related to treatment response; combined therapy did not affect serum HCV quasispecies.

Development of cutaneous sarcoidosis in a patient with chronic hepatitis C treated with interferon alpha 2b.

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology that most commonly affects young adults. A probable induction of sarcoidosis by interferons (IFN) has been published. To this date, few cases of cutaneous sarcoidosis inpatients with chronic hepatitis C under interferon treatment have been reported. OBJECTIVE: We describe a 50-year-old woman with chronic hepatitis C who developed lesions of cutaneous sarcoidosis three months after IFN treatment. CONCLUSIONS: The possible role of INF therapy in the development of cutaneous sarcoidosis in a patient with chronic hepatitis C should be considered.

Human cystic echinococcosis: contributions to the natural history of the disease.

In areas where human cystic echinococcosis (CE) is endemic, the results of ultrasonographic or X-ray examinations have revealed a surprisingly high prevalence of abdominal cysts in asymptomatic individuals. The results of preliminary studies indicate that the ratio of liver infection:lung infection (LI:LU) is much higher in the asymptomatic individuals (9:1 or 7:1) than is usual among symptomatic cases of liver CE (2:1). This difference may indicate that, compared with lung cysts, liver cysts rarely cause morbidity, perhaps because they grow at a slower rate than those in the lungs. In an attempt to explore this possibility, the published results of ultrasonographic and radiological surveys on general populations and the records of autopsies and hospital-based investigations of symptomatic cases of liver CE were reviewed. In general populations, the overall prevalence of cysts in the liver (2.5%) was found to be much higher than that of cysts in the lungs (0.3%), giving a LI:LU ratio of 8.3:1. In the symptomatic cases, however, LI:LU ratios were only 2.5:1 (based on hospital records) or 4.1:1 (based on autopsy records). In addition, the estimated mean growth rate of the cysts in 53 surgical cases of CE from the province of Río Negro in Argentina was found to be significantly higher than that of the cysts in 89 asymptomatic cases detected during ultrasonographic surveys in the same area.

[Pancreatic tumor: an unusual presentation of an occult breast carcinoma]. / Tumor de páncreas: presentación infrecuente de un carcinoma de mama oculto.

A case of cholestasis due to a synchronous pancreatic head metastasis from an occult lobular breast carcinoma is presented. The patient had a clinical and radiological picture compatible with a pancreatic head primary tumor with cholestasis and ascites. Ultrasonographically guided fine needle aspiration cytology demonstrated a metastatic breast lobular cancer (positive for cytokeratin AE1 and AE3, cytokeratin 7 and epithelial membrane antigen and negative for cytokeratin 20, CA 19.9, CA 125, CEA and estrogenic receptors). The same cytologic findings were observed in skin and subcutaneous armpit nodules. Clinical and radiological breast examination was unable to demonstrate any tumor in the breast. Pancreatic metastases are rare events and the majority of them are secondary to renal and lung cancer and rarely to breast cancer. In these latter cases, metastases are usually disclosed after a disease-free interval of months or years between primary tumor resection and recognition of the pancreatic tumor. Synchronous presentation is extremely rare. Metastases of epithelial origin are uncommon in pancreas and generally are first misdiagnosed as primary pancreatic cancer. Fine needle aspiration is a useful tool for the differential diagnosis in patients with widespread disease.

Tumor de páncreas: presentación infrecuente de un carcinoma de mama oculto / Pancreatic tumor: an unusual presentation of an occult breast carcinoma

Se presenta un caso de tumor de cabeza de páncreas con colestasis debido a una metástasis de un carcinoma lobular oculto de mama. El cuadro es interpretado inicialmente como un carcinoma de páncreas diseminado, con ascitis, colestasis e implantes peritoneales. La biopsia de lesiones de piel y celular subcutánea que resultan en metástasis de carcinoma lobular de mama, confirmado con inmunomarcación (positiva para citoqueratinas clon AE1 y AE3, citoqueratina 7 y antígeno epitelial de membrana y negativa para citoqueratina 20, CA 19.9, CA 125, CEA y receptores estrogénicos) hacen a la presunción de metástasis pancreática. Ésta presunción se confirma mediante PAAF ecoguiada. Las metástasis en páncreas de tumores primitivos de origen epitelial son infrecuentes y en general se presentan como imágenes nodulares indistinguibles de los tumores primitivos. Se observan habitualmente en casos de diseminación masiva por carcinoma de riñon o de pulmón siendo raras las metástasis de carcinoma de mama, las cuales se presentan habitualmente con el antecedente de cáncer de la misma. El diagnóstico del tumor pancreático debe ser efectuado por anatomía patológica. Este es un caso atípico en su forma de presentación, dada la aparición de colestasis debida a un tumor metastático a nivel de cabeza de páncreas sincrónico con un carcinoma lobular de mama oculto.

Tumor de páncreas: presentación infrecuente de un carcinoma de mama oculto / Pancreatic tumor: an unusual presentation of an occult breast carcinoma

Se presenta un caso de tumor de cabeza de páncreas con colestasis debido a una metástasis de un carcinoma lobular oculto de mama. El cuadro es interpretado inicialmente como un carcinoma de páncreas diseminado, con ascitis, colestasis e implantes peritoneales. La biopsia de lesiones de piel y celular subcutánea que resultan en metástasis de carcinoma lobular de mama, confirmado con inmunomarcación (positiva para citoqueratinas clon AE1 y AE3, citoqueratina 7 y antígeno epitelial de membrana y negativa para citoqueratina 20, CA 19.9, CA 125, CEA y receptores estrogénicos) hacen a la presunción de metástasis pancreática. Esta presunción se confirma mediante PAAF ecoguiada. Las metástasis en páncreas de tumores primitivos de origen epitelial son infrecuentes y en general se presentan como imágenes nodulares indistinguibles de los tumores primitivos. Se observan habitualmente en casos de diseminación masiva por carcinoma de riñon o de pulmón siendo raras las metástasis de carcinoma de mama, las cuales se presentan habitualmente con el antecedente de cáncer de la misma. El diagnóstico del tumor pancreático debe ser efectuado por anatomía patológica. Este es un caso atípico en su forma de presentación, dada la aparición de colestasis debida a un tumor metastático a nivel de cabeza de páncreas sincrónico con un carcinoma lobular de mama oculto. (Au)

Tumor de páncreas: presentación infrecuente de un carcinoma de mama oculto. / [Pancreatic tumor: an unusual presentation of an occult breast carcinoma]

A case of cholestasis due to a synchronous pancreatic head metastasis from an occult lobular breast carcinoma is presented. The patient had a clinical and radiological picture compatible with a pancreatic head primary tumor with cholestasis and ascites. Ultrasonographically guided fine needle aspiration cytology demonstrated a metastatic breast lobular cancer (positive for cytokeratin AE1 and AE3, cytokeratin 7 and epithelial membrane antigen and negative for cytokeratin 20, CA 19.9, CA 125, CEA and estrogenic receptors). The same cytologic findings were observed in skin and subcutaneous armpit nodules. Clinical and radiological breast examination was unable to demonstrate any tumor in the breast. Pancreatic metastases are rare events and the majority of them are secondary to renal and lung cancer and rarely to breast cancer. In these latter cases, metastases are usually disclosed after a disease-free interval of months or years between primary tumor resection and recognition of the pancreatic tumor. Synchronous presentation is extremely rare. Metastases of epithelial origin are uncommon in pancreas and generally are first misdiagnosed as primary pancreatic cancer. Fine needle aspiration is a useful tool for the differential diagnosis in patients with widespread disease.

Identification of 2 novel isolates of hepatitis E virus in Argentina.

Hepatitis E virus (HEV) has been identified in 2 Argentine patients with acute hepatitis who reported no history of travel to regions in which HEV is considered endemic. These isolates are the first to be identified in South America. By use of degenerate primers from open reading frames 1 and 2, HEV sequences were obtained from these patients' serum and compared with published HEV sequences. The Argentine isolates are different from all previously identified HEV isolates and are most closely related to each other. The Argentine isolates are distinct from the most geographically related isolate from Mexico as well as isolates from other endemic (China, Southeast Asia, and India) and nonendemic (the United States and Europe) regions. Phylogenetic analysis indicate that the Argentine isolates represent a new genotype of HEV, genotype 8, distinct from the Burmese-like genotype 1, Mexican genotype 2, US genotype 3, Chinese/Taiwan genotype 4, and European genotypes 5-7.

[Asymptomatic carriers of hydatidosis: epidemiology, diagnosis, and treatment]. / Portadores asintomáticos de hidatidosis: epidemiología, diagnóstico y tratamiento.

Until a short time ago, hydatidosis was considered a pathology that could only be resolved surgically. However, in recent years progress has been made with the epidemiology, diagnosis, and treatment of the disease, and new information on the natural history of hydatidosis has helped define new criteria for its treatment. It is now known that as many as 67% of the carriers of liver cysts who are asymptomatic remain so throughout their lives. This situation produces special results in immunologic testing. Enzyme-linked immunosorbent assay (ELISA) has a sensitivity of 63% and a specificity of 97% with asymptomatic carriers, while the double diffusion arc 5 test (DD5) achieves a sensitivity of only 31% with the same population. On the other hand, imaging studies based on ultrasonography have become the method of choice to detect asymptomatic carriers. Ultrasonography studies are 49% to 73% more sensitive than serological tests, and they can even be used as a part of epidemiological surveillance systems and to monitor control programs. Treatment schemes have also been modernized. Treating asymptomatic carriers chemotherapeutically with albendazole produces favorable results in as many as 69% of cases, while such minimally invasive surgical treatments as puncture-aspiration-injection-reaspiration (PAIR) reduce average cyst volume by as much as 66%. These factors have made it possible for hospital services in the province of Río Negro, Argentina, to establish a treatment scheme for asymptomatic carriers. It is based on the monitoring of small cysts (type Ia on the modified Gharbi scale); initial treatment with albendazole, followed by PAIR if there is no response, in larger or more complex cysts (types Ib, II, and III); and follow-up of inviable or dead cysts (types IV and V).

Relationship between diversity of hepatitis C quasispecies and histological severity of liver disease.

The aim of this work was to assess if the diversity of hepatitis C virus (HCV) quasispecies is related to histological severity and duration of infection in a cohort of untreated patients with an estimated onset of the disease. A total of 27 patients with diagnosis of chronic liver disease and history of blood transfusion (n = 16) or intravenous drug use (IDU) (n = 11) were included. All were anti-HCV positive and had detectable serum HCV-RNA. The onset and the duration of the disease were estimated from the time of the transfusion or the first drug injection. Patients who consumed drugs for more than 2 years, or were coinfected with HBV or HIV were excluded. History of alcohol intake (> 80 g/day), ALT level and age at infection were recorded. Histological assessment of grading and staging was performed according to Knodell score. The quasispecies diversity was investigated by single strand conformation polymorphism (SSCP) targeted to HVR-E2 region and SSCP pattern was evaluated as a single or multiple bands. The number of quasispecies did not correlate with the estimated duration of the disease. Patients who acquired hepatitis C by blood transfusion did not differ in number of bands from patients who were IDU. There was no correlation between the heterogeneity of HCV quasispecies and age, serum ALT, Knodell score, HAI and fibrosis. In conclusion the quasispecies diversity of E2 had no correlation with grade and stage of chronic HCV infection and the presence of quasispecies was independent of the duration of the disease.

Diagnosis of human hydatidosis. Predictive value of a rural ultrasonographic survey in an apparently healthy population.

The usefulness of ultrasonography (US) in the early diagnosis of hydatidosis, applied in large-scale surveys to populations lacking clinical symptoms of the disease, has been amply documented. However, the rate of false positive and negative results is poorly described. Due to this, the present paper is aimed to evaluate the sensitivity, specificity and predictive value of a conventional rural ultrasonographic survey in comparison with higher imaging complexity. Accordingly, during 1997 and 1998 a total of 1054 children from 7 to 14 years of age were evaluated by means of US, in the town of Ingeniero Jacobacci, Province of Rio Negro, Argentina, employing a portable device for population studies. All detected cases were referred to a high complexity center specialized in imaging diagnosis for their re-evaluation with US, CT scanning and X-rays. A control group comprising 3 children negative by US for each positive case in the mass screening survey was selected and reexamined by US and X-rays and CT scanning in doubtful situations. Twenty-seven asymptomatic carriers were referred with images compatible with hydatid cysts, while 66 were classified as disease free. At reexamination, 24 of those diagnosed as carriers and the totality of those classified as healthy were confirmed. On the basis of our results, a sensitivity of 100%, a specificity of 95.6% and a global test value of 96.7% were estimated.