Hepatitis E and pregnancy: current state.

Hepatitis E virus (HEV) is responsible for more than 50% of acute viral hepatitis cases in endemic countries. Approximately 2 billion individuals live in hepatitis E-endemic areas and, therefore, are at risk of infection. According to World Health Organization, HEV causes about 20.1 million infections and 70 000 deaths every year. In developing countries with poor sanitation, this disease is transmitted through contaminated water and is associated with large outbreaks, affecting hundreds or thousands of people. In developed countries, autochthonous cases of HEV have been increasingly recognized in the past several years. Hepatitis E virus typically causes an acute, self-limiting illness similar to other acute viral hepatitis, such as hepatitis A or B, with about 0.2% to 1% mortality rate in the general population. However, the course of hepatitis E in pregnancy is different than the mild self-constraining infection described in other populations. During pregnancy, HEV infection can take a fulminant course, resulting in fulminant hepatic failure, membrane rupture, spontaneous abortions, and stillbirths. Studies from various developing countries have shown a high incidence of HEV infection in pregnancy with a significant proportion of pregnant women progressing to fulminant hepatitis with a fatality rate of up to 30%. The present review will highlight new aspects of the HEV infection and pregnancy.

Microbiological diagnosis of human papilloma virus infection. / Diagnóstico microbiológico de la infección por virus del papiloma humano.

Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future.

Indigenous tropical spastic paraparesis in Madrid (Spain). Experience on screening of human T-lymphotropic virus. / Paraparesia espástica tropical autóctona en la Comunidad de Madrid. Experiencia en el cribado del virus linfotrópico de células T humanas tipo I.

We have recently documented a case of tropical spastic paraparesis by HTLV-I in a Spanish patient. HTLV-I infection is rare in Europe, and hardly ever is accompanied by symptoms, but if it does it could trigger a major health issue. This case is presented here, as well as a discussion on the situations in which HTLV-I detection is justified. An analysis was made of the HTLV diagnostic requests at our centre during 2014-2015 (n=123). The diagnostic algorithm was: 1) Enzyme immunoassay, 2) Reverse hybridization, and 3) Proviral DNA detection by PCR. The results showed several situations of HTLV screening, emphasising those related to paraparesis (22%). Seven cases of HTLV-I infection were found: five in patients from endemic regions, one in an HIV-infected patient, and the case of TSP mentioned above. HTLV-I surveillance in non-endemic regions is a challenging issue, as the cost-benefit ratio is not well-established. This case report emphasises the importance of including HTLV within the differential diagnosis of insidious spastic paraparesis.

Patients infected with HIV are at high-risk for hepatitis E virus infection in Spain.

Hepatitis E virus is responsible for sporadic cases of acute, self-limited viral hepatitis not only in endemic but also in industrialized countries. In addition, some reports confirm that it can cause chronic infection and even cirrhosis in immunosuppressed and also in patients infected with HIV. There are few data about prevalence and incidence of HEV chronic infection in HIV-HEV coinfected individuals in Spain. The aim of this study is to investigate the prevalence of anti-HEV IgG in a representative sample of 448 patients infected with HIV and determine the role of age, gender, and CD4 counts in the detection of anti-HEV IgG antibodies in blood. In addition, the clinical features and ALT levels in relation to the presence of anti-HEV IgM and/or HEV-RNA in the blood of these patients were investigated. Anti-HEV IgG antibodies were detected in serum using a commercial enzyme immunoassay. All positive samples were studied further for the presence of anti-HEV IgM antibodies. In addition, HEV RNA was amplified by reverse transcriptase (RT)-nested PCR in all serum samples with IgM anti-HEV. The overall prevalence of anti-HEV IgG was 10.4% (45/448, 95% C.I. 7.2-12.8%). HEV-RNA was found in only one patient out of the 45 anti-HEV IgG positive samples studied. Regarding to gender and CD4 count, no difference in seroprevalence could be observed. This prevalence data suggest that patients infected with HIV can be considered a risk group for HEV infection and that chronic coinfection HEV-HIV seems to be a very rare event.

Hepatitis E: current status.

Acute hepatitis E is a very common disease in developing countries, to the point that, according to World Health Organization estimates, one third of the world's population has been exposed to HEV. It also causes outbreaks in refugee camps or after natural disasters such as floods or earthquakes. Sporadic cases of acute hepatitis have been observed in practically all European countries and other developed geographical areas, not only in travelers from endemic countries but also in people with no risk factors. But, lately, new aspects of this infection are appearing in industrialized countries such as the possibility of the disease becoming chronic in transplant patients, the immunocompromised in general, and even in patients with previous liver disease who are immunocompetent. In this comprehensive review, we summarize the current knowledge on HEV infection.

[HBeAg-positive chronic hepatitis B treatment with oral antiviral agents: experience and results in clinical practice]. / Tratamiento de la hepatitis crónica B antígeno e positiva con antivirales orales: experiencia y resultados en la práctica clínica.

INTRODUCTION: Due to globalization and migratory movements, HBeAg+ chronic hepatitis B is becoming increasingly important in Spain. OBJECTIVE: To analyze the epidemiological features, progression, and treatment response to oral antiviral agents (OA) in HBeAg+ chronic hepatitis B patients in our area. MATERIAL AND METHODS: We analyzed 436 patients with chronic hepatitis B infection followed up at the Ramón y Cajal Hospital from 1990 to June 2012. RESULTS: Sixty-five patients (14.9%) had HBeAg+ chronic hepatitis B. Seven patients in the immunotolerant phase were not treated, while the remaining 58 received treatment. Four patients were excluded: two due to severe acute hepatitis, one due to hepatitis C virus coinfection and another because of a Delta virus coinfection. Of the remaining 54 patients, 19 received interferon with or without OA, and 35 received only OA. Two patients treated for less than 1 month were not included in the analysis. The analysis was finally performed in 33 patients. The mean duration of treatment was 46.81 months (6-138). Lamivudine was the most frequently prescribed drug (39.39%) followed by tenofovir (24.24%) and entecavir (21.21%). The mean age was 42.08±14 years and 75.75% (25/33) of the patients were male. Nineteen of 33 patients (57.57%) achieved seroconversion to anti-HBe, and 27.27% (9/33) showed clearance of HBsAg. There was no evidence of HBsAg reversion after a mean follow-up of 35.6 months. There were 8 cases of resistance in 7 patients: 7 to lamivudine and 1 to adefovir. CONCLUSIONS: Approximately 15% of chronic hepatitis B patients in our area are HBeAg+. Treatment with OA achieves a high seroconversion rate (57.57%) and a considerable percentage of HBsAg clearance (27.27%).

Comparison of the performance of carcinogenic HPV typing of the Roche Linear Array and Qiagen LiquiChip® HPV assays.

BACKGROUND: Cervical cancer is caused by high-risk types of human papillomavirus (HPV). DNA testing of such high-risk types of HPV could improve cervical screening.The aim of the study was to compare the sensitivities and positive predictive values of two commercially available typing assays (Qiagen LQ and Roche LA) and to comparatively assess the distribution of HPV types with these two assays. METHODS: The study population comprised 311 ASCUS + women with abnormal pap tests who were HCII positive and who were admitted to three European referral gynecology clinics between 2007 and 2010 (Madrid, Marseille and Milan). All patients underwent LQ and LA tests. RESULTS: The sensitivity of the two assays for HPV typing was 94% for LQ and 99% for LA (compared with HCII). The overall concordance between LQ and LA was 93%. The three prevalent genotypes, HPV16, HPV18, and HPV31, were identified with a high concordance using the two assays: kappa 0.93, 0.83, and 0.91, respectively. Mixed genotypes were more frequently detected by LA than by LQ: 52% vs. 18%, respectively (p < .0001). CONCLUSIONS: These assays have a good clinical sensitivity for detecting HPV types in CIN2+ patients and allow the virus type to be detected in the same experiment. Our study revealed no significant difference between LQ and LA for CIN2+ or CIN3+ diagnosis, indicating similar distributions of HPV types and a mixed genotype detection that is higher for LA than for LQ.

[Acute, chronic and fulminant hepatitisE: seven years of experience (2004-2011)]. / Hepatitis agudas, crónicas y fulminantes por virus de la hepatitisE: 7años de experiencia (2004-2011).

OBJECTIVE: To study the clinical and epidemiological profiles of in 43cases of acute hepatitis, 5cases of fulminant hepatitis, and one of chronic hepatitis due to hepatitis E virus (HEV), detected over a 7-year period. PATIENTS: Forty-nine individuals (33male and 10female) treated between 2004 and 2011 in the Hospital Ramón y Cajal (Comunidad de Madrid, Spain). The diagnosis was made by the detection of IgG and IgM anti-HEV and RNA HEV in serum samples. Acute hepatitisE was defined by the presence of IgM anti-HEV and/or RNA HEV in serum, and chronic hepatitisE if the ARN was detectable more than 6months. Fulminant hepatitisE was diagnosed if encephalopathy was observed in addition to IgM anti-HEV and/or RNA HEV in serum. RESULTS: The median age was 46.67 and 49.6years in acute hepatitisE and fulminant hepatitisE, respectively. The risk factors recorded were travel to endemic areas in 13patients, 4were in contact with animals, 4suffered from hepatic steatosis due to alcohol consumption, 3consumed uncontrolled foods, and 2drank water from streams. DISCUSSION: HEV is the cause of acute self-limited hepatitis, although 36.73% of the studied cases had to be hospitalised. However a small number of patients, 10.2%, had fulminant hepatitis requiring liver transplant. Chronic hepatitisE is very infrequent in immunocompetent individuals. The increase in incidence of hepatitisE is due to the introduction of better diagnostic tests in recent years.

[Quantification of HIV-1 viral load]. / Determinación de la carga viral del VIH-1.

Quantification of the viral load of human immunodeficiency virus type 1 (HIV-1) is an essential marker for the follow-up of HIV-infected patients and for monitoring antiretroviral treatment. The current methodology used in most Clinical Microbiology Departments is semi- or fully-automated real-time PCR, which has several advantages such as a wider range of quantification, higher sensitivity (<40 copies/mL) and rapid results due to the automated extraction systems. On the whole, almost all the available commercialized platforms have these advantages in addition to correctly detecting and quantifying the different subtypes and recombinant forms of HIV-1 that can infect patients. This latter point is very troublesome due to the wide variation of this virus and the continuous appearance of unusual variants and subtypes susceptible to quantification.

[Chronic hepatitis E in an immunocompetent patient]. / Hepatitis crónica E en paciente inmunocompetente.

Hepatitis E virus (HEV) is a Herpesvirus, with four different genotypes. Genotypes 1 and 2 often cause acute hepatitis, which presents as outbreaks in endemic regions of Asia and Africa. Genotypes 3 and 4 cause sporadic cases of acute hepatitis in Europe and North America, where it is considered a zoonosis. Symptoms usually resolve spontaneously, but in recent years cases have been detected that progress to chronic liver disease mainly in immunocompromised patients (patients with solid organ transplants, lymphoma, human immunodeficiency virus, primary immunodeficiencies, and those under treatment with corticosteroids and immunosuppressive agents..). We report the case of a healthy, immunocompetent man who developed an episode of acute HEV hepatitis, which progressed to chronic liver disease with fibrosis grade III/IV in the liver biopsy within a year and half.

Current Knowledge on Hepatitis E.

Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin(®).

Hepatitis E: an emerging disease.

Currently, the infection with the hepatitis E virus represents the most frequent cause for acute hepatitis and jaundice in the world. According to WHO estimations, around two billion people, representing one third of the world's population, live in endemic areas for HEV and, therefore, are at risk of infection. In developed countries, the circulation of the virus in both human and animal (swine, boar, deer) sewage has been confirmed; however, the incidence rate is low compared to that of developing countries where outbreaks of acute hepatitis transmitted via the fecal-oral route are originated, more frequently in the flooding season or after natural disasters, combined with deficient sanitary conditions. There are currently 4 known genotypes of HEV. Genotypes 1 and 2 are isolated in all human epidemic outbreaks in developing countries, while genotypes 3 and 4 are isolated not only in humans but also in animals, in both developing and industrialized countries. These data support genotypes 3 and 4 having zoonotic nature. The diagnosis of this disease is based in the detection of anti-HEV IgG and IgM in blood serum using enzyme-linked immunosorbent methods. However, the method that best confirms the diagnosis is the RT-PCR, which detects HEV RNA in blood serum and also provides the genotype. The clinical course is generally that of an acute hepatitis which in some cases may require hospitalization and that, in transplant patients or HIV infected individuals can become a chronic hepatitis. Furthermore, the virus constitutes an important risk for pregnant women. The hepatitis E can present a wide range of symptoms, from a subclinical case to chronic liver disease with extrahepatic manifestations. For this reason, the diagnostic is challenging if no differential diagnosis is included. There is no specific antiviral drug for hepatitis E, but satisfactory results have been observed in some patients treated with pegylated interferon alfa2a and/or ribavirin. This revision is an update of all the molecular, epidemiological, clinic and preventive knowledge on this emergent disease up to date.

[Hepatitis E. Current perspectives]. / Estado actual de la hepatitis E.

Infection with hepatitis E virus (HEV) is highly prevalent in developing countries and the WHO estimates one third of the world population has had contact with the virus. Its diagnosis and epidemiology are well known in endemic countries but, recently, there have been sporadic cases in developed countries in patients with no history of travel. Currently in these countries, hepatitis E is considered a zoonosis yet there remain to be known other routes of transmission. Another interesting aspect is that HEV can cause chronic hepatitis in transplanted patients, other immunocompromised patients and even in immunocompetent people. There have also been reported cases of fulminant hepatitis and other extrahepatic manifestations. The diagnosis is based on serological studies and detection of viral RNA in blood and feces. The vaccine is a good option to prevent this infection that affects a large number of people in deprived geographical areas but unfortunately it is not available yet.

[Chronic hepatitis E]. / Hepatitis crónica E.

The hepatitis E virus is an RNA virus with 4 genotypes. Genotypes 1 and 2 only affect humans and produce epidemic acute hepatitis in endemic regions (Asia and Africa). Genotypes 3 and 4 are considered a zoonosis and produce episodic acute hepatitis in non-endemic areas (America and Europe). However, in the last 3 years there have been cases of chronic HEV hepatitis, mainly in immunosuppressed patients. Here we review the known data of chronic hepatitis E in terms of evolution and treatment.

Prevalence and Distribution of High-Risk Genotypes of HPV in Women with Severe Cervical Lesions in Madrid, Spain: Importance of Detecting Genotype 16 and Other High-Risk Genotypes.

Background. Persistent infection with high-risk human papillomavirus (HR-HPV) has been demonstrated to be the necessary causal factor for developing cervical cancer. To know the most prevalent HR-HPV in different geographical areas is important to design diagnostic tests and implementation of vaccines. Objectives. The goal of this study is to evaluate the prevalence of HR-HPV in a total of 1001 patients, 198 with normal cytology results, 498 with low-grade squamous intraepithelial lesion (LSIL), and 205 with high-grade squamous intraepithelial lesion (HSIL) who attended our gynaecology department for opportunistic screening of HPV infection. Study design. Cervical samples were taken in a PreservCyt vial (Cytyc Corporation, Boxborough, MA). Hybrid capture assay was carried out following the manufacturer's instructions (Digene Corp., Gaithersburg, MD). All samples were further studied with polymerase chain reaction (PCR) (Linear Array HPV Genotyping Test, Roche Diagnostics, Mannheim, Germany). Results. Genotype 16 was the most prevalent HR-HPV in the three groups, 17.8% in the patients with normal cytology results, 22.3% in the LSIL group, and 60% in the HSIL group. Genotype 18 had a very low prevalence in all groups. Other HR-HPV genotypes such as genotype 31, genotype 58 and genotype 52 were found in significant numbers in HSIL patients. Discussion. Our data show that genotypes 16, 31, 58, and 52 are the most prevalent HR-HPV in cervical samples with severe intraepithelial lesion in Spain. There may be some geographical variation in prevalence of carcinogenic types, and it must be considered for designing diagnostic tests and vaccine.

Fulminant hepatitis E in a woman taking oral contraceptive medication.

We describe a fulminant autochthonous hepatic failure caused by hepatitis E (HEV) in a patient admitted in our hospital for liver-transplant evaluation. The only risk factor recorded for this severe course was the use of oral contraceptives that are known to mimic a hormonal status similar to pregnancy. The diagnosis was based on the presence of IgG and IgM anti-HEV in the serum of the patient and confirmed by the isolation of a strain of HEV genotype 3f from a blood sample obtained the fourth day after hospital admission. HEV genotype 3 is present in human and swine populations in Spain. The patient began to recover while waiting for a liver transplant. To our knowledge, this is the first report of fulminant hepatitis E in a non-pregnant European patient on oral contraceptives.