Jean-Marie Péron

Hepatitis E Virus and Chronic Hepatitis in Organ-Transplant Recipients

Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.

Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease

Background  Hepatic venous pressure gradient (HVPG) is a prognostic marker in patients with cirrhosis. Transient elastography measures liver stiffness (LS).

Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and In Vivo

Background Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation. Principal Findings Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth. Conclusion These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.

Hepatitis E Virus Genotype 3 Diversity, France

We characterized 42 hepatitis E virus (HEV) genotype 3 strains from infected patients in France in 3 parts of the genome and sequenced the full-length HEV genotype 3f genome found in Europe. These strains are closely related to swine strains in Europe, which suggests zoonotic transmission of HEV in France.

Acute hepatitis E in south-west France over a 5-year period

BACKGROUND Hepatitis E was found in people living in industrialized countries who had not travelled to highly endemic areas. OBJECTIVES To study the cases of acute hepatitis E confirmed thanks to viral genomic detection over a 5 years period in south-west France. STUDY DESIGN 62 cases of hepatitis E were identified between 2003 and 2007. Their demographic, clinical, and virological features were analyzed. RESULTS Cases of acute hepatitis E occurred regularly throughout this period. No seasonal variation was found. Patients, usually male (sex ratio=1.95), were adults living in both urban and rural areas. Sixty (96.8%) patients had not travelled abroad during the 6 months before diagnosis. Clinical manifestations ranged from asymptomatic infection to severe hepatitis. HEV was genotyped in 55 specimens. All the patients who had not travelled abroad were infected with genotype 3. CONCLUSION The incidence of hepatitis E in south-west France was stable from 2003 to 2007, 96.8% of the cases were autochthonous. There was an age-related increase in the disease and patients tended to be men. The predominant genotype and subtype was 3f. However, contaminations pathways involved in hepatitis E in our area remain to clarify.

Hepatitis E virus excretion can be prolonged in patients with hematological malignancies.

BACKGROUND Hepatitis E virus (HEV) is transmitted via the fecal-oral route and locally acquired sporadic hepatitis E can occur in Western countries. Chronic hepatitis E virus infections have been recently described in solid organ transplant recipients. There is little data on the evolution of hepatitis E in patients immunocompromised for other reasons. OBJECTIVES The aim of this study was to evaluate the clinical course of hepatitis E in patients immunocompromised because of hematological malignancies. STUDY DESIGN Starting on November 2003, all patients in the Toulouse University Hospital Hematology Department with unexplained elevated transaminases were tested for hepatitis E using viral RNA detection in serum or stools and serology. RESULTS Acute hepatitis E was diagnosed in six middle-aged hematology patients. All cases were autochthonous. HEV strains were genotype 3. All patients had a significant increase of transaminases (6-95 upper limit normal) and only two had HEV IgG. Five patients were asymptomatic and one had jaundice. Transmission of HEV occurred between two patients who had overlapping stays in the hematology ward. All five evaluable patients ultimately cleared their HEV but viremia was prolonged over 6 months in three patients and specific treatment had to be postponed in two patients. CONCLUSION Screening for HEV should be carried out routinely in hematology patients with elevated transaminases, and patient-to-patient transmission is a concern. Further studies are required to determine whether management of malignancy, particularly stem-cell transplantation should be adapted to HEV status.

Hepatitis E is an autochthonous disease in industrialized countries

OBJECTIVES Hepatitis E virus (HEV) is responsible for acute hepatitis predominantly in developing countries. In Western Europe and in the US, cases of acute HEV infection are uncommon and occur primarily in travelers returning from endemic countries. The aim of this study was to describe patients with acute hepatitis E in South West France and compare them with patients with acute hepatitis A. METHODS 23 consecutive patients over 13 months were analysed. Acute hepatitis E was diagnosed on the presence of specific serum antibodies or viral RNA detection in serum or stools. Real time PCR products from viraemic patients were sequenced. RESULTS All the HEV sequences belonged to genotype 3. Two patients (8%) died during their hospital stay, both suffered from severe underlying disease. Only 3 patients (13%) had travelled outside of Europe, within 3 months of the onset of disease. When compared to 23 patients with acute hepatitis A at the same hospital and during the same time frame, HEV-infected patients were older (54.4 +/- 16.6 vs 24.5 +/- 16.6, P<0.05), had lower ALT levels (55.4 X upper normal limit +/- 48.6 vs 107.8 X upper normal limit +/- 82.8, P<0.05) and had lower incidence of recent travel outside of Europe (13% in the hepatitis E group vs 60% in the hepatitis A group, P<0.05). CONCLUSIONS Hepatitis E can be considered an autochthonous infection in South West France. All strains sequenced were related to genotype III. When compared to hepatitis A, HEV-infected patients were older, had lower ALT levels and had a lower incidence of travel outside of Europe.

Good Performance of Immunoglobulin M Assays in Diagnosing Genotype 3 Hepatitis E Virus Infections

ABSTRACT We have evaluated three anti-hepatitis E virus (anti-HEV) immunoglobulin M (IgM) assays, the EIAgen HEV IgM assay (Adaltis), the HEV IgM enzyme-linked immunosorbent assay 3.0, and the Assure HEV IgM rapid test (MP Diagnostics), for the routine detection of acute genotype 3 HEV. Their sensitivities were fairly good (90%, 88%, and 82%), and their specificities were excellent (100%, 99.5%, and 100%).

Acute autochthonous hepatitis E in western patients with underlying chronic liver disease: a role for ribavirin?

further observation and evaluation. Unfortunately, the objective parameters before discharge such as Post-Anesthetic Discharge Scoring System or Aldrete scoring system were not used. The long term follow up and side effects related to sedation were not done in our study. Regarding the hypoxemia events, all the subjects received supplementary oxygen by nasal prongs. The hypoxemia events, which were slight and transient, were noticed only in the cirrhotic group. The statement that this group might be more prone to develop desaturation could be true, albeit, with no statistical significance. The American Society of Anesthesiologists Physical Status (ASA) score was not calculated, although, this parameter may influence the recovery time [2]. In conclusion, we agree that it is better and safer to apply a multiple psychometric tests before discharging, but this can offset the advantage of the reduced recovery time in patients sedated with propofol. Longer follow up period can easily be taken even by a phone call 1–2 days after the procedure. According to this approach, MHE can be diagnosed and treated rapidly. Finally, a discharge from the hospital at 2 h post endoscopy seems to be very safe [3]. Conflict of interest

Performance of anti-HEV assays for diagnosing acute hepatitis E in immunocompromised patients

Hepatitis E virus is an emerging concern in immunocompromised patients, who may become chronically infected. This prompted us to assess the performance of two anti-HEV IgG and IgM assays for diagnosing acute HEV infections. The specificities of the assays were estimated by testing samples from 2 to 3 year-old French children and blood donors and their sensitivities by testing 40 immunocompromised patients acutely infected. Both anti-HEV IgM assays were highly specific (99.6% and 100%). The sensitivity of the Adaltis was 87.5%, and that of Wantai was 85%. The specificities of anti-HEV IgG Wantai (97.8%) and Adaltis tests (89.5%, p=0.1) were similar but the Wantai test was more sensitive (45%) than the Adaltis test (15%, p<0.001). None of the samples was anti-HEV IgM negative and IgG positive. We conclude that these anti-HEV IgM assays performed well in immunosuppressed subjects with acute hepatitis E and can be used as first line virological tools. Testing for anti-HEV IgG and IgM simultaneously at the acute phase did not improve the diagnostic performance. In contrast, molecular detection of HEV RNA appears essential to exclude an HEV infection in patients who are negative for anti-HEV IgM and to assess the evolution of hepatitis E 3 months thereafter.