Occurrence of cytomegalovirus hepatitis in liver transplant patients

The differential diagnosis of liver dysfunction after orthotopic liver transplantation can be difficult. Cytomegalovirus (CMV) hepatitis is one possibility. This report reviews our experience with 17 cases of pathologically proven CMV hepatitis following liver transplantation and demonstrates the need for percutaneous liver biopsies to establish the diagnosis. There were seven pediatric patients (ages 2–11 years, five males, two females) and ten adult patients (ages 17–53 years, eight males, two females). The most common symptoms were prolonged fever (15 patients, with a mean duration of 22 ± 5.5 days), elevation in total bilirubin (14 patients), and elevation in liver enzymes (15 patients); all symptoms were also found in rejection. Leukopenia and thrombocytopenia, reported to frequently occur with CMV infection, were found in only three and five patients, respectively. Twelve patients with the above symptoms underwent percutaneous biopsy on one or more occasions to differentiate CMV hepatitis from rejection. The diagnosis was made at retransplantation in five patients. CMV hepatitis followed treatment for acute rejection in 14 patients and occurred without additional immunosuppression in three patients. All patients were maintained on cyclosporine and prednisone. Acute rejection episodes were treated with a 5‐day tapering dose of steroids (17 courses in 12 patients), OKT3 monoclonal antibody [Ortho (4 patients)] antithymocyte globulin [Upjohn (2 patients)], and azathioprine (1 patient). CMV was isolated from urine (nine patients), blood (nine patients), throat (seven patients), lungs (two patients), and other organs (two patients). CMV was cultured from the liver biopsy specimens in five of the seven attempts in pediatric patients. When the diangosis was confirmed in the absence of rejection, immunosuppression was routinely lowered. When rejection occurred concomitantly with CMV hepatitis, therapy had to be individualized. Retrospectively, three patients treated for rejection were noted at retransplantation to have only CMV hepatitis, and all three paients died. A high index of suspicion and the judicioususe of liver bopsies is essential in order to differentiate CMV hepatitis from other causes of posttransplant liver dysfunction. Copyright © 1988 Wiley‐Liss, Inc., A Wiley Compan

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland

We investigated trends in first time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991 2006. We identified new cases of HCC through record linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI):0.9 11.6%, P¼0.021). The adjusted relative risk of HCC was greater for males (hazard ratio¼2.7, 95% CI: 1.7 4.2), for those aged 60 years or older (hazard ratio ¼2.7, 95% CI: 1.9 4.1) compared with 50 59 years, and for those with a previous alcohol related hospital admission (hazard ratio¼2.5, 95% CI: 1.7 3.7). The risk of individuals diagnosed with HCV developing HCC was greatlyincreased compared with the general Scottish population (standardised incidence ratio¼127, 95% CI: 102 156). Owing to the advancing age of the Scottish HCV diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system

Safety and Immunogenicity of a New Trivalent Inactivated Split-virus Influenza Vaccine in Healthy Korean Children: A Randomized, Double-blinded, Active-controlled, Phase III Study

We report results of a randomized, double-blinded, active-controlled, phase III study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (GC501) manufactured by the Green Cross Corporation in Korea. A total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either GC501 or control. Of the GC501 recipients, seroconversion occurred in 48.5% for A/H1N1, 67.7% for A/H3N2 and 52% for influenza B. The proportion of subjects who had post-vaccination hemagglutination-inhibition titers of 1:40 or greater was 90.7% for A/H1N1, 86.8% for A/H3N2 and 82.4% for influenza B in the GC501 recipients. No serious adverse events related to vaccination, or withdrawals because of adverse events were reported. The majority of solicited adverse events were mild in intensity. GC501 vaccine has good tolerability and favorable immunogenicity in children aged 6 months to < 18 yr. The addition of one more brand of influenza vaccine may allow for better global accessibility of vaccine for epidemics or future pandemics

Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009

<p>Abstract</p> <p>Background</p> <p>Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis.</p> <p>Methods</p> <p>Between 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing - at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms.</p> <p>Results</p> <p>237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted.</p> <p>Conclusions</p> <p>Post-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.</p

Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species

BACKGROUND: Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. METHODS: A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. RESULTS: There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. CONCLUSION: Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC

Reassortment and Mutations Associated with Emergence and Spread of Oseltamivir-Resistant Seasonal Influenza A/H1N1 Viruses in 2005–2009

A dramatic increase in the frequency of the H275Y mutation in the neuraminidase (NA), conferring resistance to oseltamivir, has been detected in human seasonal influenza A/H1N1 viruses since the influenza season of 2007–2008. The resistant viruses emerged in the ratio of 14.3% and quickly reached 100% in Taiwan from September to December 2008. To explore the mechanisms responsible for emergence and spread of the resistant viruses, we analyzed the complete genome sequences of 25 viruses collected during 2005–2009 in Taiwan, which were chosen from various clade viruses, 1, 2A, 2B-1, 2B-2, 2C-1 and 2C-2 by the classification of hemagglutinin (HA) sequences. Our data revealed that the dominant variant, clade 2B-1, in the 2007–2008 influenza emerged through an intra-subtype 4+4 reassortment between clade 1 and 2 viruses. The dominant variant acquired additional substitutions, including A206T in HA, H275Y and D354G in NA, L30R and H41P in PB1-F2, and V411I and P453S in basic polymerase 2 (PB2) proteins and subsequently caused the 2008–2009 influenza epidemic in Taiwan, accompanying the widespread oseltamivir-resistant viruses. We also characterized another 3+5 reassortant virus which became double resistant to oseltamivir and amantadine. Comparison of oseltamivir-resistant influenza A/H1N1 viruses belonging to various clades in our study highlighted that both reassortment and mutations were associated with emergence and spread of these viruses and the specific mutation, H275Y, conferring to antiviral resistance, was acquired in a hitch-hiking mechanism during the viral evolutionary processes

Epidemiological Characteristics of 2009 (H1N1) Pandemic Influenza Based on Paired Sera from a Longitudinal Community Cohort Study

Steven Riley and colleagues analyze a community cohort study from the 2009 (H1N1) influenza pandemic in Hong Kong, and found that more children than adults were infected with H1N1, but children were less likely to progress to severe disease than adults