Acoustic radiation force impulse (ARFI) imaging with Virtual Touch Tissue Quantification in liver disease associated with cystic fibrosis in children

Purpose

Cystic-fibrosis-associated liver disease (CFLD) may lead to portal hypertension (PHT) and cirrhosis. Clinical signs and biochemistry of liver involvement are not discriminating. The aim of the study was to evaluate the performance of acoustic radiation force impulse (ARFI) with virtual tissue quantification in comparison with clinical signs, biochemistry and standard hepatic ultrasound (US) patterns.

Materials and methods

Virtual Touch Tissue Quantification, an implementation of US ARFI with shear-wave velocity (SWV) measurements was used in 75 children with cystic fibrosis (CF) and suspected CFLD to quantify hepatic stiffness. In each patient, ten measurements of SWV were performed on the right hepatic lobe. Patients were also evaluated by standard diagnostic tools (standard US, liver- and lung function tests, oesophagogastroscopy).

Results

Among CF patients, median SWV was significantly higher in patients with clinical, biochemical and US signs of hepatic involvement than in patients without US evidence of liver disease 1.08 m/s [(95% confidence interval (CI), 1.02?C1.14]. Median SWV values in patients with portal hypertension, splenomegaly and oesophageal varices were 1.30 (95% CI, 1.17?C1.43), 1.54 (95% CI, 1.32?C1.75) and 1.63 (95% CI, 1.26?C1.99), respectively. Differences were significant (p<0.001).

Conclusions

ARFI is an innovative screening technique able to help identify CFLD in children.     

Evidence for the transmission of parvovirus B19 in patients with bleeding disorders treated with plasma‐derived factor concentrates in the era of nucleic acid test screening

BACKGROUND: Parvovirus B19 (B19V) is a small, nonenveloped virus that typically causes a benign flu‐like illness that occurs most frequently in childhood. The virus is resistant to current viral inactivation steps used in the manufacture of antihemophilic factor concentrates and B19V transmission through these products has been documented. Since 2000, B19V nucleic acid test (NAT) screening of plasma pools has been implemented to further decrease the viral burden in these products, but no study has examined populations using these products to assess the impact of the screening on B19V transmission. STUDY DESIGN AND METHODS: Blood specimens obtained from participants of a surveillance system established in federally supported specialized bleeding disorders clinics were used in a B19V seroprevalence study. RESULTS: A total of 1643 specimens from 1043 participants age 2 to 7 years born after B19V NAT screening was implemented were tested. Age‐specific prevalence rates were generally higher for subjects exposed to either plasma‐derived products alone or in combination with other products compared to subjects with no exposure to antihemophilic products. Overall, compared to participants unexposed to blood or blood products, those exposed to plasma‐derived products alone were 1.7 times more likely to have antibodies to B19V (p = 0.002). CONCLUSION: These results are consistent with continued B19V transmission through plasma‐derived factor concentrates. Effective viral inactivation and detection processes are needed to protect users of these products from infection with B19V or other new or emerging viruses.     

Optimizing factor prophylaxis for the haemophilia population: where do we stand?

Summary. The hallmark of severe haemophilia, defined as a circulating level of factor (F) VIII (haemophilia A cases) or FIX (haemophilia B cases) of < 1%, is recurrent bleeding into muscles and joints (haemarthroses) from an early age of life. The inevitable result of such bleeding is progressive joint damage, leading to disabling arthritis that is typically evident within the first 2 decades of life in people with haemophilia who have limited or no access to regular factor replacement therapy, or those in whom factor replacement therapy is ineffective because of the presence of high‐titre inhibitors. For children with severe haemophilia and no evidence of inhibitors, the unwanted musculoskeletal complications of severe haemophilia can be effectively prevented by the early initiation of a programme of long‐term factor prophylaxis. In order to achieve the best outcome (a perfect musculoskeletal status for age) the programme of prophylaxis should be started before the onset of joint damage (primary prophylaxis). The gold standard primary prophylaxis regimen (the Malmö protocol) was pioneered and tested in Sweden and involves the infusion of 20–40 IU of FVIII per kg body weight on alternate days (minimum three times per week) for haemophilia A cases, and 20–40 IU kg^?1 of FIX twice weekly for haemophilia B cases. This protocol is, however, demanding on peripheral veins and very expensive. Modifications of the parent protocol such as starting primary prophylaxis with once‐weekly infusions via peripheral veins with rapid escalation to full‐dose prophylaxis or dose escalation based on frequency of bleeding are increasingly implemented in haemophilia treatment centres in countries that can afford the high cost of such programmes. These modified programmes can be achieved in the majority of young children with severe haemophilia without the need for central venous access devices (e.g. Port‐a‐Caths) and with avoidance of device‐associated complications such as infection and thrombosis. In at least one centre, experience with arteriovenous fistulae as a strategy to ensure reliable venous access is being accumulated. The issues of compliance (adherence) to recommended prophylaxis protocols and when, if ever, to stop a programme of primary prophylaxis once started are real and require ongoing prospective studies. Such studies should incorporate outcome measures such as health‐related quality‐of‐life and economic analyses.     

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

Aims/hypothesis The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing bilio-pancreatic diversion (BPD).Subjects and methods We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic–hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52±7 kg/m², mean±SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery.Results BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341±79 ml min⁻¹ m⁻², post-BPD 511±57 ml min⁻¹ m⁻², lean 478±49 ml min⁻¹ m⁻²). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min⁻¹ m⁻² l mmol⁻¹, median [interquartile range]) compared with lean subjects (82 [98]; p≤0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r ²=0.67, partial r=−0.76 and −0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement.Conclusions/interpretation Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity.     

Extragenital lichen sclerosus and atrophicus treated with topical steroids and retinoids in a child with vitiligo

Lichen sclerosus and atrophicus (LSA) most commonly affects the anogenital region. Extragenital involvement is rare, and women are reported to be affected 6 to 10 times more often than men. The aetiology of LSA is unclear, but genetic, physiological and environmental factors are thought to be involved. Several lines of evidence support the hypothesis of an autoimmune basis for LSA; an increased incidence of tissue-specific antibodies and an association with autoimmune disorders such as vitiligo, alopecia areata, thyroid disease and pernicious anaemia have been reported. We describe a paediatric patient with extragenital LSA associated with vitiligo who was successfully treated with topical steroids and retinoids.     

Analysis of TPI gene promoter variation in three sub‐Saharan Africa population samples

Population samples from Angola, Mozambique, and S. Tomé e Príncipe were screened for the TPI gene promoter variants ‐5A→G, ‐8G→A and ‐24T→G. Three haplotypes were identified in the three populations: the haplotype ‐5A‐8G‐24T (average frequency 65.3%) and two less common haplotypes ‐5G‐8G‐24T (average frequency 24.7%) and ‐5G‐8A‐24T (average frequency 10.0%). A population sample from Central Portugal showed the haplotype ‐5A‐8G‐24T in 139 chromosomes and one subject heterozygous for haplotype ‐5G‐8A‐24G. The exact test of sample differentiation among three groups of malaria‐infected individuals classified according to the severity of the disease showed no significant differences. We confirmed TPI gene diversity in sub‐Saharan Africa, but we could not detect any association between TPI promoter variation and a malarial protective effect. Larger scale epidemiological studies are thus required to clarify this putative mechanism of natural host defense against this worldwide public health problem. Am. J. Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.