Me Lai

Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children

We investigated the course of distinct episodes of acute non-A, non-B (NANB) hepatitis in three polytransfused thalassaemic children. In each case, the first episode was associated with the appearance of serum hepatitis C virus (HCV) RNA and anti-HCV seroconversion. The second episode was accompanied by the reappearance of HCV viraemia, which in two patients was due to reinfection with a different HCV strain and in the third could be the result of either reactivation of primary infection or reinfection with a new but closely related strain. Thus HCV infection may not induce protective immunity, which has implications for vaccine development.

Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C

The purpose of this study was to determine whether interferon-alfa (IFN-alpha) therapy benefits patients with transfusion-dependent thalassemia and chronic active hepatitis C, and whether their iron burden modifies the response to this therapy. We conducted a controlled trial of recombinant IFN-alpha (3 million units per square meter of body surface area, three times a week for 15 months) in 65 patients with thalassaemia major and chronic active hepatitis C; 14 of them were untreated control subjects. In 21 of the 51 treated patients, alanine aminotransferase values returned to normal within 6 months, and hepatitis C virus ribonucleic acid was no longer detected in serum; no changes were detected among control subjects. The response to IFN-alpha therapy was inversely related (p < 0.002) to the liver iron burden as assessed by atomic absorption, the histologic semiquantitative method, or both methods. During 3 years of follow-up, two responder patients had relapses. We conclude that IFN-alpha represents a useful therapeutic option for children with transfusion-dependent thalassemia and chronic active hepatitis C with a mild to moderate iron burden.

High prevalence of thyroid dysfunction in adult patients with β-thalassemia major submitted to amiodarone treatment

Amiodarone may induce hyper- or hypothyroidism. Patients with β-Thalassemia Major (β-Thal) have an increased prevalence of primary hypothyroidism and often require amiodarone for hemosyderotic cardiomyopathy. Aim of this study was to retrospectively evaluate thyroid function in β-Thal adult patients on long-term amiodarone. The study group consisted of twenty-two (21 males, 1 female; age: 23-36 yr) β-Thal patients submitted to long-term (3-48 months) amiodarone therapy from January 1991 to July 1996. Controls included 73 β-Thal patients (23 males and 50 females aged 25-35 yr) not treated with amiodarone. In all cases serum free thyroid hormones, thyrotropin and thyroid autoantibodies were evaluated. A higher prevalence of overt hypothyroidism (5/22 [22.7%]) as compared to controls (3/73 [4.1%], p=0.02) was found in β-Thal patients ≤3 months after starting amiodarone, while the prevalence of subclinical hypothyroidism was similar in amiodarone-treated (18.2%) and untreated (15%) β-Thal patients. Overt hypothyroidism resolved spontaneously after amiodarone withdrawal in 1 case, while the remaining patients were maintained euthyroid on amiodarone by L-thyroxine administration. After 21-47 months of amiodarone therapy, 3 patients (13.6%) developed thyrotoxicosis (2 overt and 1 subclinical), which remitted shortly after amiodarone withdrawal. No case of hyperthyroidism was observed in β-Thal controls (p=0.012 vs amiodarone-treated patients). In conclusion, amiodarone administration is often associated in adult β-Thal patients to a rapid progression of the pre-existing subclinical hypothyroidism, but transient thyrotoxicosis may also be observed after a longer period of therapy. These findings should be carefully considered in the management of these patients.

Carrier detection and early diagnosis of Wilson's disease by restriction fragment length polymorphism analysis.

Wilsons disease, a rare autosomal recessive disorder, has been recently mapped to the long arm of chromosome 13 (q14.1). In this study, we carried out linkage analysis between three chromosome 13 DNA markers, D13S1, D13S10, D13S2, the locus for the red cell enzyme esterase D (ESD), and the Wilsons disease locus (WND) in 17 Wilsons disease families of Italian descent, mostly from Sardinia. We confirmed a tight linkage [theta = 0.00, Z (theta) = 4.07] between the WND and ESD loci, and provided suggestive evidence for linkage [theta = 0.00, Z(theta) = 1.85] of the WND locus with D13S10. Multipoint linkage analysis indicated the following order: centromere-D13S1-D13S10-WND-ESD-D13S2. RFLP analysis at these two loci in our families allowed us either to define the carrier status (50%) or to exclude the homozygous state (25%) in the great majority of unaffected sibs.

A multicentric seroepidemiological survey of HTLV-I/II in Italy

BACKGROUND Several studies carried out in the USA and in Europe have shown the presence of HTLV-I/II antibodies in subjects belonging to high-risk groups for HIV infection as well as blood donors. Concern about the presence of HTLV-I/II markers in the normal population, as well as the efficient transmission of HTLV-I/II by whole blood or infected blood cells have led several countries to include screening for anti-HTLV-I/II among the mandatory serological testing of blood donors. OBJECTIVE In order to assess the risk of HTLV-I/II infection related to blood transfusions, a multicentric survey for antibodies against HTLV-I and HTLV-II was carried out involving 10 Italian sites during the spring of 1991. STUDY DESIGN Serum specimens were collected from 14,598 blood donors, 1,411 injecting drug users, 1,015 thalassemics, 142 hemophiliacs and 138 hemodialysis patients. HTLV antibodies were detected by a screening EIA which combines a viral lysate with a recombinant HTLV-I env protein (p21e). The serological confirmation was performed by a semi-automated dot-blot immunoassay that detects gag p19 and p24 and env p21e specific antibodies, while the discrimination of HTLV-I and HTLV-II reactivities was carried out by EIAs employing synthetic peptides of the ENV region specific for each virus. RESULTS The seroprevalence of confirmed positives was 0.034% among blood donors and 3.61% among IDUs, while no sample of the other categories could be confirmed, although several were indeterminate and one thalassemic reacted against HTLV-I on peptide testing. HTLV-I reactivity was observed in one blood donor, while all 38 of the 51 confirmed seropositive IDUs reacted only to the HTLV-II synthetic peptide. CONCLUSIONS These data confirm a high prevalence of HTLV-II among Italian IDUs and show an HTLV-I/II seroprevalence among blood donors very similar to that which was found in the USA volunteer blood donors. A surveillance program among blood donors seems advisable in order to establish the possible need of a mandatory screening for HTLV-I/II.