A prospective study of hepatocellular carcinoma incidence in thalassemia

Hepatocellular carcinoma (HCC) is a complication of cirrhosis. Due to blood transfusions, patients with beta-thalassemia (thal) are often infected with either hepatitis C virus (HCV) or hepatitis B virus (HBV). In the past, many patients did not survive long enough to develop HCC. The recent improvements in prognosis have helped in the diagnosis of HCC that has developed. The aim of this study was to evaluate HCC incidence in beta-thal. We performed liver ultrasound (US) on all adults without a previous diagnosis of HCC. Risk factors (iron overload, HCV infection, HBV infection, cirrhosis) were evaluated. One hundred and eight thalassemia patients have been evaluated; of whom three were excluded (two patients as they were under the age of 18 years and one patient because he had a previous history of HCC). Seventy-two patients [31 had thalassemia major (TM), 41 had thalassemia intermedia (TI)] with risk factors (iron overload in 72, HCV infection in 46, HBV infection in two, cirrhosis in 10) and 33 (four with TM and 29 with TI) without risk factors underwent liver US. Overall, two patients were found to have a newly developed HCC. Of these two patients, one was treated with surgery and the other with percutaneous radiofrequency. Further follow-up did not show any evidence of recurrence after 23 and 15 months, respectively. Ultrasound screening can allow early detection and treatment of HCC in thalassemia patients.     

High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.     

HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients

BACKGROUND: Hypersensitivity reaction to nevirapine, which in some cases can be fatal, shows a higher prevalence in Sardinia in comparison with other Italian regions. OBJECTIVE: This study demonstrates that hypersensitive reaction to nevirapine in Sardinian HIV-infected patients is associated with the HLA Cw8-B14 haplotype. These two HLA class I antigens are in strong linkage disequilibrium in the Sardinian population. METHODS: Forty-nine Sardinian HIV-positive patients treated with nevirapine were studied. Thirteen (26%), developed a hypersensitive reaction thus requiring the drug to be discontinued. HLA class I and II molecular typing was performed in both nevirapine-hypersensitive and nevirapine-tolerant patients. To avoid biased representation of the allele frequencies in the two groups of treated patients, molecular typing was also performed in 82 HIV-positive patients who had not been treated with nevirapine. RESULTS: Considerable overlap was observed for the clinical, immunological and demographic characteristics of the 13 hypersensitive patients and 36 tolerant patients. Clinical parameters included viral load, status of HIV infection, CD4 and CD8 cell counts, hepatitis C virus/hepatitis B virus co-infections. Forty-six percent (6/13) of the nevirapine-hypersensitive subjects had the HLA-Cw8 and HLA-B14(65) antigens compared with 5% (2/36) of the nevirapine-tolerant group (P = 0.004; Pc = 0.05). CONCLUSION: In agreement with other recent reports, the utility of HLA typing in HIV patients to identify genetic factors that may confer susceptibility to drug-induced hypersensitive reaction was confirmed. A careful choice of antiretroviral therapy in susceptible individuals should significantly reduce the risk of severe hypersensitive reaction.     

Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality

BACKGROUND: Splanchnic thrombosis is a surgical challenge in liver transplantation (LT). The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution. AIM: The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution. PATIENTS AND METHODS: Between 1999 and 2004, 366 liver transplants were performed in 335 patients. Forty-two patients [12.5%: portal vein thrombosis (PVT) group] had portal thrombosis at the time of LT. We analyzed the technical aspects and compared their evolution with a group of patients without portal thrombosis (n = 293; no-PVT group). Retransplantations were excluded. RESULTS: Of the 42 patients with thrombosis, 18 had partial thrombosis and 16 complete thrombosis [six included the proximal superior mesenteric vein (SMV) and in two the whole splanchnic system]. In 12 cases, usual T-T anastomosis was performed and in 16 cases a thrombectomy was carried out; there were five cases of anastomosis at confluence of the SMV, five cases of anastomosis to a collateral vein, three cases of venous graft, and one case of cavoportal hemitransposition. The operative time was higher in PVT group (417 +/- 103 min vs. 363 +/- 83; p = 0.0005), as RBC transfusion (2.4 +/- 3.1 vs. 1.9 +/- 2.3; p = 0.04), and hospital stay (20.9 +/- 14.9 d vs. 15.1 +/- 10.6; p = 0.002). However, there were no differences in hospital mortality (4% vs. 7.8%; p = 0.98), primary dysfunction (4.8% vs. 7.8%; p = 0.44), or three-yr-actuarial survival (75% vs. 77%; p = 0.95). The incidence of post-transplant thrombosis was higher in the PVT group (15% vs. 2.4%; p = 0.0005). CONCLUSIONS: Portal thrombosis is associated with greater operative complexity and rethrombosis, but has no influence on overall morbidity and mortality.     

Effect of drug-test interactions on length of hospital stay

PURPOSE: To evaluate the impact of drug-laboratory test interactions on the length of stay of hospitalised patients. METHODS: Observational study of 404 discharges from the Internal Medicine Services of a tertiary hospital. Databases with information on general data, medication and tests performed were linked with the potential interactions described in the literature. This revealed the potential interactions between drugs and laboratory tests (PIDL) in each patient. Several linear regression models, adjusted for confounders, were performed to test the effect of both the number of PIDL and their influence on tests results (false positive/negative) on the length of stay. RESULTS: A total of 19 741 PIDL were detected; 5954 could give rise to potential false positive (PFP) results and 8442 to potential false negative (PFN) ones. Each PFP was related to an increase of 0.051 days in stay duration (CI95% 0.001-0.102) and each PFN to 0.045 days (CI95% 0.008-0.081). Globally, 303 and 380 days of hospitalisation could be attributed to false positives and false negatives, which could account for 9.8% of the total stay of these patients. CONCLUSIONS: These results show that the interactions between drugs and laboratory tests produce a statistically and clinically significant increase in the duration of hospital stay.     

Aripiprazole in the treatment of schizophrenia: a consensus report produced by schizophrenia experts in Italy

Schizophrenia is generally a chronic and disabling mental illness. Pharmacological therapy, which is used for relief of acute psychotic episodes and prevention of subsequent relapse, is essential for the effective management of schizophrenia. In order to alleviate the positive symptoms of schizophrenia, all antipsychotic agents act on the dopaminergic system. However, strong, high-affinity dopamine D(2)-receptor blockade may also be responsible for debilitating extrapyramidal symptoms (EPS) and hyperprolactinaemia. Unlike conventional antipsychotic agents, atypical antipsychotics also exert activity at other receptors, and it is generally acknowledged that, compared with conventional antipsychotics, atypical agents are associated with a broader spectrum of clinical efficacy and are better tolerated. However, other adverse effects such as weight gain and metabolic changes are cause for concern with some atypical antipsychotics. The novel atypical antipsychotic agent aripiprazole is a partial agonist at D(2) receptors that has been shown in clinical trials to be effective in treating both the positive and the negative symptoms of schizophrenia, and to be well tolerated, with a low propensity for EPS and no clinically significant weight gain, hyperprolactinaemia or corrected QT-interval prolongation. Aripiprazole thus provides clinicians with another treatment option, and in October 2005, schizophrenia experts participated in an expert consensus meeting that aimed to agree on a set of guidelines for best-practice use of aripiprazole in the acute and long-term management of schizophrenia in Italy. This report describes the outcome of the meeting. Our recommendations for dosage and administration of aripiprazole are in agreement with the manufacturer's prescribing information. Ideally, optimal dosing should be evaluated on an individual basis, taking into account patients' characteristics such as the presence or absence of agitation. Overall, in our experience, aripiprazole is generally a well accepted, well tolerated, safe and broadly effective first-line antipsychotic agent. Switching to aripiprazole from maintenance therapy with another antipsychotic also works well, provided the change is made gradually, involving tapering of the original medication.     

Nitric oxide: emerging concepts about its use in cell-based therapies

Regenerative medicine is an emerging clinical discipline in which cell-based therapies are used to restore the functions of damaged or defective tissues and organs. Along with the well-established use of cells derived from bone marrow or pancreatic islets, novel approaches of cell therapy have recently emerged that appear particularly promising; that is, those using cell-based vaccines and stem cells. This review focuses on the recent developments of these experimental therapeutic approaches and their drawbacks, with specific focus on dendritic cell vaccines in tumours and mesoangioblasts in muscular dystrophies. The authors discuss how the unique properties of a gaseous messenger, NO, may be exploited to overcome some of the drawbacks of these cell-based approaches in combined therapies based on NO-releasing drugs and cell delivery.     

PEG-interferon alpha-2b for acute hepatitis C: a review

Acute infection due to hepatitis C virus results in a chronic progression in 50-84% of cases. In the light of the risk of developing chronic disease and the response rate to treatment once the disease is established, it is very important to consider early treatment of acute hepatitis C before it progresses to the chronic form. The aim of this review is to evaluate the real efficacy and tolerance of Peg-interferon alpha-2b in monotherapy and in association with ribavirin in the treatment of patients affected by acute C hepatitis, to delineate the viral factors correlated with the sustained virological response and to consider when treatment should be started in relation to onset and what is the optimal duration of therapy. Also the pharmacodynamic and pharmacokinetic characteristics of PEG-IFN alpha-2b and ribavirin are reassessed. The analysis of literature demonstrates that Peg-interferon alpha-2b treatment is efficacious in terms of attaining sustained virological response (71-94% of cases). Treatment must be started within three months of onset and must be prolonged for three months. Only two studies have provided evidence the needed of a prolonged treatment for six months for genotype 1 infections. In all studies therapy has been generally well tolerated. Sustained virological response is independent of baseline viral load and of HCV genotypes in patients treated for six months, while in subjects treated for three months it seems to be dependent on HCV-genotype, with genotype 1 characterized by a less favourable outcome. Combination therapy with ribavirin does not seem to increase the response rate but could be proposed as a second choice to patients not responding to IFN monotherapy.