M. L. Bacchi Reggiani

Higher doses of peginterferon alpha-2b administered twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study

Summary.  Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha‐2b + ribavirin with higher doses of Peginterferon alpha‐2b administered twice weekly + ribavirin. Sixty‐five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha‐2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naïve patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 19% (8 of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha‐2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules.

Densitometric CT evaluation of acute and chronic thromboembolic filling defects of the pulmonary arteries before and after contrast injection.

PurposeThe aim of this study was to assess the baseline computed tomography (CT) attenuation of acute and chronic pulmonary thromboemboli, their contrast enhancement (CE), correlation with haematocrit (Ht) levels and the presence of hypertrophic bronchial arteries.Materials and methodsFrom January 2006 to October 2009, we measured the baseline and postcontrast attenuation values of acute pulmonary thrombi emboli on CT angiograms of 86 patients with acute pulmonary embolism (PE) and those of chronic thrombi in 29 patients with pulmonary hypertension of various origins. The attenuation of acute thrombi was correlated with Ht and CE of chronic thrombi with the presence of hypertrophic bronchial arteries.ResultsAcute emboli had a mean baseline attenuation of 54.9 Hounsfield units (HU) and showed no CE. The attenuation of acute thrombi was not dependent on Ht. Chronic thrombi had a mean baseline attenuation of 33.8 HU, and 54% of thrombi showed significant CE. In 57% of cases, a collateral circulation had developed. In 76.5% of cases, CE and hypertrophic bronchial arteries coexisted (p=0.026). Neither thrombotic CE nor bronchial artery hypertrophy predominated in any one of the diseases associated with chronic thrombosis.ConclusionsBefore contrast administration, acute emboli coare prevalently hyperattenuating and therefore more conspicuous. Only chronic thrombi exhibit CE, and CE is significantly associated with the development of collateral circulation, which may be involved in the process of thrombotic recanalisation.RiassuntoObiettivoScopo del presente lavoro è stato valutare la densità basale dei trombi polmonari acuti e cronici, il loro contrast enhancement (CE), la correlazione con i valori di ematocrito (Ht) e la presenza di arterie bronchiali ipertrofiche (IB).Materiali e metodiDa gennaio 2006 a ottobre 2009 sono stati calcolati i valori densitometrici basali e postcontrastografici dei trombi acuti ricavati dalle angiotomografie computerizzate (TC) di 86 pazienti con embolia polmonare acuta e dei trombi cronici di 29 pazienti con ipertensione polmonare di diversa eziologia. La densità dei trombi acuti è stata correlata all’Ht e il CE dei trombi cronici alla presenza di IB.RisultatiGli emboli acuti hanno mostrato densità basale media di 54,9 UH e non hanno mostrato CE. La densità dei trombi acuti non dipendeva dall’Ht. I trombi cronici hanno mostrato densità basale media di 33,8 UH; nel 54% dei casi mostravano significativo CE. Il 57% dei casi sviluppa circoli collaterali. Nel 76,5% dei casi CE e IB erano concomitanti (p=0,026). Né il CE trombotico né l’ipertrofia delle arterie bronchiali prevalevano in una delle patologie associate a trombosi cronica.ConclusioniIn fase pre-contrastografica i trombi polmonari acuti sono prevalentemente iperdensi e quindi meglio identificabili. Solo i trombi cronici mostrano CE; il CE si associa significativamente allo sviluppo di circoli collaterali che potrebbero essere implicati nel processo di ricanalizzazione trombotica.

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

Incidence of hepatocellular carcinoma in hepatitis C virus‐related cirrhosis is 4% per year. Although cost‐effective, current screening could be improved.

A cross-sectional study on the comparison of five ultrasound measurements to estimate central venous pressure in spontaneously breathing and ventilated patients

The correlation of the inferior vena cava (IVC) diameter and the internal jugular vein (IJV) diameter with Central Venous Pressure (CVP) was already tested. Few reports compared IVC and IJV ultrasound measures in the same population. No data there are on the correlation of the internal jugular vein diameter and CVP in ventilated patients.

Does biological therapy affect interferon-γ release assay response? A long-term follow-up of patients with psoriasis using QuantiFERON-TB

DEAR EDITOR, Patients with psoriasis treated with biological drugs are at increased risk of reactivation of latent tuberculosis infection (LTBI). Therefore screening for active or latent TB is mandatory before initiating therapy. Interferon (IFN)-c release assays (IGRAs) are in vitro tests approved for the detection of LTBI and are based on the measure of IFN-c secreted by T lymphocytes sensitized to Mycobacterium tuberculosis (MTB) antigens. Furthermore, IGRAs provide both a negative and a positive (T-cell mitogen phytohaemagglutinin) control, thus allowing a more comprehensive evaluation of the host immune reactivity. Published evidence suggests that IGRAs maintain their diagnostic sensitivity for LTBI better than the tuberculin skin test (TST) in patients with chronic inflammatory diseases. However, few studies on the performance of IGRAs in patients with psoriasis have been carried out, most of them analysing agreement with TST. The aim of this study was to assess the frequency of LTBI and the host immune reactivity by QuantiFERON-TB Gold InTube (QFT-IT; Qiagen, Hilden, Germany), a commercially available IGRA, in patients with psoriasis and psoriatic arthritis before and during biological treatment. The protocol for this study was approved by the Ethics Committee of the S. OrsolaMalpighi University Hospital. We retrospectively evaluated 188 patients (121 male and 67 female; mean age 50 9 13 0 years, range 18–83; 94 7% Italian born) with mild-to-severe psoriasis (mean Psoriasis Area and Severity Index 13 2 4 9), who were candidates for biological therapy. Fifty-one patients (27 1%) had one or more comorbidities, such as cardiovascular diseases (n = 29), diabetes (n = 17) or obesity (n = 15). Thirty-four (18 1%) were under immunosuppressive therapy at the time of QFT-IT screening, including ciclosporin (n = 20), methotrexate (n = 10) and corticosteroids (n = 4). According to the current recommendations for Italian dermatologists, the screening algorithm included medical history, chest X-ray and QFT-IT, interpreted as positive, negative or indeterminate according to the manufacturer’s instructions. In order to exclude active TB, microbiological standard analysis was performed. A diagnosis of LTBI was based on a positive QFT-IT test in conjunction with no radiological finding suggestive of active TB and negative microbiological assay. For cases of LTBI, a standard prophylactic treatment with isoniazid for 6 months was started 1 month before biological therapy. In case of indeterminate QFT-IT, patients underwent an infectivology consultation and, if necessary, started treatment with isoniazid; these patients were strictly monitored by serial QFT-IT. The study flowchart is depicted in Figure 1. At baseline (t0), 21 patients (11 2%) tested QFT-IT positive and 163 (86 7%) negative; results for four patients (2 1%) were indeterminate, two of whom were under methotrexate treatment. The mean age of patients with positive QFT-IT (59 1 10 4 years) was significantly higher than that of patients with a negative result (48 9 13 5 years) (P = 0 001). After screening, 118 patients (62 8%) started a biological treatment: 106 (89 8%) based on antitumour necrosis factor (anti-TNF)-a blockers (44 etanercept, 44 adalimumab, 18 infliximab), 11 (9 3%) with ustekinumab and one (0 8%) with efalizumab. Concomitantly, most of the patients under immunosuppressive treatment interrupted it. In order to evaluate whether any reversion or conversion could occur during treatment, patients who received biological therapy for longer than 12 months (n = 82) were monitored yearly with QFT-IT for a mean of 25 2 13 2 months. After the first year of biological treatment (t1), 92 7% of patients confirmed the previous QFT-IT result. Out of 10 patients who tested positive for QFT-IT at screening, nine confirmed their positive results during follow-up, maintaining a high level of IFN-c in response to MTB-specific antigens (mean value 6 07 4 93 IU mL 1 at t0, 6 03 5 04 IU mL 1 at t1 and 7 08 5 00 IU mL 1 at t2). In contrast, the only patient with LTBI who showed a reversion at t1 had a baseline QFT-IT value of 0 67 IU mL . Among 68 cases testing QFT-IT negative at screening (t0), two patients experienced a conversion to positive QFT-IT with IFN-c values < 1 IU mL 1 at t1 and t3. Among four patients with an indeterminate result at t0, LTBI was excluded in three of them, who became QFT-IT negative within 3 months, while one patient with risk factors for LTBI started prophylaxis and became QFT-IT positive. A longitudinal analysis of all patients with LTBI (n = 13) treated with isoniazid did not show significant changes in IFN-c response to MTB-specific antigens during biological therapy. To determine whether immune response could be influenced by biological therapy, the trend of IFN-c release in response to QFT-IT mitogen at screening and after 1 year of treatment was analysed. The number of patients with mitogen value