Minimal residual disease monitoring in early stage follicular lymphoma can predict prognosis and drive treatment with rituximab after radiotherapy.

Since 2000, we have investigated 67 consecutive patients with stage I/II follicular lymphoma (FL) for the presence of BCL2/IGH rearrangements by polymerase chain reaction (PCR), real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR). All patients were treated with involved-field radiotherapy (IF-RT) (24-30 Gy). From 2005, patients with minimal residual disease (MRD) after IF-RT received rituximab (R) (375 mg/m2 , 4 weekly administrations). The median follow-up is 82 months (17-196). At diagnosis, 72% of patients were BCL2/IGH+. Progression-free survival (PFS) was significantly better in patients with undetectable/low levels (<10-5 ) of circulating BCL2/IGH+ cells at diagnosis and in those who were persistently MRD- during follow-up (P = 0·0038). IF-RT induced an MRD- status in 50% of cases; 16/19 (84%) MRD+ patients after IF-RT became MRD- after R treatment. A significantly longer PFS was observed in MRD+ patients treated with R compared to untreated MRD+ patients (P = 0·049). In early stage FL, both circulating levels of BCL2/IGH+ cells at diagnosis and MRD status during follow-up bear prognostic implications. Standard IF-RT fails to induce an MRD-negative status in half of patients. Most patients become MRD- following treatment with R and this is associated with a significantly better PFS.

Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study.

Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02_AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7-80.9] and in drug users (OR 27.8; interval 4.9-186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.

Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15.

BACKGROUND: Hepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies. STUDY: Countries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases. RESULTS: Surveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs. CONCLUSION: Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the 'One Health' approach to better informing on human exposure to HEV.

Etiology of and risk factors for transient and persistent aminotransferase elevation in a population of virus-free blood donors: a multicentre study.

AIM: We evaluated the etiology and risk factors for transient and persistently elevated aspartate and/or alanine aminotransferase levels in virus-free blood donors. INCLUSION CRITERIA: HBsAg/HBV-DNA and anti-HCV/HCV-RNA negative blood donors with elevated aspartate aminotransferase and/or alanine aminotransferase, observed in 5 blood transfusion centres in Italy from 2004 to 2005. Aspartate aminotransferase/alanine aminotransferase levels were measured at entry and every 2 months during a period of 6 months. RESULTS: 291 individuals were evaluated (144 with persistent and 147 with transient abnormal aminotransferases). High body mass index was the most frequent (75.5%) etiological factor and was more common in the persistent elevated levels group, compared to the transient elevated levels group (82.0% vs 65.3%; p<0.01). Excessive alcohol intake (>2 units/day) was reported in 23.6%, with no differences between the two groups. Instead, recent use of medication or paint exposure were most frequently associated with transient elevated levels than persistent elevated levels (61.6% vs 23.3% for drugs and 13.7% vs 4.3% for paint, p<0.001). Considering the participants with transient elevated levels as controls, the multivariate analysis showed that high body mass index was the only independent predictor of persistent elevated aminotransferase levels (OR=5.3; 95%CI=1.88-13.42 for those with body mass index>29.9). CONCLUSIONS: In virus-free blood donors, excessive body mass index is the most frequent etiological factor of abnormal aminotransferases and it is the sole risk factor associated with persistently elevated aminotransferases.

Use of hierarchical models to evaluate performance of cardiac surgery centres in the Italian CABG outcome study.

BACKGROUND: Hierarchical modelling represents a statistical method used to analyze nested data, as those concerning patients afferent to different hospitals. Aim of this paper is to build a hierarchical regression model using data from the "Italian CABG outcome study" in order to evaluate the amount of differences in adjusted mortality rates attributable to differences between centres. METHODS: The study population consists of all adult patients undergoing an isolated CABG between 2002-2004 in the 64 participating cardiac surgery centres.A risk adjustment model was developed using a classical single-level regression. In the multilevel approach, the variable "clinical-centre" was employed as a group-level identifier. The intraclass correlation coefficient was used to estimate the proportion of variability in mortality between groups. Group-level residuals were adopted to evaluate the effect of clinical centre on mortality and to compare hospitals performance. Spearman correlation coefficient of ranks (rho) was used to compare results from classical and hierarchical model. RESULTS: The study population was made of 34,310 subjects (mortality rate = 2.61%; range 0.33-7.63). The multilevel model estimated that 10.1% of total variability in mortality was explained by differences between centres. The analysis of group-level residuals highlighted 3 centres (VS 8 in the classical methodology) with estimated mortality rates lower than the mean and 11 centres (VS 7) with rates significantly higher. Results from the two methodologies were comparable (rho = 0.99). CONCLUSION: Despite known individual risk-factors were accounted for in the single-level model, the high variability explained by the variable "clinical-centre" states its importance in predicting 30-day mortality after CABG.

Correlation of alcohol consumption with liver histological features in non-cirrhotic patients.

BACKGROUND AND AIMS: The association between alcohol consumption and the risk of liver disease remains unclear. The aim of our study was to determine liver morphological features directly related to the mean lifetime daily alcohol intake (LTDAI) in non-cirrhotic patients. METHODS: Medical records of all consecutive patients who reported alcohol consumption up to the time of hospital admission and who had undergone a liver biopsy in the Gastroenterology Unit of the University Hospital Centre of Tirana (Albania), were reviewed. Patients with established cirrhosis and/or with other possible causes of liver damage were excluded by the study. RESULTS: The histological features revealed in the biopsy samples of 51 non-cirrhotic patients were: steatosis in 46 patients (91%), six of whom (13%) showed also alcoholic foamy degeneration; alteration of hepatocytes in 40 patients (78%), diffuse mononuclear inflammation in 37 patients (73%), polymorphonuclear inflammation in 11 patients (22%) and perivenular fibrosis in 18 patients (35%). Diffuse steatosis was directly correlated with alcohol consumption (P<0.01). No association was found between alcohol consumption and the presence of degenerative alterations of hepatocytes, Mallory bodies or hepatocellular necrosis. Fibrosis was more prevalent in patients who reported a LTDAI > or = 80 g in comparison with patients who reported a LTDAI > or = 40 to <80 g (48% vs 25%; P<0.05). CONCLUSION: In non-cirrhotic patients liver steatosis and fibrosis were more common features among patients who reported a higher alcoholic consumption, but no clear-cut association between typical histological features of alcoholic liver disease and alcohol consumption was found.