Immunogenicity and safety of an adjuvanted influenza vaccine in patients with decompensated cirrhosis

The immunogenicity and tolerability of an adjuvanted trivalent influenza vaccine was evaluated in 20 patients with cirrhosis due to chronic HBV or HCV infections and eight healthy age matched controls. Seroconversion or a four-fold or greater increase in HI antibody titres to each antigen occurred in 75-85% of the patients and in 100% of the controls. One month after vaccination, the geometric mean antibody titres were significantly higher than baseline in both groups of vaccinees. A mild and transient erythema at the inoculation site was the only side effect for both groups. The results justify the use of an adjuvanted influenza vaccine, given as single-dose, in patients with advanced liver disease

Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in 'real world' patients with chronic hepatitis C

BACKGROUND: Interferon-alpha plus ribavirin therapy for chronic hepatitis C is associated with adverse effects that lead to therapy discontinuation in up to 27% of patients in randomized controlled trials. AIM: To examine the causes and predictive factors for therapy discontinuation in patients treated in current clinical practice. METHODS: We retrospectively enrolled 441 consecutive patients, scheduled to receive interferon-alpha + ribavirin for chronic hepatitis C, in five centres. Patients had been treated with 3 or 6 MU interferon-alpha three times a week plus ribavirin, 800-1200 mg daily, for 6 or 12 months. RESULTS: One hundred and eight [24.5%; confidence interval (CI), 20.5-28.8%] patients failed to finish combination therapy because of adverse events. The discontinuation rate was higher during the first 6 months of treatment; anaemia was an important cause (36.1% of discontinuations); unexplained lipothymia resulted in discontinuation in 11 patients. Female gender [hazard ratio (HR) = 1.85; CI, 1.17-2.92], an interferon-alpha dose > 15 MU/week (HR = 1.79; CI, 1.12-2.86) and no previous interferon-alpha treatment (HR = 1.63; CI, 1.04-2.57) were independent factors associated with discontinuation. The simultaneous presence of these factors identified patients at high risk for discontinuation [odds ratio (OR) = 10; CI, 3.98-25.13]. CONCLUSIONS: The study identified some predictive factors for adverse event-related discontinuation, which may improve the safety profile and effectiveness of interferon-alpha + ribavirin combination therapy in chronic hepatitis C

Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome

Objective: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-seropositive individuals. The aim of the study was to compare the main features of HCC in HIV-seropositive individuals with those in to HIV-negative patients. Patients and methods: All HIV-infected subjects with a diagnosis of HCC included in three cancer registry databases were enrolled in the study as cases. HCC cases that occurred in the province of Brescia, North Italy, in the period 1995–1998 and all cases reported at the Italian Liver Cancer Project were enrolled as controls. All data were collected using a standardized case report form. The main clinical and epidemiological characteristics of patients with HCC and their survival were compared between HIV-positive and uninfected subjects. Results: Forty-one HIV-infected subjects with HCC were identified. Multivariate analysis adjusted for age and sex identified an association between HIV infection and HCV infection [odds ratio (OR), 11; P ¼ 0.005], and infiltrating tumours and/or extranodal metastasis at presentation (OR ¼ 11.8; P , 0.001). HIV infection was independently associated with shorter survival (hazard ratio, 1.63; P ¼ 0.015). Conclusions: HCC in HIV-infected patients is mainly associated with underlying chronic hepatitis C and has a more aggressive clinical course. Thus, preventative strategies (including the treatment of hepatitis C) should be implemented in the management of HIV/HCV-coinfected patients

Impact of telaprevir in HCV patients with cirrhosis and RVR: real-life data from Boceprevir or Telaprevir based "triple therapy" experience in southern Italy

Background and Rationale of Study: The real-life data of triple therapy-based treatment in patients with chronic hepatitis C were investigated in this survey of 12 clinical centers of southern Italy. This retrospective study analyzed data from 176 consecutive patients. Methods: 125 (70%) patients were treated with telaprevire, and 51(30%) with boceprevir. There were no differences in demographic characteristics between the groups. The degree of Liver Fibrosis (LF) was evaluated according to Liver Biopsy (LB) and/or Transient Elastography (TE). 53/176 patients (30%) had liver cirrhosis. Sixteen patients (9%) were treatment naive, and the remaining were not: 92 were non-responders (52, 84%), 63 relapsed (35,79%), and 5 discontinued treatment (2, 8%). Results: Overall, the rapid Virological Response (RVR) rate was 67.6%. Of the 103 patients who had follow-up for at least 12 weeks after the end of treatment, 61 (59, 2%) achieved a Sustained Virological Response (SVR). According to multivariate analysis for SVR, RVR was the only independent predictive factor of SVR, irrespective of the degree of LF and the type of response to previous treatments. In telaprevir-treated patients, the rate of RVR was similar in patients with F0-F2, F3 and F4 fibrosis (85%, 84%, 78%, respectively), and the SVR rates among RVR patients was similar irrespective of LF. Conclusions: Data from this real-life study confirm the efficacy reported in clinical trials, although cirrhosis appears to play a smaller role in influencing treatment efficacy. Moreover, RVR is the only independent predictive factor of response regardless of cirrhosis. Based on RVR and for patients with cirrhosis, a shorter therapy might be considered, at least with telaprevir-based therapy

Corrigendum: No change in the mucosal gut microbiome is associated with celiac disease-specific microbiome alteration in adult patients (American Journal of Gastroenterology (2016) 111 (1659-1661) DOI: 10.1038/ajg.2016.227)

The title should read: No Change in the Mucosal Gut Mycobioma Is Associated with Celiac Disease-Specific Microbiome Alteration in Adult Patients

Metagenomics reveals dysbiosis and a potentially pathogenic N. flavescens strain in duodenum of adult celiac patients

OBJECTIVES: Celiac disease (CD)-associated duodenal dysbiosis has not yet been clearly defined, and the mechanisms by which CD-associated dysbiosis could concur to CD development or exacerbation are unknown. In this study, we analyzed the duodenal microbiome of CD patients. METHODS: The microbiome was evaluated in duodenal biopsy samples of 20 adult patients with active CD, 6 CD patients on a gluten-free diet, and 15 controls by DNA sequencing of 16S ribosomal RNA libraries. Bacterial species were cultured, isolated and identified by mass spectrometry. Isolated bacterial species were used to infect CaCo-2 cells, and to stimulate normal duodenal explants and cultured human and murine dendritic cells (DCs). Inflammatory markers and cytokines were evaluated by immunofluorescence and ELISA, respectively. Results: Proteobacteria was the most abundant and Firmicutes and Actinobacteria the least abundant phyla in the microbiome profiles of active CD patients. Members of the Neisseria genus (Betaproteobacteria class) were significantly more abundant in active CD patients than in the other two groups (P=0.03). Neisseria flavescens (CD-Nf) was the most abundant Neisseria species in active CD duodenum. Whole-genome sequencing of CD-Nf and control-Nf showed genetic diversity of the iron acquisition systems and of some hemoglobin-related genes. CD-Nf was able to escape the lysosomal compartment in CaCo-2 cells and to induce an inflammatory response in DCs and in ex-vivo mucosal explants. Conclusions: Marked dysbiosis and an abundance of a peculiar CD-Nf strain characterize the duodenal microbiome in active CD patients thus suggesting that the CD-associated microbiota could contribute to the many inflammatory signals in this disorder