C4BQ0: a genetic marker of familial HCV-related liver cirrhosis.

Source Department of Medicine and Pneumology, V Cervello Hospital, Via Trabucco 180, 90146 Palermo, Italy. [email protected] Abstract BACKGROUND AND METHODS: Host may have a role in the evolution of chronic HCV liver disease. We performed two cross-sectional prospective studies to evaluate the prevalence of cirrhosis in first degree relatives of patients with cirrhosis and the role of two major histocompatibility complex class III alleles BF and C4 versus HCV as risk factors for familial clustering. FINDINGS: Ninety-three (18.6%) of 500 patients with cirrhosis had at least one cirrhotic first degree relative as compared to 13 (2.6%) of 500 controls, (OR 7.38; CI 4.21-12.9). C4BQ0 was significantly more frequent in the 93 cirrhotic patients than in 93 cirrhotic controls without familiarity (Hardy-Weinberg equilibrium: chi2 5.76, P = 0.016) and in 20 families with versus 20 without aggregation of HCV related cirrhosis (29.2% versus 11.3%, P = 0.001); the association C4BQ0-HCV was found almost only in cirrhotic patients with a family history of liver cirrhosis. CONCLUSIONS: Our studies support the value of C4BQ0 as a risk indicator of familial HCV related cirrhosis

Il contributo delle reti sanitarie “spontanee” al miglioramento degli outcome: Opportunità e sfide nella prospettiva della progettazione dei sistemi di programmazione e controllo

Il presente lavoro intende discutere il contributo che i sistemi di Programmazione e Controllo possano fornire al regolatore regionale nello sviluppo di politiche di rete in sanita. Lo scritto esamina le esperienze sulla costituzione e sull’amministrazione di reti sanitarie "spontanee" maturate da ISMETT (Istituto mediterraneo per i trapianti e terapie ad alta specializzazione), struttura ospedaliera istituita in Sicilia nel 1998 per l’erogazione di prestazioni di cura a elevata complessita. L’analisi del caso consentira di illustrare in che modo le reti sanitarie "spontanee" possano contribuire a un miglioramento della "salute" e generare outcome di carattere economico e sociale per l’intera comunita.The article aims to explore how Planning Control systems may support network-oriented policy-making in the health care sector. This work examines the case of ISMETT (Mediterranean Institute for high specialized transplants and therapies), a Sicilian hospital established in 1998 to provide high specialized and complex transplants and therapies. ISMETT pertains to several networks and it has a long-time experience in establishing and governing such inter-organizational relationships. The analysis of the case illustrates how health care networks may contribute to improve health and generate social and economic outcomes for the community

Disseminated non-Hodgkin's lymphoma and chronic hepatitis C: a case report

Hepatitis C virus (HCV) infection is occasionally associated to B-cell type non-Hodgkin's lymphoma. Evidence showing a possible etiological link between HCV and lymphoma has been reported from areas of high HCV prevalence. We describe the case of a 68-year-old woman with B-cell non-Hodgkin's lymphoma mainly involving the skin. Typical manifestations of disease were cutaneous nodules, red-violet in color, scattered on the entire body and adherent to the subcutaneous tissue. A 3-cm nodule excised from the leg was found at histology to consist of centroblastic-like B cells, which stained positively for CD45, CD20 and CD79a. Although the patient was treated with different chemotherapy schedules, she died 1 year later with a diagnosis of disseminated lymphoma. Our report suggests that HCV, a trigger for clonal B-cell proliferation, predisposing to immunological disorders, such as mixed cryoglobulinemia and B-cell malignancies, may also account for the "rare" extranodal high-grade non-Hodgkin's lymphoma. Further observations suggest that treating HCV infection with antiviral therapy could help to prevent the development of B-cell non-Hodgkin's lymphoma

Management of liver failure: from transplantation to cell-based therapy

The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiological role of endogenous stem cells in liver regeneration and on the therapeutic benefits of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells. Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed

Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis

Background: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. Methods: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenemresistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macrophage phenotypic expression. Results: hA-MSCs added to AF significantly reduce the proliferation of both bacterial strains at 24 h and diversely affect M1 and M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection, in a bacterial strain-dependent fashion. Conclusion: This study shows the potential usefulness of hA-MSC in treating ascites infected with carbapenem-resistant bacteria and lays the foundation to further investigate antibacterial and anti-inflammatory roles of hA-MSC in in vivo models

Use of hepatitis C-positive deceased liver donors in response to the organ shortage in an endemic area

The region of Sicily, Italy, is witnessing a chronic organ shortage. Thus, to face this critical issue, the use of marginal donors has increased over time. An example of marginal donor expansion is the use of liver donors who are positive for the hepatitis C antibody (HCV+) for HCV+ patients requiring liver transplantation (LT). In view of new advances in HCV therapy, including direct-acting agents (DAAs) to treat HCV in the post-transplant setting, our study focused on a monocentric experience in a series of consecutive LTs performed in adult patients receiving HCV+ liver donor allografts. From 2003 to 2016 at our institute we performed 10 LT using HCV+ deceased donors. In particular, the pre-LT histological examination in 1 case showed a framework of moderate steatosis (35% microvesicular and 10% macrovesicular) with micro/macrovesicular steatosis <10% in all the other cases. A fibrous framework of 1/6 according to the Ishak score in a single case, and 2/6 in 2 cases, were highlighted, while there was no fibrosis in the other 7 cases. A picture of periportal inflammation was still detected in 4 cases, with no evidence of inflammatory lesions in the remaining cases. The patient survival was 100% at 1 and 3 years, and 85.7% at 5 years post-LT. One-, three- and five-year graft survivals were 100.0%, 88.9%, and 71.4%, respectively. Only 1 patient underwent re-LT after 2 years, because of chronic rejection. Based on our experience using HCV+ deceased liver donors with a moderate degree of fibrosis, we believe that accepting marginal donors is a feasible therapeutic option when facing a liver donor shortage