1,721,002 research outputs found
Hepatitis C virus-associated B-cell non-Hodgkin's lymphoma: clinical and therapeutic challenges
No full textHepatitis C virus (HCV) is a major cause of liver-related morbidity and is strongly associated with B cell lymphoproliferative disorders. Data from epidemiological, biological and clinical investigations support the hypothesis of a pathogenetic role of HCV in at least a subgroup of patients with B-cell non-Hodgkin's lymphoma (B-NHL). Morphologically, HCV-associated B-NHL represents a variety of histological subtypes. The comprehension of the mechanisms of HCV persistence and of its role in the lymphomagenesis will be useful to set new strategies with the aim to prevent and treat HCV-associated B-NHLs. This hypothesis of a virus-induced mechanism of lymphomagenesis arises from the growing evidence that successful antiviral treatment is often linked to regression of some types of HCV-related indolent B-NHLs
The expanding spectrum of HCV-related cryoglobulinemic vasculitis: a narrative review
No full textCryoglobulinemic vasculitis (CV) is a small-to-medium-vessel vasculitis that appears in 10–15 % of patients chronically infected with hepatitis C virus (HCV). The classic symptom triad of CV, purpura/asthenia/arthralgia, is accompanied by clinical features that include glomerulonephritis, neuropathy, interstitial pneumonitis, and cardiomyopathy, ranging in their severity from mild to life threatening. The risk of developing non-Hodgkin lymphoma is also higher. The cumulative 10-year survival rate of CV patients is significantly lower than in the age- and sex-matched general population, with death typically caused by nephropathy, malignancies, liver involvement, and severe infections. Unfailing serological stigmata include both a cryoglobulin IgM fraction with rheumatoid factor activity and decreased complement C4 levels. On peripheral B cells, the expression of the CD81 B cell receptor is reduced while that of the CD19 receptor is increased. A monoclonal B cell lymphocytosis develops in almost one-third of patients. HCV-related proteins (but not HCV-RNA genomic sequences) can be detected on biopsy samples by immunofluorescence and immunohistochemistry and involve the vessel lumen, vessel walls, and the perivascular spaces of the skin, kidney, and peripheral nerves, supporting the pathogenetic role of HCV in the onset of a widespread microvasculitis. Based on the demonstration of HCV infection in the large majority of CV patients, a therapeutic regimen consisting of once-weekly pegylated interferon-α and the daily administration of ribavirin results in a sustained virologic response in ~50 % of patients. In those with refractory and relapsing disease, addition of the anti-CD20 monoclonal antibody rituximab has significantly increased the overall response rates. The extension to CV of latest-generation direct-acting antivirals, strikingly successful in non-CV HCV-positive patients, has yielded high complete response rates according to the few studies published thus far
IN SITU SIMULTANEOUS DETECTION OF HEPATITIS C VIRUS RNA AND HEPATITIS C VIRUS-RELATED ANTIGENS IN HEPATOCELLULAR CARCINOMA
No full textBackground: The overwhelming evidence that chronic infection with the hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) is based on epidemiologic, casecontrol, and cohort studies as well as laboratory investigations. To address better the pathogenesis of HCV infection at a single cell level, the authors developed a specific reproducible method for the simultaneous detection of HCV specific sequences and antigens in liver tissue, using a combination of nonradioactive in situ hybridization and immunohistochemistry. Methods: After immunoistochemical staining of the liver sections for E2/NS-1, C22–3, C33c, C100–3 and NS-5 antigens with immunogold-silver technique, in situ hybridization was performed on the same sections using digoxigenin-labeled HCV 5 NonCoding
specific probes. The hybridization signal was detected by an antidigoxigenin, Fab fragment-alkaline phosphatase conjugate. This simultaneous detection permitted the subcellular localization of HCV RNA and antigens with excellent preservation of tissue morphology and absence of background staining. In addition the types and percentages of cells harboring HCV in tissue could be determined. Results: The in situ detection of HCV showed positive signals in both cancerous and noncancerous areas of liver tissue in six of six HCV-infected patients with HCC and in none of four controls, including three HCV negative HCC patients and one patient with epithelioid hemangioendothelioma. Two classes of infected cells were distinguished throughout the liver: (1) cells containing large amounts of negative-stranded HCV RNA, which were probably undergoing active viral replication; and (2) cells displaying positive-stranded HCV RNA only, with unpredictable levels of viral replication. Both types expressed core, envelope, and NS-3, -4, -5 proteins. HCV RNA and antigens were exclusively cytoplasmic. Detection of viral proteins was highly predictive of the presence of large amounts of HCV RNA in the same cell. Fewer HCV positive cells were consistently demonstrated in the cancerous area. Conclusions: These findings support the contention that HCVinfects hepatocytes and replicates in them, even after their malignant transformation
Direct-acting antiviral agents in the therapy of hepatitis C virus-related mixed cryoglobulinaemia: a single-centre experience
Full text linkThe efficacy and safety of direct-acting antiviral agents (DAAs) were evaluated in a cohort of prospectively enrolled patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC), an immune complex-mediated vasculitis of small and medium vessels in which the pathogenetic role of HCV has been clearly established
Transarterial Chemoembolization Plus Sorafenib: A Sequential Therapeutic Scheme for HCV-Related Intermediate-Stage Hepatocellular Carcinoma: A Randomized Clinical Trial.
No full textBackground. Recurrence of hepatocellular carcinoma (HCC) is a major problem after surgical or ablative treatments. The aim of this prospective, single-center, placebo-controlled, randomized, double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization (TACE) combined with sorafenib as a sequential treatment regimen in delaying time to progression (TTP) of intermediate-stage HCC in patients with chronic hepatitis C virus (HCV) infection. Material and Methods. Between October, 2007 and January, 2011, 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure. All had Child-Pugh class A disease. They were randomized 1: 1 to receive sorafenib at a dose of 400 mg twice daily or placebo. Endpoints were the TTP and the rates of adverse events and toxicity. Results. Sixty-two of 80 patients (77%), 31 in the sorafenib group and 31 in the control group, completed the study. The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group (hazard ratio, 2.5; 95% confidence interval, 1.66-7.56; p <. 001). Metachronous, multicentric HCC progression occurred less frequently in sorafenib-treated patients (p <. 05). Adverse reactions to sorafenib caused withdrawal from the study of 9 (22%) patients. Conclusion. A conventional TACE procedure followed by sorafenib treatment resulted in a significantly longer TTP in patients with intermediate-stage HCV-related HCC, with no unexpected side effects. The Oncologist 2012; 17: 359-36
H. pylori infection and gastric cancer: state of the art (review).
No full textGastric cancer (GC) is one of the leading types of cancer worldwide, particularly in East Asian populations. Helicobacter pylori (HP) infection has been established as a major risk factor for GC. Although more than 50% of the world population is infected with this bacterium, less than 2% develop GC. Therefore, further risk factors (such as host genetic polymorphisms and lifestyle, as well as environmental and epigenetic factors) may also play a role in its occurrence. The correlation between HP infection and GC represents a typical model of a multi‐step process, characterized by some pre-neoplastic lesions with a high risk of progression (atrophic gastritis, intestinal metaplasia and dysplasia). In addition, HP also plays an oncogenic role in the development of mucosa‐associated lymphoid tissue (MALT) lymphoma, that accounts for approximately 3% of all gastric tumors. Hyperplastic polyps often arise in patients with atrophic gastric mucosa and HP‐associated gastritis (25% of cases); however, their malignant transformation is rare (<3% of cases). A number of trials have demonstrated the possibility of cancer prevention through HP screening and eradication, particularly in high‐risk populations, whereas it may not be cost‐effective in areas of low risk. In this review, we discuss i) the complex pathogenetic mechanisms of gastric carcinogenesis in which HP is involved; ii) the main approaches to the diagnosis, prevention, surveillance and treatment of pre-malignant lesions associated with HP infection; iii) the most effective way to detect GC in its earlier stages; and iv) the most important contribution to reducing the burden of GC
Impact of Cryoglobulinemic Syndrome on the Outcome of Chronic Hepatitis C Virus Infection: A 15-Year Prospective Study.
No full textAbstract: We evaluated the influence of cryoglobulinemic syndrome (CS) on the outcome of chronic hepatitis C virus (HCV) infection in a 15-year prospective study. We assessed a cohort of 950 chronically HCV-infected patients, collected from the beginning of 1990 to the end of 2010. All patients had received a liver histologic diagnosis. Mixed cryoglobulinemia (MC) was determined in 246 patients (25.8%), of whom 184 also had CS. They were assessed every 3 months for 15 years, at least; 141 patients with CS and 601 without MC completed the study.
No spontaneous clearance of cryoglobulins was noted. Type II to type III spontaneous switching was ascertained in 1.6% (0.08%/yr) patients. The estimated progression rate of liver fibrosis was lower in CS(+) than in MC(−) patients (p < 0.05). The 15-year cumulative probability of developing cirrhosis and/or hepatocellular carcinoma was higher in MC(−) than in CS(+) patients (24.9% vs. 14.2%, p < 0.005 and 20.3% vs. 7.5%, p = 0.003, respectively). Renal insufficiency, neurologic impairment, or B-cell non-Hodgkin lymphoma were significantly more frequent in CS(+) than in MC(−) patients (32.6% vs. 3%, p < 0.0001; 31.2% vs. 4.8%, p < 0.0001; and 15% vs. 7.1%, p = 0.003, respectively). However, in spite of different morbidity features and causes of death, the 15-year survival rate was similar in the 2 groups (70.2% vs. 71.7%). Antiviral therapy had an undisputable impact on patient outcome.
This 15-year prospective cohort study shows that, although CS has no influence on the overall survival of HCV-infected patients, it significantly modifies the natural history of chronically HCV-infected patients
Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis
No full textImmunoglobulin variable region heavy chain (IgVH ) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-time reverse transcription-polymerase chain reaction (RT-PCR). The features of activation-induced cytidine deaminase (AID) protein and mRNA transcripts were explored in liver tissue biopsies and portal tracts isolated using laser capture microdissection. In chronically HCV-infected patients, AID mRNA expression was almost threefold higher in those with than in those without CV and sevenfold higher than in healthy subjects (median-fold: 6·68 versus 2·54, P = 0·03 and versus 0·95, P = 0·0003). AID transcript levels were significantly higher in polyclonal than in clonally restricted B cell preparations in either CV or non-CV patients (median-fold, 15·0 versus 2·70, P = 0·009 and 3·46 versus 1·58, P = 0·02, respectively). AID gene expression was found to be related negatively to age and virological parameters. AID protein was found in portal tracts containing inflammatory cells that, in several instances, expressed AID mRNA transcripts. Our data indicate that the aberrant expression of AID may reflect continuous B cell activation and sustained survival signals in HCV-related CV patients
Barrett's esophagus and esophageal cancer: An overview.
No full textAlthough esophageal cancer (EC) is the eighth most common cancer in several European countries, it is one of deadliest worldwide. The most frequent predisposing factor implicated in its development is Barrett's esophagus (BE), an acquired metaplastic transformation of the esophageal lining cells from normal squamous epithelium into specialised or intestinal-like columnar epithelium. The major risk factor for BE is gastroesophageal reflux disease. Although BE is in itself a benign and often asymptomatic disorder, its clinical importance stems from the recognition that it represents the main precursor lesion for the development of esophageal adenocarcinoma (AC), a tumor that is rapidly increasing especially in developed countries and is associated with a low survival rate. This paper provides an overview of the epidemiology and natural history of BE as well as of the possible pathogenetic mechanisms underlying the development of BE and its progressive transition to AC. New diagnostic tests are described, recommendations for screening and surveillance are provided and surgical and ablative procedures to treat dysplastic lesions and early neoplasia are discussed. Claimed chemopreventive agents and biomarkers that in the near future may help identify people with a higher risk of EC are also considered
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