Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population

Background & Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age-and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. Results: Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1-25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3-94.8) and 62.9% (95% CI, 45.9-75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72-1.35), with an SMR for non-SVR patients of 3.85 (95% CI,, for untreated of 3.01 (95% CI, 2.64-3.42) and for decompensated of 6.70 (95% CI,. Conclusions: Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable

Using landscape structure to develop quantitative baselines for protected area monitoring

Changes in habitat extent as well as landscape and habitat structure are often caused by human pressure within protected areas and at their boundaries, with consequences for biodiversity and species distributions. Thus quantitative spatial information on landscape mosaic arrangements is essential, for monitoring for nature conservation, as also specified by frameworks such as the Convention on Biological Diversity (CBD), and the European Union’s Habitat Directive. While measuring habitat extent is a relatively straightforward task, approaches for measuring habitat fragmentation are debated. This research aims to delineate a framework that enables the integration of different approaches to select a set of site- and scale-specific indices and synthetic descriptors and develop a comprehensive quantitative assessment of variations in human impact on the landscape, through assessment of habitat spatial patterns, which can be used as a baseline for monitoring. This framework is based on the use of established methodologies and free software, and can thus be widely applied across sites. For each landscape and observation scale, the framework permits the identification of the most relevant indices, and appropriate parameters for their computation. We illustrate the use of this framework through a case study in a protected area in Italy, to indicate that integrated information from multiple approaches can provide a more complete understanding of landscape and habitat spatial pattern, especially related to locations experiencing disturbance and pressure. First, identification of a parsimonious set of traditional LPIs for a specific landscape and spatial scale provides insights on the relation between landscape heterogeneity and habitat fragmentation. These can be used for both change assessment and ranking of different sections of the study area according to a fragmentation gradient in relation to matrix quality. Second, morphological spatial pattern analysis (MSPA), provides a pixel based structural characterisation of the landscape. Third, compositional characterisation of the landscape at the pixel level is provided by landscape mosaic analysis. These three approaches provide quantitative assessments through indices which can be used singly or in combination to derive three synthetic descriptors for a comprehensive quantitative baseline representation of landscape structure that can be used for monitoring: the first descriptor, landscape diversity profiling, based on the output of landscape mosaic analysis, at the landscape level, complements the evaluation which at the pixel level can be obtained by more complex modelling; the second descriptor, obtained combining of the outputs of MSPA and the landscape mosaic analysis, informs on the local structural pattern gradient across the landscape space; the third descriptor, derived from the integration of selected LPIs and those derived from MSPA into a discontinuities detection procedure, allows for the identification of “critical points” of transitions in management where threats to biodiversity and ecosystems integrity may be likely. The framework developed has significant potential to capture information on major landscape structural features, identify problematic areas of increased fragmentation that can be used to prioritise research, monitoring and intervention, and provide early warning signals for immediate response to pressures increasing habitat fragmentation, with the goal of facilitating more effective management

Interferon lambda-3 is not associated with clinical outcome in patients with HCV-induced compensated cirrhosis: a long-term cohort study

Background: Interferon Lambda-3 (IFN-\u3bb3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-\u3bb3 genotype influences liver disease progression remains unclear. Methods: We determined IFN-\u3bb3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-\u3bb3 genotype and clinical outcome. Results: IFN-\u3bb3 was determined in 264 patients (52% males, mean age 57 \ub1 8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p < 0.0001). Univariate and multivariate analyses found no association between IFN-\u3bb3 (CC vs. non-CC genotype) and disease progression. Conclusion: IFN-\u3bb3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease

The Circulating Level of Soluble Receptor for Advanced Glycation End Products Displays Different Patterns in Ulcerative Colitis and Crohn's Disease: A Cross-Sectional Study

RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity