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Background: The long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored. Methods and Findings: We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis and of dying during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained virological response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in both cohorts had a statistically significantly increased hazard of cirrhosis compared to never treated patients, as stratified by pretreatment liver fibrosis stage and adjusted for clinical and psychosocial risk factors that disproportionately affect patients who were ineligible for treatment (Veterans Affairs HR = 2.35, CI 1.18–4.69, mean follow-up 10 years, and University Hospital HR = 5.90, CI 1.50–23.24, mean follow-up 7.7 years). Despite their increased risk for liver disease progression, the overall survival of nonresponders in both cohorts was not significantly different from that of never treated patients. Conclusion: These unexpected findings suggest that patients who receive interferon-α based therapies but fail to clear the hepatitis C virus may have an increased hazard of cirrhosis compared to untreated patients. [ABSTRACT FROM AUTHOR]

We assessed associations between indicators for moisture in office buildings and weekly, building-related lower respiratory and mucous membrane symptoms in office workers, using the U.S. EPA BASE data, collected in a representative sample of 100 U.S. office buildings. We estimated the strength of associations between the symptom outcomes and moisture indicators in multivariate logistic regression models as odds ratios (ORs) and 95% confidence intervals (CI), controlling for potential confounding factors and adjusting for correlation among workers in buildings. This analysis identified associations between building-related symptoms and several indicators of moisture or contamination in office buildings. One set of models showed almost a tripling of weekly building-related lower respiratory symptoms in association with lack of cleaning of the drip pans under air-conditioning cooling coils (OR [CI] = 2.8 (1.2-6.5)). Other models found that lack of cleaning of either drip pans or cooling coils was associated with increased mucous membrane symptoms (OR [CI] = 1.4 (1.1-1.9)). Slightly increased symptoms were also associated with other moisture indicators, especially mucous membrane symptoms and past water damage to building mechanical rooms (OR [CI] = 1.3 (1.0-1.7)). Overall, these findings suggest that the presence of moisture or contamination in ventilation systems or occupied spaces in office buildings may have adverse respiratory or irritant effects on workers. The analysis, however, failed to confirm several risks identified in a previous study, such as condition of drain pans or outdoor air intakes, and other hypothesized moisture risks. Studies with more rigorous measurement of environmental risks and health outcomes will be necessary to define moisture-related risks in buildings. [ABSTRACT FROM AUTHOR]

The immune function test is an integrated measure of total mitogen-inducible CD4(+) T cell metabolic activity in the peripheral blood, and it is used to guide the dosing of immunosuppressive medications after solid organ transplantation. Recently, low CD4(+) T cell metabolic activity due to pharmacologic immunosuppression has been linked to rapidly progressive cirrhosis in hepatitis C virus (HCV)-infected liver transplant recipients. We speculate that either cirrhosis or HCV might adversely affect the CD4(+) T cell reactivity even in the absence of immunosuppressive medications. We thus performed this assay on a cohort of untransplanted hepatology patients who were not taking immunomodulatory drugs. Low mitogen-stimulated CD4(+) T cell metabolic reactivity was more commonly seen in untransplanted patients with HCV cirrhosis or with cirrhosis due to other causes but not in control patients or in those with chronic HCV in the absence of cirrhosis. The lowest mean CD4(+) T cell reactivities were seen in patients with both cirrhosis and HCV. Caution should be exercised when immune function test results are used to guide immunomodulatory therapy in transplant recipients with suspected cirrhosis, as low immune function test results may be a consequence of hepatic cirrhosis or of pharmacologic immunosuppression.