Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.     

A review of the physiological and immunological functions of biliary epithelial cells: targets for primary biliary cirrhosis, primary sclerosing cholangitis and drug-induced ductopenias

Our understanding of biliary epithelial cells (BEC) in physiobiology and immunology has steadily expanded. BEC transports IgA as well as IgM into bile, synthesizes and secretes various chemokines, cytokines, and expresses adhesion molecules involved in cell interaction and signal transduction. These then suggest a myriad of potential roles for BEC in defense from invading microorganisms as well as the pathogenesis of diverse immunologically driven diseases such as primary biliary cirrhosis (PBC), graft-versus-host disease, and primary sclerosing cholangitis (PSC). Despite the progress, there still remain many areas of BEC biology that require further investigation. Most importantly, it remains to be clarified that the extent to which the immunologic activities observed in BEC represent a BEC response to tissue injury or whether BEC themselves are the active participants in the pathogenesis of various cholestatic immunological diseases, including PBC and PSC.     

Automated intensive care unit risk adjustment: results from a National Veterans Affairs study

CONTEXT: Comparison of outcome among intensive care units (ICUs) requires risk adjustment for differences in severity of illness and risk of death at admission to the ICU, historically obtained by costly chart review and manual data entry. OBJECTIVE: To accurately estimate patient risk of death in the ICU using data easily available in hospital electronic databases to permit automation. DESIGN AND SETTING: Cohort study to develop and validate a model to predict mortality at hospital discharge using multivariate logistic regression with a split derivation (17,731) and validation (11,646) sample formed from 29,377 consecutive first ICU admissions to medical, cardiac, and surgical ICUs in 17 Veterans' Health Administration hospitals between February 1996 and July 1997. MAIN OUTCOME MEASURES: Mortality at hospital discharge adjusted for age, laboratory data, diagnosis, source of ICU admission, and comorbid illness. RESULTS: The overall hospital death rate was 11.3%. In the validation sample, the model separated well between survivors and nonsurvivors (area under the receiver operating characteristic curve = 0.885). Examination of the observed vs. the predicted mortality across the range of mortality showed the model was well calibrated. CONCLUSIONS: Automation could broaden access to risk adjustment of ICU outcomes with only a small trade-off in discrimination. Broader use might promote valid evaluation of ICU outcomes, encouraging effective practices and improving ICU quality.     

抗CD20单抗（Rituximab）作为B细胞淋巴瘤老龄患者初始治疗的新标准

背景侵袭性B细胞淋巴瘤是目前最常见的非霍奇金淋巴瘤类型,主要包括弥漫大B细胞淋巴瘤(DLBCL)和套细胞淋巴瘤(MCL)。超过60%的患者被诊断出B细胞淋巴瘤时年龄都在60岁以上。在过去的30年间,CHOP方案(环磷酰胺、多柔比星、长春新碱、泼尼松)是治疗DLBCL的金标准。年龄较轻的患者