Oral budesonide for the therapy of post-liver transplant de novo inflammatory bowel disease: a case series and systematic review of the literature.

BACKGROUND: The therapy for posttransplant IBD is clinically challenging. Patients receiving liver transplants are immunosuppressed to prevent rejection, but via an unknown mechanism develop de novo IBD in spite of receiving some of the same medications used for therapy in traditional IBD. In the published literature most of the patients who developed de novo IBD were treated with traditional corticosteroids. Exposure to systemic corticosteroids increases risks of infection, diabetes mellitus, and osteoporosis among other complications. Budesonide, a luminally active steroid with low systemic absorption, is an established therapeutic agent for IBD that should receive special considerations as first-line therapy in this patient population. METHODS: We describe 3 cases of de novo IBD after liver transplantation. None of these patients had a history of IBD prior to their transplant. All 3 were treated with oral budesonide in lieu of systemic corticosteroids. Additionally, a Medline MeSH search was performed using the terms "inflammatory bowel disease" and "liver transplant" as part of a systematic review of the literature. RESULTS: All 3 cases of de novo post transplant IBD went into clinical remission with oral budesonide. The Medline search ultimately revealed 19 case reports, case series or retrospective reviews on de novo post liver transplant IBD. Most reports focused on the diagnosis and risk factors and did not have an emphasis on therapy. CONCLUSIONS: Given the track record for budesonide in traditional IBD, and its documented efficacy and systemic steroid-sparing benefit, in our opinion this drug should be considered first-line therapy for de novo posttransplant IBD.

Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response.

UNLABELLED: The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation. CONCLUSION: These data suggest that ISG inducibility is important for the treatment response and that ribavirin may improve outcomes by enhancing hepatic gene responses to peginterferon. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy.

Impact of donor age and year of transplant on graft survival in liver transplant recipients with chronic hepatitis C.

Studies suggest donor age and year of transplantation are associated with low graft survival in liver transplant recipients with hepatitis C. We sought to determine if advanced donor age and recent year of transplantation are associated with graft survival in hepatitis C recipients and to determine if the effect of donor age on graft survival is specific to hepatitis C. We analyzed the United Network for Organ Sharing liver transplant database from 1994 to 2002. Six thousand four hundred and four subjects transplanted for end-stage liver disease from chronic hepatitis C met our criteria. One-year graft survival in hepatitis C recipients with organs from donors <40 years old and >or=60 years old was 84% and 73%, p = 0.003, respectively. These rates in recipients with cholestatic liver disease and alcoholic liver disease were 85% and 82%, respectively, p = 0.11 and 82% and 78%, respectively, p = 0.14. Three-year graft survival in hepatitis C recipients transplanted from 1994 to 1995 and 1996 to 1999 was 67% and 69%, respectively, p = 0.10. Graft survival in hepatitis C recipients has not declined in recent years. Older donor age is associated with lower short-term graft survival in recipients with hepatitis C, but not in recipients with cholestatic or alcoholic liver disease.

Management of newly diagnosed hepatitis C virus infection.

All patients with chronic hepatitis C virus infection are potential candidates for antiviral therapy. Careful patient selection can optimize the response to therapy and enhance safety. Pegylated forms of interferon, when combined with ribavirin, can "cure" the majority of patients undergoing therapy, and these agents have become the new standard of care for chronic hepatitis C. Careful and timely management of side effects, which are experienced by all patients, can improve adherence to antiviral therapy and further improve response rates.

A population-based cohort study comparing laparoscopic cholecystectomy and open cholecystectomy.

OBJECTIVES: Laparoscopic cholecystectomy (LC) has become a popular alternative to open cholecystectomy (OC). Previous studies comparing outcomes in LC and OC used small selected cohorts of patients and did not control for comorbid conditions that might affect outcome. The aims of this study were to characterize the morbidity, mortality, and costs of LC and OC in a large unselected cohort of patients. METHODS: We used the population-based North Carolina Discharge Abstract Database (NCHDAD) for January 1, 1991, to September 30, 1994 (n = 850,000) to identify patients undergoing OC and LC. We identified the indications for surgery, complications, and type of perioperative biliary imaging used. We compared length of stay, hospital charges, complications, morbidity, and mortality between OC and LC patients. To account for variations in outcomes from differences in age and comorbidity between the OC and LC groups, we used the age-adjusted Charlson Comorbidity Index in regression analyses quantifying the association between type of surgery and outcome. RESULTS: Our cohort consisted of 43,433 patients (19,662 LC and 23,771 OC). The mean age-adjusted Charlson Comorbidity Index score was slightly higher for the OC compared to the LC group (4.3 vs 4.1, p < 0.05). The OC patients had longer hospitalizations, generated more charges ($12,125 vs $9,139, p < 0.05), and required home care more often. The crude risk ratio comparing risk of death in OC to LC was 5.0 (95% CI = 3.9-6.5). After controlling for age, comorbidity, and sex, the odds of dying in the OC group was still 3.3 times (95% CI = 1.4-7.3) greater than in the LC group. In the LC group, the number of patients with acute cholecystitis rose over the study period, whereas the number of patients with chronic cholecystitis declined. In the OC group, the number of patients with acute and chronic cholecystitis declined. The use of intraoperative cholangiography was greater in the OC group but declined in both groups over the study period. The use of ERCP was greater in the LC group and increased in both groups over time. CONCLUSIONS: The introduction of LC has resulted in a change in the management of cholecystitis. Despite a higher proportion of patients with acute cholecystitis, the risk of dying was significantly less in LC than in OC patients, even after controlling for age and comorbidity. Based on lower costs and better outcomes, LC seems to be the treatment of choice for acute and chronic cholecystitis.