Screening Indication Associated With Lower Likelihood of Minor Adverse Events in Patients Undergoing Outpatient Colonoscopy.

We sought to determine, among outpatients at one university hospital endoscopy center, rates of self-reported minor adverse events (MAEs) at 2, 14, and 30 days postcolonoscopy and to identify predictors of MAEs at Day 2 postcolonoscopy. A single-center longitudinal cohort study with follow-ups at Days 2, 14, and 30 postcolonoscopy was conducted in Montreal, Canada. Baseline self-report data included patient age, gender, gastrointestinal discomforts and other discomforts in the preceding month, and comorbidity. Intracolonoscopy procedures and the method of insufflation were obtained from endoscopy reports. Minor adverse event data were obtained by either phone or Internet survey. Multivariate logistic regression was used to identify predictors of MAEs at Day 2. Of 705 individuals approached, 420 (mean age = 58.7 years; SD = 8.4, 45.7% female) were eligible and consented to study participation, and 378 (90%) participated in at least one follow-up. At Days 2, 14, and 30, 86 (25.1%), 46 (13.7%), and 13 (3.1%) patients, respectively, experienced at least one MAE. At the Day 30 follow-up, 2 (0.53%) patients reported having experienced a serious adverse event. The multivariable analysis results showed that screening compared with nonscreening colonoscopy was protective for MAEs at 2 days (OR = 0.5, 95% CI [0.3, 0.9]). We found that 25% of patients experienced at least one MAE at 2 days postcolonoscopy, and screening compared with nonscreening colonoscopy patients were half as likely to experience these early MAEs. Nurses may use these findings to educate and reassure patients about colonoscopy risks. Large, longitudinal multicenter studies are needed to corroborate our findings.

A review of direct-acting antivirals for the treatment of hepatitis C in patients with advanced chronic kidney disease.

Historically, standard treatment of hepatitis C virus (HCV) infection in patients with renal impairment has been limited by low cure rates and poor tolerability. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV with impressive cure rates >90% and low rates of adverse events. Despite these major advancements, treatment of patients with HCV and advanced chronic kidney disease (CKD) is a major challenge due to the lack of efficacy and safety data in this patient population. The purpose of this review is to summarize the available data for efficacy and safety of the following DAAs in treating HCV patients with advanced Stage 4 and 5 CKD: simeprevir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, dasabuvir, grazoprevir, elbasvir and daclatasvir.

Successful Treatment of Hepatitis C with Simeprevir, Sofosbuvir, and Ribavirin in an HIV Coinfected Liver Transplant Patient with Advanced Chronic Kidney Disease.

Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year-old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting.

Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients.

OBJECTIVE: Review pharmacokinetics of new direct-acting antivirals (DAAs) for hepatitis C (HCV) infection and interactions with concomitant immunosuppressant and antiretroviral therapies (ART). DATA SOURCES: MEDLINE (1948-January 2015), EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January 2015), Google, and Google Scholar were searched combining the terms simeprevir, sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir, dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV, antiretroviral, immunosuppressant, transplant. Articles, conference proceedings, abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Literature on pharmacokinetic or pharmacodynamic interactions with DAAs and immunosuppressants or ART was considered for inclusion. Pertinent information was extracted and summarized in the review. In the absence of data, pharmacokinetic and pharmacodynamic principles were used to predict the likelihood of interactions. DATA SYNTHESIS: DAA pharmacokinetics are reviewed and drug interaction data are presented with provision of management strategies. Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most susceptible to drug interactions with immunosuppressants and ART mainly due to the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and OATP1 involvement and is not recommended for use in combination with several HIV antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin inhibitors is required with concomitant simeprevir. Few clinically significant interactions are expected with sofosbuvir or ledipasvir. Limited data suggest that daclatasvir may be coadministered with immunosuppressants but requires dose adjustments with certain ARVs. CONCLUSIONS: None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.