Danny J. Avalos

Sofosbuvir and simeprevir for treatment of hepatitis C virus infection in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection occurs universally in the allograft in the absence of effective antiviral therapy before liver transplantation (LT). Antiviral therapy with sofosbuvir and simeprevir has proven to be highly effective and well tolerated in the nontransplant setting for treatment of HCV genotype 1 infection; therefore, we sought to evaluate the efficacy and safety of this regimen in LT recipients with recurrent HCV infection. This was a retrospective analysis of a single‐center treatment protocol of patients with HCV genotype 1 infection who received a 12‐week combination regimen of sofosbuvir and simeprevir. Sixty‐one patients (35 with genotype 1a and 26 with genotype 1b) completed treatment with simeprevir and sofosbuvir. Three patients received additional ribavirin. Laboratory data and clinical assessments performed at the baseline, on treatment, at the end of treatment, and 12 weeks after the completion of antiviral therapy [sustained virological response at 12 weeks (SVR12)] were analyzed. The median time after LT was 5.4 years [interquartile range (IQR), 1.9‐8.4 years], and tacrolimus was the most commonly used immunosuppressive agent (80.3%). Overall, SVR12 was achieved in 93.4% [95% confidence interval (CI), 84%‐97%] of LT recipients treated with 12 weeks of sofosbuvir and simeprevir. When they were analyzed according to the HCV subtype, LT recipients with genotype 1b had a 100% SVR12 rate (95% CI, 87%‐100%), whereas SVR12 was 89% (95% CI, 74%‐95%) for those with genotype 1a. Advanced fibrosis (METAVIR F3‐F4) was associated with diminished antiviral efficacy in LT recipients with genotype 1a [SVR12, 67% (95% CI, 39%‐86%); P = 0.01]. Overall, the incidence of adverse events (AEs) was low, and no severe AEs occurred during treatment. In conclusion, treatment with a 12‐week regimen of sofosbuvir and simeprevir was well tolerated and resulted in a high SVR12 rate for LT recipients with recurrent HCV genotype 1 infection. Genotype 1a patients with advanced fibrosis of the allograft were more likely to relapse. Liver Transpl 21:823‐830, 2015.

Treating Inflammatory Bowel Disease in Pregnancy: The Issues We Face Today.

Many women of childbearing age are living with inflammatory bowel disease [IBD], yet there are limited studies on the use of IBD medications in pregnancy. In this review, we provide a comprehensive update on the safety of these medications during pregnancy, particularly thiopurines and biologicals. Antibiotics, steroids, and aminosalicylates are relatively low risk for use in pregnancy, and growing evidence supports the safety of immunomodulators and anti-tumour necrosis factor agents as well. Available studies on infliximab, adalimumab, and certolizumab pegol show no increase in adverse events during pregnancy or perinatally. Similarly, studies on lactation demonstrate that concentrations of subcutaneous anti-tumour necrosis factor biologicals are undetectable, and levels of thiopurines and infliximab are negligible in breast milk. Less is known about anti-integrins in pregnancy [eg natalizumab and vedolizumab] but currently available data suggest they may be safe as well. Although more studies are needed to examine the long-term effects of these medications on offspring, the available data provide reassuring information for providers caring for women of childbearing age.

Inflammatory bowel disease is presenting sooner after immigration in more recent US immigrants from Cuba

Despite a rising incidence of inflammatory bowel disease (IBD) in Hispanics in the United States, there are no studies examining the relationship between immigrant generation and IBD onset among Hispanics.

Can adjusting BMI for age and sex provide for a better predictor of colonic neoplasia

Objective The aim of this study was to evaluate the influence of BMI on colonic neoplasia in average-risk patients aged between 40 and 59 years, analyzed by sex. Methods A total of 4443 patients aged between 40 and 59 years undergoing a first-time screening or average-risk colonoscopy were included in this study. Data on demographics, smoking, and BMI were collected and correlated to the presence of adenomas and advanced adenomas. Results We evaluated 1197 colonoscopies in patients aged between 40 and 49 years, and 3246 in those aged between 50 and 59 years. Among men between 40 and 49 years, increasing BMI [odds ratio (OR)=1.05, 95% confidence interval (CI): 1.00–1.09] and BMI of at least 27 (OR=1.95, 95% CI: 1.15–3.29) were predictors of adenomas. Younger men with a BMI of at least 27 were more likely to have proximal adenomas (OR=2.23, 95% CI: 1.14–4.37) but not advanced adenomas. There was no relation between BMI and adenomas in younger women. Among women aged between 50 and 59 years, increasing BMI (OR=1.03, 95% CI: 1.01–1.05) and a BMI of at least 24 (OR=1.43, 95% CI: 1.06–2.94) was found to be correlated with adenomas, and increasing BMI was also found to be associated with proximal adenomas (OR=1.67, 95% CI: 1.13–2.45). Among men aged between 50 and 59 years, there was no relation between BMI and adenomas, but there was a positive correlation for advanced adenomas (OR=1.05, 95% CI: 1.002–1.09). Among women aged between 50 and 59 years, BMI was not predictive of advanced adenomas. Conclusion The association between BMI and adenoma differs by age and sex. If BMI is utilized to refine screening practices for colorectal cancer, its influence on sex and age should be taken into account.

Hispanic Americans and Non-Hispanic White Americans Have a Similar Inflammatory Bowel Disease Phenotype: A Systematic Review with Meta-Analysis

BackgroundInflammatory bowel disease (IBD) is a devastating immune-mediated disease on the rise in Hispanics living in the USA. Prior observational studies comparing IBD characteristics between Hispanics and non-Hispanic whites (NHW) have yielded mixed results.AimsWe performed a meta-analysis of observational studies examining IBD phenotype in Hispanics compared to NHW.MethodsWe conducted a systematic search of US-based studies comparing IBD subtype (Ulcerative Colitis: UC or Crohn’s disease: CD) and phenotype (disease location and behavior) between Hispanics and NHW. We evaluated differences in age at IBD diagnosis, the presence of family history and smoking history. A random effects model was chosen “a priori.” Categorical and continuous variables were analyzed using odds ratio (OR) or standard mean difference (SMD), respectively.ResultsSeven studies were included with 687 Hispanics and 1586 NHW. UC was more common in Hispanics compared to NHW (OR 2.07, CI 1.13–3.79, p = 0.02). Location of disease was similar between Hispanics and NHW except for the presence of upper gastrointestinal CD, which was less common in Hispanics (OR 0.58, CI 0.32–1.06, p = 0.07). Hispanics were less likely to smoke (OR 0.48, CI 0.26–0.89, p = 0.02) or have a family history of IBD (OR 0.35, CI 0.22–0.55, p < 0.001). CD behavior classified by Montreal classification and age at IBD diagnosis were similar between Hispanics and NHW.ConclusionUC was more common among US Hispanics compared to NHW. Age at IBD diagnosis is similar for both Hispanics and NHW. For CD, disease behavior is similar, but Hispanics show a trend for less upper gastrointestinal involvement. A family history of IBD and smoking history were less common in Hispanics.

Hispanics Coming to the US Adopt US Cultural Behaviors and Eat Less Healthy: Implications for Development of Inflammatory Bowel Disease

IntroductionThe incidence of inflammatory bowel disease (IBD) among US Hispanics is rising. Adoption of an American diet and/or US acculturation may help explain this rise.AimsTo measure changes in diet occurring with immigration to the USA in IBD patients and controls, and to compare US acculturation between Hispanics with versus without IBD. Last, we examine the current diet of Hispanics with IBD compared to the diet of Hispanic controls.MethodsThis was a cross-sectional study of Hispanic immigrants with and without IBD. Participants were recruited from a university-based GI clinic. All participants completed an abbreviated version of the Stephenson Multi-Group Acculturation Scale and a 24-h diet recall (the ASA-24). Diet quality was calculated using the Healthy Eating Index (HEI-2010).ResultsWe included 58 participants: 29 controls and 29 IBD patients. Most participants were Cuban or Colombian. Most participants, particularly those with IBD, reported changing their diet after immigration (72% of IBD and 57% of controls). IBD participants and controls scored similarly on US and Hispanic acculturation measures. IBD patients and controls scored equally poorly on the HEI-2010, although they differed on specific measures of poor intake. IBD patients reported a higher intake of refined grains and lower consumption of fruits, whereas controls reported higher intake of empty calories (derived from fat and alcohol).ConclusionThe majority of Hispanics change their diet upon immigration to the USA and eat poorly irrespective of the presence of IBD. Future studies should examine gene–diet interactions to better understand underlying causes of IBD in Hispanics.

Diabetic gastroparesis: current challenges and future prospects

Diabetic gastroparesis (DMGP) is a condition of delayed gastric emptying after gastric outlet obstruction has been excluded. Symptoms of nausea, vomiting, early satiety, bloating, and abdominal pain are associated with DMGP. Uncontrolled symptoms can lead to overall poor quality of life and financial burdens on the healthcare system. A combination of antiemetics and prokinetics is used in symptom control; metoclopramide is the main prokinetic available for clinical use and is the only U.S. Food and Drug Administration-approved agent in the United States. However, a black box warning in 2009 reporting its association with tardive dyskinesia and recommending caution in chronically using this agent beyond 3 months has decreased its role in clinical practice. There is an unmet need for new prokinetics with good efficacy and safety profiles. Currently, there are several new drugs with different mechanisms of action in the pipeline that are under investigation and show promising preliminary results. Surgically combining gastric electrical stimulation with pyloroplasty is considered “gold” standard. Advances in therapeutic endoscopic intervention with gastric per-oral endoscopic pyloromyotomy have also been shown to improve gastric emptying and gastroparesis (GP) symptoms. In this review, we will comment on the challenges encountered when managing patients with DMGP and provide an update on advances in drug development and endoscopic and surgical interventions.

Tu1064 Insurance Approval Patterns for IFN-Free Regimens in HCV: Impact of National Guidelines

Introduction: Patients infected with the hepatitis C virus (HCV) have long been awaiting interferon-free regimens. The possibility of using two Direct Acting Antivirals (DAAs) became a possibility in clinical practice in December 2013, albeit at a significant financial cost. Guidelines were released in part by the AASLD on January 30th, 2014 with specific treatment recommendations in various patient populations. Included in these recommendations was that patients who have received a liver transplant should be treated with 12 or 24 weeks of daily sofosbuvir and simeprevir. We examined approval patterns for DAAs and factors affecting patient access. Methods: This was an IRB approved retrospective review. Two hundred and forty-five consecutive patients whose prescriptions for IFN-free regiments submitted by the University of Miami Hepatology Faculty were included and 82 pending prescriptions were not included. Most patients (96%) were genotype 1a or 1b, and 66 were post-transplant. 86% of prescriptions were for 12 weeks of sofosbuvir and simeprevir, and the remainder was for sofosbuvir and ribavirin. Type of insurance was noted. Those who required foundation assistance were excluded from the analysis. Statistical analysis with parametric, non-parametric or multivariate analysis was performed using JMP SAS software. Results: 71% of prescriptions were filled at an estimated cost of

Mo1077 Clinical Efficacy of Same Day CT Colonography Following Incomplete Colonoscopy

26,090,000. A prior authorization was submitted to every insurance company on each case. There was a significant change in the approval pattern after the release of the AASLD guidelines (80 vs. 64%, p= 0.0057). After this date, post-liver transplant patients were also significantly more likely to have an IFN-free regimen approved (90 vs. 69%, p=0.04). There was also significant variation by medical insurance company. Patients with Medicare or Medicaid were most likely to have their drug approved compared with private insurance (85 vs. 68%, p=0.01). Conclusions: National guidelines appear to affect insurance company approval process. Approval rates in liver transplant patients significantly increased after AASLD guidelines indicated that they should be treated with interferon-free regimens. Those with public insurance were most likely to be approved compared to private insurance. National societies need to continue to make specific recommendation for the benefit of patient care.

Embedded Pork Bone Causing Esophageal Perforation and an Esophagus-Innominate Artery Fistula

Background: Colonoscopy is the preferred screening method for colorectal cancer (CRC) but may be incomplete in 4% to 25% of cases. CT colonography (CTC) is an adjunct to evaluate the colon after an incomplete colonoscopy (IC). No study has focused on same day CTC after an IC. Our primary aim was to determine the yield of same day CTC after IC. Methods: Our institution has the capability to perform same day CTC in patients with an incomplete colonoscopy. This was a retrospective review of all CTC done immediately following IC from January 2008 to December 2012. 198 CTC met inclusion criteria. Descriptive statistics were used. Results: Of 198 patients with IC and CTC 50 patients had 61 intracolonic findings. 23/50 (46%) were screening procedures, 1/50 (2%) high risk screening, 17/50 (34%) had a diagnostic colonoscopy and 9/50 (18%) surveillance colonoscopy. 10/50 patients had 12 findings on CTC on areas that were not reached by incomplete colonoscopy. 6 of these 10 patients had a follow up intervention: 2 had retrograde double balloon enteroscopy and 4 had colonoscopies. 3 findings correlated with CTC (1 ascending colon adenocarcinoma and 2 polyps) and 3 did not ( normal colonoscopy/DBE). 40 patients had 49 colonic findings on CTC on areas reached but not described during IC. 19/49 (39%) findings were not described during the initial colonoscopy. Only 6 of these 40 pts had a repeat colonoscopy. 9 findings did not correlate with subsequent complete colonoscopy. Only 1 CTC finding correlated with repeat colonoscopy. There were 30 colonic findings on CTC in areas that were reached and described during the incomplete colonoscopy. Nineteen were sigmoid diverticular strictures with no additional findings in the rest of the colon, 10 were diverticulosis of the sigmoid and 1 ascending colon adenocarcinoma with no synchronous lesions. Conclusions: Same day CTC can be of added value in patients with incomplete colonoscopy. Potential benefits include no need to repeat bowel cleansing and no extra day lost from work. Our data showed that correlation of findings by CTC in areas not visualized by incomplete colonoscopy was poor as 50% of patients had CTC abnormalities which did not correlate with a repeat colonoscopy. When CTC described an abnormality in an area already reached but not described during IC correlation was also poor as only one patient had correlation between CTC and repeat colonoscopy. When CTC reported the same findings described during IC correlation was 100%. More data on the efficacy and cost-effectiveness of same day CTC compared to repeating a colonoscopy or maybe performing a retrograde overtube assisted enteroscopy is needed to determine which effort is worthwhile.