Gurshawn Singh

Features of Patients With Gastrointestinal Bleeding After Implantation of Ventricular Assist Devices

BACKGROUND & AIMS Ventricular assist devices (VADs) are used to treat patients with end-stage heart disease. However, patients with VADs frequently develop gastrointestinal (GI) bleeding. We investigated the incidence, etiology, and outcome of GI bleeding in patients with VADs. METHODS In a retrospective study, we analyzed data from 391 consecutive patients (mean age, 53.9 ± 14.2 years; 81% male) who underwent VAD implantation for end-stage heart disease from January 2000 through May 2012 at the Cleveland Clinic. Multivariable logistic regression analysis was used to identify factors independently associated with GI bleeding in patients with VADs. RESULTS Sixty-two patients (15.9%) had GI bleeding. The risk of GI bleeding increased by 10% for every 5-year increase in age (P = .006). GI bleeding was also associated with lower body mass index (P = .046), current smoking (P = .007), and lower baseline levels of hemoglobin (P < .001). Bleeding was primarily overt (79%), and most patients presented with hematochezia (43.5%). Causes of bleeding were primarily vascular malformations (26.5%) and ulcers (26.5%). Patients who received VADs as their only therapy, rather than as a bridge-to-transplantation, were more likely to have GI bleeding (P = .008). Colonoscopy detected GI bleeding with the highest diagnostic yield; most bleeding was associated with colonic lesions (51.4%). Overall mortality was 39.4%, and 2 deaths were directly related to GI bleeding. CONCLUSIONS On the basis of a large case series analysis, GI bleeding is common after implantation of VADs (15.9% of patients have at least 1 episode of bleeding). Episodes were mostly overt and predominantly from the lower GI tract; colonoscopy is the best method of detection.

The successful use of telaprevir to treat hepatitis C recurrence after liver transplantation in an HIV co-infected patient.

The protease inhibitors, telaprevir (TVR) and boceprevir, have revolutionized the treatment of chronic hepatitis C virus (HCV) genotype 1 infection (1). Both medications are substrates and inhibitors of the cytochrome P450 3A (CYP3A) which are important for the metabolism of many commonly used medications including those used to treat human immunodeficiency virus (HIV) infection and immunosuppressive agents (2). Therefore, these protease inhibitors are not currently approved by the Food and Drug Administration for use in orthotopic liver transplantation (OLT) recipients or HIV co-infected patients because of concerns about serious drug interactions. Limited data are available on using TVR-based triple therapy to treat HCV recurrence after OLT (3) and in HIV co-infected patients (4). Since the introduction of highly active antiretroviral therapy (HAART), chronic HCV infection has become a major cause of morbidity and mortality in the HIVinfected population, and OLT has been performed in selected HIV-HCV coinfected patients (5, 6). HCV recurrence after OLT in co-infected patients is a major issue with significant effect on transplant outcomes (7, 8). This provides rationale for treating HCV recurrence with the highly effective protease inhibitors despite concerns about interactions with both immunosuppressive and HIV medications. Here we report our experience in treating recurrent HCV after OLT in a patient with HIV co-infection with TVRbased triple therapy. A 62-year-old white man with a history of HIV infection, chronic HCV genotype 1b infection complicated by the development of cirrhosis, and hepatocellular carcinoma underwent OLT in August 2011. He developed recurrent hepatitis C with a grade 2/4 inflammation, and stage 2/4 fibrosis disease was found on his liver biopsy approximately 9 months after transplantation. HAART regimen included emtricitabine-tenofovir 200 to 300 mg daily, etravirine 200 mg twice daily, and darunavir-ritonavir 600 to 100 mg twice daily owing to failure of several previous regimens and development of significant HIV resistance. His CD4 count was 461 cells/KL and he was negative for HIV-1 RNA by polymerase chain reaction. His immunosuppression regimen consisted of tacrolimus 0.5 mg every 15 days (because he was on HIV protease inhibitors) and mycophenolate mofetil 500 mg twice daily. His transaminases were in the 150 to 300 U/L range. His baseline HCV RNA was at 4,920,000 IU/mL, and his interleukin 28B genotype was CT. Before starting TVR-based triple therapy, we stopped his darunavir-ritonavir and started raltegravir 400 mg twice daily to avoid having the patient on both HCV and HIV protease inhibitors. His tacrolimus level was increased to 0.5 mg twice daily during the transitioning period. On day 1 of TVR-based therapy, the patient was started on TVR 750 mg thrice daily, ribavirin 400 mg twice daily, and pegylated interferon >2a 180 Kg weekly. In addition, he took 0.5 mg of tacrolimus, and the tacrolimus level was checked at 12 and 24 hours and every other day thereafter for 2 weeks to assess tacrolimus pharmacokinetics. No additional tacrolimus was given until the level was around 4 to 6 ng/mL. The mean area under the concentration time curve (AUC) for tacrolimus while on TVR was 348 ngIhr/mL compared to an TABLE 1. Laboratory tests and virological responses

Hereditary Hemorrhagic Telangiectasia With Liver Vascular Malformation Presenting With High-Output Heart Failure.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease manifested by formation of telangiectasias and visceral vascular malformations of organ systems, including the skin, lungs, gastrointestinal tract, brain, and liver. Hepatic involvement may lead to portal hypertension, high-output cardiac failure, and biliary strictures.1 Diagnosis requires patients to have 3 of 4 clinical characteristics: epistaxis, telangiectasia on the skin, visceral lesions, and a first-degree relative with HHT.2 Management involves controlling the source of bleeding by packing the nasopharynx, endoscopic therapies, or pulmonary or hepatic embolization.3

Hepatitis C treatment with triple therapy in a patient with hemophilia A

We report a case of successful treatment of chronic hepatitis C infection with telaprevir-based triple therapy in a patient with hemophilia A complicated by factor VIII inhibitor. A twenty-two years old male with hereditary hemophilia A and high-titer factor VIII inhibitor was taking maintenance doses of recombinant factor VIII. He visited our clinic for treatment of his chronic hepatitis C with the newly instituted protease inhibitor based therapy. He was diagnosed with hepatitis C genotype 1a at one year of age. He was initiated on telaprevir, ribavirin and peg-interferon for treatment of hepatitis C and qualified for response-guided therapy. He completed treatment at 24 wk with minimal adverse effects. Notably, after 4 wk of hepatitis C treatment, his factor VIII inhibitor screen was negative and the dose for recombinant factor VIII decreased by half of the initial dosing before he was treated for hepatitis C. We suspect that suppressing hepatitis C may help decrease factor VIII inhibitor level and the need for recombinant factor VIII.

P-130 Upper Gastrointestinal Tract Involvement Mediated by IgG4 in Patients with Ulcerative Colitis, A Retrospective Study

BACKGROUND: Involvement of upper GI tract (UGI) in patients with Ulcerative Colitis (UC) can occur. How ever the frequency, type of involvement and its pathogenesis is largely unknown and matter of active research currently. The aim of the study was to study the type and frequency of involvement of UGI tract in patients with UC and study its possible association with IgG4. METHODS: We performed a retrospective chart review of 887 patients with UC. Ninety-eight (11%) had a simultaneous EGD and Colonoscopy performed with biopsies. Demographic and clinical data along with endoscopic and histologic features of upper GI and colon were reviewed, and demographic and clinical data between patients with normal and abnormal duodenal histology were compared. Factors associated with duodenal inflammation were investigated. Patients with identified inflammation on EGD were re reviewed by pathologist and stained with IgG4 and CD 138 stains. RESULTS: Of the 98 patients with UC, 38 (38.8%) had biopsy of stomach (N = 38) and 36(36.7%) had biopsy of duodenum (N = 36) Thirty patients (30.6%) had some forms of upper GI tract involvement. On histology, 8 had active duodenitis and 4 had chronic duodenitis (Table 1). Prior exposure to immunomodulator therapy was associated with a lower risk for duodenal inflammation (Table 2). Of the 30 patients 6 patients had stained positively for IgG4 stains. Rest 24 patients had either weak IgG4 activity or no activity at all, Compared with control group which did not show any significant IgG4 activity (Table 3). CONCLUSIONS: Upper GI involvement, both gastric and duodenal, is known to occur in both Crohn’s disease and Ulcerative Colitis. Frequency and type of inflammation in upper gastro intestinal biopsies in patients with Ulcerative Colitis has not been well-studied. One unique upper gastrointestinal inflammation in Ulcerative Colitis patients is diffuse chronic duodenitis. We are increasingly seen role of IgG4 in patients with IBD especially with pouchitis. It also has been implicated in patients with autoimmune pancreatitis and PSC. This finding has various clinical implications as far as the treatment of these subsets of patient go and further randomized studies are needed to further study the same. Table. No title available. Table. No title available. Table. No title available.