Ravish Parekh

Liver Injury Secondary to Anti-TNF-Alpha Therapy in Inflammatory Bowel Disease: A Case Series and Review of the Literature

Background. Biologic therapy to inhibit tumor necrosis factor-alpha (TNF-α) is an effective, safe treatment for patients with inflammatory bowel disease (IBD). All TNF-α inhibitors have been associated with liver toxicity, but many of these cases have been reported in patients receiving therapy for rheumatologic disease. Herein we report the first single-center case series of TNF-α antagonist related liver injury in patients with IBD. Methods. A retrospective case series was performed at the Henry Ford Inflammatory Bowel Diseases Center. IRB approval was obtained. Results. 2 patients were treated with infliximab, whereas the 3rd patient was treated with adalimumab for IBD. All 3 patients had negative viral markers, normal autoimmune serologies, and normal biliary imaging studies. Liver biopsy was performed in all 3 patients, and evidence of portal inflammation was seen. Liver enzymes normalized after discontinuation of therapy in all patients, and no long term effects have been observed. One patient was successfully transitioned from infliximab to adalimumab without relapse of either IBD or liver injury. Conclusion. Liver injury secondary to TNF-α antagonist is an underrecognized, important clinical entity with potentially serious consequences. The mechanism of drug-induced injury is idiosyncratic. Larger cohort studies are needed to establish risk factors and injury patterns related to hepatotoxicity in these patients.

A rare case of central nervous system tuberculosis.

Intracranial abscess is an extremely rare form of central nervous system (CNS) tuberculosis (TB). We describe a case of central nervous system tuberculous abscess in absence of human immunodeficiency virus (HIV) infection. A 82-year-old Middle Eastern male from Yemen was initially brought to the emergency room due to altered mental status and acute renal failure. Cross-sectional imaging revealed multiple ring enhancing lesions located in the left cerebellum and in bilateral frontal lobe as well as in the inferior parietal lobe on the left. The patient was placed on an empiric antibiotic regimen. Preliminary testing for infectious causes was negative. Chest radiography and CT of chest showed no positive findings. He was not on any immunosuppressive medications and human immunodeficiency virus (HIV) enzyme immunoassay (EIA) test was negative. A subsequent MRI one month later showed profound worsening of the lesions with increasing vasogenic edema and newly found mass effect impinging on the fourth ventricle. Brain biopsy showed focal exudative cerebellitis and inflamed granulation tissue consistent with formation of abscesses. The diagnosis of CNS TB was finally confirmed by positive acid-fast bacilli (AFB) cultures. The patient was started on standard tuberculosis therapy but expired due to renal failure and cardiac arrest.

119 Validation of a Predictive Rule for Severe Acute Lower Intestinal Bleeding

Background: Acute lower gastrointestinal bleeding (LGIB) accounts for about 30 percent of episodes of gastrointestinal bleeding. It encompasses a wide spectrum of symptoms ranging from trivial hematochezia to massive hemorrhage with shock. Identifying those who will later develop severe bleeding is a challenge. Strate and colleagues have identified predictors of severity in patients with acute lower intestinal bleeding. The aim of this study was to provide external validation for the Strate clinical prediction rule for severe acute LGIB. Methods: We retrospectively selected patients with a principal diagnosis of LGIB between January 2007 and August 2011 at a busy urban hospital. Predictor variables were those from Strates original study: heart rate ≥ 100/min, systolic blood pressure ≤ 115 mmHg, syncope, nontender abdominal exam, rectal bleeding in the first 4 hours of evaluation, aspirin use, and >2 comorbid conditions. Severe LGIB was defined as the presence of any of the following: transfusion of ≥2 units of red blood cells in the first 24 hours, recurrent rectal bleeding after 24 hours of stability (requiring additional blood transfusions), need for ICU placement or readmission for acute LGIB within one week of discharge. An overall risk score was created by adding the number of predictive factors present. Patients were stratified into 3 risk groups: low (no risk factors), moderate (1-3 risk factors), and high (>3 risk factors). Results: Analysis was performed on 378 patients. The risk of severe bleeding in each category was: low risk 31%, moderate risk 55%, and high risk 84%. The area under the receiver operating characteristic curve (AUROC) was 0.70 with good calibration (H-L chi sq.= 0.98). The magnitude of the risk score was significantly correlated with need for blood transfusions, ICU placement and length of stay but not with need for surgery or death. Inclusion of additional variables including age, gender, actual heart rate and systolic blood pressure did not improve the AUROC for the prediction of severe bleeding. Conclusions: Strate and colleagues developed a promising clinical prediction rule for acute severe LGIB. The risk factors are simple and available within 4 hours of presentation. However, we find the predictive ability of the rule to be lower than in the original study as evidenced by the lower AUROC (0.70 versus 0.75). The Strate LGIB score does not have sufficient discriminatory power to improve the triage of patients to appropriate levels of care, nor promote a more standardized approach to acute LGIB. Further research is needed to improve our ability to identify patients presenting with LGIB who are at high risk for severe bleeding.

Tumor Necrosis Factor Alpha Inhibition for Inflammatory Bowel Disease after Liver Transplant for Primary Sclerosing Cholangitis

Background Outcome data regarding the use of tumor necrosis factor alpha inhibitors (anti-TNFα) in patients with inflammatory bowel disease (IBD) after liver transplant (LT) for primary sclerosing cholangitis (PSC) are scant. Methods We performed a retrospective chart review to investigate outcomes among a series of post-liver-transplant PSC/IBD patients receiving anti-TNFα therapy at Henry Ford Health System ((HFHS), Detroit, MI). Results A total of five patients were treated with anti-TNFα agents for IBD after LT for PSC from 1993 through 2015. Two patients were treated with adalimumab, and three were treated with infliximab. Three patients were hospitalized with severe posttransplant infections. Two patients developed posttransplant lymphoproliferative disease (PTLD); one of these patients died due to complications of PTLD. Conclusion Anti-TNFα treatment following LT worsened the disease course in our patients with concurrent PSC/IBD and led to serious complications and surgical intervention. Larger studies are needed to evaluate the side effects and outcomes of the use of such agents in this patient population. Until then, clinicians should have a high threshold to use anti-TNFα therapy in this setting.

Sa1929 Helicobacter pylori Eradication: A Single-Center Quality Improvement Study

Background: Given the close relationship between Helicobacter pylori (Hp) infection and gastric cancer, accurate diagnosis of Hp infection is important in subjects with high gastric cancer risk. At present, Hp infection is often diagnosed based on serum levels of antiH. pylori IgG antibody. However, this test is known to show false negatives for some patients. We investigated the characteristics of Hp in falsely sero-negative patients in relation to serum pepsinogen as a serum marker of gastric atrophy. Methods: A total of 276 outpatients at the University Hospital of Hamamatsu University School of Medicine who underwent gastroscopy for screening of Hp infection were enrolled. For diagnosis of Hp infection, PCR using gastric juice samples and culture tests were performed. Serum levels of pepsinogen I (PGI), pepsinogen II (PGII), and anti-H. pylori IgG antibodies (anti-Hp IgG) were measured. The ratios of PGl to PGII (PGI/PGII ratios) were calculated as a serological marker of gastric atrophy. A PGI/PGII ratio , 3.0 indicated severe gastric atrophy and increased gastric cancer risk. Samples with an anti-Hp IgG titer , 10 U/ml were diagnosed as sero-negative for Hp. If the PCR or culture test was positive, the subject was diagnosed as infected with Hp. However, if a subjects was positive based on only the PCR test, had a titer value of , 10 U/ml, and had no atrophy endoscopically, they were deemed false-positive for PCR and excluded from the analysis. Results: Of the 276 subjects, 6 were diagnosed as false-positive for PCR. Of the remaining 270, 24 were not infected with Hp or negative for anti-Hp IgG (Hp-/IgG-), 219 were infected with Hp and positive for anti-Hp IgG (Hp+/IgG+), 16 were infected with Hp but negative for negative for anti-Hp IgG (Hp+/IgG-) and therefore considered falsely sero-negative for Hp infection, and 11 were not infected with Hp but positive for anti-Hp IgG (Hp-/IgG+) and therefore considered falsely sero-positive for Hp infection. Serum PGI/PGII ratios in the Hp-/IgG-, Hp+/IgG+, Hp+/IgG-, and Hp-/IgG+ groups were 5.46, 2.55, 2.59, and 5.28 respectively. The mean of serum PGI/PGII ratios in the falsely sero-negative group was lower than those of the Hp-/IgGor Hp-/IgG+ groups (P ,0.001 and 0.003), and its subjects were considered to be at risk for severe gastric atrophy that was the same as that of the Hp+/IgG+ group. Of the 16 subjects, 15 were positive for the PCR test alone. Conclusion: The results of the present study suggest that individuals who are falsely sero-negative for Hp infection have high risk of severe atrophic gastritis. Although the serological test for Hp is a simple and easy assay for use in screening of Hp infection, it carries risk of false negatives. In contrast, the PCR method can cause false positives but can diagnose Hp infection in sero-negative subjects who are at high risk for gastric cancer.