Vilas R. Patwardhan

Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study.

Background:Infliximab (IFX) is effective in the treatment of inflammatory bowel disease; however, the effect is often not durable. It is unknown if proactive therapeutic concentration monitoring (TCM) of IFX improves outcomes. Methods:This is a retrospective observational study examining the use of proactive TCM and titration of IFX to a target concentration for patients with inflammatory bowel disease in clinical remission at a tertiary care center. The primary aim was to describe the clinical course of patients who had proactive TCM. A secondary analysis was done to assess if this strategy was superior to the standard of care. Results:Forty-eight patients were identified as having proactive TCM. Fifteen percent had an initial undetectable trough concentration. Twenty-five percent (12 of 48) of patients escalated IFX after the first proactive TCM while 15% (7 of 48) of patients de-escalated IFX therapy over the study period. A control group of 78 patients was identified. Patients who had proactive TCM had a greater probability of remaining on IFX than controls (hazard ratio, 0.3; 95% confidence interval, 0.1–0.6; log rank test; P = 0.0006). The probability of remaining on IFX was greatest for patients who achieved a trough concentration >5 &mgr;g/mL (hazard ratio, 0.03; 95% confidence interval, 0.01–0.1; P < 0.0001 versus trough <5 &mgr;g/mL). Fewer patients in the proactive TCM group stopped IFX (10% versus 31%, P = 0.009). Conclusions:In this pilot observational study, proactive TCM of IFX frequently identified patients with low or undetectable trough concentrations and resulted in a greater probability of remaining on IFX.

The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: a prospective study

OBJECTIVES:Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.METHODS:We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.RESULTS:We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006–0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18–28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861–6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216–1.89, P=0.40).CONCLUSIONS:Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Refining the Ammonia Hypothesis: A Physiology-Driven Approach to the Treatment of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to account for these other factors instructs a solid foundation for the effective treatment and prevention of hepatic encephalopathy.

Review article: the management of portal hypertensive gastropathy and gastric antral vascular ectasia in cirrhosis.

Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are important causes of both acute and chronic gastrointestinal bleeding in patients with cirrhosis.

Treatment cessation in noncirrhotic, e-antigen negative chronic hepatitis B is safe and effective following prolonged anti-viral suppression with nucleosides/nucleotides.

The treatment of HBeAg‐negative chronic hepatitis B (CHB) is considered to be open‐ended, with no guidelines for treatment cessation.

Acute hepatitis C infection lowers serum lipid levels

Summary.  Chronic hepatitis C infection is associated with hypolipidaemia that resolves with viral clearance. Lipid levels in a subgroup of patients rebound to levels that may increase the risk of coronary heart disease. The impact of acute hepatitis C infection and its clearance on lipid levels is unknown. We undertook a retrospective evaluation of subjects with acute hepatitis C infection evaluating lipid levels before, during and following acute infection. Thirty‐eight subjects with acute hepatitis C infection had lipid levels available. Twelve patients had pre‐infection and intra‐infection lipid levels available. Cholesterol (197.8–152.4 mg/dL, P = 0.025), low‐density lipoprotein (LDL) (116.1–76.3 mg/dL, P = 0.001) and non‐high‐density lipoprotein (non‐HDL) cholesterol (164.0–122.7 mg/dL, P = 0.007) decreased dramatically during acute hepatitis C virus infection. Nineteen patients who achieved viral clearance had lipid levels available during infection and following resolution of infection. In these patients, cholesterol (145.0–176.0 mg/dL, P = 0.01), LDL (87.0–110.1 P = 0.0046) and non‐HDL cholesterol (108.6–133.6 mg/dL, P = 0.008) increased significantly. No change was seen in patients who developed chronic infection. Four patients had lipid levels before, during and following resolution of infections and had increased postinfection LDL, cholesterol and non‐HDL cholesterol from pre‐infection levels, indicating acute infection may be associated with an increase in postinfection lipid levels and may confer an increased risk of coronary heart disease. Acute hepatitis C infection results in hypolipidaemia with decreased LDL, cholesterol and non‐HDL cholesterol levels that increase following infection resolution. Levels may increase above pre‐infection baseline lipid levels and should be monitored.

Fellowship Colonoscopy Training and Preparedness for Independent Gastroenterology Practice.

Goals: To objectively assess when gastroenterology (GI) fellows achieve technical competency to perform colonoscopy independently. Background: New guidelines to assess the procedural competency of GI fellows in training have been developed. Although comprehensive, they do not account for the quality metrics to which independently practicing gastroenterologists are held. Study: We performed a prospective study examining consecutive colonoscopies performed by GI fellows from November 2013 through March 2014 at an academic medical center. Using a brief postprocedure questionnaire and the online medical record, we measured rates of independent fellow cecal intubation rate (CIR), insertion time to the cecum (cecal IT), and independent polypectomy rate. Our secondary outcomes were adenoma detection rate and polyp detection rate. Results: A total of 898 colonoscopies performed by 10 GI fellows were analyzed. In the multivariate analysis, CIR [odds ratio (OR)=1.29, P=0.012], cecal IT (&bgr;-coefficient=0.19, P=0.006), and rates of unassisted independent snare polypectomy (OR=1.36, P<0.001) all improved significantly with increased number of procedures performed (OR and &bgr;-coefficient per 100 colonoscopies performed). After performing 500 colonoscopies, fellows achieved a mean CIR>90%, cecal IT between 7 and 10 minutes, and independent polypectomy rate of 90% with further improvement in cecal IT to <7 minutes, and independent snare polypectomy of >95% after 700 cases. Conclusions: Current procedural recommendations for fellowship training may underestimate the technical skill necessary for independent GI practice upon completion of fellowship. Technical proficiency in snare polypectomy may lag behind proficiency in cecal intubation.

Risk Factors for Adverse Outcomes in Patients Hospitalized With Lower Gastrointestinal Bleeding

OBJECTIVE To determine which risk factors and subtypes of lower gastrointestinal bleeding (LGIB) are associated with adverse outcomes after hospital discharge (30-day readmissions, recurrent LGIB, and death). PATIENTS AND METHODS We conducted a prospective observational study of consecutive patients admitted with LGIB to Beth Israel Deaconess Medical Center from April 1, 2013, through March 30, 2014. Patients were contacted 30 days after discharge to determine hospital readmissions, recurrent LGIB, and death. Multivariable Cox proportional hazards regression models were used to describe associations of variables with 30-day readmissions or recurrent LGIB. Logistic regression was used to determine association with mortality. RESULTS There were 277 patients hospitalized with LGIB. Of the 271 patients surviving to discharge, 21% (n=57) were readmitted within 30 days, 21 of whom were admitted for recurrent LGIB. The following factors were associated with 30-day readmissions: developing in-hospital LGIB (hazard ratio [HR], 2.26; 95% CI, 1.08-4.28), anticoagulation (HR, 1.82; 95% CI, 1.05-3.10), and active malignancy (HR, 2.33; 95% CI, 1.11-4.42). Patients discharged while taking anticoagulants had higher rates of recurrent bleeding (HR, 2.93; 95% CI, 1.15-6.95). Patients with higher Charlson Comorbidity Index scores (odds ratio [OR], 1.57; 95% CI, 1.25-2.08), active malignancy (OR, 6.57; 95% CI, 1.28-28.7), and in-hospital LGIB (OR, 11.5; 95% CI, 2.56-52.0) had increased 30-day mortality risk. CONCLUSION In-hospital LGIB, anticoagulation, and active malignancy are risk factors for 30-day readmissions in patients hospitalized with LGIB. In-hospital LGIB, Charlson Comorbidity Index scores, and active malignancy are risk factors for 30-day mortality.

High Glasgow Blatchford Score at admission is associated with recurrent bleeding after discharge for patients hospitalized with upper gastrointestinal bleeding

BACKGROUND AND STUDY AIMS Upper gastrointestinal bleeding (UGIB) is associated with significant morbidity. The Glasgow Blatchford Score (GBS) can predict endoscopic intervention and in-hospital death, but the ability to predict post-discharge outcomes is unknown. The aims of the study were to determine whether the admission GBS is associated with post-discharge rebleeding and 30-day readmission following hospitalization for UGIB. PATIENTS AND METHODS In this prospective, observational, cohort study, consecutive patients who were hospitalized with UGIB were enrolled. Admission GBS scores were calculated, and patients with GBS > 7 were classified as high risk. Patients were contacted 30 days following discharge to determine: 1) rate of hospital readmission due to rebleeding, 2) all-cause readmissions, and 3) mortality. Multivariable Cox regression was used to determine associations between GBS, rebleeding, and readmission. RESULTS A total of 336 patients with UGIB were identified. Patients with high risk GBS were older (68 vs. 62 years; P = 0.01), and were more likely to receive blood (85 % vs. 39 %; P < 0.01) and require intensive care unit admission (64 % vs. 50 %; P = 0.02). Of the 309 patients who survived to discharge, 61 (20 %) were readmitted within 30 days, 25 (8 %) of whom had rebleeding. On multivariable analysis adjusting for the need for endoscopic intervention, high risk GBS patients had higher rebleeding rates (hazard ratio [HR] 3.32, 95 % confidence interval [CI] 1.26 - 11.4). On multivariable analysis, patients with more co-morbidities (HR 1.06, 95 %CI 1.01 - 1.11) and cirrhosis (HR 2.23, 95 %CI 1.19 - 4.04) had higher 30-day readmission rates. CONCLUSIONS High GBS scores were associated with higher rebleeding rates following discharge. Patients with high GBS scores (> 7) should be monitored following discharge as they have a high risk of rebleeding.

Reappraisal of the hepatitis C virus-positive donor in solid organ transplantation.

Purpose of reviewHepatitis C virus (HCV)-positive donor allografts may be considered for HCV-positive recipients, but are underutilized. With new effective antiviral treatments, we aim to review data on the use of HCV-positive allografts in solid organ transplantation and place them in the context of the changing HCV landscape. Recent findingsHepatitis C is the most common indication for liver transplant in the USA and Europe and a significant comorbidity in patients on the waitlist for nonliver solid organ transplantation. Patients with HCV on the waitlist for nonliver solid organ transplantation have worse outcomes compared with those without HCV. However, survival after transplantation is improved compared with those who remain on the waitlist. There has been concern that use of HCV-positive allografts would lead to worse post-transplant outcomes. However, more recent data suggest that transplant outcomes for recipients who accept HCV-positive donor allografts may be comparable with those who receive HCV-negative allografts. Emerging treatments to eradicate HCV have further improved the course of HCV-positive individuals, with improved efficacy and reduced side-effects. SummaryIn view of the changing landscape of hepatitis C treatment and reduced wait time on the transplant waiting lists for those accepting HCV-positive donors, future use of select HCV-positive donors in solid organ transplantation should be encouraged.