Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations.

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.

Effect of small bowel transit time on accuracy of video capsule endoscopy in evaluating suspected small bowel bleeding.

BACKGROUND: Obscure small bowel bleeding is defined as gastrointestinal bleeding (GIB) that is unidentifiable with esophagogastroduodenoscopy and a colonoscopy with video capsule endoscopy (VCE) being the next gold standard step for evaluation. Small bowel transit time (SBTT) is a metric of a VCE study that is defined as the time the capsule takes to travel through the small intestine. AIM: To determine if SBTT within the VCE study, correlates to overall detection of obscure small bowel bleeds. Furthermore, we attempted to identify any existing correlation between SBTT and re-bleeding after a negative VCE study. METHODS: This is a single center retrospective analysis of VCE studies performed for overt and occult GIB at Einstein Medical Center, Philadelphia, between 2015 and 2019. Inclusion criteria primarily consisted of patients 18 years or older who had a VCE study done as part of the workup for a GIB. Patients with incomplete VCEs, poor preparation, or with less than 6 mo of follow up were excluded. A re-bleeding event was defined either as overt or occult within a 6-mo timeframe. Overt re-bleeding was defined as Visible melena or hematochezia with > 2 gm/dL drop in hemoglobin defined an overt re-bleeding event; whereas an unexplained > 2 gm/dL drop in hemoglobin with no visible bleeding defined an occult re-bleed. RESULTS: Results indicated that there was a significant and positive point biserial correlation between SBTT of 220 min and detection of a bleeding focus with a statistically significant p value of 0.008. However, the area under the curve was negligible when trying to identify a threshold time for SBTT to discriminate between risk of re-bleeding events after a negative VCE. CONCLUSION: In terms of SBTT and association with accuracy of VCE finding a bleeding focus, 220 min was found to be adequate transit time to accurately find a bleeding focus, when present. It was found that no threshold SBTT could be identified to help predict re-bleeding after a negative VCE.

Lupus nephritis: maintenance therapy for lupus nephritis--do we now have a plan?

Lupus nephritis (LN) increases the morbidity and mortality of patients with SLE. This review compares the randomized, controlled trials that examined various maintenance regimens available to treat LN. Currently, mycophenolate mofetil (MMF) and azathioprine (AZA) are the most popular therapeutic agents used for long-term maintenance of LN. Long-term maintenance with MMF is recommended as the first choice after achieving remission with cyclophosphamide or MMF induction. MMF is effective in consolidating remission and preventing relapse and CKD in patients of diverse races and ethnicities. Long-term maintenance with AZA is the recommended second choice, especially when patients develop intolerance of or contraindications to MMF. Azathioprine is particularly effective in consolidating remission and preventing relapse and CKD in patients who receive an induction regimen of cyclophosphamide. To date, there are no data on how rapidly maintenance therapies can be withdrawn; however, it is recommended that the immunosuppressive therapy be maintained indefinitely, unless it is contraindicated, in patients at high risk for progression to CKD.