No abstract

Introduction: Amyloidosis is a rare disease that is defined by deposition of extracellular fibrils from immunoglobulin light chains which results in organ dysfunction. Many patients with primary systemic amyloid have hepatic involvement. Hepatic amyloid deposition is characterized by mild hepatomegaly and occasional elevated liver enzymes. Ultrasound may reveal a heterogenous echogenicity of the liver and Computed Tomography (CT) may reveal decreased parenchymal attenuation. Biopsy is the gold standard for diagnosis, seen as extracellular amorphous material, and Congo red staining will reveal apple-green birefringence under polarized light. Whereas amyloidosis is most often systemic, there are rare cases of isolated hepatic amyloid deposition. Leukocyte cell-derived chemotaxin 2 (ALECT-2) is a novel amyloid subtype, previously thought to be found in renal amyloid with a predominance in Hispanic patients but has recently been reported in the liver. We present a rare case of isolated hepatic amyloidosis without systemic involvement. Case Description/Methods: A 53-year-old Hispanic female with history of diabetes mellitus, hyperlipidemia, and nonalcoholic fatty liver disease presented to hepatology clinic for liver enzyme elevation. Lab studies were significant for AST 36 U/L, ALT 67 U/L, Alkaline Phosphatase, total bilirubin 2.7 mg/dL, positive anti-smooth muscle antibody (22 U), immunoglobulin G 1049 mg/dL, normal anti-nuclear antibody screen and normal anti-mitochondrial antibody. CT showed post cholecystectomy changes, a calcified granuloma in the right hepatic lobe, but otherwise normal liver. Liver biopsy showed focal amyloid deposition, mild steatosis, mild lobular activity, and rare ballooning hepatocytes without fibrosis. Positron emission tomography-CT, bone marrow biopsy, urine and serum protein electrophoresis were unremarkable. Further amyloid testing showed leukocyte chemotactic factor-2 (ALECT-2) amyloidosis. A referral for second opinion and experimental treatment options was recommended, however the patient declined. The patient has had stable lab values over the last two years with observation. Discussion: This is a rare case of isolated hepatic amyloidosis, highlighting the need for maintaining a broad differential diagnosis in a patient presenting with elevated liver enzymes. Given the rare nature of this condition, it is important to demonstrate this patient's presentation and two-year outcomes with observation, given lack of available treatment regimens.

No abstract

INTRODUCTION: Chronotherapy is the timing of medication according to biological rhythms of the host to optimize drug efficacy and minimize toxicity. Efficacy and myelosuppression of azathioprine/6-mercaptopurine (AZA/6-MP) are correlated with the metabolite 6-thioguanine, while the metabolite 6-methylmercaptopurine correlates with hepatotoxicity. METHODS: This was a single-center, 10-week prospective crossover trial involving 26 participants with inactive inflammatory bowel disease (IBD) on a stable dose and time of AZA or 6-MP therapy. Participants were switched to the opposite delivery time (morning or evening) for 10 weeks, and metabolite measurements were at both time points. RESULTS: In the morning vs evening dosing, 6-thioguanine levels were 225.7 ± 155.1 vs 175.0 ± 106.9 ( P < 0.01), and 6-methylmercaptopurine levels were 825.1 ± 1,023.3 vs 2,395.3 ± 2,880.3 ( P < 0.01), with 69% (18 out of 26) of participants had better metabolite profiles in the morning. Participants with optimal dosing in the morning had an earlier chronotype by corrected midpoint of sleep. DISCUSSION: In the first study on a potential role of chronotherapy in IBD, we found (i) morning dosing of AZA or 6-MP resulted in more optimal metabolite profiles and (ii) host chronotype could help identify one-third of patients who would benefit from evening dosing. Circadian regulation of metabolic enzymes of AZA/6-MP activity in the liver is the likely cause of these differences. This pilot study confirms the need to incorporate chronotherapy in future multicenter clinical trials on IBD disease.

INTRODUCTION: About 1-4% of all gastrointestinal malignancies are primary non-Hodgkin Lymphoma (NHL) and the most common pathologic subtype is diffuse large B-cell lymphoma (DLBCL). Risk factors include environmental exposure, Epstein Barr Virus (EBV), immunosuppression, Helicobacter Pylori (H.Pylori), and human T-cell leukemia virus type 1. The majority of patients are males over the age of 40. Patients can present with vague abdominal pain, dyspepsia, vomiting, weight loss, and bleeding. Endoscopic findings vary and include ulcers, erosions, nodules, mass, erythema, and gastric fold thickening. With appropriate therapy, the 5 year survival can be up to 90%. This case illustrates a rare presentation of gastric DLBCL, emphasizes the importance of both a broad differential diagnosis in the immunocompromised and prompt endoscopy in those with alarm symptoms. CASE DESCRIPTION/METHODS: An 18 year old male with selective IgA deficiency and a family history of Crohn’s in his father presented with 3 months of cramping abdominal pain, diarrhea with small amounts of blood and tenesmus. He also reported night sweats and a 10 pound weight loss. History was negative for fevers, localizing infectious symptoms, arthralgias, skin or visual manifestations of IBD. Laboratory evaluation revealed normal WBCs at 7.2 × 109/L with relative lymphocytosis [lymphocytes: 68% (Norm 18-52%), Neutrophils: 22% (Norm 18-52%)]. The rest of labs including Hbg, liver enzymes, albumin and CRP were normal. Given concern for Crohn’s, EGD and colonoscopy were performed. Colonoscopy to the terminal ileum with ileal and colonic biopsies was normal. EGD revealed a 1 cm non-bleeding cratered gastric ulcer with elevated edges and mild erythema in the gastric body. Biopsy of the ulcer demonstrated atypical dense lymphoid cell infiltrate with morphology and immunohistochemical features consistent with EBV + DLBCL. Duodenal biopsies were negative for Celiac disease. Gastric biopsies were negative for H. Pylori. He completed chemotherapy with R-CHOP and is in remission. DISCUSSION: This case illustrates a rare presentation of primary gastric DLBCL, given his young age and presentation with bleeding (occurring in ∼10% of cases). Even though this patient had a seemingly classic presentation for Crohn’s Disease, it is critical to maintain a broad differential diagnosis in immunocompromised patients and prioritize endoscopy in those with type B symptoms (weight loss, night sweats) in order to lead to prompt diagnosis and treatment.