Resmetirom: An Orally Administered, Smallmolecule, Liver-directed, ß-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty liver disease, including non-alcoholic fatty liver (NAFL) and its more progressive form, non-alcoholic steatohepatitis (NASH). The prevalence of NAFLD/NASH along with type 2 diabetes and obesity is rising worldwide. In those who develop NASH, unlike those with bland steatosis (NAFL), lipotoxic lipids drive hepatocyte injury, inflammation and stellate cell activation leading to progressive accumulation of collagen or fibrosis, ultimately leading to cirrhosis and increased risk of hepatocellular carcinoma. Hypothyroidism is associated with NAFLD/NASH; specifically, intrahepatic hypothyroidism drives lipotoxicty in preclinical models. Agonists of thyroid hormone receptor (THR)-ß, which is primarily found in the liver, can promote lipophagy, mitochondrial biogenesis and mitophagy, stimulating increased hepatic fatty acid ß-oxidation, and thereby decreasing the burden of lipotoxic lipids, while promoting low-density lipoprotein (LDL) uptake and favourable effects on lipid profiles. A number of THR-ß agonists are currently being investigated for NASH. This review focuses on resmetirom, an orally administered, once-daily, small-molecule, liver-directed, ß-selective THR agonist, as it is furthest along in development. Data from completed clincal studies outlined in this review demonstrate that resmetirom is effective in reducing hepatic fat content as measured by magnetic resonance imaging-derived proton density fat fraction, reduces liver enzymes, improves non-i nvasive markers of liver fibrogenesis and decreases liver stiffness, while eliciting a favourable cardiovascular profile with a reduction in serum lipids, including LDL cholesterol. Topline phase III biopsy data showed resolution of NASH and/or fibrosis improvement after 52 weeks of treatment, with more detailed peer-reviewed findings anticipated in order to certify these findings. Longer term clinical outcomes from both MAESTRO-NASH and MAESTRO-NASH OUTCOMES will be a pivotal juncture in the drug's road towards being approved as a NASH therapeutic.

Evaluation of Liver Disease in Pregnancy.

Liver disease in pregnancy often requires diagnostic and therapeutic considerations that are unique to pregnancy. Liver disease in pregnancy is commonly thought of as either liver disease unique to pregnancy, chronic liver disease, or liver disease coincidental to pregnancy. This review summarizes the approach to evaluation of liver disease in pregnancy.

A case of unusual presentation of acute esophageal necrosis with pneumonia.

Acute esophageal necrosis (AEN) is a rare and often fatal pathology of unclear etiology affecting the distal two-thirds of the esophagus. Typically, elderly patients with multiple comorbidities present with signs of upper gastrointestinal (GI) hemorrhage. On endoscopy, the mucosa is black due to ischemic necrosis, resulting in the commonly used term "black esophagus." We present a rare case of a 61-year-old male presenting with shortness of breath and hematemesis diagnosed as AEN through endoscopy. This case illustrates the importance of considering AEN as part of differential diagnoses in a rising elderly population with multiple comorbidities that present with upper GI hemorrhage. Treatment should be aimed at maintaining hemodynamic stability with high-dose proton pump inhibitors.

Chronic Pancreatitis Leading to Pancreatogenic Diabetes Presenting in Diabetic Ketoacidosis: A Rare Entity.

Diabetes mellitus type 3c (DM3c) is an uncommon cause of diabetes due to pancreatic pathology. Its prevalence reaches about 5-10% among all diabetics in the Western world, largely due to chronic pancreatitis. DM3c occurs due to the destruction of the endocrine islet cells. Glucagon and insulin levels are both decreased due to the destruction of alpha and beta cells, respectively. This makes the development of diabetic ketoacidosis (DKA) a rare process in patients with DM3c because of the destruction of glucagon, which facilitates ketone production. We report a case of DM3c presenting with DKA. The patient presented with a history of chronic pancreatitis and was on pancreatic enzyme replacement therapy. Prior records revealed that HbA1c levels were normal. Prior computed tomography evidence revealed diffuse pancreatic calcifications. The patient was admitted for DKA, presenting with hyperglycemia, blood glucose of 703 mg/dL, bicarbonate of 16 mmol/L, ketones in the urine and acetone in the blood. The patient's anion gap corrected for albumin was 27. The patient was admitted to the medical intensive care unit where he was treated with intravenous (IV) insulin and IV hydration. Once the anion gap closed, the patient was transitioned to long-acting insulin. HbA1c level on admission was elevated, autoimmune causes of diabetes were sent and were negative, ruling out late onset type 1 diabetes. This shows that although it is a rare phenomenon, diabetics with DM3c can present in DKA.