Hepatic Amyloidosis With Multiorgan Involvement.

Amyloidosis is a diverse entity that poses both diagnostic and treatment challenges. Whether systemic or local, amyloidosis has varied manifestations including occasional hepatic involvement. Hepatic amyloidosis, although rare, should be on the differential for those with unexplained hepatomegaly, cholestasis, alkaline phosphatase elevations, other associated organomegaly, and those with certain epidemiologic risks. In this study, we report a case of a man with systemic amyloid light chain amyloidosis with multiorgan involvement, acute liver injury, cholestasis, nephrotic syndrome, cardiomegaly, and bleeding diathesis.

Severe Cholestatic Drug-Induced Liver Injury With Cephalosporin Use.

Drug-induced liver injury (DILI) is a phenomenon that occurs with nearly all classes of medications. Cholestatic DILI represents a fraction of these cases and can present as bland cholestasis, cholestatic hepatitis, secondary sclerosis cholangitis, and vanishing bile duct syndrome. Risk factors have been identified for cholestatic DILI, including older age, genetic determinants, and certain medications such as amoxicillin-clavulanate. Here, we describe a complicated case of severe cholestatic DILI secondary to cephalosporin use. A 27-year-old female presented to the hospital initially with fever and abdominal pain for four weeks after an emergency C-section for pre-eclampsia and hemolysis, elevated liver enzymes, lowered platelets (HELLP) syndrome. She was found to have a retroperitoneal abscess and underwent bilateral drain placement. She was initially started on cefazolin, and then coverage was broadened to cefepime. Shortly after, alkaline phosphatase (ALP) rose and peaked at 3498 IU/L, with aspartate aminotransferase (AST) and alanine transaminase (ALT) elevated at 274 IU/L and 122 IU/L, respectively. Extensive testing for secondary causes and a liver biopsy were consistent with DILI. Liver enzymes down-trended with the cessation of cefepime. This case report highlights that prompt recognition of the culprit medication is paramount to recovering normal liver function.

Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1.

NAD(+) is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+)-consuming enzymes. Nicotinamide riboside is a recently discovered eukaryotic NAD(+) precursor converted to NAD(+) via the nicotinamide riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a K(m) for nicotinamide riboside of 22 microm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake.