HIV Treatment Produces Economic Returns Through Increased Work And Education, And Warrants Continued US Support

Federal expenditures are under scrutiny in the United States, and the merits of continuing and expanding the President’s Emergency Plan for AIDS Relief (PEPFAR) to support access to antiretroviral therapy have become a topic of debate. A growing body of research on the economic benefits of treatment with antiretroviral therapy has important implications for these discussions. For example, research conducted since the inception of PEPFAR shows that HIV-infected adults who receive antiretroviral therapy often begin or resume productive work, and that children living in households with infected adults who are on treatment are more likely to attend school than those in households with untreated adults. These benefits should be considered when weighing the overall benefits of providing antiretroviral therapy against its costs, particularly in the context of discussions about the future of PEPFAR. A modest case can also be made in favor of having private companies in HIV-affected countries provide antiretroviral therapy to their employees and dependents, thus sharing some of the burden of funding HIV treatment

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Bile formation is an important function of the liver. Bile salts are a major constituent of bile and are secreted by hepatocytes into bile and delivered into the small intestine, where they assist in fat digestion. In the small intestine, bile salts are almost quantitatively reclaimed and transported back via the portal circulation to the liver. In the liver, hepatocytes take up bile salts and secrete them again into bile for ongoing enterohepatic circulation. Uptake of bile salts into hepatocytes occurs largely in a sodium-dependent manner by the sodium taurocholate cotransporting polypeptide NTCP. The transport properties of NTCP have been extensively characterized. It is an electrogenic member of the solute carrier family of transporters (SLC10A1) and transports predominantly bile salts and sulfated compounds, but is also able to mediate transport of additional substrates, such as thyroid hormones, drugs and toxins. It is highly regulated under physiologic and pathophysiologic conditions. Regulation of NTCP copes with changes of bile salt load to hepatocytes and prevents entry of cytotoxic bile salts during liver disease. Canalicular export of bile salts is mediated by the ATP-binding cassette transporter bile salt export pump BSEP (ABCB11). BSEP constitutes the rate limiting step of hepatocellular bile salt transport and drives enterohepatic circulation of bile salts. It is extensively regulated to keep intracellular bile salt levels low under normal and pathophysiologic situations. Mutations in the BSEP gene lead to severe progressive familial intrahepatic cholestasis. The substrates of BSEP are practically restricted to bile salts and their metabolites. It is, however, subject to inhibition by endogenous metabolites or by drugs. A sustained inhibition will lead to acquired cholestasis, which can end in liver injury