Despite increasing interest and research, there remains uncertainty around the mechanism of HCV-associated cognitive impairment and other CNS effects. Imaging studies have suggested evidence of CNS immune activation[1, 9, 10] and alterations in neurotransmission in HCV infection, yet it is unclear whether this is associated
with a direct effect of viral penetration into the CNS or a result of peripheral factors acting across the blood-brain barrier. HCV genomes have isolated by a number of groups in human microglial cells and recent data show that human brain endothelial cells support productive but low-level infection by HCV. The potential importance of an extrahepatic, immune-privileged site goes beyond the neurocognitive symptoms in this infection, particularly selleck kinase inhibitor as we move into the era of interferon-free, direct-acting antiviral therapy. The expected major improvements in sustained virological responses after finite short-course combination therapies will depend on adequate drug penetration to all sites. The era of interferon-free regimens will greatly reduce the neurocognitive burden posed by interferon and offers further opportunities to test the relationships between HCV infection and
CNS symptoms. In the absence of the deleterious effect of interferon, we should expect an accelerated improvement in neurocognitive symptoms if, as suggested, they are directly attributable to selleckchem HCV per se and the promise of high-level, permanent viral eradication
becomes reality. Jasmohan S. Bajaj, M.D., M.Sc.1 “
“Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and Exoribonuclease levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation. Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P < 0.05). Transforming growth factor-β and α-SMA expressions were also reduced by caffeine. Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.