Cerebral Amyloid Angiopathy and the Fibrinolytic System: Is Plasmin a Therapeutic Target?

Cerebral amyloid angiopathy is a devastating cause of intracerebral hemorrhage for which there is no specific secondary stroke prevention treatment. Here we review the current literature regarding cerebral amyloid angiopathy pathophysiology and treatment, as well as what is known of the fibrinolytic pathway and its interaction with amyloid. We postulate that tranexamic acid is a potential secondary stroke prevention treatment agent in sporadic cerebral amyloid angiopathy, although further research is required

Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure

Background Chronic hepatitis C (CHC) is associated with systemic insulin resistance, yet there are limited data on the tissue‐specific contribution in vivo to this adverse metabolic phenotype, and the effect of HCV cure. Methods We examined tissue‐specific insulin sensitivity in a cohort study involving 13 patients with CHC compared to 12 BMI‐matched healthy control subjects. All subjects underwent a two‐step clamp incorporating the use of stable isotopes to measure carbohydrate and lipid flux (hepatic and global insulin sensitivity) with concomitant subcutaneous adipose tissue microdialysis and biopsy (subcutaneous adipose tissue insulin sensitivity). Investigations were repeated in seven patients with CHC following antiviral therapy with a documented sustained virological response. Results Adipose tissue was more insulin resistant in patients with CHC compared to healthy controls, as evidence by elevated glycerol production rate and impaired insulin‐mediated suppression of both circulating nonesterified fatty acids (NEFA) and adipose interstitial fluid glycerol release during the hyperinsulinaemic euglycaemic clamp. Hepatic and muscle insulin sensitivity were similar between patients with CHC and controls. Following viral eradication, hepatic insulin sensitivity improved as demonstrated by a reduction in endogenous glucose production rate. In addition, circulating NEFA decreased with sustained virological response (SVR) and insulin was more effective at suppressing adipose tissue interstitial glycerol release with a parallel increase in the expression of insulin signalling cascade genes in adipose tissue consistent with enhanced adipose tissue insulin sensitivity. Conclusion Chronic hepatitis C patients have profound subcutaneous adipose tissue insulin resistance in comparison with BMI‐matched controls. For the first time, we have demonstrated that viral eradication improves global, hepatic and adipose tissue insulin sensitivity.</p

C-ISLE: Grazoprevir/Elbasvir plus Sofosbuvir in Treatment-naive and Treatment-experienced HCV GT3 Cirrhotic Patients Treated for 8, 12 or 16 weeks

Meeting Abstract Conference: 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Location: Boston, MA Date: NOV 11-15, 2016 Sponsor(s):Amer Assoc Study Liver Di

Occult hepatitis B virus infection in Greek patients with chronic hepatitis C and in patients with diverse non-viral hepatic diseases

Occult hepatitis B virus (HBV) infection has been reported in patients with chronic hepatitis C who are negative for HBV surface antigen (HBsAg). However, the significance of 'silent' HBV in hepatitis C virus (HCV) infection is unknown. We investigated 540 subjects for the presence of occult HBV in Greek HCV patients, patients with nonviral liver diseases and healthy donors in an attempt to determine the frequency and importance of this phenomenon. One hundred and eighty-seven anti-HCV(+)/HBsAg(-) patients' sera were investigated for the presence of HBV-DNA by polymerase chain reaction. Two hundred and eighty-two selected blood donors (positive for antibodies to HBV core antigen) and 71 patients with various nonviral hepatic diseases consisted the control groups [both controls were anti-HCV(-)/HBsAg(-)]. HBV-DNA was detected in 26.2% of HCV-infected patients vs 8.5% of patients with nonviral diseases (P = 0.003) and 0/282 of donors (P = 0.0000). HBV-DNA was neither associated with HBV markers, nor with the clinical status of HCV and nonHCV patients. Neither epidemiological, histologic and virologic data nor the response to therapy were associated with the HBV-DNA detection. Hence one quarter of HCV-infected patients had occult HBV infection. Similar findings were not found in both control groups. Occult HBV infection in Greek patients with chronic hepatitis C does not seem to modify the progression of chronic liver disease. Further studies of longer duration are needed in order to clarify the role of 'silent' HBV infection in HCV-infected patients