Milestones in the discovery of hepatitis C.

The discovery of hepatitis C has been a landmark in public health as it brought the opportunity to save millions of lives through the diagnosis, prevention and cure of the disease. The combined work of three researchers, Alter H, Houghton M and Rice C, which set the basis for the diagnosis, treatment and prevention of hepatitis C apart from laying the ground work for a new approach to study infections in general and developing new antiviral agents. This is a story of a transfusion-associated infection. A series of clinical studies demonstrated the existence of an infectious agent associated with hepatitis. That was followed by the identification of what was later known to be the hepatitis C virus (HCV) and the development of diagnostic tests. It all preceded the full molecular identification and demonstration of a causal effect. Finally it ended up with the development and discovery of a new class of therapeutic drugs, the direct acting antivirals, which are now used not only to cure the disease but most probably, to eliminate the problem. This work started with Dr Alter H who demonstrated that a new virus was responsible for the majority of post-transfusion hepatitis followed by Houghton M who cloned the virus and developed the blood test to identify those cases that carried the virus. Finally, the work of Rice C demonstrated that a cloned HCV produced after applying molecular biology techniques could cause long-standing infection and cause the same disease as the one observed in humans

It’s a Man’s World: Does Orthotopic Liver Transplantation in the Elderly Male Confer an Additional Risk on Survival?

BACKGROUND: Orthotopic liver transplantation (OLT) in a well-selected population is a highly successful procedure, with one-year survival rates reported to be as high as 90%. Advanced age is considered to be a contraindication. Survival rates in patients >60 years of age appear to be comparable with those of younger patients. However, little objective data exist on the outcomes of patients >65 years of age undergoing OLT

Actions of thalidomide in producing vascular relaxations

We have investigated the cardiovascular actions of thalidomide in vivo and in vitro. Blood pressure was recorded in pentobarbitone anaesthetized rats. Isometric contractions were examined in rings of rat tail artery and aorta. Radioligand binding studies of α1A- and α1B-adrenoceptor sites were carried out in membranes of rat submandibular gland and spleen, respectively. In pentobarbitone anaesthetized rats, thalidomide and the T-type calcium channel blocker NNC55-0396 (both 1mg/kg, i.v.) significantly reduced blood pressure. In rat tail artery, thalidomide (10-100μM) produced relaxations of phenylephrine (1μM) induced contractions. Also in tail artery, thalidomide (100μM) significantly reduced the contraction to phenylephrine (1μM), but not KCl (40mM), produced by calcium restoration, and NNC55-0396 (100μM) had similar actions to thalidomide. Glibenclamide (10μM), calphostin C (1μM) or SB203580 (1μM) failed to affect the inhibitory actions of thalidomide, and thalidomide did not affect contractions to caffeine (10mM). Ligand binding studies found no evidence for α1A- or α1B-adrenoceptor affinity of thalidomide, and functional studies in rat aorta found no evidence for α1D-adrenoceptor affinity. It is concluded that thalidomide has previously unreported vascular relaxant actions. Relaxant actions in vitro do not seem to involve α1-adrenoceptors, caffeine sensitive calcium stores, glibenclamide sensitive potassium channels, protein kinase C (PKC) or P38 mitogen activated protein kinase (P38 MAP kinase). However, actions of thalidomide resembled those of the T-type calcium channel blocker NNC 55-0396. Further study is necessary to establish the mode of action of thalidomide in causing relaxations

Interventions for improving medication adherence in solid organ transplant recipients

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to look at the benefits and harms of using interventions for improving adherence to immunosuppressant therapies in solid organ transplant recipients, including paediatric and adult heart, lung, kidney, liver and pancreas transplant recipients

The use of transient elastography and fibrotest for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis

IMPORTANCE There is a need for noninvasive tools to monitor hepatotoxicity in patients with psoriasis who are receiving methotrexate sodium. OBJECTIVE To evaluate the use of transient elastography (TE) and FibroTest (FibroSURE in the United States), an indirect serum marker of fibrosis, in this population. DESIGN, SETTING, AND PARTICIPANTS Patients receiving methotrexate therapy for psoriasis between January 2008 and September 2009 were recruited from a dermatology outpatient department. Transient elastography and FibroTest were performed, and patients with abnormal results were considered for liver biopsy. Serial procollagen III peptide (PIIINP) results were recorded. INTERVENTIONS Transient elastography uses pulse-echo ultrasonography to measure liver stiffness, and this result is an indirect measure of hepatic fibrosis. FibroTest is an indirect serum marker of hepatic fibrosis. MAIN OUTCOMES AND MEASURES Procollagen III peptide, TE, and FibroTest results, as well as the need for liver biopsy in this cohort. RESULTS Seventy-seven patients (41 male [ 53%]) were included. Fifty (65%) patients had a valid TE assessment, and 9 (18%) had an abnormal result (range, 7.1-11.3 kPa). Being overweight or obese increased the possibility of obtaining an invalid TE result significantly (P = .01). On univariate analysis body mass index (r = 0.40, P = .005) and age (r = 0.52, P = .005) were correlated with abnormal TE results. Seventy-one patients received a FibroTest and 11 of 70 analyzed (16%) had an abnormal result (METAVIR score >F1). Age (r = 0.31, P = .009), cumulativemethotrexate dose (r = 0.31, P =.01), and duration of methotrexate therapy (r = 0.36, P = .002) were correlated with abnormal FibroTest results. There was no correlation between PIIINP levels and TE results or between PIIINP levels and FibroTest results. Steatosis was demonstrated in all 5 patients who received liver biopsies during the study. Two patients had hepatic fibrosis, with 1 showing a sinusoidal pattern of fibrosis attributed to steatohepatitis. CONCLUSIONS AND RELEVANCE Transient elastography and FibroTest are effective noninvasive tools for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. We propose that the need for liver biopsy could be reduced if abnormalities in at least 2 tests (serial PIIINP, TE, or FibroTest) are required before biopsy is considered. This strategy should be evaluated in prospective studies