Oral Anticoagulation in Patients With Liver Disease

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are “auto-anticoagulated” and thus protected from thrombotic events. Warfarin and non–vitamin K–antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.     

Infections in Patients With Rheumatoid Arthritis Undergoing Anti-TNFα Drug Therapy

Infections are more frequent in patients with rheumatoid arthritis (RA). The capacity of the anti-TNF drugs (infliximab, etanercept, and adalimumab) to increase the risk of infections has been a motive of discussion during the past years. Only in two of the trials that have allowed the marketing of the infliximab and adalimumab more serious infections were observed. TB was not observed in the trials. Nevertheless, later they have been published not controlled studies that show infections and TB in patients with RA that receive anti-TNFα drugs. The disagreement between the trials and the not controlled studies has been the motive of the accomplishment of metaanalysis which study the frequency of infections in patients with RA that receive anti-TNFα drugs. The three metaanalysis published show an increase of the risk of infections in patients with AR in treatment with infliximab and with adalimumab, specially when they administer high doses. This risk does not seem to increase with etanercept, probably due to the fact that doses superior to the recommended ones have not been used in the analyzed trials. Increased risk of infections was not detected in the trials, but the metaanalysis increases the statistical power and allow demonstrating increased risk of infections. A causal relation exists between the administration of anti-TNFα and the development of infections, fulfilling all the criteria of causality.     

The Effects of N-Acetylcysteine on Bile Duct Ligation–Induced Liver Fibrosis in Rats

Stellate cells are activated by free radicals, and synthesize collagen. N-acetylcysteine (NAC) is a precursor of reduced glutathione and a potent scavenger of hydroxyl radicals and has potential antifibrotic effects. We aimed to test the effects of NAC on bile duct ligation (BDL) induced liver damage in rats. Forty-seven Wistar rats were divided into 5 groups: group 1, BDL + NAC (n = 10); group 2, BDL (n = 10); group 3, sham + NAC (n = 10); group 4, sham (n = 10); and group 5, control group (n = 10). NAC (50 μmol/kg per day) or saline of single doses were administered intraperitoneally for 28 days. Serum biochemical and liver oxidative stress parameters were studied. Liver collagen level was determined by the method of Lopez de Leon and Rojkind. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. Aspartate aminotransferase (AST) and alkaline phosphatase levels in the BDL + NAC group were lower than the BDL group and were higher than the control groups (all P < .001). Malondialdehyde, luminal, and glutathione levels in group 1 were lower than the BDL group (P = .01, P = .002, and P < .001) and higher than the control groups (all P < .001). NAC had no effect on alanine aminotransferase (ALT), gammaglutamyl transferase, bilirubin, albumin, or lucigenin levels. Liver collagen levels were higher in the BDL groups (P < .001); however, NAC had no effect on the collagen levels. The BDL groups showed stage 3 fibrosis; all the control groups were normal. NAC improved some biochemical parameters (AST, alkaline phosphatase) and oxidative stress parameters (malondialdehyde, luminol, glutathione) in the BDL model. NAC was found to be effective on cholestasis-induced hepatotoxicity. However, NAC was inefficient as an antifibrotic agent within a 1-month period of administration in the BDL model.     

Sirolimus Attenuates Reduced-Size Liver Ischemia–Reperfusion Injury But Impairs Liver Regeneration in Rats

Background  

Evidence has suggested that immunosuppressive drugs impact ischemia–reperfusion injury.     

Predicting Mortality in Patients With “Malignant” Middle Cerebral Artery Infarction Using Susceptibility-Weighted Magnetic Resonance Imaging: Preliminary Findings

To evaluate malignant middle cerebral artery (MCA) infarction (defined as space-occupying edema in more than 50% to 75% of the MCA territory) on magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) sequence and assess the usefulness of SWI findings, diffusion-weighted imaging (DWI) findings, and apparent diffusion coefficient (ADC) as predictors of clinical outcome.Data from 16 patients with large MCA infarction previously admitted to our institution between December 2009 and October 2012 were retrospectively collected and analyzed. Within 7 days after stroke onset, 1 neurologist and 1 neuroradiologist estimated the area of infarction on DWI/ADC and extent of prominent vessel sign (PVS) on SWI images using the Stroke Program Early MR Score (SPEMRS). The PVS on SWI was defined as a local prominence of hypointense vessels with either increased vessel number or diameter in the target area, when compared with the number or diameter of the contralateral MCA territory vessels.Six patients died and 10 survived. Although the DWI/ADC-SPEMRS and clinical profiles were similar between the nonsurvivor and survivor groups, SWI-SPEMRS was significantly lower in the nonsurvivor group (P < 0.001).The area of deoxygenation on SWI in patients with malignant MCA infarction can predict mortality. Lower SWI-SPEMRS is a potentially better predictor of poor outcome than lower DWI-SPEMRS. A larger prospective study is needed to clarify the role of SWI as a therapeutic guide in malignant MCA.     

Aspiration–sclerotherapy Results in Effective Control of Liver Volume in Patients with Liver Cysts

PURPOSE: To study the extent to which aspiration-sclerotherapy reduces liver volume and whether this therapy results in relief of symptoms. RESULTS: Four patients, group I, with isolated large liver cysts, and 11 patients, group II, with polycystic livers, underwent aspiration-sclerotherapy. Average volume of aspirated cyst fluid was 1,044 ml (range 225-2,000 ml) in group I and 1,326 ml (range 40-4,200 ml) in group II. Mean liver volume before the procedure was 2,157 ml (range 1,706-2,841 ml) in group I and 4,086 ml (range 1,553-7,085 ml) in group II. This decreased after the procedure to 1,757 ml (range 1,479-2,187 ml) in group I. In group II there was a statistically significant decrease to 3,347 ml (range 1,249-6,930 ml, P = 0.008). Volume reduction was 17.1% (range -34.7% to -4.1%) and 19.2% (range -53.9% to +2.4%) in groups I and II, respectively. Clinical severity of all symptoms decreased, except for involuntary weight loss and pain in group II. CONCLUSION: Aspiration-sclerotherapy is an effective means of achieving liver volume reduction and relief of symptoms.