Terlipressin in the management of liver disease.

INTRODUCTION: Terlipressin is a synthetic vasopressin analog which has been recently approved in the United States by the Food and Drug Administration for the treatment of hepatorenal syndrome. Terlipressin stimulates vasopressin receptors located on the smooth muscle vasculature of the splanchnic circulation and renal tubules which results in splanchnic vasoconstriction with improved renal perfusion and antidiuretic activity, respectively. AREAS COVERED: In this review, we discuss available data regarding the FDA approved use of terlipressin, safety, and tolerability, as well as highlight alternative uses in chronic liver disease currently still under investigation. EXPERT OPINION: Terlipressin is more efficacious compared to other vasoactive agents including midodrine octreotide and norepinephrine in reversal of hepatorenal syndrome and improves short-term survival. Other potential applications of terlipressin's vasoconstrictor actions reported in the literature include management of variceal hemorrhage and other complications of portal hypertension.

The Clinical Spectrum and Manifestations of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is characterized by abrupt decompensation in a patient with chronic liver disease with extrahepatic organ dysfunction and is implicated in an increased risk of mortality. ACLF may be present in approximately 20% to 40% of hospitalized cirrhosis. There are several diagnostic scoring systems for ACLF; one defined by the North American Consortium for Study of End-stage Liver Disease is the presence of acutely decompensated cirrhosis complicated by failure of two or more organ systems: circulatory, renal, neurological, coagulopathy, and/or pulmonary.

Evaluation Within 30 Days of Referral for Liver Transplantation is Associated with Reduced Mortality: A Multicenter Analysis of Patients Referred Within the VA Health System.

BACKGROUND: Successful liver transplantation offers the possibility of improved survival among patients with decompensated cirrhosis. However, there is wide variability in access to care and promptness of the transplant evaluation process in the United States. METHODS: We performed a multicenter retrospective study of 1118 patients who underwent evaluation for liver transplantation at the 6 Veterans Affairs' transplant centers from 2013 to 2018. Of these, 832 patients were evaluated within 30 d and 286 > 30 d after referral. We studied the differential effects of the time from referral to evaluation on pretransplant and posttransplant mortality and transplant list dropout and explored predictors of early transplant evaluation. RESULTS: Patients in the early evaluation group had a shorter adjusted time from referral to listing by 29.5 d (95% confidence interval [CI] -50.4, -8.5, P < 0.006), and referral to transplantation by 115.1 d (95% CI -179.5, -50.7, P < 0.0001). On a multivariable Cox hazard model, evaluation within 30 d of referral was associated with a significantly lower pretransplant mortality (adjusted hazard ratio [aHR] 0.70, 95% CI 0.54-0.91, P < 0.01), but not associated with transplant list dropout (aHR 0.95, 95% CI 0.65-1.39, P = 0.79) or posttransplant death (aHR 1.88, 95% CI 0.72-4.9, P = 0.20). An early evaluation within 30 d was positively associated with a higher MELD at referral (aHR 1.03, 95% CI 1.01-1.06, P = 0.006) and negatively associated with distance from the transplant center (aHR 0.99, 95% CI 0.99-0.99, P = 0.045). CONCLUSIONS: Evaluation of patients referred for liver transplantation within 30 d is associated with a reduction in pretransplant mortality.

Socioeconomic And Survival Differences Among Minorities With Hepatocellular Carcinoma In Florida.

BACKGROUND: Disparities in hepatocellular carcinoma (HCC) have been partly attributed to low socioeconomic status among minorities. We investigated associations between race, socioeconomic characteristics, geographic characteristics and survival in HCC patients in Florida. METHODS: Using the Florida Cancer Data System (FCDS), we analyzed HCC cases diagnosed between 1/1/2004 and 12/31/2013. To ascertain population-level socioeconomic characteristics, we linked FCDS to the 2010-2014 US Census American Community Survey and the 2013 Florida Behavioral Risk Factor Surveillance System. We also estimated patient distance to liver transplant and academic cancer centers. Using Cox proportional hazards, we modeled the association between race and survival. RESULTS: Of 10,852 patients, 13.1% were Black, 67.1% White, 15.7% Hispanic, and 3.2% Asian. At diagnosis, Blacks were younger with more extensive disease, p <0.001. Transplants were performed in 9.3% of Hispanics, 7.5% of Whites, 5.8% of Asians and 4.2% of Blacks, p <0.001. Median survival was longest in Hispanics and shortest in Blacks, p<0.001 When adjusted for gender, age, payer, SEER stage, surgery type, and receipt of treatment, Blacks had a 17% increased risk of death [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.29] and Whites a 9% increased risk of death [HR 1.09, 95% CI 1.02-1.17] compared to Hispanics. As a group, Hispanics lived closest to any transplant or academic cancer center, p <0.001. Neighborhood poverty level was highest where Hispanic patients lived, p <0.001. CONCLUSION: Though socioeconomic differences may contribute to disparities, Hispanics survived longer than Blacks and Whites in Florida despite living in the most socioeconomically depressed neighborhoods. Increased access to transplant likely contributed to improved survival. Additional research is needed to identify which individual socioeconomic and geographic determinants contribute most to disparities.

Cholestatic liver diseases: new targets, new therapies.

Cholestatic liver diseases result from gradual destruction of bile ducts, accumulation of bile acids and self-perpetuation of the inflammatory process leading to damage to cholangiocytes and hepatocytes. If left untreated, cholestasis will lead to fibrosis, biliary cirrhosis, and ultimately end-stage liver disease. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the two most common chronic cholestatic liver diseases affecting adults, and their etiologies remain puzzling. While treatment with ursodeoxycholic acid (UDCA) has significantly improved outcomes and prolonged transplant-free survival for patients with PBC, treatment options for UDCA nonresponders remain limited. Furthermore, there is no available medical therapy for PSC. With recent advances in molecular biochemistry specifically related to bile acid regulation and understanding of immunologic pathways, novel pharmacologic treatments have emerged. In this review, we discuss the standard of care and emphasize the various emerging treatments for PBC and PSC.

Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study.

BACKGROUND: Methylsulfonylmethane (MSM) has been reported to provide anti-inflammatory and antioxidant effects in both animal and man. Strenuous resistance exercise has the potential to induce both inflammation and oxidative stress. Using a pilot (proof of concept) study design, we determined the influence of MSM on markers of exercise recovery and performance in healthy men. METHODS: Eight, healthy men (27.1 ± 6.9 yrs old) who were considered to be moderately exercise-trained (exercising <150 minutes per week) were randomly assigned to ingest MSM at either 1.5 grams per day or 3.0 grams per day for 30 days (28 days before and 2 days following exercise). Before and after the 28 day intervention period, subjects performed 18 sets of knee extension exercise in an attempt to induce muscle damage (and to be used partly as a measure of exercise performance). Sets 1-15 were performed at a predetermined weight for 10 repetitions each, while sets 16-18 were performed to muscular failure. Muscle soreness (using a 5-point Likert scale), fatigue (using the fatigue-inertia subset of the Profile of Mood States), blood antioxidant status (glutathione and Trolox Equivalent Antioxidant Capacity [TEAC]), and blood homocysteine were measured before and after exercise, pre and post intervention. Exercise performance (total work performed during sets 16-18 of knee extension testing) was also measured pre and post intervention. RESULTS: Muscle soreness increased following exercise and a trend was noted for a reduction in muscle soreness with 3.0 grams versus 1.5 grams of MSM (p = 0.080), with a 1.0 point difference between dosages. Fatigue was slightly reduced with MSM (p = 0.073 with 3.0 grams; p = 0.087 for both dosages combined). TEAC increased significantly following exercise with 3.0 grams of MSM (p = 0.035), while homocysteine decreased following exercise for both dosages combined (p = 0.007). No significant effects were noted for glutathione or total work performed during knee extension testing (p > 0.05). CONCLUSION: MSM, especially when provided at 3.0 grams per day, may favorably influence selected markers of exercise recovery. More work is needed to extend these findings, in particular using a larger sample of subjects and the inclusion of additional markers of exercise recovery and performance.