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Introduction. Metabolic-associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome (MS). MAFLD patients have a higher prevalence of COVID-19. MAFLD is also associated with worse clinical outcomes of COVID-19, such as disease severity, ICU admission rate, and higher mortality rates. However, this evidence has not been well characterized in the literature. This meta-analysis aims to determine the clinical outcomes of COVID-19 among MAFLD patients compared to the non-MAFLD group. Methods. A comprehensive search was conducted in CINAHL, PubMed/Medline, and Embase for studies reporting MAFLD prevalence among COVID-19 patients and comparing clinical outcomes such as severity, ICU admission, and mortality among patients with and without MAFLD. We calculated the pooled prevalence of MAFLD among COVID-19 patients. Also, the pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated for clinical outcomes of COVID-19. Results. Twenty observational studies met inclusion criteria involving 13,036 overall study participants, including 2,374 MAFLD patients. The prevalence of COVID-19 among MAFLD patients was 0.28 (95% CI: 0.19-0.39). MAFLD was associated with the COVID-19 disease severity OR: 2.61 (95% CI: 1.77-3.83). Similarly, MAFLD was associated with an increased risk of ICU admission compared to the non-MAFLD group OR: 1.46 (95% CI: 1.12-1.91). Lastly, the association between MAFLD and COVID-19 mortality was not statistically significant OR: 1.25 (95% CI: 0.66-2.37). Conclusions. There was a higher prevalence of MAFLD among COVID-19 patients than the non-MAFLD group. Moreover, MAFLD patients had an increased risk of COVID-19 disease severity and ICU admission rate.

To analyze demographic, psychosocial, and clinical factors in pediatric liver transplant recipients for their association with death or loss to follow up in adulthood. We aimed to better understand known health disparities in transplant outcomes and identify potentially modifiable risk factors prior to transfer.A retrospective cohort study of children who underwent liver transplantation at a large tertiary transplant center and were transferred to adult care between 2000 and 2015.During the study period, 101 qualifying patients were transferred. Ninety-three individuals followed with an adult provider, while 8 were lost to follow up. In total 23 of 93 patients died after transfer (24.7%). Several childhood factors were associated with adult death: Black race [odds ratio (OR) 6.59, P0.001]; psychiatric illness or substance use (OR 2.81, P = 0.04); failure to graduate high school before transfer (OR 9.59, P0.001); posttransplant tacrolimus medication-level variability index2.5 (OR 5.36, P = 0.04); provider documentation of medication nonadherence (OR 4.72, P = 0.02); acute cellular rejection (OR 4.44, P = 0.03); the presence of diabetes mellitus (OR 5.71, P = 0.001), and chronic kidney disease (OR 2.82, P = 0.04). Failure to graduate HS was associated with loss to follow up ( P0.001). On multivariate analysis, Black race, substance use, diabetes, and failure to graduate HS retained association with adult death (each P0.05).Complex, intertwined patient characteristics are associated with increased odds of death in pediatric liver transplant recipients transferred to adult care. Early recognition of high-risk patients and intervention for modifiable factors, such as improved HS graduation and substance use prevention, may improve long-term outcomes.

Background: There is compelling evidence to support behavioral interventions as the first-line approach for bedtime resistance in young children. Among the behavioral treatment options, extinction ("cry it out") has the most extensive empirical support and tends to produce the most rapid gains. There are well known problems with the use of extinction, however, including side effects (extinction burst, spontaneous recovery) and poor acceptance, not to mention that extinction fails to teach children appropriate replacement behaviors (what "to do"). This study introduces a new behavioral sleep intervention, the Excuse Me Drill, designed to address some of the limitations of extinction. The EMD was formally evaluated for the first time using a multiple-baseline research design across four participants with sleep disturbance.Participants: Participants included four children who were clinically referred to outpatient pediatric psychology clinics for the treatment of behavioral insomnia of childhood, and included one 2-year-old female, two 7-year-old females, and one 7-year-old male. All participants had a history of dependent sleep onset at bedtime (i.e., parents remained in the child's bedroom upon sleep onset). Methods: A non-concurrent multiple baseline design across participants was used to experimentally evaluate the effectiveness of the EMD. During baseline, parents collected data on independent sleep onset and disruptive bedtime behaviors, but conducted the bedtime routine as usual. Immediately following baseline, parents implemented the EMD protocol until data indicated that children were consistently initiating sleep independently. Follow-up data were collected to determine the extent to which children continued to initiate sleep independently at bedtime in absence of the EMD. Results: Outcomes were promising as the EMD successfully taught all four children to initiate sleep independently and produced notable decreases in disruptive bedtime behavior. Results were maintained at follow-up for three of four participants. In addition, parents rated the EMD to be a socially acceptable procedure for their children. Conclusions: Results of this study indicate that the EMD was effective in promoting independent sleep onset and reducing disruptive bedtime behavior that maintained over time. The EMD should be considered to be a viable alternative to traditional extinction procedures for pediatric sleep disturbance. Implications for practice, limitations, and direction for future research are discussed.

The Johns Hopkins University School of Medicine organized 2 multistakeholder symposia on February 2, 2018 and January 11, 2019 to address the problem of high graft failure in adolescent and young adult (AYA) solid organ transplant (SOT) recipients. Participants included international experts in transplantation, behavioral psychology, patient/parent advocacy, and technology. The objectives of the symposia were as follows: (1) to identify and discuss the barriers to and facilitators of effective transfer of care for AYA SOT recipients; (2) to actively explore strategies and digital solutions to promote their successful transfer of care; and (3) to develop meaningful partnerships for the successful development, evaluation, implementation, and dissemination of these digital solutions. Additionally, data were collected from 152 AYA SOT recipients demonstrating a substantial gap in how this population uses technologies for health-related activities, alongside an increased interest in an app to help them manage their transplant.

Hepatic epithelioid hemangioendothelioma (HEHE) is an exceedingly rare vascular tumor first described by Weiss and Enzinger in 1982.1 It is a neoplasm that can arise in many different parts of the body, but most frequently involves the liver, lung, and bone.2 It disproportionately affects females with a ratio of 3:2 and 50% of cases are discovered incidentally. HEHE is misidentified in up to 80% of cases. It can be mistaken for angiosarcoma, metastatic carcinoma, hepatocellular carcinoma (HCC), or cholangiocarcinoma. While 25 – 40% of patients are asymptomatic, common presenting symptoms include right upper-quadrant pain, fatigue, nausea, vomiting, weakness, ascites, anorexia, and weight loss.2–4 Up to 37% of patients have distant metastases at the time of diagnosis and rapid progression is seen in up to 75% of cases where there are multifocal lesions.2,4 This report presents a unique case of HEHE found incidentally on computerized tomography (CT).

The initial "Frontiers in Fontan Failure" conference in 2015 in Atlanta, GA, provided an opportunity for experts in the field of pediatric cardiology and adult congenital heart disease to focus on the etiology, physiology, and potential interventions for patients with "Failing Fontan" physiology. Four types of "Fontan Failure" were described and then published by Dr Book et al. The acknowledgment that even Dr Fontan himself realized that the Fontan procedure "imposed a gradually declining functional capacity and premature late death after an initial period of often excellent palliation." The purpose of the second "Frontiers in Fontan Failure" was to further the discussion regarding new data and technologies as well as novel interventions. The 2017 "Frontiers in Fontan Failure: Innovation and Improving Outcomes" was sponsored by Children's Healthcare of Atlanta, Sibley Heart Center Cardiology, and Emory University School of Medicine. Future directions in the management of Fontan failure include further investigations into the risk of sudden cardiac death and how to properly prevent it, achievable interventions in modifying the Fontan physiology to treat or prevent late complications, and improved and refined algorithms in Fontan surveillance. Finally, further research into the interventional treatment of lymphatic-related complications hold the promise of marked improvement in the quality of life of advanced Fontan failure patients and as such should be encouraged and contributed to.

Objective To analyze the long-term outcomes in pediatric liver transplant recipients after they have transferred to an adult provider and assess for racial disparities in health outcomes. Study design This is a single-center, retrospective review of pediatric patients who underwent liver transplantation between July 1990 and August 2015 at a tertiary healthcare system with a large transplant center. Patient mortality and retransplantation were assessed after transfer to adult care. Results There were 120 patients who were transferred, of whom 19 did not meet the inclusion criteria. Of the remaining 101 patients, 64 (63%) transferred care to a nearby affiliated tertiary adult facility, 29 (29%) were followed by other healthcare systems, and 8 (8%) were lost to follow-up. Of the patients followed at our affiliated adult center, 18 of the 64 (28%) died. Of those 18 deaths, 4 (22%) occurred within the first 2 years after transfer, and 10 (55%) within 5 years of transfer. Four patients were retransplanted by an adult provider, of whom 2 eventually received a third transplant. African Americans had higher rates of death after transfer than patients of other races (44% mortality vs 16%, representing 67% of all cases of death; P = .032), with nearly 50% mortality at 20 years from time of transplantation. Conclusions Death is common in pediatric liver transplant recipients after transfer to adult care, with African Americans having disproportionately higher mortality. This period of transition of care is a vulnerable time, and measures must be taken to ensure the safe transfer of young adults with chronic health care needs.

SummaryBackground Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. Aim To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients Methods This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. Differences between SVR cohorts and predictors of SVR were analysed in an intention-to-treat (ITT) fashion. Results A total of 408 genotype 1, HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at our centre. Seventy-three patients were post-liver transplant and were treated with a median of 2.9 years from transplant. Ledipasvir/sofosbuvir achieved an SVR12 of 95.9%. African Americans made up 28.8% of the cohort. Sixty-three per cent of patients were treated previously, including 13.7% of patients previously treated with direct-acting antivirals. Only 2.7% had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease (CKD) stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR. Conclusion Our data confirm excellent SVR outcomes and favourable safety and tolerability profiles with ledipasvir/sofosbuvir without ribavirin in post-liver transplant recipients infected with HCV, despite treatment guidelines to use ribavirin.

The Johns Hopkins University School of Medicine organized 2 multistakeholder symposia on February 2, 2018 and January 11, 2019 to address the problem of high graft failure in adolescent and young adult (AYA) solid organ transplant (SOT) recipients. Participants included international experts in transplantation, behavioral psychology, patient/parent advocacy, and technology. The objectives of the symposia were as follows: (1) to identify and discuss the barriers to and facilitators of effective transfer of care for AYA SOT recipients; (2) to actively explore strategies and digital solutions to promote their successful transfer of care; and (3) to develop meaningful partnerships for the successful development, evaluation, implementation, and dissemination of these digital solutions. Additionally, data were collected from 152 AYA SOT recipients demonstrating a substantial gap in how this population uses technologies for health-related activities, alongside an increased interest in an app to help them manage their transplant.

© 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.

"Frontiers in Fontan Failure" was the title of a 2015 conference sponsored by Children's Healthcare of Atlanta and Emory University School of Medicine. In what is hoped to be the first of many such gatherings, speakers and attendees gathered to discuss the problem of long-term clinical deterioration in these patients. Specific focuses included properly defining the problem and then discussing different treatment strategies, both medical and surgical. The health of the liver after Fontan palliation was a particular point of emphasis, as were quality of life and future directions.

In this article, we review both acute and chronic liver diseases that occur as a result of heart or circulatory system failure. Ischemic hepatitis, congestive hepatopathy, cardiac cirrhosis, and Fontan liver disease are reviewed. We review clinical presentation, diagnostic data, prognosis, and available therapeutic strategies for these entities. We aim to increase awareness about cardio-hepatic disease as the prevalence of this disorder in adults is increasing. Due to advances in medical and surgical care, patients with heart disease are living longer and thus exposing long-term effects on the liver that are clinically relevant. There may be a role for dual organ transplantation in some cases, but this is a very challenging endeavor, and newer ideas about treatment or prevention are needed.

The role of ventricular dysfunction in late morbidity and mortality of univentricular hearts has been described previously. However, a significant proportion of adult Fontan patients who die or require heart transplantation do so with preserved ventricular function. The clinical deterioration in patients who have undergone Fontan palliation requires a broader view of circulatory dysfunction, one that takes into account the complex interaction of regulatory systems affecting hepatic, renal, and pulmonary blood flow, in addition to cardiac function. This review focuses primarily on the pathophysiology of multiple organ involvement in this circulatory dysfunction, with particular focus on the consequences of hepatic dysfunction and portal hypertension. The authors discuss hepatic perfusion, both in health and disease, and review the current understanding of liver histopathology and liver disease in adult Fontan patients and similar clinicopathologic states. They compare and contrast features of postsinusoidal portal hypertension with more typical adult cirrhotic disease. Finally, they delineate the related effects of portal hypertensive physiology on the systemic and pulmonary vasculature, the kidney, and the heart itself and discuss how these changes affect the care of the adult Fontan patient.

Many people believe that Somalia's economy has been in chaos since the collapse of its national government in 1991. We take a comparative institutional approach to examine Somalia's performance relative to other African countries both when Somalia had a government and during its extended period of anarchy. We find that although Somalia is poor, its relative economic performance has improved during its period of statelessness. We describe how Somalia has provided basic law and order and a currency, enabling the country to achieve the coordination that has led to improvements in its standard of living.

This paper discusses the utility of scaling laws to materials informatics and presents the algorithm Scaling LAW (SLAW), useful to obtain scaling laws from statistical data. These laws can be used to extrapolate known materials property data to untested materials by using other more readily available information. This technique is independent of a characteristic length or time scale, so it is useful for a broad diversity of problems. In some cases, SLAW can reproduce the mathematical expression that would have been obtained through an analytical treatment of the problem. This technique was originally designed for mining statistical data in materials processing and materials behavior at a system level, and it shows promise for the study of the relationship between structure and properties in materials.

The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the "real world" experience. The goal of this study was to define SVR rates in a "real world" analysis and to explore predictors of treatment response with SMV and SOF.This is a retrospective study examining the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol.The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African-American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort.Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease.

(2004). Hip‐hop white wash: The impact of Eminem on rap music and music industry economics. Socialism and Democracy: Vol. 18, Hip Hop, Race, and Cultural Politics, pp. 127-134.

A new Technical Standard that supports the clearance of materials and equipment (personal property) from U.S. Department of Energy (DOE) accelerator facilities has been developed. The Standard focuses on personal property that has the potential to be radiologically impacted by accelerator operations. It addresses material clearance programs and protocols for off-site releases without restriction on use. Common metals with potential volumetric activation are of main interest with technical bases provided in Appendices of the Standard. The clearance protocols in the Standard include three elements: 1) clearance criteria, 2) process knowledge, and 3) measurement methods. This paper presents the technical aspects of the new Standard, discusses operational experience gained in clearance of materials and equipment from several accelerator facilities at SLAC and examples as to how this Standard can be applied to benefit the entirety of the DOE Accelerator Complex.

The objective of this study was to investigate the contribution of multiple demographic and religiosity variables as predictors of ambivalent sexism toward women in a sample of LDS adults. A nationwide sample of 3563 active or former LDS participants were recruited through online social media sites and email. The research design was correlational and used survey instruments. The main findings demonstrated that gender was significantly related to the endorsement of sexism. Overall, men had greater benevolent and hostilely sexist attitudes than women. Gender also moderated the relationship between religiosity and benevolent sexism when LDS activity and affiliation were predictors, such that men's endorsement of sexism increased at a greater rate than women's. Conversely, gender moderated the relationship between all religiosity measures and hostile sexism, such that as religiosity increased, women's endorsement of hostilely sexist attitudes increased more than men's did.

We report here the isolation and characterization of two proteins, NFAR-1 and -2, which were isolated through their ability to interact with the dsRNA-dependent protein kinase, PKR. The NFAR proteins, of 90 and 110 kDa, are derived from a single gene through alternative splicing and are evolutionarily conserved nuclear phosphoproteins that interact with double-stranded RNA. Both NFAR-1 and -2 are phosphorylated by PKR, reciprocally co-immunoprecipitate with PKR, and colocalize with the kinase in a diffuse nuclear pattern within the cell. Transfection studies indicate that the NFARs regulate gene expression at the level of transcription, probably during the processing of pre-mRNAs, an activity that was increased in fibroblasts lacking PKR. Subsequent functional analyses indicated that amino acids important for NFAR's activity were localized to the C terminus of the protein, a region that was found to specifically interact with FUS and SMN, proteins also known as regulators of RNA processing. Accordingly, both NFARs were found to associate with both pre-mRNAs and spliced mRNAs in post-transcriptional studies, similar to the known splicing factor ASF/SF-2. Collectively, our data indicate that the NFARs may facilitate double-stranded RNA-regulated gene expression at the level of post-transcription and possibly contribute to host defense-related mechanisms in the cell.

Background Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events. Methods A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001 to 2011 was performed. The relationship between features of portal hypertension (VAST score ≥2, 1 point each for V arices, A scites, S plenomegaly or T hrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression. Results 73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24±11years, mean interval from Fontan 17±6years) were included in analysis. Features of portal hypertension (VAST score ≥2) were present in 26 (36%), and there were 19 major adverse events: death (n=12), transplant (n=6), and HCC (n=1). A significant relationship was found between VAST score ≥2 and major adverse events (OR=9.8, 95% CI [2.9–32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ≥2 remained significant (OR=9.1, 95% CI [1.4–57.6]). Conclusion Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings.

Liver fibrosis is a growing concern among adults with congenital heart disease, particularly for those who have undergone a Fontan operation. Liver fibrosis leads to cirrhosis, a precursor of hepatocellular carcinoma. A few cases of hepatocellular carcinoma in patients with prior palliative surgery for congenital heart disease have been identified in the literature. The current case reports the first known case of hepatocellular carcinoma in a 45-year-old male with repaired tetralogy of Fallot.

Liver fibrosis is a growing concern among adults with congenital heart disease, particularly for those who have undergone a Fontan operation. Liver fibrosis leads to cirrhosis, a precursor of hepatocellular carcinoma. A few cases of hepatocellular carcinoma in patients with prior palliative surgery for congenital heart disease have been identified in the literature. The current case reports the first known case of hepatocellular carcinoma in a 45-year-old male with repaired tetralogy of Fallot.

The critical care management of patients before liver transplantation is aimed at optimizing hepatic and extrahepatic organ function before the transplant operation, with a goal to favorably influence perioperative and postoperative graft and patient outcomes. Critical illness in liver disease can present in the context of acute liver failure or acute on chronic liver failure. The differing pathophysiologic processes underlying these 2 types of liver failure necessitate specific approaches to their intensive care management. In their extreme presentations, both types of liver failure present as multiorgan system failure; and therefore, the critical care management of these entities requires a systematic multiorgan system approach to address hepatic and extrahepatic organ dysfunction. This review provides a multiorgan system–based description of critical care management of acute liver failure and acute on chronic liver failure before liver transplantation.

Peripheral inflammatory states and their behavioral consequences including fatigue have been well-documented. One mechanism that may contribute to inflammation-induced behavioral changes is alterations in central nervous system (CNS) glutamate metabolism. To examine the role of CNS glutamate in inflammation-induced fatigue, proton magnetic resonance spectroscopy ( MRS ) was conducted in 12 patients with hepatitis C (HCV) before and after 4 weeks of treatment with interferon ( IFN )- alpha compared to 12 HCV patients awaiting IFN-alpha therapy. IFN-alpha is an inflammatory cytokine well-known to induce symptoms of fatigue in a high percentage of patients. Compared to controls, the glutamate /creatine ratio in the left basal ganglia significantly increased following 4 weeks of IFN-alpha administration ( p glutamate /creatine ratio was in turn significantly correlated with increases in fatigue severity ( r = 0.435, p = 0.034). Increased glutamate concentrations in the left basal ganglia are consistent with previously reported alterations in basal ganglia function following IFN-alpha treatment in cancer patients and patients with HCV. The data are also consistent with changes in basal ganglia function in healthy volunteers administered immune stimuli including endotoxin or typhoid vaccination. These data suggest that altered glutamate metabolism possibly as a result of altered glial function may contribute to basal ganglia changes following acute and chronic immune activation.