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In the past decade, metagenomics studies exploring tick microbiota have revealed widespread interactions between bacteria and arthropods, including symbiotic interactions. Functional studies showed that obligate endosymbionts contribute to tick biology, affecting reproductive fitness and molting. Understanding the molecular basis of the interaction between ticks and their mutualist endosymbionts may help to develop control methods based on microbiome manipulation. Previously, we showed that Rhipicephalus microplus larvae with reduced levels of Coxiella endosymbiont of R. microplus (CERM) were arrested at the metanymph life stage (partially engorged nymph) and did not molt into adults. In this study, we performed a transcriptomic differential analysis of the R. microplus metanymph in the presence and absence of its mutualist endosymbiont. The lack of CERM resulted in an altered expression profile of transcripts from several functional categories. Gene products such as DA-P36, protease inhibitors, metalloproteases, and evasins, which are involved in blood feeding capacity, were underexpressed in CERM-free metanymphs. Disregulation in genes related to extracellular matrix remodeling was also observed in the absence of the symbiont. Taken together, the observed alterations in gene expression may explain the blockage of development at the metanymph stage and reveal a novel physiological aspect of the symbiont-tick-vertebrate host interaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guizzo, Tirloni, Gonzalez, Farber, Braz, Parizi, Dedavid e Silva, da Silva Vaz and Oliveira.)

Background: During the COVID-19 pandemic, there has been a reduction in emergency department visits and hospital admissions. We hypothesized that hemodialysis patients were decreasing their hospital visits and increasing their dialysis adherence during the COVID-19 pandemic., Material and Methods: This is a retrospective analysis of hemodialysis patients treated in the seven American Renal Associates (ARA) dialysis centers in the Dallas-Fort Worth metropolitan area. We conducted a "before-and-after" study using existing clinical data to examine patient adherence with hemodialysis between January 1 and March 14, 2020 (pre-COVID) and March 15 to May 18, 2020 (COVID) time periods. Data points included missed treatments, shortened treatments, post-dialysis weight, and hospital visits. Finally, we conducted an anonymous survey in which patients reported their hemodialysis adherence., Results: Data analysis was performed on 556 patients. Significantly fewer patients missed a single treatment in the COVID vs. pre-COVID time periods (44.1 vs. 58.6%; p < 0.001). Significantly fewer patients finished their treatment with a post-dialysis weight more than 1 kg above their estimated dry weight in the COVID vs. pre-COVID time periods (31.7 vs. 38.9%, p = 0.01). Finally, there was a reduction in total hospital visits during the COVID vs. pre-COVID periods (12.6 vs. 19.4%; p = 0.002). The anonymous survey showed patients reporting increased adherence with hemodialysis and restriction of salt and water intake., Conclusion: The COVID time period was associated with increased adherence with hemodialysis and decreased hospital visits, and patients were conscious of these changes.

Purpose of Review: Living donor transplantation provides the best possible recipient outcomes in solid organ transplantation. Yet, identifying potential living donors can be a laborious and resource intensive task that heavily relies on the recipient's means and social network. Social media has evolved to become a key tool in helping to bring recipients and potential living donors together given its ease of utilization, widespread access, and improved recipient's comfort with public solicitation. However, in the USA, formal guidelines to direct the use of social media in this context are lacking., Recent Findings: To better inform the landscape and opportunities utilizing social media in living donation, the OPTN Living Donor Committee surveyed US transplant programs to explore programs' experiences and challenges when helping patients use social media to identify potential living donors (September 2019). A large majority of survey participants ( N  = 125/174, 72%) indicated that their program provided education to use social media to identify potential living donors and most programs tracking referral source confirmed an increase utilization over time. The use of social media was compounded with program and recipient's challenges including concerns about privacy, inadequate technology access, and knowledge gaps. In this review, we discuss the results of this national survey and recent literature, and provide suggestions to inform program practices and guidance provided to patients wishing to use social media to identify potential living donors., Summary: Transplant programs should become competent in the use of social media for potential living donor identification to empower patients interested in using this tool. Social media education should be provided to all patients regardless of voiced interest and, when appropriate, revisited at multiple time points. Programs should consider developing a "team of experts" that can provide focused education and support to patients embarking in social media living donor campaigns. Care should be taken to avoid exacerbating disparities in access to living donor transplantation. Effective and timely guidance to patients in the use of social media could enhance the identification of potential living donors., Supplementary Information: The online version contains supplementary material available at 10.1007/s40472-022-00382-1., Competing Interests: Conflict of InterestSAB, LAC, and LL are UNOS staff members, and the other authors served as volunteer members of the OPTN/UNOS Living Donor Committee. ST is an employee of CareDx. KLL is a Senior Scientist of the SRTR, receives research funding related to living donation from the National Institutes of Health (R01DK120551), and is also supported by the Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation. KLL is chair of the American Society of Transplantation Living Donor Community of Practice, a member of the ASN policy and Advocacy Committee, and a member of the National Kidney Foundation Transplant Advisory Committee. Unrelated to this work, KLL receives consulting fees from CareDx and speaker honoraria from Sanofi., (© The Author(s) 2022.)

Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m 2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m 2 ; 95% CI, 17.7-25.7) at GFR <60 mL/minute/1.73 m 2 ; of these, chronic kidney disease-Epi-CysC (10.3 mL/minute/1.73 m 2 ; 95% CI, 2.1-18.4) and GFR Assessment in Liver Disease (12.6 mL/minute/1.73 m 2 ; 95% CI, 7.2-18.0) were the least biased followed by Royal Free Hospital (15 mL/minute/1.73 m 2 ; 95% CI, 5.5-24.6) and Modification of Diet in Renal Disease 6 (15.7 mL/minute/1.73 m 2 ; 95% CI, 10.6-20.8); however, there was an overlap in the precision of estimates, and the studies were limited. In ascites, overestimation of GFR was common (+8.3 mL/minute/1.73 m 2 ; 95% CI, -3.1 to 19.7). However, overestimation of GFR by 10 to 20 mL/minute/1.73m 2 is common in patients with cirrhosis with most equations in ascites and/or kidney dysfunction. A tailored approach is required especially for decisions regarding dual-organ transplantation., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Anomalous coronary arteries occur in as many as 12% of patients with tetralogy of Fallot (TOF). In patients with this condition, pulmonary hypoplasia can be prohibitive in performing a valve-sparing repair, subsequently resulting in various techniques to preserve the anomalous coronary artery. The management strategy is often complex in such a situation. We report on a case of TOF with an anomalous right coronary artery crossing the right ventricular outflow tract, with an unusual course of the right ventricular (RV) branch, which precluded placement of a valved conduit. In this case, we performed a successful repair with mobilization of the anomalous coronary artery and reconstruction of the right ventricular outflow tract with a limited transannular patch., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2020.)

Background: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe., Methods: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons., Results: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group., Conclusions: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2-5% of the infected individuals. Host genetic background might play a role in disease progression. Several previous studies across many countries report HLA haplotype to be one such factor. Here, we sequenced HLA-A, -B and -C of 66 individuals by Sequence-Based Typing (SBT), and compared the frequency of different alleles among ATLL patients, HAM/TSP patients, asymptomatic carriers and non-infected individuals living in Argentina., Results: The frequency of HLA-A, -B and -C alleles largely matched that of the general population in Argentina. We identified HLA-A*02, HLA-B*35 and HLA-C*07 as associated to protection from ATLL (p = 0.031), susceptibility to HAM/TSP (p < 0.001) and susceptibility to ATLL (p = 0.017), respectively. We also found a strong correlation between high proviral load (PVL) and disease (p = 0.008), but were unable to identify any particular allele associated with high or low PVL., Conclusions: We have found HLA-A*02, HLA-B*35 and HLA-C*07 to be associated to protection from ATLL (HLA-A*02) and susceptibility to HAM/TSP (HLA-B*35) or to ATLL (HLA-C*07), respectively. Whereas HLA-A*02 protection from ATLL has already been extensively described in other regions of the world, this is the first report that links HLA-B*35 and an increased susceptibility to HAM/TSP. As for HLA-C*07 it has previously been associated to susceptibility to HAM/TSP in other countries but in our population it has been linked to ATLL.

Stray dogs are one of the main reservoirs of intestinal parasitic infections and some have zoonotic potential. An epidemiological survey was carried out between September 2017 and May 2018 in Mexicali Valley, this area sacrifices around 92,470 head of cattle monthly, which represents 27% of the national slaughter and has 71,307 hectares for crops. In this period the Municipal Animal Control Center during their routine visits to the Mexicali Valley captured 103 dogs. All the dogs were evaluated using copromicroscopic techniques to detect intestinal parasites. The general frequency of parasitic infections was 28.15% (29/103), the most frequent parasite being Dipylidium caninum 16.50% (17/103), followed by Taenia spp. 6.79% (7/103), Taenia hydatigena 2.91% (3/103), Taenia serialis 0.97% (1/103), Taenia pisiformis (0.97%) , Toxocara canis 3.88% (4/103), Toxascaris leonina 1.94% (2/103), and Cystoisospora spp. 1.94% (2/103). No significant statistical associations were found between parasitic infections and the studied variables (sex, age, and size) however; there was a significant statistical association with the capture area. Most of the parasites found in this survey have potential to affect the human population and animal production.

Cercospora kikuchii (Tak. Matsumoto & Tomoy.) M.W. Gardner 1927 is an ascomycete fungal pathogen that causes Cercospora leaf blight and purple seed stain on soybean. Here, we report the first draft genome sequence and assembly of this pathogen. The C. kikuchii strain ARG&#95;18&#95;001 was isolated from soybean purple seed collected from San Pedro, Buenos Aires, Argentina, during the 2018 harvest. The genome was sequenced using a 2 × 150 bp paired-end method by Illumina NovaSeq 6000. The C. kikuchii protein-coding genes were predicted using FunGAP (Fungal Genome Annotation Pipeline). The draft genome assembly was 33.1 Mb in size with a GC-content of 53%. The gene prediction resulted in 14,856 gene models/14,721 protein coding genes. Genomic data of C. kikuchii presented here will be a useful resource for future studies of this pathosystem. The data can be accessed at GenBank under the accession number VTAY00000000 https://www.ncbi.nlm.nih.gov/nuccore/VTAY00000000., (© 2019 The Authors.)

Background & Aims: Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to 2016., Methods: We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change., Results: Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans., Conclusions: We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample., Methods: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index., Results: The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p < 0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks., Conclusions: Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study.

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR < 30 mL/min/1.73 m 2 . Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m 2 , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001-2015). GRAIL had less bias and was more accurate and precise as compared with CKD-EPI, MDRD-4, and MDRD-6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m 2 , the median difference (eGFR-mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m 2 as compared with CKD-EPI: 8.70 (18.24) mL/min/1.73 m 2 , MDRD-4: 8.82 (17.38) mL/min/1.73 m 2 , and MDRD-6: 6.53 (14.42) mL/min/1.73 m 2 . Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m 2 versus 36.1% (CKD-EPI), 36.1% (MDRD-4), and 52.8% (MDRD-6) (P < 0.01). An eGFR < 30 mL/min/1.73 m 2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% versus 22.0% CKD-EPI versus 23.1% MDRD-4 versus 48.3% MDRD-6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR., (© 2018 by the American Association for the Study of Liver Diseases.)

Physical inactivity is estimated to be the fourth leading cause of global mortality. Strategies to increase physical activity (PA) increasingly emphasize environmental and policy changes including the modification of neighborhood environments to promote walking and other forms of healthy activity. Open Streets (OS) initiatives, an important and growing strategy to modify neighborhood environments for PA, create temporary parks for recreational activity by closing streets to motor vehicle traffic, thereby offering health and community building benefits. We used the Stanford Neighborhood Discovery Tool (DT)-photo/voice software on a tablet-to train neighborhood residents to act as "citizen scientist" observers of the local built environment on a non-event day and during an OS initiative. The purposes of this project were as follows: (1) to assess adult residents' perceptions of neighborhood characteristics of the OS initiative in three socioeconomically diverse sites and (2) to test the DT for use in three international urban settings with OS initiatives; Bogota, Colombia; San Francisco, USA; and Temuco, Chile, among a multigenerational, multiethnic sample of adults including, for the first time, a vulnerable population of homeless adults (Bogota). Using the DT, participants walked an OS route taking photos and recording reasons for the photos, then completed a 25-item demographic/environmental observation survey and a 16-item Reflection Survey on perceived environmental changes. A total of 18 themes were reported by participants with areas of overlapping themes (e.g., Community and Social Connectedness) and areas where a single site reported a theme (e.g., Social Isolation in Older Adults). Ten of the 18 themes were identified by at least two sites including "Bike Resources" and "Services", indicating the value of programming at OS initiatives. The themes of "Festive Environment" and "Family Friendly Environment" reflect the quality of the overall environment for participants. Four themes (Community and Social Connectedness, Family Friendly Environment, PA, and Safety) were reported by all sites. Three of the four unifying themes were also ranked among the highest reported categories of "seemed better" on the Reflection Survey (Ease of Walking, Overall Safety of Neighborhood, and Friendliness of Environment), providing additional confirmation of the shared experience of social, health, and psychological benefits from OS initiatives. OS initiatives offer a global strategy for increasing neighborhood opportunities for PA and a potential site for training citizen scientists to document environmental influences on PA.

Background & Aims: Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States., Methods: Using the United Network for Organ Sharing (UNOS) registry, we collected data on patients with PBC on the liver transplant waitlist, and performed analysis with a focus on ethnicity and race-based variations clinical manifestations, waitlist mortality and LT rates from 2000 to 2014. Outcomes were adjusted for demographics, complications of portal hypertension, and Model for End-stage Liver Disease score at time of waitlist registration., Results: Although the number of white PBC waitlist registrants and additions decreased from 2000 to 2014, there were no significant changes in the number of Hispanic PBC waitlist registrants and additions each year. The proportion of Hispanic patients with PBC on the liver transplant waitlist increased from 10.7% in 2000 to 19.3% in 2014. Hispanics had the highest percentage of waitlist deaths (20.8%) of any ethnicity or race evaluated. After adjusting for demographic and clinical characteristics, Hispanic patients with PBC had the lowest overall rate for undergoing LT (adjusted hazard ratio, 0.71; 95% CI, 0. 60-0.83; P < .001) and a significantly higher risk of death while on the waitlist, compared to whites (adjusted hazard ratio, 1.41; 95% CI, 1.15-1.74; P < .001). Furthermore, Hispanic patients with PBC had the highest proportion of waitlist removals due to clinical deterioration., Conclusions: In an analysis of data from UNOS registry focusing on outcomes, we observed differences in rates of LT and liver transplant waitlist mortality of Hispanic patients compared with white patients with PBC. Further studies are needed to improve our understanding of ethnicity and race-based differences in progression of PBC., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF., Aim: To evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF., Methods: Data from a combined treatment cohort of 2 hepatology centres, which included patients previously treated with SIM/SOF ± RBV for 12 weeks but failed to achieve SVR and then underwent retreatment with LDV/SOF ± RBV, were analysed (n = 30). LDV/SOF ± RBV was administered for 12-24 weeks based on the discretion of the treating hepatologist., Results: Of the 30 patients, 23 (77%) were male, 77% were Caucasian and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had decompensated, Child's class B or C cirrhosis. Three patients were liver transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved SVR. Treatment was well tolerated with 37% reporting no adverse events. The most common adverse events were fatigue, headache, insomnia and nausea. Two patients with Child's B cirrhosis required hospitalization during treatment for variceal haemorrhage and abdominal pain respectively. However, no treatment discontinuations or deaths occurred., Conclusion: Single tablet fixed-dose combination LDV/SOF ± RBV is efficacious and well tolerated in patients who previously failed treatment with SIM/SOF, including those with decompensated cirrhosis and recurrent hepatitis C following liver transplantation., (© 2018 John Wiley & Sons Ltd.)

The use of hepatitis C virus (HCV)-positive organs in liver transplantation (LT) has increased in the era of direct-acting antiviral therapy. A rising demand for organs, the increased ability to effectively treat HCV infection in the transplant setting, and an unprecedented increase in HCV-positive donors have all contributed to this trend. A recent abrupt rise in opioid use in the United States has resulted in a surge of injection drug use, transmission of HCV, and opioid-related overdose deaths. Geographical areas most affected by the opioid epidemic have experienced a rapid increase in recovery and utilization of HCV-positive donor organs, in which the proportion of deceased donor LTs in the United States from donors who are HCV positive has increased nearly 2-fold within the last 3 years. The prospect of expanding the organ donor pool with HCV-positive donors and achieving acceptable posttransplant outcomes has generated much interest in the areas of liver, kidney, and thoracic transplantation, including the potential for transplanting organs from HCV positive donors into HCV-negative recipients. Developing strategies to ensure appropriate selection of potential recipients of HCV-positive organs, initiating timely antiviral therapy, and defining associated risks will be critical in achieving optimal posttransplant outcomes in this setting. (Hepatology 2018;67:1600-1608)., (© 2017 by the American Association for the Study of Liver Diseases.)

The Ciclovías comprise worldwide programs in which streets are closed to motor-vehicles and open to individuals for leisure activities. Currently, 93% of the regular programs are in Latin American countries (LAC). The aims of this study were to describe the characteristics of regular Ciclovías in 7 LAC and to analyze the factors that influence the sustainability and scaling-up of five case studies. We conducted a survey of 67 Ciclovías in 2014-2015. In addition, we conducted semi-structured interviews with current and former program coordinators and reviewed policy documents from Ciclovías in 5 LAC. The greatest expansion of Ciclovías has occurred since 2000. The number of participants per event ranged from 40 to 1,500,000 (mean 41,399±193,330; median 1600), and the length ranged from 1 to 113.6km (mean 9.1±16.4; median 3). Ciclovía routes connect low-middle and high income neighborhoods (89.3%), and include the participation of minority populations (61.2%). The main complementary activity offered was physical activity (PA) classes (94.0%), and 80.0% of the programs included strategies to promote biking. All five case studies met definitions for sustainability and scaling-up. All programs shared some level of government support, alliances, community appropriation, champions, compatibility with the mission of the host organization, organizational capacity, flexibility, perceived benefits, and funding stability. However, they differed in operational conditions, political favorability, sources of funding, and number of alliances. The Ciclovías of LAC showed heterogeneity within their design and sustainability factors. Both their heterogeneity and flexibility to adjust to changes make them promising examples of socially inclusive programs to promote PA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Comparability of population surveys across countries is key to appraising trends in population health. Achieving this requires deep understanding of the methods used in these surveys to examine the extent to which the measurements are comparable. In this study, we obtained detailed protocols of 8 nationally representative surveys from 2007-2013 from Brazil, Chile, Colombia, Mexico, the United Kingdom (England and Scotland), and the United States-countries that that differ in economic and inequity indicators. Data were collected on sampling frame, sample selection procedures, recruitment, data collection methods, content of interview and examination modules, and measurement protocols. We also assessed their adherence to the World Health Organization's "STEPwise Approach to Surveillance" framework for population health surveys. The surveys, which included half a million participants, were highly comparable on sampling methodology, survey questions, and anthropometric measurements. Heterogeneity was found for physical activity questionnaires and biological samples collection. The common age range included by the surveys was adults aged 18-64 years. The methods used in these surveys were similar enough to enable comparative analyses of the data across the 7 countries. This comparability is crucial in assessing and comparing national and subgroup population health, and to assisting the transfer of research and policy knowledge across countries., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only)., Conclusion: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56)., (© 2017 by the American Association for the Study of Liver Diseases.)

Direct-acting antivirals for hepatitis C virus infection may revolutionize treatment among persons with substance use disorders. Despite persons with substance use disorders having the highest hepatitis C virus prevalence and incidence, the vast majority have not engaged into care for the infection. Previously, interferon-based treatments, with substantial side effects and the propensity to exacerbate mental health conditions, were major disincentives to pursuit of care for the infection. Direct-acting antivirals with viral eradication rates of >90%, significantly improved side effect profiles, and shorter treatment duration are dramatic improvements over prior treatment regimens that should promote widespread hepatitis C virus care among persons with substance use disorders. The major unmet need is strategies to promote persons with substance use disorders engagement into care for hepatitis C virus. Although physical integration of treatment for substance use and co-occurring conditions has been widely advocated, it has been difficult to achieve. Telemedicine offers an opportunity for virtual integration of behavioral and medical treatments that could be supplemented by conventional interventions such as hepatitis C virus education, case management, and peer navigation. Furthermore, harm reduction and strategies to reduce viral transmission are important to cease reinfection among persons with substance use disorders. Widespread prescription of therapy for hepatitis C virus infection to substance users will be required to achieve the ultimate goal of global virus elimination. Combinations of medical and behavioral interventions should be used to promote persons with substance use disorders engagement into and adherence with direct-acting antiviral-based treatment approaches. Ultimately, either physical or virtual colocation of hepatitis C virus and substance use treatment has the potential to improve adherence and consequently treatment efficacy.

Lower-income populations are hit harder by the diabetes epidemic as regards both prevalence and the risk of complications. Food Insecurity is one of the mechanisms through which poverty may predispose people with low socio-economic status to poorer control and higher complication rates. The United Nations Food and Agriculture Organization defined food security as "the right to have access to sufficient nutritional and culturally acceptable food choices." Adults suffering from diabetes with limited income have a 40% greater chance of having food insecurity and an inadequate blood glucose control. Such patients have a two-fold greater risk of developing severe hypoglycemia. In addition, several studies have shown that social vulnerability resulting from food insecurity, low socioeconomic status, low educational levels, and poor health education is an independent risk factor for hypoglycemia, even after conventional predictors are controlled. This review analyzes the literature available on social vulnerability as a non-conventional risk factor for development of hypoglycemia in diabetic subjects., (Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.)

Renal cell carcinoma (RCC) has a high incidence in the kidney transplant population and annual surveillance detects these tumors early in their natural history. Minimal guidelines exist regarding RCC surveillance in ESRD patients awaiting transplant. A retrospective review of our kidney transplant database examined the outcomes of annual ultrasonographic surveillance during initial kidney transplant evaluation and upon annual reassessment. Of 2642 patients listed for transplant, 145 patients were found to have masses during initial kidney transplant evaluation or annual imaging consistent with new complex cystic disease or RCC. A total of 71 patients had RCC identified, with 52 found on initial kidney transplant evaluation and 19 identified on annual surveillance. Male gender and African-American race were independently associated with RCC (P<.05). RCC was detected a median of 2.0 years after listing (two annual ultrasonography studies). Patients with complex cysts were more likely to undergo transplantation (48.7%) compared to patients with RCC (21.1%; P<.001). There was no significant difference in survival between RCC patients and those found to have complex cystic disease, suggesting incidental RCC can be diagnosed early in the natural history and at a curable stage through implementation of a biennial surveillance program., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The origins of convolution and its further and rather complex historical development were dealt with in detail by Alejandro Dominguez in a previous article [1]. We saw there that it can be traced back to the middle of the 18th century; however, its modern form and use are not more than 50 or 60 years old.

Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Purpose: While technology is a major driver of many of society's comforts, conveniences, and advances, it has been responsible, in a significant way, for engineering regular physical activity and a number of other positive health behaviors out of people's daily lives. A key question concerns how to harness information and communication technologies (ICT) to bring about positive changes in the health promotion field. One such approach involves community-engaged "citizen science," in which local residents leverage the potential of ICT to foster data-driven consensus-building and mobilization efforts that advance physical activity at the individual, social, built environment, and policy levels., Method: The history of citizen science in the research arena is briefly described and an evidence-based method that embeds citizen science in a multi-level, multi-sectoral community-based participatory research framework for physical activity promotion is presented., Results: Several examples of this citizen science-driven community engagement framework for promoting active lifestyles, called "Our Voice", are discussed, including pilot projects from diverse communities in the U.S. as well as internationally., Conclusions: The opportunities and challenges involved in leveraging citizen science activities as part of a broader population approach to promoting regular physical activity are explored. The strategic engagement of citizen scientists from socio-demographically diverse communities across the globe as both assessment as well as change agents provides a promising, potentially low-cost and scalable strategy for creating more active, healthful, and equitable neighborhoods and communities worldwide.

Hepatocellular carcinoma (HCC) remains a major cause of mortality in patients with chronic liver disease worldwide. Early detection of HCC is critical to providing effective treatment and can have a significant impact on survival. In addition, effective surveillance following hepatic resection or locoregional ablative therapy can identify early recurrence and optimize long-term outcomes. Currently available serum tumor markers, including alpha-fetoprotein (AFP), are characterized by low sensitivity in the detection of HCC. Advances in genomic, proteomic, metabolomic, and glycomic profiling may provide a means to identify unique molecular signatures and characterization of complex processes associated with HCC incidence and recurrence. The development of highly sensitive and specific serum biomarkers for HCC may greatly enhance early detection rates, risk assessment in treatment candidates, and identification of potential new targets for anticancer therapy.

Purpose: To review the literature on the interventions used in the promotion of colorectal cancer (CRC) screening in the Hispanic population., Organizing Construct: CRC screening and Hispanic Americans., Methods: Literature published between 1999 and 2010 was reviewed using PubMed, Cumulative Index to Nursing and Allied Health Literature Plus, and Cochrane Library using the key words colorectal cancer, colorectal cancer screening, and Hispanic Americans., Findings: The studies reviewed highlighted various methods of culturally appropriate CRC screening promotion in Hispanic Americans. All studies showed an increase in fecal occult blood test (FOBT) completion and to some degree an improvement in overall CRC knowledge., Conclusions: The need for increased CRC screening and awareness studies in the Hispanic population is apparent. Future studies should use colonoscopy, a more sensitive test, to better evaluate CRC screening outcomes in Hispanics., Clinical Relevance: Participation in isolated studies involving FOBT does not necessarily lead to long-term understanding of CRC and the appropriate screening needed, hence the need for ongoing CRC education and promotion in primary care., (© 2012 Sigma Theta Tau International.)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death (1). Chronic infection with hepatitis B virus (HBV) is a major risk factor for HCC, accounting for more than one half of cases worldwide (2). Early detection of HCC in populations with chronic HBV infection through surveillance methods is critically important in providing definitive treatment for HCC and has a major impact on patient outcomes (3), including a survival benefit as demonstrated in one prospective randomised controlled trial (4). Efforts to identify populations and individuals with HBV infection who are at high risk may contribute to the development of surveillance strategies with the greatest impact on patient outcomes; however, the implementation of an individualised approach to surveillance can be challenging. This Perspective aims to explore risk factors associated with HCC in patients with chronic HBV infection, recent data on developing scoring systems to assess risk, and how these may impact surveillance strategies.

Genome-wide association studies have recently identified single nucleotide polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who are undergoing therapy with pegylated interferon (IFN) a and ribavirin. IL-28B encodes IFN-λ3, a type III IFN involved in host antiviral immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms, rs1 2979860 and rs8099917, are strong pretreatment predictors of early viral clearance and SVR in patients with genotype 1 HCV infection. Variations in the distribution of IL-28B alleles may partly explain differences in SVR rates among ethnic groups. Further investigations have implicated IL-28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL-28B may be a key factor involved in host immunity against HCV. Clinical trials of IFN-λ as a therapeutic agent for chronic HCV infection are currently underway. The use of IL-28B polymorphisms as a predictive tool will have a major impact on treatment strategies for chronic HCV infection, particularly in the context of emerging therapies and direct-acting antiviral agents.

Early diagnosis of hepatocellular carcinoma (HCC) has a significant impact on survival by implementation of effective treatment strategies, including hepatic resection, locoregional ablative therapy, and liver transplantation. The use of serum tumor markers and biopsy are particularly important for diagnosis of small hepatic lesions with atypical features on imaging studies. α-Fetoprotein remains the most frequently used tumor marker for the diagnosis of HCC. The development of novel serum biomarkers for HCC, identification of molecular markers for tissue immunohistochemistry, and emergence of new diagnostic techniques such as proteomic profiling may improve the early detection rate of HCC in the future., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Viral hepatitis is a major cause of chronic liver disease, liver failure, and hepatocellular carcinoma worldwide, resulting in significant morbidity and mortality. New insights into the pathogenesis and molecular biology of hepatitis viruses have led to the discovery of novel antiviral agents. Likewise, a greater understanding of the natural history of chronic infection, predictors of disease progression, and predictors of virologic response to therapy has resulted in more effective treatment strategies. Recent data have increasingly demonstrated that the ability to achieve a successful response to antiviral therapy may significantly reduce the risk of progressive liver disease and hepatocellular carcinoma. Immunization practices and the use of potent antiviral therapy may have a major impact in reducing the burden of chronic liver disease and the incidence of hepatocellular carcinoma associated with chronic hepatitis B and chronic hepatitis D. Individualized treatment strategies and the development of direct acting antiviral agents may lead to further improvements in the ability to achieve a sustained virologic response to therapy in chronic hepatitis C. With new advances in the treatment of chronic hepatitis, efforts to optimize viral suppression while reducing the potential for antiviral drug resistance will become increasingly important.

Hepatitis C virus (HCV) is the most common indication for liver transplantation in the United States, and recurrent disease associated with HCV is a major cause of allograft loss and mortality. Up to 30% of transplant recipients with HCV will develop progressive fibrosis and cirrhosis within 5 years of transplantation. Several recipient, donor, and viral factors have been identified as risk factors for disease progression. Likewise, immunosuppression with pulse corticosteroids or T-cell-depleting therapies such as muromonab-CD3 have been linked to HCV-associated allograft failure. Antiviral therapy with peginterferon alfa and ribavirin should be considered in select transplant recipients with recurrent HCV infection, as achievement of sustained virologic response is associated with increased allograft and patient survival; however, efficacy may be limited by poor tolerability, requirement for dose reductions, and treatment discontinuation. The use of emerging therapies such as direct-acting antiviral agents and steroid-sparing immunosuppression may play a major role in further advances associated with post-transplant management of recurrent HCV infection.

Hepatitis B virus is a major cause of chronic liver disease worldwide and is associated with an increased risk of hepatocellular carcinoma, progressive hepatic fibrosis and end-stage liver disease. Suppression of HBV replication is recognized as the primary on-treatment goal of antiviral therapy, as reduction of serum HBV DNA to low or undetectable levels is highly likely to have a positive impact on long-term clinical outcomes in HBV-associated chronic liver disease. Entecavir is an oral nucleoside analogue that effectively inhibits HBV polymerase, resulting in rapid viral suppression. Long-term data on patients receiving entecavir for chronic hepatitis B have demonstrated high potency, a low incidence of antiviral drug resistance and good tolerability, making entecavir an ideal first-line agent for the treatment of chronic hepatitis B.

Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in the liver. In animal models, HSC apoptosis is the predominant clearance mechanism of activated HSC, although data evaluating whether the same processes occur in humans are limited. We conducted a cross-sectional study to evaluate the association between HSC apoptosis and fibrosis stage in subjects with chronic hepatitis C virus (HCV) infection (n = 44) and HCV-negative controls with normal liver histology (n = 9). We used immunohistochemical techniques to identify activated (alpha-smooth muscle actin+), proliferative (Ki-67+) and apoptotic (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling+) HSC in liver biopsy specimens from all subjects. The same pathologist enumerated positive cells per high-power field (HPF, x 200) in 20 periportal/lobular areas. HSC apoptosis was decreased in HCV-positive subjects compared with controls (median 0.4, range 0.0-3.1 vs 1.1, 0.2-3.5 cells/HPF, P = 0.02). Among HCV-positive subjects, HSC apoptosis was decreased in those with moderate to advanced fibrosis (P = 0.04) compared with those with mild fibrosis. By multivariate analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence interval 0.01-0.28 cells/HPF) per increase in fibrosis stage (P = 0.04). While the number of activated and proliferative HSC was significantly increased in HCV-infected subjects compared with that in uninfected controls, the numbers of these cells did not differ between HCV-infected subjects with mild vs moderate/advanced fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased in HCV-infected subjects with advanced fibrosis. In chronic HCV infection, inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses.

A significant proportion of patients with chronic hepatitis C virus (HCV) infection who undergo antiviral therapy have persistent or recurrent viremia and fail to achieve a sustained virologic response (SVR). Factors associated with treatment failure include HCV genotype 1 infection, high serum HCV RNA levels, and advanced fibrosis. Consensus interferon (CIFN) is a synthetic type I interferon derived from a consensus sequence of the most common amino acids found in naturally occurring alpha interferon subtypes. Several prospective clinical studies have demonstrated that CIFN may be a treatment option in patients who have failed prior interferon-based therapy, including those who have failed combination therapy with standard interferon or peginterferon plus ribavirin. Daily CIFN in combination with ribavirin may be an effective regimen in this setting; however, optimal dose and treatment duration of CIFN therapy have not been well established. Patients who achieve viral suppression during prior interferon-based therapy and those who do not have advanced fibrosis have a greater likelihood of achieving a SVR with CIFN retreatment. Individualized therapy targeting specific patient groups will be an important consideration in the successful management of prior treatment failures. Additional prospective studies are required in order to identify optimal treatment strategies for the use of CIFN in these patients.

Although epidemiologic studies have documented that hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients have accelerated fibrogenesis, especially those with CD4+ cell counts <200 cells/mm(3), the pathogenic mechanisms are poorly understood. We investigated whether severe immunodeficiency in co-infection is associated with changes in intrahepatic inflammatory cytokine mRNA levels. We measured interferon (IFN)-gamma, tumour necrosis factor-alpha, transforming growth factor (TGF)-beta(1), interleukin (IL)-4, IL-10, IL-12p35 and IL-12p40 mRNA levels by real-time PCR performed on liver samples from HCV mono-infected (n = 19) and HCV/HIV co-infected (n = 24) patients. Co-infected patients had decreased intrahepatic mRNA levels of IFN-gamma (P = 0.09), IL-4 (P = 0.05) and IL-12p35 (P = 0.04) compared with mono-infected patients, while IL-10 was increased (P = 0.07). In co-infected patients, IFN-gamma mRNA levels increased linearly with increasing peripheral CD4+ cell counts by 1.23 times relative to the calibrator for every 100 CD4+ cells/mm(3) increase (P = 0.02). No other cytokines were significantly associated with CD4+ cell counts. In conclusion, HIV-induced lymphopenia may result in hepatic inflammatory cytokine suppression in HCV/HIV co-infection. Intrahepatic IFN-gamma levels are significantly reduced in patients with advanced immunodeficiency. Further studies are needed to assess whether decreased IFN-gamma secretion by HCV-specific CD4+ cells may account for accelerated fibrogenesis in these patients.

The lower limit of detection of most polymerase chain reaction (PCR) assays for hepatitis C virus (HCV) RNA is 50 IU/ml, compared to 5 IU/ml for the transcription-mediated amplification (TMA) method. We retrospectively reviewed 57 patients to assess the predictive value of a positive TMA in the setting of a negative PCR during antiviral therapy. Patients were divided into (1) PCR-/TMA+ (discordant; n=21) and (2) PCR-/TMA-(concordant; n=36). Sustained virologic response (SVR) was decreased in the discordant group (48% vs. 75%; P=0.04). In discordant patients, SVR was more frequent in patients who had one positive TMA than in those who had two or more positive TMAs or one positive TMA and recurrent HCV RNA detectability by PCR during treatment (78% vs. 25%; P=0.03). Breakthrough occurred more frequently in discordant patients (24% vs. 3%; P=0.02). A positive TMA on two or more occasions in patients who have become PCR-negative on therapy indicates a high likelihood of treatment failure.

Background and Aims: The significance of normal alanine aminotransferase (ALT) levels in patients with HIV/hepatitis C virus (HCV) coinfection is not well understood., Methods: We performed a cross-sectional retrospective analysis on consecutive HIV/HCV-coinfected patients (n = 89) who underwent a liver biopsy during a 2-year period. Similar data were also collected on HCV-monoinfected patients (n = 117)., Results: Mean ALT levels and the percentage of patients with normal ALT (< or =40 U/L) levels were similar in HIV/HCV-coinfected (mean +/- SD, 81.7 +/- 56.1 U/L; 21%) and HCV-monoinfected patients (97.3 +/- 100.7 U/L; 18%; P = 0.19 and 0.54, respectively). Coinfected patients, however, had significantly advanced necroinflammation (P= 0.001) and fibrosis (P = 0.02) compared with monoinfected patients. The percentage of patients with advanced necroinflammation (grades 3 or 4) was lower in HCV-monoinfected patients with normal ALT levels compared with those with elevated ALT (5% vs 20%, respectively). In contrast, the percentage of coinfected patients with advanced necroinflammation was similar whether the patient had normal or elevated ALT levels (32% vs 37%, respectively)., Conclusions: In coinfected patients, normal ALT levels are not an indicator of mild necroinflammation and may not portend a more benign disease course.