Intraoperative Troponin Elevation in Liver Transplantation Is Independently Associated With Mortality: A Prospective Observational Study.

Intraoperative factors implicated in postoperative mortality after liver transplantation (LT) are poorly understood. Because LT is a particularly demanding procedure, we hypothesized that intraoperative myocardial injury may be frequent and independently associated with early postoperative outcomes. We aimed to determine the association between intraoperative high-sensitivity troponin (hsTn) elevation during LT and 30-day postoperative mortality. A total of 203 adult patients undergoing LT were prospectively included in the cohort and followed during 1 year. Advanced hemodynamic parameters and serial high-sensitivity troponin T (hsTnT) measurements were assessed at 6 intraoperative time points. The optimal hsTnT cutoff level for intraoperative troponin elevation (ITE) was identified. Patients were classified into 2 groups according to the presence of ITE. Independent impact of ITE on survival was assessed through survival curves and multivariate Cox regression analysis. Intraoperative cardiac function was compared between groups. Troponin levels increased early during surgery in the ITE group. Troponin values at abdominal closure were associated with 30-day mortality (area under the receiver operating caracteristic curve, [AUROC], 0.73; P = 0.005). Patients with ITE showing values of hsTnT ≥61 ng/L at abdominal closure presented higher 30-day mortality (29.6% versus 3.4%; P < 0.001). ITE was independently associated with 30-day mortality (hazard ratio, 3.8; 95% confidence interval, 1.1-13.8; P = 0.04) and with worse overall intraoperative cardiac function. The hsTnT upper reference limit showed no discriminant capacity during LT. Intraoperative myocardial injury identified by hsTn elevation is frequently observed during LT, and it is associated with myocardial dysfunction and short-term mortality. Determinations of hsTn may serve as a valuable intraoperative monitoring tool during LT.

Comparing UAV-Based Technologies and RGB-D Reconstruction Methods for Plant Height and Biomass Monitoring on Grass Ley.

Pastures are botanically diverse and difficult to characterize. Digital modeling of pasture biomass and quality by non-destructive methods can provide highly valuable support for decision-making. This study aimed to evaluate aerial and on-ground methods to characterize grass ley fields, estimating plant height, biomass and volume, using digital grass models. Two fields were sampled, one timothy-dominant and the other ryegrass-dominant. Both sensing systems allowed estimation of biomass, volume and plant height, which were compared with ground truth, also taking into consideration basic economical aspects. To obtain ground-truth data for validation, 10 plots of 1 m² were manually and destructively sampled on each field. The studied systems differed in data resolution, thus in estimation capability. There was a reasonably good agreement between the UAV-based, the RGB-D-based estimates and the manual height measurements on both fields. RGB-D-based estimation correlated well with ground truth of plant height ( R 2 > 0.80 ) for both fields, and with dry biomass ( R 2 = 0.88 ), only for the timothy field. RGB-D-based estimation of plant volume for ryegrass showed a high agreement ( R 2 = 0.87 ). The UAV-based system showed a weaker estimation capability for plant height and dry biomass ( R 2 < 0.6 ). UAV-systems are more affordable, easier to operate and can cover a larger surface. On-ground techniques with RGB-D cameras can produce highly detailed models, but with more variable results than UAV-based models. On-ground RGB-D data can be effectively analysed with open source software, which is a cost reduction advantage, compared with aerial image analysis. Since the resolution for agricultural operations does not need fine identification the end-details of the grass plants, the use of aerial platforms could result a better option in grasslands.

Teaching Cultural Competence to Psychiatry Residents: Seven Core Concepts and Their Implications for Therapeutic Technique.

The authors describe the Tulane Model for teaching cultural competence to psychiatry residents in order to outline an innovative approach to curricula development in academic psychiatry. The authors focus on the didactic experience that takes place during the first and second postgraduate years and present seven core concepts that should inform the emerging clinician's thinking in the formulation of every clinical case. The authors discuss the correspondence between each core concept and the Outline for Cultural Formulation, introduced in Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and updated in DSM-5. The authors illustrate how each of the core concepts is utilized as a guideline for teaching residents a process for eliciting culturally relevant information from their patients and their personal histories and how to apply that knowledge in the assessment and treatment of patients in clinical settings.

Thermally tunable polarization by nanoparticle plasmonic resonance in photonic crystal fibers.

A photonic crystal fiber selectively filled with silver nanoparticles dispersed in polydimethylsiloxane has been numerically studied via finite elements analysis. These nanoparticles possess a localized surface plasmon resonance in the visible region which depends on the refractive index of the surrounding medium. The refractive index of polydimethylsiloxane can be thermally tuned leading to the design of polarization tunable filters. Filters found with this setup show anisotropic attenuation of the x-polarization fundamental mode around α(x) = 1200dB/cm remarkably higher than the y-polarization mode. Moreover, high fiber birefringence and birefringence reversal is observed in the spectral region of the plasmon.

Alcohol abuse in deceased liver donors: impact on post-transplant outcomes.

BACKGROUND: Many deceased liver donors with a history of alcohol abuse are excluded based upon medical history alone. This paper summarizes the transplant outcomes for a large number of deceased liver donors with a documented history of alcohol abuse. METHODS: The records for 1478 consecutive deceased liver donors were reviewed (2001-2012). As per the United Network for Organ Sharing criteria, heavy alcohol use by an organ donor is defined as chronic intake of two or more drinks per day. Donors with a documented history of alcohol abuse were divided into three groups according to duration of abuse (<10 years, 10-24 years and 25 + years). Reperfusion biopsies are reported. Outcomes include biopsy appearance, early graft function and early and late graft survival. RESULTS: There were 161 donors with alcohol abuse: <10 years (29%); 10-24 years (42%); and ≥25 years (29%). Risk of 90-day graft loss for these three groups was: 0%, 3% and 2%, compared to 3% for all other donors (P = 0.62). Graft survival at 1 year for donor grafts with and without alcohol abuse was 89% and 87% (P = 0.52). There was no difference in early graft function. Cox proportional hazards modelling for graft survival demonstrates no statistically significant difference in survival up to 10 years post-transplant. CONCLUSIONS: This study demonstrates successful transplantation of a large number of deceased donor liver grafts from donors with a documented history of alcohol abuse (n = 161; 11% of all grafts). These extended criteria donor allografts may, therefore, be utilized successfully with similar outcomes.

Emerging challenges in managing hepatitis B in HIV patients.

Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV. In developed countries, hepatitis B exhibits particular features in the HIV population. First, HBV infection is less frequently misdiagnosed than in the general population. Second, nucleos(t)ide analogs active against HBV are widely used as part of antiretroviral combinations and are taken by most HIV patients. Lastly, as the HIV population ages given the success of antiretroviral therapy, non-AIDS co-morbidities are becoming a major cause of disease, for which specific drugs are required, increasing the risk of interactions and hepatotoxicity. Furthermore, concern on HBV reactivation is rising as immunosuppressive drug therapies are increasingly been used for cancers and other non-malignant conditions. In this scenario, new challenges are emerging in the management of hepatitis B in HIV-positive individuals. Among them, major interest is focused on failures to suppress HBV replication, HBV breakthroughs and reactivations, the meaning of isolated anti-HBc, screening for liver cancer, and the complexity arising when hepatitis viruses C and/or D are additionally present. This review will focus on these challenges and the major advances in HBV coinfection in HIV.

Quantifying efficacy and limits of unmanned aerial vehicle (UAV) technology for weed seedling detection as affected by sensor resolution.

In order to optimize the application of herbicides in weed-crop systems, accurate and timely weed maps of the crop-field are required. In this context, this investigation quantified the efficacy and limitations of remote images collected with an unmanned aerial vehicle (UAV) for early detection of weed seedlings. The ability to discriminate weeds was significantly affected by the imagery spectral (type of camera), spatial (flight altitude) and temporal (the date of the study) resolutions. The colour-infrared images captured at 40 m and 50 days after sowing (date 2), when plants had 5-6 true leaves, had the highest weed detection accuracy (up to 91%). At this flight altitude, the images captured before date 2 had slightly better results than the images captured later. However, this trend changed in the visible-light images captured at 60 m and higher, which had notably better results on date 3 (57 days after sowing) because of the larger size of the weed plants. Our results showed the requirements on spectral and spatial resolutions needed to generate a suitable weed map early in the growing season, as well as the best moment for the UAV image acquisition, with the ultimate objective of applying site-specific weed management operations.

Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis.

BACKGROUND: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. METHODS: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. RESULTS: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. CONCLUSIONS: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.

mRNA Decapping Activator Pat1 Is Required for Efficient Yeast Adaptive Transcriptional Responses via the Cell Wall Integrity MAPK Pathway.

Cellular mRNA levels, particularly under stress conditions, can be finely regulated by the coordinated action of transcription and degradation processes. Elements of the 5'-3' mRNA degradation pathway, functionally associated with the exonuclease Xrn1, can bind to nuclear chromatin and modulate gene transcription. Within this group are the so-called decapping activators, including Pat1, Dhh1, and Lsm1. In this work, we have investigated the role of Pat1 in the yeast adaptive transcriptional response to cell wall stress. Thus, we demonstrated that in the absence of Pat1, the transcriptional induction of genes regulated by the Cell Wall Integrity MAPK pathway was significantly affected, with no effect on the stability of these transcripts. Furthermore, under cell wall stress conditions, Pat1 is recruited to Cell Wall Integrity-responsive genes in parallel with the RNA Pol II complex, participating both in pre-initiation complex assembly and transcriptional elongation. Indeed, strains lacking Pat1 showed lower recruitment of the transcription factor Rlm1, less histone H3 displacement at Cell Wall Integrity gene promoters, and impaired recruitment and progression of RNA Pol II. Moreover, Pat1 and the MAPK Slt2 occupied the coding regions interdependently. Our results support the idea that Pat1 and presumably other decay factors behave as transcriptional regulators of Cell Wall Integrity-responsive genes under cell wall stress conditions.

Boosting precision crop protection towards agriculture 5.0 via machine learning and emerging technologies: A contextual review.

Crop protection is a key activity for the sustainability and feasibility of agriculture in a current context of climate change, which is causing the destabilization of agricultural practices and an increase in the incidence of current or invasive pests, and a growing world population that requires guaranteeing the food supply chain and ensuring food security. In view of these events, this article provides a contextual review in six sections on the role of artificial intelligence (AI), machine learning (ML) and other emerging technologies to solve current and future challenges of crop protection. Over time, crop protection has progressed from a primitive agriculture 1.0 (Ag1.0) through various technological developments to reach a level of maturity closelyin line with Ag5.0 (section 1), which is characterized by successfully leveraging ML capacity and modern agricultural devices and machines that perceive, analyze and actuate following the main stages of precision crop protection (section 2). Section 3 presents a taxonomy of ML algorithms that support the development and implementation of precision crop protection, while section 4 analyses the scientific impact of ML on the basis of an extensive bibliometric study of >120 algorithms, outlining the most widely used ML and deep learning (DL) techniques currently applied in relevant case studies on the detection and control of crop diseases, weeds and plagues. Section 5 describes 39 emerging technologies in the fields of smart sensors and other advanced hardware devices, telecommunications, proximal and remote sensing, and AI-based robotics that will foreseeably lead the next generation of perception-based, decision-making and actuation systems for digitized, smart and real-time crop protection in a realistic Ag5.0. Finally, section 6 highlights the main conclusions and final remarks.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Temperature-frequency converter using a liquid crystal cell as a sensing element.

A new temperature-frequency converter based on the variation of the dielectric permittivity of the Liquid Crystal (LC) material with temperature has been demonstrated. Unlike other temperature sensors based on liquid crystal processing optical signals for determining the temperature, this work presents a system that is able to sense temperature by using only electrical signals. The variation of the dielectric permittivity with temperature is used to modify the capacitance of a plain capacitor using a LC material as non-ideal dielectric. An electric oscillator with an output frequency depending on variable capacitance made of a twisted-nematic (TN) liquid crystal (LC) cell has been built. The output frequency is related to the temperature of LC cell through the equations associated to the oscillator circuit. The experimental results show excellent temperature sensitivity, with a variation of 0.40% of the initial frequency per degree Celsius in the temperature range from -6 °C to 110 °C.

Plant functional diversity is affected by weed management through processes of trait convergence and divergence.

Weed management involving tillage and/or herbicides has generally led to a decline of plant diversity in agroecosystems, with negative impacts on ecosystem services provision. The use of plant covers has become the predominant alternative in vineyard management, with numerous studies focusing on analyzing the advantages and disadvantages of plant covers compared to the aforementioned management. Although the impacts of weed management on taxonomic diversity have been widely studied, many gaps remain on their effects on plant functional diversity. As plant functional diversity is linked to the delivery of key ecosystem services in agroecosystems, understanding these effects could enable the development of more sustainable practices. From 2008 to 2018, a long-term trial was carried out in a Mediterranean vineyard to assess different agricultural practices. In this article, we examined how weed management, as well as irrigation use, could affect plant functional diversity. Based on 10 functional traits, such as plant height, specific leaf area or seed mass, we measured different indices of functional diversity and used null models to detect processes of trait convergence and divergence. Our results revealed that weed management and irrigation use had a significant effect on plant functional diversity. Mown plots showed the highest functional richness but were functionally convergent, since mowing was a strong functional filter on most of the traits. Tillage also behaved as a functional filter on some vegetative traits, but favored the divergence of certain reproductive traits. Herbicide-treated and irrigated plots showed the highest values of functional divergence by promoting more competitive species with more divergent trait values. The effect of weed management on these community assembly processes was shaped by the use of irrigation in vineyard rows, leading to functional divergence in those vegetative traits related to resource acquisition and seed mass. These results suggest that greater functional diversity may be associated with the bias caused by higher occurrence of competitive species (e.g. Convolvulus arvensis, Sonchus asper) with contrasting values for certain traits. Therefore, since these species are considered harmful to crops, higher plant functional diversity might not be a desirable indicator in agroecosystems.

Systematic Identification of Essential Genes Required for Yeast Cell Wall Integrity: Involvement of the RSC Remodelling Complex.

Conditions altering the yeast cell wall lead to the activation of an adaptive transcriptional response mainly governed by the cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) pathway. Two high-throughput screenings were developed using the yTHC collection of yeast conditional mutant strains to systematically identify essential genes related to cell wall integrity, and those required for the transcriptional program elicited by cell wall stress. Depleted expression of 52 essential genes resulted in hypersensitivity to the dye Calcofluor white, with chromatin organization, Golgi vesicle transport, rRNA processing, and protein glycosylation processes, as the most highly representative functional groups. Via a flow cytometry-based quantitative assay using a CWI reporter plasmid, 97 strains exhibiting reduced gene-reporter expression levels upon stress were uncovered, highlighting genes associated with RNA metabolism, transcription/translation, protein degradation, and chromatin organization. This screening also led to the discovery of 41 strains displaying a basal increase in CWI-associated gene expression, including mainly putative cell wall-related genes. Interestingly, several members of the RSC chromatin remodelling complex were uncovered in both screenings. Notably, Rsc9 was necessary to regulate the gene expression of CWI-related genes both under stress and non-stress conditions, suggesting distinct requirements of the RSC complex for remodelling particular genes.

Genome-wide survey of yeast mutations leading to activation of the yeast cell integrity MAPK pathway: novel insights into diverse MAPK outcomes.

BACKGROUND: The yeast cell wall integrity mitogen-activated protein kinase (CWI-MAPK) pathway is the main regulator of adaptation responses to cell wall stress in yeast. Here, we adopt a genomic approach to shed light on two aspects that are only partially understood, namely, the characterization of the gene functional catalog associated with CWI pathway activation and the extent to which MAPK activation correlates with transcriptional outcomes. RESULTS: A systematic yeast mutant deletion library was screened for constitutive transcriptional activation of the CWI-related reporter gene MLP1. Monitoring phospho-Slt2/Mpk1 levels in the identified mutants revealed sixty-four deletants with high levels of phosphorylation of this MAPK, including mainly genes related to cell wall construction and morphogenesis, signaling, and those with unknown function. Phenotypic analysis of the last group of mutants suggests their involvement in cell wall homeostasis. A good correlation between levels of Slt2 phosphorylation and the magnitude of the transcriptional response was found in most cases. However, the expression of CWI pathway-related genes was enhanced in some mutants in the absence of significant Slt2 phosphorylation, despite the fact that functional MAPK signaling through the pathway was required. CWI pathway activation was associated to increased deposition of chitin in the cell wall - a known survival compensatory mechanism - in about 30% of the mutants identified. CONCLUSION: We provide new insights into yeast genes related to the CWI pathway and into how the state of activation of the Slt2 MAPK leads to different outcomes, discovering the versatility of this kind of signaling pathways. These findings potentially have broad implications for understanding the functioning of other eukaryotic MAPKs.

Hypocalcemia and a Positive Metabolic Screen for Severe Combined Immunodeficiency in an 11-Day-Old Male With DiGeorge Syndrome.

22q11 deletion syndrome (22q11DS), also known as DiGeorge syndrome or velocardiofacial syndrome, is the most common human genetic microdeletion. Hypocalcemia secondary to hypoparathyroidism is a common finding in this condition and may present with seizures. We describe a case of an 11-day-old male presenting with hypocalcemic seizures and a positive newborn screen for severe combined immunodeficiency as the primary manifestations of 22q11DS. Given the potential for wide phenotypic variability, clinicians should maintain a high index of suspicion for this syndrome, especially in the neonate presenting with hypocalcemia.

High-Throughput Phenotyping of Bioethanol Potential in Cereals Using UAV-Based Multi-Spectral Imagery.

Bioethanol production obtained from cereal straw has aroused great interest in recent years, which has led to the development of breeding programs to improve the quality of lignocellulosic material in terms of the biomass and sugar content. This process requires the analysis of genotype-phenotype relationships, and although genotyping tools are very advanced, phenotypic tools are not usually capable of satisfying the massive evaluation that is required to identify potential characters for bioethanol production in field trials. However, unmanned aerial vehicle (UAV) platforms have demonstrated their capacity for efficient and non-destructive acquisition of crop data with an application in high-throughput phenotyping. This work shows the first evaluation of UAV-based multi-spectral images for estimating bioethanol-related variables (total biomass dry weight, sugar release, and theoretical ethanol yield) of several accessions of wheat, barley, and triticale (234 cereal plots). The full procedure involved several stages: (1) the acquisition of multi-temporal UAV images by a six-band camera along different crop phenology stages (94, 104, 119, 130, 143, 161, and 175 days after sowing), (2) the generation of ortho-mosaicked images of the full field experiment, (3) the image analysis with an object-based (OBIA) algorithm and the calculation of vegetation indices (VIs), (4) the statistical analysis of spectral data and bioethanol-related variables to predict a UAV-based ranking of cereal accessions in terms of theoretical ethanol yield. The UAV-based system captured the high variability observed in the field trials over time. Three VIs created with visible wavebands and four VIs that incorporated the near-infrared (NIR) waveband were studied, obtaining that the NIR-based VIs were the best at estimating the crop biomass, while the visible-based VIs were suitable for estimating crop sugar release. The temporal factor was very helpful in achieving better estimations. The results that were obtained from single dates [i.e., temporal scenario 1 (TS-1)] were always less accurate for estimating the sugar release than those obtained in TS-2 (i.e., averaging the values of each VI obtained during plant anthesis) and less accurate for estimating the crop biomass and theoretical ethanol yield than those obtained in TS-3 (i.e., averaging the values of each VI obtained during full crop development). The highest correlation to theoretical ethanol yield was obtained with the normalized difference vegetation index (R 2 = 0.66), which allowed to rank the cereal accessions in terms of potential for bioethanol production.

Author Correction: Signalling through the yeast MAPK Cell Wall Integrity pathway controls P-body assembly upon cell wall stress.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Signalling through the yeast MAPK Cell Wall Integrity pathway controls P-body assembly upon cell wall stress.

Post-transcriptional control of mRNA is a key event in the regulation of gene expression. From yeast to human cells, P-bodies are cytoplasmic RNA-protein aggregates that play an essential role in this process, particularly under stress conditions. In this work, we show that in the model yeast Saccharomyces cerevisiae cell wall stress induces the formation of these structures. This effect is dependent on multiple elements in the Cell Wall Integrity (CWI) MAPK signalling pathway, a signal transduction cascade responsible for the maintenance of cell integrity under adverse environmental conditions. Remarkably, P-body assembly requires the catalytic activity of the MAPK of the pathway, Slt2/Mpk1. In accordance with the control exerted by this signalling pathway, the timing of P-body formation is similar to that of the activation of the CWI pathway. Noticeably, mRNAs whose expression is regulated by this pathway localize in P-bodies after the cell is exposed to stress following a temporal pattern coincident with CWI pathway activation. Moreover, when these mRNAs are overexpressed in a mutant background unable to form visible P-bodies, the cells show hypersensitivity to agents that interfere with cell wall integrity, supporting that they play a role in the mRNA lifecycle under stress conditions.

Low rate of adverse hepatic events associated with fosamprenavir/ritonavir-based antiretroviral regimens.

PURPOSE: To appraise the incidence of liver toxicity in a population of patients receiving fosamprenavir/ritonavir (FPV/r) with a high frequency of viral hepatitis co-infection. METHOD: 636 patients, 341 (54%) with HCV antibodies and 38 (5.6%) bearing serum HBsAg, were recruited. All of them received FPV/r 700/100 twice every day. 93 (27%) patients who tested positive for HCV antibodies showed an AST to platelet ratio index (APRI) higher than 1.5, consistent with significant liver fibrosis. RESULTS: After a median (range) follow-up time of 6.91 (0.46-20.66) months, 3 (0.47%) patients developed grade 3 ALT elevation. All the former patients were hepatitis virus co-infected, 2 with hepatitis C virus and 1 with hepatitis B virus. The frequency of grade 3 ALT elevation in patients with HCV antibodies was 0.58% and in those harbouring HBsAg it was 2.63%. 4 (0.62%) patients suffered from a liver decompensation and 1 died due to a hepatic cause while on follow-up. No patients with APRI equal to or higher than 1.5 showed grade 3 ALT elevation. CONCLUSION: The incidence of adverse hepatic events in patients receiving FPV/r including combinations seems to be low, even in subjects co-infected with hepatitis virus and in those with significant liver fibrosis.