Impact of sustained virologic response on glucose parameters among patients with chronic hepatitis C treated with direct-acting antivirals.

Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

Progress towards elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission update.

The top 20 highest burdened countries (in disability-adjusted life years) account for more than 75% of the global burden of viral hepatitis. An effective response in these 20 countries is crucial if global elimination targets are to be achieved. In this update of the Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis, we convene national experts from each of the top 20 highest burdened countries to provide an update on progress. Although the global burden of diseases is falling, progress towards elimination varies greatly by country. By use of a hepatitis elimination policy index conceived as part of the 2019 Commission, we measure countries' progress towards elimination. Progress in elimination policy has been made in 14 of 20 countries with the highest burden since 2018, with the most substantial gains observed in Bangladesh, India, Indonesia, Japan, and Russia. Most improvements are attributable to the publication of formalised national action plans for the elimination of viral hepatitis, provision of publicly funded screening programmes, and government subsidisation of antiviral treatments. Key themes that emerged from discussion between national commissioners from the highest burdened countries build on the original recommendations to accelerate the global elimination of viral hepatitis. These themes include the need for simplified models of care, improved access to appropriate diagnostics, financing initiatives, and rapid implementation of lessons from the COVID-19 pandemic.

Celiac trunk stenosis by median arcuate ligament in orthotopic liver transplantation: a potential hidden foe to the biliary tree.

BACKGROUND: Celiac trunk compression by the median arcuate ligament (MAL) increases the risk of ischemic complications following gastrointestinal surgical procedures. Previous studies suggest increased risk of hepatic artery thrombosis (HAT) in orthotopic liver transplant (OLT) recipients. The aim of this study is to investigate the impact of untreated MAL compression (MAL-C) on biliary complications in OLT. METHODS: Contrast-enhanced imaging was used to classify celiac trunk stenosis by MAL-C. Medical records were reviewed to extract pre-transplant, transplant and post-transplant data. Patients were divided into two groups: no MAL compression (nMAL-C) and MAL-C. The primary endpoint was biliary complications. Secondary endpoints were HAT and graft survival. RESULTS: 305 OLT were performed from 2010 to 2021, of which 219 were included for analysis: 185 (84.5%) patients without and 34 (15.5%) with MAL-C. The incidence of HAT was 5.9% in both groups. Biliary complications were more common in the MAL-C group (35.3% vs. 17.8%, p = 0.035). Graft survival was decreased in patients with MAL-C (p = 0.035). CONCLUSIONS: MAL-C of the celiac trunk was associated with increased risk of biliary complications and inferior graft survival in OLT patients. These findings highlight the importance of preoperative screening and treatment of MAL in this population.

Probing Mastoparan-like Antimicrobial Peptides Interaction with Model Membrane Through Energy Landscape Analysis.

Antimicrobial Peptides (AMPs) have emerged as promising alternatives to conventional antibiotics due to their capacity to disrupt the lipid packing of bacterial cell membranes. This mechanism of action may prevent the development of resistance by bacteria. Understanding their role in lipid packing disruption and their structural properties upon interaction with bacterial membranes is highly desirable. In this study, we employed Molecular Dynamics simulations and the Energy Landscape Visualization Method (ELViM) to characterize and compare the conformational ensembles of mastoparan-like Polybia-MP1 and its analogous H-MP1, in which histidines replace lysine residues. Two situations were analyzed: (i) the peptides in their free state in an aqueous solution containing water and ions and (ii) the peptides spontaneously adsorbing onto an anionic lipid bilayer, used as a bacteria membrane mimetic. ELViM was used to project a single effective conformational phase space for both peptides, providing a comparative analysis. This projection enabled us to map the conformational ensembles of each peptide in an aqueous solution and assess the structural effects of substituting lysines with histidines in H-MP1. Furthermore, a single conformational phase space analysis was employed to describe structural changes during the adsorption process using the same framework. We show that ELViM provides a comprehensive analysis, able to identify discrepancies in the conformational ensembles of these peptides that may affect their affinity to the membrane and adsorption kinetics.

Alchemical Calculation of Relative Free Energies for Charge-Changing Mutations at Protein-Protein Interfaces Considering Fixed and Variable Protonation States.

The calculation of relative free energies (ΔΔG) for charge-changing mutations at protein-protein interfaces through alchemical methods remains challenging due to variations in the system's net charge during charging steps, the possibility of mutated and contacting ionizable residues occurring in various protonation states, and undersampling issues. In this study, we present a set of strategies, collectively termed TIRST/TIRST-H+, to address some of these challenges. Our approaches combine thermodynamic integration (TI) with the prediction of pKa shifts to calculate ΔΔG values. Moreover, special sets of restraints are employed to keep the alchemically transformed molecules separated. The accuracy of the devised approaches was assessed on a large and diverse data set comprising 164 point mutations of charged residues (Asp, Glu, Lys, and Arg) to Ala at the protein-protein interfaces of complexes with known three-dimensional structures. Mean absolute and root-mean-square errors ranging from 1.38 to 1.66 and 1.89 to 2.44 kcal/mol, respectively, and Pearson correlation coefficients of ∼0.6 were obtained when testing the approaches on the selected data set using the GPU-TI module of Amber18 suite and the ff14SB force field. Furthermore, the inclusion of variable protonation states for the mutated acid residues improved the accuracy of the predicted ΔΔG values. Therefore, our results validate the use of TIRST/TIRST-H+ in prospective studies aimed at evaluating the impact of charge-changing mutations to Ala on the stability of protein-protein complexes.

Low hepatic artery resistive index on Doppler ultrasound performed on the first post-liver transplant day is associated both with hepatic artery thrombosis and decreased graft survival.

PURPOSE: Although liver transplantation (LT) outcomes have improved significantly over the last decades, early vascular complications are still associated with elevated risks of graft failure. Doppler ultrasound (DUS) enables detection of vascular complications, provides hepatic artery Resistive Index (RI). The aim of our study was to evaluate the association of the RI parameters of DUS performed in the first post-transplant week with post-transplant outcomes. METHODS: All consecutive patients undergoing a first LT between 2001 and 2019 at a single center were included. Patients were divided into two groups: RI < 0.55 and RI ≥ 0.55. Patients were also divided according to the presence or absence of hepatic artery thrombosis (HAT). Graft survival was compared between groups. RESULTS: Overall, 338 patients were included. HAT occurred in 23 patients (6.8%), of which 7 were partial and 16, complete. Biliary complications were more common in patients with HAT (10 [43.5%]) vs. 38 [12.1%] [p < 0.001]). Graft survival was lower for patients with HAT (p = 0.047). Also, RI < 0.55 was associated with increased incidence of HAT (p < 0.001). Additionally, patients with RI < 0.55 on post-operative day 1 had decreased graft survival as compared to patients with RI > 0.55 (p = 0.041). RI on post-operative day 3 and 5 was not predictive of inferior graft outcomes. CONCLUSIONS: Intensive use of DUS in the early post-LT period offers the possibility of early diagnosis of vascular complications, guiding medical and surgical management of HAT. Additionally, according to our data, low RI (< 0.55) on the first postoperative day also is a predictor of HAT and decreased graft-survival.

Kinetic and structural studies of Mycobacterium tuberculosis dihydroorotate dehydrogenase reveal new insights into class 2 DHODH inhibition.

Tuberculosis (TB) is a leading cause of death worldwide. TB represents a serious public health threat, and it is characterized by high transmission rates, prevalence in impoverished regions, and high co-infection rates with HIV. Moreover, the serious side effects of long-term treatment that decrease patient adherence, and the emergence of multi-resistant strains of Mycobacterium tuberculosis, the causing agent of TBs, pose several challenges for its eradication. The search for a new TB treatment is necessary and urgent. Dihydroorotate dehydrogenase (DHODH) is responsible for the stereospecific oxidation of (S)-dihydroorotate (DHO) to orotate during the fourth and only redox step of the de novo pyrimidine nucleotide biosynthetic pathway. DHODH has been considered an attractive target against infectious diseases. As a first step towards exploiting DHODH as a drug target against TB, we performed a full kinetic characterization of both bacterial MtDHODH and its human ortholog (HsDHDOH) using both substrates coenzyme Q0 (Q0) and vitamin K3 (K3). MtDHODH follows a ping-pong mechanism of catalysis and shares similar catalytic parameters with the human enzyme. Serendipitously, Q0 was found to inhibit MtDHODH (KI (Q0) = 138 ± 31 µM). To the best of our knowledge, Q0 is the first non-orotate like dihydroorotate-competitive inhibitor for class 2 DHODHs ever described. Molecular dynamics simulations along with in silico solvent mapping allowed us to successfully probe protein flexibility and correlate it with the druggability of binding sites. Together, our results provide the starting point for the design of a new generation of potent and selective inhibitors against MtDHODH.

Percutaneous ethanol injection is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation.

PURPOSE: Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE. METHODS: All consecutive cirrhotic patients with HCC enlisted for OLT (2011-2020) at a single center were analyzed. Patients were divided into three LRT modality groups: PEI, TACE, and PEI+TACE. The primary study outcome was waitlist dropout due to tumor progression beyond Milan criteria. A comparison of post-transplant outcomes of patients as stratified by LRT modality also was performed. RESULTS: One hundred twenty-nine patients were included (PEI=56, TACE=43, PEI+TACE=30). The dropout rate due to tumor progression was not different among the three groups: PEI=8.9%, TACE=14%, PEI+TACE=16.7% (p=0.54). Thirteen (76.4%) patients underwent OLT after successful downstaging (3 [75%] in the PEI group, 5 [83.3%] in the TACE group, and 5 [71.4%] in the PEI+TACE group). For the 96 patients undergoing OLT, 5-year post-transplant recurrence-free survival was PEI=55.6% vs. TACE=55.1% vs. PEI+TACE=71.4% (p=0.42). Complete/near-complete pathological response rate was similar among groups (p=0.82). CONCLUSION: Dropout rates and post-transplant recurrence-free survivals related to PEI were comparable to those of TACE. This study supports the use of PEI alone or in combination with TACE for HCC patients awaiting OLT whenever RFA is not an option.

The top-100 cited articles on post-traumatic stress disorder: a historical bibliometric analysis.

This is a bibliometric analysis of the most-cited articles on post-traumatic stress disorder (PTSD) with the objective of identifying citation patterns for researchers, journals, centers, periods, topics, and nations. A search was conducted in Thomson Reuters' WoS Core Collection employing the expression TI = (posttraumatic stress disorder OR post-traumatic stress disorder OR PTSD). The 100 most-cited articles were downloaded, and the relevant data were extracted and analyzed. These studies had a total of 69,649 citations, ranging from a minimum of 360 to a maximum of 6029 citations, with an average of 696.49, a standard deviation of 720.92, mode of 369, and a median of 512. Eighty-eight percent of the most-cited articles on PTSD originated from the USA, with just six cities accounting for 52% of the publications and the Boston area alone responsible for almost one-fifth of the total output. The universities of Yale and Harvard headed the ranking of institutions with larger numbers of highly-cited articles. Female researchers represented 42.3% of all authors, 51% of the first authors, and 48% of the corresponding authors. The proportion of M.D. authors decreased significantly between the 1980-1999 (42%) and the 2000-2019 (27.2%) periods while that of Ph.D. authors increased from 44% to 57.4%. The most studied population was military veterans (28%). Female victims of sexual or physical violence, traumatized children, and adult survivors of childhood abuse were assessed in only 6-7% of the most-cited publications. Ten clinical trials evaluated psychological interventions but only three investigated pharmacotherapy. We concluded that influential research on PTSD remains centralized in the USA. A balanced gender representation in publications was found. There was a heavy reliance on combat veterans as the study population. Few highly-cited studies on the pharmacotherapy for PTSD were identified. Focused efforts are needed to address these challenges.

Biological and economic responses to increasing nitrogen rates in Mombaça guinea grass pastures.

Nitrogen fertilization has been recognized as an essential tool towards the establishment of sustainable intensification of pasture-based livestock systems using tropical perennial grasses if, for a given ecosystem it is capable of increasing forage growth, stocking rates and animal performance. This study assessed pasture growth traits, nutritive value, animal and economic responses of Panicum maximum cv. Mombaça guinea grass pastures subjected to different levels of N fertilization (100 (N100), 200 (N200), and 300 (N300) kg N ha-1 yr-1). Pastures were managed under rotational stocking to maintain similar pre (80-90 cm) and post-grazing (45 cm) canopy heights. A partial budget and a Benefit-Cost Analysis were used to assess the economic returns on increasing N fertilization. N300 resulted in greater post-grazing herbage mass. A slightly higher neutral fiber and acid lignin detergent was observed at N100 (P < 0.05); crude protein increased linearly, and in vitro digestible organic matter reached maximum value at 265.4 kg N ha-1 yr-1. Annual averages of animal weight gain were 515, 590 and 660 g d-1, respectively, for N100, N200 and N300. There was a decrease from 3.7 to 1.9 kg of body weight gain per kg of additional N applied when increasing N rates from 100 to 200 and from 100 to 300 kg ha-1. The net profit improved with increasing N levels, but at reducing rates, reaching its maximum at the N300 level. The change from 100 to 200 kg N ha-1 presented the best return, with USD 3.73 for each additional dollar invested, while the change from 200 kg N ha-1 to 300 kg N ha-1 was economically less than optimal, recouping only USD 1.60 for each dollar. The N300 rate presented the highest net profit per hectare (accounting profit), even in a pessimist scenario (25% reduction in production). Despite being profitable, the N300 rate was less than optimal from an economic standpoint, since an additional 100 kg of Nitrogen ha-1 to change from N200 to N300 level reduced both the net returns and the Benefit-Cost ratio. Our results suggest that the economically optimal level of N fertilization for Mombaça guinea grass pasture should be between 200 and 300 kg ha-1.

Severe hepatopulmonary syndrome with hypoxemia refractory to liver transplant: Recovery after 67 days of ECMO support.

Hepatopulmonary syndrome (HPS) is a complication of end stage liver disease (ESLD) and is manifested by severe hypoxemia, which usually responds to liver transplantation (LT). As compared to patients undergoing LT for other etiologies, patients with HPS present an increased risk of postoperative morbidity and mortality. There is no effective treatment for patients whose hypoxemia does not respond to LT. This subset of patients is at a highly increased risk of death. There are very few reports on the use of extracorporeal membrane oxygenation (ECMO) in this setting with rapid response. However, there is no prior report of ECMO utilization for longer than 4 weeks. We present the case of a 17 year-old male patient who underwent LT for ESLD secondary to chronic portal vein thrombosis and HPS. He received a liver from a deceased donor and presented with severe HPS after LT, requiring ECMO support for 67 days. The patient was discharged home and is breathing in ambient air. He is currently asymptomatic and has a normal liver function.

Computational study on the allosteric mechanism of Leishmania major IF4E-1 by 4E-interacting protein-1: Unravelling the determinants of m7GTP cap recognition.

During their life cycle, Leishmania parasites display a fine-tuned regulation of the mRNA translation through the differential expression of isoforms of eukaryotic translation initiation factor 4E (LeishIF4Es). The interaction between allosteric modulators such as 4E-interacting proteins (4E-IPs) and LeishIF4E affects the affinity of this initiation factor for the mRNA cap. Here, several computational approaches were employed to elucidate the molecular bases of the previously-reported allosteric modulation in L. major exerted by 4E-IP1 (Lm4E-IP1) on eukaryotic translation initiation factor 4E 1 (LmIF4E-1). Molecular dynamics (MD) simulations and accurate binding free energy calculations (ΔGbind ) were combined with network-based modeling of residue-residue correlations. We also describe the differences in internal motions of LmIF4E-1 apo form, cap-bound, and Lm4E-IP1-bound systems. Through community network calculations, the differences in the allosteric pathways of allosterically-inhibited and active forms of LmIF4E-1 were revealed. The ΔGbind values show significant differences between the active and inhibited systems, which are in agreement with the available experimental data. Our study thoroughly describes the dynamical perturbations of LmIF4E-1 cap-binding site triggered by Lm4E-IP1. These findings are not only essential for the understanding of a critical process of trypanosomatids' gene expression but also for gaining insight into the allostery of eukaryotic IF4Es, which could be useful for structure-based design of drugs against this protein family.

The effect of acidic pH on the adsorption and lytic activity of the peptides Polybia-MP1 and its histidine-containing analog in anionic lipid membrane: a biophysical study by molecular dynamics and spectroscopy.

Antimicrobial peptides (AMPs) are part of the innate immune system of many species. AMPs are short sequences rich in charged and non-polar residues. They act on the lipid phase of the plasma membrane without requiring membrane receptors. Polybia-MP1 (MP1), extracted from a native wasp, is a broad-spectrum bactericide, an inhibitor of cancer cell proliferation being non-hemolytic and non-cytotoxic. MP1 mechanism of action and its adsorption mode is not yet completely known. Its adsorption to lipid bilayer and lytic activity is most likely dependent on the ionization state of its two acidic and three basic residues and consequently on the bulk pH. Here we investigated the effect of bulk acidic (pH 5.5) and neutral pH (7.4) solution on the adsorption, insertion, and lytic activity of MP1 and its analog H-MP1 to anionic (7POPC:3POPG) model membrane. H-MP1 is a synthetic analog of MP1 with lysines replaced by histidines. Bulk pH changes could modulate this peptide efficiency. The combination of different experimental techniques and molecular dynamics (MD) simulations showed that the adsorption, insertion, and lytic activity of H-MP1 are highly sensitive to bulk pH in opposition to MP1. The atomistic details, provided by MD simulations, showed peptides contact their N-termini to the bilayer before the insertion and then lay parallel to the bilayer. Their hydrophobic faces inserted into the acyl chain phase disturb the lipid-packing.

Modulatory Effects of Acidic pH and Membrane Potential on the Adsorption of pH-Sensitive Peptides to Anionic Lipid Membrane.

Anionic lipid membrane electrostatic potential and solution pH can influence cationic peptide adsorption to these bilayers, especially those containing simultaneously acid and basic residues. Here, we investigate the effects of the pH solution on MP1 (IDWKKLLDAAKQIL-NH2) adsorption to anionic (7POPC:3POPG) lipid vesicles in comparison to its analog H-MP1, with histidines substituting lysines. We used the association of adsorption isotherms and constant pH molecular dynamic simulations (CpHMD) to explore the effects of membrane potential and pH on peptides' adsorption on this lipid membrane. We analyzed the fluorescence and zeta potential adsorption isotherms using the Gouy-Chapman theory. In CpHMD simulations for the peptides in solution and adsorbed on the lipid bilayer, we used the conformations obtained by conventional MD simulations at a µs timescale. Non-equilibrium Monte Carlo simulations provided the protonation states of acidic and basic residues. CpHMD showed average pKa shifts of two to three units, resulting in a higher net charge for the analog than for MP1, strongly modulating the peptide adsorption. The fractions of the protonation of acidic and basic residues and the peptides' net charges obtained from the analysis of the adsorption isotherms were in reasonable agreement with those from CpHMD. MP1 adsorption was almost insensitive to solution pH. H-MP1 was much more sensitive to partitioning, at acidic pH, with an affinity ten times higher than in neutral ones.

Transient Elastography in HIV Infected Patients with Liver Steatosis Identifies a High-Risk Group for Non-Alcoholic Steatohepatitis.

OBJECTIVE: The study aimed to assess the role of TE in HIV-infected patients with NAFLD. METHODS: HIV-infected patients undergoing ART were enrolled between August 2016 and February 2017, following the inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria included pregnancy, alcohol intake ≥20g/day and co-infection with hepatitis B or C. Patients underwent an abdominal US to diagnose liver steatosis. Significant fibrosis (≥F2) was considered when APRI>1.0, FIB4>3 and liver stiffness ≥7.1kPa. Subjects with TE ≥7.1kPa were prescribed a liver biopsy and the NAFLD Scoring System ≥3 was considered as a diagnosis of NASH. The poisson regression model was used to identify factors associated with liver steatosis. RESULTS: 98 patients were included. The mean age of the subjects was 49±11 years and 53 (54.1%) were males. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male sex (PR= 2.18) and higher BMI (PR=1.08). Among the 31 patients with NAFLD, 26 showed results for TE, APRI and FIB4. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients (26.9%) had a TE result ≥7.1kPa, which was associated with higher triglyceride levels, FIB4 score and CAP values. Liver biopsy was perfomed on six of those with TE ≥7.1kPa and NASH was found in 5 (83.3%) and liver fibrosis without NASH in one. CONCLUSION: NAFLD prevalence in HIV-infected patients is higher than the general population. TE ≥7.1kPa was not able to diagnose significant fibrosis but accurately detect a subgroup of patients at a high risk for NASH among HIV monoinfected individuals with steatosis.

Impact of intraoperative blood salvage and autologous transfusion during liver transplantation for hepatocellular carcinoma.

PURPOSE: Intraoperative blood salvage (IBS) with autologous blood transfusion is controversial in liver transplantation (LT) for hepatocellular carcinoma (HCC). This study evaluated the role of IBS usage in LT for HCC. METHODS: In a retrospective cohort study at a single center from 2002 to 2018, the outcomes of LT surgery for HCC were analyzed. Overall survival and disease-free survival of patients who received IBS were compared with those who did not receive IBS. Cancer recurrence, length of hospital stay, post-transplant complications, and blood loss also were evaluated. The primary aim of this study was to evaluate overall mid-term and long-term survival (4 and 6 years, respectively). RESULTS: Of the total 163 patients who underwent LT for HCC in the study period, 156 had complete demographic and clinical data and were included in the study. IBS was used in 122 and not used in 34 patients. Ninety-five (60.9%) patients were men, and the mean patient age was 58.5 ± 7.6 years. The overall 1-year, 5-year, and 7-year survival in the IBS group was 84.2%, 67.7%, and 56.8% vs. 85.3%, 67.5%, and 67.5% in the non-IBS group (p = 0.77). The 1-year, 5-year, and 7-year disease-free survival in the IBS group was 81.6%, 66.5%, and 55.4% vs. 85.3%, 64.1%, and 64.1% in the non-IBS group (p = 0.74). For patients without complete HCC necrosis (n = 121), the 1-year, 5-year, and 7-year overall survival rates for those who received IBS (n = 95) were 86.2%, 67.7%, and 49.6% vs. 84.6%, 70.0%, and 70.0% for 26 patients without IBS (p = 0.857). For the same patients, the 1-year, 5-year, and 7-year disease-free survival in the IBS group was 84.0%, 66.8%, and 64.0% vs. 88.0%, 72.8%, and 72.8% in the non-IBS group (p = 0.690). CONCLUSION: IBS does not appear to be associated with worse outcomes in patients undergoing LT for HCC, even in the presence of viable HCC in the explant. There seems to be no reason to contraindicate the use of IBS in LT for HCC.

Sinusoidal obstruction syndrome secondary the intake of Senecio brasiliensis: A case report.

Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease histologically characterized by edema, necrosis, detachment of endothelial cells in small sinusoidal hepatic and interlobular veins and intrahepatic congestion, which leads to portal hypertension and liver dysfunction. In the Western world, most HSOS cases are associated with myeloablative pretreatment in a hematopoietic stem cell transplantation setting. Here we report a case of a 54 years old female patient, otherwise healthy, with no history of alcoholic ingestion, who presented with jaundice and signs of portal hypertension, including ascites and bilateral pleural effusion. She had no history of liver disease and denied any other risk factor for liver injury, except Senecio brasiliensis ingestion as a tea, prescribed as a therapy for menopause. Acute viral hepatitis and thrombosis of the portal system were excluded in complementary investigation, as well as sepsis, metastatic malignancy and other liver diseases, setting a RUCAM score of 6. Computed tomography demonstrated a diffuse liver parenchymal heterogeneity (in mosaic) and an extensive portosystemic collateral venous circulation, in the absence of any noticeable venous obstruction. HSOS diagnosis was confirmed through a liver biopsy. During the following-up period, patient developed refractory pleural effusion, requiring hemodialysis. Right before starting anticoagulation, she presented with abdominal pain and distention, with findings compatible of mesenteric ischemia by computed tomography. A laparotomy was performed, showing an 80cm segment of small bowel ischemia, and resection was done. She died one day after as a result from a septic shock refractory to treatment. The presented case was related to oral intake of S. brasiliensis, a plant containing pyrrolidine alkaloids, which are one of the main causes of HSOS in the East, highlighting the risk of liver injury with herbs intake.

Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort.

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

Hepatic steatosis among people living with HIV in Southern Brazil: prevalence and risk factors.

Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.

Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.