Role of Plasma Exchange and Combining Therapies in Dengue-Associated Acute Liver Failure: A Systematic Review of Individual Cases.

Background/Aims: Dengue-associated acute liver failure (ALF) poses a significant risk for mortality, especially in regions lacking access to liver transplantation. Although Plasma Exchange (PLEX) is recognized as a potential therapeutic intervention for dengue-associated ALF, data on its efficacy remain limited. This systematic review aimed to comprehensively examine the literature on PLEX and other combination therapies for dengue-associated ALF. It focused on assessing their effectiveness, safety profile, and potential implications for therapeutic interventions. Methods: In this study, we conducted a systematic review to assess the efficacy and safety of PLEX and other combination therapies in patients with dengue-associated ALF. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria were used to search the PubMed, Scopus, Embase, Ovid, and Google Scholar databases. Studies published in English between 2019 and May 2024 were included. The titles and abstracts were reviewed for discrepancies, and any differences were resolved through discussion. Results: Among the 713 studies assessed for review, 9 met the eligibility criteria. Studies have demonstrated that PLEX, both alone and in combination with other therapies, such as continuous renal replacement therapy (CRRT), improves liver function, survival rates, and neurological outcomes in patients with dengue virus. Both high- and low-volume plasma exchanges were effective. Conclusion: This systematic review highlights the beneficial role of PLEX and the potential benefits of combination therapies in the treatment of rare and severe forms of dengue-associated ALF. However, given the limited sample sizes and the necessity for well-designed studies, further investigations are needed to determine the optimal volume of PLEX and the efficacy of additional therapeutic strategies.

Napabucasin deactivates STAT3 and promotes mitoxantrone-mediated cGAS-STING activation for hepatocellular carcinoma chemo-immunotherapy.

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.

Adverse Outcome Pathways Mechanistically Describing Hepatotoxicity.

Adverse outcome pathways (AOPs) describe toxicological processes from a dynamic perspective by linking a molecular initiating event to a specific adverse outcome via a series of key events and key event relationships. In the field of computational toxicology, AOPs can potentially facilitate the design and development of in silico prediction models for hazard identification. Various AOPs have been introduced for several types of hepatotoxicity, such as steatosis, cholestasis, fibrosis, and liver cancer. This chapter provides an overview of AOPs on hepatotoxicity, including their development, assessment, and applications in toxicology.

Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

Reproductive and developmental safety evaluation of Thymelaea hirsuta (L.) leaves aqueous extract in Wistar albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The popularity of herbal medicine is expanding globally due to the common belief that herbal products are natural and nontoxic. Thymelaea hirsuta leaves are traditionally used for the treatment of recurrent abortion in humans and animals. However, a lack of safety evaluation of the plant, particularly in pregnant women, raises serious concerns regarding its potential embryotoxic effects. AIM OF THE STUDY: Therefore, the present study investigated the safety of Thymelaea hirsuta leaves aqueous extract (THLE) during pregnancy and lactation following maternal rat treatment. MATERIALS AND METHODS: THLE phytochemical compounds were identified using high-performance liquid chromatography (HPLC). THLE was orally administered to pregnant rats and lactating dams at dosages of 0, 250, 500, and 1000 mg/kg/day. At the end of the study, dam s' and pups' body weights, serum biochemical and hematological indices, and histopathological changes were investigated. For the fetal observation and histopathological changes were also evaluated. RESULTS: Our findings revealed that THLE is rich in different phenolic and flavonoid compounds. However, biochemical and hormonal parameters such as ALT, AST, and prolactin were significantly increased in dams treated with a higher dosage of THLE when compared to the control dams (P ≤ 0.05). Additionally, external, visceral and skeletal examinations of fetuses revealed a marked increase of malformation rates in treated fetuses. CONCLUSIONS: The results revealed that higher oral dosing of THLE during pregnancy could affect embryonic development in rats, while lower doses are safe and can be used during pregnancy and lactation to attain its beneficial effects.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

Liver Resection for Hepatocellular Carcinoma: Recent Advances.

Hepatocellular carcinoma (HCC) represents a significant global health burden. Surgery remains a cornerstone in the curative treatment of HCC, and recent years have witnessed notable advancements aimed at refining surgical techniques and improving patient outcomes. This review presents a detailed examination of the recent innovations in HCC surgery, highlighting key developments in both surgical approaches and adjunctive therapies. Advanced imaging technologies have revolutionized preoperative assessment, enabling precise tumour localization and delineation of vascular anatomy. The use of three-dimensional rendering has significantly augmented surgical planning, facilitating more accurate and margin-free resections. The advent of laparoscopic and robotic-assisted surgical techniques has ushered in an era of minimal access surgery, offering patients the benefits of shorter hospital stays and faster recovery times, while enabling equivalent oncological outcomes. Intraoperative innovations such as intraoperative ultrasound (IOUS) and fluorescence-guided surgery have emerged as valuable adjuncts, allowing real-time assessment of tumour extent and aiding in parenchyma preservation. The integration of multimodal therapies, including neoadjuvant and adjuvant strategies, has allowed for 'bio-selection' and shown the potential to optimize patient outcomes. With the advent of augmented reality and artificial intelligence (AI), the future holds immense potential and may represent significant strides towards optimizing patient outcomes and refining the standard of care.

Integration of network pharmacology, UHPLC-Q exactive orbitrap HRMS technique and metabolomics to elucidate the active ingredients and mechanisms of compound danshen pills in treating hypercholesterolemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypercholesterolemia (HLC) was a key risk factor for cardiovascular disease (CVD) characterized by elevated cholesterol levels, particularly LDL. While traditional Chinese medicine preparations Compound Danshen Pills(CDP) has been clinically used for hypercholesterolemia and coronary heart disease, its specific therapeutic effect on HLC remains understudied, necessitating further investigation into its mechanisms. AIM OF THE STUDY: The aim of this study was to explore the potential of CDP in treating HLC and elucidate its underlying mechanisms and active components. MATERIALS AND METHODS: A hypercholesterolemic lipemia rat model induced by a high-fat diet was employed. Network pharmacology combined with UHPLC-Q exactive orbitrap HRMS technique was used to predict the active components, targets and mechanisms of CDP for HLC. Histological analysis and serum biochemical assays were used to assess the therapeutic effect of CDP and its main active ingredient Sa B on hypercholesterolemic lipemia rat model. Immunofluorescence assays and western blotting were used to verify the mechanism of CDP and Sa B in the treatment of HLC. Metabolomics approach was used to demonstrate that CDP and Sa B affected the metabolic profile of HLC. RESULTS: Our findings demonstrated that both CDP and its main active ingredient Sa B significantly ameliorated hypercholesterolemic lipemic lesions, reducing levels of TC, LDL, AST, ALT, and ALP. Histological analysis revealed a decrease in lipid droplet accumulation and collagen fiber deposition in the liver, as well as reduced collagen fiber deposition in the aorta. Network pharmacology predicted potential targets such as PPARα and CYP27A1. Immunofluorescence assays and western blotting confirmed that CDP and Sa B upregulated the expression of Adipor1, PPARα and CYP27A1. Metabolomics analyses further indicated improvements in ABC transporters metabolic pathways, with differential metabolites such as riboflavin, taurine, and choline showed regression in levels after CDP treatment and riboflavin, L-Threonine, Thiamine, L-Leucine, and Adenosine showed improved expression after Sa B treatment. CONCLUSION: CDP and Sa B have been shown to alleviate high-fat diet-induced hypercholesterolemia by activating the PPAR pathway and improving hepatic lipid metabolism. Our study demonstrated, for the first time, the complex mechanism of CDP, Sa B in the treatment of hypercholesterolemia at the protein and metabolic levels and provided a new reference that could elucidate the pharmacological effects of traditional Chinese medicine on hypercholesterolemia from multiple perspectives.

Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe.

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

Identification of Senkyunolide I as a novel modulator of hepatic steatosis and PPARα signaling in zebrafish and hamster models.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver-related morbidity and mortality, with hepatic steatosis being the hallmark symptom. Salvia miltiorrhiza Bunge (Smil, Dan-Shen) and Ligusticum striatum DC (Lstr, Chuan-Xiong) are commonly used to treat cardiovascular diseases and have the potential to regulate lipid metabolism. However, whether Smil/Lstr combo can be used to treat NAFLD and the mechanisms underlying its lipid-regulating properties remain unclear. PURPOSE: To assess the feasibility and reliability of a short-term high-fat diet (HFD) induced zebrafish model for evaluating hepatic steatosis phenotype and to investigate the liver lipid-lowering effects of Smil/Lstr, as well as its active components. METHODS: The phenotypic alterations of liver and multiple other organ systems were examined in the HFD zebrafish model using fluorescence imaging and histochemistry. The liver-specific lipid-lowering effects of Smil/Lstr combo were evaluated endogenously. The active molecules and functional mechanisms were further explored in zebrafish, human hepatocytes, and hamster models. RESULTS: In 5-day HFD zebrafish, significant lipid accumulation was detected in the blood vessels and the liver, as evidenced by increased staining with Oil Red O and fluorescent lipid probes. Hepatic hypertrophy was observed in the model, along with macrovesicular steatosis. Smil/Lstr combo administration effectively restored the lipid profile and alleviated hepatic hypertrophy in the HFD zebrafish. In oleic-acid stimulated hepatocytes, Smil/Lstr combo markedly reduced lipid accumulation and cell damage. Subsequently, based on zebrafish phenotypic screening, the natural phthalide senkyunolide I (SEI) was identified as a major molecule mediating the lipid-lowering activities of Smil/Lstr combo in the liver. Moreover, SEI upregulated the expression of the lipid metabolism regulator PPARα and downregulated fatty acid translocase CD36, while a PPARα antagonist sufficiently blocked the regulatory effect of SEI on hepatic steatosis. Finally, the roles of SEI on hepatic lipid accumulation and PPARα signaling were further verified in the hamster model. CONCLUSIONS: We proposed a zebrafish-based screening strategy for modulators of hepatic steatosis and discovered the regulatory roles of Smil/Lstr combo and its component SEI on liver lipid accumulation and PPARα signaling, suggesting their potential value as novel candidates for NAFLD treatment.

Effect of Immunosuppressive Regimens on Metabolic Dysfunction-associated Fatty Liver Disease Following Liver Transplantation.

Background: Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored. Methods: A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. Results: A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15-0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01-2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease. Conclusions: Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

Adverse Events and Outcomes of High-volume Plasma Exchange in 50 Acute Liver Failure Patients: A Monocentric Retrospective Real-world Study.

Background and aims: Acute liver failure (ALF) is a condition that mostly requires Intensive Care Unit (ICU) admission and sometimes necessitates emergency liver transplantation. High-volume plasma exchange (HVPE) may improve transplant-free survival (TFS) in ALF. Our study assessed complications of HVPE therapy and outcome in ALF patients. Methods: We conducted a single-center retrospective study of all patients admitted to the ICU for ALF and who underwent HVPE between June 2016 and June 2021. The plasmapheresis technique used was centrifugation, and the volume exchanged was calculated as 15% of the ideal body weight. Dedicated staff prospectively collected clinical adverse effects, while biological data were retrospectively collected. The primary outcome was the rate of severe adverse effects (SAE, defined as severe manifestations of hypotension, allergy, metabolic disturbances or other life-threatening event) that occurred during HVPE sessions. Factors influencing day-21 TFS were also studied. Results: One hundred twenty sessions were performed in 50 patients. The main etiology for ALF was paracetamol (52% of the patients). During the session, hemoglobin, platelet, transaminases, ammonia and bilirubin decreased, coagulation factors increased, and creatinine and lactate remained unchanged. At least one SAE was reported for 32 out of 120 sessions (26.7% [19%-35.5%], mostly severe alkalosis [24/117], hypotension [4/120] and hypocalcemia [4/119]). Arterial pH ≤ 7.43 following HVPE and paracetamol etiology were negatively and positively associated with day-21 TFS, respectively. Conclusion: Severe adverse effects were frequent during HVPE performed for ALF, mainly severe alkalosis, hypotension and hypocalcemia. Post-HVPE, pH and paracetamol etiology were prognosis markers.

Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. Methods: MASLD patients seen in our out-patient department underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as a liver stiffness measurement of ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel diabetes-visceral fat 15 (DVF15) score. Results: We analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, P < 0.001) and elevated levels of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, Fibosis-4, aspartate-aminotransferase-to platelet-ratio index, and NAFLD fibrosis scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and a visceral fat level of >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the receiver operating characteristic curve of 0.664 (P < 0.001). Conclusion: Our study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or a visceral fat level of >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

The Impact of Gender and Race on Outcomes for Hospitalized Hepatitis A Patients Stratified by Liver Disease Severity.

Background: The incidence of hepatitis A virus (HAV) infection is on the rise, with a minority of patients at risk for poor outcomes. This study investigates the prognostic impacts of race and gender on hospital outcomes among admitted HAV-infected patients. Methods: Using the National Inpatient Sample from 2012 to 2017, patients admitted with HAV were selected and stratified by gender (male and female) and race (White, Black, Hispanic, Asian-Pacific Islander, Other). Propensity score-matching and statistical analysis were implemented with comparison to the controls ("Female" and "White"). Primary endpoints included mortality, length of stay (LOS), and hospitalization costs, while secondary endpoints consisted of hepatic-related medical complications such as ascites, hepatic encephalopathy, varices, and acute liver failure. Results: Females with compensated cirrhosis had increased odds of mortality (aOR 2.59, 95% CI: 1.14-5.91, P = 0.02). Otherwise, no other differences in mortality were detected between genders and races. Females had a shorter hospital LOS (aOR 0.97, 95% CI: 0.96-0.98, P < 0.001), lower adjusted cost ($12,241 vs. $13,510, aOR 0.92, 95% CI: 0.92-0.92, P < 0.001), lower odds of esophageal varices (aOR 0.74, 95% CI: 0.57-0.97, P = 0.03) and hepatic encephalopathy (aOR 0.67, 95% CI: 0.53-0.84, P < 0.001) compared to males. Black patients exhibited higher LOS (aOR 1.06, 95% CI: 1.04-1.08, P < 0.001) and adjusted costs ($13,392 vs $12,592, aOR 1.02, 95% CI: 1.02-1.03, P < 0.001). Hispanic patients exhibited higher rates of esophageal varices (aOR 2.19, 95% CI: 1.28-3.76, P = 0.005) and adjusted costs ($14,202 vs. $12,381, aOR 1.07, 95% CI: 1.07-1.07, P < 0.001), and Asian patients experienced higher adjusted costs ($18,426 vs. $13,137, aOR 1.10, 95% CI: 1.10-1.10, P < 0.001) compared to White patients. Conclusion: Various nuanced impacts of gender and race on hospitalization outcomes in HAV infection were observed, with only one subgroup analysis demonstrating a higher rate of mortality. Further research is warranted to better understand these findings and their implications.

Evolving Global Etiology of Hepatocellular Carcinoma (HCC): Insights and Trends for 2024.

The epidemiology of HCC is changing all over the world and the incidence of HCC is expected to continue increasing over the next 30 years. The changes are in the predisposing factors. Hepatitis B and hepatitis C as predisposing etiologies are decreasing while NAFLD/MAFLD is increasing. The increase in MAFLD is so great that despite the decrease in hepatitis B and C, the overall incidence of HCC is increasing. HCC in persons below the age of 20 years has distinct characteristics different from that of HCC in adults. The changing etiology of hepatocellular carcinoma has implications for the early detection, prevention, the stage of HCC at time of detection and in the treatment of HCC. The extent of these changes and their significance are discussed.

Estudio de la citoqueratina- 18 como marcador no invasivo en pacientes con enfermedad de hígado graso no alcohólico

Introducción: La enfermedad por hígado graso no alcohólico es una de las principales causas de afección hepática. La citoqueratina 18 surge como marcador no invasivo para la valoración de fibrosis hepática. El objetivo del trabajo fue validar el uso de la citoqueratina 18 en sangre periférica en el diagnóstico y evolución de los pacientes con enfermedad por hígado graso no alcohólico. Metodología: Para validar la citoqueratina 18 en el diagnóstico se realizó un estudio de tipo caso-control. El grupo caso fueron los pacientes mayores de 18 años, de ambos sexos, con diagnóstico de enfermedad por hígado graso no alcohólico vinculado al síndrome metabólico, captados entre 2/2/2019 al 2/2/2020. El grupo control fueron personas donantes de sangre. Se parearon 1-1 por edad y sexo. Se cuantificó la citoqueratina 18 en sangre periférica de ambos grupos. Para validar la citoqueratina 18 en la evolución de los pacientes con enfermedad de hígado graso no alcohólico se realizó un trabajo prospectivo, longitudinal. El grupo de pacientes captados fueron seguidos durante un año bajo tratamiento estándar, finalizando el mismo se realizó la cuantificación de citoqueratina 18 en sangre periférica. Las variables continuas se expresan con la media y desvío estándar. Se analizó con test de t Student, error α < 5% Resultados: 13 pacientes integran el grupo caso (12 mujeres), de 53 ± 11 años, con IMC 35.01 ± 8.9 kg/m2. El valor de citoqueratina 18 pre-tratamiento fue de 1410 ± 120 UI, y el valor post-tratamiento fue de 117 ± 56, p < 0,005.El grupo control fueron 13 personas (12 mujeres), de 43,4 ± 8,1 años e IMC 28,10 ± 5,4 kg/m2 El valor de citoqueratina 18 fue de 193 ± 7.2 UI, p < 0.005 vs grupo caso pretratamiento. Conclusiones: La citoqueratina 18 es más elevada en los pacientes con enfermedad hígado graso no alcohólico, siendo estadísticamente significativa y disminuye con el tratamiento con significación estadística, pudiendo constituirse en un marcador útil en este grupo de pacientes.

Introduction: Nonalcoholic fatty liver disease is one of the main causes of liver disease. Cytokeratin 18 emerges as a non-invasive marker for the assessment of liver fibrosis. The objective of the work was to validate the use of cytokeratin 18 in peripheral blood in the diagnosis and evolution of patients with non-alcoholic fatty liver disease. Methodology: To validate cytokeratin 18 in the diagnosis, a case-control study was carried out. The case group was patients over 18 years of age, of both sexes, with a diagnosis of non-alcoholic fatty liver disease linked to metabolic syndrome, recruited between 2/2/2019 to 2/2/2020. The control group were blood donors. They were matched 1-1 for age and sex. Cytokeratin 18 was quantified in peripheral blood of both groups. To validate cytokeratin 18 in the evolution of patients with non-alcoholic fatty liver disease, a prospective, longitudinal study was carried out. The group of patients recruited were followed for one year under standard treatment, at the end of which cytokeratin 18 was quantified in peripheral blood. Continuous variables are expressed with the mean and standard deviation. It was analyzed with Student's t test, α error < 5%. Results: 13 patients make up the case group (12 women), 53 ± 11 years old, with BMI 35.01 ± 8.9 kg/m2. The pre-treatment cytokeratin 18 value was 1410 ± 120 IU, and the post-treatment value was 117 ± 56, p < 0.005. The control group was 13 people (12 women), 43.4 ± 8.1 years and BMI 28.10 ± 5.4 kg/m2 The cytokeratin 18 value was 193 ± 7.2 IU, p < 0.005 vs. pretreatment case group. Conclusions: Cytokeratin 18 is higher in patients with non-alcoholic fatty liver disease, being statistically significant, and decreases with treatment with statistical significance, and may become a useful marker in this group of patients.

Introdução: A doença hepática gordurosa não alcoólica é uma das principais causas de doença hepática. A citoqueratina 18 surge como um marcador não invasivo para avaliação de fibrose hepática. O objetivo do trabalho foi validar o uso da citoqueratina 18 no sangue periférico no diagnóstico e evolução de pacientes com doença hepática gordurosa não alcoólica. Metodologia: Para validar a citoqueratina 18 no diagnóstico, foi realizado um estudo caso-controle. O grupo caso foi composto por pacientes maiores de 18 anos, de ambos os sexos, com diagnóstico de doença hepática gordurosa não alcoólica ligada à síndrome metabólica, recrutados entre 02/02/2019 a 02/02/2020. O grupo controle eram doadores de sangue. Eles foram comparados em 1 a 1 por idade e sexo. A citoqueratina 18 foi quantificada no sangue periférico de ambos os grupos. Para validar a citoqueratina 18 na evolução de pacientes com doença hepática gordurosa não alcoólica, foi realizado um estudo prospectivo e longitudinal. O grupo de pacientes recrutados foi acompanhado durante um ano sob tratamento padrão, ao final do qual a citoqueratina 18 foi quantificada no sangue periférico. As variáveis ​​contínuas são expressas com média e desvio padrão. Foi analisado com teste t de Student, erro α < 5%. Resultados: Compõem o grupo caso 13 pacientes (12 mulheres), 53 ± 11 anos, com IMC 35,01 ± 8,9 kg/m2. O valor de citoqueratina 18 pré-tratamento foi de 1410 ± 120 UI e o valor pós-tratamento foi de 117 ± 56, p < 0,005. O grupo controle foi de 13 pessoas (12 mulheres), 43,4 ± 8,1 anos e IMC 28,10 ± 5,4 kg/m2 O valor da citoqueratina 18 foi de 193 ± 7,2 UI, p < 0,005 vs. grupo de casos pré-tratamento. Conclusões: A citoqueratina 18 é maior em pacientes com doença hepática gordurosa não alcoólica, sendo estatisticamente significativa, e diminui com o tratamento com significância estatística, podendo se tornar um marcador útil neste grupo de pacientes.

Highly sensitized patients listed for heart after liver transplantation with or without domino.

For patients with end-stage heart disease and borderline hemodynamics, high human leukocyte antigen allosensitization presents a barrier to heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant on a single patient without liver disease. We describe this patient's course to date as well as 4 subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.

Sarcopenia in cirrhosis: From pathophysiology to interventional therapy.

Sarcopenia, characterized by the loss of skeletal muscle mass and function, is a significant complication in patients with cirrhosis. This condition not only exacerbates the overall morbidity and mortality associated with liver disease but also complicates patient management, increasing the risk of hospitalization, infections, and hepatic encephalopathy. Despite its clinical significance, sarcopenia in cirrhotic patients remains underdiagnosed and undertreated. This review aims to summarize current knowledge on the pathophysiology of sarcopenia in cirrhosis, including mechanisms such as altered metabolism, hormonal imbalances, and inflammation. Additionally, we explore diagnostic challenges and discuss emerging therapeutic strategies, including nutritional support, exercise, and pharmacological interventions. By highlighting the gaps in existing research and proposing directions for future studies, this review seeks to improve the management and outcomes of cirrhotic patients affected by sarcopenia.

Imaging features of hepatic angiosarcoma: retrospective analysis of two centers.

PURPOSE: Identifying primary hepatic angiosarcoma (PHA) preoperatively is challenging, often relying on postoperative pathology. Invasive biopsy increases bleeding risk, emphasizing the importance of early PHA diagnosis through imaging. However, comprehensive summaries of ultrasound, abdominal computed tomography (CT), magnetic resonance imaging (MRI), and whole- body positron emission tomography-CT (PET-CT) in this context are lacking. This study aimed to investigate the comprehensive imaging characteristics of PHA. PATIENTS AND METHODS: Imaging data were collected from 7 patients diagnosed with PHA via pathology between January 2000 and December 2019 in two provincial grade III hospitals. All patients underwent routine color ultrasound examinations before surgery, with 3 patients receiving contrast-enhanced ultrasound (CEUS).CT scans, both plain and enhanced, were performed on 5 patients, and whole-body PET-CT examinations were conducted on 2 patients. RESULTS: Among the 7 patients with PHA, 4 presented with a single solid intrahepatic mass (2 of which were large), 1 with a single exophytic macroblock type, 1 with a mixed type featuring multiple masses and nodules, and 1 with a multiple nodule type. Conventional ultrasound of PHA showed uneven echoes within the tumor, potentially accompanied by septal zone echoes, and a blood flow grade of 0-I. CEUS displayed early-stage circular high enhancement, a central non-enhancement area, and a "vascular sign" around the tumor. CT scans revealed low-density shadows in the plain scan stage, high peripheral ring enhancement, and punctate nodular enhancement in the arterial phase, with varying intensities and the presence of a "vascular sign." During the portal vein stage, the interior of the tumor was consistently unfilled and exhibited structural disorder. PET-CT showed low-density lesions in the liver and low fluorodeoxyglucose metabolism. CONCLUSIONS: Imaging diagnosis plays a crucial role in PHA diagnosis. When liver tumor imaging matches the above characteristics, consider PHA.

Hepatitis C virus attributable liver cancer in the country of Georgia, 2015-2019: a case-control study.

BACKGROUND: Hepatitis C virus (HCV) infection can lead to a type of primary liver cancer called hepatocellular carcinoma (HCC). Georgia, a high HCV prevalence country, started an HCV elimination program in 2015. In addition to tracking incidence and mortality, surveillance for the HCV-attributable fraction of HCC is an important indicator of the program's impact. This study assesses HCV infection-attributable HCC in the Georgian population. METHODS: This case-control study utilized HCV programmatic and Georgian Cancer Registry data from 2015-2019. Bivariate logistic regression and age- and sex-stratified analyses assessed HCV and liver cancer association. HCV-attributable liver cancer proportions for the HCV-exposed and total population were calculated. A sub-analysis was performed for HCC cases specifically. RESULTS: The total study population was 3874 with 496 liver cancer cases and 3378 controls. The odds for HCV-infected individuals developing liver cancer was 20.1 (95% confidence interval [CI] 15.97-25.37), and the odds of developing HCC was 16.84 (95% CI 12.01-23.83) compared to the HCV-negative group. Odds ratios varied across strata, with HCV-infected older individuals and women having higher odds of developing both liver cancer and HCC. A large proportion of liver cancer and HCC can be attributed to HCV in HCV-infected individuals; however, in the general population, the burden of liver cancer and HCC cannot be explained by HCV alone. CONCLUSION: HCV was significantly associated with a higher risk of developing liver cancer and HCC in the Georgian population. In addition, given Georgia's high HCV burden, increased HCC monitoring in HCV-infected patients is needed.