Progressive Liver Damage Research Articles

Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice.

Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen (APAP). However, the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear. To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation. A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury. C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment. We detected the effects of C2-FH on liver function, inflammatory response and complement activation. Additionally, RNA-sequencing (RNA-Seq) analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury. C2-FH inhibited the increase in serum alanine aminotransferase activity, aspartate aminotransferase activity and lactate dehydrogenase, and reduced liver tissue necrosis caused by APAP. Moreover, it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury. RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury. C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.

Hepatitis B Virus-Associated Liver Carcinoma: The Role of Iron Metabolism and Its Modulation.

Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Iron, a central co-factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV-related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV-associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV-associated HCC and potentially identify novel therapeutic avenues for intervention.

A Cascade Activation Probe with Double-Enhanced Near-Infrared Imaging for Monitoring Peroxynitrite Fluctuations in Vivo.

Monitoring peroxynitrite (ONOO-) fluctuations is particularly important for assessing pathological progression and oxidative damage due to their crucial role in maintaining the redox balance of organisms. However, due to the lack of efficient tools for differentially monitoring ONOO- fluctuations at different concentration ranges in vivo, the precise detection of endogenous ONOO- fluctuations under pathological conditions in living systems remains challenging. Herein, we rationally designed a double-enhanced emission cascade activatable near-infrared (NIR) fluorescent probe (B-TCF) for the measurement of ONOO-, which consists of a borate ester response group and a malononitrile hemicyanine fluorophore. Especially, after sequential oxidative hydrolysis of the borate ester group and xanthene skeleton, B-TCF exhibited a sequentially double-enhanced NIR emission response at 776 and 625 nm for different ONOO- concentration ranges. Moreover, B-TCF revealed excellent and promising performance for ONOO- in terms of high selectivity, sensitivity, and reaction rate (k = 28.2 M-1 s-1). Motivated by the two-step emission signal enhancement and large wavelength shift in the NIR region, B-TCF enabled discriminative imaging of ONOO- with the low and high concentrations in living cells. Importantly, B-TCF was successfully applied for assessing the pathological progression of isoniazid and acetaminophen-induced liver damage in vivo by detecting the endogenous different ONOO- levels. Overall, this study not only demonstrates the first double-enhanced emission cascade activatable NIR fluorescent probe for measuring the dynamic variation of ONOO- in related diseases but also shows great potential as an effective molecular tool for evaluating the various stages of drug-induced liver damage.

Azithromycin induces liver injury in mice by targeting the AMPK/Nrf2 pathway

Background Azithromycin is an antibacterial and anti-inflammatory drug widely used for the treatment of various diseases, including those caused by atypical pathogens, bacterial or viral infections, chronic sinusitis, and bronchial asthma, particularly in pediatric patients. However, concerns have emerged regarding its hepatotoxicity and its precise mechanism of action remains unclear. Objective To investigate the molecular mechanisms responsible for azithromycin-induced acute liver injury to advance our understanding of the progression and pathogenesis of antibiotic-induced liver damage, and to improve prevention and treatment strategies. Materials and methods C57BL/6 mice, Nrf2-/- mice, and primary hepatocytes were used. Primary hepatocytes from mice were isolated using a two-step perfusion method and cultured in vitro via the ‘sandwich’ culture model. Results The exposure to azithromycin resulted in increased apoptosis and reactive oxygen species (ROS) levels. In mouse models, intraperitoneal administration of azithromycin at varying concentrations and time points substantially induced hepatic disarray, swelling, and dysfunction. Azithromycin markedly upregulated the mRNA and protein levels of phosphorylated adenosine-activated protein kinase (AMPK) while downregulating nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NADPH: quinone oxidoreductase 1 (NQO-1). Moreover, HO-1 and NQO-1 protein levels remained largely unaffected in primary hepatocytes co-cultured with azithromycin in Nrf2-/- mice. Conclusions Our findings suggest that azithromycin-induced acute liver injury is mediated by suppression of Nrf2 activation and ROS production. This sheds light on the potential mechanisms involved in azithromycin-induced liver damage, underscoring the importance of exploring targeted interventions to mitigate the hepatotoxic effects.

Point Shear Wave Elastography for Assessment of Liver Stiffness in Normal Individuals and in Patients With Non-alcoholic Fatty Liver Disease.

Background Non-alcoholic fatty liver disease (NAFLD) is an increasing health issue worldwide, driven by rising rates of diabetes, obesity, and hypertriglyceridemia. Often asymptomatic, NAFLD is diagnosed through blood tests, imaging, and sometimes liver biopsy. Some cases advance to non-alcoholic steatohepatitis (NASH), which can lead to complications like liver cirrhosis and liver failure. While liver biopsy is the standard test for diagnosis, non-invasive methods such as shear wave elastography (SWE) offer a simpler and more reproducible alternative for diagnosing NAFLD. This is crucial for early intervention and preventing the progression of liver damage. Objectives The objectives of the study were to measure and compare liver stiffness in healthy individuals and patients with NAFLD using point shear wave elastography (pSWE), as well as to correlate liver stiffness in NAFLD patients with the ultrasonographic grades of fatty liver. Materials and methods This observational study was carried out at Dr. D. Y. Patil Medical College, Hospitaland Research Centre in Pune, India, from December 2022 to April 2024. The study involved 82 participants in total, with 41 patients diagnosed with NAFLD (cases) and 41 healthy individuals with a sonographically normal liver (controls). pSWE was performed on each participant to measure liver stiffness, with results expressed in kilopascals (kPa). The procedure was conducted using a Samsung HS70A ultrasound machine (Samsung Electronics Pvt. Ltd., Seoul, South Korea). Data analysis was performed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, USA). Non-parametric tests, such as the Mann-Whitney test and Kruskal-Wallis test, were used to evaluate the significance of differences. A p-value of less than 0.05 was considered statistically significant. Results The mean liver stiffness, measured in kilopascals (kPa), was higher in NAFLD patients (cases) (10±5.1 kPa) than in normal individuals (controls) (4.4±0.7 kPa). This difference was statistically significant, with a p-value of less than 0.001. A positive correlation (rho=0.848, p<0.001) was found between the ultrasonographic grade of fatty liver and liver stiffness in NAFLD patients. Conclusion Our study demonstrated that individuals with NAFLD exhibited significantly higher liver stiffness compared to healthy individuals, as measured by ultrasound SWE. These findings suggest that pSWE could serve as a valuable, non-invasive diagnostic tool for assessing liver stiffness in NAFLD patients. Additionally, pSWE holds the potential for evaluating and monitoring the progression of the disease. However, further research with larger sample sizes is necessary to determine the prognostic significance of liver stiffness in these patients.

Association between Liver Damage and Disease Progression Markers with Mortality Risk and Mechanical Ventilation in Hospitalized COVID-19 Patients: A Nationwide Retrospective SARSTer Study.

(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718-0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727-0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients.

Hépatocarcinomes liés à l’infection par le VHB et potentielles nouvelles stratégies thérapeutiques

AbstractHepatocellular carcinomas (HCC) are the most common primary liver tumours. They are the second leading cause of cancer-related mortality worldwide. The main etiological factors include viral hepatitis B and C, chronic alcohol intake and metabolic syndromes. We will focus this review on the impact of hepatitis B virus (HBV) infection and the progression of liver damage to HCC. Both direct and indirect mechanisms of HBV infection contribute to the emergence of HCC. We will address these two types of mechanisms by focusing on direct viral effects, explored in numerous in vivo and in vitro studies. Published results can sometimes be contradictory. They vary depending on the study model, the viral sequence, the level of HBV expression, the type of viral genome transferred (partial or complete), the transfer method, generating a stable or transient expression, and many other parameters. Nevertheless, the knowledge acquired recently on the viral cycle, and in particular on the nature of the hepatocyte receptor of HBV, allows today to reproduce in vitro a complete viral cycle in different experimental models and thus, to better appreciate the pro-tumor activities of HBV infection.This review is obviously not exhaustive and the knowledge, particularly on the clinical and therapeutic management of HCC, whether associated with the presence of HBV or not, is currently evolving with the rise of combined immunotherapies.

Antibiotic effects on gut microbiota modulate diet-induced metabolic dysfunction-associated steatohepatitis development in C57BL/6 mice.

The potential involvement of the gut microbiota in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis has garnered increasing attention. In this study, we elucidated the link between high-fat/cholesterol/cholate-based (iHFC)#2 diet-induced MASH progression and gut microbiota in C57BL/6 mice using antibiotic treatments. Treatment with vancomycin (VCM), which targets gram-positive bacteria, exacerbated the progression of liver damage, steatosis, and fibrosis in iHFC#2-fed C57BL/6 mice. The expression levels of inflammation- and fibrosis-related genes in the liver significantly increased after VCM treatment for 8 weeks. F4/80+ macrophage abundance increased in the livers of VCM-treated mice. These changes were rarely observed in the iHFC#2-fed C57BL/6 mice treated with metronidazole, which targets anaerobic bacteria. A16S rRNA sequence analysis revealed a significant decrease in α-diversity in VCM-treated mice compared with that in placebo-treated mice, with Bacteroidetes and Firmicutes significantly decreased, while Proteobacteria and Verrucomicrobia increased markedly. Finally, VCM treatment dramatically altered the level and balance of bile acid (BA) composition in iHFC#2-fed C57BL/6 mice. Thus, the VCM-mediated exacerbation of MASH progression depends on the interaction between the gut microbiota, BA metabolism, and inflammatory responses in the livers of iHFC#2-fed C57BL/6 mice.

«ДОРОЖНАЯ КАРТА» БИОМАРКЕРОВ ПРИ ЕСТЕСТВЕННОМ ТЕЧЕНИИ HBV-ИНФЕКЦИИ

Background. Hepatitis B virus (HBV) causes both acute and chronic infection that can be asymptomatic or mild, occur as severe or fulminant hepatitis. Testing for HBV markers and establishing a diagnosis of hepatitis B are a key component affecting the epidemic process and allowing people with CHB to receive effective care to prevent or slow down progressive liver damage. Objective. To present a diagnostic «road map» of HBV biomarkers for doctors of various specialties involved in the diagnosis, treatment, screening and prevention of HBV infection. Material and methods. An electronic search was carried out on PubMed, UpToDate, Scopus, Web of Science, elibrary, CDC, ECDC, WHO/WHO using key words. In accordance with the specified search criteria and the purpose of the study; the titles, abstracts and full texts of scientific articles were studied, that is fully reflected in the list of references. Results. There have been provided a description of CHB natural history, its well-known diagnostic markers and new serological opportunities for medical monitoring, such as nuclear antigen (HBcrAg), pregenomic RNA (pgRNA) as well as quantitative determination of antibodies - qAnti-HBc. The diagnostic and prognostic effectiveness of “classical” and “new” biomarkers when used together opens up new opportunities for solving epidemiological or clinical problems. Conclusions. The unavailability of new tests in the form of commercial diagnostic kits complicates the use of some of them, at least that of HBcrAg, pgRNA, qAnti-HBc, which are on the “waiting list” for implementation.

Effects of a multicomponent lifestyle modification intervention on liver function, lipid profile, and body composition in adults with elevated hepatic steatosis index

Parallel to the escalating burden of obesity is the steadily increasing prevalence of metabolic dysfunction associated steatotic liver diseases (MASLD), a chronic condition that progresses from simple steatosis to advanced stages of steatohepatitis, fibrosis, and cirrhosis (1-2). MASLD, regarded as the hepatic manifestation of metabolic syndrome is known to be exacerbated by unhealthy lifestyle choices and the presence of comorbidities such as diabetes, dyslipidemia, and obesity (3-4). Therefore, early identification of the general population at risk of MASLD and the development of multicomponent interventions that can prevent the progression of liver damage and mitigate associated adverse cardiometabolic health outcomes are important. Our study aimed to evaluate the effects of a lifestyle modification program on glucose levels, lipid profile, liver function, and body composition measures in community-living adults with elevated hepatic steatosis index in Mumbai, India.Adults (n= 231, mean age 46.1(13.7) years), 58.6% men) were screened for risk of MASLD using a non-invasive screening tool, Hepatic Steatosis Index (HSI) (calculated as (HSI)= 8 x (ALT/AST ratio) +BMI (+2, if female; +2, if diabetes mellitus) (5). Eligible participants with HSI &gt;36 (predictive of the presence of MASLD) were randomized to receive either a multicomponent lifestyle intervention (experimental group, EG) comprising weekly sessions of individualized dietary counseling (Participants having BMI &gt;23kg/m2 (n = 36) received hypocaloric diets with 40% carbohydrates, 40% fat and 30% proteins (WLD) and those having BMI &lt;22.9kg/m2 (n= 22) received weight maintenance diet (WMD) plans including 55% carbohydrates, 15% protein and 30% fats) and fortnightly group sessions of structured exercise and nutrition education or a standard of care package (control group, CG, n= 43) including general healthy eating and activity guidelines for the 8- week study duration. Paired t test and independent sample t tests were used to determine within and between group changes in variables from baseline to endline.Trial Registration: This study is registered as CTRI/2022/05/042927.Overall, the prevalence of MASLD was 52.2%, 32.8% were hypertensive, and 26.7% and 15.4% had diabetes and hypertriglyceridemia respectively. The intervention (WLD) resulted in decreased weight (mean (M)= 3.4 kg, standard error (SE) = 1.88 k, p = 0.02), body fat percent (M = 2.2%, SE = 1.1%, p= 0.042), serum triglycerides (M=28.8mg/dL, SE 8.5mg/dL, p&lt;0.001) and AST (M= 3.8 U/L, SE= 2.2U/L, p &lt;0.05) values. The WMD group reported improvements in serum cholesterol levels, and ALT/ AST ratio as compared to CG (p &lt;0.001). In WMD, HDL-C increased from 45.8 mg/dl to 47.2 mg/dl and the mean AST values reduced from 28.8 (10.6) U/L to 25.6 (9.9) U/L, but these changes were not statistically significant.Multicomponent lifestyle modification programs integrating diet, physical activity and education are effective strategies to improve liver outcomes and optimize cardiometabolic health in people with MASLD.

Correlation of Simple Laboratory Result Parameters to CTP and MELD Scores, and the Diagnostic Role of Simple Laboratory Indexes to Cirrhosis Decompansation

BackgroundCirrhosis of the liver is a final condition of all chronic liver diseases. Liver cirrhosis is the leading cause of increasing morbidity and mortality in adults worldwide. Systemic inflammation has been suggested to play an important role in causing progressive liver damage and is one of the leading causes of compensated and decompensated liver cirrhosis.Aim of StudyEvaluate the correlation of neutrophil-lymphocyte ratio (NLR), albumin-bilirubin ratio (ABR), albumin-bilirubin score (ALBI), aspartate aminotransferase to platelet ratio (APRI), albumin-creatinine ratio (ACR), lymphocyte-monocyte ratio (LMR), de ritis ratio to the severity of liver cirrhosis as assessed by CTP score and MELD score. In addition, this study also evaluated the diagnostic ability of NLR, ABR, ALBI, APRI, ACR, LMR, de ritis ratio, and CTP and MELD scores in predicting decompensated liver cirrhosis.MethodWe conducted a cross-sectional study involving patients diagnosed with liver cirrhosis at Prof DR IGNG Ngoerah General Hospital. All patients were diagnosed based on clinical history, physical examination, and investigations. This study enrolled 96 cirrhotic patients regardless of etiology. Laboratory examination results recorded platelets, neutrophils, lymphocytes, monocytes, AST, ALT, albumin, and creatinine. Then NLR, ACR, APRI, LMR, de raitis, ALBI, and ABR are calculated. CTP and MELD scores were calculated by taking data from the patient's medical recordResultOf the 96 patients tested in our study, the majority were male (66). The study found a significant moderate to very strong relationship to the MELD score between ACR, APRI, ALBI, ABR, LMR, WBC, sodium, and albumin. Neutrophil to lymphocyte ratio, ACR, De ritis, APRI, LMR, ALBI, ABR, sodium levels, and albumin have a moderate to very strong significant relationship to CTP score. ACR, De ritis, APRI, LMR, ALBI, ABR, WBC, sodium, and albumin levels with respective cut-offs £ 3.6; ≥ 1.5; ≥ 0.3; £ 2.8; ≥ 0.7; £1.6; ≥ 6.7, £ 136.50, and £ 3.0 can be used to help predict decompensated cirrhosisConclusionIn addition to using the CTP score and MELD score as a tool to predict the severity of liver cirrhosis, data from laboratory examination results in the form of albumin and ABR levels can help establish the diagnosis of decompensated cirrhosis. The sensitivity and specificity of ABR were 96.8% and 75.4% with a cut-off of £ 1.6, while albumin levels were 93.5% and 81.5% with an amount off of £ 3.0.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.45<FIB-4<3.25; FIB-4>3.25), respectively group 1,2,3. At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.45<FIB-4<3.25 (24.1%, group 2) and 69 a FIB-4>3.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.45<FIB-4<3.25 (34.4%, group 2) and 76 a FIB-4>3.25 (42.3%, group 3). FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Potential Hepatoprotective Effects of Allicin on Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Oxidative Stress, Inflammation, and Apoptosis.

The global burden of liver disease is enormous, which highlights the need for effective hepatoprotective agents. It was reported that allicin exhibits protective effects against a range of diseases. In this study, we further evaluated allicin's effect and mechanism in acute hepatic injury. Liver injury in mice was induced by intraperitoneal injection with 1% CCl4 (10 mL/kg/day). When the first dose was given, CCl4 was given immediately after administration of different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day), and then different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day) were administrated every 12 h. The animals were dissected 24 h after the first administration. The findings demonstrated a significant inhibition of CCl4-induced acute liver injury following allicin treatment. This inhibition was evidenced by notable reductions in serum levels of transaminases, specifically aspartate transaminase, along with mitigated histological damage to the liver. In this protective process, allicin plays the role of reducing the amounts or the expression levels of proinflammatory cytokines, IL-1β, IL-6. Furthermore, allicin recovered the activities of the antioxidant enzyme catalase (CAT) and reduced the production of malondialdehyde (MDA) in a dose-dependent manner, and also reduced liver Caspase 3, Caspase 8, and BAX to inhibit liver cell apoptosis. Further analysis showed that the administration of allicin inhibited the increased protein levels of Nuclear factor-erythroid 2-related factor 2 (Nrf2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), which is related to inflammation and oxidative stress. The in vitro study of the LPS-induced RAW264.7 inflammatory cell model confirmed that allicin can inhibit important inflammation-related factors and alleviate inflammation. This research firstly clarified that allicin has a significant protective effect on CCl4-induced liver injury via inhibiting the inflammatory response and hepatocyte apoptosis, alleviating oxidative stress associated with the progress of liver damage, highlighting the potential of allicin as a hepatoprotective agent.

Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways.

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.

Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and β-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.

Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. To determine the role and mechanism of UGT1A1 in liver damage progression. We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.

El estrés psicosocial en la esteatosis hepática asociada a disfunción metabólica (MASLD): sobreposición desfavorable

The metabolic dysfunction-associated steatotic liver disease (MASLD)(1) is considered the leading cause of liver disease worldwide. It is a complex pathology, which includes a spectrum of diseases ranging from steatosis to advanced forms of liver damage, such as cirrhosis. Its prevalence has increased in recent years, becoming a relevant public health problem. It is characterized by fat accumulation in hepatocytes, which induces lipotoxicity, oxidative stress, inflammation, and consequently, liver damage. The mechanisms involved in MASLD progression are not fully understood. Also, the factors that determine the heterogeneous susceptibility towards liver fibrosis among patients, remain unresolved. In recent years, chronic stress has been described as a relevant risk factor in the progression of MASLD. The presence of stress is associated with alterations in the gut-liver-brain axis, which promotes systemic low-grade inflammation that reinforces the liver damage progression. This review aims to discuss the evidence about the role of psychosocial stress in MASLD and its association with the pathogenic mechanisms involved in liver damage.

Serodiagnosis of Hepatitis B Surface Antigen and Anti Hepatitis C Virus among Hemodialysis Patients in Khartoum State- Sudan

Background: Hepatitis B virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans through immune energy. Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes progressive liver damage. In hemodialysis (HD), blood is removed from the patient with needles and plastic tubing and pumped past the dialysis membrane. Poisons and toxins cross the dialysis membrane into the dialysate, which is then discarded, and the blood is returned to the patient. Objectives: The study aimed to detect HBsAg and anti-HCV in HD patients and the control group. Methods: A retrospective case-control, a hospital-based study was carried out on 110 participants 60 HD patients and 50 control, 60 males and 50 females, ages between 20 -39 years 27 participants and ages between 40-59 years 32 participants and ages more than 60 51 participants, ELISA method was used to detect HBsAg and anti-HCV in HD patients and control sera, the study was carried out during the period from August 2021 to January 2022. Results: In this study, the overall prevalence of HBV infection among HD patients and the control group was 26.3% (2/110), and among HD patients was 45 % (27/60), while it was 4% (2/50) among the control group any non – HD patient, co-patient, hospital staff and the overall prevalence of HCV was 1,8 % (2/110) and it was 3.3% (2/60) among the HD patients, 0% (0/50) among the control group. There was a significant association between HBV infection and HD (P value 0.019). Conclusions: The prevalence of HBV among HD patients was very high (45%). The results emphasize the need to carry out proactive tasks for early diagnosis by using highly sensitive and specific methods such as PCR technique, treatment of infected individuals, and vaccinating those with non-protective anti-HB antibodies to reduce morbidity and mortality in HD patients.

MiRNA-221: A Potential Biomarker of Progressive Liver Injury in Chronic Liver Disease (CLD) due to Hepatitis B Virus (HBV) and Nonalcoholic Fatty Liver Disease (NAFLD).

Background: Early detection of progressive liver damage in chronic liver disease (CLD) patients is crucial for better treatment response. Several studies have shown the association of microRNA (miRNA) in the progression of CLD in regulating cell proliferation, fibrosis, and apoptosis as well as in carcinogenesis. Objectives: The study was aimed at determining the expression of miRNA-221 among different stages of fibrosis in CLD patients due to hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD) and thus evaluate its role as an early biomarker in CLD. Methods: A total of 100 participants (75 CLD patients and 25 healthy control) were recruited in this cross-sectional study and divided into four groups, of which 25 as healthy control, 25 in CLD without fibrosis, 25 were CLD with fibrosis, and 25 were CLD with cirrhosis. Total RNA was extracted from plasma followed by cDNA synthesis, and finally, the expression of miRNA-221 was analyzed for its diagnostic potential as a single biomarker using the qRT-PCR method. Results: The plasma level of miRNA-221 was significantly upregulated in different fibrosis stages of CLD (p < 0.05), and this upregulation was positively correlated with the progression of fibrosis (p < 0.05). Significantly increased expression of miRNA-221 was found in NAFLD patients compared to HBV patients in the CLD without fibrosis patient group (p < 0.05), while expression of miRNA-221 was significantly upregulated among HBV patients in the CLD with the fibrosis group. miRNA-221 showed high diagnostic accuracy in discriminating different stages of fibrosis from healthy control (p < 0.05). Conclusion: miRNA-221 may be used as a potential plasma biomarker for early prediction of fibrosis progression in CLD patients.