Treatment Of Chronic Liver Diseases Research Articles

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.

Statins in chronic liver disease: review of literature and future role.

Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, anti-proliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and non-viral etiologies of CLD and HCC, and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

Identification of the Microbiome Associated with Prognosis in Patients with Chronic Liver Disease.

We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509-17.793; p < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151-9.6555; p < 0.001). Incertae sedis from Ruminococcaceae showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; p = 0.002), whereas increased Veillonella presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922-6.2664; p = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient's prognosis.

Boldine protects against carbon tetrachloride-induced chronic liver injury by regulating NF-κB signaling pathway.

Sustained liver injuries predominantly promote oxidative stress and inflammation that lead to the progression of chronic liver disease (CLD), including fibrosis, cirrhosis, and hepatocellular carcinoma. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects. Currently, there is no definitive treatment option available for CLD. Therefore, we investigated the hepatoprotective effect of boldine against carbon tetrachloride (CCl4 )-induced chronic liver injury in rats. CCl4 (2 mL/kg., b.w., i.p.) was administered twice weekly for 5 weeks to induce chronic liver injury in rats. Separate groups of rats were given boldine (20 mg/kg b.w., and 40 mg/kg b.w.) and silymarin (100 mg/kg b.w.) orally, daily. Serum transaminases, lipid peroxidation, and antioxidant levels were measured, and nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (cox-2), interleukin-1 β (IL-1β), and α-smooth muscle actin (α-SMA) gene and protein expressions were evaluated. CCl4 administration increased liver marker enzymes of hepatotoxicity in serum and oxidative stress markers, inflammatory genes and α-smooth muscle actin expression in liver tissue. Boldine concurrent treatment suppressed CCl4 -induced elevation of transaminase levels in serum, restored enzymic and non-enzymic antioxidants, and downregulated NF-κB, TNF-α, Cox-2 and IL-1β expressions, thereby suppressing hepatic inflammation. Boldine administration also repressed α-SMA expression. The results of this study demonstrate the antioxidant, anti-inflammatory, and antifibrotic properties of boldine, and it can be a potential therapeutic candidate in the treatment of CLD.

QUALITY ASSESSMENT OF SILYBUM MARIANUM FRUITS GROWN IN THE REPUBLIC OF BURYATIA

Introduction. Medicines of plant origin are widely used in the complex therapy of various diseases. Among the medicines of plant origin used for the treatment of chronic liver diseases, the most popular are preparations based on Silybum marianum (L.) Gaertn.). The aim of this work was to Silybum marianum fruits to evaluate the possibility of obtaining raw materials of pharmacopoeial quality in the dry-steppe zone of the Republic of Buryatia. Material and methods. The object of the study was Silybum marianum fruits of the varieties Debut and Start, obtained from experimental fields in Ivolginsky district of the Republic of Buryatia, as well as samples of Silybum marianum fruits received for analysis at the Testing Center of FGBNU VILAR from different regions of the Russian Federation. Results. As a result of the research it was found that climatic and geographical conditions of the dry-steppe zone of the Republic of Buryatia allow successful cultivation of Silybum marianum and obtaining raw materials (fruits) of pharmacopoeial quality. Conclusion. Silybum marianum fruits obtained from plants of the Start variety are not inferior to similar raw materials harvested in other regions of the Russian Federation in the content of the sum of flavolignans.

Up-to-date Epidemiology of Chronic Hepatitis C Virus Infection among Bulgarian Patients: a Single Centre Experience

Epidemiological data about chronic infection with Hepatitis C virus (HCV) are limited in Bulgaria. The aim of this study was to determine the Viremic Rate and the distribution of HCV genotypes in one centre for diagnosis and treatment of chronic liver diseases. Geographic patterns of genotype distribution and associations of genotype with viral load, gender and age were investigated. Serum samples from 1731 individuals with a positive HCV Antibody Test, collected between 2016 and 2019, were analysed. HCV RNA levels were determined by HCV quantitative RNA real time polymerase chain reaction. Individuals with detectable HCV RNA further underwent HCV genotyping analysis using the Versant HCV Genotype Assay (LiPA) 2.0. The mean age of all patients was 52.9±15.3 (17–87). Among those, 54.1% were men and 45.9% women. Most patients came from the south-western region of Bulgaria (21.7%). Viral load was proven in 1385 out of 1731 individuals (VR=80%). Genotype 1 (G1) was the predominant genotype (89.8%), followed by G3 (8.5%), G2 (0.9%), G4 (0.6%) and G5 (0.1%). Among individuals with G1, infection with subtype 1b was seen in 77.4% and with subtype 1a in 22.6%. Viral load was not found to be dependent on age or gender. Viral load was higher in patients with G1 compared to G3 ($$p=0.001$$). Finally, patients with G1b were significantly older than patients with G1a ($$p&lt;0.001$$) and G3 ($$p&lt;0.001$$). VR in the studied population (80%) appears to be higher than the VR reported for Central Europe (73.3%). In Bulgaria, the most prevalent genotype is G1 (89.8%). This is a higher rate in comparison to the observed G1 rate in Central Europe (70%). The second most prevalent genotype is G3 (8.5%), with fewer cases identified than in Central Europe (21%).

3D‐Printed Lipid Mesophases for the Treatment of Chronic Liver Disease

AbstractAlthough lipid‐based formulations are an attractive approach for enhancing the oral bioavailability of lipophilic drugs, their addition into solid oral dosage forms has been proven challenging due to their high viscosity and heat sensitivity. Therefore, unlike the traditional tableting process, this study employed semi‐solid extrusion 3D‐printing to produce–at room temperature–gastro‐resistant printlets containing a high percentage of bioactive lipids for the effective delivery of lipophilic drugs through self‐emulsification. The bio‐compatible lipidic mesophase ink, owing to a tunable 3D nanostructure, is employed as a starting material to produce printlets via additive manufacturing. An active lipid mixture – with antifibrotic properties – is blended with the antioxidant vitamin E and water, and the ink printability is optimized by carefully tailoring its composition, and thus its phase identity. The obtained printlets disintegrated upon contact with intestinal fluids forming colloidal structures that enhanced the solubility of a poorly water‐soluble drug. The printlets exhibited antifibrotic activity on human hepatic stellate cells, LX‐2, suggesting that the generated self‐emulsified colloidal structures made both the fibrosis‐resolving bioactive excipients and the drug promptly available, enhancing their cell uptake and, in turn, their therapeutic activity.

Human amniotic epithelial cells (HAECS); a potential cell type for the hepatic disorders.

To isolate a homogenous population of human amniotic epithelial cells (hAECs) from the amniotic membrane of the human placenta and differentiate them into hepatic-like cells with the help of small molecules. hAECs were isolated by using the enzymatic digestion method and characterized for the presence of specific stem cell markers. In-vitro, hepatic differentiation of hAECs was carried out by using a combination of small molecules. Differentiated cells were observed under a live cell imaging microscope for morphological changes followed by gene and protein expression analysis by qPCR and immunocytochemistry respectively. The isolated hAECs attained characteristic cuboid epithelial shape and express stem cells marker. The hepatic differentiation method was optimized based on soluble chemical compounds supplied in the culture medium. The differentiated hAECs phenotypically acquire hepatic-like cell features and expressed hepatic markers as well as hepatic protein albumin at immature levels. The isolated population of hAECs is highly proliferative. Moreover, hepatic markers expression in the isolated hAECs makes them an exclusive source for the treatment of chronic liver diseases.

Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.

There exists a huge number of patients suffering from chronic liver disease worldwide. As a disease with high incidence and mortality worldwide, strengthening the research on the pathogenesis of chronic liver disease and the development of novel drugs is an important issue related to the health of all human beings. Phosphorylation modification of proteins plays a crucial role in cellular signal transduction, and phosphatases are involved in the development of liver diseases. Therefore, this article summarized the important role of protein phosphatases in chronic liver disease with the aim of facilitating the development of drugs targeting protein phosphatases for the treatment of chronic liver disease.

Mesenchymal Stem Cell-Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?

Chronic liver conditions are associated with high mortality rates and have a large adverse effect on human well-being as well as a significant financial burden. Currently, the only effective treatment available for the effects of liver failure and cirrhosis resulting from the progression of several chronic liver diseases is liver transplantation carried out at the original location. This implies that developing novel and effective treatments is imperative. Regenerative medicine has long been associated with stem cell therapy. Mesenchymal stem cells (MSCs), a type of cell with great differentiation potential, have become the preferred source for stem cell therapy. According to recent studies, MSCs' paracrine products-rather than their capacity for differentiation-play a significant therapeutic effect. MSC exosomes, a type of extracellular vesicle (MSC-EV), came into view as the paracrine substances of MSCs. According to research, MSC exosomes can maintain tissue homeostasis, which is necessary for healthy tissue function. All tissues contain them, and they take part in a variety of biological activities that support cellular activity and tissue regeneration in order to preserve tissue homeostasis. The outcomes support the use of MSCs and the exosomes they produce as a therapeutic option for a range of diseases. This review provides a brief overview of the source of MSC-EVs and outlines their physiological roles and biochemical capabilities. The elucidation of the role of MSC-EVs in the recovery and repair of hepatic tissues, as well as their contribution to maintaining tissue homeostasis, is discussed in relation to different chronic liver diseases. This review aims to provide new insights into the unique roles that MSC-EVs play in the treatment of chronic liver diseases.

Long-Term Social Outcomes of Pediatric Liver Transplant Recipients: Transition From Childhood to Adulthood.

Chronic disorders may negatively affect people's learning status, marital status, occupational life, and social life. Liver transplant is the only curative treatment for chronic liver diseases. This study was undertaken to evaluate the psychosocial effects of liver transplant in adult patients who had undergone liver transplant during the pediatric period compared with psychosocial facts in the general population. We retrospectively reviewed adult patients (>18 years of age) who had received liver transplant as children. We compared sex, age at the time of transplant, current age, type of donor, graft survival status, marital status, age at first delivery, number of children, educational status, and occupational status in the study population versus the general (normal) population. To compare the liver transplant patients included in the study with the general population correctly, we used data from the Turkish Statistical Institute. Among 77 liver transplant patients included in our study, the mean age at transplant was 10.9 years (range, 0.5-16 y) and the mean age at the time of the study was 25.2 years (range, 18-42 y). Of the patients, 61 (79.2%) were single and 16 (20.8%) were married. Patients in the study population married at a younger age than the general population (25.5 vs 28.1 y for men, 24.3 vs 25.4 y for women). Of 16 married patients, 9 (56.2%) had a healthy child or children. The percentage of patients who graduated from higher education or were continuing their higher education process was higher in our study population than in the general population (36.3% vs 22.8%). Among our study population, 37 patients (48%) were workers. Liver transplant had no negative effects on the social, educational, and professional lives among adults in our study who received transplants in the pediatric period.

Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis

Ethnopharmacological relevanceJiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature “Treatise on Febrile Diseases”. As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). Aim of studyThe current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. Materials and methodsMolecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. ResultsOur results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. ConclusionIn conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.

Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment

The liver has a remarkable regenerative capacity. Nevertheless, under chronic liver-damaging conditions, this capacity becomes exhausted, allowing the accumulation of fibrotic tissue and leading to end-stage liver disease. Enhancing the endogenous regenerative capacity by targeting regeneration breaks is an innovative therapeutic approach. We set up an in vivo functional genetic screen to identify such regeneration breaks. As the top hit, we identified Microfibril associated protein 4 (Mfap4). Knockdown of Mfap4 in hepatocytes enhances cell proliferation, accelerates liver regeneration, and attenuates chronic liver disease by reducing liver fibrosis. Targeting Mfap4 modulates several liver regeneration-related pathways including mTOR. Our research opens the way to siRNA-based therapeutics to enhance hepatocyte-based liver regeneration.

Fecal Microbiota Transplantation in Liver Cirrhosis.

The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.

Amniotic Membrane and Its Derivatives: Novel Therapeutic Modalities in Liver Disorders.

The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation and fibrosis which develop into cirrhosis. The human amniotic membrane (hAM), the innermost layer of the fetal placenta, is composed of multiple layers that include growth-factor rich basement membrane, epithelial and mesenchymal stromal cell layers. hAM possesses distinct beneficial anti-fibrotic, anti-inflammatory and pro-regenerative properties via the secretion of multiple potent trophic factors and/or direct differentiation into hepatic cells which place hAM-based therapies as potential therapeutic strategies for the treatment of chronic liver diseases. Decellularized hAM is also an ideal scaffold for liver tissue engineering as this biocompatible niche provides an excellent milieu for cell proliferation and hepatocytic differentiation. Therefore, the current review discusses the therapeutic potential of hAM and its derivatives in providing therapeutic solutions for liver pathologies including acute liver failure, metabolic disorders, liver fibrosis as well as its application in liver tissue engineering.

Efficacy of different doses of magnesium isoglycyrrhizinate in the treatment of chronic liver disease with elevated ALT: a meta-analysis

Objective: To investigate the efficacy and safety profile of different doses of magnesium isoglycyrrhizinate in the treatment of chronic liver disease with elevated alanine aminotransferase (ALT). Methods: Computer retrieval of literature was conducted in the CNKI, Wanfang, and PubMed databases from the establishment of the databases until February 2023. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included literature after screening the literature and extracting the data. RevMan 5.4 and Stata 15.0 software were used to analyze the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total effective rate, and incidence of adverse events. Results: Finally, 10 articles were selected, including a total of 1 522 cases. All the included studies were of good quality and at low risk of bias. Meta-analysis results showed that compared with 100 mg/d magnesium isoglycyrrhizinate injection, 200 mg/d magnesium isoglycyrrhizinate injection had significantly reduced patients' ALT [MD = -30.73, 95% confidence interval (CI): -52.52 ~ -8.94, Z = 2.76, P = 0.006; I (2) = 98%, P < 0.001], AST (MD = -34.30, 95% CI: -57.78 ~ -10.82, Z = 2.86, P = 0.004; I (2) = 99%, P < 0.001) and TBil (MD = -15.37, 95% CI: -27.66 ~ -3.09), Z = 2.45, P = 0.01; I (2) = 98%, P < 0.001) levels. The total effective rate reported in seven articles showed no heterogeneity among the studies (I (2) = 0.0%, P = 0.98). The total effective rate was higher in 200 mg/d magnesium isoglycyrrhizinate injection than that of 100 mg/d magnesium isoglycyrrhizinate injection (OR = 3.49, 95% CI: 2.05 ~ 5.95, Z = 4.59, P < 0.001), and there was no statistically significant difference in adverse reactions. Conclusion: 200 mg/d magnesium isoglycyrrhizinate injection can more rapidly and effectively improve the levels of ALT, AST, and TBil in patients with chronic liver disease, with an increased total effective rate and a good safety profile.

Frequency of significant steatosis and compensated advanced chronic liver disease among adults with chronic liver disease.

With changes in the epidemiology and treatment of chronic liver disease (CLD), the impact of various etiologies of liver disease on steatosis and advanced fibrosis are uncertain. A retrospective study was conducted among liver disease patients of various etiologies undergoing transient elastography (TE) over a 9-year duration. Data for 2886 patients were analyzed and had the following demographics: The median age was 60 (IQR: 45-69) years, 51% were males, and ethnicity was predominantly Chinese (52.5%), followed by Malays (34%) and Indians (12.3%). The median CAP score was 272 (IQR: 219-319) dB/m and the median liver stiffness measurement (LSM) score was 6.5 (IQR: 4.9-9.7) kPa. Hepatic steatosis occurred across the spectrum of etiologies of CLD. Among patients with steatosis, the most common etiologies were nonalcoholic fatty liver disease (NAFLD) at 62% and chronic hepatitis B (CHB) at 26.3%. TE findings suggestive of cACLD (10.1-15kPa) and highly suggestive of cACLD (>15kPa) were observed in 11.3% and 12.4% of patients, respectively. NAFLD was found to be the most common etiology for cases with suggestive of cACLD (47.2%) and highly suggestive of cACLD (41.5%). Hepatic steatosis is common in CLD, regardless of etiology. Compared with other etiologies, NAFLD is now the leading cause of cACLD.

Assessing Thrombocytopenia and Chronic Liver Disease in Southeast Asia: A Multicentric Cross-Sectional Study.

Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease (CLD) across 15 Southeast Asian (India, Pakistan, and Bangladesh) tertiary care centers over a three-month period. The study focused on assessing the fibrosis index (FI) and Model for End-Stage Liver Disease (MELD)-sodium (Na) score's capacity to grade and predict the progression and outcomes of patients with already diagnosed CLD. Methods The cross-sectional study enrolled 377 CLD patients. The study utilized admission registries from 15 tertiary care hospitals in Southeast Asia, spanning from April 2023 to June 2023. Various descriptive variables were collected, including gender, tobacco use (specifically, chewed tobacco), underlying etiology, presence of anemia, leukopenia, pancytopenia, infectious state, and liver cirrhosis diagnosed via traditional ultrasonography. This study examined liver failure indicators, including alanine transaminase levels, compensation status, TCP, and liver transplant (LT) listing. The MELD-Na score was the focus of frequency and percentage analysis. MELD-Na and FI medians and standard deviations were provided. Results The study of 377 patients with CLDfound that TCP was present in 4% of patients and leukopenia was present in 12% of patients. The risk of TCP was significantly higher in leukopenic patients (89.5%) than in non-leukopenic patients (52.5%) (p = 0.003). The most common CLD cause was undiagnosable (31%), followed by autoimmune (26%), hepatitis C virus (21%), hepatitis B virus (14%), and schistosomiasis (8%). The majority of patients (98%) had decompensated liver disease. Of the patients,64% had TCP, while 36% did not. The illness severity indicators MELD score and FI had mean ± SD values of 16.89 ± 6.42 and 4.1 ± 1.06, respectively. Similarly, the prevalence of LTneeds among traditional ultrasonography-diagnosed cirrhotic patients was 83.1%, compared to 59.6% among non-cirrhotic patients (p = 0.001). Conclusion Leukopenia and TCP may be linked, which may affect CLD treatment and prognosis in this population.Non-invasive indicators like the FI and MELD-Na score can detect liver fibrosis and severity without invasive procedures, enhancing patient management. These findings highlight the need to improve early diagnosis methods for CLD in Southeast Asia and raise awareness among clinicians about effective diagnostic strategies for non-infectious causes of CLD.

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis

Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury.

Oxidative stress plays a vital role in the pathogenesis and progression of various liver diseases. Traditional medicinal herbs have been used worldwide for the treatment of chronic liver diseases due to their high phytochemical constituents. The present study investigated the phytochemical properties of Croton gratissimus (lavender croton) leaf herbal tea and its hepatoprotective effect on oxidative injury in Chang liver cells, using an in vitro and in silico approach. C. gratissimus herbal infusion was screened for total phenolic and total flavonoid contents as well as in vitro antioxidant capacity using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) methods. Oxidative hepatic injury was induced by incubating 0.007 M FeSO4 with Chang liver cells which has been initially incubated with or without different concentrations (15-240 μg/mL) of C. gratissimus infusion or the standard antioxidants (Gallic acid and ascorbic acid). C. gratissimus displayed significantly high scavenging activity and ferric reducing capacity following DPPH and FRAP assays, respectively. It had no cytotoxic effect on Chang liver cells. C. gratissimus also significantly elevated the level of hepatic reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities as well as suppressed the malondialdehyde (MDA) level in oxidative hepatic injury. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the herbal tea revealed the presence of 8-prenylnaringenin, flavonol 3-O-D-galactoside, caffeine, spirasine I, hypericin, pheophorbide-a, and 4-methylumbelliferone glucuronide. In silico oral toxicity prediction of the identified phytochemicals revealed no potential hepatotoxicity. Molecular docking revealed potent molecular interactions of the phytochemicals with SOD and catalase. The results suggest the hepatoprotective and antioxidative potentials of C. gratissimus herbal tea against oxidative hepatic injury.