جستجوی مقالات مرتبط با کلیدواژه « liver fibrosis » در نشریات گروه « پزشکی »

The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis.

For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system.

Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice’s tail vein. Fourteen days’ post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson’s trichrome (MT) staining.

Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT.

These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.

 Macrophages play a significant role in both the development and regression of liver fibrosis, engaging in related pro-inflammatory and anti-inflammatory processes. In recent years, an increasing number of studies have elucidated the mechanisms by which macrophages influence liver fibrosis.

 This bibliometric analysis aims to investigate the research trends in liver fibrosis regulation by macrophages through a systematic literature review.

 We conducted a search for literature, including research articles and reviews, using the keywords 'liver fibrosis and macrophages' and 'liver cirrhosis and macrophages' in the Web of Science database, covering the period from 2007 to 2023. We retrieved and analyzed publications on liver fibrosis mediated by macrophages from the Web of Science Core Collection database on October 8, 2023. Visualization analysis was performed using CreateSpace (version 6.1.R6), VOSviewer (version 1.6.19), and Scimago Graphica (version 1.0.34.0).

 We identified a total of 1732 records in the WoSCC, of which 1664 papers were ultimately included in our analysis. China emerged as the country with the most significant number of publications, while Germany and the University of California San Diego stood out for their influence, with centralities of 0.41 and 0.14, respectively. Frank Tacke was identified as the most prolific author, contributing 49 papers. Hepatology was the journal with the highest number of publications and citations. The most frequently mentioned keywords in this field were liver fibrosis, expression, hepatic stellate cells, activation, inflammation, and macrophages.

 The study of macrophage-mediated liver fibrosis, particularly the mechanisms regulating the heterogeneity of hepatic macrophages, is a mature and promising research area. Macrophage-based therapies for liver fibrosis are anticipated to be crucial topics in the future. Bibliometric analysis offers valuable insights for future basic research directions and clinical practice.

This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis.

The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated.

Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0 - S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94).

There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.

 Hepatitis C and B virus infections significantly contribute to global chronic liver disease mortality.

 This study explores the role of serum markers (AST/ALT ratio, APRI Score, FIB-4 Score, and Forns index) in non-invasively assessing liver damage in patients with chronic hepatitis C and B.

 In this single-center, retrospective, observational study, we analyzed data from 327 patients to establish correlations between serological markers and fibrosis grade using Spearman's correlation. Receiver operator characteristic (ROC) analysis evaluated the ability of these markers to predict advanced fibrosis.

 In hepatitis B and C cohorts, all markers show significant positive correlations with liver fibrosis (P < 0.001). FIB-4 and the Forns index exhibit moderate correlation (Spearman’s rho 0.48), while AST/ALT and APRI score show mild correlation (Spearman’s rho 0.21 and 0.31). In hepatitis C, the Forns index (0.814) and FIB-4 (0.80) outperform other markers. In hepatitis B, Forns (AUC = 0.73), APRI (AUC = 0.68), and FIB-4 (AUC = 0.68) demonstrate significant predictive ability.

 FIB-4 and the Forns index hold clinical significance as fibrosis biomarkers in the management of chronic viral hepatitis. FIB-4 is a universal marker, while the interpretation of the Forns index requires consideration of the etiology of chronic viral hepatitis.

 This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis.

 The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated.

 Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0 - S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94).

 There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world. Previous studies revealed that cholecystectomy may be considered a risk factor for the development of NAFLD. The aim of this study was to compare the amount of liver fibrosis, determined by elastography, between patients with NAFLD with and without a history of cholecystectomy.

In this descriptive-analytical cross-sectional study, 50 patients with NAFLD were divided into two groups: one with a history of cholecystectomy and the other without. No significant differences were found between these two groups in terms of age or sex distribution. Liver fibrosis was measured for all patients using an elastography imaging system. Subsequently, the data related to liver fibrosis, along with the demographic information of the patients, were statistically analyzed using SPSS software version 22.

The mean elastography score in all patients was 10.66 ± 12.18 kPa (the elasticity scale ranging from 3.80 to 66.40 kPa). The group with a history of cholecystectomy had a significantly higher mean elastography score (13.39 ± 16.20 kPa) compared with the group without cholecystectomy (7.93 ± 4.99 kPa) (P = 0.02). Additionally, there was a significant positive correlation between body mass index (BMI) and the mean elastography score in the group of patients with a history of cholecystectomy.

The mean elastography score of patients with NAFLD with a history of cholecystectomy was approximately twice as high as that of non-cholecystectomy patients.

Persistent liver damage contributes to the development of liver fibrosis, marked by an accumulation of extracellular matrix. Macrophages play a pivotal role in this process, with the CCL2-CCR2 and CX3CR1-CX3CL1 axes serving as key regulators of macrophage recruitment, liver infiltration, and differentiation. In this study, utilizing a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis, we aimed to investigate the impact of imatinib and bone marrow-derived mesenchymal stem cells (BM-MSCs) on the expression of these axis.

Sixteen Sprague-Dawley rats were divided into four groups: healthy, liver fibrosis, imatinib-recipient, and BM-MSC-recipient. Treatment effects were evaluated using histopathology and Sirus-red staining. Quantitative real-time PCR was employed to analyze changes in the expression of the genes CCL2, CCR2, CX3CL1, and CX3CR1.

Histopathological assessments revealed the efficacy of imatinib and BM-MSCs in mitigating liver fibrosis. Our findings demonstrated a significant reduction in CCL2 and CCR2 expression in both imatinib and BM-MSCs treatment groups compared to the liver fibrosis group. Conversely, the gene expression of CX3CL1 and CX3CR1 increased in both therapeutic groups compared to the liver fibrosis groups.

The notable decrease in CCL2-CCR2 genes in both therapeutic groups suggests that BM-MSCs and imatinib may contribute to a decline in inflammatory macrophages within the liver. The lower CCL2-CCR2 expression in imatinib-recipient rats indicates better efficacy in modulating the recruitment of inflammatory macrophages. The elevated expression of CX3CL1 in BM-MSC-recipient rats suggests a greater impact on the polarization of LY6Chigh (inflammatory) to LY6Clow (anti-inflammatory) macrophages, warranting further investigation.

Liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. The goal of this investigation was to look into the anti-fibrotic effect of apigenin (APG), an antioxidant found in various plants, versus thioacetamide (TAA)-triggered hepatic scarring in rats and the potential mechanisms behind it.

TAA was administered thrice weekly (100 mg/kg, i.p.) for two weeks to produce hepatic scarring. APG was administered after TAA for 14 days (5 or 10 mg/kg, orally). Thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated.

TAA increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (FAK), hypoxia-inducible factor-1α (HIF-1α), and inflammatory cytokines, decreased interleukin-10 (IL-10), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and elevated serine-threonine protein kinase (AKT) expression. Furthermore, TAA increased hepatic contents of collagen I, connective tissue growth factor (CTGF), hydroxyproline, and alpha-smooth muscle actin. On the other hand, APG evaded these changes and mitigated the harmful effects of TAA in a dose-dependent way. Histopathological and immunohistochemical observations reinforced these biochemical outcomes.

APG can potentially alleviate liver fibrosis mediated via FAK and HIF1 inhibiting signaling pathways.

Free cholesterol in the diet can cause liver fibrosis by accumulating in Hepatic stellate cells (HSCs). The rate of mortality of this disease is high worldwide and there is no definite remedy for it, but might be treated by anti-fibrotic therapies. MSCs-derived exosomes are known as the new mechanism of cell-to-cell communication, showing that exosomes can be used as a new treatment. In this study, we investigated the ability of exosomes of WJ-MSCs as a new remedy to reduce cholesterol-induced liver fibrosis in the LX2 cell line.

MSCs were isolated from Wharton’s jelly of the umbilical cord and the exosomes were extracted. The LX2 cell line was cultured in DMEM medium with 10% FBS, then cells were treated with 75 and 100 μM concentrations of cholesterol for 24 hr. The mRNA expression of TGF-β, αSMA, and collagen1α genes, and the level of Smad3 protein were measured to assess liver fibrosis. 

Cholesterol increased the expression of TGF-β, αand -SMA, and collagen1α genes by increasing the phosphorylation of the Smad3 protein. Treatment with Exosomes significantly reduced the expression of TGF-β, α-SMA, and collagen1α genes (fibrosis genes). Treatment with exosomes prevented the activation of HSCs by inhibiting the phosphorylation of the Smad3 protein. 

The exosomes of WJ-MSCs can inhibit the TGFβ/Smad3 signaling pathway preventing further activation of HSCs and progression of liver fibrosis. So, the exosomes of WJ-MSCs s could be introduced as a treatment for liver failure.

 Activated hepatic stellate cells (HSC) through the TGF-β signaling pathway are likely to exacerbate liver fibrosis, which is a later stage of NASH, a condition in which, in addition to HSC activation, the overexpression of extracellular matrix (ECM) proteins, specifically collagen-I α and α-SMA, is expected. MicroRNA-126a, a modulator of HSC activation, influences the phosphorylation of Smad2/3.

 This study aimed to investigate the impact of exosomes on miRNAs implicated in the progression of liver fibrosis by focusing on the role of miR-126a in the HSC-T6 cell line.

 In the present study, we investigated the effects of exosomes derived from LPS-stimulated mesenchymal stem cells (MSCs) on the expression of miR-126a and the phosphorylation of Smad3c in the HSC-T6 cell line. First, HSC-T6 cells were cultured in DMEM supplemented with 10% FBS. Next, we isolated exosomes derived from MSCs using the ExoCib kit. Finally, we examined the gene expression levels of collagen-Iα, α-SMA, and miR-126a using real-time PCR.

 The results showed that treatment with TGFβ1 increased the phosphorylation of p-Smad3c (P < 0.0001), as well as the expression of α-SMA and Collagen-Iα. Conversely, miR-126a expression was down-regulated after treatment with TGFβ1 (P < 0.01). However, exposure to LPS-treated MSC-derived exosomes resulted in a significant decrease in the levels of p-Smad3c phosphorylation (P < 0.001) and the gene expression of α-SMA and Collagen-Iα, accompanied by the up-regulation of miR-126a (P < 0.05).

 Based on our observations, MSCs-derived exosomes were able to reduce the expression of the genes associated with hepatic fibrosis, such as collagen-Iα and α-SMA. Furthermore, exosomes inhibited Smad3c phosphorylation by increasing miR-126a expression, ultimately hindering the progression of liver fibrosis. Therefore, exosomes should be recognized as a valuable and beneficial therapeutic tool for liver fibrosis.

Activated cells which are called star-shaped cells, are some of the key factors in the development of liver fibrosis. Activation of NADPH oxidase (NOX) is associated with increased HSCs activity and progression of hepatic fibrosis. In this study, the effects of human exosomes derived from WJ-MSCs on NOX1, NOX2, and NOX4 gene expression in TGF-β-induced hepatic fibrosis were investigated.

LX2 cell line was treated with 2 ng/ml TGF-β for 24 hr, in order to induce liver fibrosis after starvation. In the next step, the cells were treated with several concentrations of the exosomes derived from WJ-MSCs (10, 20, 30, 40, and 50 μg/ml). Finally, Smad3C phosphorylated protein expression level and NOX1, NOX2, and NOX4 gene expression levels were measured.

The results demonstrated that the level of NOX1, NOX2, and NOX4 mRNA expressions decreased significantly during 24 hrs at concentrations of 40 and 50 μg/ml of WJ-MSCs exosomes in TGF-β-induced-HSCs. The p-Smad3C proteins were significantly decreased (fold change: 1.83, P-value<0.05) after exposure to WJ-MSC-derived exosomes. 

Treatment with exosomes prevents further activation of HSCs by inhibiting the level of Smad3C phosphorylation. The experimental data of our study suggested that in liver fibrosis, the protection of HSCs activation against TGF-β by inhibiting the NOX pathway via human exosomes of WJ-MSCs is extremely important. It needs further research as a treatment method.

Mesenchymal stem cells (MSCs) are the most promising tools for cell treatment and human tissue regeneration, e.g., in liver fibrosis. Mesenchymal stem cells repair tissue damage through paracrine mediators such as exosomes. Types and concentrations of inflammatory mediators, including transforming growth factor-beta (TGFβ1), in MSCs microenvironment can affect MSCs’ function and therapeutic potency.

This experimental study aimed to explore the effects of Wharton jelly MSCs (WJ-MSCs) exosomes on fibrotic gene expression and Smad2/3 phosphorylation (phospho-Smad2/3 (p-Smad2/3)). Moreover, we further investigated whether WJ-MSCs pretreatment with different concentrations of TGFβ1 changes the anti-fibrotic properties of their exosomes.

After isolation from the umbilical cord, WJ-MSCs were characterized by observing differentiation and measuring surface biomarkers using flowcytometry. The WJ-MSC-derived exosomes were extracted and identified using transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. Real-time PCR and western blot for extracellular matrix (ECM) and p-Smad2/3 expression detection were used to investigate the effect of exosomes from untreated and TGFβ1-pretreated WJ-MSCs on activated hepatic stellate cells (HSCs).

Phospho-Smad2/3, α-smooth muscle actin (α-SMA), and collagen1α1 levels were enhanced following treatment with TGFβ1, whereas E-cadherin was decreased. However, the outcomes were reversed after treatment with WJ-MSC-derived exosomes. Exosomes from TGFβ1-pretreated WJ-MSCs induced a significant decrease in p-Smad2/3 levels in activated HSCs, accompanied by the upregulation of E-cadherin gene expression and downregulation of α-SMA and collagen1α1 when compared to untreated WJ-MSC-derived exosomes. The p-Smad2/3 proteins were significantly decreased (fold change: 0.23, P-value < 0.0001) after exposure to low-dose TGFβ1-pretreated WJ-MSC-derived exosomes (0.1 ng/mL), showing the best effect on activated HSCs.

Exosomes derived from untreated WJ-MSCs could regress TGFβ-Smad2/3 signaling and the expression of fibrotic markers in activated LX-2 cells. However, these effects were significantly profound with applying exosomes derived from 0.1 ng/mL TGFβ-pretreated WJ-MSCs. We also observed the dose-response effects of TGFβ on WJ-MSCs-derived exosomes. Therefore, exosomes derived from TGFβ-pretreated WJ-MSCs may be critical in improving fibrosis and benefit liver fibrosis patients.

Interaction between immune modulators and inflammatory factors is considered as one of the main underlying pathologies of non-alcoholic fatty liver disease (NAFLD). Hence we aimed to assess the association between these cytokines and melatonin.

We enrolled adult patients diagnosed with fatty liver by ultrasonography in a crosssectional study. All of them underwent Fibroscan evaluation. The subjects who met the inclusion and exclusion criteria for NAFLD were involved. A normal group who did not have NAFLD, viral or non-viral hepatitis, and without a history of pancreatobiliary surgery, bariatric surgery, and intake of any medication that influence the liver was also selected. The participants were categorized into the three following groups: 1) fibrosis>9.1 kPa and steatosis>290 dbm, 2) fibrosis: 6-9.0 kPa and steatosis 240-290 dbm, and 3) normal group with fibrosis<6.0 kPa and steatosis<240 dbm. Laboratory assessment and a questionnaire including demographic, anthropometric, laboratories, and clinical data were completed for each of them.

Totally 97 subjects were enrolled in the present study. The mean age of the subjects was 42.2±11.3 years. 60% of them (59 patients) were female. Serum levels of melatonin, interleukin (IL)-1B, IL-18, and IL-33 increased according to the advancing of NAFLD state. Based on multiple linear regression model, melatonin was significantly associated with IL-1B (β=2.8, P<0.001,95% CI=1.41-4.19), IL-18 (β=0.018, P=0.0005, 95% CI=0.006-0.03), and IL-33 (β=0.31, P=0.045, 95% CI=0.008-0.62) after adjustment for other variables.

Melatonin level has a strong association with these cytokines. This linkage probably influences on the development and progression of NAFLD. Therefore it can be hypothesized that the therapeutic approach that affects this process may have a significant impact.

COVID 19 may affect organs other than lungs, including liver, leading to parenchymal changes. These changes are best assessed by unenhanced computed tomography (CT). We aim to investigate the effect of COVID 19 on liver parenchyma by measuring the attenuation in CT scan Hounsfield unit (HU).

A cohort of patients, who tested COVID 19 polymerase chain reaction positive, were enrolled and divided into two groups: fatty liver (FL) group (HU ≤ 40) and nonfatty liver (NFL) group (HU > 40) according to liver parenchyma attenuation measurements by high resolution noncontrast CT scan. The CT scan was performed on admission and on follow up (10–14 days later). Liver enzyme tests were submitted on admission and follow up.

Three hundred and two patients were enrolled. Liver HU increased significantly from 48.9 on admission to 53.4 on follow up CT scan (P<0.001) in all patients. This increase was more significant in the FL group (increased from 31.9 to 42.9 [P =0.018]) Liver enzymes were abnormal in 22.6% of the full cohort. However, there was no significant change in liver enzymes between the admission and follow up in both groups.

The use of unenhanced CT scan for assessment of liver parenchymal represents an objective and noninvasive method. The significant changes in parenchymal HU are not always accompanied by significant changes in liver enzymes. Increased HU values caused by COVID 19 may be due to either a decrease in the fat or an increase in the fibrosis in the liver.

In the last two decades, the simple low-cost abdominal ultrasound (US) examination for the diagnosis of advanced fibrosis and cirrhosis was displaced by very expensive and not readily available modern imaging systems like magnetic resonance imaging (MRI), computed tomography (CT) scan and transient elastography. The aim of this study is to evaluate and emphasize the potential of US for diagnosis of advanced liver fibrosis and cirrhosis.

US, laboratory tests (blood counts, transaminases, aspartate platelet ratio index [APRI], international normalized ratio [INR], serum albumin and bilirubin) and liver biopsy were performed on 197 patients with chronic liver diseases. Development of liver fibrosis was categorized in six stages, with stages 1–3 considered as mild to moderate and stages 4–6 as advanced fibrosis. Sonographic parameters (interrupted liver surface line, nodularity of liver surface, biconvexity of liver edges, grade of liver angle, caudate lobe diameter, parenchyma echotexture and spleen size) were obtained. All variables were dichotomized into zero and one and compared with respect to the different stages of liver fibrosis. The sensitivity, specificity, and positive and negative predictive values of all variables as well as their summations scores through receiver operating characteristic (ROC) curve analysis were calculated for the correct histologic diagnosis.

Totally, 39 cases had severe fibrosis and cirrhosis and 158 had mild to moderate fibrosis. The area under the curve by ROC curve analysis of sonographic variables (surface nodularity, angle of left lobe, echotexture of liver and spleen size) was 85%, that of laboratory data (APRI, serum albumin and INR combined) was 83.8%, that of APRI alone was 81.8% and all combined (sonography and lab data together) was 92.4% for the correct diagnosis.

The simple US examination, alone or combined with lab data, is able to diagnose advanced fibrosis and cirrhosis with excellent accuracy, making the use of other modern imaging modalities unnecessary.

Liver fibrosis eventually develops into cirrhosis and hepatic failure, which can only be treated with liver transplantation. We aimed to assess the potential role of hydrogen sulfide (H2S) alone and combined with bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis induced by bile-duct ligation (BDL) and to compare their effects to silymarin. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), and alkaline phosphatase (ALP) were investigated in serum. Gene expression levels of CBS (cystathionine β-synthase), CSE (cystathionine γ-lyase), and alpha-smooth muscle actin (α- SMA) were measured in liver tissues using RT-PCR. Hepatic protein kinase (Akt) was assessed by Western blot assay. Liver oxidative stress markers, malondialdehyde (MDA), and reduced glutathione (GSH) were analyzed by the colorimetric method. Lipocalin-2 (LCN2) and transforming growth factor-β (TGF-β) were measured using ELIZA. Liver tissues were examined by H&E and Masson trichome staining for detection of liver necrosis or fibrosis. Caspase 3 expression was evaluated by immunohistochemistry.  H2S and BM-MSCs ameliorated liver function and inhibited inflammation and oxidative stress detected by significantly decreased serum ALT, AST, ALP, TB, and hepatic MDA, Akt, TGF-β, LCN2, and α-SMA expression and significantly increased CBS and CSE gene expression levels. They attenuated hepatic apoptosis evidenced by decreased hepatic caspase expression. Combined treatment with H2S and BM-MSCs could attenuate liver fibrosis induced by BDL through mechanisms such as anti-inflammation, anti-oxidation, anti-apoptosis, anti-fibrosis, and regenerative properties indicating that using H2S and MSCs may represent a promising approach for management of cholestatic liver fibrosis.