High fiber dietary and sodium butyrate attenuate experimental autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier.

Autoimmune hepatitis (AIH) is chronic autoimmune liver disease accompanied with the imbalance of Treg/Th17 and increased intestinal permeability. We investigated the effects of a high fiber diet and sodium butyrate on the Treg/Th17 and intestinal barrier function in an experimental autoimmune hepatitis. Intraperitoneal injection of hepatic antigen (S100) was used to induce experimental autoimmune hepatitis mice model and mice were divided into normal control, S100 model control, S100 plus high fiber diet and S100 plus sodium butyrate. Serum aminotransferases and liver histology were examined. Short chain fatty acids in feces were determined by HPLC. The ratio of CD4 + C25 + Foxp3+ Treg and CD4 + IL-17 + Th17 were evaluated by flow cytometry. Tight junction proteins Zonula ocluden, Occludin and Claudin-1 were used to assess intestinal barrier function, so does Escherichia coli protein in the liver. Mice fed with either high fiber diet or sodium butyrate showed significantly lower levers of serum aminotransferases and minor liver injury compared to that of model control. Moreover, the ratio of Treg/Th17 was significantly higher in high fiber diet and sodium butyrate fed mice than that in model control. Furthermore, high fiber diet and sodium butyrate significantly increased intestinal tight junction proteins and decreased Escherichia Coli protein in the liver. In conclusion, high fiber diet and sodium butyrate can attenuate development of autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier function.

Enhanced recovery in the management of mild gallstone pancreatitis: a prospective cohort study.

PURPOSE: The aim of this study was to establish enhanced recovery protocols for the management of mild gallstone pancreatitis. METHODS: Sixty consecutive patients were divided into enhanced recovery and traditional recovery (TR) groups in a randomized observational study. The basic enhanced recovery elements included early laparoscopic cholecystectomy, restrictive endoscopic intervention, and early oral nutrition. The incidence of complications, readmission, length of stay, and total medical cost were analyzed during the hospital course. RESULTS: The length of hospital stay and medical cost were significantly lower in the enhanced recovery group in comparison to the TR group: 5.9 days vs. 10.6 days (P < 0.01) and ¥10,023 vs. ¥15,035 (P < 0.01). The complications and readmission rates in the two groups were similar. CONCLUSIONS: The implementation of enhanced recovery protocols is feasible in the management of mild gallstone pancreatitis. The utilization of these protocols can achieve shorter hospital stays and reduced costs, with no increase in either the re-admission or peri-operative complication rates.

miRNA-432 and SLC38A1 as Predictors of Hepatocellular Carcinoma Complicated with Alcoholic Steatohepatitis.

Alcoholic steatohepatitis (ASH) is asymptomatic in the early stages and is typically advanced at the time of diagnosis. With the global rise in alcohol abuse, ASH is currently among the most detrimental diseases around the world. Hepatocellular carcinoma (HCC) is one of the final outcomes of numerous liver diseases. However, at present, HCC screening is mostly focused on liver cancer development. Moreover, there is no effective biomarker to predict the prognosis and recurrence of liver cancer. Meanwhile, there are limited studies on the prognosis and recurrence of HCC patients complicated with ASH. In this study, using bioinformatic analysis as well as cellular and animal models, we screened the differentially expressed (DE) miRNA-432 and SLC38A1 gene in ASH. Based on our analysis, miRNA-432 targeted SLC38A1, and the levels of miRNA-432 and SLC38A1 could accurately predict the overall survival (OS) and relapse free survival (RFS) in patients with liver cancer. Hence, these two genetic elements have the potential to synergistically predict the prognosis and recurrence of HCC complicated with ASH.

Risk factors of severe ischemic biliary complications after liver transplantation.

BACKGROUND: Ischemia-related biliary tract complications remain high after orthotopic liver transplantation. Severe ischemic biliary complications often involve the hepatic duct bifurcation and left hepatic duct, resulting finally in obstructive jaundice. Prevention and management of such complications remain a challenge for transplant surgeons. METHODS: All 160 patients were followed up for at least 180 days after transplantation. One-way analysis of variance (ANOVA) and comparative univariate analysis were made using 3 groups (no complications; mild complications; severe complications), to analyze risk factors associated with biliary complications. Multiple logistic regression and linear regression analysis were used to analyze independent risk factors for severe ischemic biliary complications, after excluding other confounding factors. RESULTS: By ANOVA and comparative univariate analysis, the risk factors associated with biliary complications were preoperative bilirubin level (P=0.007) and T-tube stenting of the anastomosis (P=0.016). Multiple logistic regression analysis showed that the use of T-tube and preoperative serum bilirubin were not independent risk factors for severe ischemic biliary complications after orthotopic liver transplantation. Chi-square analysis indicated that in the incidence of severe ischemic biliary lesions, bile duct second warm ischemic time longer than 60 minutes was a significant risk factor. Linear regression demonstrated a negative correlation between cold preservation time and warm ischemia time. CONCLUSIONS: Preoperative serum bilirubin level and the use of T-tube stenting of the anastomosis were independent risk factors for biliary complications after liver transplantation, but not for severe ischemic biliary complications. The second warm ischemia time of bile duct longer than 60 minutes and prolonged bile duct second warm ischemia time combined with cold preservation time were significant risk factors for severe ischemic biliary complications after liver transplantation with grafts from non-heart-beating donors.

MicroRNA-29c Acting on FOS Plays a Significant Role in Nonalcoholic Steatohepatitis Through the Interleukin-17 Signaling Pathway.

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.

Preventive effects of autologous bone marrow mononuclear cell implantation on intrahepatic ischemic-type biliary lesion in rabbits.

BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation on neovascularization and the prevention of intrahepatic ITBL in a rabbit model. METHODS: The rabbits were divided into control, experimental model, and cell implantation groups, with 10 in each group. The model of intrahepatic ITBL was established by clamping the hepatic artery and common bile duct. Autologous BM-MNCs were isolated from the tibial plateau by density gradient centrifugation and were implanted through the common hepatic artery. Changes in such biochemical markers as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total bilirubin and direct bilirubin were measured. Four weeks after operation, cholangiography, histopathological manifestations, differentiation of BM-MNCs, microvessel density and the expression of vascular endothelial growth factor were assessed. RESULTS: Compared with the experimental model group, the BM-MNC implantation group showed superiority in the time to recover normal biochemistry. The microvessel density and vascular endothelial growth factor expression of the implantation group were significantly higher than those of the control and experimental model groups. The ITBL in the experimental model group was more severe than that in the implantation group and fewer new capillary blood vessels occurred around it. CONCLUSIONS: Implanted autologous BM-MNCs can differentiate into vascular endothelial cells, promote neovascularization and improve the blood supply to the ischemic bile duct, and this provides a new way to diminish or prevent intrahepatic ITBL after liver transplantation.

Autoimmune pancreatitis: report of two cases and literature review.

BACKGROUND: Autoimmune pancreatitis (AIP) is a unique chronic inflammation of the pancreas in which autoimmune mechanisms are involved in the pathogenesis. It is characterized by clinical, histopathological, radiographic, serologic and therapeutic features. Since it was first described in 1995, increasing numbers of AIP patients have been diagnosed. METHODS: In this study, the data from 2 patients with AIP who had elevation of serum immunoglobulin G, positive autoantibody, swelling of the pancreas and narrowing of the main pancreatic duct on imaging were analyzed retrospectively. RESULTS: With the initial diagnosis of AIP, both patients underwent regular prednisone therapy, which was initiated at a dose of 40 mg per day with a tapering schedule of 5 mg every 2 weeks. The patients responded very well to treatment with prednisone. CONCLUSIONS: AIP is a relatively new disease entity. Although it is diagnosed by distinct characteristics of the clinical, radiologic, histopathologic, and serologic findings, many questions require further clarification, including its relationship to other autoimmune diseases and misdiagnosis as pancreaticobiliary malignancies.

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis.

BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R15)) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R15) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R15 and MELD score increased. There were significant statistical differences in K value, R15 and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R15) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P<0.05), while a positive correlation was observed between R15 and MELD score (r=0.804, P<0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R15 have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.

Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice.

BACKGROUND: Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice. METHODS: We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis. RESULTS: IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis. CONCLUSION: The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.

Process optimization for the rapid production of Enterovirus 71.

Enterovirus 71 (EV71) infection can cause hand-foot-and-mouth disease (HFMD). Inactivated EV71 vaccine was effective to prevent EV71 derived HFMD. A highly efficient and economical process for producing EV71 is needed. In our study, the epidemic strain of EV71 (EV71-2013ZJHFMD) was obtained and purified. The Vero cells were cultured for production of EV71. The mini-bioreactor vessel (Amprotein Inc., China) packed with a 0.6 g polymer fiber carrier was used to determine the best seeding cell density, multiplicity of infection (MOI) and temperature. Then the optimized procedure was further applied in a 10 L disposable perfusion bioreactor ACPB (AmProtein Current Perfusion Bioreactor). The Vero cell culture and viral titer were monitored. The seeding density of 1.5 × 107 cells per 0.6 g disk was considered to be the most appropriate for the culture. The best MOI was 0.1 and the temperature was 32 °C. The total cell number increased from 1.5 × 109 to 3.0 × 1010. The maximum viral titers reached 1.0 × 108/mL 3 days post-infection in our optimized special culture procedure (serum-free during the harvest period, supplemented with 0.25% Lactalbumin Hydrolysate). The total volume of the harvested supernatant was 25 L and the total virus yield was 1.93 × 1012. The procedure using Vero cells grown on polymer fiber paper carriers was effective for the large-scale production of EV71.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p.

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Synergistic effects of Lactobacillus rhamnosus culture supernatant and bone marrow mesenchymal stem cells on the development of alcoholic steatohepatitis in mice.

The gut microbiota has been shown to play an important role in chronic liver disease. It has been found that both Lactobacillus rhamnosus and its culture supernatant have the potential to mitigate alcoholic steatohepatitis. However, the exact mechanism is still not fully understood. Bone marrow mesenchymal stem cells have immunosuppressive effects with few side effects. The synergistic effect between Lactobacillus rhamnosus culture supernatant and bone marrow mesenchymal stem cells (BMMSCs) deserves further observation. In this study, a mouse model of chronic alcoholic hepatitis was established by eight weeks of Lieber-DeCarli liquid diet feeding; and LGG-s, BMMSCs or a combination of the two were used to explore a new therapeutic method for alcoholic liver disease and to study the mechanism. The results showed that the combined LGG-s and BMMSC treatment might have a synergistic effect and could improve the symptoms of alcoholic hepatitis by regulating inflammation, autophagy and lymphocyte subsets through the PI3k/NF-kB and PI3K/mTOR pathways. With the treatment, the autophagy rate accelerated, and alcohol-induced natural killer B (NKB) cell and follicular helper T (TFH) cell numbers decreased. These findings suggest that the development of alcoholic hepatitis may occur via PI3K/NF-kB and PI3K/mTOR pathway overactivation as well as through NKB and TFH cell imbalances. Moreover, LGG-s and BMMSCs can regulate these factors and alleviate the disease.

Laparoscopic cystogastrostomy for the treatment of pancreatic pseudocysts: a case report.

Pancreatic pseudocysts (PPs) are collections of pancreatic secretions that are lined by fibrous tissues and may contain necrotic debris or blood. The interventions including percutaneous, endoscopic or surgical approaches are based on the size, location, symptoms and complications of a pseudocyst. With the availability of advanced imaging systems and cameras, better hemostatic equipments and excellent laparoscopic techniques, most pseudocysts can be found and managed by laparoscopy. We describe a case of a 30-year-old male patient with a pancreatic pseudocyst amenable to laparoscopic cystogastrostomy. An incision was made through the anterior gastric wall to expose the posterior gastric wall in close contact with the pseudocyst using an ultrasonically activated scalpel. Then, another incision was made for cystogastrostomy to obtain complete and unobstructed drainage. The patient recovered well after operation and was symptom-free during a 6-mo follow-up, suggesting that laparoscopic cystogastrostomy is a safe and effective alternative to open cystogastrostomy for minimally invasive management of PPs.

The Combined Effect of Nonalcoholic Fatty Liver Disease and Metabolic Syndrome on Osteoporosis in Postmenopausal Females in Eastern China.

The present study evaluated the potential combined effects of NAFLD and MetS on the development of osteoporosis. The relationship between NAFLD and MetS and osteoporosis was assessed in 938 postmenopausal female participants. Moderate and severe NAFLDs were combined as significant NAFLD (SNAFLD). All the subjects were divided into 4 subgroups based on the status of SNAFLD and MetS. Relative excess risk of interaction (RERI), attributable proportion (AP) of interaction, and synergy index (SI) were used to investigate the additive interaction of those two factors. NAFLD, SNAFLD, and MetS were independent factors for osteoporosis with the adjustment of age and other confounders. The incidence of osteoporosis in MetS (+) SNAFLD (+) group was significantly higher than that in other three groups. RERI was 2.556 (95% CI = 0.475-4.636), AP was 0.454 (95% CI = 0.201-0.706), and SI was 2.231 (95% CI = 1.124 to 4.428), indicating the significant combined interaction of SNAFLD and MetS on the development of osteoporosis. SNAFLD and MetS are independent risk factors for osteoporosis in postmenopausal females, respectively. Moreover, SNAFLD and MetS have an additive effect on the development of osteoporosis.

Patients with chronic hepatitis C receiving sofosbuvir and ribavirin-based treatment, with or without interferon in Zhejiang, China: An observational study.

Hepatitis C virus (HCV) is one of the most important virus as the cause of liver disease in China. The aim of the present study was to explore whether sofosbuvir and ribavirin-based treatment can cure patients with chronic hepatitis C in eastern China. We examined a cohort of HCV-monoinfected patients and 9 patients agreed to participate in our treatment and research. The patients were diagnosed with chronic hepatitis C with or without cirrhosis. Nine patients including 4 female and 5 male met the requirements for selection and were willing to participate in this experiment. Sofosbuvir and ribavirin-based treatment with or without interferon was given to the patients. Viral loads, cytokines, and chemokines were recorded during treatment and after treatment. After 2 weeks of sofosbuvir and ribavirin-based treatment, the viral load of patients decreased to limits of detection. Eight patients were cured. Patients had rapid virological response (RVR) with undetectable viral load at week 4 and sustained virological response (SVR). The interferon-inducible protein-10 (IP-10) decreased after the treatment. However, the patient with cirrhosis failed, as the virus reappeared during SVR4. At the same time, the IP-10 dramatically increased as the relapse of the HCV virus. In summary, the IP-10 has the potential to be the biomarker for the prognostic of HCV.

Interaction of smoking and metabolic syndrome in increasing the recurrence risk of colorectal cancer in a Chinese male cohort: a retrospective study.

Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma (CRC) prognosis remains debatable. Therefore, the present study aimed to examine the individual and combined effects of smoking and MetS on the prognosis of patients with localized CRC, including stage I to III disease. The relationship among smoking status, MetS, and CRC was assessed in 838 Chinese male patients. Cox proportional hazards regression analysis was used to evaluate CRC prognosis adjusted for clinicopathological variables. Relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate additive interactions between smoking and MetS. The presence of MetS was an independent risk factor for low rates of recurrence-free survival (RFS) but not for overall survival (OS). However, smoking was independently associated with both poor RFS and OS. Furthermore, the recurrence risk for current smokers with MetS was 1.62 times as high as the sum of risks in patients exposed to each risk factor alone. In conclusion, current smoking habit is a risk factor for both recurrence and cancer-specific mortality in CRC patients, while MetS is an independent predictor for CRC recurrence. Furthermore, these two factors have an additive effect on the recurrence risk of CRC.

Comparative efficacy and tolerability of treatments for adult autoimmune hepatitis: A systematic review and network meta-analysis.

The most suitable treatment regimen for autoimmune hepatitis (AIH) in adults remains unknown and requires further investigation. The current study therefore aimed to integrate evidence to provide hierarchies of the comparative efficacies of treatments measured by clinical and biochemical remission. A Bayesian-framework network meta-analysis of randomized controlled trials (RCTs) was preformed to compare eight treatments for AIH. Eligible RCTs were identified by searching Embase, Pubmed and the Cochrane Library for publications between 1966 and April 2017. All outcomes were independently extracted from the included studies by two authors. A total of six RCTs were subsequently included in the current study. The network of comparisons on remission indicated that patients treated with prednisone (pred) experienced significantly increased rates of remission compared with those treated with azathioprine [AZA; odds ratio (OR), 0.21; 95% confidence interval (CI), 0.06-0.71] and budesonide (bude) + AZA significantly increased remission compared with placebo treatment (OR, 36.66; 95% CI, 1.40-962.49) or AZA (OR, 10.30; 95% CI, 1.50-70.70). Based on the cumulative ranking probabilities, bude + AZA (89.4) was ranked first, pred (69.1) was ranked second, pred + AZA (63.2) was ranked third and placebo (7.8) treatment was ranked last. Bude + AZA may be the most appropriate candidate for the treatment of non-cirrhotic patients. However, bude + AZA as frontline therapy for AIH requires more large-scale studies with a longer duration of follow-up histology and a focus on dose-response. Additionally, development of other prospective treatments, which may be used as alternative therapy or first line therapy, and their subsequent evaluation in clinical RCTs is required.

The relationship between obesity and the severity of non-alcoholic fatty liver disease: systematic review and meta-analysis.

INTRODUCTION: A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic factors and prognosis, but the results were conflicting and inconclusive. Areas covered: In this meta-analysis, the liver function, histopathology, metabolic complications, patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic polymorphism and prognosis were compared between non-obese and obese NAFLD. Pubmed, EMBASE, Cochrane databases were searched to identify eligible studies. The odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models. Expert commentary: This meta-analysis indicated that for NAFLD patients, obesity (according to ethnic-specific BMI cut-off points to define obesity) could predict a worse long-term prognosis. However, obesity may not be an independent factor for the development of NASH or advanced fibrosis in NAFLD patients and NAFLD should be considered as potential population for pharmacologic treatment regardless of obesity. In addition, PNPLA3 rs738409 may be more relevant to the progression of non-obese NAFLD when compared to obese NAFLD. Importantly, large-sample, long-term follow-up cohort studies based on liver biopsy are highly needed due to limited liver pathology and long-term follow-up data at present.

BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte. Before the experiments, BMSCs were infected with pre-miR-223 and transfected with miR-223 inhibitor respectively. Exosomes from bone marrow stem cells were isolated by ultracentrifugation. Liver injury was evaluated by serum levels of ALT and AST as well as liver histology. Inflammation and cell death were examined by inflammatory cytokines and lactase dehydrogenase respectively. Both BMSCs-exo and BMSCs-exomiR-223(+) significantly reversed either S100 or LPS/ATP induced injury in mice and hepatocytes. Meanwhile, the expressions of cytokines, NLRP3 and caspase-1 were also downregulated by BMSCs-exo and BMSCs-exomiR-223(+) at both protein and mRNA levels in mice and hepatocytes. Moreover, BMSCs-exomiR-223(-) reverses the effects of BMSCs-exo and BMSCs-exomiR-223(+) in mouse AIH and in hepatocytes. In conclusion, bone marrow stem cell derived exosomes can protect liver injury in an experimental model of autoimmune hepatitis and the mechanism could be related to exosomal miR-223 regulation of NLRP3 and caspase-1.