Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.
Animals ; Cell Differentiation ; Cell Proliferation ; Hepatocytes/immunology/metabolism/pathology/*transplantation ; Humans ; Liver/immunology/metabolism/pathology/physiopathology/*surgery ; Liver Cirrhosis/diagnosis/immunology/metabolism/physiopathology/*surgery ; Liver Regeneration ; *Mesenchymal Stem Cell Transplantation/adverse effects ; *Mesenchymal Stromal Cells/immunology/metabolism/pathology ; Phenotype ; Regenerative Medicine/*methods ; Risk Factors ; Signal Transduction ; Treatment Outcome

OBJECTIVE: To investigate the influence of endoscopic variceal ligation (EVL) on liver function and analyze the risk factors of rebleeding after EVL. METHODS: A total of 137 cirrhotic patients with esophageal varices who received EVL were retrospectively analyzed, and divided into group A, B, and C according to the Child-Pugh scores of liver function. We compared the liver function 1 week preoperatively and postoperatively. The patients were further divided into a rebleeding group and a non-rebleeding group after the EVL, and risk factors about rebleeding were analyzed. RESULTS: There was no significant difference on ALT, AST, T-Bil, and D-Bil either preoperatively or postoperatively in group A, B, and C (P>0.05). Thirteen patients (9.49%) rebled after the EVL. The course of disease, liver function, prothrombin time, and mass ascites were the risk factors of rebleeding. CONCLUSION EVL has no obvious effect on liver function, and the course of disease, liver function, prothrombin time and mass ascites are risk factors of rebleeding after EVL.
Adult ; Endoscopy ; methods ; Esophageal and Gastric Varices ; etiology ; surgery ; Female ; Gastrointestinal Hemorrhage ; etiology ; prevention & control ; surgery ; Humans ; Ligation ; methods ; Liver ; physiopathology ; Liver Cirrhosis ; complications ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Secondary Prevention

OBJECTIVETo evaluate the correlations between MELD score and left ventricular function in patients with end-stage liver disease.

METHODSA total of 92 patients who prepared for orthotopic liver transplantation from January 2002 to May 2008 were enrolled in this study. Of these Patients, 75 were males and 17 were females, and the mean age was 50.3+/-9.5 years; 85 were cirrhosis, 7 were cirrhosis with primary liver cancer. Preoperative information, including biochemical parameters, coagulation parameters, indicators of hepatitis virology, two-dimensional echocardiography and electrocardiogram were collected. According to MELD (the Model for End-stage Liver Disease) scoring system, these subjects were categorized into three groups: MELD score is less than or equal to 9 points (31 cases, 33.7%); 10 is less than or equal to MELD score is less than or equal to 19 points (45 cases, 48.9%); MELD score is more than or equal to 20 points (16 cases, 17.4%). The relationships between MELD score and classification and cardiac function were determined by chi-square test, analysis of variance, rank sum test and correlation analysis, et al.

RESULTSMELD score was significantly correlated with left atrial diameter (LAD), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDD), aortic flow (AF), cardiac output (CO), QRS interval (QRSI) and corrected QT interval (QTc) (r = 0.317, 0.341, 0.228, 0.387, 0.325, 0.209 and 0.347, respectively; P value less than 0.01, respectively); except QRSI, these variables and left ventricular posterior wall thickness (LVPWT) were also correlated with INR (a MELD component) (r = 0.282, 0.319, 0.322, 0.435, 0.275, 0.320 and 0.237, respectively; P value less than 0.01, respectively); LAD, LVEDD, AF, CO and QTc were correlated with serum total bilirubin (r = 0.241, 0.219, 0.357, 0.246 and 0.253, respectively; P value less than 0.05, respectively); IVST and E/A ratio (A blood flow [from left atrium to left ventricular] velocity ratio between early diastole [E wave] and late diastole[A wave] ) were correlated with serum creatinine (r = 0.216 and -0.343; P value less than 0.05 and 0.01); the proportion of E/A is less than or equal to 1 in all subjects was 46.7% (43/92), and 48.4% (15/31), 35.6% (16/45) and 75.0% (12/16) in each group, besides, there was statistically significant difference between 10 is less than or equal to MELD score is less than or equal to 19 points group and MELD score is more than or equal to 20 points group (X2 = 7.359, P = 0.009).

CONCLUSIONSThere are different degrees of left ventricular structure, function and electrophysiological changes in patients with end-stage liver disease, these anomalies also will be increased with the MELD score increasing.

Adult ; End Stage Liver Disease ; physiopathology ; surgery ; Female ; Humans ; Liver Cirrhosis ; physiopathology ; surgery ; Liver Failure ; physiopathology ; surgery ; Liver Neoplasms ; physiopathology ; surgery ; Liver Transplantation ; Male ; Middle Aged ; Ventricular Function, Left

OBJECTIVETo observe the occurrence and progression of liver fibrosis induced by pig serum exposure and bile duct ligation, and analyze the relationship between hepatic inflammation and liver fibrosis.

METHODSChronically immune-mediated liver fibrosis was induced in rats by weekly injection of pig serum (IPS) into the peritoneal cavity at 3 ml/kg for 12 weeks. Cholestatic fibrosis was induced by common bile duct ligation (BDL). The Knodell score was used to evaluate the histological changes in the liver, and immunohistochemistry was performed using anti-SMA, anti-ED1, anti-CK7, and anti-CD45 antibodies. Quantitative real time PCR (qPCR) analysis was employed to quantify the mRNA expression of the genes related to inflammation, including interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), transforming growth factor-beta, platelet-derived growth factor A, as well as the genes associated with fibrogenesis, namely collagen 1, alphaSMA, MMP-9 and TIMP-1.

RESULTSKnodell scores for periportal necrosis, intralobular degeneration and focal necrosis, and portal inflammation were all significantly higher in the BDL group than in the IPS group (P<0.01), whereas the scores for fibrosis was higher in the IPS group (P<0.05). Immunohistochemistry showed obvious inflammation with numerous alphaSMA-positive cells in the liver of the rats in BDL group; the liver of the rats in IPS group showed numerous alphaSMA-positive myofibroblasts with limited inflammatory cell infiltration. qPCR demonstrated a significant up-regulation of the genes related to extracellular matrix remodeling such as collagen 1 (P<0.01), alphaSMA (P<0.01), MMP-9 (P<0.01) and TIMP-1 (P<0.01) in the rat liver in IPS group compared with those in the normal control group, and the mRNA expressions of the inflammation-related cytokines, except for RANTES, were comparable with those in the control. In contrast, the BDL group showed a significant up-regulation of all the pro-inflammatory genes examined with also increased expression of the fibrogenesis-related genes (P<0.05).

CONCLUSIONLiver fibrosis induced by IPS is characterized by active ECM remodeling in the absence of obvious inflammation, indicating that chronic development of liver fibrosis can be independent of active hepatic inflammation. BDL-induced liver fibrosis highlights obvious inflammation and fibrous proliferation in the liver.

Animals ; Bile Ducts ; surgery ; Cholestasis ; complications ; physiopathology ; Ligation ; Liver Cirrhosis, Experimental ; etiology ; immunology ; pathology ; Male ; Rats ; Rats, Inbred F344 ; Serum ; immunology ; Swine

Humans ; Hypertension, Portal ; physiopathology ; surgery ; Liver ; physiopathology ; Liver Cirrhosis ; complications ; Liver Transplantation ; Portasystemic Shunt, Transjugular Intrahepatic

OBJECTIVETo evaluate the predictive value of portal vein flow rate preoperative for portal vein thrombosis (PVT) after periesophagastric devascularization in hepatitis B cirrhosis-related portal hypertension.

METHODSFrom January 2007 to July 2008, 45 patients with portal hypertension caused by hepatitis B cirrhosis were performed splenectomy with peri-esophagogastric devascularization in the same medical group in West China Hospital of Sichuan University. The portal vein flow rate and the diameter of portal vein were measured with doppler sonography respectively before and after the operation. At the same time, the level of PT and PLT were detected. The weight of spleens were measured after operation.

RESULTSThirteen cases suffered from PVT postoperatively. Portal vein flow rate was significantly lower in patients with PVT postoperation than that in patients without PVT (P < 0.01). In patients with PVT (n = 13) postoperation, the preoperative portal vein flow rate was (19.5 +/- 5.3) cm/s. Among the 13 cases, there were 12 cases whose flow rate were lower than 25 cm/s, and 1 case whose flow rate was 32. 3 cm/s; In patients without PVT (n = 32), the preoperative portal vein flow rate was (9.6 +/- 8.0) cm/s. In patients with lower rate (n = 17), the incidence rate of PVT was 70.6%; in patients with higher rate (n = 28), the incidence rate of PVT was 3.6%. The incidence rate of PVT in patients with lower rate was significantly lower than patients with higher rate (P < 0.01). The diameter of portal vein in patients with PVT was significantly wider than patients without PVT. The diameter of portal vein was negative correlative with the portal vein flow rate. The value 25 cm/s was of diagnostic efficiency, the sensitivity was 92.3%, and specificity was 70.6%.

CONCLUSIONSThe portal vein flow rate preoperative can be used as an early predictor of portal vein thrombosis after periesophagastric devascularization in hepatitis B cirrhosis-related portal hypertension to give a guide to clinical work.

Adult ; Aged ; Blood Flow Velocity ; Female ; Humans ; Hypertension, Portal ; etiology ; physiopathology ; surgery ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Portal Vein ; diagnostic imaging ; physiopathology ; Postoperative Complications ; diagnosis ; etiology ; Preoperative Care ; Risk Factors ; Splenectomy ; Ultrasonography ; Venous Thrombosis ; diagnosis ; etiology

OBJECTIVETo evaluate the effect of living donor liver transplantation on the treatment of severe hepatitis.

METHODS18 patients with severe hepatitis received liver transplantation (transplanted severe hepatitis group), 28 patients with sever hepatitis received non surgical treatment (non-transplanted severe hepatitis group), and 30 patients with end stage liver cirrhosis (without cancer) received liver transplantation (transplanted cirrhosis group). The vital sign, blood coagulation, and renal function were monitored during operation. After liver transplantation, patients received immunosuppressive therapy (including tacrolimus or cyclosporine A, mycophenolate, mofetil and corticosteroids), intensive care, antiviral therapy (including lamivudine and HBIg) and other treatments (including restoration of liver function and prevention of blood coagulation). Pre-operation data, operation procedure, liver function, renal function and the operation complications of three groups were compared, and survival rate at 1, 6 and 12 months after operation was followed.

RESULTSThere was no significant difference in the operation time, warm ischemia time, hypothermic ischemia time and Graft-to-recipient weight ratio between the two transplantation groups. The blood loss volume and blood transfusion volume in the transplanted severe hepatitis group were higher than that those in the cirrhosis transplantation group (t = 0.001, 0.004). The levels of TBil, ALT and AST at day 7 after operation were (100.5 +/- 96.4)mumol/L, (215.3 +/- 195.7) U/L , (209.8 +/- 188.6) U/L in the transplanted severe hepatitis group, and (53.3 +/- 31.9)mumol/L, (56.3 +/- 22.1) U/L, (51.3 +/- 13.5) U/L in the transplanted cirrhosis group (t = 0.017, 0.021, 0.004). However, there was no significant difference in the levels of Alb and Cr between these two groups (P > 0.05). Survival rate was 88.89%, 83.33% 83.33% in the transplanted severe hepatitis group, and 96.67%, 93.33% 93.33% in the transplanted cirrhosis group at 1, 6 and 12 months after transplantation.

CONCLUSIONLiving donor liver transplantation is one of effect ways for the treatment of severe hepatitis.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hepatitis B ; physiopathology ; surgery ; Humans ; Immunoglobulins ; therapeutic use ; Immunosuppressive Agents ; therapeutic use ; Kidney Function Tests ; Lamivudine ; therapeutic use ; Liver Cirrhosis ; physiopathology ; surgery ; Liver Function Tests ; Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Postoperative Complications ; therapy ; Postoperative Period ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the effect of autologous bone marrow-derived stem cell (BMSCs) transplantation in the treatment of liver failure and decompensated hepatic cirrhosis.

METHODSBone marrow was harvested (65-95 ml) from 24 patients in the transplantation group. The BMSCs were isolated and infused into liver or spleen of patients via hepatic or splenic artery. At different time points after the transplantation, the patients' liver function and prothrombin time (PT) were evaluated, and the survival rate and symptoms of the patients were recorded.

RESULTSAll the serum biochemical indexes remained stable 2 weeks after the transplantation, and at 4 weeks after transplantation, albumin level increased significantly in comparison with the preoperative level (P<0.05). At 12 weeks, the albumin level further increased (P<0.01) along with Pre-ALB (P<0.01), while total bilirubin, tolal bile acid, PT and fibrinogen were all significantly lowered (P<0.05), and globulin, ALT, and AST remained unchanged (P>0.05). One week after the transplantation, improved appetite was observed in 22 cases (91.67%), and 21 cases (87.5%) showed better physical strength; at 2 weeks, hepatic face improved in 15 cases (62.5%), and spider telangiectasia was significantly reduced in one case; at 12 weeks, the survival rate of the patients was 62.5%, and 9 died or gave up treatment due to chronic liver failure complicated by spontaneous bacterial peritonitis, hepatorenal syndrome, or DIC. No complications associated with the transplantation occurred in these patients.

CONCLUSIONBMSC transplantation can significantly improve the liver function of patients with terminal liver disease with good safety and effectiveness.

Adolescent ; Adult ; Aged ; Bone Marrow Transplantation ; methods ; Female ; Humans ; Liver Cirrhosis ; physiopathology ; surgery ; Liver Failure ; physiopathology ; surgery ; Liver Function Tests ; Male ; Middle Aged ; Stem Cell Transplantation ; methods ; Transplantation, Autologous ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the characteristics of autophagy in fibrotic and postoperative remnant liver.

METHODSMale Wistar rats were randomly divided into three groups: control group; fibrosis group, which received the solution of CCl4 in oil twice a week for 5 weeks; and hepatectomy group, which underwent 70% hepatectomy. Liver tissues and plasma were harvested 18 hours after the surgery. The rats' general conditions and plasma liver function were observed. Histopathological characteristics and regeneration were observed with microscope and transmission electron microscope. Qualitative analysis of autophagosome was made base on the data from transmission electron microscope.

RESULTSCompared with the control group, plasma total protein and albumin level significantly decreased in the fibrosis group (P < 0.01). Proliferating cell nuclear antigen (PCNA) index was 85%-95% in the fibrosis group. Plasma alanine aminotransferase and aspartate aminotransferase levels significantly increased in the hepatectomy group compared with the control group (P < 0.01), while the autophagical index significantly decreased in both the fibrosis group and hepatectomy group compared with the control group (-95%, P < 0.01; -19%, P < 0.05, respectively). PCNA index was 20%-30% in the hepatectomy group.

CONCLUSIONSAutophagy is weakened after fibrosis and hepatectomy, although it differs between these two processes. Proper regulation of autophagy may help facilitate the recovery of the residual liver function after hepatectomy.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Autophagy ; Disease Models, Animal ; Hepatectomy ; Humans ; Liver ; metabolism ; pathology ; physiopathology ; surgery ; Liver Cirrhosis ; metabolism ; pathology ; physiopathology ; surgery ; Male ; Proliferating Cell Nuclear Antigen ; metabolism ; Random Allocation ; Rats ; Rats, Wistar

Hemodynamics ; Humans ; Hypertension, Portal ; etiology ; physiopathology ; surgery ; Liver Cirrhosis ; complications ; physiopathology ; surgery ; Liver Transplantation ; Postoperative Period