| Objective: Hepatitis B virus (HBV)-related acute-on-chronic liver failure(ACLF) is a life-threatening syndrome that is characterized by variantcomplications such as progressive jaundice, hepatic encephalopathy, ascites,hepatorenal syndrome and so on. The mortality of HBV-related ACLF remainsvery high. To date, treatment options are limited. Bone-marrow-derived stemand progenitor cells have the capacity to migrate into the liver anddifferentiate into functional hepatocytes. In the present study, we detected theexpression of SDF-lα mRNA in liver tissues, the expression and thedistribution of intrahepatic SDF-lα and ki-67, as well as serum levels ofSDF-lα in patients with HBV-related ACLF, and we further explored thevariation of serum SDF-lα levels in HBV-related ACLF patients with differentoutcomes to analyze the role of SDF-lα in the homing of liver stem cells.Methods: Thirty patients with HBV-related ACLF,27patients withchronic hepatitis B (CHB) and20healthy controls (HC) were involved in ourstudy. Moreover, liver tissues were obtained from10HBV-related ACLFpatients,10CHB patients and8liver donors during liver transplantations andliver biopsy. The patients were recruited at the Third Hospital of HebeiMedical University and The Fifth Hospital of Shijiazhuang from March2011to November2012. The diagnoses of HBV-related ACLF and CHB wereaccording to the Diagnostic and Treatment Guidelines for Liver Failure (2006)and the Guidelines on Prevention and Treatment for Chronic Hepatitis B inChina (2010) issued by the Chinese Society of Hepatology and the ChineseSociety of Infectious Disease. Serum biochemical parameters, coagulationfunction parameters and serum HBV DNA load were detected. The SDF-lαmRNA expression in liver tissues was detected by quantitative real-timepolymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression and the distribution of SDF-lα and ki-67. The serumSDF-lα concentrations were detected by enzyme-linked immunosorbentassays. Moreover, the variation of serum SDF-lα levels in HBV-related ACLFpatients with different outcomes, the relationships between the serum SDF-lαlevels and the HBV DNA load and model of end-stage liver disease (MELD)scores were analyzed separately.Results:1Demographic and clinical characteristics of the studied subjectsThere was no significant difference in sex ratio and age among the threegroups. HBV-related ACLF patients displayed higher levels of alaninetransaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL),direct bilirubin (DBIL) and international normalized ratio (INR) than CHBpatients and healthy controls (all P<0.01). The HBV DNA load wascomparable between HBV-related ACLF patients and CHB patients (P>0.05).2Increased intrahepatic SDF-lα mRNA expresssion in patients with ACLFA total of8patients with HBV-related ACLF,10patients with CHB and8healthy controls received SDF-lα mRNA expression detection. Patients withACLF had significantly higher expression of SDF-lα mRNA (3.4±1.02) thanCHB patients (2.16±1.19) and healthy controls (1.00)(P<0.05or P<0.01).Similarly, there was a significant difference in relative levels of SDF-lαmRNA between CHB patients and healthy controls (P<0.05).3SDF-lα and ki-67were highly expressed in liver tissues of ACLFpatientsA total of10patients with HBV-related ACLF,10patients with CHB and6normal controls received detection of SDF-lα and ki-67expression. Theaverage absorbance of SDF-lα were (0.345±0.095),(0.178±0.116) and(0.051±0.022), in ACLF, CHB patients and healthy controls respectively.There were significant differences between each group (all P<0.01). Theexpression of SDF-lα in ACLF group was highest, and healthy controls wasthe lowest. Moreover, in ACLF patients, SDF-lα distribution was extended tobile ductule and hepatic progenitor cells. Meanwhile, obvious ductular reaction can be observed. However, SDF-lα was expressed only in bile duct inhealthy controls. Similarly, The higher expression of ki-67were detected inliver sections in patients with ACLF (171.2±52.8/hpf) compared with CHBpatients (42.4±17.8/hpf) and healthy controls (42.4±17.8/hpf)(both P<0.01).The CHB patients presented with significantly higher ki-67protein expressionthan healthy controls (P<0.01). The distribution of Ki-67was predominantlyseen in the portal areas, and occasionally scattered in the liver parenchyma.4Decreased peripheral blood SDF-lα concentrations in ACLF patientsA total of30patients with HBV-related ACLF,27patients with CHB and20normal controls received serum SDF-lα levels detection. The serum SDF-lαlevels in ACLF patients (1717.33±458.07pg/ml) were significantly lower thanCHB patients (2638.96±574.04pg/ml) and healthy controls (2378.20±660.09pg/ml)(both P<0.01). However, no statistical difference was found betweenCHB patients and healthy controls.(P>0.05).5Changes of the concentrations of peripheral blood SDF-lα in ACLFpatients with different outcomesAccording to the prognosis at the28-day observation, the ACLF patients(n=30) were divided into survival group (n=11) and non-survival group (n=19). The survival ACLF patients (1497.69±408.55pg/ml) had significantlylower serum SDF-lα levels compared with the non-survival patients(1844.50±445.84pg/ml)(P<0.05).6The correlation between peripheral blood SDF-lα concentrations andHBV DNA load and MELD scoreNo correlation was found between the serum SDF-lα levels and HBVDNA load (r=0.21, P=0.27) and the MELD score (r=0.17, P=0.38).Conclusions:1The stem cells participate to liver regeneration in patients withHBV-related ACLF.2The SDF-lα gradient between the injured liver and peripheral blood inpatients with HBV-related ACLF, SDF-lα increase in the injured liver, and adecrease in peripheral blood, may facilitate the homing and engraftment of stem cells to the liver.3The lower levels of peripheral blood SDF-lα may induce more stem cellsmigration, and therefore may indicate better short-term prognosis in ACLFpatients. |
