PURPOSE: The present study aimed to investigate the role of hepatic venous pressure gradient (HVPG) for prediction of long-term mortality in patients with decompensated cirrhosis. MATERIALS AND METHODS: Clinical data from 97 non-critically-ill cirrhotic patients with HVPG measurements were retrospectively and consecutively collected between 2009 and 2012. Patients were classified according to clinical stages and presence of ascites. The prognostic accuracy of HVPG for death, survival curves, and hazard ratios were analyzed. RESULTS: During a median follow-up of 24 (interquartile range, 13-36) months, 22 patients (22.7%) died. The area under the receiver operating characteristics curves of HVPG for predicting 1-year, 2-year, and overall mortality were 0.801, 0.737, and 0.687, respectively (all p<0.01). The best cut-off value of HVPG for predicting long-term overall mortality in all patients was 17 mm Hg. The mortality rates at 1 and 2 years were 8.9% and 19.2%, respectively: 1.9% and 11.9% with HVPG < or =17 mm Hg and 16.2% and 29.4% with HVPG >17 mm Hg, respectively (p=0.015). In the ascites group, the mortality rates at 1 and 2 years were 3.9% and 17.6% with HVPG < or =17 mm Hg and 17.5% and 35.2% with HVPG >17 mm Hg, respectively (p=0.044). Regarding the risk factors for mortality, both HVPG and model for end-stage liver disease were positively related with long-term mortality in all patients. Particularly, for the patients with ascites, both prothrombin time and HVPG were independent risk factors for predicting poor outcomes. CONCLUSION: HVPG is useful for predicting the long-term mortality in patients with decompensated cirrhosis, especially in the presence of ascites.
Adult ; Aged ; Ascites/mortality ; Female ; Hepatic Veins/*physiopathology ; Humans ; Kaplan-Meier Estimate ; Liver Cirrhosis/blood/complications/diagnosis/*mortality/*physiopathology ; Liver Failure/diagnosis/*mortality/physiopathology ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Venous Pressure

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

OBJECTIVETo investigate the correlation between four serum fibrosis markers and liver function in patients with infantile hepatitis syndrome (IHS), and to explore the clinical significance of these markers in the diagnosis of IHS and the assessment of disease severity.

METHODSA retrospective study was performed on 60 patients with IHS who were divided into hepatic fibrosis and normal groups based on ultrasound diagnosis. Levels of four liver fibrosis markers, i.e., hyaluronic acid (HA), type III procollagen (PC-III), type IV collagen (IV.C), and laminin (LN), were compared between the two groups, and the correlation between these markers and liver function was analyzed.

RESULTSLevels of liver function markers (alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil), and total bile acid (TBA)) in the hepatic fibrosis group were significantly higher than those in the normal group (P<0.05). Levels of HA and IV.C in the hepatic fibrosis group were significantly higher compared with those in the normal group (P<0.05). Furthermore, HA, IV.C, and PC-III levels were positively correlated with those of ALT, TBil, GGT, DBil, IBil, and TBA (r=0.25-0.49), and the strongest correlation existed between HA/IV.C and ALT/jaundice markers.

CONCLUSIONSAssay measuring serum fibrosis markers (HA, IV.C, and PC-III) in combination with liver function tests and ultrasound examination has an important clinical value in the early diagnosis of IHS and evaluation of disease severity.

Biomarkers ; blood ; Collagen Type III ; blood ; Collagen Type IV ; blood ; Female ; Hepatitis ; blood ; diagnosis ; physiopathology ; Humans ; Hyaluronic Acid ; blood ; Infant ; Laminin ; blood ; Liver ; physiopathology ; Liver Cirrhosis ; blood ; diagnosis ; Male ; Retrospective Studies ; Syndrome

Portal hypertension is a severe consequence of chronic liver diseases and is responsible for the main clinical complications of liver cirrhosis. Hepatic venous pressure gradient (HVPG) measurement is the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >10 mmHg. In this condition, the complications of portal hypertension might begin to appear. HVPG measurement is increasingly used in the clinical fields, and the HVPG is a robust surrogate marker in many clinical applications such as diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who had a reduction in HVPG of > or =20% or to < or =12 mmHg in response to drug therapy are defined as responders. Responders have a markedly decreased risk of bleeding/rebleeding, ascites, and spontaneous bacterial peritonitis, which results in improved survival. This review provides clinical use of HVPG measurement in the field of liver disease.
Chronic Disease ; Hemodynamics ; Hemorrhage/etiology ; Hepatic Veins/physiology ; Humans ; Hypertension, Portal/complications ; Liver Cirrhosis/diagnosis ; Liver Diseases/complications/*physiopathology ; Portal Pressure

High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
Causality ; Comorbidity ; Diabetes Complications/diagnosis/epidemiology/physiopathology ; Elastic Modulus ; Elasticity Imaging Techniques/methods/statistics & numerical data ; End Stage Liver Disease/*epidemiology/physiopathology/*ultrasonography ; Fatty Liver/*epidemiology/physiopathology/*ultrasonography ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Incidence ; Liver/physiopathology/ultrasonography ; Liver Cirrhosis/*epidemiology/physiopathology/*ultrasonography ; Male ; Middle Aged ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity

High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
Causality ; Comorbidity ; Diabetes Complications/diagnosis/epidemiology/physiopathology ; Elastic Modulus ; Elasticity Imaging Techniques/methods/statistics & numerical data ; End Stage Liver Disease/*epidemiology/physiopathology/*ultrasonography ; Fatty Liver/*epidemiology/physiopathology/*ultrasonography ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Incidence ; Liver/physiopathology/ultrasonography ; Liver Cirrhosis/*epidemiology/physiopathology/*ultrasonography ; Male ; Middle Aged ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity

OBJECTIVETo investigate the risk factors for and the prognosis of acute kidney injury (AKI) in decompensated cirrhotic patients.

METHODSA total of 126 patients with decompensated cirrhosis and with (n =60) or without (n =66, control group) AKI were enrolled in this retrospective analysis. Follow-up was carried out on all patients, with durations ranging from less than 1 year to up to 4 years. Blood biochemistry, liver and renal functional parameters and prognosis of these patients were recorded. Logistic regression analysis was used to evaluate possible risk factors for decompensated cirrhotic patients developing AKI.

RESULTSThe patients with AKI had a significantly lower survival rate than the patients without AKI (55.0% vs.83.3%, x2 =13.270, p =0.001). Unconditional multivariate logistic regression analysis identified risk factors of AKI development in decompensated cirrhotic patients as increased serum creatinine (odds ratio (OR):1034), increased total bilirubin (OR:1.005), increased international normalized ratio (INR; OR:2.471), decreased plasma sodium concentration (OR:0.910), decreased serum cholinesterase (OR:0.999), and decreased glomerular filtration rate (GFR; OR:0.972) (all P less than 0.05).

CONCLUSIONThe development of acute kidney injury represents an adverse prognosis in decompensated cirrhotic patients. An increase in serum creatinine, total bilirubin or INR or a decrease in plasma sodium concentration, serum cholinesterase or GFR may be early-warning factors of development of AKI in decompensated cirrhotic patients.

Acute Kidney Injury ; diagnosis ; etiology ; Adult ; Case-Control Studies ; Female ; Humans ; Kidney Function Tests ; Liver Cirrhosis ; complications ; physiopathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: Several noninvasive methods have recently been developed for the evaluation of liver fibrosis. The accuracy of transient elastography (TE), acoustic-radiation-force impulse (ARFI) elastography, and real-time elastography (RTE) in predicting liver fibrosis were evaluated. METHODS: Seventy-four patients who had undergone a liver biopsy within the previous 6 months were submitted to evaluation with TE, ARFI, and RTE on the same day. RESULTS: There were significant correlations between fibrosis stage and liver stiffness measurement (LSM) using the three tested methods: TE, r2=0.272, P=0.0002; ARFI, r2=0.225, P=0.0017; and RTE, r2=0.228, P=0.0015. The areas under the receiver operating characteristic curves (AUROC) for the diagnosis of significant fibrosis (> or =F2, Metavir stage) by TE, ARFI, RTE, TE/platelet count (PLT), velocity of shear wave (Vs)/PLT, and elasticity score (Es)/PLT were 0.727, 0.715, 0.507, 0.876, 0.874, and 0.811, respectively. The AUROC for the diagnosis of cirrhosis by TE, ARFI, RTE, TE/PLT, Vs/PLT, and Es/PLT were 0.786, 0.807, 0.767, 0.836, 0.819, and 0.838, respectively. Comparisons of AUROC between all LSMs for predicting significant fibrosis (> or =F2) produced the following results: TE vs. RTE, P=0.0069; ARFI vs. RTE, P=0.0277; and TE vs. ARFI, P=0.8836. Applying PLT, the ability of each LSM to predict fibrosis stage significantly increased: TE/PLT vs. TE, P=0.0004; Vs/PLT vs. ARFI, P=0.0022; and Es/PLT vs. RTE, P<0.0001. However, the ability to predict cirrhosis was not enhanced, combining LSM and PLT. CONCLUSIONS: TE and ARFI may be better methods for predicting significant liver fibrosis than RTE. This predictive ability increased significantly when accounting for platelet count. However, all of the measures had comparable efficacies for predicting cirrhosis.
Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; *Elasticity Imaging Techniques ; Female ; Humans ; Liver/pathology ; Liver Cirrhosis/diagnosis/*physiopathology ; Male ; Middle Aged ; Odds Ratio ; Platelet Count ; Predictive Value of Tests ; ROC Curve ; Serum Albumin/analysis ; Severity of Illness Index

This study was aimed to investigate the imaging features of collateral circulation in Budd-Chiari syndrome (BCS) and hepatitis B related liver cirrhosis (LC) with multi-detector computed tomography (MDCT), and to discuss the value of MDCT in differential diagnosis of Budd-Chiari syndrome and hepatitis B related LC. Sixty cases of LC confirmed by medical history and laboratory examination and 15 cases of BCS proven by histopathology or ultrasonography were recruited in the present study. Morphological changes and anatomic characteristics were assessed with three dimensional (3D) vascular reconstruction of MDCT in all 75 cases. There were significantly more subjects with caudate lobe enlargement in BCS (11 cases, 73%) than in LC (5 cases, 8%). In BCS group, extrahepatic collateral circulation of ascending lumbar and azygous collateral pathways were found in 9 cases and epigastric varicose veins in 8 cases. Intrahepatic venous collaterals were documented in 12 cases combined with ascending lumbar and azygous vein collaterals in 9 cases and retroperitoneal varicose vein plexus in 6 cases. These intra- and extra-hepatic venous collaterals were not dectected in patients with LC. Morphological changes of the caudate lobe and the enhanced pattern of liver parenchyma were significantly different between patients with BCS and LC. Thus, it could be well concluded that contrast-enhanced CT scan and 3D CT angiography are very useful in differential diagnosis of BCS and LC.
Adult ; Angiography ; methods ; Budd-Chiari Syndrome ; diagnostic imaging ; physiopathology ; Collateral Circulation ; physiology ; Diagnosis, Differential ; Female ; Hepatic Veins ; diagnostic imaging ; Hepatitis B ; complications ; Humans ; Liver Cirrhosis ; diagnostic imaging ; physiopathology ; virology ; Male ; Middle Aged ; Multidetector Computed Tomography ; methods ; Young Adult

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan(R)) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.
Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/epidemiology/physiopathology ; Chronic Disease ; *Elasticity Imaging Techniques ; Hepatitis B/drug therapy/physiopathology ; Hepatitis C/drug therapy/physiopathology ; Humans ; Liver Cirrhosis/*diagnosis/ultrasonography ; Liver Neoplasms/epidemiology/physiopathology ; Recurrence