Development of a nomogram for the prediction of acute kidney injury after liver transplantation: a model based on clinical parameters and postoperative cystatin C level.

BACKGROUND: Acute kidney injury (AKI) is common after liver transplantation (LT). We developed a nomogram model to predict post-LT AKI. METHODS: A total of 120 patients were eligible for inclusion in the study. Clinical information was extracted from the institutional electronic medical record system. Blood samples were collected prior to surgery and immediately after surgery. Univariable and multivariate logistic regression were used to identify independent risk factors. Finally, a nomogram was developed based on the final multivariable logistic regression model. RESULTS: In total, 58 (48.3%) patients developed AKI. Multivariable logistic regression revealed four independent risk factors for post-LT AKI: operation duration [odds ratio (OR) = 1.728, 95% confidence interval (CI) = 1.121-2.663, p = 0.013], intraoperative hypotension (OR = 3.235, 95% CI = 1.316-7.952, p = 0.011), postoperative cystatin C level (OR = 1.002, 95% CI = 1.001-1.004, p = 0.005) and shock (OR = 4.002, 95% CI = 0.893-17.945, p = 0.070). Receiver operating characteristic curve analysis was used to evaluate model discrimination. The area under the curve value was 0.815 (95% CI = 0.737-0.894). CONCLUSION: The model based on combinations of clinical parameters and postoperative cystatin C levels had a higher predictive performance for post-LT AKI than the model based on clinical parameters or postoperative cystatin C level alone. Additionally, we developed an easy-to-use nomogram based on the final model, which could aid in the early detection of AKI and improve the prognosis of patients after LT.

Acute kidney injury (AKI) is one of the most common and important complications after liver transplantation (LT).We developed a nomogram model to predict post-LT AKI based on clinical parameters and postoperative cystatin C level.The model based on combinations of clinical parameters and postoperative cystatin C levels had a higher predictive performance, which could aid in the early detection of AKI and improve the prognosis of patients after LT.

Clinical characteristics of liver failure with hemophagocytic lymphohistiocytosis.

Liver failure with hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome with high mortality. The aim of this study was to decipher clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis after definite diagnosis of liver failure and to provide clues for early diagnosis and treatment of HLH in patients with liver failure. Eleven patients diagnosed with liver failure and HLH were retrospectively investigated in this study. All patients presented with jaundice, persistent high-grade fever, pancytopenia, splenomegaly, evidence of hemophagocytes in the bone marrow and laboratory abnormalities indicating HLH. The average interval from the earliest diagnosis of liver failure to a definitive diagnosis of HLH was 17.27 days. Six (54.55%) patients died during follow-up. For patients with liver failure after admission and subsequently definitively diagnosed with HLH, bilirubin and INR were significantly decreased. HLH is definitely diagnosed at an intermediate or late stage when patients have already suffered from liver failure. The initial dose of glucocorticoid (methylprednisolone) was decreased to 1-1.5 mg/kg/d and gradually reduced thereafter. In conclusion, for patients with liver failure, HLH should be screened as early as possible upon persistent fever, splenomegaly and unexplained pancytopenia. For patients with liver failure and HLH, the dosage of glucocorticoid should be reduced to avoid serious side effects.

The assessment of multipotent cell transplantation in acute-on-chronic liver failure: a systematic review and meta-analysis.

Acute-on-chronic liver failure (ACLF) is a serious life-threatening disease with high prevalence. Liver transplantation is the only efficient clinical treatment for ACLF. Because of the rapid progression and lack of liver donors, it is urgent to find an effective and safe therapeutic approach to ACLF. Recent studies showed that multipotent cell transplantation could improve the patients' liver function and enhance their preoperative condition. Cells such as mesenchymal stem cells, bone marrow mononuclear cells and autologous peripheral blood stem cells, which addressed in this study have all been used in multipotent cell transplantation for liver diseases. However, its clinical efficiency is still debatable. This systematic review and meta-analysis explored the clinical efficiency of multipotent cell transplantation as a therapeutic approach for patients with ACLF. A detailed search of the Cochrane Library, MEDLINE, and Embase databases was conducted from inception to November 2017. The outcome measures were serum albumin, prothrombin time, alanine aminotransferase, total bilirubin, platelets, hemoglobin, white blood cells, and survival time. The quality of evidence was assessed using GRADEpro and Jaded scores. A literature search resulted in 537 citations. Of these, 9 articles met the inclusion criteria. It was found that multipotent cell transplantation was able to alleviate liver damage and improve liver function. Multipotent cell transplantation can also enhance the short-term and medium-term survival rates of ACLF. All 9 research articles included in this analysis reported no statistically significant adverse events, side effects, or complications. In conclusions, this study suggested that multipotent cell transplantation could be recommended as a potential therapeutic supplementary tool in clinical practice. However, clinical trials in large-volume centers still needed.

Clinical performance of stem cell therapy in patients with acute-on-chronic liver failure: a systematic review and meta-analysis.

BACKGROUND: Stem cell therapy has been applied in the treatment of acute-on-chronic liver failure (ACLF). However, its clinical efficiency is still debatable. The aim of this systematic review and meta-analysis is to evaluate the clinical efficiency of stem cell therapy in the treatment of ACLF. METHODS: The Cochrane Library, OVID, EMBASE, and PUBMED were searched to December 2017. Both randomized and non-randomized studies, assessing stem cell therapy in patients with ACLF, were included. The outcome measures were total bilirubin (TBIL), alanine transaminase (ALT), international normalized ratio (INR), albumin (ALB), and the model for end-stage liver disease (MELD) score. The quality of evidence was assessed by GRADEpro. RESULTS: Four randomized controlled trials and six non-randomized controlled trials were included. The TBIL levels significantly decreased at 1-, 3-, 12-month after the stem cell therapy (p = 0.0008; p = 0.04; p = 0.007). The ALT levels decreased significantly compared with the control group in the short-term (p < 0.00001). There was no obvious change in the INR level compared with the control groups (p = 0.64). The ALB levels increased markedly as compared with the control groups (p < 0.0001). The significant difference can be found in MELD score between stem cell therapy and control groups (p = 0.008). Further subgroup analysis for 3-month clinical performance according to the stem cell types have also been performed. CONCLUSION: This study suggests that the clinical outcomes of stem cell therapy were satisfied in patients with ACLF in the short-term. MSCs may be better than BM-MNCs in the stem cells transplantation of ACLF. However, more attention should focus on clinical trials in large-volume centers.

Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma.

This study aimed to determine if the immunoscore (IS) staging system would be a potential prognostic factor in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) in China.IS was performed in a consecutive cohort of HBV-HCC patients (n= 92). CD3+, CD8+, and CD45RO+ T cells were quantified by immunohistochemical analyses. The patients were stratified into 5 IS groups: I0, I1, I2, I3, I4 for every 2 cell phenotypes (IS1 (CD8/CD45RO, IS2 (CD3/CD8), and IS3 (CD3/CD45RO), respectively. ImagePro Plus software was used in the calculation of the paraffin-embedded tumor sections.The staining of CD3+, CD8+, and CD45RO+ cells in the HBV-HCC tissue demonstrated that there were higher density and larger area of lymphocytes in the invasive margins (IM) region than in the center (CT). Univariate analysis showed that preoperative TNM staging (P = .01), serum gamma-glutamyl transpeptidase (GGT) level (P = .03), vascular invasion (P = .00), and density of CD3+T (CT) (P = 0.01) were correlated significantly with disease-free survival (DFS); serum alpha-fetoprotein (AFP) level (P = .02), tumor size (P = .00), serum cholinesterase (CHE) (P = .04), and GGT level (P = .01), density of CD3+T(CT) (P = .00), CD8+T(CT)(P = .00), CD45RO+T(CT) (P = .00), and CD45RO+T (IM) (P = .02) were correlated with overall survival (OS). Multivariate analysis showed that TNM staging was not an independent prognostic factor of DFS and OS. Our results showed ISs did not have a significantly correlation with DFS (P = .35, .19, and .07, respectively), but it was correlated significantly with OS (P = .00, .00, and .00, respectively). There were statistical differences among the OS of every ISs subgroup except I0 and I1 by the Cox regressions analysis.The IS staging was closely related to the outcome of patients. It can compensate the TNM tumor classification system in predicting the prognosis of HBV-HCC patients.

Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

MicroRNAs (miRNAs) represent a class of evolutionarily conserved, non-coding small RNAs (18-25 nt) that have emerged as master regulators of several biological processes. Recently, circulating miRNAs have also been reported to be promising biomarkers for various pathological conditions. In the present study, we report the comparative expression profiling of microRNA-101 (miR-101) in serum and tissue samples from chronic hepatitis B (CHB), HBV-associated liver cirrhosis (HBV-LC), and HBV-associated hepatocellular carcinoma (HBV-HCC) patients and healthy controls. The serum miR-101 levels were found to be significantly downregulated in the HBV-HCC patients compared with the HBV-LC patients (P<0.001), CHB patients (P<0.001) and healthy controls but were upregulated in the HBV-LC patients compared with the CHB patients (P<0.001) and healthy controls (P<0.001). Consistent with the serum data, the expression of miR-101 was also upregulated and downregulated in the HBV-LC and HBV-HCC tissue samples, respectively. A receiver operating characteristic (ROC) analysis of serum miR-101 yielded an area under the ROC curve (AUC) of 0.976 with 95.5% sensitivity and 90.2% specificity when differentiating between HBV-HCC and HBV-LC. Our results suggest that the serum miR-101 level can serve as a potential non-invasive biomarker to differentiate HBV-HCC from HBV-LC.

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy.

Acute-on-chronic liver failure (ACLF) is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells (mDCs) and the efficacy of methylprednisolone (MP) treatment for hepatitis B virus (HBV)-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at 10-day intervals; 26 patients received conservative medical (CM) management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

[Correlation research of isolated liver tissue pathology and clinical diagnosis in patients with chronic severe hepatitis B].

To study the coincidence rate of clinical diagonisis with pathological diagnosis for chronic severe hepatitis, and to screen out clinical indicators consistent with pathological diagnosis. Fifty-one patients diagnosed as chronic severe hepatitis and underwent liver transplantation in Beijing You'an hospital from November 2004 to June 2009 participated in this study. The clinical data were selected as following: ALT, AST, urea nitrogen, creatinine, glucose, cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase, serum potassium, serum sodium, prothrombin activity and blood ammonia level. The width of the portal vein and splenic vein thickness were measured by color Doppler ultrasound and were compared in different groups. Data were ananlyzed with independent sample t test and F test. The coincidence rate between clinical and pathological diagnoses in this study was 64.7%. ALT and AST levels for Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L, 67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0 U/L (P is less than to 0.01) respectively, with statistically significant difference existed. The mean level of ALT in Chronic severe hepatitis group was significantly different in the situations of onset less than 30 days or more than 30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to 0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The coincidence rate of clinical with pathological diagnoses for Chronic Severe Hepatitis was low, increased ALT and AST levels would help improve the diagnostic accuracy.

Resting energy expenditure and substrate metabolism in patients with acute-on-chronic hepatitis B liver failure.

GOALS: This study was designed to characterize the energy metabolism in the patients with acute-on-chronic liver failure (ACLF). BACKGROUND: Protein-energy malnutrition usually occurs in the patients with chronic liver disease and is exacerbated during the progression of liver failure. Unfortunately, there is limited study to fully elucidate the energy metabolism in the patients with ACLF. STUDY: A retrospective cohort was designed with a total of 282 patients (100 patients with ACLF, 100 with liver cirrhosis, and 82 with chronic hepatitis B). Resting energy expenditure and the oxidation rates of glucose, lipid, and protein were assessed by indirect heat measurement using the critical care monitor and desktop analysis system, nutritive metabolic investigation system. Survival rate was estimated with the Kaplan-Meier method. RESULTS: There was no significant difference in resting energy expenditure among the patients with ACLF, the liver cirrhosis, and the chronic hepatitis (1402.05±480.07 kcal/d in patients with ACLF, 1274.27±316.36 kcal/d in patients with liver cirrhosis, and 1396.77±384.80 kcal/d in patients with chronic hepatitis). Respiratory quotient (RQ) was significantly lower in the patients with ACLF than those in the liver cirrhosis and the chronic hepatitis B (P=0.000). In patients with ACLF, RQ of the nonsurvival group was significantly lower than the survival group (P=0.000). It is identified from receiver operating characteristic curve analysis that a RQ cutoff value of 0.83 (area under the receiver operating characteristic curve, 0.760) is favorable to predict good prognosis in patients with liver failure, which has a sensitivity of 73.68%, a specificity of 74.42%, and positive predictive value of 79.2% and negative predictive value of 68.1%. CONCLUSIONS: In patients with ACLF, RQ was significantly lower in the nonsurvival group than the survival group, thus suggesting that RQ may be used as an indicator of prognosis of liver failure.