CT radiomics for noninvasively predicting NQO1 expression levels in hepatocellular carcinoma.

Using noninvasive radiomics to predict pathological biomarkers is an innovative work worthy of exploration. This retrospective cohort study aimed to analyze the correlation between NAD(P)H quinone oxidoreductase 1 (NQO1) expression levels and the prognosis of patients with hepatocellular carcinoma (HCC) and to construct radiomic models to predict the expression levels of NQO1 prior to surgery. Data of patients with HCC from The Cancer Genome Atlas (TCGA) and the corresponding arterial phase-enhanced CT images from The Cancer Imaging Archive were obtained for prognosis analysis, radiomic feature extraction, and model development. In total, 286 patients with HCC from TCGA were included. According to the cut-off value calculated using R, patients were divided into high-expression (n = 143) and low-expression groups (n = 143). Kaplan-Meier survival analysis showed that higher NQO1 expression levels were significantly associated with worse prognosis in patients with HCC (p = 0.017). Further multivariate analysis confirmed that high NQO1 expression was an independent risk factor for poor prognosis (HR = 1.761, 95% CI: 1.136-2.73, p = 0.011). Based on the arterial phase-enhanced CT images, six radiomic features were extracted, and a new bi-regional radiomics model was established, which could noninvasively predict higher NQO1 expression with good performance. The area under the curve (AUC) was 0.9079 (95% CI 0.8127-1.0000). The accuracy, sensitivity, and specificity were 0.86, 0.88, and 0.84, respectively, with a threshold value of 0.404. The data verification of our center showed that this model has good predictive efficiency, with an AUC of 0.8791 (95% CI 0.6979-1.0000). In conclusion, there existed a significant correlation between the CT image features and the expression level of NQO1, which could indirectly reflect the prognosis of patients with HCC. The predictive model based on arterial phase CT imaging features has good stability and diagnostic efficiency and is a potential means of identifying the expression level of NQO1 in HCC tissues before surgery.

Development and validation of a nomogram model for predicting chronic kidney disease after liver transplantation: a multi-center retrospective study.

Chronic kidney disease (CKD) is a frequent complication after liver transplantation (LT) and associated with poor prognosis. In this study, we retrospectively analyzed 515 adult patients who underwent LT in our center. They were randomly divided into a training set (n = 360) and an internal test set (n = 155). Another 118 recipients in other centers served as external validation set. Univariate and multivariate COX regression analysis were used to determine risk factors. A nomogram model was developed to predict post-LT CKD. The incidence of post-LT CKD in our center was 16.9% (87/515) during a median follow-up time of 22.73 months. The overall survival of recipients with severe CKD (stage IV and V) were significantly lower than those with non or mild CKD (stage III) (p = 0.0015). A nomogram model was established based on recipient's age, anhepatic phase, estimated glomerular filtration rate and triglyceride levels at 30 days after LT. The calibration curves for post-LT CKD prediction in the nomogram were consistent with the actual observation in both the internal and external validation set. In conclusion, severe post-LT CKD resulted in a significantly reduced survival in liver recipient. The newly established nomogram model had good predictive ability for post-LT CKD.

Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. METHODS: A total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate (P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794-0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models (P < 0.001). CONCLUSIONS: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

Prediction model based on blood urea nitrogen and the leukocyte count for intestinal necrosis in patients with portal vein system thrombosis: a retrospective study.

BACKGROUND: Portal vein system thrombosis (PVST) is a serious and potentially fatal disease. No definite parameter can predict intestinal necrosis in patients with PVST to justify early surgical intervention. The current study aimed to explore a simple and accurate model to predict the occurrence of intestinal necrosis in patients with PVST. METHODS: Records of patients admitted to our emergency department with PVST from January 2010 to October 2018 were reviewed. Clinical parameters, including patient history, physical examination, and the results of laboratory investigations, were analyzed. RESULTS: Sixty-nine patients (27 females) were included. All patients were admitted to our emergency department because of abdominal pain. Fourteen patients required exploratory laparotomy, and intestinal necrosis was confirmed. Seven patients received thrombolytic therapy, and the other 48 patients had completed anticoagulation successfully. According to multivariate logistic regression, high blood urea nitrogen (BUN) (OR: 1.413, P=0.048) and the leukocyte count (OR: 1.180, P=0.005) were associated with intestinal necrosis, and a prediction model for intestinal necrosis (PMIN) based on the BUN and leukocyte count was established. CONCLUSIONS: The PMIN score could effectively predict intestinal necrosis in patients with PVST.

Silencing of microRNA-375 affects immune function in mice with liver failure by upregulating astrocyte elevated gene-1 through reducing apoptosis of Kupffer cells.

This study aims to investigate how microRNA-375 (miR-375) improves immune function by regulating liver macrophages (Kupffer cells) in mice with liver failure. Forty mice were divided into ConA-1h, ConA-3h, ConA-6h, and control groups, with 10 mice in each group. Mice models of liver failure were established by injecting concanavalin A (ConA) solution via the tail veins of mice, and then primary Kupffer cells were isolated and cultured. Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay were conducted to examine the expressions of miR-375, astrocyte elevated gene-1 (AEG-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1ß in Kupffer cells of mice with liver failure as well as after silencing of miR-375. Flow cytometry was used to determine cell apoptosis. During the liver failure process, miR-375, IL-6, TNF-α, and IL-1ß expressions were increased over time, while AEG-1 expression decreased over time in the control, ConA-1h, ConA-3h, and ConA-6h groups. Opposite alternations were observed after silencing of miR-375. Dual-luciferase reporter gene assay showed that AEG-1 was a target gene of miR-375. Flow cytometry determination showed that the ratio of apoptotic Kupffer cells decreased after silencing of miR-375. Overexpression of AEG-1 could rescue the suppression of IL-6, TNF-α, and IL-1ß expressions in Kupffer cells after the short-term induction of ConA and further inhibit cell apoptosis. Our study provides evidence that miR-375 could regulate Kupffer cells to improve immune function in mice with liver failure.

Acute Liver Allograft Rejection After Living Donor Liver Transplantation: Risk Factors and Patient Survival.

BACKGROUND: Acute rejection (AR) is an important problem after liver transplantation. We aim to evaluate the incidence and risk factors of AR and to identify significant prognostic factors that can influence posttransplant survival in living donor liver transplantation. METHODS: A retrospective database of 169 consecutive adult patients who underwent living donor liver transplantation from June 2001 to August 2015 was reviewed. The patients were divided into an AR group and nonAR group. The clinical data of the 2 groups were compared. RESULTS: The median follow-up time for this study was 90.7 months (range: 0.03-124.9 months). Twenty five (14.8%) patients developed AR with a median period of 158 days (3-1,975 days) after transplantation. A multivariate analysis revealed that high posttransplant model for predicting mortality score (hazard ratio, [HR] = 3.462; P = 0.023) was an independent risk factor for AR. Multivariate analysis was used to evaluate factors that influenced the overall survival and revealed that ABO-incompatibility (HR = 2.702; P = 0.01) and patient age ≥50 years (HR = 1.733; P = 0.045) were independent prognostic factors for overall survival after living donor liver transplantation. CONCLUSIONS: Higher posttransplant model for predicting mortality score was associated with AR after living donor liver transplantation. ABO-incompatibility and patient age ≥50 years were independent prognostic factors for overall survival.

Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial.

More sensitive biomarker is urgently needed to reduce the mortality caused by the worldwide prevalent liver cancer. This study aims to assess whether quantitative measurement of heat shock protein 90alpha (Hsp90α) in plasma can improve the diagnosis accuracy and monitor treatment response of liver cancer patients. We analyzed the data from an official (registered at ClinicalTrial.gov: NCT02324127), large-scale (1647 enrollments), and multicenter (three independent hospitals) clinical trial, which quantitatively measured plasma Hsp90α by ELISA for patients with liver cancer, patients with at-risk liver diseases (including hepatitis, liver cirrhosis, focal nodular hyperplasia), and healthy individuals. Diagnostic performance of plasma Hsp90α was evaluated by the calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). ROC curve showed plasma Hsp90α can discriminating liver cancer with a sensitivity of 92.7% and specificity of 91.3% from non-liver cancer control. Similar results were noted in detecting early-stage liver cancer (sensitivity 91.4%, specificity 91.3%). In a parallel study compared with AFP20, plasma Hsp90α exhibited a significantly higher diagnostic performance (sensitivity 93.3% vs 61.1%) in discriminating hepatocellular carcinoma (HCC) from the control. Furthermore, plasma Hsp90α measurement maintained distinctly excellent diagnostic accuracy in distinguishing AFP-negative HCC patients (sensitivity 93.9%, specificity 91.3%) and AFP-limited liver cancer (sensitivity 96.6%, specificity 90.3%). In the efficacy monitoring study, levels of plasma Hsp90α were dramatically decreased after surgery (P=0.005), and correlated significantly with tumor size during interventional therapy (P≤0.05). These findings highlight that plasma Hsp90α as a biomarker for the diagnosis of liver cancer, and can be used to evaluate the therapeutic efficacy of liver cancer patients underwent surgery, or interventional therapy.

The phospholipase A2 activity of peroxiredoxin 6 promotes cancer cell death induced by tumor necrosis factor alpha in hepatocellular carcinoma.

In this study, we used proteomic profiling to compare hepatocellular carcinoma (HCC) and peri-tumoral tissues to identify potential tumor markers of HCC. We identified eight differentially expressed proteins (>3-fold), including Peroxiredoxin 6 (PRDX6). PRDX6 is a bifunctional enzyme with both peroxidase and calcium-independent phospholipase A2 (iPLA2) activity. We found that peri-tumoral tissues expressed higher levels of PRDX6 mRNA (n = 59, P = 0.018) and protein (n = 265, P < 0.001) than HCC tissues, and that decreased expression of PRDX6 in HCC tissues was an independent risk factor indicating a poor prognosis (n = 145, P = 0.007). Combining the examination of serum PRDX6 with α-fetoprotein improved the diagnostic sensitivity of tests for HCC compared to α-fetoprotein alone (85.0% vs 50.0%, n = 40). We found that PRDX6 induced S phase arrest in HCC cells and inhibited HCC tumorigenicity in mice injected with cancer cells. When treated with H2 O2 , PRDX6 inhibited apoptosis. When treated with tumor necrosis factor alpha (TNF-α), PRDX6 promoted apoptosis. Inhibition of iPLA2 activity of PRDX6 decreased the apoptosis induced by TNF-α. In conclusion, PRDX6 inhibited the carcinogenesis of HCC, and the iPLA2 activity of PRDX6 promoted cancer cell death induced by TNF-α. © 2015 Wiley Periodicals, Inc.

Inflammatory pseudotumor mimicking primary hepatic malignant tumor with hepatitis B virus-related cirrhosis: A case report.

Inflammatory pseudotumors (IPT) of the liver are fairly uncommon lesions. IPTs are difficult to diagnose due to the absence of specific symptoms. The correct diagnosis is easily missed, particularly in livers with hepatitis B virus (HBV)-related cirrhosis. The current study presents the case of a 58-year-old male with a ten-year history of HBV infection, who was diagnosed with a primary liver tumor by computed tomography (CT) and magnetic resonance imaging (MRI). The α-fetoprotein levels ranged within normal limits. A local resection was performed and the histopathological analysis identified IPT of the liver. The patient recovered well following surgery.

Chronic cholecystitis with hilar bile duct stricture mimicking gallbladder carcinoma on positron emission tomography: A case report.

Thickening of the gallbladder wall is observed in patients with gallbladder carcinoma, as well as in those with chronic cholecystitis. It is difficult to distinguish between benign and malignant gallbladder wall thickening with conventional diagnostic imaging techniques, such as abdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), particularly in patients with bile duct strictures. Currently, the fluorine-18 2-fluorodeoxyglucose positron emission tomography/CT (F-18 FDG PET/CT) scan is widely used in the differentiation of cholecystitis from gallbladder carcinoma. However, the F-18 FDG PET/CT scan may also be responsible for false-positive diagnosis. This case report focuses on a 74-year-old male who presented with thickening of the gallbladder wall and hilar bile duct stricture, originally misdiagnosed as gallbladder carcinoma by US and MRI. F-18 FDG PET/CT also demonstrated increased activity. This case was ultimately proven to be chronic cholecystitis by postoperative pathological examination and it is presented in order to emphasize the significance of considering the possibility of false-positive diagnosis by PET/CT, as a result of inflammatory lesions. Therefore, PET/CT should not be considered the gold standard for the discrimination between benign and malignant gallbladder wall thickening.

An effective model for predicting acute kidney injury after liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication in the early period after liver transplantation (LT), posing an enormous obstacle to treatment efficiency and patient survival. However, the exact influencing factors of AKI are still unclear and a predictive model is desperately required in the clinic. METHODS: Data of 102 consecutive LTs were reviewed. A model for predicting AKI was established and further validated in a prospective study of 44 patients receiving LT. RESULTS: The incidence of AKI was 32.4%. AKI patients showed a significantly lower survival rate than non-AKI patients. Multivariate analysis demonstrated the independent influencing factors of AKI were preoperative serum creatinine >1.2 mg/dl, intraoperative urine output

Outcome of patients with hepatorenal syndrome type 1 after liver transplantation: Hangzhou experience.

BACKGROUND: Patients with hepatorenal syndrome (HRS) type 1 have an extremely poor prognosis. Liver transplantation (LT) is the only treatment that can cure terminal stage liver disease and reverse HRS. However, the data showing the impact of LT on patients with HRS type 1 are limited. METHODS: The outcome and prognostic factors of 32 patients with HRS type 1 receiving LT were investigated. The natural course of renal recovery and the efficacy of continuous post-LT veno-veno hemodialysis (CVVH) were also evaluated. RESULTS: Overall patient mortality was 34.4% (11/32), with eight patients died during the first month after LT. Scoring model was based on independent prognostic factors for the model end-stage liver diseases (MELD) (risk ratio=1.169) and serum sodium (risk ratio=0.769). High MELD score (>36) or low serum sodium (< or =126 mEq/L) or both were associated with reduced patient survival. HRS was resolved in 30 patients (median time, 24 days). Eight patients received post-LT CVVH. The need for CVVH was associated with higher pretransplant serum creatinine, longer duration of HRS, more pretransplant CVVH, more intraoperative blood products infusion, lower intraoperative urine output, and higher serum creatinine at 1 week posttransplant. However, serum creatinine at 1 month posttransplant and patient survival did not differ significantly between patients with and without CVVH. CONCLUSION: Patients developing HRS type 1 in the absence of high MELD score and low serum sodium would benefit from LT.

Hepatoprotective effects of marine and kuhuang in liver transplant recipients.

We aimed to assess the effects of traditional Chinese medicine; marine (MT) and kuhuang (KH), either alone or in combination, on the early graft function of the recipients and overall patient survival rate after liver transplantation (LT) by using diammonium glycyrrhizinate (DG) as a positive control. A total of 151 subjects undergoing LT were included in this prospective study. According to the different regimens given in the first two post-transplant weeks, they were divided into DG group (n = 49), DG + KH group (n = 36), MT group (n = 42) and MT + KH group (n = 24). The graft function in the early post-transplant period and patient survival rate were examined. During the first two post-transplant weeks, there was no significant difference in total bilirubin, alanine transaminase, aspartate transaminase, serum creatinine, and prothrombin time between MT group and DG group. Patient survivals in these two groups were also similar. Compared to DG group, DG + KH group showed a significantly lower total bilirubin value on post-transplant day 5 (3.2 +/- 2.1 mg/dL vs. 5.7 +/- 5.6 mg/dL, p < 0.01) and day 7 (2.8 +/- 1.8 mg/dL vs. 5.8 +/- 6.1 mg/dL, p < 0.01), and higher patient survival. There was no significant difference between DG + KH group and MT + KH group. In conclusion, MT provides an alternative to DG after LT. The combination of MT and KH is highly effective in decreasing the total blirubin in the early post-transplant period and improving patient survival.

Post-transplant diabetes mellitus in liver transplantation: Hangzhou experience.

BACKGROUND: Diabetes mellitus (DM) is a frequent and serious complication in patients with liver diseases. We aimed to assess the prevalence and consequences of post-transplant DM (PTDM) in Chinese patients with HBV-related liver diseases and to determine the possible risk factors. METHODS: Altogether 165 patients with HBV infection and undergoing cadaveric related liver transplantation (LT) were enrolled. The clinical data of patients with (PTDM group) and without PTDM (non-PTDM group) were compared. RESULTS: Of the 165 patients, 28 had DM and 12 had impaired fasting glucose (IFG) before LT. Patients with pre-transplant DM or IFG had a survival rate similar to that of the others. Forty patients (24.2%) developed PTDM with a mean time of 36+/-17 days (range 2-300 days) after LT. Of those, 32 developed PTDM within 3 months post-LT and 29 needed insulin treatment. Pre-transplant hepatic encephalopathy and tacrolimus application were found more frequently in the PTDM group than in the non-PTDM group. The plasma tacrolimus levels were notably higher at 1 and 3 months post-LT in the PTDM group than those in the non-PTDM group. Compared to the non-PTDM group, the PTDM group showed remarkably poorer survival and tumor-free survival in patients with hepatocellular carcinoma, and significantly higher incidence of sepsis, fungal infection, chronic kidney diseases and biliary complications after LT. CONCLUSIONS: Pre-transplant DM did not affect the patient survival after LT. Since PTDM is common, it has a negative impact on outcome and may contribute to tumor recurrence. Pre-transplant hepatic encephalopathy, a tacrolimus-based regimen, and high levels of tacrolimus are clearly associated with the occurrence of PTDM.