Liver Function Grade Research Articles

Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study.

Changes in alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) levels in patients with primary liver cancer (PLC) after radiofrequency ablation (RFA). Hepatocellular carcinoma is a malignant tumor with high incidence worldwide. As a common local treatment, RFA has attracted much attention for its efficacy and influence on liver function. To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA. The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected. The chi-square test was used to compare the data between groups. The Kaplan-Meier method and Cox regression were used to analyze the associations between serum ALP and GGT levels and overall survival, progression-free survival (PFS) and clinical characteristics of patients before treatment. The 1-year survival rates of patients with normal (≤ 135 U/L) and abnormal (> 135 U/L) serum ALP before treatment were 91% and 79%, respectively; the 2-year survival rates were 90% and 68%, respectively; and the 5-year survival rates were 35% and 18%, respectively. The difference between the two groups was statistically significant (P = 0.01). Before treatment, the 1-year survival rates of patients with normal serum GGT levels (≤ 45 U/L) and abnormal serum GGT levels (> 45 U/L) were 95% and 87%, the 2-year survival rates were 85% and 71%, and the 5-year survival rates were 37% and 21%, respectively. The difference between the two groups was statistically significant (P < 0.001). Serum ALP [hazard ratio (HR) = 1.766, 95% confidence interval (95%CI): 1.068-2.921, P = 0.027] and GGT (HR = 2. 312, 95%CI: 1.367-3.912, P = 0.002) is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor. The 1-year PFS rates were 72% and 50%, the 2-year PFS rates were 52% and 21%, and the 5-year PFS rates were 14% and 3%, respectively. The difference between the two groups was statistically significant (P < 0001). The 1-year PFS rates were 81% and 56% in patients with normal and abnormal serum GGT levels before treatment, respectively; the 2-year PFS rates were 62% and 35%, respectively; and the 5-year PFS rates were 18% and 7%, respectively, with statistical significance between the two groups (P < 0.001). The serum ALP concentration (HR = 1. 653, 95%CI: 1.001-2.729, P = 0.049) and GGT (HR = 1.949, 95%CI: 1.296-2.930, P = 0.001) was closely associated with PFS after RFA in patients with PLC. The proportion of male patients with abnormal ALP levels is high, the Child-Pugh grade of liver function is poor, and the incidence of ascites is high. Among GGT-abnormal patients, the Child-Pugh grade of liver function was poor, the tumor stage was late, the proportion of patients with tumors ≥ 5 cm was high, and the incidence of hepatic encephalopathy was high. Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA, and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

O255: Is a low calorie "liver shrinking" diet predictive of long term weight loss and metabolic improvement after sleeve gastrectomy?

Abstract Introduction Limited evidence exists regarding pre-operative “liver shrinking” diet, but a two-week period of low calorie diet (LCD) is mandated before bariatric surgery, with weight outcomes rarely measured. Longer periods of LCD can ameliorate obesity, diabetes and metabolic-associated-fatty-liver disease (MAFLD). Primary aim to determine if response to LCD is predictive of long-term weight loss. Secondary aim to determine if alteration in liver function, and MAFLD, correlate with weight change after diet/ in follow up. Methodology Patients undergoing sleeve gastrectomy recruited and weight, blood plasma and 16S rRNA faecal microbiome profile recorded at baseline, following two-week LCD and at six-months, with liver biopsy at surgery (6). Results First nine patients had median baseline BMI 47.3kg/m2, and 34.7 kg/m2 at 6-months (-12.3kg/m2). Median excess weight loss was 8.6% (6.35kg) after LCD and 47.57% (34.65kg) at 6-months. Spearman’s Rank Correlation was weakly positive (0.5) for absolute weight loss between LCD and follow up, and was 0.25 using excess weight loss (non-significant). Change in liver function and MAFLD grade did not correlate with weight loss following LCD and at 6-months. Conclusions Weight loss response to LCD correlated poorly with long-term weight loss (analysing by absolute/ excess weight). Liver health and MAFLD did not predict 6-month weight loss. A dramatic response to LCD may not manifest in longer term metabolic improvement after surgery. We will also report on faecal microbiome; it appears more complex mechanisms underpin weight change and response to dietary manipulation in the surgical cohort than can be extrapolated from population studies.

Clinical Analysis of 128 Children and Adolescents with Echinococcosis

Objective: To comprehend the clinical characteristics and treatment approaches for children and adolescents in Qinghai Province with two types of echinococcosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE). Methods: A total of 128 pediatric inpatients with echinococcosis at the People’s Hospital of Qinghai Province and the Clinical Research Institute of Echinococcosis of Qinghai Province between January 2016 and December 2021 were chosen as subjects. Demographic and clinical data were collected, and double data entry was executed using EpiData 3.02. Factors influencing the cure of echinococcosis were analyzed with echinococcosis cure as the dependent variable, employing statistical analysis via SPSS 19.0. Results: Of the cases, 35.9% had CE, and 64.1% had AE. Both types were observed in patients of all ages, with the majority aged 13–18. The number of cysts and their sizes varied between CE and AE. Complications were prevalent, including liver, gallbladder, lung, and nutritional complications. Univariate analyses revealed significant differences in outcomes based on factors such as cyst size (for CE), liver function grade (for AE), hydatid hypersensitivity test, operation, and length of hospital stay (P &lt; 0.05). Conclusion: This comprehensive analysis of hospitalized cases sheds light on the clinical data of echinococcosis in children and adolescents in Qinghai Province. The findings contribute to a scientific foundation for formulating effective prevention and control measures tailored to this demographic, facilitating an improved understanding of echinococcosis in Qinghai province.

Evaluation of Liver Functionality after Liver Stereotactic Body Radiation Therapy (SBRT) Using Blood Tests and Imaging Examinations

Several studies have shown that liver function can be evaluated after hepatic stereotactic body radiation therapy (SBRT) using galactosyl human serum albumin (GSA) liver scintigraphy and Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). However, there are no reports investigating the relationship (including Chile-Pugh classification) between imaging and blood tests. Therefore, we investigated the changes that occur in the liver between before and after SBRT by combining imaging (GSA, computed tomography (CT), and MRI) with blood tests that assess total liver function (albumin-bilirubin (ALBI) grade, ICG-R15). We decided to find a method that could assess liver reserve capacity locally and globally MATERIALS/METHODS: Of the 23 patients who underwent hepatic SBRT, 12 patients underwent GSA, MRI, and ICG-R15 testing before treatment, 1 month after treatment, and 3 months after treatment. All patients underwent imaging studies and blood tests at the beginning of treatment, 1 month after treatment, and 3 months after treatment ended. The evaluation items were as follows: 1) changes over time in Child-Pugh classification, ICG-R15, and ALBI values before and after SBRT; 2) changes over time in GSA count and ICG; and 3) selection of the optimal sequence for recognizing radiation hepatitis on MRI. The ICG values were 14.4 before RT, 17.1 after 1 month, and 17.6 after 3 months. ICG worsened after 1 month of treatment, but was similar after 3 months. ALBI values were -2.61 before RT, -2.67 after 1 month, and -2.71 after 3 months. ALBl worsened slightly over time. Regarding the ICG-R15, there was an average worsening of 2.8 after 1 month of treatment compared with before SBRT, but only of 0.5 between 1 month and 3 months after SBRT. Therefore, evaluation using ICG-R15 after SBRT after 1 month alone may be sufficient.

Symptom aggravation after withdrawal of metal chelating agent therapy in patients with Wilson's disease.

To study the aggravation of clinical symptoms after discontinuation of metal chelating agent therapy in Wilson's disease (WD) patients, analyze the causes of aggravation, and observe the prognosis. 40 WD patients (cerebral type 30 cases and hepatic type 10 cases) who stopped using metal chelating agent were selected, 40 WD patients with normal therapy, and 10 normal control cases were selected. All patients underwent neurological symptom evaluation using modified Young scale, Child-Pugh liver function grading, metal metabolism, and disease typing. Magnetic sensitivity imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy imaging (MRS) were performed. According to the imaging results, WD patients were divided into metal deposition stage, fiber damage stage, and neuron necrosis stage. All patients were treated with metal chelating agent for 6 months. The score of modified Young scale in drug withdrawal group was lower than that in normal treatment group before drug withdrawal (p=.032). The score of modified Young scale was higher after drug withdrawal than before (p=.011). The number of Child-Pugh B-grade patients after drug withdrawal was more than that before drug withdrawal and in normal treatment group. The proportion of patients in the stage of neuronal necrosis after drug withdrawal (25%) was higher than that before drug withdrawal (10%) (p=.025). After drug withdrawal, urine copper was significantly higher than that before drug withdrawal and in the normal treatment group (p=.032, .039). After the withdrawal group resumed metal chelating agent treatment, 34.2% of neurological symptoms worsened. WD patients showed neurological symptoms aggravation and increased liver injury after metal chelating agent withdrawal. Increased metal deposition and new nerve injury occurred in the brain. After re-treatment, the aggravated neurological symptoms of WD patients are difficult to reverse.

Evaluation of liver function using Gd-EOB-DTPA-enhanced MRI with T1 mapping

PurposeTo evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function.MethodsSeventy-two patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions at Beijing Friendship Hospital from August 2020 to March 2022 were prospectively enrolled, and variable-flip-angle T1 mapping was performed before and 20 min after enhancement. The Child–Pugh (C-P) score and albumin-bilirubin (ALBI) grade of liver function were assessed using the clinical data of the patients. Correlation analysis was used to evaluate the correlation between T1 mapping parameters and liver function grading and laboratory tests. Nonparametric tests were used to compare the differences among different liver function groups. The liver function classification efficiency of each image index was evaluated with receiver operating characteristic (ROC) curves.ResultsT1post was positively correlated with the C-P grade and the ALBI grade (r = 0.717 and r = 0.652). ΔT1 was negatively correlated with the C-P grade and the ALBI grade (r = -0.790 and r = -0.658). T1post and ΔT1 significantly differed among different liver function grades (p < 0.05). For the C-P grade, T1post and ΔT1 were significantly different between each pair of groups (p < 0.05), and ΔT1 had a better diagnostic efficiency than T1post. For the ALBI grade, ΔT1 and T1post were significantly different between the NLF and ALBI1 groups (p < 0.05), and ΔT1 had a better diagnostic efficacy than T1post. T1post significantly differed between the ALBI1 and ALBI2 + 3 groups (p < 0.05), while ΔT1 had a weak ability to differentiate between these two groups.ConclusionT1post and ΔT1 were strongly correlated with the two liver function grades and can be noninvasive imaging indexes for evaluating liver function.

Hepatic Steatosis in Spinal Muscular Atrophy: Evidence for a Primary Hepatic Defect and Implications (S33.009)

<h3>Objective:</h3> To investigate evidence of hepatic steatosis in patients with spinal muscular atrophy (SMA) and SMA patient-derived induced pluripotent stem cell (iPSC) models of disease. <h3>Background:</h3> SMA is generally regarded as a motor neuron disease but increasing evidence of extra-neuronal manifestations suggest that these may become future co-morbidities when lifespan is prolonged. Hepatocellular microsteatosis has been noted in mouse models and pediatric autopsies, but it is unclear whether this is a primary defect from hepatocyte Survival Motor Neuron (SMN) deficiency or secondary to muscle denervation. <h3>Design/Methods:</h3> We retrospectively analyzed clinical data from a single center cohort of pediatric and adult SMA patients without liver disease who received hepatic sonography or fibroscan. Sonographic/fibroscan steatosis grade and serum markers of liver function were reviewed. In parallel, we differentiated Type 0–3 SMA patient iPSCs into hepatocytes (iHeps) and analyzed lipid accumulation and markers of hepatocyte function compared to wild-type (WT). We CRISPR edited a SMA Type 1 iPSC line to derive isogenic carrier (1 SMN1, 1 SMN2) and isogenic WT lines (2 SMN1) and analyzed the isolated effect of SMN deficiency on iHeps. <h3>Results:</h3> Mild to moderate hepatic steatosis was present in 100% SMA patients regardless of age and therapy. Raised hepatic enzymes were found in 33% SMA patients, but serum albumin, protein and INR were normal. Compared to WT, SMA iHeps displayed significantly more lipid accumulation which did not differ by SMA Type. Isolated SMN rescue on the same genetic background by CRISPR editing ameliorated lipid accumulation. <h3>Conclusions:</h3> To our knowledge, this is the first study to present evidence that hepatic steatosis may be a primary defect in all SMA types. Imaging evidence of hepatic steatosis may be frequent and could be used as a clinical biomarker. Establishing currently lacking screening and treatment guidelines for primary extra-neuronal defects in treated SMA patients is important. <b>Disclosure:</b> Dr. Yeo has nothing to disclose. Mr. Kiat has nothing to disclose. Mr. Ng has nothing to disclose. Prof. Ong has nothing to disclose. The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care.

Risk factors of gastrointestinal polypectomy concurrent with bleeding in patients with liver cirrhosis

Objective: To investigate and analyze the occurrence and the related risk factors of gastrointestinal polypectomy accompanied by bleeding in patients with liver cirrhosis. Methods: 127 cases of gastrointestinal polyps with cirrhosis who had endoscopy at the Endoscopic Center of Tianjin Third Central Hospital between November 2017 and November 2020 were collected. At the same time, 127 cases of gastrointestinal polyps with non-cirrhosis that were treated by endoscopy were collected for comparison. The occurrence of hemorrhagic complications between the two groups was compared. The effects of age, sex, liver function, peripheral blood leukocytes, hemoglobin, platelets, blood glucose, the international normalized ratio (INR), polyp resection method, polyp location, size, number, endoscopic morphology, pathology, the presence or absence of diabetes, portal vein thrombosis, and esophageal varices on polypectomy bleeding in the cirrhosis group were analyzed. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test or Fisher's exact probability method, and multivariate logistic regression analysis were used for the comparison of categorical data between groups. Results: The number of polypectomy bleeding cases in the cirrhotic group was 21, with a bleeding rate of 16.5%. The number of bleeding cases in the non-cirrhotic group was 3, with a bleeding rate of 2.4%. The bleeding rate was higher in the cirrhosis group when polypectomy was performed (χ (2) = 14.909, P < 0.001). A univariate analysis of the risk factors for gastrointestinal polypectomy associated with bleeding in patients with liver cirrhosis showed that liver function grading, platelets, INR, hemoglobin, degree of esophageal and gastric varices, and the location, shape, size, and pathology of the polyps had a statistically significant impact on bleeding (P < 0.05). Multivariate logistic regression analysis showed that liver function grade, degree of varicose veins, and polyp location were independent risk factors for bleeding. Patients with Child-Pugh B or C grade liver function were more likely to bleed than those with Child-Pugh A grade (OR = 4.102, 95% CI 1.133 ~ 14.856), gastric polyps were more likely to bleed than colorectal polyps (OR = 27.763, 95% CI 5.567 ~ 138.460), and severe esophagogastric varices were more likely to bleed than no varices or mild to moderate varices (OR = 7.183, 95% CI 1.384 ~ 37.275). Conclusion: Cirrhotic population has higher risk of bleeding during endoscopic gastrointestinal polypectomy than the non-cirrhotic population. Cirrhotic patients with Child-Pugh grades B or C liver function, polyps located in the stomach, severe esophagogastric varices, and other high-risk factors should be listed as a relative contraindication for endoscopic polypectomy.

The prognostic value of preoperative peripheral blood inflammatory biomarkers for intrahepatic cholangiocarcinoma after radical resection

Objective: To explore the value of preoperative peripheral blood inflammatory biomarkers for predicting the prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection. Methods: A total of 124 patients who underwent radical resection for ICC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Receiver operating characteristic (ROC) curve was conducted to determine the best cut-off values of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), systemic immune inflammatory index (SII), and systemic inflammatory response index (SIRI). Univariate and multivariate analyses of prognostic factors were performed using Cox proportional hazards regression model. Based on the independent prognostic factors screened by multivariate Cox regression analysis, a nomogram model of overall survival prediction for ICC patients after radical resection was established. Results: Among the 124 patients, 87 patients died and 37 patients survived during the follow-up period. The median overall survival time of the whole patients was 21 months. ROC curve analysis showed that the areas under the curve (AUC) of NLR, PLR, LMR, SII and SIRI for predicting the overall survival of ICC patients after radical resection were 57.86%, 64.21%, 60.61%, 67.57% and 66.03%, respectively. Univariate Cox regression analysis showed that the inflammatory biomarkers of NLR, PLR, SII, and SIRI were associated with overall survival of ICC after radical resection (HR=1.787, 95%CI: 1.165-2.741; HR=1.181, 95% CI: 1.224-2.892; HR=2.412, 95% CI: 1.565-3.717; HR=1.648, 95% CI: 1.081-2.513). Multivariate Cox regression analysis showed that the inflammatory biomarker of SII was an independent prognostic factor of ICC after radical resection (HR=1.863, 95% CI: 1.161-2.989). According to the best cut-off value of SII to predict the overall survival of ICC patients after radical resection (709.86×10(9)/L), the patients were divided into low SII group (SII≤709.86×10(9)/L) and high SII group (SII>709.86×10(9)/L). In the high SII group, the proportions of NLR>3.31, PLR>3.31, SIRI>1.30×10(9)/L, carbohydrate antigen 19-9>39.0 U/ml, Child-Pugh liver function (grade B), hemi-hepatic/extended hepatectomy, combined perineural invasion, N1 stage and TNM stage (ⅢB) were higher than those in the low SII group (P<0.05). Based on the independent prognostic factors screened by multivariate Cox regression analysis, a nomogram model of overall survival prediction for ICC after radical resection was established, the C-index values of the training set and testing set were 0.774 and 0.737, respectively. Conclusions: Preoperative peripheral blood inflammatory marker SII is an independent risk factor for the prognosis of intrahepatic cholangiocarcinoma patients after radical resection. The nomogram model of overall survival prediction established that included SII has a good predictive ability and can be used to evaluate the prognosis of intrahepatic cholangiocarcinoma patients after radical resection.

A Multidisciplinary Team Approach to the Treatment of Liver Cirrhosis

ObjectiveTo explore the feasibility of treating cirrhosis using a multidisciplinary team approach (MDT) and to pinpoint the key factors influencing its implementation.MethodsThe data of 307 patients with decompensated cirrhosis were studied retrospectively. Patients who received more than two treatment measures were assigned to the MDT group (n=228), and patients who received symptomatic medical drug treatment only were assigned to the traditional treatment group (n=79). The follow-up period ranged from 4 to 10 years, and the average follow-up period was 5.7 years. The results of the biochemical tests for hepatitis B virus deoxyribonucleic acid, hepatitis C virus ribonucleic acid, and autoantibodies to liver disease were analyzed.ResultsThe differences in gender and Child–Pugh grade of liver function between the two groups were not statistically significant. The MDT group had obvious advantages over the traditional treatment group in occupational composition, etiology composition, 5-year survival rate and annual hospitalization times. The leading causes of death in the MDT group, in descending order, were liver cancer, infection, mesenteric thrombosis, and non-hepatic disease, and, in the medical treatment group, they were liver failure, gastrointestinal bleeding, infection, and liver cancer. There was a significant statistical difference between the two groups (p < 0.05). In the multidisciplinary treatment, etiological treatment was the most widely used treatment, accounting for 79.8%, followed by endoscopic treatment (33.3%), peritoneal drainage and ascites reinfusion (25%), splenectomy combined with devascularization (11.4%) and stem cell transplantation and liver transplantation (1.8%).ConclusionAn MDT can improve the efficacy and prognosis of patients with cirrhosis and improve patient compliance. After multi-disciplinary intervention, the mortality spectrum of long-term survival patients with cirrhosis changes, and the mortality rate of liver cancer and non-liver disease increases.

Effect of band ligation or combined with tissue adhesive in the treatment of gastroesophageal varices and portal vein blood flow situational changes

42 cases with gastroesophageal varices were prospectively included. The groups were treated with endoscopic band ligation or combined with tissue adhesive. The results showed that the left gastric vein internal diameter, average blood flow velocity and blood flow volume after the treatment of band ligation combined with tissue adhesive were significantly lower than that of the treatment of band ligation alone, and the differences were statistically significant (P < 0.05). Spleen and portal vein internal diameter, blood flow and average velocity, the liver and spleen size, shear wave velocity and liver function grade of the two groups after treatment did not change significantly (P > 0.05). The effective rate of band ligation combined with tissue adhesive in the treatment of esophageal and gastric varices (66.67%, 52.38%) were higher than that of band ligation alone (42.85%, 23.81%) (P > 0.05), and the re-bleeding rate of the latter was higher (9.52% and 19.05%, P > 0.05). Hence, it is suggested that the combined therapy is safe and more effective, and has no apparent effect on liver function and portal hypertension.

Clinical effects and prognosis of stereotactic body radiotherapy combined with transarterial chemoembolization for massive hepatocellular carcinoma

AbstractObjectiveWith the development of interventional therapy and precise radiotherapy, such as 3‐D conformal intensity‐modulated radiation therapy and stereotactic body radiotherapy (SBRT), transarterial chemoembolization (TACE) combined with radiotherapy has become an important method of comprehensive treatment for advanced liver cancer. However, few studies focus on the treatment of massive hepatocellular carcinoma (HCC) with SBRT. In this study, we investigated the effects and prognostic factors of whole‐body gamma‐knife SBRT combined with TACE in the treatment of massive HCC.MethodsA retrospective analysis was carried out in 81 patients with massive, who received super gamma‐knife (type SGS‐I) SBRT after TACE treatment between 2 January 2011 and 30 June 2016. The curative effects were evaluated using the Modified Response Evaluation Criteria in Solid Tumors criteria. The alpha‐fetoprotein and alanine aminotransferase levels were measured before and after treatment. Patients were followed up for overall survival and 1‐, 3‐, and 5‐year survival rates. Adverse reactions were evaluated using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria.ResultsA total of 81 patients were evaluated, including 29 patients with complete response, 48 patients with partial response, two patients with stable disease, and two patients with progressive disease; the total response rate was 95.06%. The 1‐year local control rate was 71.60%. The overall survival rates at 1, 3, and 5 years were 81.48%, 40.74%, and 16.67%, respectively. The median survival time was 15.0 months (95% CI 10.1–19.8 months). Progression‐free time was 11.0 months (95% CI 9.5–14.4 months). The alpha‐fetoprotein level after treatment was (85.53 ± 21.36) μg/L and was significantly lower than that before treatment (635.62 ± 125.83 μg/L; t = 8.189, P = 0.002). The alanine aminotransferase levels were 70.34 ± 16.60 and (54.95 ± 12.02) U/L before and after treatment, respectively, and were not significantly different (t = 1.348, P = 0.624). Multivariate analysis showed that a portal vein tumor thrombus (χ2 = 4.727, P = 0.016) and the Child–Pugh grade of liver function (χ2 = 4.893, P = 0.013) were adverse prognostic factors of overall survival. The 1‐year local control rates and the median survival times were 72.03% and 71.17%, and 16 and14 months, respectively, for the clinical target volumes ≥120 cm3 and &lt;120 cm3 subgroups; there were no statistical differences in these parameters (P = 0.923 and P = 0.845, respectively). The main adverse reactions during treatment were gastrointestinal effects, fatigue, and radioactive liver injury, mainly grades 1–2. The adverse reactions could be relieved by symptomatic treatment.ConclusionsSBRT with a super gamma‐knife combined with TACE for the treatment of massive HCC had a significant clinical effect and mild side‐effects. Therefore, this approach is worthy of clinical promotion and application.

Follistatin Like 5 (FSTL5) inhibits epithelial to mesenchymal transition in hepatocellular carcinoma.

BackgroundEpithelial to mesenchymal transition (EMT) is a key process in determining distant metastasis and intra-hepatic dissemination of hepatocellular carcinoma (HCC). Follistatin (FST) family members are considered to be an attractive therapeutic targets and prognostic indicators in cancers. As a derivative of FST, Follistatin Like 5 (FSTL5) may play a similar role in HCC cells. This study aimed to investigate the expression and function of FSTL5 in HCC and its role in EMT.MethodsFSTL5, E-cadherin and vimentin in HCC, and paracancerous tissues were detected by immunohistochemistry. Correlation of FSTL5 expression with overall survival was assessed. The proliferation and invasion of HCC cell lines SK-Hep1 and MHCC-LM3 were analyzed by cell counting kit-8 and Transwell assays. The expression of FSTL5, E-cadherin, and vimentin in HCC cells was examined by polymerase chain reaction and Western blot analysis. T-test was used to analyze the difference in proliferation and invasion ability between groups. The Spearman rank correlation test was used to detect the correlation between the expression of FSTL5 and E-cadherin or vimentin.ResultsThe expression of FSTL5 in HCC was lower than that in paracancerous tissues (9.97% vs. 82.55%, χ2 = 340.15, P < 0.001). Patients with high FSTL5 expression had a better prognosis (χ2 = 8.22, P = 0.004) and smaller tumor diameter (χ2 = 45.52, P < 0.001), less lymph node metastasis (χ2 = 5.58, P = 0.02), earlier tumor node metastasis stage (χ2 = 11.29, P = 0.001), a reduced number of tumors (χ2 = 5.05, P = 0.02), lower alpha-fetoprotein value (χ2 = 24.36, P < 0.001), more probability of hepatitis carrying (χ2 = 40.9, P < 0.001), and better liver function grade (χ2 = 5.21, P = 0.02). Immunohistochemistry showed that FSTL5 expression in HCC tissues was positively correlated with E-cadherin expression (r = 0.38, P < 0.001) and negatively correlated with vimentin expression (r = −0.385, P < 0.001). Furthermore, over-expression of FSTL5 up-regulated the expression of E-cadherin and down-regulated the expression of vimentin in SK-Hep1 (negative control [NC] vs. FSTL5-interfering group [Lv-FSTL5]: E-cadherin [t = 45.03, P < 0.001], vimentin [t = 67, P < 0.001]) and MHCC-LM3 (NC vs. Lv-FSTL5: E-cadherin [t = 50, P < 0.001], vimentin [t = 72.75, P < 0.001]) cells at mRNA level. The same as protein level. In addition, the over-expression of FSTL5 inhibited the proliferation (NC vs. Lv-FSTL5: SK-Hep1, 3 d [t = 7.324, P = 0.018], 4 d [t = 6.23, P = 0.021], 5 d [t = 10.21, P = 0.003]; MHCC-LM3, 3 d [t = 4.32, P = 0.037], 4 d [t = 7.49, P = 0.012], 5 d [t = 9.3661, P = 0.009]) and invasion (NC vs. Lv-FSTL5: SK-Hep1, t = 21.57, P < 0.001; MHCC-LM3, t = 18.04, P < 0.001) of HCC cells.ConclusionsDown-regulation of FSTL5 may contribute to EMT of HCC, and FSTL5 is a potential target in the treatment of HCC.

Effects of diabetes on the rebleeding rate following endoscopic treatment in patients with liver cirrhosis.

In the present study, the effects of diabetes on rebleeding following endoscopic treatment were assessed in patients with liver cirrhosis. A retrospective analysis of patients who underwent endoscopic variceal ligation (EVL) or endoscopic injection sclerotherapy (EIS) at the First Affiliated Hospital of Anhui Medical University (Hefei, China) between June 2015 and March 2018 was performed. The patients were divided into the EVL and the EIS groups and each group was subdivided into diabetic and non-diabetic groups. The post-operative rebleeding rate was compared between the EVL and the EIS groups and between the diabetic and non-diabetic patients. The differences in the post-operative rebleeding rate of diabetic patients with hepatogenic and non-hepatogenic diabetes and in patients with different liver function grades were also determined. In the total patient cohort, the rebleeding rate in the EVL subgroup (11.3, 16.5 and 23.5%) was not significantly different compared with that in the EIS subgroup (9.8, 17.4 and 29.3%) at 1, 3 and 6 months following surgery, respectively (P=0.724, 0.868 and 0.339). In the total diabetic group, the rebleeding rate in the EVL subgroup (25.0, 36.1 and 44.4%) was not significantly different compared with that in the EIS subgroup (20.6, 32.4 and 47.1%) at 1, 3 and 6 months following surgery (P=0.660, 0.741 and 0.826, respectively). In the EVL group, the rebleeding rate in the diabetic subgroup (25.0, 36.1 and 44.4%) was higher than that in the non-diabetic subgroup (5.1, 7.6 and 13.9%) at 1, 3, and 6 months following surgery and the differences were significant (P=0.005, <0.001 and <0.001, respectively). In the EIS group, the rebleeding rate in the diabetic subgroup (20.6, 32.4 and 47.1%) was significantly higher than that in the non-diabetic subgroup (3.4, 8.6 and 19.0%) at 1, 3 and 6 months following surgery (P=0.021, 0.004 and 0.004, respectively). Adjustment for age and liver function grade in the EVL and EIS groups was performed using binary logistic regression and the parameter diabetes was indicated to be a risk factor for post-operative rebleeding (P<0.05). No significant difference was noted in the rate of rebleeding between patients with hepatogenic diabetes and non-hepatogenic diabetes at 1, 3 and 6 months following surgery (P=0.634, 0.726 and 0.446, respectively). In the total diabetic group, the rebleeding rate in the Child-Pugh grade A subgroup (14.3, 17.9 and 25.0%) was lower than that in the Child-Pugh grade B/C subgroup (28.6, 45.2 and 59.5%) at 1, 3 and 6 months following surgery, respectively. No significant difference was noted between the two groups at 1 month following surgery (P=0.163). However, the differences were significant at 3 and 6 months following surgery (P=0.018 and 0.005, respectively). The results suggested that diabetes is a risk factor for post-operative rebleeding in patients with cirrhosis. Diabetic patients with poor liver function were more likely to bleed following surgery and the post-operative bleeding rate was not significantly different between patients with hepatogenic and non-hepatogenic diabetes. The study was registered in the Chinese Clinical Trial Registry (no. ChiCTR1800017772).

Comparison between Child-Pugh score and Albumin-Bilirubin grade in the prognosis of patients with HCC after liver resection using time-dependent ROC.

BackgroundsThe Child-Pugh score is a scoring system used to measure liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the Albumin-Bilirubin (ALBI) grade has been proposed for the evaluation of hepatic reserve function in HCC. This study aimed to assess and compare the capability of ALBI grade and Child-Pugh score in predicting overall survival (OS).MethodsA total of 196 consecutive HCC patients who treated with hepatectomy were enrolled in this retrospective study. The prognostic values of ALBI grade and Child-Pugh score in predicting postoperative OS were respectively estimated using the Kaplan-Meier method and time-dependent receiver operating curves (ROC). Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS.ResultsStratified by the Albumin-Bilirubin (ALBI) system, there were 81 (41.3%) patients with grade 1 and 115 (58.7%) patients with grade 2. The cumulative 1-, 3-, 5-year OS rates in patients with ALBI-1 were 82.7%, 51.5% and 35.5%, respectively. For patients with ALBI-2, the cumulative 1-, 3-, 5-year OS rates were 57.6%, 19.4% and 0%, respectively. Based on the Child-Pugh classification, 136 (69.4%) patients had a score of 5, and 60 (30.6%) patients had a score of 6. Patients with Child-Pugh-A5 showed a better OS than those with Child-Pugh-A6, with respective OS at 1, 3 and 5 years (72.7%, 29.2%, 20.3% vs. 53.9%, 21.1%, 0%, Log-rank P<0.001). Besides, the ALBI grade revealed two prognostic groups within Child-Pugh-A5 (P<0.001), while the Child-Pugh score did not distinguish ALBI-2 in different prognostic groups (P=0.705). The multivariate analysis indicated that both ALBI grade and Child-Pugh score could significantly stratify the patients with different OS [hazard ratio (HR), 3.088 and 1.783; 95% confidence interval (CI), 1.985 to 4.805 and 1.272 to 2.731; P<0.001 and P=0.032 for ALBI grade and Child-Pugh score, respectively]. Additionally, time-dependent ROC analysis in the entire cohort proved that the ALBI grade had a better discriminatory ability than the Child-Pugh score in predicting survival, especially for long-term outcomes. According to the subgroup analyses, the ALBI grade had a better discriminatory ability and survival prediction accuracy in overall subsets than the Child-Pugh score for the prediction of OS.ConclusionsALBI grade supplied better prognostic performance and distribution of liver function than Child-Pugh score in stratifying prognosis for HCC patients treated by hepatectomy. These results declared that ALBI grade could be an alternative liver function grading system for stratification in patients with HCC.

Comparison of albumin-bilirubin grade versus Child-Pugh score in predicting the outcome of transarterial chemoembolization for hepatocellular carcinoma using time-dependent ROC.

BackgroundThe Child-Pugh score has been used extensively to assess hepatic function and predict post-treatment outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin-bilirubin (ALBI) grade has been put forward as an objective method of evaluating liver function and predicting overall survival (OS) in HCC patients. Transarterial chemoembolization (TACE) is considered to be effective in prolonging OS among intermediate-stage HCC patients. This study aimed to explore and compare the performance of ALBI grade and Child-Pugh score in predicting outcomes for HCC patients who underwent TACE.MethodsThere were a total of 221 consecutive HCC patients enrolled in this study, all of whom received TACE and were enrolled retrospectively. The Kaplan-Meier method and time-dependent receiver operating curves (ROC) were used to estimate the discriminatory ability and survival prediction accuracy of ALBI grade and Child-Pugh score in predicting postoperative OS. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic factors for OS.ResultsOf the patients enrolled in the study, 106 (48.0%) were ALBI grade 1 and 115 (52.0%) were ALBI grade 2. Overall survival differed significantly between patients with ALBI-1 and ALBI-2 [hazard ratio (HR), 3.032; 95% CI, 2.019–4.555, P<0.001]. With regard to Child-Pugh scores, 160 (72.4%) patients had a score of A5 and 61 (27.6%) had a score of A6. There was also a difference in overall survival between patients with Child-Pugh-A5 and Child-Pugh-A6 (HR, 1.548; 95% CI, 1.066–2.247, P=0.022). In multivariate analyses, both ALBI grade and Child-Pugh score could significantly stratify the patients with different OS (HR, 2.994 and 1.545, P<0.001 and P=0.026 for ALBI grade and Child-Pugh score, respectively). Furthermore, time-dependent ROC analysis and its subgroup analyses demonstrated that the ALBI grade had a better discriminatory ability than Child-Pugh score in predicting survival.ConclusionsIn stratifying prognosis for HCC patients who had received TACE therapy, the ALBI grade provided better prognostic performance and discrimination of liver function than Child-Pugh score. These results suggest that ALBI grade could provide an alternative liver function grading system for stratification of patients with HCC.

Analysis of clinical features and targeted drug therapy of portopulmonary hypertension

Objective: To analyze the clinical characteristics and the effect of targeted drug therapy of portopulmonary hypertension (PoPH). Methods: A total of 5 patients with PoPH who were admitted to the Department of Pulmonary and Critical Care Medicine of Beijing Chao-Yang Hospital from January 1, 2017 to December 31, 2018 were included. The clinical information and follow-up data were collected. The patient's medical history, clinical manifestations, right cardiac catheterization (RHC), classification of cardiac and hepatic function, treatment and prognosis were analyzed. Results: Among the 5 patients with PoPH, 3 were male and 2 were female. The median age was 56 years. The underlying diseases of portal hypertension were all cirrhosis, and 1 patient combined with hepatopulmonary syndrome (HPS). Dyspnea was the main respiratory symptom in all the 5 patients, and the median time from symptom onset to diagnosis was 1 year (5 months to 8 years). RHC was used as the diagnostic criteria for pulmonary hypertension in all patients, with a median mean pulmonary arterial pressure of 42 mmHg (1 mmHg=0.133 kPa) and a median pulmonary vascular resistance of 538 dyn·s·cm(-5). 3 cases were in Child-Pugh liver function grade B, and 2 were in grade A. The hepatic reserve function was not matched with the severity of cardiac insufficiency. Liver transplantation was performed in 1 patient, whose right ventricular dysfunction can be alleviated by targeted drug therapy after operation. All the 5 patients received targeted drug therapy of pulmonary hypertension. In the 3 patients who were regularly treated with targeted drugs and followed up on time, the cardiac function was improved during the follow-up period. There was no improvement or even deterioration of cardiac function in 2 patients who were not regularly treated or followed up. One patient died after liver transplantation. The cause of death was severe pneumonia and right ventricular dysfunction. The survival time after transplantation was 1 year. Conclusions: In PoPH patients, the hepatic reserve function is not matched with the heart function classification. PoPH can coexist with HPS. Regular application of pulmonary hypertension targeting drugs may benefit patients with PoPH.

Clinical characteristics of the Wilson disease carrier

Objective: To study the clinical symptoms, copper metabolism and imaging characteristics of Wilson disease (WD) carriers and to explore the treatment strategy of WD carriers. Methods: Forty WD carriers, 40 WD patients and 20 normal controls from the First Affiliated Hospital of Sun Yat-sen University from July 2007 to May 2018 were included. The modified Young scale was used for neural symptom scoring, and Child grading of liver function, mental symptoms rating scale, magnetic resonance imaging (MRI) scan, susceptibility weighted imaging (SWI) inspection, metal metabolism tests were also applied to all the included subjects. Corrected phase (CP) was measured by SWI. WD carriers were divided into symptomatic group and asymptomatic group. Symptomatic WD carriers were treated with penicillamine for 2 weeks and zinc gluconate for 3 months, then their neurological symptoms, liver function grade, metal metabolism index were rechecked. Results: Six WD carriers presented with some clinical symptoms, including 5 with neurological symptoms and 4 with liver dysfunction. The score of Hamilton anxiety (HAMA) scale of symptomatic WD carriers was higher than that of normal control group (P=0.021). 85% of carriers had ceruloplasmin level less than 0.26 g/L. 80% of carriers had serum copper between normal controls and WD patients. The free copper level of WD carriers was lower than that of WD patients (P=0.012, 0.019). Urinary copper in symptomatic WD carriers was higher than normal controls (P=0.047). The CP values of thalamus, globus pallidus and putamen in symptomatic WD carriers were lower than those in normal control group. After treatment with penicillamine in symptomatic WD carriers, urinary copper was higher than that before treatment (P=0.036). After treatment, the liver enzymes of symptomatic WD carriers returned to normal, and the score of modified Young scale was lower than before treatment (P=0.031). Conclusions: Mild copper metabolism abnormality is seen in WD carriers. A few carriers have neurological symptoms such as limb tremors, or liver symptoms such as abnormal liver enzymes. Abnormal copper metabolism is more serious in symptomatic WD carriers than in asymptomatic WD carriers. Symptomatic WD carriers can be treated with zinc gluconate.

Association of PTEN expression with liver function and inflammatory changes in patients with liver cancer after chemotherapy.

This study investigated the effects of phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression on liver function classification, serum tumor markers and liver function of patients with liver cancer. A total of 63 patients with primary liver cancer treated in Xiangya Hospital (Changsha, China) were retrospectively analyzed. The difference in the PTEN expression levels in normal liver cells and liver cancer cells was compared via immunohistochemistry. According to the expression level of PTEN in the patient's pathological report, patients were divided into PTEN-positive and PTEN-negative groups. The expression level of each tumor marker in serum of patients was observed, and the association of PTEN expression level with the serum tumor markers was analyzed. Moreover, the changes in liver function and inflammatory factors before and after chemotherapy were compared. Finally, the relationship between the PTEN expression level and Child-Pugh grading of the liver function was detected. Compared with that in normal liver cells, the positive expression rate of PTEN protein in liver cancer cells was significantly decreased (P<0.05). No significant difference was found in the expression levels of serum tumor markers, except α-fetoprotein (AFP) in liver cancer patients between PTEN-positive and PTEN-negative group, indicating that PTEN expression has no significant effects on serum tumor markers. The levels of albumin (ALB), alkaline phosphatase (ALP) and prothrombin activity (PTA) were decreased significantly after chemotherapy compared with those before chemotherapy (P<0.05). Besides, the levels of inflammatory factors were remarkably reduced after chemotherapy. PTEN expression was negatively associated with liver function grading, and the higher the PTEN expression, the lower the liver function grading was. The low expression of PTEN has a certain association with the occurrence and grading of liver cancer. PTEN gene has guiding significance in predicting the occurrence, development and prognosis of liver cancer.

Stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma and oligometastatic liver disease

BackgroundTo report our experience with SBRT in primary and secondary liver tumors.MethodsWe retrospectively analysed 55 patients (70 lesions) with a median follow-up of 10 months (range 1–57) treated from 2011 to 2016. All patients had not been eligible for other local treatment options. Median age was 64 years and 64% were male. 27 patients (36 lesions) suffered from hepatocellular carcinoma (HCC, Child A:78%, Child B:18%, Child C:4%), 28 patients (34 lesions) had oligometastatic liver disease (MD). Treatment planning was based on 4D-CT usually after placement of fiducials. Dose and fractionation varied depending on localization and size, most commonly 3 × 12.5 Gy (prescribed to the surrounding 65%-isodose) in 56% and 5x8Gy (80% isodose) in 20% of the treated lesions.ResultsLocal recurrence was observed in 7 patients (13%) and 8 lesions (11%), resulting in estimated 1- and 2-year local control rates (LC) of 91 and 74%. Estimated 1- and 2-year rates of Freedom from hepatic failure (FFHF) were 42 and 28%. Number of lesions was predictive for LC and FFHF in the entire cohort. Estimated 1- and 2-year overall survival (OS) was 76 and 57%. OS was significantly affected by number of treated lesions and performance status. In the HCC subgroup, pretreatment liver function and gender were also predictive for OS. Maximum acute non-hepatic toxicity was grade 1 in 16% and grade 2 in 10% of the patients. Three HCC patients (11%) developed marked deterioration of liver function (grade 3/4).ConclusionsSBRT resulted in high local control and acceptable survival rates in patients with HCC or MD not amendable to other locally-ablative treatment options with limited toxicity. Care should be taken in HCC patients with Child B cirrhosis.