Child-Pugh Grade Research Articles

Sirotik Varis Kanamalarında Tekrar Kanama Belirleyicileri

Aim: Cirrhotic patients with acute variceal bleeding are characterized by a high mortality and rebleeding rate. The aim of this study was to explore predictors of rebleeding in cirrhotic patients. Methods: Cirrhotic patients who were admitted to the hospital were retrospectively analyzed. Rebleeding was defined as a new onset of hematemesis, hematochezia or melena after endoscopic therapy, and a period of stable vital signs and hemoglobin. Medical records as laboratory data include hemoglobin and platelet level, prothrombin time, creatinine, bilirubin, albumin level, vital signs, need of blood transfusions, comorbidities, medications, clinical findings as presence of ascites and hepatic encephalopathy, and endoscopic findings of varices were recorded and entered a computer-based database. Child-Pugh stage was also calculated and recorded. Results: 20 patients (21%) with recurrent hemorrhage after control of the variceal bleeding during the six-week follow-up period were included in this study. The level of albumin and hemoglobin in the rebleeding group were significantly lower than those in non-rebleeding group. The mean level of albumin was 2.45 mg/dL (vs. 3.05 mg/dL, p=0.01) and hemoglobin was 7.96 g/dL (vs. 9.92 g/dL, p=0.001). Ascites was seen to be significantly higher in the rebleeding group (50% vs. 14%, p=0.002). After multivariate regression analysis, we found that lower hemoglobin level and Child-Pugh grade were the only independent significant predictors for variceal rebleeding. Conclusion: Since factors such as the Child-Pugh grade, hypoalbuminemia and presence of ascites are associated with portal hypertension and hepatic failure, we found that lower hemoglobin level and Child-Pugh grade were the only independent significant predictors for variceal rebleeding.

809-P: The Effect of Various Degrees of Hepatic Impairment on the Pharmacokinetic Characteristics of Once-Weekly Insulin Icodec

Insulin icodec is a novel basal insulin being developed for once-weekly administration. This study investigated if the pharmacokinetic characteristics of icodec are affected by hepatic impairment. In an open-label, parallel-group trial, 25 individuals (13 females/12 males; mean±SD age 54±9 yrs, BMI 28.3±5.2 kg/m2) were allocated to four groups based on hepatic function: normal hepatic function (n=6), mild (Child-Pugh Classification grade A; n=6), moderate (Child-Pugh grade B; n=6), and severe (Child-Pugh grade C; n=7) hepatic impairment. Icodec was administered as a single s.c. dose (1.5 U/kg) followed by blood sampling for pharmacokinetics until 840 h (35 days) post-dose. Total exposure of icodec (AUC0-∞,SD) was greater for mild (by 13%) and moderate (by 15%) hepatic impairment vs normal hepatic function, while no difference was observed for severe hepatic impairment vs normal hepatic function (Figure). Maximum concentration of icodec was not affected by hepatic impairment after a single dose (Cmax,SD) or at simulated steady state (Cmax,SS). In conclusion, the slightly greater total exposure of icodec for mild and moderate hepatic impairment vs normal hepatic function is considered of limited clinical relevance as icodec should be dosed according to individual need. No specific dose adjustment of icodec is required in individuals with hepatic impairment. Disclosure H.Haahr: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. B.Cieslarova: None. A.M.Donatsky: Employee; Novo Nordisk. J.R.Joseph: None. N.R.Kristensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. V.Kupcová: None. J.R.Hingst: Employee; Novo Nordisk, Research Support; Pfizer Inc. Funding Novo Nordisk

Predicting symptomatic post-hepatectomy liver failure in patients with hepatocellular carcinoma: development and validation of a preoperative nomogram.

To develop and validate a nomogram based on liver stiffness (LS) for predicting symptomatic post-hepatectomy (PHLF) in patients with hepatocellular carcinoma (HCC). A total of 266 patients with HCC were enrolled prospectively from three tertiary referral hospitals from August 2018 to April 2021. All patients underwent preoperative laboratory examination to obtain parameters of liver function. Two-dimensional shear wave elastography (2D-SWE) was performed to measure LS. Three-dimensional virtual resection obtained the different volumes including future liver remnant (FLR). A nomogram was developed by using logistic regression and determined by receiver operating characteristic (ROC) curve analysis and calibration curve analysis, which was validated internally and externally. A nomogram was constructed with the following variables: FLR ratio (FLR of total liver volume), LS greater than 9.5kPa, Child-Pugh grade, and the presence of clinically significant portal hypertension (CSPH). This nomogram enabled differentiation of symptomatic PHLF in the derivation cohort (area under curve [AUC], 0.915), internal fivefold cross-validation (mean AUC, 0.918), internal validation cohort (AUC, 0.876) and external validation cohort (AUC, 0.845). The nomogram also showed good calibration in the derivation, internal validation, and external validation cohorts (Hosmer-Lemeshow goodness-of-fit test, p = 0.641, p = 0.06, and p = 0.127, respectively). Accordingly, the safe limit of the FLR ratio was stratified using the nomogram. An elevated level of LS was associated with the occurrence of symptomatic PHLF in HCC. A preoperative nomogram integrating LS, clinical and volumetric features was useful in predicting postoperative outcomes in patients with HCC, which might help surgeons in the management of HCC resection. A serial of the safe limit of the future liver remnant was proposed by a preoperative nomogram for hepatocellular carcinoma, which might help surgeons in 'how much remnant is enough in liver resection'. • An elevated liver stiffness with the best cutoff value of 9.5kPa was associated with the occurrence of symptomatic post-hepatectomy liver failure in hepatocellular carcinoma. • A nomogram based on both quality (Child-Pugh grade, liver stiffness, and portal hypertension) and quantity of future liver remnant was developed to predict symptomatic post-hepatectomy liver failure for HCC, which enabled good discrimination and calibration in both derivation and validation cohorts. • The safe limit of future liver remnant volume was stratified using the proposed nomogram, which might help surgeons in the management of HCC resection.

A prospective, single-arm, phase II clinical study of tislelizumab in combination with lenvatinib for perioperative treatment of resectable primary hepatocellular carcinoma with high risk of recurrence.

e16218 Background: Surgery is the main radical treatment for hepatocellular carcinoma (HCC), but the high postoperative recurrence rate makes the survival benefit of patients limited. Neoadjuvant therapy mainly reduces postoperative recurrence by controlling micrometastasis and reducing preoperative tumor load and other high recurrence risk factors, but there are limited data on its application in liver cancer. Tislelizumab, a PD-1 monoclonal antibody, has shown promising efficacy with acceptable safety profile in combination with lenvatinib in the first-line treatment of advanced HCC. This study aims to explore the safety and feasibility of tislelizumab combined with lenvatinib in the neoadjuvant therapy and adjuvant therapy of resectable HCC. Methods: This prospective, single-center, single-arm phase II study (NCT04834986) enrolled patients with histologically confirmed resectable HCC who were at high risk of recurrence, as assessed by the investigators before surgery. Patients did not have any medical treatment in the past, with ECOG of 0-1, and had adequate organ and bone marrow function. Eligible patients received 4 cycles with tislelizumab (200mg, d1, Q3W) combined with Lenvatinib (8mg/kg, PO, qd) and surgery was performed within 4 weeks after treatment. At 4-8 weeks after surgery, adjuvant therapy was started with tislelizumab (200mg, d1, Q3W) and lenvatinib (8mg/kg, PO, qd) for at least half a year or until disease progression or intolerance of adverse reactions. Primary endpoints were safety and feasibility; secondary endpoints were ORR, 1 and 2-years DFS%, pCR, and DFS. Results: From Sep 7,2021 to Nov 9,2022, 24 patients (median age, 57.5 years) were enrolled, with most patients were males (95.8%) and 22 patients (91.7%) had HBV infection. All patients had Child-Pugh grade A and ECOG PS 0. The median treatment period was 4 cycles. In 24 patients, 17 patients (70.8%) underwent R0 resection, 3 patients (3/17, 17.6%) achieved complete pathological response (PCR), and 6 patients (6/17, 35.3%) achieved major pathological response rate (MPR, necrosis > 70%). 3 patients (12.5%) had significant tumor shrinkage and refused surgery. 1 patient (4.2%) is waiting surgery. 3 patients (12.5%) developed disease progression. According to RECIST1.1, ORR was 54.2% (13/24, CR 1, PR 12), DCR was 87.5%. According to mRECIST, ORR was 75.0% (18/24, CR 6, PR 12), DCR was 87.5%. No grade 3 or above adverse events were observed during neoadjuvant treatment period. The most common adverse events of any grade were rash (14/24,58.3%), hypertension (5/24,20.8%) and diarrhea (4/24,16.7%). Conclusions: Tislelizumab in combination with lenvatinib was well tolerated and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: NCT04834986 .

Huaier granules for hepatocellular carcinoma recurrence after ablation: A multicenter prospective cohort study.

e16216 Background: Clinical trials had confirmed the efficacy and safety of Huaier granules in the treatment of hepatocellular carcinoma (HCC), but real-world evidence is still lacking. This prospective study aimed to evaluate the real-world effectiveness and safety of Huaier granules for HCC recurrence after ablation. Methods: Post-ablation patients with no residual lesions confirmed by imaging were enrolled in this study and divided into the Huaier granule group and the control group based on receiving Huaier granules or not. Propensity-score matching was performed according to age, gender, TACE within 3 months before ablation, alpha-fetoprotein level, time interval between ablation and enrollment, and Child-Pugh Grade in 1-(up)-to-2 ratio. The primary outcome was progression-free survival (PFS), and the secondary outcomes were local recurrence-free survival (LRFS) and adverse events (AEs). Results: There were 340 patients in the Huaier granule group and 141 patients in the control group. After propensity score matching, 189 patients and 111 patients were selected for the Huaier granule group and the control group, respectively. There was no significant difference in baseline characteristics between two groups after matching. The median follow-up time of the Huaier granule group and the control group were 49.14 weeks and 73.29 weeks, respectively. The number of PFS events were 29 (15.34%) and 27 (24.32%) in the Huaier granule group and the control group, respectively. The 48, 72, and 96-week PFS rates were 87.4%, 79.4% and 75.2% in the Huaier granule group, and 79.9%, 70.1% and 66.5% in the control group, respectively ( P=0.1649). The number of LRFS events were 27 and 25 in the Huaier granule group and the control group, respectively. In the pre-matching Huaier granule cohort, the incidence of AEs, serious AEs, and grade ≥ 3 AEs were 54 (16.56%), 30 (9.20%) and 14 (4.30%), respectively. Conclusions: This study suggested potential benefit in PFS and RFS and favorable safety profile of Huaier granules in patients with HCC after ablation. Longer-term follow-up is needed to confirm this finding.[Table: see text]

Iodine-125 Seed Strand Implantation Combined with Biliary Stent for the Treatment of Malignant Obstructive Jaundice

Extrahepatic or intrahepatic bile duct stenosis and obstruction can lead to malignant obstructive jaundice (MOJ). Surgical treatment is an effective method, but for patients who cannot undergo surgery or miss the opportunity for surgery, biliary stent combined with 125I implantation can improve obstruction symptoms, relieve biliary obstruction, and improve liver function. This study was to investigate the efficacy of 125I implantation, single biliary stent and percutaneous transhepatic drainage (PTCD) in the treatment of MOJ. 107 patients with MOJ were included. Thirty-seven patients (study group) received biliary stent implantation of 125I particle radiotherapy drainage tube, and 35 patients (sem group) received biliary stent implantation of ordinary drainage tube. 35 patients (PTCD group) underwent PTCD interventional surgery. Biliary stenosis site, Child-Pugh grade and malignant tumor were recorded in the three groups. The changes of liver function before and after treatment were detected, and the survival time, stent patency time, and the occurrence of complications were recorded. All three groups achieved technical success. Liver function was improved in all patients (TBIL, DBIL and ALT were significantly decreased, and P values were all less than 0.05). This study demonstrates that 125I seed beam implantation combined with biliary stent implantation can be considered a safe treatment option for patients with MOJ. This treatment can improve median overall survival, improve liver function, prolong stent patency time.

Lenvatinib (LEN) combined with tislelizumab (TIS) plus transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC): A single-arm, phase II clinical trial.

4111 Background: uHCC still lacks effective treatments, combination of antiangiogenic targeted drugs and immune checkpoint inhibitors showed promising efficacy. TACE induces tumor necrosis and tumor antigen release, may synergize with immunotherapy. This study was to evaluate the efficacy and safety of TACE in combination with TIS and LEN in patients with uHCC. Methods: This study was a single-center, single-arm, open-label phase II exploratory clinical study (NCT05131698). Eligible patients were BCLC C stage and not candidates for surgical resection or liver transplantation, at least one target lesion evaluable, ECOG performance status of ≤ 1, and Child-pugh grade A or B. Enrolled patients received TACE treatment (loplatin + raltitrexed + iodine oil) followed by TIS (200 mg, IV, on Day 1 of a 21-day cycle) and LEN (body weight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) daily. The primary endpoint was overall response rate (ORR) by mRECIST. The secondary endpoints included disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) and safety. Results: As of December 28, 2022, 31 enrolled patients with uHCC were treated. Median follow-up time is 11.3 months. Among all patients with BCLC C, 28 patients (90.3%) had microvascular invasion and 17 (54.8%) had portal vein tumor thrombus. As assessed by mRECIST, the ORR and DCR were 71.1% and 87.1%, respectively (2 CR, 6.6%; 20 PR, 64.5%; 5 SD, 16.1%), 4 patients developed tumor progression (12.9%). As assessed by RECIST 1.1, the ORR and DCR were 67.7% and 87.1%, respectively (1 CR, 3.2%; 20 PR, 64.5%; 6 SD, 19.4%), 4 patients developed tumor progression (12.9%). The median PFS was 10.2 months（95% CI: 4.5-NA）, and the median OS was not reached. Any grade treatment-emergent adverse events (TEAEs) occurred in 64.5% (20/31) patients. The most common TEAEs were Increased γ-glutamyl transpeptidase (35%), Increased aspartate aminotransferase (32%), thrombopenia (25%). Only 2 patients experienced grade 3 TEAE (pneumonia). No serious adverse events (SAEs) were reported. Conclusions: In this study, TACE combined with TIS and LEN showed preliminary antitumor efficacy and tolerable safety profile in uHCC. Clinical trial information: NCT05131698 . [Table: see text]

Safety and efficacy exploration of intraperitoneal perfusion of PD-1 monoclonal antibody for patients with primary liver cancer with malignant ascites: A prospective, single-arm, phase Ib clinical trial.

e16214 Background: Patients with primary liver cancer (PLC) complicated with malignant ascites (MA) have been in the end-stage of the disease (BCLC stage D or CNLC stage IV), and their survival time is less than 3 months. All guidelines recommend best supportive care (BSC), and no relative clinical trials have been involved currently. This study aims to initially explore the safety and efficacy of treatment with PD-1 monoclonal antibody (McAb) for intraperitoneal perfusion (IP) in PLC patients with malignant ascites, combined with BSC. Methods: The main inclusion criteria of this study were as follows: 1) Definitive diagnosed as advanced stage of PLC; 2) Complicated with massive MA; 3) Eastern Cooperative Oncology Group (ECOG) Performance Status was 2-3 points; 4) The expected survival time is less than 3 months. After MA fully drained, Sintilimab (PD-1 inhibitor) 100mg was injected into abdominal cavity on day 1,8,15, every 4 weeks as a cycle, until disease progression or intolerable toxicity or death of any cause. The primary endpoint was safety, while the secondary endpoint were ascites control rate (ACR), overall survival (OS), and objective response rate (ORR). Radiographic evaluation was performed using RECIST version 1.1 criteria or determined by investigator. WHO standards were used to evaluate ACR, NCI-CTC AE 4.03 grading criteria for adverse events. This study is registered with ChiCTR.org.cn ChiCTR2100043683. Results: Totally 21 cases were enrolled in this study from February 2021 to November 2022. By the last date of follow-up, 18(85.7%) cases had died. Eleven (52.4%) patients of Child-Pugh grade B, 10 (47.6%) of Child-Pugh grade C, 9 (42.9%) of ECOG2 and 12 (57.1%) of ECOG3. In terms of safety, treatment related adverse events (TRAEs) were observed in 12 (57.1%) cases, including 6 of Grade 3 (28.6%). The most common TRAEs were abdominal pain (10, 47.6%), rash (5, 23.8%), fatigue (4, 19.0%), increased blood bilirubin (3, 14.3%) and immune pituitaritis (2, 9.5%). There were no deaths observed due to TRAEs. In terms of efficacy, ACR was 43.8% (95% CI: 19.8%-70.1%) evaluated in 16 cases; The median OS was 17.6 weeks (95% CI: 8.7-79.6) in the whole group, 15.9 weeks (95% CI: 12.14-19.58) in those who had previously received PD-1 McAb for systemic therapy and 26.2 weeks in those who not received (95% CI: 14.01~38.35, P=0.717); 13 patients underwent imaging assessment, ORR was 30.8% (95%CI: 9.09%-61.43%). Conclusions: To the best of our knowledge, this study is the first IP report of clinical study on PD-1 McAb. Results showed that IP of PD-1 McAb had good safety and efficacy in end-stage PLC patients complicated with MA, and there also appears to be a control effect on liver lesions. This study is a single-arm, single-center exploratory clinical study, and a multi-center, randomized Phase III study is planned for verification. Clinical trial information: ChiCTR2100043683 .

Real-world 10-year retrospective study of the guidelines for diagnosis and treatment of primary liver cancer in China.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Many regions across the world have issued various HCC diagnosis and treatment protocols to improve the diagnosis and targeted treatment of patients with HCC. However, real-world studies analysing the practice, application value, and existing problems of the China Liver Cancer (CNLC) staging system are scarce. To analyze the current situation and problems associated with the Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China. We collected the medical records of all patients with HCC admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2011 to December 31, 2019, and recorded the hospitalization information of those patients until December 31, 2020. All information on the diagnosis and treatment of the target patients was recorded, and their demographic and sociological characteristics, CNLC stages, screening situations, and treatment methods and effects were analyzed. The survival status of the patients was obtained from follow-up data. This study included the medical records of 3022 patients with HCC. Among these cases, 304 patients were screened before HCC diagnosis; their early-stage diagnosis rate was 69.08%, which was significantly higher than that of patients with HCC who were diagnosed without screening and early detection (33.74%). Herein, patients with no clinical outcome at discharge were followed up, and the survival information of 1128 patients was obtained. A Cox model was used to analyse independent risk factors affecting overall survival, which were revealed as age > 50 years, no screening, alpha-fetoprotein > 400 ng/mL, Child-Pugh grade B, and middle and late CNLC stages. Based on the Cox model survival analysis, in our study, patients with HCC identified via screening had significant advantages in overall and tumor-free survival after hepatectomy. Early diagnosis and treatment can be achieved by screening groups at high risk for HCC based on the guidelines; however, real-world compliance is poor.

Effect of elevated serum ferritin on the risk of death in patients with decompensated cirrhosis: a meta-analysis.

It is still debatable whether serum ferritin is a potential prognostic marker in patients with decompensated cirrhosis. In this meta-analysis, we hope to investigate the relationship between elevated serum ferritin and the risk of death in patients with decompensated cirrhosis. We systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, WAN FANG, and ClinicalTrials.gov without language restrictions from inception to 3 October 2022, and finally identified a total of eight eligible studies with 1829 patients. The pooled prevalence of elevated serum ferritin in decompensated cirrhosis was 40.6% [95% confidence interval (CI) 32.1-49.2%], and it was higher in males, patients with alcohol-associated liver disease, those with Child-Pugh grade C, those with hepatic encephalopathy, and nonsurvivors. Nonsurvivors had significantly higher serum ferritin levels than survivors [mean difference 247.90; 95% CI, 130.97-364.84]. With a pooled unadjusted hazard ratio of 2.38 (95% CI, 1.78-3.18), high serum ferritin was associated with an increased risk of death in patients with decompensated cirrhosis, with low heterogeneity among the included studies. In conclusion, high serum ferritin levels were associated with mortality in patients with decompensated cirrhosis. More prospective and homogeneous clinical studies are required to validate our findings.

The pre- and postoperative nomograms to predict the textbook outcomes of patients who underwent hepatectomy for hepatocellular carcinoma.

An increasing number of studies have confirmed that non-textbook outcomes (non-TO) are a risk factor for the long-term outcome of malignant tumors. It is particularly important to identify the predictive factors of non-TO to improve the quality of surgical treatment. We attempted to construct two nomograms for preoperative and postoperative prediction of non-TO after laparoscopic hepatectomy for hepatocellular carcinoma (HCC). Patients who underwent curative-intent hepatectomy for HCC between 2014 and 2021 at two Chinese hospitals were analyzed. Using univariate and multivariate analyses, the independent predictors of non-TO were identified. The prediction accuracy is accurately measured by the receiver operating characteristic (ROC) curve and calibration curve. ROC curves for the preoperative and postoperative models, Child-Pugh grade, BCLC staging, and 8th TNM staging were compared relative to predictive accuracy for non-TO. Among 515 patients, 286 patients (55.5%) did not achieve TO in the entire cohort. Seven and eight independent risk factors were included in the preoperative and postoperative predictive models by multivariate logistic regression analysis, respectively. The areas under the ROC curves for the postoperative and preoperative models, Child-Pugh grade, BCLC staging, and 8th TNM staging in predicting non-TO were 0.762, 0.698, 0.579, 0.569, and 0.567, respectively. Our proposed preoperative and postoperative nomogram models were able to identify patients at high risk of non-TO following laparoscopic resection of HCC, which may guide clinicians to make individualized surgical decisions, improve postoperative survival, and plan adjuvant therapy against recurrence.

The Impact of Partial Splenic Embolization on Portal Hypertensive Gastropathy in Cirrhotic Patients with Portal Hypertension

This study investigated the impact of partial splenic embolization (PSE) on portal hypertensive gastropathy (PHG). We retrospectively analyzed endoscopic findings and the portal venous system of 31 cirrhotic patients with PHG. The improved group was defined as the amelioration of PHG findings using the McCormack classification. Child-Pugh scores of the improved group (18 of 31 patients) were significantly lower compared with those of the non-improved group (p = 0.018). The changes in the diameters of the portal trunk and those of the spleno-portal junction and spleen hilum in the splenic vein of the improved group were significantly larger than those of the non-improved group (p = 0.007, p = 0.025, and p = 0.003, respectively). The changes in the diameters of the portal vein and splenic hilum of the splenic vein showed significant correlations with Child-Pugh score (r = 0.386, p = 0.039; r = 0.510, p = 0.004). In a multivariate analysis of baseline factors related to the improved group, Child-Pugh grade A was significantly associated with the improvement of PHG (odds ratio 6.875, p = 0.033). PSE could be useful for PHG, especially in patients with Child-Pugh grade A, at least in the short term.

Metabolic Tumor Volume Measured by 18F-FDG PET/CT is Associated with the Survival of Unresectable Hepatocellular Carcinoma Treated with PD-1/PD-L1 Inhibitors Plus Molecular Targeted Agents.

The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with uHCC underwent the combined therapies. Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline 18F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUVmax), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors. Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥39.65 cm3 as the median value) was significantly associated with OS (P<0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P<0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups. High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.

CIRRHOSIS OF LIVER AND INSULIN RESISTANCE- AN OBSERVATIONAL STUDY IN ASSAM

Background:- The prevalence rate of Diabetes Mellitus in cirrhosis of liver varies from 35 to 71%. Diabetes developing in such cases is referred to as Hepatogenous Diabetes. Studies on insulin resistance and Cirrhosis of Liver in North-East India is, however, limited. Aims And Objectives- 1) To estimate fasting plasma glucose and fasting Insulin levels in patients with Cirrhosis of Liver. 2) To calculate HOMA-IR in these patients. Materials And Methods- Ahospital-based observational study on 110 non-Diabetic patients having Liver Cirrhosis was undertaken. Cases were divided according to Child Pugh classication into Grade A, B and C. Fasting plasma glucose and fasting Insulin were estimated in VITROS-5600 Autoanalyzer and HOMA-IR was determined for each case. Results-The mean insulin level was 5.8±2.3 in Child Pugh A, 7.5±3.5 in Child Pugh B and 22.2±11.5 in Child Pugh C. The mean HOMA-IR was 1.3±0.6 in Child Pugh A, 1.8±0.9 in Child Pugh B and 5.8±3.5 in Child Pugh C. The difference in Fasting Insulin and HOMA-IR in Child Pugh Grade A, B and C was found to be statistically signicant (p&lt;0.05). Conclusion- It can be concluded that insulin resistance is maximum in cases with Cirrhosis of Liver having highest Child Pugh grading. Follow-up studies may help in demonstrating Insulin Resistance with increasing grade of Liver Cirrhosis.

Spontaneous portosystemic shunts outside the esophago-gastric region: Prevalence, clinical characteristics, and impact on mortality in cirrhotic patients: A systematic review and meta-analysis

BackgroundSpontaneous portosystemic shunt (SPSS) other than esophago-gastric varices is one of the consequences of cirrhosis-induced portal hypertension (PHT), but its role is not fully understood. Therefore, we conducted a systematic review and meta-analysis to determine the prevalence and clinical characteristics of SPSS (excluding esophago-gastric varices) and its impact on mortality in patients with cirrhosis. MethodsEligible studies were identified from MedLine, PubMed, Embase, Web of Science, and Cochrane Library between Jan 1, 1980 and Sep 30, 2022. Outcome indicators were SPSS prevalence, liver function, decompensated events, and overall survival (OS). ResultsTotally, 2015 studies were reviewed, of which 19 studies recruiting 6884 patients were included. On pooled analysis, the prevalence of SPSS was 34.2% (26.6%∼42.1%). SPSS patients had significantly higher Child-Pugh scores and grades and Model for End-stage Liver Disease scores (all P<0.05). Moreover, SPSS patients experienced a higher incidence of decompensated events, including hepatic encephalopathy, portal vein thrombosis, and hepatorenal syndrome (all P<0.05). Additionally, SPSS patients had significantly shorter OS than the non-SPSS group (P<0.05). ConclusionsIn patients with cirrhosis, SPSS outside the esophago-gastric region is common, characterized by severe impairment of liver function, high rates of decompensated events, including HE, PVT, and hepatorenal syndrome, as well as a high mortality rate.

Correlation and efficacy of TACE combined with lenvatinib plus PD-1 inhibitor in the treatment of hepatocellular carcinoma with portal vein tumor thrombus based on immunological features.

Although the appearance of portal vein tumor thrombus (PVTT) is significantly associated with unfavorable prognosis, there is insufficient evidence to confirm the efficacy and safety of the triple combination of transarterial chemoembolization (TACE), lenvatinib, and programmed cell death-1 (PD-1) inhibitor for patients with hepatocellular carcinoma (HCC) and PVTT. Furthermore, it remains unclear which patient type can obtain the best survival benefit from this combination therapy. The data of 160 patients with HCC and PVTT treated with TACE combined with lenvatinib plus PD-1 inhibitor (TACE+LEN + PD-1 group) or TACE combined with lenvatinib (TACE+LEN group) were retrospectively collected and analyzed. To estimate the efficacy and safety of combination therapy for patients with advanced HCC, tumor response, progression-free survival (PFS), overall survival (OS), biochemical indices, and adverse events (AEs) were assessed in this study. More importantly, tumor immune-related cytokines were used to identify biomarkers predicting the therapeutic response of combination therapy. TACE+LEN + PD-1 was superior to TACE+LEN in OS (23.5 vs. 18.3 months, p=0.0002) and PFS (7.5 vs. 4.3 months, p < 0.0001). Moreover, TACE+LEN + PD-1 achieved more preferable benefits with respect to disease control rate (80.00% vs. 56.67%) and objective response rate (38.57% vs. 24.45%) compared with TACE+LEN in patients with HCC and PVTT (p=0.025). Multivariate analysis showed that Child-Pugh grade, PVTT classification, treatment option, and interleukin (IL)-6, IL-17, interferon (IFN)-α, and vascular endothelial growth factor (VEGF) levels were independent factors related to OS, whereas PVTT classification, treatment option, and IL-6 and IFN-α levels were independent factors related to PFS. Furthermore, the subgroup analysis illustrated that the inflammatory cytokines VEGF, IL-6, IL-17, and IFN-α might be novel biomarkers for predicting the survival prognosis of patients with advanced HCC and PVTT treated with TACE+LEN + PD-1. The safety in the combination group was acceptable. Compared with TACE+LEN, the triple combination treatment of TACE+LEN + PD-1 has more promising clinical outcomes and acceptable safety in patients with HCC and PVTT. Child-Pugh grade, PVTT classification, and IL-6, IL-17, IFN-α, and VEGF levels are independent prognostic factors for survival time.

Quantitative evaluation of renal tissue changes in patients with liver cirrhosis by shear wave elastography.

Hepatocirrhotic nephropathy progresses rapidly and has a poor prognosis, and early detection of renal changes in patients with cirrhosis is particularly important for its prevention and treatment. The objective of this study was to evaluate the value of shear wave elastography (SWE) in the early diagnosis of hepatocirrhotic nephropathy. 206 hepatic cirrhosis patients with normal conventional renal function were enrolled and divided into Child-Pugh grade A (Group A), Child-Pugh grade B (Group B), and Child-Pugh grade C (Group C) according to the Child-Pugh grading method. Meanwhile, 60 healthy volunteers matched in age and sex were selected as the control group. The maximum Young's modulus (Emax), average Young's modulus (Emean), and minimum Young's modulus (Emin) of the left renal parenchyma were measured by SWE in all subjects. The Emax, Emean, and Emin values of the left renal parenchyma were compared between the cirrhosis and control groups. The Emax, Emean, and Emin values of left renal parenchyma in cirrhosis group were higher than those in control group (p = 0.00, 0.00, 0.00). The Emax, Emean, and Emin values of left renal parenchyma in cirrhosis group B and group C were higher than those in control group (p = 0.00, 0.00, 0.00; p = 0.00, 0.00, 0.00), but these values in cirrhosis group A were not significantly different from control group(p = 0.48, 0.52, 0.92). Comparison of the Emax, Emean, and Emin values in left renal parenchyma of three cirrhosis groups, the values of Group B and Group C were higher than those of Group A (p = 0.00, 0.00, 0.00; p = 0.00, 0.00, 0.00), and there was no significant difference between Group B and Group C (p = 0.71, 0.18, 0.39). SWE can detect renal tissue damage in patients with liver cirrhosis earlier than changes identified during routine laboratory examination by quantitatively measuring the elastic parameters of renal parenchyma and may become a new method for early diagnosis of hepatorenal syndrome.

Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child–Pugh grade B patients with locally advanced hepatocellular carcinoma

BackgroundThe incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child–Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability.MethodsSeventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis.ResultsAmong CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child–Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child–Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674–0.926).ConclusionsThe incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.

Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans.

Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer-membrane vesicles (OMVs) of Escherichia coli, which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis. We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from E. coli in mice using mouse liver-derived cells and a mouse cirrhosis model. In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C-type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child-Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis. In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis.

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.