Child-Pugh Grade Research Articles

Evaluating the Benefits of TACE Combined with Lenvatinib Plus PD-1 Inhibitor for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

This study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus programmed death (PD)-1 inhibitor (TACE-L-P) versus TACE combined with sorafenib plus PD-1 inhibitor (TACE-S-P) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). The clinical data of patients with HCC and PVTT treated with TACE-L-P or TACE-S-P from January 2018 to March 2022 were collected. The Response Evaluation Criteria in Solid Tumors (RECIST) version1.1 and modified RECIST (mRECIST) standard were used to evaluate the therapeutic effect. The progression-free survival (PFS) and overall survival (OS) of the two groups were compared. Blood samples were collected before and after treatment to detect the changes of biochemical indicators, and the adverse events (AEs) related to treatment were recorded. A total of 165 patients were included in the study, including 80 patients receiving TACE-L-P treatment and 85 patients receiving TACE-S-P. Patients in the TACE-L-P group had longer median OS (21.7months vs. 15.6months, P = 0.0027), longer median PFS (6.3months vs. 3.2months, P < 0.0001), higher objective response rate (41.25% vs. 30.59%, P = 0.008), and higher disease control rate (86.25% vs. 62.35%, P = 0.008) than those in the TACE-S-P group. Multivariate analysis of the TACE-L-P group showed that VP classification of PVTT, Child-Pugh grade, interleukin-17 (IL-17), vascular endothelial growth factor (VEGF), procalcitonin (PCT), and C-reactive protein (CRP) were independent factors significantly affecting patients' OS (P < 0.05). There was no significant difference in the incidence and severity of AEs between the two groups. TACE-L-P treatment can improve the survival of patients with HCC and PVTT with an acceptable safety, but higher inflammatory indicators will affect the therapeutic effect.

The potential value of serum GP73 in the ancillary diagnosis and grading of liver cirrhosis

This study is to evaluate the potential value of serum GP73 in ancillary cirrhosis diagnosis. 150 cirrhotic subjects and healthy subjects were retrospectively analyzed, and the two groups were compared in terms of Child‒Pugh grade. Serum GP73 was detected by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were drawn to evaluate the diagnostic value of GP73, and the quantitative relationship between cirrhosis and GP73 was verified by logistic regression. The result showed in regard to serum biomarkers related to cirrhosis, the serum levels of GP73, TBIL, DBIL, and PT were higher and the ALB and PLT were lower in the cirrhosis group than in the control group (p = 0.000), and the area under the ROC curve of GP73 for diagnosing cirrhosis was 0.823 (p = 0.000), the cutoff value was 135 ng/ml, the sensitivity was 60.0%, and the specificity was 88.67%. Logistic regression analysis showed that GP73 > 135 ng/ml had an odds ratio of 11.735 (β= 2.463, 95% CI: 6.432-21.411, p = 0.000) for diagnosing cirrhosis. Additionally, the Child‒Pugh A, B, and C groups had different levels of GP73 (χ2 =17.840, p = 0.000). A pairwise comparison between the groups showed that there was a significant difference between grades A and B (p = 0.004) and between grades A and C (p = 0.002), but there was no significant difference between grades B and C (p = 1.000). We found serum GP73 levels were elevated in patients with cirrhosis. When the GP73 level was >135 ng/ml, the potential risk of a cirrhosis diagnosis increased approximately 12-fold.

Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients

IntroductionCombining lenvatinib with a programmed cell death protein-1 (PD-1) inhibitor has been explored for the treatment of un-resectable hepatocellular carcinoma (uHCC). This study aimed to investigate the real-world efficacy of and prognostic factors for survival associated with lenvatinib plus PD-1 inhibitor treatment in a large cohort of Asian uHCC patients even the global LEAP-002 study failed to achieve the primary endpoints.MethodsPatients with uHCC treated with lenvatinib and PD-1 inhibitors were included. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and adverse events (AEs). Prognostic factors for survival were also analyzed.ResultsA total of 378 uHCC patients from two medical centers in China were assessed retrospectively. The median patient age was 55 years, and 86.5% of patients were male. Hepatitis B virus (HBV) infection (89.9%) was the dominant etiology of uHCC. The median OS was 17.8 (95% confidence interval (CI) 14.0–21.6) months. The median PFS was 6.9 (95% CI 6.0–7.9) months. The best ORR and disease control rate (DCR) were 19.6% and 73.5%, respectively. In multivariate analysis, Child‒Pugh grade, Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group performance status score, involved organs, tumor burden score, and combination with local therapy were independent prognostic factors for OS. A total of 100% and 57.9% of patients experienced all-grade and grade 3/4 treatment-emergent AEs, respectively.ConclusionThis real-world study of lenvatinib plus PD-1 inhibitor treatment demonstrated long survival and considerable ORRs and DCRs in uHCC patients in China. The tolerability of combination therapy was acceptable but must be monitored closely.

Efficacy and Safety of TACE Combined with Regorafenib Plus PD-1 Inhibitor in the Treatment of Hepatocellular Carcinoma After Sorafenib Resistance.

To evaluate the efficacy and safety of TACE combined with regorafenib plus PD-1 inhibitor as a second-line therapy for hepatocellular carcinoma after sorafenib resistance. The clinical data of 76 patients with hepatocellular carcinoma who were drug-resistant to sorafenib from September 2018 to May 2022 in the tumor intervention department were collected. Among them, 35 patients used TACE combined with regorafenib plus PD-1 inhibitor (TACE-R-P) as second-line treatment, and the remaining 41 patients used TACE combined with regorafenib (TACE-R) as second-line treatment. The mRECIST (modified Response Evaluation Criteria in Solid Tumors) standard was used to evaluate the therapeutic effect. The progression-free survival (PFS) and overall survival (OS) of the two groups were compared. Blood samples were collected before and after treatment to detect the changes in biochemical indicators, and the adverse events (AEs) related to treatment were recorded. A total of 76 patients were included in the study, including 35 patients receiving TACE-R-P treatment and 41 patients receiving TACE-R treatment. Patients in the TACE-R-P group had longer median OS (19.7months vs 15.2months, HR:0.7716, 95% CI:0.4767-1.2490, P=0.03), longer median PFS (6.3months vs 3.8months, HR:0.6032, 95% CI:0.3727-0.9763, P=0.0029), higher objective response rate (37.14% vs 19.51%, P=0.001) and higher disease control rate (71.43% vs 48.78%, P=0.001) than those in the TACE-R group. Multivariate analysis showed that Child-Pugh grade (B/A; HR=1.283, 95% CI: 0.623-1.707, P=0.014), PVTT (Yes/No, HR=1.455, 95% CI: 0.977-2.038, P=0.018), extrahepatic metastasis (Yes/No, HR=1.766, 95% CI: 1.135-2.302, P=0.022) and treatment option (TACE-R/TACE-R-P, HR=1.930, 95% CI: 1.461-2.850, P=0.017) were independent prognostic factors for OS. There was no significant difference in the incidence and severity of AEs between the two groups. TACE-R-P treatment can be more effective than TACE-R treatment for HCC after sorafenib resistance and can be given priority as a second-line treatment for HCC.

Bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced hepatocellular carcinoma: A retrospective study.

544 Background: The combination of bevacizumab and immune checkpoint inhibitors (ICI) has demonstrated promising efficacy and safety in the first-line treatment of advanced hepatocellular carcinoma (HCC). However, this combination has not been examined in patients with previous first-line treatment of ICI and tyrosine kinase inhibitor. This study aimed to investigate the effectiveness and safety of bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced HCC. Methods: The retrospective study included patients with advanced HCC who received combined therapy of bevacizumab and atezolizumab or sintilimab after failure of lenvatinib plus ICI between July 28, 2020 and March 7, 2022. Baseline patient characteristics were collected. Treatment response, overall response rate (ORR) and disease control rate (DCR) were evaluated according to response evaluation criteria in solid tumors (RECIST) version 1.1. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Treatment-related adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: A total of 20 patients with advanced HCC were included, with a median follow-up time of 11.05 (5.03-20.63) months. Eleven patients died by the last follow-up on August 12, 2022. There were 18 males (90%) and two females (10%). The average age was 59.9±12.08 years. Seven patients (35%) had distant metastasis, and nine (45%) had vascular invasion. Liver function was classified as Child-Pugh grade A in 17 patients (85%) and grade B in three (15%). Patients with Barcelona Clinic Liver Cancer (BCLC) stages B, C and D were 1 (5%), 16 (80%) and 3 (15%), respectively. Eighteen patients (90%) had previous topical therapy. Of all patients previously administered lenvatinib plus ICI as first-line treatment, 14 (70%) had PFS longer than three months. ORR and DCR were 15% (95% confidence interval [CI], 3.2-37.9) and 55% (95% CI, 31.5-76.9), respectively. Median OS was 8.00 months (95% CI, 0.00-16.66), while median PFS was 3.80 months (95% CI, 2.41-5.19). Adverse events were observed in 14 patients (70%). Adverse events of grade 3 or worse occurred in six patients (30%). Conclusions: The combination of bevacizumab with atezolizumab or sintilimab had tolerable safety profile but poor response in the second-line treatment of HCC. Despite the satisfying efficacy as first-line therapy, this combination is not a cost-effective recommendation for advanced HCC cases who failed the first-line treatment of lenvatinib plus ICI. [Table: see text]

Usefulness of the Albumin-Bilirubin Score in Determining the Initial Dose of Voriconazole for Patients with Liver Cirrhosis.

The Child-Pugh score is widely used to assess liver function and estimate drug clearance in patients with liver cirrhosis. Recently, the albumin-bilirubin (ALBI) score, which objectively assesses liver function based only on albumin and total bilirubin levels, was developed as a new method. The purpose of this study was to analyze the relationship between the liver function assessment method and the plasma concentration of voriconazole (VRCZ), an antifungal drug for patients with liver cirrhosis. This single-center retrospective study enrolled 159 patients who received VRCZ between 2012 and 2020. In patients administered VRCZ orally, the median concentration to dose (C : D) ratio increased with the progression of Child-Pugh and ALBI grades. Positive correlations between the ALBI score and VRCZ C : D ratio were observed in patients with cirrhosis (r = 0.52 (95% confidence interval, 0.069-0.79); p < 0.05). In addition, a highly negative correlation was observed between the ALBI score and VRCZ daily maintenance dose (r=-0.79 (95% confidence interval, -0.92 to -0.50); p < 0.0001). In contrast, for patients administered VRCZ intravenously, no increase in C : D ratio was observed for both Child-Pugh and ALBI scores compared to the non-liver cirrhosis group. This may be because the injection is often used in severely ill patients, and factors other than impaired liver function may affect the plasma concentrations of VRCZ. In conclusion, the ALBI score was shown to be useful in predicting VRCZ clearance as well as the Child-Pugh score, and the initial dose of VRCZ might be determined according to the ALBI score.

MELD 3.0 Score for Predicting Survival in Patients with Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt Creation.

The selection of appropriate candidates for transjugular intrahepatic portosystemic shunt (TIPS) is important and challenging. To validate the Model for End-Stage Liver Disease (MELD) 3.0 in predicting mortality in patients with cirrhosis after TIPS creation. A total of 855 consecutive patients with cirrhosis from December 2011 to October 2019 who underwent TIPS placement were retrospectively reviewed. The prognostic value of the MELD 3.0, MELD, MELD-Na, Child-Pugh and FIPS score was assessed using Harrell's C concordance index (c-index). The Hosmer-Lemeshow test was used to test the goodness of fit of all models and the calibration plot was drawn. The c-index of the MELD 3.0 in predicting 3-month mortality was 0.727 (0.645-0.808), which were significantly superior to the MELD (0.663 [0.565-0.761]; P = 0.015), MELD-Na (0.672 [0.577-0.768]; P = 0.008) and FIPS (0.582 [0.477-0.687]; P = 0.015). The Child-Pugh score reached c-indices of 0.754 (0.673-0.835), 0.720 (0.649-0.792), 0.705 (0.643-0.766) and 0.665 (0.614-0.716) for 3-month, 6-month, 1-year, and 2-year mortality, respectively, which seems comparable to MELD 3.0. A MELD 3.0 of 14 could be used as a cut-off point for discriminating between high- and low-risk patients. The MELD 3.0 could stratify patients with Child-Pugh grade B (log-rank P < 0.001). The Child-Pugh score could stratify patients defined as low risk by MELD 3.0 (log-rank P < 0.001). The MELD 3.0 was significantly superior to the MELD, MELD-Na and FIPS scores in predicting mortality in patients with cirrhosis after TIPS creation.

Safety, efficacy and prognosis of anticoagulant therapy for portal vein thrombosis in cirrhosis: a retrospective cohort study

BackgroundThe role of anticoagulants in the treatment of cirrhotic PVT remains controversial. This study aimed to analyze the safety and efficacy of anticoagulant therapy in patients with cirrhotic portal vein thrombosis (PVT) and its impact on prognosis.MethodsA retrospective cohort study was conducted for PVT patients with liver cirrhosis in our hospital. The primary outcome of the study was the PVT recanalization rate. Other outcomes included bleeding rate, liver function, and mortality. Cox and Logistic regression were used to explore the risk factors of outcomes.ResultsThis study included 77 patients that 27 patients in the anticoagulant group and 50 in the non-anticoagulant group. Anticoagulant therapy was associated with higher rate of PVT recanalization (44.4% vs 20.0%, log-rank P = 0.016) and lower rate of PVT progression (7.4% vs 30.0%, log-rank P = 0.026), and without increasing the rate of total bleeding (14.8% vs 24%, P = 0.343), major bleeding (3.7% vs 6%, P = 0.665) and variceal bleeding (3.7% vs 16%, P = 0.109). The safety and efficacy of different anticoagulants were similar. The Child-Pugh grade of the anticoagulant therapy group was better than that of the non-anticoagulant therapy group (P = 0.030). There was no significant difference in the 2-year survival rate of the two groups.ConclusionAnticoagulants could increase the PVT recanalization rate and reduce the PVT progression rate without increasing the rate of bleeding. Anticoagulants may be beneficial to improving the liver function of patients with cirrhotic PVT. There was no significant difference in the safety and efficacy of different anticoagulants in the treatment of cirrhotic PVT.

Study of hepatic toxicity in small liver tumors after photon or proton therapy based on factors predicting the benefits of proton.

In a previous study of hepatic toxicity, the following three factors were identified to predict the benefits of proton beam therapy (PBT) for hepatocellular carcinomas (HCCs) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (1 vs ≥2), the location of tumors (hepatic hilum or others), and the sum of the diameters of lesions. The aim of this study is to analyze the association between these three factors and hepatic toxicity. We retrospectively reviewed patients of CP-A treated with PBT or photon stereotactic body radiotherapy (X-ray radiotherapy, XRT) for HCC ≤5 cm. For normal liver dose, the V5, V10, V20 (volumes receiving 5, 10, and 20 Gy at least), and the mean dose was evaluated. The albumin-bilirubin (ALBI) and CP score changes from the baseline were evaluated at 3 and 6 months after treatment. In 89 patients (XRT: 48, PBT: 41), those with two or three (2-3) predictive factors were higher normal liver doses than with zero or one (0-1) factor. In the PBT group, the ALBI score worsened more in patients with 2-3 factors than those with 0-1 factor, at 3 months (median: 0.26 vs 0.02, p = 0.032) and at 6 months (median: 0.35 vs 0.10, p = 0.009). The ALBI score change in the XRT group and CP score change in either modality were not significantly different in the number of predictive factors. The predictive factor numbers predicted the ALBI score change in PBT but not in XRT. This study suggest that the number of predictive factors previously identified (0-1 vs 2-3) were significantly associated with dosimetric parameters of the normal liver in both modalities. In the proton group, the number of predictive factors was associated with a worsening ALBI score at 3 and 6 months, but these associations were not found in the photon SBRT group.

Age independent survival benefit for patients with small hepatocellular carcinoma undergoing percutaneous cryoablation: A propensity scores matching study.

Hepatocellular carcinoma (HCC) is the major cause of malignancy-related deaths worldwide, and its incidence is likely to increase in the future as life expectancy increases. Therefore, the management of elderly patients with HCC has become a global issue. Aim of this study was to assess whether elderly patients with small HCC could obtain survival benefit from cryoablation (CRYO) in a real-world. From July 2007 to June 2013, 185 patients with small HCC who underwent curative-intent percutaneous CRYO. All patients were divided into three groups according to age distribution. Overall survival (OS) and tumor-free survival (TFS) were compared between among of groups before and after the 1:1 propensity score matching, respectively. Univariate and multivariate Cox analyses were performed to determine the potential relationships between variables and prognostic outcomes. One hundred and eighty-five patients (144 men, 41 women) received CRYO for small HCC, including 59 patients with age <50 years, 105 patients with age between 50 and 65 years, and 21 patients with age >65 years. The three age groups showed significant differences in the terms of underlying chronic liver disease and the number of patients with minor postoperative complications. After propensity score matching, the younger and elderly groups showed significant differences in mean OS (P=0.008) and tumor progression (P=0.050). However, no significant differences were shown in mean progression-free survival (PFS) (P=0.303). The Cox multivariate analysis showed that the Child-Pugh grade (HR=3.1, P<0.001), albumin (HR=0.85, P=0.004) and total of bilirubin (HR=1, P=0.024) were the independent prognostic factor for mean OS. Our propensity-score-matched study suggested that elderly patients with small HCC can achieve acceptable prognostic outcomes with PFS similar to those of younger patients with small HCC after treatment with CRYO, while Child-Pugh grade, bilirubin and serum albumin levels were associated with the prognosis of small HCCs.

Current Therapy and Liver Transplantation for Portopulmonary Hypertension in Japan.

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a good effect with PAH-specific drugs in PoPH patients, it is important to diagnose PoPH at an early stage and promptly initiate therapy. The majority of therapeutic drugs are contraindicated for Child-Pugh grade C LC, and their effects decrease in the severe PAH stage. Among many LC patients, the measurement of serum brain natriuretic peptide levels might be useful for detecting PoPH. Previously, liver transplantation (LT) for PoPH was contraindicated; however, the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs. In Japan, new registration criteria for deceased-donor LT have been established for PoPH patients. PoPH patients with a mean pulmonary arterial pressure &lt;35 mmHg and pulmonary vascular resistance &lt;400 dyn/s/cm-5 are indicated for LT, regardless of whether they are using therapeutic drugs. Combined with PAH-specific drugs, LT may lead to excellent long-term outcomes in PoPH patients. We aimed to review current therapies for PoPH, including LT.

Durable Stable Disease by Atezolizumab/Bevacizumab Can Provide Long-term Survival of Patients With Hepatocellular Carcinoma Lung Metastases.

Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response. A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child-Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child-Pugh Grade of A and a performance status of 0. Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life.

Red Blood Cell Distribution Width as a Potential Valuable Survival Predictor in Hepatitis B Virus-related Hepatocellular Carcinoma.

Objectives: Red blood cell distribution width (RDW) is a widely used clinical parameter recently deployed in predicting various cancers. This study aimed to evaluate the prognostic value of RDW in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: We conducted a retrospective study of 745 patients with HBV-related HCC, 253 patients with chronic hepatitis B (CHB), and 256 healthy individuals to compare their hematological parameters and analyze their RDW levels. Potential risk factors for long-term all-cause mortality in patients with HBV-related HCC were predicted using Multivariate Cox regression. A nomogram was generated, and its performance was evaluated. Results: The RDW of patients with HBV-related HCC was significantly higher than that of those with CHB and healthy controls. In the former, splenomegaly, liver cirrhosis, larger tumor diameter, multiple tumor number, portal vein tumor thrombus, and lymphatic or distant metastasis were significantly increased, and the later the Child-Pugh grade and Barcelona clinic liver cancer stage, the higher the RDW. Furthermore, multivariate Cox regression analysis identified RDW as an independent risk factor for predicting long-term all-cause mortality in patients with HBV-related HCC. Finally, we successfully generated a nomogram incorporating RDW and validated its predictive ability. Conclusions: RDW is a potentially valuable hematological marker for predicting the survival and prognosis of patients with HBV-related HCC. The nomogram incorporating RDW can be used as an effective tool to plan the individualized treatment of such patients.

Multiparametric MRI combined with liver volume for quantitative evaluation of liver function in patients with cirrhosis.

PURPOSE We aimed to establish a liver function evaluation model by combining multiparametric magnetic resonance imaging (MRI) with liver volume (LV) and further verify the effectiveness of the model to evaluate liver function. METHODS This retrospective study included 101 consecutive cirrhosis patients (69 cases for modeling group and 32 cases for validation group) who underwent gadoxetic acid-enhanced MRI. Five signal intensity parameters were obtained by measuring the signal intensities of the liver, spleen, and erector spinae before and 20 minutes after gadoxetic acid disodium enhancement. The dif fusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were obtained from intravoxel incoherent motion diffusion-weighted imaging. The LV parameters (Vliver, Vspleen, and Vliver/Vspleen) were obtained using 3-dimensional image generation software. The most effec tive parameter was selected from each of the 3 methods, and a multivariate regression model for liver function evaluation was established and validated. RESULTS In the modeling group, relative enhancement (RE), D*, and Vliver/Vspleen showed significant dif ferences among the different liver function groups (P < .001). Receiver operating characteristic analysis showed that these parameters had the highest area under the curve (AUC) values for dis tinguishing Child-Pugh A from Child-Pugh B and C groups (0.917, 0.929, and 0.885, respectively). The following liver function model was obtained by multivariate regression analysis: F(x)=3.96 - 1.243 (RE) - 0.034 (D*) - 0.080 (Vliver/Vspleen) (R2=0.811, P < .001). In the patients with cirrhosis, the F(x) of Child-Pugh A, B, and C were 1.16 ± 0.44, 1.95 ± 0.29, and 2.79 ± 0.38, respectively. In the validation group, the AUC for F(x) to distinguish Child-Pugh A from Child-Pugh B and C was 0.973. CONCLUSION Combining multiparametric MRI with LV effectively distinguished patients with different Child Pugh grades. This model could hence be useful as a novel radiological marker to estimate the liver function.

Management of Cholelithiasis in Cirrhotic Patients.

Gallstone disease (GD) is a common disease worldwide and has a higher incidence in cirrhotic patients than in the general population. The main indications for cholecystectomy surgery in cirrhotic patients remain symptomatic cholelithiasis and its complications. Over the past two decades, numerous published reports have attested to the feasibility and safety of laparoscopic cholecystectomy in cirrhotic patients. Surgery in patients with liver cirrhosis represents an additional source of stress for an already impaired liver function and perioperative complications are remarkably high compared to non-cirrhotic patients, despite significant advances in surgical management. Therefore, preoperative risk stratification and adequate patient selection are mandatory to minimize postoperative complications. We have conducted a systematic review of the literature over the last 22 years for specific information on indications for surgery in cirrhotic patients and individual percentages of Child-Pugh grades undergoing treatment. There are very few reported cases of cholecystectomy and minimally invasive treatment, such as percutaneous transhepatic cholecystostomy (PTC), in patients with Child-Pugh grade C cirrhosis. With this work, we would like to pay attention to the treatment of cholelithiasis in cirrhotic patients who are still able to undergo cholecystectomy, thus also encouraging this type of intervention in cases of asymptomatic cholelithiasis in patients with Child-Pugh grades A and B.

Perioperative factors related to the prognosis of elderly patients with hepatocellular carcinoma

Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). The treatment of elderly patients with HCC has always been difficult. With the development of geriatrics and geriatric surgery, the number of elderly patients with HCC undergoing hepatectomy has gradually increased. To further improve the long-term prognosis of elderly patients with hepatocellular carcinoma undergoing surgery, it is necessary to study the related perioperative factors. Our aim was to study the impact of preoperative and intraoperative factors on the long-term survival of elderly patients with HCC who underwent hepatectomy. A total of 151 elderly patients with HCC who underwent hepatectomy were retrospectively studied. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors. The 1-, 3-, 5- and 10-year overall survival rates of elderly patients with HCC who underwent resection were 79.5%, 60.8%, 46.6%, and 25.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis: Child-Pugh grade (B/C versus A: HR[hazard ratio] = 2.318, P = 0.019), alpha-fetoprotein value (> 20ng/ml versus ≤ 20ng/ml: HR = 1.972, P = 0.005), resection style (anatomical versus no anatomical: HR = 1.976, P = 0.006), and intraoperative blood loss (> 400ml versus ≤ 400ml: HR = 2.008, P = 0.003). Poor survival of elderly patients with HCC who underwent hepatectomy was correlated with the preoperative and intraoperative factors of Child-Pugh grade, Alpha-fetoprotein value, resection style, and intraoperative blood loss.

Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma.

Lenvatinib is a standard first-line systemic therapy in advanced hepatocellular carcinoma (aHCC) and is widely used in all lines. However, the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTAs) after the progression of lenvatinib treatment are unclear. The aim of this study was to evaluate the anticancer effects of ICI plus MTA in patients with aHCC who progressed after lenvatinib. We retrospectively included aHCC patients treated with ICI plus MTA after the progression of lenvatinib from two medical centers. Participants who continued lenvatinib treatment were classified into the "ICI+Lenva" group, while the "ICI+Others" group included patients receiving other MTAs. The efficacy endpoints were progression-free survival (PFS), post-progression survival (PPS), overall survival (OS), and tumor response following RECIST v1.1. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0. In this study, 85 eligible aHCC patients were enrolled, including 58 in the ICI+Lenva group and 27 in the ICI+Others group. At a median follow-up time of 22.8 months, the median PPS and PFS were 14.0 (95% CI: 9.0-18.2) and 4.5 months (95% CI: 3.5-8.3), respectively. The objective response and disease control rates were 10.6% and 52.9%, respectively. No significant differences were observed in any of the efficacy endpoints between the two groups. Prolonged PPS was associated with Child-Pugh grade A, AFP < 400 IU/ml, and concomitant locoregional treatment. All patients experienced adverse events (AEs), but no fatal AEs were observed. ICI plus MTA in aHCC patients after the progression of lenvatinib presented high antitumor activity and safety. Patients could continue lenvatinib treatment and receive ICIs as well as locoregional treatment to achieve better OS.

Hepatic artery intervention combined with immune-targeted therapy is superior to sequential therapy in BCLC-C hepatocellular carcinoma

BackgroundHepatic artery intervention combined with immunotarget therapy exerts excellent disease control and prolongs survival. However, the arrangement of hepatic artery intervention and systemic therapy confuses clinical decisions.MethodsA two-center, retrospective clinical study was approved by the Institutional Ethics Committee. From December 2018 to February 2022, patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) who received targeted therapy plus PD-1 inhibitors with or without hepatic artery intervention were included. According to the treatment mode, the patients were assigned to three groups: initial hepatic artery intervention combined with immunotarget therapy, immunotarget therapy sequential hepatic artery interventional therapy, and immunotarget therapy only. The survival, response, and adverse events were compared among the three groups. Subgroup analysis and univariate and multivariate prognostic analyses were also evaluated.ResultsThe median follow-up time was 18.3 months (95% CI 16.7 to 20.0 months). A total of 163 patients with BCLC-C stage HCC were assigned to three groups: initial hepatic artery intervention plus PD-1 inhibitors plus targeted therapy (HPT, n = 66), PD-1 inhibitors plus targeted therapy followed by hepatic artery intervention (PTH, n = 56) and PD-1 inhibitors plus targeted therapy (PT, n = 41). The median progression-free survival was 8.37 months (95% CI 6.35–10.39) with HPT versus 5.3 months (95% CI 3.48–7.12) with PTH versus 6.33 months (95% CI 3.75–8.92) with PT. The progression-free survival of the HPT group was better than that of the PTH group (HR 0.66, 95% CI 0.45–0.97, p = 0.027) and PT group (HR 0.60, 95% CI 0.39–0.92, p = 0.01). The median overall survival was 14.6 months (95% CI 10.6–18.7) with HPT, 10.0 months (95% CI 8.2–11.8) with PTH and 11.3 months (95% CI 8.3–14.3) with PT. The 1-year overall survival (OS) rates in the HPT, PTH and PT groups were 50%, 33.9%, and 34.1%, respectively. Overall survival was significantly longer in the HTP group than in the PT group (HR 0.60, 95% CI 0.361–0.996, p = 0.032). Compared with the PTH group, the overall survival of the HTP group had a prolonged survival trend (HR 0.66, 95% CI 0.416–1.032, p = 0.059). All treatment modalities were deemed equally safe. Multivariate analysis suggested that the mode of treatment, albumin level, Child‒Pugh grade and hepatectomy history were independent prognostic factors for BCLC-C HCC patients.ConclusionsInitial hepatic artery intervention combined with immunotarget therapy gained survival benefits with tolerable side effects compared with immunotarget sequential hepatic artery intervention and immunotarget therapy alone. Multivariate analysis suggested that liver reserve function was closely correlated with prognosis.

Simultaneous CSM-TACE with CalliSpheres® and partial splenic embolization using 8spheres® for hepatocellular carcinoma with hypersplenism: Early prospective multicenter clinical outcome.

Primary hepatocellular carcinoma is often complicated with hepatitis and liver cirrhosis. Some patients develop different degrees of splenomegaly, hypersplenism and hypohepatia due to the aggravation of liver cirrhosis, which to some extent interfere with the treatment of tumors and even affect the prognosis of patients. In this study, we prospectively evaluate the efficacy and safety of simultaneous CalliSpheres® microspheres transcatheter arterial chemoembolization (CSM-TACE) and partial splenic embolization (PSE) using 8spheres® for hepatocellular carcinoma (HCC) with hypersplenism. Ninety consecutive HCC patients with hypersplenism who underwent CSM-TACE were selected: 32 patients in CSM-TACE+PSE group, and 58 patients in CSM-TACE group. The peripheral blood cell counts (leukocyte, platelet (PLT), liver function and red blood cell (RBC)), CSM-TACE and/or PSE related complications, and the tumor control rate at 1 month after CSM-TACE were compared. The survival time and prognostic factors were also observed. Before CSM-TACE, there were no significant differences in sex, age, Child-Pugh grade, tumor size, and alpha-fetoprotein (AFP) between the two groups. After CSM-TACE, the PLT and white blood cell (WBC) counts in CSM-TACE+PSE group were significantly higher than those in the CSM-TACE group (P<0.05). There were no significant differences in RBC before and after treatment (P > 0.05). In the CSM-TACE group, there were no significant differences in WBC, PLT, and RBC before and after treatment (P > 0.05). There was no significant difference in liver function at 1 month after treatment between the two groups. The cholinesterase (CHE) level in the CSM-TACE+PSE group after CSM-TACE+PSE was obviously higher than that before CSM-TACE+PSE and higher than that in the CSM-TACE group (P<0.05). However, the level of CHE returned to the preoperative level 1 month after CSM-TACE in the CSM-TACE group. The objective response rate (ORR) and median overall survival (OS) in the CSM-TACE+PSE group were higher than those in the CSM-TACE group (P<0.05). The adverse reactions of the two groups were fever, abdominal pain, stomach discomfort, nausea, and vomiting, and no serious complications occurred. The degree of abdominal pain and fever in the experimental group was lower than that in the control group (P > 0.05). Simultaneous CSM-TACE and PSE using domestic embolization particles for HCC with hypersplenism have good safety and efficacy and has a low incidence of PSE-related adverse events, it is conducive to improving liver function reserve, and can further improve the median OS.

Establishment of a risk assessment system for complications of hepatectomy based on preoperative variables

To reduce the incidence of postoperative complications, it is important to predict them and intervene before surgery if necessary. However, there is no ideal system to evaluate the overall risk of postoperative complications of liver surgery on the basis of preoperative variables. Therefore, this study aimed to design and validate a risk assessment system to predict postoperative complications of hepatectomy on the basis of preoperative variables. Binomial logistic regression was used to derive the “hepatectomy overall risk formula” (HORF) for predicting postoperative complications on the basis of preoperative variables. Multivariate analysis revealed that Child-Pugh grade B–C (odds ratio [OR] = 1.984, p = 0.002), medical diseases requiring drug treatment (OR = 1.883, p = 0.003), major hepatectomy (OR = 1.947, p < 0.001), adjacent organ invasion (OR = 3.616, p = 0.023), and preoperative hospital stay > 7 days (OR = 1.565, p = 0.004) were independent risk factors for postoperative complications of hepatectomy. The area under the curve for the HORF was 0.736. The optimal cut-off value for predicting complications was 0.32 (32%). The area under the curve for the HORF in the validation dataset was 0.727. The HORF can accurately predict postoperative complications of hepatectomy on the basis of preoperative variables, and thus enables the determination of the necessity for intervention before surgery.