Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach.

BACKGROUND: With advances in technology, laparoscopic liver resection is widely accepted. Laparoscopic liver resection under hemihepatic vascular inflow occlusion has advantages over the conventional total hepatic inflow occlusion using the Pringle's maneuver, especially in patients with cirrhosis. METHOD: From November 2011 to August 2012, eight consecutive patients underwent laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach with biliary bougie assistance. RESULTS: The types of liver resection included right hepatectomy (n=1), right posterior sectionectomy (n=1), left hepatectomy and common bile duct exploration (n=1), segment 4b resection (n=1), left lateral sectionectomy (n=2), and wedge resection (n=2). Four patients underwent right and 4 left hemihepatic vascular inflow occlusion. Four patients had cirrhosis. The mean operation time was 176.3 minutes. The mean time taken to achieve hemihepatic vascular inflow occlusion was 24.3 minutes. The mean duration of vascular inflow occlusion was 54.5 minutes. The mean intraoperative blood loss was 361 mL. No patient required blood transfusion. Postoperatively, one patient developed bile leak which healed with conservative treatment. No postoperative liver failure and mortality occurred. The mean hospital stay of the patients was 7 days. CONCLUSION: Our technique of hemihepatic vascular inflow vascular occlusion using the lowering of hilar plate approach was safe, and it improved laparoscopic liver resection by minimizing blood loss during liver parenchymal transection.

Adult Langerhans cell histiocytosis with multi­system bone, skin, lung and liver involvement: A case report.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disorder marked by the uncontrolled proliferation and accumulation of immature myeloid dendritic cells, which originate from the bone marrow. Although LCH can involve various organs, including bone, lymph nodes and skin, multi-system bone, liver and lung involvement with LCH is rare in adults. A case of a 49-year-old man diagnosed with multi-system, aggressive LCH involving bone, skin, lung and liver is presented in the present study. The initial radio-clinic presentation of the patient was initially suggestive of a bone tumor. The current case report aims to draw attention to this rare disease and discuss the diagnostic approach and therapeutic management, which should be noted to help physicians more rapidly identify, diagnose and treat comparable cases.

L-GrAFT7 has High Accuracy in Predicting Early Allograft Failure after Liver Transplantation: A Multicenter Cohort Study in China.

Background and Aims: Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking. Methods: A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group. Results: L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group. Conclusions: The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Preservation of Porcine Donation after Circulatory Death (DCD) Liver by Perfusion and Orthotopic Liver Transplantation.

Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue, clinical application of MP technology for donor liver preservation is underway. Simultaneously, efforts are focused on the development of various MP instruments, validated through relevant animal model experiments. Effective large animal trials play a pivotal role in clinical applications. However, challenges persist in the ex vivo preservation of DCD livers and the transplantation procedure in pigs. These hurdles encompass addressing the prolonged preservation of donor livers, conducting viability tests, alleviating ischemic injuries, and shortening the anhepatic phase. The use of a variable temperature-controlled MP device facilitates the prolonged preservation of DCD livers through sequential Dual Hypothermic Oxygenated Machine Perfusion (DHOPE) and Normothermic Machine Perfusion (NMP) modes. This protocol enhances the porcine OLTx model by improving the quality of DCD livers, optimizing the anastomosis technique, and reducing the duration of the anhepatic phase.

Effects of Preservation of Donor Liver Gastroduodenal Artery on Post-Transplant Biliary Complications in 187 Liver Transplant Recipients: A Retrospective Study.

BACKGROUND This retrospective study aimed to evaluate the effects of preservation of the donor liver gastroduodenal artery on post-transplant biliary complications in 187 liver transplant recipients. MATERIAL AND METHODS The clinical data of 187 liver transplantation recipients were retrospectively analyzed. Recipients were divided into conventional and modified groups. The technical point of the modified group is to preserve at least 2 cm of the distal gastroduodenal artery, and pay special attention to preserve the superior pancreaticoduodenal artery to ensure the distal blood supply to the common bile duct. RESULTS The modified group had significantly shorter operative time (7.17 vs 7.98) h (P<0.001) and less intraoperative blood loss (2715.40 vs 3434.93) ml (P=0.003) than the conventional group. The incidence of postoperative biliary complications (including anastomotic biliary leakage, ischemic bile duct stenosis, and anastomotic bile duct stenosis) in the modified group (4/114, 4.1%) was significantly lower (15/73, 20.5%) (P<0.001). There was no significant difference in the intraoperative cold and warm ischemia time and postoperative hospital stay length between the 2 groups. In addition, there was no significant difference in the effect of cardiac-death and brain-death sources on perioperative biliary complications, while the peak postoperative transaminase and total bilirubin were higher in patients receiving the donor liver of cardiac death (P<0.05). CONCLUSIONS Preserving the integrity of the donor gastroduodenal artery and surrounding tissue is beneficial to protect the blood supply of the extrahepatic bile duct, and can reduce the incidence of biliary complications.

Entecavir Monotherapy Prevents Hepatitis B Virus Recurrence After Liver Transplant for Chronic Hepatitis B Patients: A Long-Term Retrospective Study.

BACKGROUND: Limited data are available on the use of oral antiviral therapy, particularly the long-term use of entecavir monotherapy in patients with hepatitis B virus (HBV)-related diseases after liver transplant (LT). METHODS: The clinical data on consecutive patients who underwent LT for HBV-related diseases from 2011 to 2019 were prospectively collected and retrospectively analyzed. All patients received entecavir monotherapy alone during the follow-up period; viral serology/load and liver biochemical tests were performed regularly. RESULTS: Among the total of 89 patients were patients with decompensated cirrhosis (n = 27 [30%]), acute-on-chronic HBV (n = 21 [24%]), and hepatocellular carcinoma (HCC) (n = 41 [46%]). The median age of the patients was 50 years (range, 42-58 years), and the median follow-up was 37 months (range, 1-96 months). Before LT, 45 (51%) patients did not receive, whereas 44 (49%) were currently receiving, oral antiviral therapy. At the time of LT, serum level of HBV DNA of 34 (38%) patients was >20 IU/mL, with the median level being 270,000 IU/mL (range, 4270-2,020,000), and 53 patients (59%) had undetectable levels of HBV DNA (≤20 IU/mL). The cumulative rate of hepatitis B surface antigen loss was 79.8%, 100%, and 100% after 1 month, 1 year, and 5 years, respectively. Hepatitis B surface antigen positivity returned after seroclearance in 1 patient, who died of HCC recurrence with an undetectable level of HBV DNA. The overall survival rates at 1, 3, and 5 years after LT were 94.51%, 86.84%, and 85.27%, respectively. During the follow-up period, no entecavir adverse reactions or dose reductions were observed. CONCLUSIONS: Long-term entecavir monotherapy was highly effective in preventing HBV reactivation and HBV-related diseases.

Development and validation of a prognostic classifier based on HIF-1 signaling for hepatocellular carcinoma.

HIF-1 (hypoxia-inducible factor 1) signaling played a vital role in HCC (hepatocellular carcinoma) prognosis. We aimed to establish an accurate risk scoring system for HCC prognosis prediction and treatment guidance. 424 samples from TCGA (The Cancer Genome Atlas) and 445 samples from GSE14520 dataset were included as the derivation and validation cohort, respectively. In the derivation cohort, prognostic relevant signatures were selected from sixteen HIF-1 related genes and LASSO regression was adopted for model construction. Tumor-infiltrating immune cells were calculated using CIBERSORT algorithm. HIF-1 signaling significantly increased in HCC samples compared with normal tissues. Scoring system based on SLC2A1, ENO1, LDHA and GAPDH exhibited a continuous predictive ability for OS (overall survival) in HCC patients. PCA and t-SNE analysis confirmed a reliable clustering ability of risk score in both cohorts. Patients were classified into high-risk and low-risk groups and the survival outcomes between the two groups showed significant differences. In the derivation cohort, Cox regression indicated the scoring system was an independent predictor for OS, which was validated in the validation cohort. Different infiltrating immune cells fraction and immune scores were also observed in different groups. Herein, a novel integrated scoring system was developed based on HIF-1 related genes, which would be conducive to the precise treatment of patients.

Zygomatic bone metastasis from hepatocellular carcinoma and the therapeutic efficacy of apatinib: A case report and literature review.

RATIONALE: Hepatocellular carcinoma (HCC) metastases to the zygomatic bone are extremely uncommon, and the treatment of target drugs against such case is unknown. PATIENT CONCERNS: A 48-year-old male patient was admitted to our hospital under suspicion of an advanced liver tumor due to an increase in levels of alpha-fetoprotein (AFP) after radiofrequency ablation for independent nodule in his liver 1 month before. He had a hepatitis B virus (HBV) history for 20 years without treatment. DIAGNOSIS AND INTERVENTIONS: A diagnosis of primary HCC was made based on pathological examination following right hepatectomy. Seven months after the surgery, a mass in S8 was identified and treated by ARF. Twenty days later, a right zygomatic mass was observed and the incisional biopsy revealed metastasis from HCC. Due to side effects of chemotherapy, the metastatic zygomatic mass was treated with radioactive seed implantation. Despite these interventions, there was steady increase in AFP values as well as increase in size of the zygomatic mass. Hence, the patient was started on apatinib with a dose of 500 mg/day from 1 to 28 days per cycle for a duration of 10 months. OUTCOMES: The AFP values were significantly decreased but the size of the zygomatic mass continued to increase indicating progression of disease. But the progression-free survival was more than 10 months. The patient exhibited adverse reactions which were controllable by symptomatic treatments. As of last follow-up, the patient is unwell with pain in the face, blurred vision in the right eye, dyscrasia, and exhibited difficulty in opening his mouth. LESSONS: HCC metastases to the zygomatic bone are very aggressive with a very low incidence and immunohistochemistry is useful diagnostic indicators. Still now, there is no optimal treatment strategy for these patients. Apatinib may be a promising drug in the treatment of HCC metastases to the zygomatic bone.

T cell receptor repertoire profiling predicts the prognosis of HBV-associated hepatocellular carcinoma.

Tumor-infiltrating T cell repertoire has been demonstrated to be closely associated with anti-tumor immune response. However, the relationship between T cell repertoire in tumor tissue and prognosis has never been reported in Hepatocellular carcinoma (HCC). We performed the high-throughput T cell receptor (TCR) sequencing to systematically characterize the infiltrating T cell repertoires of tumor and matched adjacent normal tissues from 23 HBV-associated HCC patients. Significant differences on usage frequencies of some Vß, Jß, and Vß-Jß paired genes have been found between the 2 groups of tissue samples, but no significant difference of TCR repertoire diversity could be found. Interestingly, the similarity of TCR repertoires between paired samples or the TNM stage alone could not be helpful to evaluate the prognosis of patients very well, but their combination could serve as an efficient prognostic indicator that the patients with early stage and high similarity showed a better prognosis. This is the first attempt to assess the potential value of TCR repertoire in HCC prognosis, and our findings could serve as a complement for the characterization of TCR repertoire in HCC.

The power of tumor sizes in predicting the survival of solitary hepatocellular carcinoma patients.

BACKGROUND: Vascular invasion, rather than tumor size, was applied into the 7th edition of the AJCC TNM staging system to predict survival of solitary hepatocellular carcinoma (HCC) patients. However, does this mean tumor size is of little value in prognostic prediction? The current study was designed to explore the prognostic ability of tumor sizes in solitary HCC. METHODS: A total of 18 591 patients with solitary HCC categorized as T1 and T2 were retrieved from the Surveillance Epidemiology and End Results (SEER) database. The Cox proportional hazards regression model was adopted to evaluate the impact of tumor sizes on overall survival (OS) and disease-specific survival (DSS) in general and in subgroups stratified by vascular invasion and surgery type. RESULTS: Large tumor sizes (>39 mm) were associated with unfavorable clinicopathologic characteristics. Compared with tumors ≤30 mm, tumors between 31-50 mm and tumors >50 mm showed significantly worse OS and DSS in general using multivariate analysis (all P < 0.001). In subgroup analyses, for patients without vascular invasion, tumor size was a notable prognostic indicator for OS in the radiofrequency ablation group (P < 0.001), rather than in the liver resection or transplantation group. Nevertheless, for patients with vascular invasion, tumor sizes exhibited a notable impact on OS in the liver resection and transplantation group. CONCLUSIONS: The AJCC TNM staging system for solitary HCC would be more comprehensive if tumor sizes were integrated into the T2 classification. Additionally, for T1 patients, tumor sizes play no role in the choice between resection and transplantation.

Laparoscopic right hemihepatic vascular inflow occlusion by lowering of the hilar plate.

INTRODUCTION: Laparoscopic liver resection under hemihepatic vascular inflow occlusion has advantages over the conventional Pringle's maneuver, especially in patients with cirrhosis. However, laparoscopic hemihepatic vascular inflow occlusion is technically challenging. SUBJECTS AND METHODS: From March 2013 to August 2013, 8 consecutive patients who underwent laparoscopic liver resection under right hemivascular inflow occlusion using the lowering of the hilar plate approach. RESULTS: There were 3 women and 5 men, with a mean age of 52.6 years (range, 44-73 years). The pathologies were hepatocellular carcinoma (n=3), sarcomatoid liver carcinoma (n=1), hepatic vascular epithelial tumor (n=1), hemangioma (n=2), and colorectal liver metastases (n=1). The types of resection included right hepatectomy (n=3), right anterior sectionectomy (n=1), segments 5 and 6 resection (n=1), and segment 6 resection (n=2). All patients underwent right hemivascular inflow occlusion. The mean operation time was 186.2 minutes (range, 100-280 minutes). The mean time taken to prepare for hemivascular inflow occlusion was 17.8 minutes (range, 15-20 minutes). The mean intraoperative blood loss was 218.8 mL (range, 100-300 mL). The mean duration of vascular control was 25.6 minutes (range, 15-40 minutes). No patients developed postoperative liver failure. There was no postoperative morbidity or mortality. The mean hospital stay was 6 days (range, 5-7 days). CONCLUSIONS: Hemihepatic vascular inflow occlusion using the lowering of the hilar plate approach was safe and feasible. It facilitated laparoscopic liver resection by minimizing blood loss during liver parenchymal transection.