Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound

BACKGROUND Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)represent the predominant histological types of primary liver cancer,comprising over 99%of cases.Given their differing biological behaviors,prognoses,and treatment strategies,accurately differentiating between HCC and ICC is crucial for effective clinical management.Radiomics,an emerging image processing technology,can automatically extract various quantitative image features that may elude the human eye.Reports on the application of ultrasound(US)-based radiomics methods in distinguishing HCC from ICC are limited.METHODS In our retrospective study,we included a total of 280 patients who were diagnosed with ICC(n=140)and HCC(n=140)between 1999 and 2019.These patients were divided into training(n=224)and testing(n=56)groups for analysis.US images and relevant clinical characteristics were collected.We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models.We compared the diagnostic performances of these ultrasomics models with that of radiologists.RESULTS Four distinct ultrasomics models were constructed,with the number of selected features varying between models:13 features for the US model;15 for the contrast-enhanced ultrasound(CEUS)model;13 for the combined US+CEUS model;and 21 for the US+CEUS+clinical data model.The US+CEUS+clinical data model yielded the highest area under the receiver operating characteristic curve(AUC)among all models,achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort.This performance exceeded even the most experienced radiologist(AUC=0.964).The AUC for the US+CEUS model(training cohort AUC=0.964,test cohort AUC=0.955)was significantly higher than that of the US model alone(training cohort AUC=0.822,test cohort AUC=0.816).This finding underscored the significant benefit of incorporating CEUS information in accurately distin-guishing ICC from HCC.CONCLUSION We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC,which outperformed experienced radiologists.

TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Hemoperitonium: Atypical Presentation Caused by Spontaneous Rupture of Hepatocellular Carcinoma in an Undiagnosed Patient

Introduction: Acute hemoperitoneum due to the spontaneous rupture of hepatocellular carcinoma (HCC) is a rare case of non-traumatic intra-abdomen bleeding that requires a high index of suspicion to approach, especially if no known history of HCC. It can mislead the physicians when the patient presents in an atypical way. Case Presentation: In this case report, we describe a fortuitous rupture of hepatocellular carcinoma in a 58-year-old male who was not previously diagnosed as having HCC and who came with atypical symptoms and signs of hemoperitoneum. He was then treated by trans-arterial embolectomy. Discussion: Diagnosis of hemoperitoneum in a case with bradycardia and hypotension is uncommon, as it goes more towards cardiogenic shock than hypovolemic shock, especially in a patient who is previously not symptomatic and has no risk factor for hepatocellular carcinoma. Conclusion: physicians should be alert to the possibility of encountering a hemorrhagic shock, although no trauma injury in any hypotensive patient with no clear reason for his condition.

Research Progress of circRNAs during Epithelial- Mesenchymal Transition of Hepatocellular Carcinoma

Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor in promoting tumor cell invasion and metastasis.Circular RNA(circRNA)is involved in regulating EMT in hepatocarcinoma cells through multiple pathways,thereby affecting the occurrence and progression of hepatocellular carcinoma.This article mainly reviews the research progress of circRNA related to EMT core transcription factors,circRNA that promotes EMT in liver cancer,and circRNA that inhibits EMT in liver cancer.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)is an effective treatment for primary hepatocellular carcinoma(PHC).Radioactive iodine therapy has been used in the treatment of advanced PHC,especially in patients with portal vein tumor thrombosis.However,data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce.AIM To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography(CT).METHODS For this study,98 advanced PHC patients were recruited and divided randomly into the study and control groups.Patients in the study group were treated with TACE combined radioactive iodine implantation therapy.Patients in the control group were treated with only TACE.The tumor lesion length,clinical effect,serum alpha-fetoprotein(AFP)and CT perfusion parameters were compared before and after therapy,and statistical analysis was performed.RESULTS There was no significant difference in tumor length and serum AFP between the study and control groups(P>0.05)before treatment.However,the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy.After 3 mo of treatment,the complete and partial remission rate of the study group was 93.88%,which was significantly higher than the control group(77.55%)(P<0.05).Before treatment,there were no significant differences between the two groups on the perfusion CT variables,including the lesion blood volume,permeability surface,blood flow,hepatic artery flow and mean transit time(P>0.05).After 3 mo of treatment,all perfusion CT variables were lower in the study group compared to the control group(P<0.05).The survival time of patients in the study group was 22 mo compared to 18 mo in the control group,which was significantly different[log rank(Mantel-Cox)=4.318,P=0.038].CONCLUSION TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions,thereby improving the clinical efficacy and prolonging the survival time of patients.

Effects of kanglaite capsules combined with transcatheter arterial chemoembolization （TACE） on patients with mid or late-stage primary hepatocellular carcinoma （HCC）

Objective： To observe the clinical effects of kanglaite （KLT） capsules combined with transcatheter arterial chemoembolization （TACE） in treating patients with mid or late-stage primary hepatocellular carcinoma （HCC）. Methods： Sixty-five cases were randomly divided into 2 groups, 32 patients in combination group received the treatment of KLT capsules ＋ TACE and 33 patients in control group were treated with TACE alone. The objective response rate （RR）, serum alpha fetoprotein （AFP）, peripheral blood T lymphocyte subgroups （T-LS）, quality of life （QOL）, time to progression （TTP） and adverse reaction were observed and compared between 2 groups. Results： The objective response rate and serum alpha fetoprotein levels had no significant difference between the two groups （P 〉 0.05）. Combination group was superior to control group in quality of life （QOL）, time to progression （TTP）, peripheral blood T lymphocyte subgroups （CD3＋, CD4＋, CD4＋／CD8 ratio） and liver adverse reactions, with significant differences （P 〈 0.05）. Conclusion： KLT capsules combined with TACE is an effective method to treat primary hepatocellular carcinoma （HCC） patients who have lost the opportunity of surgical therapy.

Liver Resection for Spontaneous Rupture of Primary Hepatocellular Carcinoma

Objective To study the effect of liver resection for spontaneous rupture of primary hepatocellulal carcinoma (PHCC). Methods The clinical data of 12 patients with ruptured PHCC treated by liver resection in Xiangya Hospital since 1970 were analyzed retrospectively. Results There were 10 males and 2 females with mean age of 42 (ranged 22–65) years in this series. Of the 12 patients, 11 underwent emergent hepatectomy and one 2-stage hepatectomy, including left segmental liver resection in 6 patients, left median lobectomy in 1, left hemihepatectomy in 1, partial right hepatectomy in 2, and tumor resection in 2. There was no operative death in 11 patients with liver function in grade A of Child-Paugh classification, but 1 patient with grade B liver function died of liver failure after operation. The operative mortality was 8.3%. In 11 survived patients, the postoperative median survival time was 16.5 months. The 1?, 3?, 5-year survival rate was 72.7%, 18.2%, 9.1% respectively; among them one patient has been alive free of the tumor for 25 years and 9 months. Conclusion Liver resection is the best treatment for ruptured PHCC when possible, which can result in long survival time. Key words liver resection - spontaneous ruptare - primary hepatocellular carcinoma

Surgical treatment for recurrent hepatocellular carcinoma:Current status and challenges

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020.It includes hepatocellular carcinoma(HCC)(representing 75%-85%of cases),intrahepatic cholangiocarcinoma(representing 10%-15%of cases),and other rare types.The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years;however,high tumor recurrence rates continue to limit long-term survival,even after radical surgical resection(exceeding 50%recurrence).For resectable recurrent liver cancer,surgical removal[either salvage liver transplantation(SLT)or repeat hepatic resection]remains the most effective therapy that is potentially curative for recurrent HCC.Thus,here,we introduce surgical treatment for recurrent HCC.Areas Covered:A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022.Expert commentary:In general,long-term survival after the reresection of recurrent liver cancer is usually beneficial.SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients;however,SLT is constrained by the supply of liver grafts.SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival.When considering the similar overall survival rate and the current situation of donor shortages,repeat liver resection remains an important option for recurrent HCC.

Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

Combination of serum tumor markers dickkopf-1,DCP and AFP for the diagnosis of primary hepatocellular carcinoma

Objective:To evaluate the detection accuracy of the biomarkers dickkopf-1,DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers.Methods:The study was composed of three groups,one with HCC patients,one with non-HCC liver diseases and one with healthy controls.Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA.The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel.Results:The HCC group showed higher levels of dickkopf-1,DCP and AFP than the other two groups(P<0.05).Dickkopf-1 showed better sensitivity(73.26%vx.58.13%.P<0.05) and better specificity(44.00%vs.29.00%,P>0.05) than AFP.DCP also had better sensitivity(74.42%vs.58.13%.P<0.05) than AFP,but their specificity was similar(30.00%vs.29.00%.P>0.05).The combination of the biomarkers as a scrum panel produced much better sensitivity(93.02%) and specificity(78.00%) than each of the markers individually(P<0.05).Conclusion:The combination of AFP.DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone.The tests are convenient and inexpensive,and may serve as a valuable addition to current options for the diagnosis of HCC.

Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients:Incidence and risk factors

AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma(HCC) in Chinese patients with primary biliary cirrhosis(PBC).METHODS: We reviewed the data of 52 PB Cassociated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13%(52/1255) and was significantly higher in the males(9.52%) than in the females(3.31%). Among the 52 PBC patients with HCC, 55.76%(29/52) were diagnosed with HCC and PBC simultaneously, and 5.76%(3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCCwere more likely than the females to have undergone blood transfusion(18.75% vs 8.33%, P = 0.043), consumed alcohol(31.25% vs 8.33%, P = 0.010), smoked(31.25% vs 8.33%, P = 0.010), had a family history of malignancy(25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase(P < 0.05). Conditional logistic regression analysis revealed that body mass index(BMI) ≥ 25 [adjusted odds ratio(AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake(AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.

Diagnostic value of imaging examinations in patients with primary hepatocellular carcinoma

Primary hepatocellular carcinoma(PHC) includes hepatocellular carcinoma, intrahepatic cholangiocarcinoma and other pathological types and is characterized by rapid progression. Most of the clinical diagnoses are made at late stage or when distant metastasis occurs, increasing the difficulty of treatment and resulting in a poor prognosis. Therefore, the early diagnosis of PHC plays an important role in timely treatment and the improvement of prognosis. The gold standard for the diagnosis of primary liver cancer is liver biopsy, but it has limitations as an invasive examination. Presently, imaging has become the first choice for the diagnosis of liver cancer. We here summarize the new methods and techniques of imaging in diagnosis and evaluation of primary liver cancer in recent years, including ultrasonography, computed tomography perfusion imaging, diffusion-weighted imaging technology-voxel incoherent motion, diffusion tensor imaging, iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantification, dynamic enhanced magnetic resonance imaging and hepatocyte-specific contrast medium imaging. Imaging diagnosis can not only evaluate the degree of differentiation, blood supply and perfusion, and invasiveness of the lesion, but also predict the prognosis, evaluate liver function, andprovide references for clinical diagnosis and treatment.

Emergency caudate lobectomy for ruptured hepatocellular carcinoma with multiple primary cancers

We report a case of metachronous multiple primary malignancies involving both rectum and liver with colonic metastasis from hepatocellular carcinoma(HCC) through hematogenous pathway.A 72-year-old woman was admitted to the emergency department with right upper abdominal pain for 4 h.Considering her surgical history of Mile's procedure plus liver resection for rectal cancer with liver metastasis three years ago and the finding of urgent computed tomography scan on admission,the preoperative diagnosis was spontaneous rupture of rectal liver metastasis located in caudate lobe and colonic metastasis from rectal cancer. The patient underwent an emergency isolated caudate lobectomy at a hemorrhagic shock status.Pathology reported a primary HCC in the caudate lobe and colonic metastasis of HCC with tumor embolus in the surrounding vessels of the intestine.No regional lymph node involvement was found.It is hypothesized that HCC may disseminate hematogenously to the ascending colon,thus making it a rare case.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.

Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study

Objective: To observe the clinical efficacy of tran- scatheter arterial chemoembolization (TACE) and TACE+MLT (melatonin) on inoperable advanced primary hepatocellular carcinoma. Methods: From January 1997 to January 1998, one hundred patients with inoperable advanced primary hepatocellular carcinoma were treated separately by TACE (50) and TACE+MLT (20 mg/d at 8:00 PM orally, 7 days before TACE) (50). Results: The effective rates (WHO standards) of TACE and TACE+MLT were 16% and 28% respec- tively (P<0.05). After TACE or TACE+MLT, the resection rate at two-stage of TACE was 4% or 14% (P<0. 01). The 0.5-, 1- and 2-year survival rates in the TACE group were 82%, 54% and 26% respectively; in the TACE+MLT group 100%, 68% and 40% respectively. The results were significantly better in the TACE+MLT group than in the TACE group. MLT could protect liver function from the damage caused by TACE. The IL-2 levels of all pa- tients significantly increased, whereas sIL-2R expres- sions decreased after TACE+MLT as compared with the TACE group (P<0.01). Conclusions: With definite protection and treatment effect on the liver function damage caused by TACE, MLT can enhance the immunological activities of pa- tients. It also can improve the effect of TACE by in- creasing the survival and resection rate after two- stage operation.

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)].Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and Liver Transplantation

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.