Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide,with a 5-year relative survival rate of approximately 18%.The similarity between incidence and mortality(830000 deaths per year)underscores the bleak prognosis associated with the disease.HCC is the fourth most common malignancy and the second leading cause of cancer death in China.Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus(HBV)or hepatitis C virus(HCV)infection,alcoholism or alcoholic steatohepatitis,nonalcoholic fatty liver disease,or nonalcoholic steatohepatitis.Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC.Although the total number of human immunodeficiency virus(HIV)-infected patients is declining globally the incidence of HCC is increasing in HIVinfected patients,especially those who are coinfected with HBV or HCV.As a result,people infected with HIV still face unique challenges in terms of their risk of developing HCC.AIM To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection.METHODS The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed.Among these,27 patients underwent hepatectomy(operation group)and 29 patients received conservative treatment(nonoperation group).All patients signed informed consents in line with the provisions of medical ethics.The general data,clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified.RESULTS The median disease-free survival(DFS)and overall survival(OS)of HIV-HCC patients in the surgical group were 13 months and 17 months,respectively,and the median OS of patients in the nonsurgical group was 12 months.The OS of the surgical group was significantly longer than that of the control group(17 months vs 12 months,respectively;P<0.05).The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis,postoperative microvascular invasion(MVI),a CD4+T-cell count<200/μL,Barcelona stage C-D,and men who have sex with men(MSM;P<0.05).CONCLUSION Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination,late tumor detection,late BCLC stage,CD4+T<200/μL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy.In addition,there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV,Child-Pugh score,alpha-fetoprotein measurement value,and HART-efficient antiretroviral therapy after the diagnosis of HIV(P<0.05).Therefore,these factors may also affect the survival and prognosis of patients.

Clinical study of standard residual liver volume and transient elastography in predicting poor prognosis of patients after hemihepatectomy

BACKGROUND Liver cancer resection,especially in patients with hemihepatectomy or extended hemihepatectomy,often leads to poor prognosis,such as liver insufficiency and even liver failure and death,because the standard residual liver volume(SRLV)cannot be fully compensated after surgery.AIM To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches.METHODS The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed.The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy.It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation.RESULTS The liver stiffness measure(LSM)value and SRLV were associated with liver dysfunction after hemihepatectomy.Logistic regression analysis showed that an LSM value≥25 kPa[odds ratio(OR)=6.254,P<0.05]and SRLV≤0.290 L/m^(2)(OR=5.686,P<0.05)were independent risk factors for postoperative liver dysfunction.The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score(P<0.05).CONCLUSION SRLV and LSM values can be used to evaluate the safety of hemihepatectomy.The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.

Effect of NDC80 in human hepatocellular carcinoma

AIM To investigate the role of nuclear division cycle(NDC)80in human hepatocellular carcinogenesis.METHODS NDC80 gene expression was analyzed by real-time reverse transcription polymerase chain reaction in 47paired hepatocellular carcinoma(HCC)and adjacent tissues.The HCC cell line SMMC-7721 was transfected with lentivirus to silence endogenous NDC80 gene expression,which was confirmed by real-time polymerase chain reaction and western blotting.The effects of NDC80silencing on SMMC-7721 cell proliferation were evaluated by Cellomics Array Scan VTI imaging.Cell cycle analysis and apoptosis were detected with flow cytometry.Colony formation was assessed by fluorescence microscopy.RESULTS NDC80 expression levels in HCC tissues were significantly higher than those in the adjacent tissues.Functional studies demonstrated that NDC80 silencing significantly reduced SMMC-7721 cell proliferation and colony formation.Knockdown of NDC80 resulted in increased apoptosis and cell cycle arrest at S-phase.NDC80 contributed to HCC progression by reducing apoptosis and overcoming cell cycle arrest. CONCLUSION Elevated expression of NDC80 may play a role in promoting the development of HCC.

Mucosal-associated invariant T cells in hepatitis B virus-related liver failure

BACKGROUND Liver failure has high mortality and poor prognosis,and establishing new reliable markers for predicting its prognosis is necessary.Mucosal-associated invariant T(MAIT)cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease,and their potential role in liver failure remains unclear.AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus(HBV)-related liver failure.METHODS We recruited 55 patients with HBV-related liver failure,48 patients with chronic hepatitis B and 40 healthy controls(HCs)from Nantong Third People’s Hospital Affiliated to Nantong University.Peripheral blood mononuclear cells were isolated,and the percentage and number of circulating MAIT cells were detected by flow cytometry.Plasma levels of interleukin(IL)-7,IL-12p70,IL-18 and interferon-αwere measured by Luminex assay.RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients(percentage:2.00±1.22 vs 5.19±1.27%,P<0.0001;number:5.47±4.93 vs 84.43±19.59,P<0.0001)compared with HCs.More importantly,there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure.Circulating MAIT cells partially recovered after disease improvement,both in percentage(4.01±1.21 vs 2.04±0.95%,P<0.0001)and in cell count(17.24±8.56 vs 7.41±4.99,P<0.0001).The proportion(2.29±1.01 vs 1.58±1.38%,P<0.05)and number(7.30±5.70 vs 2.94±1.47,P<0.001)of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group,and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells(both percentage and cell count)predicted poor overall survival(P<0.01).Also,the levels of IL-12(20.26±5.42 pg/mL vs 17.76±2.79 pg/mL,P=0.01)and IL-18(1470.05±1525.38 pg/mL vs 362.99±109.64 pg/mL,P<0.0001)were dramatically increased in HBV-related liver failure patients compared with HCs.CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.

Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice

BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.

Cyr61 Alleviates Cholangitis by Inhibiting Cytotoxic Effects of CD8^(+) T Cells on Biliary Epithelial Cells

Objective:Primary biliary cholangitis(PBC)is a chronic progressive cholestatic liver disease.In recent years,researchers have found that cysteine-rich angiogenic inducer 61(Cyr61,also known as CCN1)has a potential role in reducing portal inflammation in patients with PBC.This study aimed to explore the relationship between Cyr61 and PBC to provide new ideas and an experimental basis for the clinical treatment of PBC.Methods:After induction of the overexpression of Cyr61 in a mouse model of PBC using recombinant adenovirus,hematoxylin and eosin staining and pathological scores were used to indicate intrahepatic inflammation and bile duct damage.Real-time PCR was used to detect changes in inflammation-related cytokines in the liver.To further study the mechanism,we assessed whether Cyr61 protects bile duct epithelial cells from cytotoxic effects.Results:Serum and hepatic Cyr61 levels were increased in the murine model of PBC.Overexpression of Cyr61 alleviated hepatic inflammation and bile duct injury in vivo.Cyr61 inhibited the cytotoxic effects of CD8^(+)T cells by acting on biliary epithelial cells(BECs)in vitro.Conclusion:Our results provide novel insight into the pathogenesis of PBC and suggest that Cyr61 plays a dominant role in the cytotoxic effects on BECs in PBC.Consequently,therapeutic strategies targeting Cyr61 could be a potent therapy for PBC.