BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.
Aged ; Antiviral Agents/*therapeutic use ; Bilirubin/blood ; Carcinoma, Hepatocellular/*therapy ; Chemoembolization, Therapeutic/*adverse effects ; Female ; Gastrointestinal Hemorrhage/etiology ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B/complications/*drug therapy ; Humans ; Hypoalbuminemia/etiology ; Incidence ; Liver/physiopathology ; Liver Diseases/epidemiology/*etiology ; Liver Neoplasms/*therapy ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Treatment Outcome

OBJECTIVETo explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE).

METHODSA retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects.

RESULTSThe patients of preoperative TACE therapy group had a higher level of γ-glutamyl transpeptidase before operation (119.52±98.83) U/L vs. (67.39±61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60±95.43) min vs. (218.70±75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30-d death neither in the treatment group and matched control group.

CONCLUSIONSPreoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery.

Carcinoma, Hepatocellular ; blood supply ; therapy ; Case-Control Studies ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Hepatectomy ; methods ; Humans ; Liver ; physiopathology ; Liver Neoplasms ; blood supply ; therapy ; Operative Time ; Preoperative Period ; Recovery of Function ; Retrospective Studies ; gamma-Glutamyltransferase ; analysis

Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/physiopathology/*radiography ; Female ; Humans ; Liver Neoplasms/drug therapy/physiopathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo investigate whether the ERK/FoxO3a signal axis could induce the inhibitory effect of vitexin 1 (VB-1) in HepG2 cell proliferation.

METHODThe MTT method was adopted to observe the effect of different concentrations of VB-1 on human hepatoma carcinoma cell line HepG2 and immortalized human embryo liver cell line L-02. The cell growth was assessed by the clone formation assay. The protein phosphorylation levels of ERK1/2 and FoxO3a were measured by the western blot.

RESULTVB-1 inhibited the viability of HepG2 cell line in a concentration-dependent manner, with a weak effect on L-02 cell line. VB-1 could effectively inhibit the anchorage-dependent growth of HepG2 cells, and reduce the expression levels of pERK1/2 and pFoxO3a in a concentration-dependent manner. MEK1/2 inhibitor PD98059 could enhance VB-1' s effect in inhibiting HepG2 cell proliferation and ERK1/2, FoxO3a phosphorylation.

CONCLUSIONVB-1 inhibits the proliferative activity of hepatoma carcinoma cell line HepG2 by blocking the ERK/FoxO3a signal axis.

Apigenin ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; genetics ; metabolism ; Growth Inhibitors ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Signal Transduction ; drug effects

OBJECTIVEThe efficiency network is a complicated network for revealing the efficient mechanism of traditional Chinese medicines (TCMs) and relations among efficiencies. The efficiency-property relations were used to establish a warm-pungent-liver efficiency network to explain the principle of treating hepatoma with medicines invigorating blood circulation and eliminating blood stasis. Safflower, a warm-pungent medicine distributing along the live meridian, was taken for example to discuss the efficiency network' s application in the identification of active ingredients of TCMs and the combination.

METHODIn the early stage of this study, combined warm-pungent-liver medicines distributed along the liver meridian and invigorating blood circulation and eliminating blood stasis were taken as the study objects to collect the pharmacological effect data of warm-pungent-liver medicines and obtain the pharmacological effect combinations with the highest blood circulation-invigorating association by the association rules and the chi-square test. The pharmacological target data recorded in the DrugBank database is used to establish the warm-pungent-liver efficiency network according to the principle line of "efficiency-property-pharmacology-target-protein interaction" under the background of the protein interaction network.

RESULTThe blood circulation-invigorating medicines could directly treat hepatoma by impacting protooncogene, cancer suppressor gene, cell apoptosis and anti-inflammation, and indirectly treat hepatoma by resisting coagulation and adhesion, regulating local blood circulation, preventing cancer cell metastasis and enhancing the tissues' sensitivity to the anticancer drugs. Among the active ingredients of safflower screened based on the blood circulation-invigorating network targets, carthamin yellow, quercetin and luteolin have been proved to have the anti-hepatoma effect in literatures, which indicated the reliability of this study's results and the purpose of the efficiency network.

CONCLUSIONThe efficiency network is an effective method for revealing the TCM's mechanism, and lays a foundation for discovering key active ingredients of TCMs for treating specific diseases.

Antineoplastic Agents, Phytogenic ; chemistry ; therapeutic use ; Blood Circulation ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Gene Regulatory Networks ; drug effects ; Humans ; Liver ; blood supply ; drug effects ; Liver Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology

OBJECTIVETo investigate the anti-proliferative effects of curcumol, an herbal extract from curcuma, in human hepatocarcinoma HepG2 cells, and its possible molecular mechanism.

METHODThe effects of curcumol on human hepatocarcinoma cells were assessed in vitro. Proliferation of HepG2 cells treated with various concentration (2.5-10 mg x L(-1)) of curcumol was determined using the MTT assay and the distribution of cell cycle of HepG2 cells was analyzed using the FCM technique. Expression of 14 cell cycle regulation-related genes were assessed by TaqMan real-time polymerase chain reaction (RT-PCR) method and Western blot.

RESULTCurcumol significantly inhibited the proliferation of HepG2 cells and induced G1 phase arrest in a dose- and time-dependent manner. The mRNA levels of pRB1, cyclin D1, CDK2, CDK8 and p27KIP1 were elevated, while cyclin A1 decreased, in both of the low (25 mg x L(-1)) and the high dose (100 mg x L(-1)) treatment of curcumol. There were no significant changes in the expression of either cyclin E1 or CDK4. The expression of p53 and its target genes p21WAF1 and Wip1 protein were increased.

CONCLUSIONCurcumol can inhibit the proliferation of HepG2 cells in vitro and induce G1 arrest of cell cycle through mechanisms activating p53 and pRB pathways that involve genes of cyclin A1, CDK2, CDK8, p21WAF1 and p27KIP1.

Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Sesquiterpenes ; pharmacology

AIMS: To investigate the antitumor effects of extracts from Oxytropis falcata on human hepatocellular carcinoma SMMC-7721 cells in vitro and in transplanted murine H22 tumors in vivo. METHODS: Cell proliferation, cell cycle distribution and apoptosis in SMMC-7721 cells were determined and tumor growth inhibition in H22 tumors was investigated. Cell cycle distribution was analyzed by flow cytometry with propidium iodide (PI) and Annexin V-FITC/ PI double staining. RESULTS: MTT assay revealed that essential oil and flavonoids of O. falcata (named EOOF and FOF) inhibited proliferation of SMMC-7721 cells in a dose-dependent manner. The IC50 value of EOOF and FOF were 0.115 and 0.097 mg·mL(-1), respectively. Cell cycle was arrested at G(1) phase, and induction of apoptosis occurred in SMMC-7721 cells when subjected to FOF. Growth inhibition in H22 solid tumors transplanted mice was significantly pronounced after being treated with FOF, and the inhibition ratio were 56.1% and 70.8% at the concentration of 30 and 60 mg·kg(-1). CONCLUSION The results suggest that FOF promotes apoptosis in SMMC-7721 cells and inhibits H22 tumor growth, resulting in a potential antitumor effect on hepatic cancer.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Growth Inhibitors ; administration & dosage ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Oxytropis ; chemistry

OBJECTIVETo compare the efficacies of portal vein stenting and transcatheter arterial chemoembolization (TACE) combined therapy performed with or without endovascular implantation of iodine-125 (125I) seeds strand in patients with hepatocellular carcinoma (HCC) and main portal vein tumor thrombus (MPVTT).

METHODSOne-hundred-and-six patients with HCC complicated by MPVTT who were treated with portal vein stents and TACE, either with (Group A, n=56) or without (Group B, n=50) endovascular implantation of 125I seeds strand, between July 2005 and April 2011, were retrospectively analyzed. Overall survival, stent patency, and procedure-related adverse events were compared between the two groups.

RESULTSThe technical success rate was 100% for placement of 125I seeds strands and stents in the obstructed main portal vein. No serious procedure-related adverse events were recorded. Group A had significantly higher median survival (335 days vs. group B: 146 days; P=0.001, hazard ratio (HR)=2.244). Additionally, group A had significantly higher median stent patency (400 days vs. group B: 190 days; P=0.005, HR=2.479).

CONCLUSIONThe combination therapeutic strategy of portal vein stenting and TACE with endovascular implantation of 125I seeds strands improves the survival of HCC patients with MPVTT complication.

Carcinoma, Hepatocellular ; complications ; therapy ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Female ; Humans ; Iodine Radioisotopes ; administration & dosage ; therapeutic use ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Portal Vein ; physiopathology ; surgery ; Retrospective Studies ; Stents ; Treatment Outcome ; Venous Thrombosis ; complications ; therapy

BACKGROUND/AIMS: We evaluated changes in liver function parameters and risk factors for the deterioration of liver function 12 months after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC). METHODS: The subjects in this retrospective study comprised 102 patients with HCC who had undergone RFA therapy and exhibited no recurrence of HCC 12 months thereafter. Serial changes in serum total bilirubin and albumin, prothrombin time, and Child-Pugh score were evaluated before RFA and 3, 6, 9, and 12 months thereafter. Deterioration of liver function was defined when the Child-Pugh score increased by at least 2 at 12 months after RFA therapy. We determined the factors related to aggravation of liver function after RFA therapy. RESULTS: Liver function had deteriorated 12 months after RFA in 29 patients (28.4%). Serum albumin levels decreased significantly from before (3.7+/-0.1 g/dL, mean+/-SD) to 12 months after RFA therapy (3.3+/-0.1 g/dL, P=0.002). The Child-Pugh score increased significantly during the same time period (from 6.1+/-0.2 to 7.2+/-0.3, P<0.001). Pre-RFA thrombocytopenia (< or =100,000/mm3) was revealed as a significant risk factor for the deterioration of liver function after RFA. However, no patients had episodes of bleeding as a complication of RFA. CONCLUSIONS: Among the liver-function parameters, serum albumin level was markedly decreased in HCC patients over the course of 24 months after RFA therapy. A pre-RFA thrombocytopenia represents a major risk factor for the deterioration of liver function.
Adult ; Aged ; Aged, 80 and over ; Bilirubin/blood ; Carcinoma, Hepatocellular/complications/physiopathology/*therapy ; Catheter Ablation/*adverse effects ; Down-Regulation ; Female ; Humans ; Liver Neoplasms/*complications/physiopathology/*therapy ; Male ; Middle Aged ; Odds Ratio ; Prothrombin Time ; Retrospective Studies ; Risk Factors ; Serum Albumin/analysis ; Severity of Illness Index ; Thrombocytopenia/*complications

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan(R)) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.
Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/epidemiology/physiopathology ; Chronic Disease ; *Elasticity Imaging Techniques ; Hepatitis B/drug therapy/physiopathology ; Hepatitis C/drug therapy/physiopathology ; Humans ; Liver Cirrhosis/*diagnosis/ultrasonography ; Liver Neoplasms/epidemiology/physiopathology ; Recurrence