Liver Cancer Recurrence Research Articles

Influence of baseline MELD score in the efficacy of treatment of hepatitis C with simeprevir and sofosbuvir

IntroductionThere are few published studies on predictors of response to treatment with sofosbuvir and simeprevir in HCV patients. ObjectiveThe objective of the study was to analyse possible predictors of response to simeprevir (SMV) and sofosbuvir (SOF) in patients infected with hepatitis C genotypes 1 or 4. Patients and methodsProspective observational cohort study in 12 hospitals. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Results204 patients (62.3% male, mean age 55 years) were included: 186 (91.2%) genotype 1 (60.3% 1b 25% 1a) and 18 (8.8%) genotype 4. 132 (64.7%) cirrhotic (87.9% Child A), 33 (16.2%) F3, 31 (15.2%) F2, 8 (3.9%) F0–1. 80.8% MELD<10. 93 (45.6%) naive. Ribavirin was added in 68 (33.3%). Mean baseline viral load 2,151,549IU/ml (SD: 2,391,840). Treatment duration 12 weeks in 93.1%. 4 discontinued therapy: suicide, psychotic attack, hyperbilirubinaemia and liver cancer recurrence. 190 (93.1%) achieved SVR12. There were no differences in SVR12 depending on the genotype, treatment duration, ribavirin use, prior therapy, viral load (VL) or baseline platelets. In univariate analysis, undetectable VL at 4 weeks (p=0.042), absence of cirrhosis (p=0.021), baseline albumin ≥4g/dl (p=0.001) and MELD<10 (p<0.0001) were associated with higher SVR12. In multivariate analysis, only baseline MELD score <10 patients had higher SVR12 (p<0.001). ConclusionsThe combination of simeprevir and sofosbuvir in patients infected with genotype 1 and 4 hepatitis C is highly effective. It is a safe therapy, especially in patients without ribavirin. This combination was more effective in patients with a MELD score below 10.

Correlations of pri-Let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer after transcatheter arterial chemoembolization

Background and aimSingle nucleotide polymorphisms (SNPs) within miRNAs could change their production or affinity with target genes, thus leading to malignant diseases. This study aims to explore correlations of pri-let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer (PLC) after a transcatheter arterial chemoembolization (TACE) surgical procedure. Materials and methodsA total of 302 PLC patients treated with hepatoprotective therapies after TACE were selected to and assigned into recurrent and non-recurrent groups. Genotypes of pri-let-7a-1 rs1073997 and pri-let-7a-2 rs629367 were analyzed by Taqman assay. The relationship between PLC with the mutation of each SNP was determined by a multivariate logistic regression analyses. Moreover, the association between survival and pri-let-7 gene polymorphisms was analyzed by the Kaplan-Meier method. The Progress Free Survival (PFS) curve, correlation of pri-let-7a-1 rs629367 with alcohol, HBsAg-positive and TNM III/IV were analyzed by a stratified analysis. Additionally, the risk factors for the recurrence of PLC were analyzed by a multivariate logistic regression analyses. ResultsResults showed that the allelic frequency of the pri-let-7a-2 rs629367 SNP in the recurrent group was higher than that of the non-recurrent group. The distribution of CC genotype was significantly higher than non-CC genotype in the recurrent group. Alcohol consumption, positive expression of hepatitis B surface antigen (HBsAg), AC + CC genotype of rs629367 and TNM III/IV were determined to be the risk factors for the recurrence and metastasis of PLC after TACE. We found a positive correlation between pri-let-7a-2 rs629367 with alcohol consumption, HBsAg-positive and TNM III/IV. The median PFS of HBsAg-positive and TNM III/IV patients with the AC + CC genotype of rs629367 was shorter than those with non-AC + CC genotype. ConclusionOur findings provide evidence that patients with PLC that carry the AC + CC genotype of pri-let-7a-2 rs629367 after TACE have a worse prognosis than those who carry the AA genotype. We speculate that the pri-let-7 rs629367 SNP could be used as a predictor of recurrence and metastasis after TACE for patients with PLC.

Impression of direct-acting antiviral agents in the treatment of recurrent hepatocellular carcinoma related to chronic hepatitis C

The treatment of chronic hepatitis C has gradually entered into the era of direct-acting antiviral agents (DAAs) from the era of pegylated interferon-α combined with ribavirin, which has a high curative effect, good tolerability, and complete patient-friendly oral form of administration. Sustained virologic response (SVR) acquired by pegylated interferon-α plus ribavirin therapy has been widely recognized by scholars in reducing the recurrence of primary liver cancer and liver cancer, especially in cirrhotic patients. The clinical application time of DAAs is short and its report is inconsistent with the increase or decrease of primary liver cancer and liver cancer recurrence. Simultaneously, the effect of SVR in people with hepatocellular carcinoma on DAAs seems to be different from those in patients without hepatocellular carcinoma. This article reviews some of the existing reports in order to increase the understanding of DAAs and liver cancer and serve the long-term benefit of clinical treatment.

Inhibition of CREB binding protein-beta-catenin signaling down regulates CD133 expression and activates PP2A-PTEN signaling in tumor initiating liver cancer cells

BackgroundThe WNT-beta-catenin pathway is known to regulate cellular homeostasis during development and tissue regeneration. Activation of WNT signaling increases the stability of cytoplasmic beta-catenin and enhances its nuclear translocation. Nuclear beta-catenin function is regulated by transcriptional co-factors such as CREB binding protein (CBP) and p300. Hyper-activated WNT-beta-catenin signaling is associated with many cancers. However, its role in inducing stemness to liver cancer cells, its autoregulation and how it regulates tumor suppressor pathways are not well understood. Here we have investigated the role of CBP-beta-catenin signaling on the expression of CD133, a known stem cell antigen and PP2A-PTEN pathway in tumor initiating liver cancer cells.MethodsHuman hepatoblastoma cell line HepG2 and clonally expanded CD133 expressing tumor initiating liver cells (TICs) from premalignant murine liver were used in this study. CBP-beta-catenin inhibitor ICG001 was used to target CBP-beta catenin signaling in liver cancer cells in vitro. Western blotting and real time PCR (qPCR) were used to quantify protein expression/phosphorylation and mRNA levels, respectively. CBP and CD133 gene silencing was performed by siRNA transfection. Fluorescence Activated Cell Sorting (FACS) was performed to quantify CD133 positive cells. Protein Phosphatase (PP2A) activity was measured after PP2AC immunoprecipitation.ResultsCBP inhibitor ICG001 and CBP silencing significantly reduced CD133 expression and anchorage independent growth in HepG2 and murine TICs. CD133 silencing in TICs decreased cell proliferation and expression levels of cell cycle regulatory genes, CyclinD1 and CyclinA2. ICG001 treatment and CBP silencing reduced the levels of phosphoSer380/Tyr382/383PTEN, phosphoSer473-AKT, Phospho-Ser552beta-catenin in TICs. ICG001 mediated de-phosphorylation of PTEN in TICs was PP2A dependent and partly prevented by co-treatment with PP2A inhibitor okadaic acid.ConclusionsCBP-beta-catenin signaling promotes stemness via CD133 induction and cell proliferation in TICs. We found a novel functional link between CBP-beta-catenin and PP2A-PTEN-AKT pathway in liver TICs. Therefore, CBP-beta-catenin-PP2A-PTEN-AKT signaling axis could be a novel therapeutic target to prevent liver tumor initiation and cancer recurrence.

Hepatitis C eradication with DAA and risk of liver cancer recurrence: The debate unrests.

Hepatitis C eradication with DAA and risk of liver cancer recurrence: The debate unrests.

The mechanism and current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation

The recurrence rate of hepatocellular carcinoma (HCC) after liver transplantation is still high, seriously affecting the long-term survival rate. The current research results show that the mechanism of postoperative recurrence of liver cancer is mainly related to residual micro-lesions, hepatitis, regeneration and immunosuppression. Milan criteria for liver transplantation, tumor vascular invasion, degree of differentiation, surgical procedures, and the use of calcineurin immunosuppressive agents are risk factors for recurrence of HCC after liver transplantation, and biomarkers such as genes and miRNAs that respond to biological characteristics of the tumor have been gradually used in HCC recurrence risk stratification and predicting prognosis. The use of mTOR inhibitors, preoperative interventional treatment before liver transplantation and non -tumor ablation technique are the main effective methods to prevent the recurrence of HCC. Hepatectomy is still the most effective treatment for patients with recurrent HCC after transplantation, and intervention with sorafenib in combination with mTOR inhibitors can benefit the survival of most patients.

NF-κB-regulated miR-155, via repression of QKI, contributes to the acquisition of CSC-like phenotype during the neoplastic transformation of hepatic cells induced by arsenite.

Chronic exposure to arsenite can cause various human tumors. For the initiation and recurrence of human liver cancer, the acquisition of CSC-like properties is essential. In various cancers, microRNAs (miRNAs) act as regulators in induction of CSC-like properties. Liver cancers over-express miR-155, but the mechanism relating miR-155 and arsenite-induced liver cancer is unknown. Here, we show that long-term exposure of L-02 cells to arsenite increases miR-155 levels by activation of NF-κB and leads to the acquisition of CSC-like properties. In spheroids formed from arsenite-transformed L-02 cells, the levels of miR-155 positively relate to the levels of CD90, EpCAM, and OCT4. Inhibition of miR-155, by reduction of SOX2 and OCT4, results in suppression of spheroid formation. Luciferase reporter assays indicate that QKI is a target of miR-155. Inhibition of QKI expression by miR-155 promotes arsenite-induced acquisition of CSC-like properties, whereas QKI over-expression has the opposite effect. Collectively, the findings demonstrate that miR-155, driven by NF-κB, reduces QKI expression and is involved in acquisition of the CSC-like phenotype during neoplastic transformation of hepatic cells induced by arsenite.

Sialyl Lewisx expression at the invasive front as a predictive marker of liver recurrence in stage II colorectal cancer.

Sialyl Lewisx (SLX) is a carbohydrate ligand for endothelial selectin that participates in cell adhesion, proliferation and scattering. It plays an important role in cancer cell adhesion to vascular endothelial cells, leading to hematogenous metastasis. The prognostic significance of SLX expression level at the invasive front in patients with stage II colorectal cancer (CRC) was examined. A total of 209 patients with stage II CRC curatively resected between 1997 and 2000 were enrolled. The preoperative serum SLX levels measured by radioimmunoassay and SLX immunoexpression levels at the invasive front, and at the non-invasive frontal region determined by tissue microarray were analyzed. SLX expression at the invasive front was positively associated with tumor invasion depth (P=0.007) and tumor budding grade (P=0.038). Disease-free survival curves differed between the high and low SLX-expression groups (5-year survival rates, 77.0 and 89.7%, respectively; P=0.036). Liver cancer recurrence was more frequent in the high-expression group than in the low-expression group (15.9 and 2.4%; P=0.002). Multivariate analysis revealed that its expression (hazard ratio, 5.26; P=0.015) and venous invasion (hazard ratio, 4.14; P=0.040) were independent predictive markers of liver cancer recurrence. Neither the preoperative serum SLX level nor SLX expression at the non-invasive frontal region showed any association with histopathological features or disease-free survival. SLX expression level at the invasive front is a promising marker for identifying patients with stage II CRC with a high risk of liver cancer recurrence.

Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts hepatocellular carcinoma incidence and recurrence in nucleos(t)ide analogue therapy for chronic hepatitis B.

Hepatocellular carcinoma (HCC) occurs in chronic hepatitis B (CH-B) patients even after treatment with nucleos(t)ide analogues (NAs) by a mechanism involving an association between the oncogenic factors of integrated HBV and liver fibrosis. An association has been demonstrated between advanced chronic liver disease and elevated levels of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP), a recently discovered serum liver fibrosis marker. Moreover, hepatitis B core-related antigen (HBcrAg) reflects intracellular HBV protein production and its relationship with liver carcinogenesis has been reported. This study aimed to determine whether the incidence and recurrence of HBV-related liver cancer could be predicted using these serum markers. We evaluated 141 CH-B cases treated for more than 1year with NAs. We compared 17 HCC cases with 124 non-HCC cases and evaluated serum WFA(+)-M2BP, HBV markers including HBcrAg, and other clinical factors. We also evaluated 71 CH-B-related HCC cases who started or continued NAs and compared the incidence and recurrence of HCC after successful cancer treatment. Multivariate analysis showed that the incidence of HCC was significantly associated with higher histological stage and grade before NA treatment and with WFA(+)-M2BP and HBcrAg positivity during NA treatment. The cumulative incidence of HCC was strongly associated with higher WFA(+)-M2BP levels and HBcrAg positivity. HCC recurrence after anti-cancer therapy was also significantly associated with higher WFA(+)-M2BP levels compared with those in cases without recurrence during follow-up. Serum WFA(+)-M2BP and HBcrAg are useful diagnostic tests for predicting the development and recurrence of HBV-related HCC during NA treatment.

Pure laparoscopic right hemihepatectomy for hepatocellular carcinoma via the anterior approach

Objective To study the feasibility and safety of pure laparoscopic right hemihepatectomy for hepatocellular carcinoma via the anterior approach. Methods The data of five patients with hepatocellular carcinoma who underwent pure laparoscopic right hemihepatectomy at the First People's Hospital of Foshan between December 2013 and December 2016 were retrospectively analyzed. Patients' operation time, blood loss, blood transfusion rate, surgical margins, hospital stay, complication and short term outcomes were reviewed. Results All the five patients completed pure laparoscopic right hemihepatectomy without conversion to open surgery. The average (range) operation time was 6.0 (5~8) h. The average blood loss was 340 (110~600) ml. No patient received blood transfusion. The average surgical margin was 2.4 (1~4.5) cm. The average postoperative hospital stay was 7 (4~15) d. The average follow-up was 22 (2~38) months. Three patients experienced postoperative complications, which included ascites, pleural effusion, and ascites accompanied by biliary leakage, respectively. The last patient recovered well from drainage. No liver failure, cancer recurrence or death was noted. Conclusions This study demonstrated that pure laparoscopic right hemihepatotectomy via the anterior approach is a minimally invasive procedure which has the advantage of fast postoperative recovery. It was feasible and safe to treat hepatocellular carcinoma with favorable short-term outcomes. Key words: Liver neoplasm; Laparoscopic hepatectomy; Anterior approach; Hepatic pedicle

Influencia de la puntuación MELD basal en la eficacia del tratamiento de la hepatitis C con sofosbuvir y simeprevir

IntroductionThere are few published studies on predictors of response to treatment with sofosbuvir and simeprevir in HCV patients. ObjectiveThe objective of the study was to analyse possible predictors of response to simeprevir (SMV) and sofosbuvir (SOF) in patients infected with hepatitis C genotypes 1 or 4. Patients and methodsProspective observational cohort study in 12 hospitals. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Results204 patients (62.3% male, mean age 55 years) were included: 186 (91.2%) genotype 1 (60.3% 1b 25% 1a) and 18 (8.8%) genotype 4. 132 (64.7%) cirrhotic (87.9% Child A), 33 (16.2%) F3, 31 (15.2%) F2, 8 (3.9%) F0-1. 80.8% MELD<10. 93 (45.6%) naive. Ribavirin was added in 68 (33.3%). Mean baseline viral load 2,151,549 IU/ml (SD: 2,391,840). Treatment duration 12 weeks in 93.1%. 4 discontinued therapy: suicide, psychotic attack, hyperbilirubinaemia and liver cancer recurrence. 190 (93.1%) achieved SVR12. There were no differences in SVR12 depending on the genotype, treatment duration, ribavirin use, prior therapy, viral load (VL) or baseline platelets. In univariate analysis, undetectable VL at 4 weeks (p=0.042), absence of cirrhosis (p=0.021), baseline albumin ≥ 4g/dl (p=0.001) and MELD<10 (p<0.0001) were associated with higher SVR12. In multivariate analysis, only baseline MELD score <10 patients had higher SVR12 (p<0.001). ConclusionsThe combination of simeprevir and sofosbuvir in patients infected with genotype 1 and 4 hepatitis C is highly effective. It is a safe therapy, especially in patients without ribavirin. This combination was more effective in patients with a MELD score below 10.

Risk of liver cancer recurrence assessed with antivirals

Risk of liver cancer recurrence assessed with antivirals

Effects of quantum dots on the ROS amount of liver cancer stem cells

Liver cancer (LC) is a serious disease that threatens human lives. LC has a high recurrence rate and poor prognosis. LC stem cells (LCSCs) play critical roles in these processes. However, the mechanism remains unclear. Reactive oxygen species (ROS) can be used to determine cell apoptosis and proliferation. However, studies of the effects of exogenous nanomaterials on LCSC ROS changes are rarely reported. In this work, quantum dots (QDs) were prepared using a hydrothermal method, and QDs were further modified with polyethylene glycol (PEG) and bovine serum albumin (BSA) using a chemical approach. The effects of QDs, PEG-modified QDs (PEG@QDs) and BSA-modified QDs (BSA@QDs) on the amounts of ROS in liver cancer PLC/PRF/5 (PLC) cells and liver cancer stem cells (LCSCs) were principally investigated. The results showed that when the concentration of QDs, PEG@QDs, and BSA@QDs were 10nM and 90nM, the ROS amount in PLC cells increased by approximately 2- to 5-fold. However, when the concentrations of these nanomaterials were 10nM and 90nM, ROS levels in LCSCs were reduced by approximately 50%. This critical path potentially leads to drug resistance and recurrence of LC. This work provides an important indication for further study of LC drug resistance and recurrence.

The degree of ischemia reperfusion injury of donor liver is a prognostic predictor of recurrence of hepatocellular carcinoma after liver transplantation

Objective To investigate the relationship between the degree of ischemia reperfusion injury (IRI) of donor liver and the expression of Yes-associated protein (YAP) or the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). Methods The clinical date of 69 patients undergoing LT for HCC were retrospectively analyzed and the samples of the donor liver were collected to detect the degree of IRI and the expression of YAP in donor livers. Factors might influence the postoperative disease-free survival (DFS) after LT were analyzed using the Coxregression model. The survival curve was drawn by Kaplan-Meier method. Results The slight ischemia reperfusion injury of donor livers were 58% (40/69), the positive expressions of YAP were 46.4% (32/69). The expression of YAP in donor liver was related to the degree of IRI (χ2=7.369, P=0.007). The result of multivariate analysis showed that the degree of IRI of donor livers, American Joint Committee on cancer (AJCC) stages Ⅲ were independent risk factors influencing tumor recurrence after LT. Conclusion The degree of IRI of donor liver is an independent risk factor for recurrence of HCC after LT. The degree of IRI of donor livers can affect the expression of YAP. Enhancement of YAP expression may be an important mechanism of HCC recurrence after LT with moderate IRI in donor liver. Key words: Liver transplantation; Recurrence of liver cancer; Yes-assoclated protein; Ischemia reperfusion injury; Tumor free survival

Value of texture analysis in evaluating liver cancer recurrence after transarterial chemoembolization

Objective: To investigate the feasibility of contrast-enhanced computer tomography (CT) texture analysis in predicting early recurrence after transarterial chemoembolization (TACE) in patients with liver cancer. Methods: A retrospective analysis was performed for 47 patients with liver cancer confirmed by liver biopsy and digital subtraction angiography who underwent upper abdominal contrast-enhanced CT scan before TACE, and according to the presence or absence of focal recurrence within half a year, these patients were divided into early recurrence (ER) group and non-early recurrence (NER) group. The texture analysis was used to delineate tumor boundary layer by layer on the axial contrast-enhanced CT image before liver cancer surgery, and related parameters of tumor heterogeneity, including entropy, mean, non-uniformity, skewness, and kurtosis, were obtained. The independent samples t-test was used for comparison of texture parameters between the two groups. The receiver operating characteristic (ROC) curve was used for the analysis of entropy, mean, and non-uniformity, and the area under the ROC curve (ROC), optical cut-off value, sensitivity, and specificity were calculated to evaluate the efficiency of texture analysis in predicting early focal recurrence after TACE. Results: There were 20 patients in the ER group and 27 in the NER group. The ER group had a maximum major axis length of 88.2±36.3 mm and a maximum minor axis length of 41.4±21.4 mm, and the NER group had a maximum major axis length of 66.9±30.2 mm and a maximum minor axis length of 29.3±19.8 mm; the ER group had significantly higher maximum major and minor axis lengths than the NER group (t = 4.89 and 4.62, P < 0.001). The ER group had significantly higher entropy and non-uniformity values than the NER group, and there were no significant differences in skewness and kurtosis between the two groups. Entropy, non-uniformity, and mean had high efficiency in predicting early recurrence after TACE, and the optimal cut-off value of entropy was 4.135. Conclusion: Volumetric texture analysis of contrast-enhanced CT images before liver cancer surgery has a high value in predicting early recurrence after TACE.

Hepatitis C treatment and liver cancer recurrence: cause for concern?

Unprecedented discoveries have led to the development of novel targeted therapies for hepatitis C virus (HCV). These treatments—direct-acting antivirals (DAAs)— provide an extraordinary rate of sustained virological response (undetectable HCV blood concentrations for 6 months), curing chronic disease in most patients. However, recent studies suggest a potentially aggressive and early form of recurrent hepatocellular carcinoma in patients successfully treated with DAAs. These studies have sparked controversy as they have exposed potentially unwanted and unexpected consequences of the new HCV treatments.

The Path to Cancer and Back: Immune Modulation During Hepatitis C Virus Infection, Progression to Fibrosis and Cancer, and Unexpected Roles of New Antivirals.

Hepatitis C virus (HCV) infection affects over 130 million individuals worldwide, and it is the number 1 reason for liver transplantation in the United States. HCV infection progresses in a slow chronic fashion eliciting a strong but ineffective immune response, mainly characterized by NK cell dysfunction and T cell exhaustion. The chronic hepatic inflammation leads to liver fibrosis, cirrhosis, and cancer in a significant number of patients. In recent years, groundbreaking research has led to the discovery of new HCV-specific direct-acting antivirals (DAAs), which have an unprecedented efficacy to clear the virus, and establish a sustained virological response. Indeed, curing HCV infection with an oral medication is now reality. The effects of DAAs in mitigating the HCV-related complications of liver fibrosis and cancer are yet largely unknown. Nonetheless, recent controversial reports suggest a potential increase in liver cancer recurrence upon use of DAAs. In the current article, we review the most important immune-mediated mechanisms underlying HCV chronicity and the development of liver fibrosis and cancer. Furthermore, we discuss recent concern on use of the new agents.

LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression.

Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal.

Cu isotopic signature in blood serum of liver transplant patients: a follow-up study.

End-stage liver disease (ESLD) is life-threatening and liver transplantation (LTx) is the definitive treatment with good outcomes. Given the essential role of hepatocytes in Cu homeostasis, the potential of the serum Cu isotopic composition for monitoring a patient’s condition post-LTx was evaluated. For this purpose, high-precision Cu isotopic analysis of blood serum of ESLD patients pre- and post-LTx was accomplished via multi-collector ICP-mass spectrometry (MC-ICP-MS). The Cu isotopic composition of the ESLD patients was fractionated in favour of the lighter isotope (by about −0.50‰). Post-LTx, a generalized normalization of the Cu isotopic composition was observed for the patients with normal liver function, while it remained light when this condition was not reached. A strong decrease in the δ65Cu value a longer term post-LTx seems to indicate the recurrence of liver failure or cancer. The observed trend in favour of the heavier Cu isotopic composition post-LTx seems to be related with the restored biosynthetic capacity of the liver, the restored hepatic metabolism and/or the restored biliary secretion pathways. Thus, Cu isotopic analysis could be a valuable tool for the follow-up of liver transplant patients and for establishing the potential recurrence of liver failure.

Molecular mechanism and pathological evaluation strategies for recurrence and metastasis of liver cancer

The strong invasiveness and metastasis of hepatocellular carcinoma (HCC) are not only the important pathological mechanisms of high recurrence rate and poor long-term outcome, but also the important pathological basis for developing individualized regimens to control metastasis and recurrence in clinical practice. This article introduces the important molecular events in invasion-metastasis cascade discovered in recent years, including the formation mechanism of metastatic niches, methods for molecular pathological evaluation, and standardized pathological diagnosis.