Long-term Prognosis Of Hepatocellular Carcinoma Research Articles

Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is among the most common malignant liver tumors. Despite progress in anticancer drugs and surgical approaches, early detection of HCC remains challenging, often leading to late-stage diagnosis where rapid disease progression precludes surgical intervention, leaving chemotherapy as the only option. However, the systemic toxicity, low bioavailability, and significant adverse effects of chemotherapy drugs often lead to resistance, rendering treatments ineffective for many patients. This article outlines how nanoparticles, following functional modification, offer high sensitivity, reduced drug toxicity, and extended duration of action, enabling precise targeting of drugs to HCC tissues. Combined with other therapeutic modalities and imaging techniques, this significantly enhances the diagnosis, treatment, and long-term prognosis of HCC. The advent of nanomedicine provides new methodologies and strategies for the precise diagnosis and integrated treatment of HCC.

Circulating tumor cells participate in the formation of microvascular invasion and impact on clinical outcomes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Although the treatment strategies have been improved in recent years, the long-term prognosis of HCC is far from satisfactory mainly due to high postoperative recurrence and metastasis rate. Vascular tumor thrombus, including microvascular invasion (MVI) and portal vein tumor thrombus (PVTT), affects the outcome of hepatectomy and liver transplantation. If vascular invasion could be found preoperatively, especially the risk of MVI, more reasonable surgical selection will be chosen to reduce the risk of postoperative recurrence and metastasis. However, there is a lack of reliable prediction methods, and the formation mechanism of MVI/PVTT is still unclear. At present, there is no study to explore the possibility of tumor thrombus formation from a single circulating tumor cell (CTC) of HCC, nor any related study to describe the possible leading role and molecular mechanism of HCC CTCs as an important component of MVI/PVTT. In this study, we review the current understanding of MVI and possible mechanisms, discuss the function of CTCs in the formation of MVI and interaction with immune cells in the circulation. In conclusion, we discuss implications for potential therapeutic targets and the prospect of clinical treatment of HCC.

Expert consensus on transarterial chemoembolization refractoriness and subsequent therapies in hepatocellular carcinoma

Transarterial chemoembolization (TACE) is the fundamental method for the treatment of unresectable hepatocellular carcinoma (HCC). Nevertheless, ineffective repeat TACE may lead to damage on liver function and therefore have negative effect on long-term prognosis of HCC. The concept of "TACE failure/refractoriness" was then proposed to avoid ineffective repeat TACE. Nevertheless, whether the existing definitions of "TACE failure/refractoriness" are applicable to Chinese HCCs remains to be discussed. Combining reported clinical evidence with experts' opinion, the Chinese College of Interventionalists (CCI) TACE Refractoriness Collaboration Group proposed the CCI definition and expert consensus on TACE refractoriness in 2021. The CCI definition and expert consensus aims to make the concept of TACE refractoriness more scientific and objective, so as to better guide clinical practice of TACE for patients with HCC in China.

Identification of the Immune Subtype of Hepatocellular Carcinoma for the Prediction of Disease-Free Survival Time and Prevention of Recurrence by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.

BackgroundThe main factors affecting the long-term prognosis of hepatocellular carcinoma (HCC) patients undergoing radical surgery are recurrence and metastasis. However, the methods for predicting disease-free survival (DFS) time and preventing postoperative recurrence of HCC are still very limited.MethodsIn this study, immune cell abundances in HCC samples were analyzed by single-sample gene set enrichment analysis (ssGSEA), while the prognostic values of immune cells for DFS time prediction were evaluated by the least absolute shrinkage and selection operator (LASSO) and subsequent univariate and multivariate Cox analyses. Next, a risk score was constructed based on the most prognostic immune cells and their corresponding coefficients. Interactions among prognostic immune cells and the specific targets for the prevention of recurrence were further identified by single-cell RNA (scRNA) sequencing data and CellMiner.ResultsA novel efficient T cell risk score (TCRS) was constructed based on data from the three most prognostic immune cell types (effector memory CD8 T cells, regulatory T cells and follicular helper T cells) for identifying an immune subtype of HCC patients with longer DFS times and inflammatory immune characteristics. Functional differences between the high- and low-score groups separated by TCRS were clarified, and the cell-cell communication among these immune cells was elucidated. Finally, fifteen hub genes that may be potential therapeutic targets for the prevention of recurrence were identified.ConclusionsWe constructed and verified a useful model for the prediction of DFS time of HCC after surgery. In addition, fifteen hub genes were identified as candidates for the prevention of recurrence, and a preliminarily investigation of potential drugs targeting these hub genes was carried out.

The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy

The long-term prognosis of hepatocellular carcinoma (HCC) treated at a very-early-stage (the Barcelona Clinical Liver Cancer (BCLC) classification stage 0) was unclear, especially in terms of background liver disease. This single-center, retrospective study included 302 patients with BCLC stage 0 HCC treated with radiofrequency ablation (RFA) and followed for at least six months. We examined the impact of background liver disease on overall survival and recurrence. The median age was 72 (range; 36-91) years; the median tumor diameter was 15 (range; 8-20) mm. The etiologies of background liver disease were hepatitis B virus infection (HBV) in 24 cases, hepatitis C virus infection (HCV) in 195 cases, and non-viral (NBNC) in 83 cases. Among the patients with HCV, 63 had achieved sustained virological response (SVR) by antiviral therapy (HCV SVR) before developing HCC (n = 37) or after HCC treatment (n = 26), and 132 had active HCV infection (HCV non-SVR). The median overall survival was 85 (95% CI; 72-98) months, and the median recurrence-free survival was 26 (95% CI; 20-30) months. Active infection with hepatitis C virus negatively contributed to overall survival (HR 2.91, 95% CI 1.31-3.60, p = 0.003) and recurrence-free survival (HR 1.47, 95% CI 1.06-2.05, p = 0.011). The prognosis of RFA treatment for very early-stage HCC was favorable. Achieving SVR in hepatitis C was important for further prognosis improvement.

Long-term Outcomes of Open versus Minimally Invasive Hepatectomy for Hepatocellular Carcinoma: A Single-Center Experience in the USA

Introduction: Surgical resection is the treatment of choice for hepatocellular carcinoma (HCC). With advances in technology, minimally invasive surgery has become the standard of care in most fields of general surgery, including hepatectomy. We compared the clinicopathologic features and long-term prognosis of HCC between open hepatectomy (OH) and minimally invasive hepatectomy (MIH).

The effect of bile duct tumor thrombus on the long-term prognosis of hepatocellular carcinoma patients after liver resection: a systematic review and meta-analysis.

BackgroundThe effect of bile duct tumor thrombus (BDTT) on the postoperative long-term prognosis of hepatocellular carcinoma (HCC) patients is still under debate.MethodsThe PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched to collect the clinicopathologic characteristics, perioperative indices, and postoperative survival outcomes in the BDTT and non-BDTT groups of HCC patients from inception to February 1, 2020. The study outcomes were extracted by two independent investigators.ResultsA total of 15 studies involving 6,484 patients were included. The meta-analysis revealed that the levels of serum total bilirubin and alkaline phosphatase were notably higher in patients with HCC and BDTT than those without BDTT. Meanwhile, HCC patients with BDTT had more aggressive biological characteristics, such as poor tumor differentiation, macrovascular invasion, and lymph node metastasis, as compared to patients without BDTT. The 1-year [odds ratio (OR) 0.39, 95% confidence interval (CI): 0.31–0.48, P<0.01], 3-year (OR 0.33, 95% CI: 0.22–0.51, P<0.01) and 5-year overall survival (OS) rates (OR 0.31, 95% CI: 0.20–0.49, P<0.01) of the BDTT group were significantly worse than those of the non-BDTT group. The hazard ratio of HCC with BDTT was 4.27 (95% CI: 3.47–5.26, P<0.01) within 5 years after hepatectomy.ConclusionsHCC patients with BDTT had worse OS compared to patients free of BDTT after surgery. BDTT may be a potential prognostic factor for HCC patients.

Resection of hepatocellular carcinoma in patients with portal hypertension: long-term results based on direct intraoperative measurement of portal venous pressure

Introduction: The existence of differences in long-term prognosis of hepatocellular carcinoma (HCC) patients with or without portal hypertension (PH) undergoing hepatic resection remains controversial. Our aim was to clarify the long-term prognosis of HCC patients with PH undergoing hepatectomy. PH diagnosis was based on intraoperative portal venous pressure (PVP) measurement. Materials and Methods: Between May 2001 and April 2005, 68 patients with HCC underwent liver resection. PVP was directly measured at the beginning of surgery. Patients were divided into a high (&gt;11 mm Hg) (n=33) or a low (≤11 mm Hg) (n=35) PVP group. Clinicopathologic factors and postoperative outcomes were compared between the 2 groups, with tumor staging stratification according to Milan criteria (selection criteria for patients receiving transplantation). Median follow-up time was 101 months. Results: Postoperative mortality was 0. Median PVP was 10.7 mm Hg (range; 2.9–23.5 mm Hg). Compared with patients with low PVP, patients with high PVP had lower platelet counts, lower serum albumin levels, higher ALT concentration, higher international normalized ratio, higher Model for End-Stage Liver Disease (MELD score), and increased blood loss and blood transfusion. Multivariate logistic regression analysis revealed factors related to high PVP: serum albumin level &lt;3.6 g/dL (odd ratio: 5.532, 95% confidence interval: 1.286-23.79, P=0.022), and MELD score &gt;6 (odd ratio: 5.585; 95% confidence interval: 1.638-19.040, P=0.006). Postoperative morbidity was comparable between the 2 groups. Overall survival and disease-free survival rates in the high PVP group were significantly lower than in the low PVP group (P&lt;0.05). Subgroup analysis showed that, for patients within Milan criteria, those in the high PVP group had lower overall survival (P=0.032) and disease-free survival (P=0.016) than in those in the low PVP group. For patients outside the Milan criteria, no differences in survival were observed. Conclusions: In patients with early stage HCC undergoing resection, high PVP is associated with impaired long-term prognosis. For these patients, close follow-up and early salvage liver transplants for recurrent disease may be necessary to improve long-term prognosis after surgery.

The predictive values of serum dickkopf-1 and circulating tumor cells in evaluating the efficacy of transcatheter arterial chemoembolization treatment on hepatocellular carcinoma.

In this study, we aim to explore the values of serum dickkopf-1 (DKK1) and circulating tumor cells (CTCs) in predicting the efficacy and prognosis of transcatheter arterial chemoembolization (TACE) treatment on patients with hepatocellular carcinoma (HCC). We did a retrospective analysis on 155 HCC patients who underwent TACE treatment. The patients were divided into response group (complete response and partial response) and nonresponse group (stable disease and progressive disease), and their changes in serum DKK1 and CTCs after TACE were recorded. Receiver operating characteristic curve and survival analysis were used to assess the predictive values of DKK1 and CTCs for TACE efficacy and long-term prognosis of HCC. We found that the levels of preoperative DKK1 and CTCs in patients with HCC had a moderate positive correlation (r = 0.54). After TACE treatment, the serum DKK1 and CTCs in the response group were significantly decreased compared to pretreatment levels (P < .05), whereas the nonresponse group showed significantly increased serum DKK1 and CTCs levels (P < .05). The largest area under the curve (AUC) was achieved when using >0.02 μg/L reduction in DKK1 level after 4 weeks of TACE to predict the efficacy of TACE treatment (AUC = 0.913, 95% confidence interval: 0.856–0.952, P < .001), with the sensitivity of 78.26% and the specificity of 88.07%. The overall survival, disease-free survival, and 5-year survival rates were all significantly lower in the patients with positive preoperative levels of serum DKK1 and CTCs. COX multivariate regression analysis showed that Eastern Cooperative Oncology Group score, and preoperative levels of serum DKK1 and CTCs are independent influencing factors for the prognosis of patients with HCC. Overall, our results demonstrated that serum DKK1 and CTCs levels were good biomarkers for predicting the efficacy and prognosis of TACE treatment in patients with HCC. Moreover, these parameters exhibited different characteristics, and might have different potential applications.

Association of Tumor Grade With Long-Term Survival in Patients With Hepatocellular Carcinoma After Liver Transplantation

BackgroundAssociation of tumor grade and the prognosis of hepatocellular carcinoma (HCC) patients after liver transplantation (LT) had not been clearly illustrated. The objective of the current study was to investigate the impact of tumor grade on the long-term survival of patients with HCC receiving LT. MethodsData from Surveillance, Epidemiology, and End Results Program (SEER) 18 registry for 2004–2015 was extracted for the present study. Propensity score matching was performed to eliminate possible bias. In addition, multivariable analysis was utilized to adjust for confounding factors. The primary endpoints were overall survival (OS) and disease-specific survival (DSS). ResultsA total of 802 patients diagnosed with HCC receiving LT between 2004–2015 included in the SEER registry were analyzed in the study. In the multivariable adjusted cohort (OS: n = 802; DSS: n = 640), a worse prognosis was observed in OS (HR, 1.57; 95% CI, 1.13–2.19; P = .008) and DSS (HR, 2.62; 95% CI, 1.44–4.77; P = .002) for patients with moderate/poor-differentiated tumors compared to patients with well-differentiated tumors. In stratified analyses, the salutary effects of well-differentiation on OS and DSS were consistent across all examined subgroups. In the propensity-matched cohort, the univariable analysis showed that patients with moderate/poor-differentiated tumors still had worse OS (HR 1.60, 95% CI 1.12–2.28, P = .010) and DSS (HR 2.54, 95% CI 1.36–4.74, P = .003) compared to patients with well-differentiated tumors. ConclusionTumor grade of differentiation had a statistically significant effect on the long-term prognosis of HCC after LT.

Multicentre study of the prognostic impact of preoperative bodyweight on long-term prognosis of hepatocellular carcinoma.

Whether preoperative bodyweight is associated with long-term prognosis in patients after liver resection for hepatocellular carcinoma (HCC) is controversial. This study aimed to investigate the relationship of patient weight with long-term recurrence and overall survival (OS) after curative liver resection for HCC. Data for patients with HCC who underwent curative liver resection between 2000 and 2015 in five centres in China were analysed retrospectively in three groups according to their preoperative BMI: underweight (BMI 18·4 kg/m2 or less), normal weight (BMI 18·5-24·9 kg/m2 ) and overweight (BMI 25·0 kg/m2 or above). Patients' baseline characteristics, operative variables and long-term survival outcomes were compared. Univariable and multivariable Cox regression analyses were performed to identify risk factors for OS and recurrence-free survival (RFS) after resection. Of 1524 patients, 107 (7·0 per cent) were underweight, 891 (58·5 per cent) were of normal weight and 526 (34·5 per cent) were overweight. Univariable analyses showed that underweight and overweight patients had poorer OS (both P < 0·001) and RFS (both P < 0·001) than patients of normal weight. Multivariable Cox regression analysis also identified both underweight and overweight to be independent risk factors for OS (hazard ratio (HR) 1·22, 95 per cent c.i. 1·19 to 1·56, P = 0·019; and HR 1·57, 1·36 to 1·81, P < 0·001, respectively) and RFS (HR 1·28, 1·16 to 1·53, P = 0·028; and HR 1·34, 1·17 to 1·54, P < 0·001). Underweight and overweight patients appear to have a worse prognosis than those of normal weight following liver resection for HCC.

High-biologically effective dose palliative radiotherapy for a tumor thrombus might improve the long-term prognosis of hepatocellular carcinoma: a retrospective study

BackgroundThis study aimed to highlight the type of tumor thrombus and identify the prognostic factors influencing the long-term survival outcomes in patients with hepatocellular carcinoma (HCC) having a tumor thrombus. A tumor thrombus in HCC is associated with poor prognosis.MethodsEighty patients diagnosed with HCC having a tumor thrombus between May 2006 and April 2014 were enrolled in this study. Age, gender, clinical characteristics, laboratory findings, Child-Pugh classification, performance status (ECOG), types of tumor thrombi, radiotherapy method, biologically effective dose (BED), and primary treatment method were analyzed to identify the prognostic factors associated with the overall survival (OS) rates. Statistical analyses were performed using SPSS version 19.0.ResultsThe median follow-up duration was 24 months (range 6–90). The 1-, 3-, and 5-year OS rates of the patients were 77.6%, 37.6%, and 18.8%, respectively. On univariate analysis, gender, radiotherapy method, BED, types of tumor thrombi, Child-Pugh classification, ECOG, and total bilirubin were associated with OS (P < 0.001, P = 0.001, P = 0.016, P = 0.003, P < 0.001, P < 0.001, P = 0.039, respectively). The prognostic factors for OS in multi-variate analyses were gender (P < 0.001), BED (P = 0.044), Child Pugh classification (P = 0.020), performance status (ECOG) (P = 0.004), and types of tumor thrombi (P = 0.001). The median OS for the high-BED group was better than that for the low-BED groups (42 months vs. 19 months, P = 0.016).ConclusionsGender, BED, performance status (ECOG), Child-Pugh classification, and types of tumor thrombi seemed to affect OS, and a stepwise decrease in survival was observed with the types of tumor thrombi ranging from I to IV. High-BED palliative radiotherapy might improve the long-term outcomes for patients with HCC having a tumor thrombus.

Effects of perioperative transfusion of blood components on the long-term prognosis of hepatocellular carcinoma

Objective: To investigate the effects of perioperative transfusion of blood components on the long-term prognosis of hepatocellular carcinoma (HCC) patients. Methods: A total of 339 patients with primary HCC who underwent curative hepatectomy between January 2003 and December 2010 at the Cancer Hospital, Chinese Academy of Medical Sciences were enrolled. The clinical data of the patients were retrospectively analyzed. These patients were divided into non-transfusion, fresh frozen plasma (FFP) transfusion only and concentrated red cells (CRC) transfusion groups. Disease-free survival and overall survival were estimated using the Kaplan-Meier method, and Cox regression was performed to identify clinicopathological factors related with survival. Results: Among the 339 patients, the 1-, 3- and 5-year disease-free survival rates were 63.1%, 35.4% and 22.4%, respectively, and the median disease-free survival was 22 months. While the 1-, 3- and 5-year overall survival rates were 90.5%, 69.5% and 56.4%, respectively, and the median overall survival was 72 months. The median disease-free survivals of the non-transfusion (n=181), FFP transfusion only (n=48) and CRC transfusion (n=110) groups were 28, 22 and 12 months, respectively, while the median overall survivals of the three groups were 99, 63 and 40 months respectively. Significant differences in the disease-free and overall survivals were observed among the three groups (both P<0.01). Multivariate Cox regression analyses showed that FFP transfusion only (HR=1.658, P=0.026), CRC transfusion (HR=1.470, P=0.030), serum alpha-fetoprotein>400 μg/L (HR=1.686, P=0.002), albumin<35 g/L (HR=1.782, P=0.047), tumor capsule (HR=0.597, P=0.012), tumor necrosis (HR=1.820, P=0.001) and the TNM stage Ⅲ or above (HR=2.537, P=0.000) were independent predictors of overall survival after hepatectomy. Conclusion: Both perioperative FFP only transfusion and CRC transfusion may have detrimental effect on the long-term prognosis of HCC.

Synergistic effect of cytokine-induced killer cell with valproate inhibits growth of hepatocellular carcinoma cell in a mouse model

ABSTRACTObjective: Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK– and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC. Methods: Upregulation of natural killer group 2D (NKG2D) ligands (retinoic acid early inducible 1 [RAE-1], mouse; major histocompatibility complex class I polypeptide-related sequence A [MIC-A], human) were evaluated by FACS. VPA concentrations that did not reduce tumor volume were calculated to avoid VPA cytotoxicity in a C3H mouse model of HCC. CIK cells were generated from mouse splenocytes using interferon gamma, a CD3 monoclonal antibody, and interleukin 2. The potential synergistic effect of CIK cells combined with VPA was evaluated in the mouse model and tissue pathology was investigated. Results: After 40 h of incubation with VPA, RAE-1 and MIC-A expression were increased in 4 HCC cell lines compared with that in control (2.3-fold in MH-134, 2.4-fold in Huh-7, 3.7-fold in SNU-761, and 6.5-fold in SNU-475). The maximal in vivo VPA dosage that showed no significant cytotoxicity compared with control was 10 mg/kg/day. CIK cells were well generated from C3H mouse splenocytes. After 7 d of treatment with CIK cells plus VPA, a synergistic effect was observed on relative tumor volume in the mouse model of HCC. While the relative tumor volume in untreated control mice increased to 11.25, that in the combination treatment group increased to only 5.20 (P = 0.047). Conclusions: The VPA-induced increase in NKG2D ligands expression significantly enhanced the effects of CIK cell therapy in a mouse model of HCC.

Proper hepatic pedicle clamping during hepatectomy is associated with improved postoperative long-term prognosis in patients with AJCC stage IIIB hepatocellular carcinoma.

Intermittent hepatic pedicle clamping (HPC) is often performed during hepatectomy. Whether it affects the long-term prognosis of hepatocellular carcinoma (HCC) patients is still controversial. This study evaluated the impact of HPC in patients with different stages of HCC. The study included 1401 patients who underwent hepatectomy in the primary cohort with 129 AJCC stage IIIB HCC patients; there were 80 AJCC stage IIIB HCC patients in the validation cohort. In each cohort, patients were placed in the long-term HPC (LTHPC) group or the short-term HPC (STHPC) group based on the cut-off time of HPC estimated by the receiver-operating characteristic (ROC) curve. Although HPC did not show significant effects on the prognosis of stage I–IIIA HCC patients in the primary cohort, 1−, 3−, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates of stage IIIB HCC patients who received LTHPC (HPC time > 12 minutes) were significantly higher than those with STHPC (HPC time ≤ 12 minutes or received no HPC), similar in the validation cohort. Multivariate analysis demonstrated HPC time was an independent protective factor for RFS and OS in stage IIIB HCC patients. Herein, we report that proper HPC improved the postoperative prognosis of stage IIIB HCC patients and served as an independent protective factor.

Identification of β-glucosidase 1 as a biomarker and its high expression in hepatocellular carcinoma is associated with resistance to chemotherapy drugs

Context and objective: Long-term prognosis of hepatocellular carcinoma (HCC) patients is challenging, and novel biomarkers are needed to predict patient risk and serve as potential therapeutic target.Results: We found β-glucosidase 1 is significantly overexpressed and activated in primary HCC tissue and multiple HCC cell lines. β-Glucosidase 1 expression is associated with predicting prognosis of HCC patients under chemotherapy. Silencing β-glucosidase 1 inhibits growth and survival of HCC cells, with preferential inhibitory effects on high β-glucosidase 1-expressing cells. Combination of chemo drug with β-glucosidase 1 inhibitor sensitized HCC cells to chemotherapy.Conclusion: Our data support β-glucosidase 1 as a HCC biomarker due to its prognosis significance.

TAK-242 can be the potential agents for preventing invasion and metastasis of hepatocellular carcinoma

The long-term prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory even after surgical resection and chemoembolization because of a high recurrence rate. However, fewer agents are currently available to block or postpone HCC progression. Recent studies show that the activation of toll-like receptor 4 (TLR4)-NF-kappaB(NF-κB) signaling pathway can lead to the expression of interleukin (IL)-1, IL-6, IL-10, nitric oxide (NO) and tumor necrosis factor (TNF)-α, and promote chronic liver inflammation and malignant tumor development. A new small molecule TAK-242 (Resatorevid) can selectively inhibit TLR4-mediated signaling pathway and suppress the expression of inflammatory mediators. But the researches have not been reported whether TAK-242 can inhibit liver tumor growth and invasion. So it suggested a new hypothesis that TAK-242 selectively blocks the TLR4-NF-κB pathway and is hoped to be a potential and creative drug for preventing invasion and metastasis of HCC.

Sustained low hepatitis B viral load predicts good outcome after curative resection in patients with hepatocellular carcinoma

Little is known about the role of hepatitis B virus (HBV) factors in the long-term prognosis of hepatocellular carcinoma (HCC) after resection. The objective of the present study was to identify the changing patterns of HBV levels and its effect on outcome after resection. This study recruited 188 patients with HBV-related HCC who underwent curative resection. Among the 188 patients, 115 were alive without recurrence at 12 months, and had serial measurements of viral levels. The mean age was 53 years and the mean follow-up period was 48.5 months. With multivariate analysis, tumor size > 5 cm (P = 0.047), Child-Pugh class B (P = 0.017), vascular invasion (P = 0.028), and HBV DNA > 10(4) copies/mL at the time of resection (P = 0.003) were independently predictive of HCC recurrence for the entire population. For the 115 patients with serial measurements of viral levels, tumor size > 5 cm, HBV DNA > 10(4) copies/mL at resection, and the absence of sustained HBV DNA level < 10(4) copies/mL, the presence of cirrhosis, and elevated aminotransferase levels (> 40 IU/L) were marginally or significantly associated with HCC recurrence and overall survival. However, on multivariate analysis, sustained HBV DNA level < 10(4) copies/mL was the only factor for both low recurrence (P = 0.002; odds ratio [OR] 3.13; 95% confidence interval [CI] 1.55-6.35) and longer survival (P = 0.002; OR 3.76; 95% CI 1.61-8.78). A high HBV replication state is among the most important predictors of adverse outcome after resection of HBV-related HCC. The sustained suppression of HBV below 10(4) copies/mL is a strong protective factor for long-term recurrence-free and overall survival.

Prognostic factors and recurrence of hepatitis B-related hepatocellular carcinoma after argon-helium cryoablation: a prospective study

To determine the long-term prognosis of hepatocellular carcinoma (HCC) after argon-helium cryoablation and identify the risk factors that predict metastasis and recurrence. A total of 156 patients with hepatitis B-related HCC less than 5 cm in diameter who underwent curative cryoablation were followed up prospectively for tumor metastasis and recurrence. Immunohistochemistry was used to analyze the expression of vascular endothelial growth factor (VEGF). HBV basal core promoter (BCP) and precore mutations were detected by DNA sequence analysis. Post-treatment prognostic factors influencing survival, tumor metastasis and recurrence were assessed by univariate and multivariate analyses. The variables included the expression of VEGF in HCC tissues, clinical and pathologic characteristics of patients, and HBV features (HBV DNA level, HBV genotype, BCP mutation). The median follow-up period of the 156 patients was 37 months (range 8-48 months). The 1-, 2-, and 3-year overall survival rates were 92, 82 and 64%, respectively. The 1-, 2-, and 3-year recurrence-free survival rates were 72, 56 and 43%, respectively. Eighty-five patients (54.5%) had tumor recurrence or metastasis. The multivariate analysis showed that Child-Pugh class and the expression of VEGF in HCC tissues could be used as independent prognostic factors for overall survival. Meanwhile, the expression of VEGF in HCC tissues and HBV BCP mutations were found to be independent prognostic factors for recurrence-free survival. Strong expression of VEGF in HCC tissues and HBV BCP mutations are important risk predictors for recurrence or metastasis of HCC smaller than 5 cm in diameter.

Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma.

The long-term prognosis of hepatocellular carcinoma (HCC) remains poor and the prediction of survival is often difficult because of the limited liver function and frequent recurrence of HCC in most patients. Therefore, a prognostic classification of HCC should account for both tumor-related variables and liver function. The value of reported prognostic factors for HCC was assessed and a new prognostic classification was established called the 'SLiDe' scoring system (S, stage; Li, liver damage; De, des-gamma-carboxy prothrombin) using 'stage' and 'liver damage' of the recently revised 4th edition of the Japanese staging system edited by the Liver Cancer Study Group of Japan, and the serum level of des-gamma-carboxy prothrombin (DCP) in 177 patients with HCC. Univariate analysis identified Child-Pugh stage, liver damage, tumor morphology, portal vein thrombosis, stage, serum level of alpha-fetoprotein (AFP), serum level of DCP, and initial treatment as significant prognostic factors. Of these, liver damage, stage, and serum level of DCP remained independent predictive factors of survival after multivariate prognostic analysis using the proportional hazards regression model. Therefore, a new prognostic scoring system (SLiDe scoring system) was derived that assigned a linear score (0/1/2/3) to these three covariates. This SLiDe scoring system was statistically a better model for predicting outcome in the present study population than the Cancer of the Liver Italian Program (CLIP) and the Japan Integrated Staging (JIS) scoring systems, as judged by the Akaike Information Criteria. The SLiDe scoring system is useful for the assessment of the prognosis of patients with HCC as long as the Japanese staging system is used, although this uses parameters such as the indocyanine green retention test and DCP, which are not examined routinely in every part of the world. Therefore, the proposed classification should be further validated in other large study populations.