Reactivation of Hepatitis B Virus in HBsAg-Negative Patients with Hepatocellular Carcinoma

Background & Aims

Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE).

Methods

A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2–3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46).

Results

During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216–116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation.

Conclusions

TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.     

Propensity Score Matching Analysis of Changes in Alpha-Fetoprotein Levels after Combined Radiotherapy and Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Background and Aim

To investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE).

Methods

A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.

Results

The median follow-up period was 11.1 months (range, 3.1–82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001).

Conclusions

AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.     

A Prognostic Score for Patients with Intermediate-Stage Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

Background

Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.

Methods

Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.

Results

The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001).

Conclusions

The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.     

Cone-Beam Computed Tomography Correlates with Conventional Helical Computed Tomography in Evaluation of Lipiodol Accumulation in HCC after Chemoembolization

Background & Aims

The amount of drug-loaded lipiodol in an HCC tumor post-transarterial chemoembolization (TACE) correlates with the risk of local tumor recurrence. Lipiodol enhancement of a tumor on conventional CT, measured in Hounsfield units (HU), can predict tumor response. Here we investigate whether cone-beam CT (CBCT) can also be used to predict tumor response, providing the benefit of being able to optimize the patient’s treatment plan intra-procedurally.

Methods

A total of 82 HCC nodules (82 patients), ≤5 cm in diameter, were treated with balloon-occluded TACE using miriplatin between December 2013 and November 2014. For each patient, both CBCT and conventional CT images were obtained post-TACE. The degree of correlation between CBCT and conventional CT was determined by comparing identical regions of interest for each imaging modality using pixel values.

Results

The pixel values from conventional CT and CBCT were highly correlated, with a Pearson correlation coefficient of 0.912 (p<0.001). The location of the nodules within the liver did not affect the results; the correlation coefficient was 0.891 (p<0.001) for the left lobe and 0.926 (p<0.001) for the right lobe. The mean pixel value for conventional CT was 439 ± 279 HU, and the mean pixel value for CBCT was 416 ± 311 HU.

Conclusions

CBCT may be used as a substitute for conventional CT to quantitatively evaluate the amount of drug-loaded lipiodol within an HCC nodule and, hence, the efficacy of TACE treatment. The major benefit of using CBCT is the ability to predict the likelihood of local recurrence intra-procedurally, enabling subsequent treatment optimization.     

Analysis of Prognostic Factors for Survival after Hepatectomy for Hepatocellular Carcinoma Based on a Bayesian Network

Background

The prognosis of hepatocellular carcinoma (HCC) after hepatectomy involves many factors. Previous studies have evaluated the separate influences of single factors; few have considered the combined influence of various factors. This paper combines the Bayesian network (BN) with importance measures to identify key factors that have significant effects on survival time.

Methods

A dataset of 299 patients with HCC after hepatectomy was studied to establish a BN using a tree-augmented naïve Bayes algorithm that could mine relationships between factors. The composite importance measure was applied to rank the impact of factors on survival time.

Results

124 patients (>10 months) and 77 patients (≤10 months) were correctly classified. The accuracy of BN model was 67.2%. For patients with long survival time (>10 months), the true-positive rate of the model was 83.22% and the false-positive rate was 48.67%. According to the model, the preoperative alpha fetoprotein (AFP) level and postoperative performance of transcatheter arterial chemoembolization (TACE) were independent factors for survival of HCC patients. The grade of preoperative liver function reflected the tendency for postoperative complications. Intraoperative blood loss, tumor size, portal vein tumor thrombosis (PVTT), time of clamping the porta hepatis, tumor number, operative method, and metastasis were dependent variables in survival time prediction. PVTT was considered the most significant for the prognosis of survival time.

Conclusions

Using the BN and importance measures, PVTT was identified as the most significant predictor of survival time for patients with HCC after hepatectomy.     

Ectopic Blood Supply of Hepatocellular Carcinoma as Depicted by Angiography with Computed Tomography: Associations with Morphological Features and Therapeutic History

Objective

To investigate the associations of ectopic blood supply of hepatocellular carcinoma (HCC) with its morphological features and therapeutic history.

Methods

Three hundred and six patients with 373 HCC lesions were enrolled in this study, and underwent biphasic contrast-enhanced scans on a 64-section MDCT. The anatomy of ectopic blood supply, morphological characteristics of HCC including the size, location and pseudocapsule, and history of transcatheter arterial chemoembolization (TACE) therapy were quantitively assessed and statistically analyzed.

Results

Ectopic blood supply was found in 30.8% (115/373) lesions. The ectopic arteries were predominantly composed of inferior phrenic artery (86/115) followed by left and right gastric artery (25/115). Tumor size, location, status of pseudocapsule, and history of TACE therapy could impact the origination of ectopic arteries (all p<0.05).

Conclusion

The ectopic feeding arteries of HCC predominantly composed of the perihepatic arteries are associated with the morphological features of the tumor and therapeutic history.     

Comparison of Long-Term Survival of Patients with BCLC Stage B Hepatocellular Carcinoma after Liver Resection or Transarterial Chemoembolization

Background and Aims

Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE).

Methods

A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan–Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model.

Results

The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE.

Conclusions

LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.     

Circulating microRNA-200 Family as Diagnostic Marker in Hepatocellular Carcinoma

Goals

In this clinical study, we aimed to evaluate the role of circulating microRNA-200 family as a non-invasive tool to identify patients with cirrhosis-associated hepatocellular carcinoma (HCC).

Background

Prognosis of HCC remains poor with increasing incidence worldwide, mainly related to liver cirrhosis. So far, no reliable molecular targets exist for early detection of HCC at surgically manageable stages. Recently, we identified members of the microRNA-200 family as potential diagnostic markers of cirrhosis-associated HCC in patient tissue samples. Their value as circulating biomarkers for HCC remained undefined.

Methods

Blood samples and clinicopathological data of consecutive patients with liver diseases were collected prospectively. Expression of the microRNA-200 family was investigated by qRT-PCR in blood serum samples of 22 HCC patients with and without cirrhosis. Serum samples of patients with non-cancerous chronic liver cirrhosis (n = 22) and of healthy volunteers (n = 15) served as controls.

Results

MicroRNA-141 and microRNA-200a were significantly downregulated in blood serum of patients with HCC compared to liver cirrhosis (p<0.007) and healthy controls (p<0.002). MicroRNA-141 and microRNA-200a could well discriminate patients with cirrhosis-associated HCC from healthy volunteers with area under the receiver-operating characteristic curve (AUC) values of 0.85 and 0.82, respectively. Additionally, both microRNAs could differentiate between HCC and non-cancerous liver cirrhosis with a fair accuracy.

Conclusions

Circulating microRNA-200 family members are significantly deregulated in patients with HCC and liver cirrhosis. Further studies are necessary to confirm the diagnostic value of the microRNA-200 family as accurate serum marker for cirrhosis-associated HCC.     

Des-γ-Carboxyprothrombin (DCP) and NX-DCP Expressions and Their Relationship with Clinicopathological Features in Hepatocellular Carcinoma

Aim

Des-γ-carboxyprothrombin (DCP) has been used as a tumor marker for hepatocellular carcinoma (HCC). Recently the DCP/NX-DCP ratio, calculated by dividing DCP by NX-DCP, has been reported useful in detecting HCC. The purpose of this study is to clarify the significance of DCP and NX-DCP expression in HCC tissues.

Methods

HCC and non-HCC tissue samples were obtained from 157 patients and were immunohistochemically examined for DCP and NX-DCP expression using anti-DCP antibody and anti-NX-DCP antibody. DCP and NX-DCP expression scores were calculated by multiplying staining intensity grade by percentage of stained area. Serum DCP and NX-DCP levels were determined in 89 patients. We evaluated the relationship between tumor expression, serum level, and pathomorphological findings.

Results

Intrahepatic metastasis (im) was significantly more frequent in cases with high DCP expression than in cases with low DCP expression. High NX-DCP expression was associated with significantly lower histological grade, and less frequent im or portal vein invasion (vp) than low NX-DCP expression. Serum DCP was correlated with DCP expression, but serum NX-DCP was not correlated with NX-DCP expression. DCP-positive (≥40 mAU/L), NX-DCP-positive (≥90 mAU/L), and DCP/NX-DCP ratio-positive (≥1.5) cases were associated with significantly larger tumor size and more frequent vp than negative cases. DCP was rarely expressed, but NX-DCP was frequently expressed in non-cancerous liver tissues. Patients with NX-DCP expression-negative tumors showed a lower survival rate than those with NX-DCP expression-positive tumors (p = 0.04), whereas the survival in serum NX-DCP-positive cases was lower than that of serum negative cases (p = 0.02).

Conclusions

DCP and NX-DCP were produced in HCC tissues, but differed in expression level and biological properties. DCP expression, serum DCP or NX-DCP level, and DCP/NX-DCP ratio were closely related to malignant properties of HCC.     

Predictive Factor of Local Recurrence after Balloon-Occluded TACE with Miriplatin (MPT) in Hepatocellular Carcinoma

Background

Miriplatin (MPT) is a novel platinum complex used in TACE that shows promise for the treatment of hepatocellular carcinoma (HCC). However, rapid washout has been reported in some cases. Therefore, various methods of administration with MPT have been attempted to increase its therapeutic efficacy. One hopeful method is balloon-occluded TACE (B-TACE), but the therapeutic efficacy of B-TACE with MPT has not been evaluated.

Aim

To investigate the treatment outcomes and factors involved in local recurrence after B-TACE with MPT in HCC.

Methods

This study included 51 patients (55 nodules) with HCC lesions equal or less than 5 cm in diameter who underwent B-TACE with MPT between January 2012 and June 2013. Local recurrence after B-TACE with MPT and factors associated with local recurrence were evaluated.

Results

The overall local recurrence rate was 11.1% at 6 months and 26.2% at 12 months. The local recurrence rate did differ significantly depending on CT values immediately after B-TACE with MPT. Multivariate analysis also showed that the CT value after B-TACE with MPT was the only factor related to local recurrence after B-TACE.

Conclusions

B-TACE with MPT achieves relatively good local control of HCC. The plain CT value immediately after B-TACE with MPT is a predictive factor for local recurrence. In patients with unsatisfactory CT values, locoregional therapy or additional treatment is required.     

Reduction in Non-Protein Respiratory Quotient Is Related to Overall Survival after Hepatocellular Carcinoma Treatment

Background

Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE.

Methodology/Principal Findings

We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ) (7 days after/before TACE) and Cancer of Liver Italian Program (CLIP) score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively). Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph.

Conclusions

The short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio) and time-fixed (CLIP score) prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease.     

Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma

Background

Needle core biopsy (NCB) is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate.

Objective

To identify the influence of number of biopsies on NCB diagnostic accuracy.

Methods

153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis.

Results

Using a 3-tier grading scheme (well, moderate and poor), the accuracy of NCB has no significant differences among different number of passes in HCC ≤5cm. For HCC >5≤8cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively). While in HCC>8cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively.

Conclusions

The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5cm.     

Long-Term Outcomes of Percutaneous Cryoablation for Patients with Hepatocellular Carcinoma within Milan Criteria

Background

Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term outcomes.

Methods

A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed.

Results

A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >10⁶ copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS.

Conclusions

Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation.     

Evolutionary Changes of Hepatitis B Virus Pre-S Mutations Prior to Development of Hepatocellular Carcinoma

Background and Aims

Deletions/mutations in the hepatitis B virus (HBV) pre-S region have been associated with hepatocellular carcinoma (HCC). We aimed to study the evolutionary changes of pre-S mutations prior to HCC development.

Methods

We studied the HBV pre-S sequences at 1 to 10 years preceding diagnosis of HCC in 74 patients with HBV-related HCC (HCC group). 148 chronic hepatitis B patients matched for sex and age in 2:1 ratio, who had been followed up for at least 3 years without HCC (HCC-free group) were recruited as controls. 56 and 47 patients of HCC and HCC-free groups respectively had serially stored sera for longitudinally examination at 1–3 years, 4–6 years, 7–9 years and ≥10 years prior to the recruitment of the study.

Results

Compared to the HCC-free group, higher frequencies of pre-S deletions and point mutations (at 11 codons) were observed in the HCC group (p<0.05). Multiple logistic regression analysis showed that pre-S deletions, point mutations at codon 51 and 167 were independent factors associated with HCC. Longitudinal observation showed that pre-S deletions and most of the 11 HCC-associated pre-S point mutations existed at least 10 years before HCC development, and were more prevalent preceding HCC development in patients from HCC groups than HCC-free group. The number of HCC-associated pre-S point mutations increased over time preceding HCC development, and correlated positively with the time to HCC diagnosis (r = 0.220, p = 0.005).

Conclusions

High prevalence and cumulative evolution of pre-S mutations preceding HCC development suggested a possible carcinogenic role of pre-S mutations and their potential application in HCC risk prediction.     

The Association between Three Cyclooxygenase-2 Polymorphisms and Hepatocellular Carcinoma Risk: A Meta-Analysis

Background

A quantity of case-control studies have been performed to address the association between three cyclooxygenase-2(COX-2) polymorphisms (-1195G/A, -765G/C and +8473T/C) and the risk of hepatocellular carcinoma (HCC). However, previous research results are inconsistent. We conducted this meta-analysis to clarify the correlation between these COX-2 polymorphisms and HCC risk.

Methods

The authors searched in PubMed, EMBASE, Google Scholar, CNKI and WanFang database for relevant articles up to April 28, 2014. The data were extracted by two independent reviewers. Odds ratios (ORs) and 95% confidence intervals were calculated.

Results

A total of 8 studies consisting of 2182 cases and 3324 controls were included in this meta-analysis. For COX-2 polymorphism -1195G/A, an association with increased risk was observed under the heterogeneous, homozygous, dominant model. However, COX-2 polymorphisms (-765G/C and +8473T/C) were not related to HCC risk in this study. We also found a similar result in the subgroup analysis of Chinese population that -1195G/A polymorphism, instead of -765G/C or +8473T/C polymorphism, was correlated with the risk of HCC.

Conclusions

Polymorphism -1195G/A of COX-2 might be associated with susceptibility to HCC, but no similar correlations were observed between polymorphisms (-765G/C and +8473T/C) and HCC risk. Further large and well-designed studies are required to validate this association.     

The Singapore Liver Cancer Recurrence (SLICER) Score for Relapse Prediction in Patients with Surgically Resected Hepatocellular Carcinoma

Background and Aims

Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection.

Methods

Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992–2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis.

Results

A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities.

Conclusion

The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.     

Comparison of Long-Term Survival of Patients with Solitary Large Hepatocellular Carcinoma of BCLC Stage A after Liver Resection or Transarterial Chemoembolization: A Propensity Score Analysis

Background

The aim of this study was to compare the long-term outcome of patients with a solitary large (>5 cm) hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage A who received liver resection (LR) or transarterial chemoembolization (TACE).

Methods

Our study examined 128 patients treated by LR and 90 treated by TACE. To reduce bias in patient selection, we conducted propensity score analysis in the present study and 54 pairs of patients after propensity score matching were generated, their long-term survival was compared using the Kaplan–Meier method. Independent predictors of survival were identified by multivariate analysis.

Results

Long-term survival was significantly better for the LR group by log-rank test (P<0.001). In multivariate analysis, tumor size, serum ALT level and TACE independently predicted survival. Despite similar baseline characteristics after propensity score matching, LR group still had significantly better survival (1 year, 68.5 vs. 55.0%; 3 years, 47.6 vs. 21.2%; 5 years, 41.3 vs. 18.5%; P = 0.007) than TACE group. The LR and TACE groups had comparable 30- and 90-day post-treatment mortality. Multivariate analysis showed that serum ALT level, serum AFP level and TACE independently predicted survival by multivariate analysis after propensity score matching.

Conclusion

Our propensity-score-matched study suggested that LR provided significantly better long-term survival than TACE for a solitary large HCC of the BCLC stage A, regardless of tumor size.     

Modifiable Prognostic Factors of Hepatocellular Carcinoma in Patients with Non-Surgical Treatment

Background & aims

Current hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment.

Methods

All HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years.

Results

A total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1^st or 2^nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1^st treatment (OR: 2.17, 95% CI: 1.35–3.48), incomplete 2^nd treatment (2.01, 1.27–3.17) and absence of anti-viral agents (1.68, 1.09–2.59) were independent poor prognostic factors.

Conclusion

Complete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible.     

Prediction of Clinical Outcomes in Hepatitis B E Antigen Negative Chronic Hepatitis B Patients with Elevated Hepatitis B Virus DNA Levels

Objectives

We investigated whether long-term clinical outcomes such as disease progression or inactive hepatitis B virus (HBV) carrier state can be predicted by baseline factors in hepatitis B e antigen (HBeAg)-negative HBV infected patients with an elevated viral load.

Methods

A retrospective cohort of 527 HBeAg-negative chronic HBV infected patients with an elevated viral load (HBV DNA ≥ 2,000 IU/ml) was assessed for disease progression defined by the development of hepatocellular carcinoma (HCC) or cirrhotic complication, as well as becoming an inactive carrier.

Results

During a median 3.6 years of follow-up, disease progression was detected in 46 patients (40 with HCC, 6 with cirrhotic complication), and 31 of 309 non-cirrhotic patients became inactive carriers. Older age, male gender, cirrhosis, high HBV DNA levels at baseline, and short antiviral therapy duration were independent risk factors for HCC. Low HBV DNA and quantitative hepatitis B surface antigen (qHBsAg) levels were independent predictors for becoming inactive carriers in patients without cirrhosis. In non-cirrhotic patients with both low qHBsAg and HBV DNA levels, the 5-year cumulative incidence of an inactive carrier was 39.8%, while that of disease progression was 1.6%.

Conclusion

HBeAg negative patients without cirrhosis can be closely monitored for becoming an inactive carrier when both HBV DNA and qHBsAg levels are low, as the risk of disease progression is low while incidence of an inactive carrier is high.