Shao-Liang Zhu

Systematic review comparing the safety and efficacy of conventional and drug‐eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma

Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug‐eluting beads (DEB‐TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB‐TACE compares with cTACE.

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.

Efficacy of hepatic resection vs transarterial chemoembolization for solitary huge hepatocellular carcinoma.

AIM To compare the efficacy of hepatic resection (HR) and transarterial chemoembolization (TACE) for patients with solitary huge (≥ 10 cm) hepatocellular carcinoma (HCC). METHODS Records were retrospectively analyzed of 247 patients with solitary huge HCC, comprising 180 treated by HR and 67 by TACE. Long-term overall survival (OS) was compared between the two groups using the Kaplan-Meier method, and independent predictors of survival were identified by multivariate analysis. These analyses were performed using all patients in both groups and/or 61 pairs of propensity score-matched patients from the two groups. RESULTS OS at 5 years was significantly higher in the HR group than the TACE group, across all patients (P = 0.002) and across propensity score-matched pairs (36.4% vs 18.2%, P = 0.039). The two groups showed similar postoperative mortality and morbidity. Multivariate analysis identified alpha-fetoprotein ≥ 400 ng/mL, presence of vascular invasion and TACE treatment as independent predictors of poor OS. CONCLUSION Our findings suggest that HR can be safe and more effective than TACE for patients with solitary huge HCC.

Meta-analysis of associations of interleukin-28B polymorphisms rs8099917 and rs12979860 with development of hepatitis virus-related hepatocellular carcinoma

Background This meta-analysis aimed to assess available evidence on possible associations of interleukin-28B polymorphisms rs8099917 and rs12979860 with development of hepatitis virus-related hepatocellular carcinoma (HCC). Methods PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association of interleukin-28B rs8099917 G/T and rs12979860 T/C polymorphisms with development of hepatitis virus-related HCC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results A total of ten studies involving 2,529 cases and 2,412 controls were included. The G-allele and GT genotype of rs8099917 were significantly associated with increased risk of hepatitis B virus (HBV)-related HCC (allelic model, OR 1.49, 95% CI 1.13–1.96, P=0.005; heterozygous model, OR 1.39, 95% CI 1.04–1.88, P=0.03). Conversely, the TT genotype was found to be significantly associated with lower risk of HBV-related HCC (dominant model, OR 0.68, 95% CI 0.51–0.91, P=0.01). Similar results were observed in the subgroup of Chinese patients and controls. In the pooled data set, the T-allele and TT genotype of rs12979860 showed a significant association with increased HCC risk (allelic model, OR 1.36, 95% CI 1.05–1.78, P=0.02; recessive model, OR 1.75, 95% CI 1.28–2.39, P=0.005; homozygous model, OR 1.99, 95% CI 1.41–2.80, P<0.001). Subgroup analysis based on ethnicity and etiology showed rs12979860 polymorphism to be significantly associated with HCC risk in Caucasians, especially hepatitis C virus-related HCC, according to all five genetic models. In contrast, only the TT genotype of rs12979860 was found to be significantly associated with increased risk of HBV-related HCC, especially in Asians. Conclusion The G-allele of rs8099917 may confer elevated risk of HBV-related HCC, while the wild-type TT genotype may protect against the disease. The T-allele of rs12979860 may increase the risk of HCC, in Caucasians, especially hepatitis C virus-related HCC. The TT genotype of rs12979860 may confer increased risk of HBV-related HCC, especially in Asians. These conclusions should be verified in large, well-designed studies.

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer (BCLC) early (A) and intermediate (B) stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival (RFS) and overall survival (OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/mL, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/mL, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/mL, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE. CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early- and intermediate-stage HCC patients with MVI.

Association of the miR-196a2 C>T and miR-499 A>G polymorphisms with hepatitis B virus-related hepatocellular carcinoma risk: an updated meta-analysis

Background This study meta-analyzed data on the possible association of the miR-196a2 C>T (rs11614913) and miR-499 A>G (rs3746444) polymorphisms with risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Databases in PubMed, EMBASE, Web of Science, China BioMedicine, and Google Scholar were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association of the miR-196a2 C>T and miR-499 A>G polymorphisms with HBV-related HCC risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results A total of 13 studies involving 3,964 cases and 5,875 healthy controls were included. Random-effect meta-analysis showed that the T allele and TT genotype of miR-196a2 C>T were associated with significantly lower HBV-related HCC risk (allelic model, OR =0.84, 95% CI =0.71–0.99, P=0.04; homozygous model, OR =0.68, 95% CI =0.47–0.98, P=0.04). In contrast, miR-499 A>G showed no significant association with HBV-related HCC risk in either overall pooled analysis or ethnic subgroup analysis according to any of the four genetic models. Based on analysis of ethnic subgroups, neither miR-196a2 C>T nor miR-499 A>G was significantly associated with risk of HBV-related HCC in Chinese population. Conclusion The polymorphism miR-196a2 C>T, but not miR-499 A>G, may be associated with decreased HBV-related HCC risk. These conclusions should be verified in large, well-designed studies.

The prediction of clinical outcome in hepatocellular carcinoma based on a six-gene metastasis signature.

Purpose: The dismal outcome of hepatocellular carcinoma (HCC) is largely attributed to its early recurrence and venous metastases. We aimed to develop a metastasis-related model to predict hepatocellular carcinoma prognosis. Experimental Design: Using microarrays, sequencing, and RT-PCR, we measured the expression of mRNAs and lncRNAs in a training set of 94 well-defined low-risk (LRM) and high-risk metastatic (HRM) HCC patients from a Shanghai cohort. We refined a metastasis signature and established a corresponding model using logistic regression analysis. The validation set consisted of 567 HCC patients from four-center cohorts. Survival analysis was performed according to the metastasis model. Results: Using relative expression of tumor to para-tumor tissues, we refined the metastasis signature of five mRNAs and one lncRNA. A generalized linear model was further established to predict the probability of metastasis (MP). Using MP cutoff of 0.7 to separate LRM and HRM in Shanghai cohort, the specificity and sensitivity of the model were 96% [95% confidence interval (CI), 85%–99%] and 74% (95% CI, 58%–86%), respectively. Furthermore, HRM patients showed a significantly shorter overall and recurrence-free survival in validation cohorts (P < 0.05 for each cohort). Early HCC patients also have a poorer outcome for multicenter HRM patients. Finally, Cox regression analysis indicated that continuous MP was an independent risk factor and associated with the recurrence and survival of HCC patients after resection (HR 2.98–16.6, P < 0.05). Conclusions: We developed an applicable six-gene metastasis signature, which is robust and reproducible in multicenter cohorts for HCC prognosis. Clin Cancer Res; 23(1); 289–97. ©2016 AACR.

Genetic polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 promoter may not be associated with development of hepatocellular carcinoma

This study meta-analyzed the literature on possible association of polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 (IL-18) promoter with risk of hepatocellular carcinoma (HCC). The analysis included 8 case-control studies on the -137 polymorphism (1,318 cases, 2,254 controls) and 7 case-control studies on the -607 polymorphism (1,262 cases, 1,696 controls). None of the five genetic models suggested a significant association between the -137 polymorphism and HCC risk: allelic model, OR 0.99, 95% CI 0.74–1.34, P = 0.97; recessive model, OR 0.98, 95% CI 0.65–1.46, P = 0.91; dominant model, OR 1.35, 95% CI 0.73–2.52, P = 0.34; homozygous model, OR 0.99, 95% CI 0.65–1.49, P = 0.95; heterozygous model, OR 0.99, 95% CI 0.66–1.48, P = 0.94. Similar results were obtained in subgroup analyses of Asian patients, Chinese patients, or patients with hepatitis B virus (HBV)-related HCC. Similar results were also obtained for the -607 polymorphism across the entire study population as well as in the three subgroups. The available evidence suggests no significant association of the -137 or -607 polymorphisms with risk of HCC in general or specifically of HBV-related HCC. These conclusions should be verified in large, well-designed studies.

Postoperative hepatitis B virus reactivation and surgery-induced immunosuppression in patients with hepatitis B-related hepatocellular carcinoma.

Hepatectomy in hepatocellular carcinoma (HCC) patients lead to postoperative hepatitis B virus (HBV) reactivation (PHR) as well as immunosuppression.

Is drug‐eluting‐bead transcatheter arterial chemoembolization (TACE) associated with better tumor response than conventional TACE in a meta‐analysis?: Authors’ reply

Dear Editor, We thank Kodama and coworkers for their letter on our review, which was critical of drug-eluting-bead transarterial chemoembolization (DEB-TACE) possibly bringing better tumor response than conventional TACE (cTACE) for inoperable hepatocellular carcinoma. Our review studied the safety and efficiency of DEB-TACE compared with cTACE depending on six trials (Ferrer et al., Lammer et al., Sacco et al., Malenstein et al., Recchia et al. and Golfieri et al.). We drew the conclusion that althoughDEB-TACE could not bring better overall survival, it brings better tumor response. However, Kodama et al. pointed out that DEB-TACE was not superior to cTACE (risk ratio [RR]=1.00, 95% confidence interval [CI] =0.83–1.21, P=0.194) on tumor response. We have re-analyzed original data from all the included studies. We acknowledge the reference errors in Supplement Table 2 of our review (revised data are shown as Table 1). In our review, we analyzed objective response (OR) rate (OR= complete response [CR]+partial response [PR]) as outcome, which was described in the section of “Types of outcome measures” and “Methods” (p. 191). Actually, OR, CR and stable disease rate were described in the five original studies (Ferrer et al., Lammer et al., Sacco et al., Malenstein et al. and Golfieri et al.). In our review, stable disease rate was not calculated. Our results of better OR were supported by another recent meta-analysis, in which the definition of OR was the same as ours. This metaanalysis included seven studies involving 700 participants. However, the data on stable disease rate was included when Kodama et al. calculated tumor response. Here, we re-analyzed the tumor response as CR and PR, respectively. Although on the outcome of CR, no significance was found between cTACE and DEB-TACE groups (RR=0.86, 95% CI=0.70–1.06), patients in the DEB-TACE group had significantly better tumor response on PR (RR=1.30, 95% CI=1.01–1.69). One of the included studies by Malenstein et al. recruited 30 patients. However, only 25 patients’ data was analyzed in the original study. In our review, intention-to-treat analysis was performed including all 30 recruited patients. Thismight have led to differences with the results of Kodama et al.