Systematic review and meta‐analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen seroconversion

Hepatitis B e antigen (HBeAg) seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg seroconversion. We performed a systematic review and meta‐analysis to determine the incidence of HCC in patients with CHB after HBeAg seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg seroconversion was pooled using a random‐effects model or fix‐effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%‐4.58%) of patients with CHB develop HCC despite HBeAg seroconversion. In patients with HBeAg seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%‐2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg seroconversion were at significantly higher risk for HCC development. HBeAg seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35‐0.97, P = .04). Despite the reduced risk with HBeAg seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg seroconversion. Long‐term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg seroconversion.     

Meta‐analysis: interferon‐alpha prevents the recurrence after curative treatment of hepatitis C virus‐related hepatocellular carcinoma

Summary. Various clinical studies have indicated that interferon (IFN)‐alpha treatment prevents the development of hepatocellular carcinoma (HCC) in people chronically infected with hepatitis C virus. However, it has been controversial whether IFN‐alpha treatment prevents HCC recurrence. The aim of this study was to identify the preventive effect of IFN‐alpha treatment after curative therapy of primary tumours within the Milan criteria (three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less) on HCC recurrence. We conducted a meta‐analysis of five trials including 355 patients (167 patients received IFN‐alpha treatment after curative therapy of primary tumours) and estimated relative risks (RRs) and 95% confidence intervals (CIs) for the effect of IFN‐alpha on HCC recurrence according to the DerSimonian and Laird method. IFN‐alpha treatment after curative therapy of primary tumours significantly prevented HCC recurrence (RR 0.33; 95%CI 0.19–0.58, P < 0.0001) without a significant heterogeneity (Q = 4.52, P = 0.34). An evaluation using the Begg method suggested no evidence of publication bias. Sub‐group analyses revealed that IFN‐alpha treatment reduced HCC recurrence in two studies achieving sustained virologic response (SVR) rates >30% (RR 0.20; 95%CI 0.05–0.81, P = 0.02) and in three studies achieving SVR rates ≤30% (RR 0.44; 95%CI 0.23–0.84, P = 0.01). In conclusion, IFN‐alpha treatment after curative treatment of primary tumour within Milan criteria may be effective for the prevention of HCC recurrence, and higher SVR rate may be associated with better preventive effect of IFN‐alpha treatment on HCC recurrence.     

Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta‐analysis

Background: Recent evidence suggests that transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) or a percutaneous ethanol injection (PEI) may have a synergistic effect in treating hepatocellular carcinoma (HCC). The aim of the current meta‐analysis was to identify the survival benefits of TACE combined with percutaneous ablation (PA) therapy (RFA or PEI) for unresectable HCC compared with those of TACE or PA alone. Methods: Randomized‐controlled trials (RCTs) published as full papers or abstracts were searched to assess the survival benefit or tumour recurrence for patients with unresectable HCC on electronic databases. The primary outcome was survival. The secondary outcomes were response to therapy and tumour recurrence. Results: Ten RCTs met the criteria to perform a meta‐analysis including 595 participants. TACE combined with PA therapy, respectively improved, 1‐, 2‐, and 3‐year overall survival compared with that of monotherapy [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.14–4.57; P=0.020], (OR=4.53, 95% CI 2.62–7.82, P<0.00001) and (OR=3.50, 95% CI 1.75–7.02, P=0.0004). Sensitivity analysis demonstrated a significant benefit in 1‐, 2‐ and 3‐year overall survival of TACE plus PEI compared with that of TACE alone for patients with large HCC lesions, but not in TACE plus RFA vs RFA for patients with small HCCs. The pooled result of five RCTs showed that combination therapy decreased tumour recurrence compared with that of monotherapy (OR=0.45, 95% CI 0.26–0.78, P=0.004). Conclusion: TACE combined with PA therapy especially PEI improved the overall survival status for large HCCs.     

Surgical and oncologic outcomes following laparoscopic versus open liver resection for hepatocellular carcinoma: A meta-analysis

Aim: Laparoscopic hepatectomy has become a common method for treatment of hepatocellular carcinoma (HCC) nowadays, but the oncologic risks of laparoscopic liver resection for HCC are still under investigation. We performed a meta‐analysis to quantitatively compare surgical and oncologic outcomes of patients with HCC undergoing laparoscopic versus open hepatectomy. Methods: Systematic review and meta‐analysis of studies comparing laparoscopic with open liver resection for HCC. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5. Results: Ten studies comprising 627 patients were eligible for inclusion. The overall rate of conversion to open surgery was 6.6%. The laparoscopic group had significantly less blood loss by 223.17 mL (95% confidence interval [CI]: ?331.81, ?114.54; P < 0.0001), fewer need for transfusions (odds ratio [OR]: 0.42, 95% CI: 0.22, .079; P = 0.007), shorter hospital stay by 5.05 days (95% CI: ?7.84, ?2.25; P = 0.0004) and fewer postoperative complications (OR: 0.50; 95% CI: 0.32, 0.77; P = 0.002). No significant differences were found concerning surgery margin (weighted mean differences [WMD], 0.55; 95% CI: ?0.71, 1.80; P = 0.39), resection margin positive rate (OR, 0.63; 95% CI: 0.25, 1.54; P = 0.31) and tumor recurrence (OR, 0.79; 95% CI: 0.49, 1.27; P = 0.33). In the 244 patients that underwent laparoscopic hepatectomy of all 10 studies included, no patients developed tumor recurrence at the site of resection margin, peritoneal dissemination or trocar‐site metastases. Conclusions: On currently available evidence, laparoscopic resection appears not to affect oncologic outcomes and increase tumor recurrence. It also offers less blood loss, decreased rate of intraoperative transfusion and shorter lengths of hospital stay. Laparoscopic resection is a safe and feasible choice for selected patients with HCC.     

Influence of clinically significant portal hypertension on surgical outcomes and survival following hepatectomy for hepatocellular carcinoma: a systematic review and meta‐analysis

Surgical resection is not indicated in patients with portal hypertension in the current guideline of Barcelona Clinic Liver Cancer (BCLC) stage. We report a systematic review and meta‐analysis to determine the impact of clinically significant portal hypertension on survival in patients with hepatocellular carcinoma (HCC) following hepatectomy. Searched data in PubMed, EMBASE, and the Cochrane Library were reviewed and 11 publications were included in the meta‐analysis. The inclusion criteria of clinically significant portal hypertension were esophageal varices and/or thrombocytopenia with splenomegaly. Pooled data were extracted and computed into odds ratios (ORs) for clinical outcome and hazard ratios (HRs) for overall survival. The final pooled data were composed of 2,285 patients. There were 775 patients with clinically significant portal hypertension (PHT group) and 1,510 patients without clinically significant portal hypertension (non‐PHT group). Pooled proportion of mortality was 6.1% (95% confidence interval [CI] 0.032–0.116) in PHT group and 2.8% (95% CI 0.014–0.054) in the non‐PHT group. The pooled proportion of morbidity was 41.7% (95% CI 0.274–0.575) in PHT group and 34.7% (95% CI 0.243–0.467) in non‐PHT group. Pooled data confirmed a significantly higher postoperative mortality in the PHT group, with OR 3.02 (P < 0.001). The PHT group also demonstrated significantly higher occurrence of postoperative complications (OR 1.39, P = 0.008), liver‐related morbidity (OR 3.10, P < 0.00001), and liver failure (OR 2.14, P = 0.0005) compared to the non‐PHT group. According to the overall survival, pooled analysis demonstrated that the PHT group demonstrated poorer survival than the non‐PHT group (HR 1.48, P = 0.007). The analyses support significantly higher rates of postoperative mortality, complications, liver‐related morbidity, liver failure, and poorer overall survival in PHT group compared with the non‐PHT group. Surgical resection should be selected carefully with strict surgical strategy in patients with clinically significant portal hypertension when surgical resection is planned.     

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

Background and Aim: 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. Methods: 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. Results: 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 > 10⁴ 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 > 10⁴ copies/mL at resection, and the absence of sustained HBV DNA level < 10⁴ 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 < 10⁴ 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). Conclusions: 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 10⁴ copies/mL is a strong protective factor for long‐term recurrence‐free and overall survival.     

Meta‐analysis: Association between hepatitis B virus preS mutation and hepatocellular carcinoma risk

Previous observational studies suggested that hepatitis B virus (HBV) preS mutation plays an important role in the existence of HBV‐related hepatocellular carcinoma (HCC). However, the results are still debatable. With an increasing number of studies about this topic, this study employed a meta‐analysis to identify the association between HBV preS mutation and HCC risk. We searched for eligible studies from PubMed, ProQuest, CINAHL, ScienceDirect and Springer databases to assess the association between HBV mutation and HCC risk. This meta‐analysis was conducted using RevMan 5.3 to provide pooled estimate for odds ratio (ORs) with 95% confidence intervals (95% CIs). Twenty‐one clinical studies were included in this meta‐analysis study which consisted of 1738 participants with HBV‐related HCC and 3740 HBsAg‐positive patients without HCC. All studies used samples of Asian population. PreS deletion was the most common mutation found in all studies. We found that ORs of HBV overall preS deletion was associated with HCC (OR = 3.28; 95% CI = 2.32‐4.65; P < .00001; random‐effects model). Each preS1 and preS2 deletion was associated with increased risk of HCC, with OR 2.42 (95% CI = 1.25‐4.68, P = .008) and 3.36 (95% CI = 2.04‐5.55, P < .00001), respectively. PreS2 start codon mutation was also significantly associated with HCC risk (OR = 2.47; 95% CI: 1.15‐5.27; P = .02; random‐effect model). The result of this meta‐analysis suggested that HBV preS deletion (all, preS1 and preS2) and preS2 start codon mutation might contribute to the increased risk of HBV‐related HCC.     

Effects of interferon therapy on development of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis: A meta-analysis of randomized controlled trials

Aim: The role of interferon (IFN) therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)‐related cirrhosis remains controversial. This meta‐analysis aimed to determine whether IFN therapy reduced the incidence of HCC in HCV‐related cirrhotic patients. Methods: We performed a meta‐analysis including eight randomized controlled trials (RCT) (a total of 1505 patients) to assess the effect of IFN therapy on prevention of HCC in patients with HCV‐related cirrhosis. The pooled odds ratios (OR) were calculated using a random or fixed effects model. Results: Our results showed that IFN therapy significantly decreased the overall HCC incidence in HCV‐related cirrhotic patients (OR, 0.29; 95% confidence interval [CI], 0.10–0.80; P = 0.02). HCC risk in patients who failed to achieve sustained virological response (SVR) in the initial IFN‐based treatment was also reduced by maintenance IFN therapy (OR, 0.54; 95% CI, 0.32–0.90; P = 0.02). Subgroup analysis indicated that IFN therapy decreased HCC incidence in HCV‐related cirrhotic patients during long‐term follow up (>48 months) evidently (OR, 0.25; 95% CI, 0.09–0.67; P = 0.006). However, subgroup analysis of four RCT with short‐term follow up (≤48 months) did not demonstrate the significant difference in HCC incidence between IFN‐treated cirrhotic patients and controls (OR, 0.78; 95% CI, 0.39–1.55; P = 0.48). Conclusion: The present study suggested that IFN therapy could efficiently reduce HCC development in patients with HCV‐related cirrhosis; this effect was more evident in the subgroup of patients with long‐term follow up (>48 months). Patients who received maintenance IFN therapy had a lower risk of HCC than controls.     

Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma

BACKGROUND/AIMS: To study the impact of hepatitis B e antigen on tumor recurrence and patients' survival after curative resection of hepatocellular carcinoma. METHODS: Two hundred and three patients with small hepatocellular carcinomas (3cm) who had undergone curative resection were divided into HBeAg-positive group and HBeAg-negative group. Clinicopathological factors and postoperative outcomes were compared between groups, and risk factors for survival and recurrence were studied. RESULTS: The median follow-up time was 32.9months. Patients with negative HBeAg had higher 5-year overall survival rates (76% vs 53.9%, hazards ratio (HR): 2.363, 95% CI: 1.335-4.181, p=0.002) and 5-year disease-free survival rates (52.9% vs 37.4%, HR: 1.603, 95% CI: 1.00-2.561, p=0.046).There was no significant difference in operative morbidity and tumor factors between the two groups, but younger age, higher serum alanine aminotransferase levels, and more macronodular cirrhosis were found in the HBeAg-positive group. Multivariate analysis revealed that age >50years, HBeAg positivity and macronodular cirrhosis were independent factors for overall survival, and HBeAg positivity and multiple tumor nodules were independent factors for disease-free survival. Positive serum HBeAg was associated with a higher risk of early recurrence (within 1year). CONCLUSIONS: HBeAg is associated with a higher risk of early recurrence and poorer survival in patients after curative resection of small HCC.     

Tenofovir versus entecavir for tertiary prevention of hepatocellular carcinoma in chronic hepatitis B infection after curative therapy: A systematic review and meta-analysis

Entecavir (ETV) and Tenofovir disoproxil fumarate (TDF) are the first-line drugs for the treatment of chronic hepatitis B virus (HBV). However, the impact of these two antiviral agents on the outcome of HBV-related hepatocellular carcinoma (HCC) after curative therapy remains to be explored. The purpose of the present study was to compare the effect of ETV and TDF on recurrence and mortality after curative treatment for HBV-related HCC. A comprehensive literature search of multiple electronic databases was conducted from 2000 to January 2022 for studies comparing ETV and TDF for HBV-related HCC patients after curative therapy. The adjusted hazard ratios (aHR) were pooled using a random-effects model. A total of nine studies with 5298 patients were included in the final meta-analysis. TDF was associated with a lower risk of HCC recurrence [aHR 0.73, 95% confidence interval (CI) 0.65–0.81] compared to HCC. TDF reduced the risk of late recurrence compared to ETV (aHR 0.58, 95% CI 0.45–0.76) but not early recurrence (aHR 0.88, 95% CI 0.76–1.02). The mortality risk was also lower with TDF compared to ETV (aHR 0.62, 95% CI 0.50–0.77). TDF was associated with a lower risk of recurrence and mortality than ETV after resection or ablation of HBV-related HCC. Further prospective randomized controlled studies are warranted to validate these results.     

Influence of hepatitis B virus reactivation on the recurrence of HBV‐related hepatocellular carcinoma after curative resection in patients with low viral load

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B‐related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV‐related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre‐operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV‐related HCC after curative resection were investigated. Fifty‐three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV‐related HCC in patients with low viral load.     

Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta‐analysis

Aim: The efficacy of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) is positive, but for postoperative HCC, many studies have reported controversial results. The present study aimed to evaluate the efficacy of postoperative adjuvant TACE for participants with HCC. Methods: Electronic and manual searches were conducted to identify randomized controlled trials (RCT) evaluating postoperative adjuvant TACE for participants with HCC. Results: Six RCT totaling 659 participants, of whom almost all were of stage IIIA HCC, were included. For the 1‐year tumor recurrence rate, hepatectomy plus TACE showed statistically significant less incidence of recurrence, with a pooled risk ratio (RR) of 0.68 (95% confidence interval [CI] = 0.55–0.84, P = 0.0003). For 1‐year mortality, the trials were favorable for TACE with a pooled risk ratio of 0.48 (95% CI = 0.35–0.65, P < 0.00001). For 3‐year mortality, the trials also revealed statistically significant less incidence, with a pooled risk ratio of 0.76 (95% CI = 0.64–0.90, P = 0.002). However, for 5‐year mortality, TACE did not demonstrate statistically significant less incidence (RR = 0.94, 95% CI = 0.81–1.08, P = 0.36). Transient fever and nausea/vomiting were reported as side‐effects of TACE but were well tolerated by most participants. Conclusion: Postoperative adjuvant TACE seems promising for participants with HCC with risk factors (multiple nodules of >5 cm or vascular invasion) but requires further trial.     

Insulin resistance raises the risk for recurrence of stage I hepatocellular carcinoma after curative radiofrequency ablation in hepatitis C virus‐positive patients: A prospective,case series study

Aim: Several studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). We conducted a prospective, case series study to test the impact of insulin resistance on the recurrence after curative radiofrequency ablation (RFA) of stage I HCC in HCV‐positive patients. Methods: From January 2006 to December 2007, 226 consecutive patients underwent treatment for primary HCC at our institutions, including 37 stage I cases. Among them, 33 were HCV‐positive, and three, six and 24 received curative surgery, transarterial chemoembolization or RFA, respectively. In the 24 patients treated with RFA, recurrence‐free survival was analyzed using the Kaplan–Meier method. The factors contributing to recurrence of HCC were subjected to univariate and multivariate analyses using the Cox proportional hazards model. Insulin resistance was estimated by the Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR). Results: Kaplan–Meier analysis showed that the recurrence‐free survival was lower in patients with higher HOMA‐IR (>2.3, P = 0.0252) or with lower serum albumin level (<3.3 g/dL, P = 0.0004). In the univariate analysis, HOMA‐IR (P = 0.0420) and albumin (P = 0.0036) were significantly associated with recurrence of HCC. Multivariate analysis revealed albumin (odds ratio = 0.01, 95% confidence interval = 0.0002–0.015, P = 0.0001) and HOMA‐IR (odds ratio = 3.85, 95% confidence interval = 1.57–14.2, P = 0.0015) to be independent predictors for recurrence of HCC. Conclusion: Serum albumin level and HOMA‐IR were independent risk factors for recurrence of stage I HCC after curative RFA in HCV‐positive patients. Patients with these factors require closer surveillance.     

HBcrAg is a predictor of post‐treatment recurrence of hepatocellular carcinoma during antiviral therapy

Background/Aims: The recurrence rate of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is high even in patients receiving curative therapy. In this study, we analysed the risk factors for tumour recurrence after curative therapy for HBV‐related HCC while under treatment with nucleot(s)ide analogues (NAs) by measuring serum HBcrAg and intrahepatic covalently closed circular DNA (cccDNA) levels to elucidate the viral status associated with HCC recurrence. Methods: We enrolled 55 patients who developed HCC during NA therapy and underwent either curative resection or percutaneous ablation for HCC. Results: Hepatocellular carcinoma recurred in 21 (38%) of the patients over a period of 2.2 (range, 0.2–7.4) years. In multivariate analysis, serum HBcrAg levels ≥4.8log U/ml at the time of HCC diagnosis (hazard ratio, 8.96; 95% confidential interval, 1.94–41.4) and portal vein invasion (3.94, 1.25–12.4) were independent factors for HCC recurrence. The recurrence‐free survival rates of the high cccDNA group were significantly lower than those of the low cccDNA group only in patients who underwent resection (P=0.0438). A positive correlation (P=0.028; r=0.479) was observed between the intrahepatic cccDNA and the serum HBcrAg levels at the incidence of HCC. Conclusion: HBcrAg is a predictor of the post‐treatment recurrence of HCC during antiviral therapy. Serum HBcrAg and intrahepatic cccDNA suppression by NAs may be important to prevent HCC recurrence.     

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment. Methods: Eighty‐eight consecutive patients who underwent percutaneous RFA as first‐line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. Results: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease‐free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101–4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086–12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170–5.191, P = 0.018) was identified for disease‐free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241–17.241, P = 0.023). Conclusion: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.     

Overexpression of Yes‐associated protein and its association with clinicopathological features of hepatocellular carcinoma: A meta‐analysis

Background

Yes‐associated protein (YAP) overexpression is reported to be associated with risk of hepatocellular carcinoma (HCC) but current studies have not explored the relationship between YAP expression with HCC clinicopathological features.

Methods

To assess these associations, a meta‐analysis was performed which included four eligible studies including 391 HCC cases and 334 controls. There were eight eligible studies to investigate the association between YAP expression in HCC and clinicopathological features of liver cancer patients. Literature was obtained from PubMed, Embase, Wangfang and China National Knowledge Infrastructure.

Results

Analysis indicated that YAP expression in HCC was greater than in adjacent non‐tumour tissue (odds ratio [OR], 15.80, 95% confidence interval [CI], 10.53‐23.70, P<.00001; heterogeneity=.30). YAP overexpression in HCC was significantly associated with vascular invasion (OR, 2.21, 95% CI, 11.64‐2.97, P<.00001, heterogeneity=.10), less cellular differentiation (OR, 2.38, 95% CI, 1.61‐3.51, P<.00001, heterogeneity=.333), tumours larger than 5 cm (OR, 2.52, 95% CI, 1.75‐3.62, P<.00001; heterogeneity=.17) and TNM tumour stage I + II (OR, 0.44, 95% CI, 0.28‐0.75, P=.00003, heterogeneity=.12).

Conclusions

Overexpression of YAP contributes to HCC formation, and its overexpression is associated with vascular invasion, low cellular differentiation tumours larger than 5 cm and TNM tumour stage III + IV.     

Association of on‐treatment serum hepatitis B surface antigen level with sustained virological response to nucleos(t)ide analog in patients with hepatitis B e‐antigen positive chronic hepatitis B

Aim: This study evaluated the on‐treatment serum hepatitis B surface antigen (HBsAg) level during nucleos(t)ide analog (NUC) therapy and the correlation with off‐treatment sustained virological response (SVR). Methods: Fifty‐one consecutive patients with hepatitis B e‐antigen (HBeAg) positive chronic hepatitis B who achieved HBeAg loss/seroconversion after NUC therapy and completed 12 months or more of additional therapy were included. Serum HBsAg and hepatitis B virus (HBV) DNA levels were determined at baseline, 3, 6, 9 and 12 months, and at the end of treatment. SVR was defined as HBV DNA levels of less than 10 000 copies/mL until 6 or 12 months off‐treatment without reappearance of HBeAg. Results: Twenty‐two (43.1%) and 13 (25.5%) patients maintained SVR at 6 and 12 months off‐treatment, respectively. In univariate analyses, a decline of HBsAg of 0.5 log₁₀ IU/mL or less at 6 months (P = 0.006) and 12 months (P = 0.013), the mean change in HBsAg level at 6 months (P = 0.024), and lamivudine or entecavir treatment (P = 0.019) were significant predictive factors for SVR at 6 months off‐treatment. A decline of HBsAg of 0.5 log₁₀ IU/mL or less at 6 months and lamivudine or entecavir treatment were independent factors on multivariate analyses (odds ratio [OR], 16.67; 95% confidence interval [CI], 1.86–142.86 [P = 0.012]; and OR, 14.83; 95% CI, 1.18–185.73 [P = 0.036]; respectively). Conclusion: On‐treatment serum HBsAg level predicted early off‐treatment SVR to NUC therapy in patients infected with genotype C.     

Meta‐analysis of alcohol consumption and risk of extrahepatic bile system cancer

Aim: Alcohol consumption increases the risk of liver cancer. However, there is still controversy regarding alcohol consumption and the risk of extrahepatic bile system cancer (EBSC). We performed a meta‐analysis to provide an overview of the relevant studies and gain more robust estimates of the relationship between alcohol consumption and risk of EBSC. Methods: Relevant studies published between January 1966 and October 2010 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between alcohol consumption and risk of EBSC was assessed by adjusted odds ratio (OR). Results: A total of 113 767 participants from 10 studies (nine case–control studies and one cohort study) were identified in this meta‐analysis. The studies provided adjusted overall OR estimates for drinkers versus non‐/low drinkers, leading to a pooled adjusted OR of 0.82 (95% confidence interval [CI] = 0.72–0.94, P for heterogeneity = 0.194, I² = 27.2%). The overall adjusted OR of hospital‐based studies and population‐based studies were 0.80 (95% CI = 0.65–0.99, P = 0.260) and 0.79 (95% CI = 0.64–0.98, P = 0.119), respectively. For the heavy drinkers, the adjusted OR significance increased to 1.58 (95% CI = 0.97–2.57, P for heterogeneity = 0.055, I² = 65.4%), but it had no statistical significance. Conclusion: There is evidence that moderate alcohol consumption lowers the risk of EBSC compared with non‐/low alcohol consumption, but not heavy alcohol consumption. Further multicenter and better controlled studies are required to confirm these findings.     

The impact of E‐cadherin expression on the prognosis of esophageal cancer: a meta‐analysis

E‐cadherin is a 120‐KD transmembrane calcium‐dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta‐analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta‐analysis was 1.33 (95% CI 1.16–1.52; z = 3.99, P = 0.00). When the study measured by enzyme‐linked immunosorbent assay is excluded, the pooled HR‐evaluated E‐cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22–1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21–1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E‐cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33–2.02). The pooled odds ratio of reduced E‐cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75–3.94), 1.77 (95% CI 1.06 ?2.97), and 3.39 (95% CI 1.85–6.23). Reduced E‐cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E‐cadherin expression is significantly associated with poorer differentiation degree.     

Maternal viral load and hepatitis B virus mother‐to‐child transmission risk: A systematic review and meta‐analysis

Aim

The aim of this study was to assess the relationship between maternal viral load and mother‐to‐child transmission (MTCT) risk in hepatitis B envelope antigen (HBeAg)‐positive mothers.

Methods

PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)‐DNA‐positive and HBV‐DNA‐negative groups. We also examined the dose–response effect of this relationship.

Results

Twenty‐one studies with 10 142 mother–child pairs were included in the studies. The mean MTCT incidence was 13.1% in the maternal HBV‐DNA‐positive group, compared with 4.2% in the negative group. The summary MTCT odds ratio of maternal HBV‐DNA positive compared with negative was 9.895 (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random‐effects model. In maternal HBV‐DNA <6 log10 copies/mL, 6–8 log10 copies/mL, and >8 log₁₀ copies/mL level stratifications, the pooled MTCT incidences were 2.754% (95% CI, 1.198–4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349–13.516%; Z = 5.43, P < 0.00001), and 14.445% (95% CI, 8.317–20.572%; Z = 4.62, P < 0.00001), respectively. A significant linear dose–response association was found between maternal viral load and MTCT risk, with the points estimate of increased MTCT risk 2.705 (95% CI, 1.808–4.047) at 6 log10 copies/mL compared with reference (3 log10 copies/mL), and 7.316 (95% CI, 3.268–16.378) at 9 log₁₀ copies/mL. A significant non‐linear dose–response association was also found between maternal viral load and HBV MTCT risk (model χ² = 23.43, P < 0.00001).

Conclusion

Our meta‐analysis indicated that maternal viral load was an important risk factor for MTCT in HBeAg‐positive mothers, and maternal viral load was dose‐dependent with HBV MTCT incidence.