Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus-related hepatocellular carcinoma after ablation therapy.

Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV-related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Patients with HBV-related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan-Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥2000 IU/mL. The median follow-up duration was 28.9 months (range, 12.0-57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P=0.026) and late (≥1 year) recurrence (HR, 0.288; P=0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P=0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. These findings show that HBeAg-negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg-negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV-related HCC.

Chung GE ，Kim W ，Lee JH ，Kim YJ ，Yoon JH ，Lee JM ，Lee JY ，Kim SH ，Kim D ，Lee HS ... -  《-》

Suppressive effects of entecavir on hepatitis B virus and hepatocellular carcinoma.

We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. We enrolled 231 nucleoside-naïve chronic hepatitis B (CHB) patients primarily treated with entecavir 0.5 mg/day for at least 6 months in our institution. Of these, 71 patients had HCC at the start of entecavir treatment (HCC group) and 160 did not (non-HCC group). We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively-treated HCC patients. The HCC and non-HCC groups had similar cumulative rates of HBV-DNA negativity, alanine aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs 95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir treatment for 12 months decreased mean Model for End-Stage Liver Disease scores in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC patients, 16 underwent curative therapies concurrently with entecavir; hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining patients received transarterial chemoembolization or conservative treatment. In a subgroup of 16 HCC patients receiving curative treatments, patients who became serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but not recurrence-free survival (P = 0.961), than those who did not. First-line entecavir monotherapy is comparably effective in CHB patients with and without HCC, and improves hepatic function in HBV-related HCC patients. An early virological response to entecavir is prognostic of improved survival following curative therapy against HBV-related HCC.

Jin YJ ，Shim JH ，Lee HC ，Yoo DJ ，Kim KM ，Lim YS ，Suh DJ ... -  《-》

Noninvasive fibrosis indices predict intrahepatic distant recurrence of hepatitis B-related hepatocellular carcinoma following radiofrequency ablation.

Intrahepatic recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) occurs as a result of direct dissemination or de novo oncogenesis. Hepatocellular carcinogenesis is related to the progression of cirrhosis, and noninvasive fibrosis scoring systems reflect the severity of hepatic fibrosis. Hence, the aim of this study was to elucidate the correlation between noninvasive fibrosis indices and intrahepatic distant recurrence (IDR) of HCC after RFA. Patients with hepatitis B virus (HBV)-related, solitary HCC undergoing RFA were prospectively enrolled. Noninvasive serum fibrosis indices were calculated at the time of RFA. IDR was defined as recurrent HCC beyond >2 cm from the ablation margin of RFA. Predictors of IDR and overall survival were analysed by a Cox regression model. Two hundred forty-six patients received RFA as initial treatment, and the median follow-up duration was 19.7 months (IQR, 11.9-29.8). Among these cases, 133 (45.9%) showed IDR after RFA. In multivariable analysis, serum alpha-fetoprotein (AFP) (HR, 1.000; 95% CI, 1.000-1.001; P = 0.001) and age-platelet index (API) (1.19; 1.01-1.39; P = 0.033) were independent predictors of IDR. In particular, patients with API ≤7 showed a significantly higher recurrence-free survival rate than patients with API >7 (P = 0.004). With regard to overall survival, male sex (4.69; 1.52-14.52; P = 0.007), serum bilirubin (2.78; 1.31-5.90; P = 0.008) and AFP (1.000; 1.000-1.001; P = 0.006) were significantly correlated with shortened survival. High levels of AFP and API predict IDR of HBV-related HCC after RFA. Therefore, noninvasive fibrosis indices could play an important role in predicting IDR of HCC following percutaneous ablation.

Seo JY ，Kim W ，Kwon JH ，Jin EH ，Yu SJ ，Kim HY ，Jung YJ ，Kim D ，Kim YJ ，Yoon JH ，Lee HS ... -  《-》

High serum hyaluronic acid and HBV viral load are main prognostic factors of local recurrence after complete radiofrequency ablation of hepatitis B-related small hepatocellular carcinoma.

Xia F ，Lai EC ，Lau WY ，Ma K ，Li X ，Bie P ，Qian C ... -  《-》

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

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. We enrolled 55 patients who developed HCC during NA therapy and underwent either curative resection or percutaneous ablation for HCC. 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 ≥4.8 log 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. 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.

Hosaka T ，Suzuki F ，Kobayashi M ，Hirakawa M ，Kawamura Y ，Yatsuji H ，Sezaki H ，Akuta N ，Suzuki Y ，Saitoh S ，Arase Y ，Ikeda K ，Kobayashi M ，Kumada H ... -  《-》