Ryota Masuzaki

Radiofrequency Ablation for Hepatocellular Carcinoma: 10-Year Outcome and Prognostic Factors

OBJECTIVES:Radiofrequency ablation (RFA) is widely performed for hepatocellular carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The objective of this study was to report a 10-year consecutive case series at a tertiary referral center.METHODS:We performed 2,982 RFA treatments on 1,170 primary HCC patients and analyzed a collected database.RESULTS:Final computed tomography images showed complete tumor ablation in 2,964 (99.4%) of 2,982 treatments performed for the 1,170 primary HCC patients. With a median follow-up of 38.2 months, 5- and 10-year survival rates were 60.2% (95% confidence interval (CI): 56.7–63.9%) and 27.3% (95% CI: 21.5–34.7%), respectively. Multivariate analysis demonstrated that age, antibody to hepatitis C virus (anti-HCV), Child-Pugh class, tumor size, tumor number, serum des-γ-carboxy-prothrombin (DCP) level, and serum lectin-reactive α-fetoprotein level (AFP-L3) were significantly related to survival. Five- and 10-year local tumor progression rates were both 3.2% (95% CI: 2.1–4.3%). Serum DCP level alone was significantly related to local tumor progression. Five- and 10-year distant recurrence rates were 74.8% (95% CI: 71.8–77.8%) and 80.8% (95% CI: 77.4–84.3%), respectively. Anti-HCV, Child-Pugh class, platelet count, tumor size, tumor number, serum AFP level, and serum DCP level were significantly related to distant recurrence. There were 67 complications (2.2%) and 1 death (0.03%).CONCLUSIONS:RFA could be locally curative for HCC, resulting in survival for as long as 10 years, and was a safe procedure. RFA might be a first-line treatment for selected patients with early-stage HCC.

Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography

Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV‐RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow‐up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person‐year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM ≤10 kPa, of 16.7 (95% confidence interval [CI], 3.71‐75.2; P < 0.001) when LSM 10.1‐15 kPa, 20.9 (95% CI, 4.43‐98.8; P < 0.001) when LSM 15.1‐20 kPa, 25.6 (95%CI, 5.21‐126.1; P < 0.001) when LSM 20.1‐25 kPa, and 45.5 (95% CI, 9.75‐212.3; P < 0.001) when LSM >25 kPa. Conclusions: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development. (HEPATOLOGY 2009.)

Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors.

Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease.

Obesity Is an Independent Risk Factor for Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients

BACKGROUND & AIMS It is not fully elucidated whether obesity enhances hepatocarcinogenesis in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between body weight and risk of hepatocarcinogenesis in chronic hepatitis C patients. METHODS We enrolled 1431 patients with chronic hepatitis C who visited our liver clinic between 1994 and 2004, excluding those with hepatocellular carcinoma (HCC) at their visit or with a previous history of HCC. They were divided into 4 groups according to body mass index (BMI): underweight (< or =18.5 kg/m(2), N = 112); normal (18.5 to less than 25 kg/m(2), N = 1023); overweight (25 to less than 30 kg/m(2), N = 265); and obese (>30 kg/m(2), N = 31). We assessed the impact of obesity on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis. RESULTS During the follow-up period (mean, 6.1 y), HCC developed in 340 patients, showing cumulative incidence rates of 10.5%, 19.7%, and 36.8% at 3, 5, and 10 years, respectively. The incidence differed significantly among the BMI groups (P = .007). Adjusting for other significant factors, overweight and obesity were shown to be an independent risk factor of HCC, with a hazard ratio of 1.86 (95% confidence interval, 1.09-3.16; P = .022) and 3.10 (95% confidence interval, 1.41-6.81; P = .005) as compared with the underweight patients. CONCLUSIONS The risk of HCC in patients with chronic hepatitis C increases in proportion to BMI in a wide range of its values, from underweight to obese.

Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences

Interleukin‐6 (IL‐6) may play a role in the pathogenesis of hepatocellular carcinoma (HCC). Recently, it was reported in mouse models that estrogen‐mediated inhibition of IL‐6 production explains the gender disparity in HCC. We conducted a retrospective cohort study to examine whether this hypothesis is applicable to human HCC. We enrolled 330 patients with chronic hepatitis C whose serum samples were collected between January 1994 and December 2002. Serum IL‐6 concentrations were measured and patients were divided into three groups according to IL‐6 levels: low, middle, and high. We evaluated the association between serum IL‐6 levels and the risk of subsequent HCC development, including subgroup analysis on each gender. During the follow‐up period (mean 9.0 yr), HCC developed in 126 patients. The incidence rates differed significantly among the three groups (p = 0.015), increasing in accordance with serum IL‐6 levels. However, unexpectedly, this tendency was significant only in female patients. In a multivariate analysis, higher serum IL‐6 level was an independent risk factor for HCC development in female patients, with a hazard ratio of 1.61. Although female patients showed a weak negative correlation between serum IL‐6 levels and estradiol levels, the lower risk of HCC in female patients cannot be fully explained by estrogen‐mediated inhibition of IL‐6 production. In conclusion, higher serum IL‐6 level was an independent risk factor for HCC development in female but not male chronic hepatitis C patients. Measurement of serum IL‐6 levels may provide useful information for predicting future HCC development in female chronic hepatitis C patients.

Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH

Background and Aim: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not beeen fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. Methods: 62 patients with naïve HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm2 in males, >90 cm2 in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients’ background, tumour-related factors and liver function-related factors. Results: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm2, p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. Conclusions: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Neoplastic seeding after radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND:Neoplastic seeding reportedly occurs in up to 12.5% of patients treated with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study is to assess the incidence, risk factors, and prognosis of neoplastic seeding after RFA among a large number of patients with a long-term follow-up.METHOD:From February 1999 to December 2004, 1,031 patients underwent a total of 1,845 treatments with RFA for a total of 3,837 HCC nodules. The following variables were assessed to elucidate the risk factors of neoplastic seeding: age, sex, positivity for viral markers, tumor size, number of tumor nodules, number of RFA sessions, tumor location, percutaneous biopsy prior to RFA, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) levels, and the degree of tumor differentiation.RESULTS:Neoplastic seeding was detected in 33 patients (3.2% per patient) at intervals of 4.8–63.8 (median, 15.2) months after RFA. On multivariate logistic regression analysis, only the poor differentiation degree was associated with the risk of neoplastic seeding (P = 0.012). Of tumor factors, tumor size, and AFP, DCP, and AFP-L3 levels were significantly associated with the poor differentiation degree. The cumulative survival rates 1 and 2 yr after the detection of neoplastic seeding were 86% and 47%, respectively.CONCLUSION:Poor differentiation degree was the risk factor of neoplastic seeding after RFA for HCC. The surrogate markers for poor differentiation degree were larger tumor size and elevated tumor marker levels. Indication for RFA should be carefully considered for HCC patients under these conditions.

Extrahepatic metastasis of hepatocellular carcinoma: incidence and risk factors

Background: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions.

Risk Assessment of Hepatocellular Carcinoma in Chronic Hepatitis C Patients by Transient Elastography

Objective The degree of liver fibrosis is the strongest indicator of risk for hepatocellular carcinoma (HCC) development. Recently developed transient elastography (Fibroscan, Echosens, France) noninvasively measures liver stiffness, and the correlation between the stiffness and liver fibrosis stage has been validated. In this cross-sectional study, we investigated the relationship between liver stiffness and HCC presence. Methods Liver stiffness was measured in chronic hepatitis C patients (85 with HCC and 180 without) by transient elastography. Multivariate logistic regression was applied to assess the association with HCC presence. We computed the receiver operating characteristics (ROC) curves concerning the prediction of HCC presence and compared the areas under ROC curve (AUROC). We also calculated stratum-specific likelihood ratios (SSLR). Results Multivariate analysis showed that HCC presence was significantly associated with liver stiffness (P<0.0001) along with age, male, and alpha-fetoprotein concentration. AUROC was 0.805, 0.741, 0.714, 0.673, 0.670, and 0.654 for liver stiffness, alpha-fetoprotein, albumin, prothrombin activity, AST-platelet ratio index, and platelet count, respectively. Other parameters showed smaller AUROC. SSLR for HCC presence by liver stiffness was 0.22 (95% confidence interval: 0.11-0.42) in <10 kPa, 0.73 (0.39 to 1.39) in 10.1 to 15 kPa, 1.30 (0.80 to 2.12) in 15.1 to 25 kPa, and 5.0 (2.96 to 8.47) in >25 kPa. Conclusions Liver stiffness measured by transient elastography is useful in demarcating chronic hepatitis C patients at a high risk for HCC, who require frequent check-up by imaging examinations.

Autotaxin as a novel serum marker of liver fibrosis

BACKGROUND The clinical significance of autotaxin (ATX), a key enzyme for the production of the bioactive lysophospholipid lysophosphatidic acid remains unknown. Serum ATX enzymatic activity reportedly increases in parallel with liver fibrosis and exhibits a gender difference. METHODS Serum ATX antigen level, measured easier than the activity, was evaluated as a marker of liver fibrosis in 2 cohorts of chronic liver disease caused by hepatitis C virus. RESULTS In the first cohort, serum ATX level correlated significantly with liver fibrosis stage and was the best parameter for prediction of cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.756 in male and 0.760 in female, when compared with serum hyaluronic acid and aminotransferase-to-platelet ratio index, an established marker of liver fibrosis. In another cohort, serum ATX level correlated significantly with liver stiffness, a novel reliable marker of liver fibrosis, being the second-best parameter in male (AUROC, 0.799) and in female (AUROC, 0.876) for prediction of significant fibrosis, and the best parameter in male (AUROC, 0.863) and the third-best parameter in female (AUROC, 0.872) for prediction of cirrhosis, both of which were judged by liver stiffness. CONCLUSIONS Serum ATX level may be a novel marker of liver fibrosis.