The combination of fatty liver and increased gamma-glutamyl transpeptidase levels as a risk factor for atherosclerotic plaque development in apparently healthy people

Background/aim: To elucidate how the combination of fatty liver and increased serum gamma-glutamyl transpeptidase (GGT) levels influences atherosclerotic plaque development in apparently healthy people. Materials and methods: The study population included people who had received an annual health checkup for more than 7 years and had no evidence of carotid plaque at baseline. We investigated the risk factors for carotid plaque occurrence using the Cox proportional hazards model. Results: A total of 107 people (76 men and 31 women; median age, 49 years) were enrolled. At baseline, fatty liver and a serum GGT level ≥50 U/L were observed in 13 and 38 people, respectively. During a median follow-up period of 13.3 years, carotid plaques appeared in 34 people. Multivariate analysis revealed that the combination of fatty liver and a serum GGT level ≥50 U/L was the only significant risk factor for carotid plaque occurrence (age- and sex-adjusted hazard ratio: 5.55; 95% confidence interval 1.70­18.14; P = 0.005). Conclusion: The combination of fatty liver and increased serum GGT levels raises the risk for atherosclerotic plaque development in apparently healthy people.

Measurement of Spleen Stiffness With Acoustic Radiation Force Impulse Imaging Predicts Mortality and Hepatic Decompensation in Patients With Liver Cirrhosis.

BACKGROUND & AIMS: Hepatic venous pressure gradient can predict mortality and hepatic decompensation in patients with cirrhosis. Measurement of hepatic venous pressure gradient requires an invasive procedure; therefore, prognostic markers are needed that do not require invasive procedures. We investigated whether measurements of spleen stiffness, made by acoustic radiation force impulse (ARFI) imaging, associated with mortality and decompensation in patients with cirrhosis, compared with liver stiffness and other markers. METHODS: We measured spleen stiffness in 393 patients diagnosed with cirrhosis (based on histologic or physical, laboratory, and radiologic findings) at a hospital in Japan from September 2010 through August 2013 (280 patients with compensated and 113 patients with decompensated cirrhosis). Patients underwent biochemical, ARFI, ultrasonography, and endoscopy evaluations every 3 or 6 months to screen for liver-related complications until their death, liver transplantation, or the end of the study period (October 2015). The primary outcome was the accuracy of spleen stiffness in predicting mortality and decompensation, measured by Cox proportional hazards model analysis. We compared spleen stiffness with other noninvasive parameters using the Harrell's C-index analysis. RESULTS: During a median follow-up period of 44.6 months, 67 patients died and 35 patients developed hepatic decompensation. In the multivariate analysis, spleen stiffness was an independent parameter associated with mortality, after adjustment for levels of alanine aminotransferase and serum sodium, and the model for end-stage liver disease score (P < .001). Spleen stiffness was associated independently with decompensation after adjustment for Child-Pugh score and model for end-stage liver disease score (P < .001). Spleen stiffness predicted mortality and decompensation with greater accuracy than other parameters (C-indexes for predicting mortality and decompensation were 0.824 and 0.843, respectively). A spleen stiffness cut-off value of 3.43 m/s identified the death of patients with a 95.3% negative predictive value and 75.8% accuracy. A spleen stiffness cut-off value of 3.25 m/s identified patients with decompensation with a 98.8% negative predictive value and 68.9% accuracy. CONCLUSIONS: Spleen stiffness, measured by ARFI imaging, can predict death of patients with cirrhosis with almost 76% accuracy and hepatic decompensation with almost 70% accuracy. It might be a useful noninvasive test to predict patient outcome. UMIN Clinical Trials Registry no. UMIN000004363.

An Image Fusion System for Estimating the Therapeutic Effects of Radiofrequency Ablation on Hepatocellular Carcinoma.

BACKGROUND: During ultrasound-guided radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), high echoic areas due to RFA-induced microbubbles can help calculate the extent of ablation. However, these areas also decrease visualization of target tumors, making it difficult to assess whether they completely cover the tumors. To estimate the effects of RFA more precisely, we used an image fusion system (IFS). PATIENTS AND METHODS: We enrolled patients with a single HCC who received RFA with or without the IFS. In the IFS group, we drew a spherical marker along the contour of a target tumor on reference images immediately after administering RFA so that the synchronized spherical marker represented the contour of the target tumor on real-time ultrasound images. When the high echoic area completely covered the marker, we considered the ablation to be complete. We compared outcomes between the IFS and control groups. RESULTS: We enrolled 25 patients and 20 controls, and the baseline characteristics were similar between the two groups. The complete ablation rates during the first RFA session were significantly higher in the IFS group compared with those in the control group (88.0% vs. 60.0%, P = 0.041). The number of RFA sessions was significantly smaller in the IFS group compared with that in the control group (1.1 ± 0.3 vs. 1.5 ± 0.7, P = 0.016). CONCLUSIONS: The study suggested that the IFS enables a more precise estimation of the effects of RFA on HCC, contributing to enhanced treatment efficacy and minimized patient burden.

GGsTop, a novel and specific γ-glutamyl transpeptidase inhibitor, protects hepatic ischemia-reperfusion injury in rats.

Ischemia-reperfusion (IR) injury is a major clinical problem and is associated with numerous adverse effects. GGsTop [2-amino-4{[3-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid] is a highly specific and irreversible γ-glutamyl transpeptidase (γ-GT) inhibitor. We studied the protective effects of GGsTop on IR-induced hepatic injury in rats. Ischemia was induced by clamping the portal vein and hepatic artery of left lateral and median lobes of the liver. Before clamping, saline (IR group) or saline containing 1 mg/kg body wt of GGsTop (IR-GGsTop group) was injected into the liver through the inferior vena cava. At 90 min of ischemia, blood flow was restored. Blood was collected before induction of ischemia and prior to restoration of blood flow and at 12, 24, and 48 h after reperfusion. All the animals were euthanized at 48 h after reperfusion and the livers were harvested. Serum levels of alanine transaminase, aspartate transaminase, and γ-GT were significantly lower after reperfusion in the IR-GGsTop group compared with the IR group. Massive hepatic necrosis was present in the IR group, while only few necroses were present in the IR-GGsTop group. Treatment with GGsTop increased hepatic GSH content, which was significantly reduced in the IR group. Furthermore, GGsTop prevented increase of hepatic γ-GT, malondialdehyde, 4-hydroxynonenal, and TNF-α while all these molecules significantly increased in the IR group. In conclusion, treatment with GGsTop increased glutathione levels and prevented formation of free radicals in the hepatic tissue that led to decreased IR-induced liver injury. GGsTop could be used as a pharmacological agent to prevent IR-induced liver injury and the related adverse events.

The superficial elevated and depressed lesion type is an independent factor associated with non-curative endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: The expanded criteria for endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) have led to an increase in the number of EGC patients who receive curative treatment involving endoscopic techniques. Identifying the factors that are associated with treatment outcomes would be helpful in the application of ESD for EGC. METHODS: Potential factors associated with incomplete ESD and with non-curative ESD were investigated using a multiple logistic regression model in EGC patients who consecutively underwent ESD according to the expanded criteria. RESULTS: A total of 363 patients with 398 EGC lesions were enrolled. The rates of complete ESD and curative ESD were 96.2 % (383/398) and 85.7 % (341/398), respectively. No significant factors associated with incomplete ESD were identified. In contrast, a tumor size >20 mm [odds ratio (OR) 3.31; 95 % confidence interval (CI) 1.74-6.29], the superficial elevated and depressed type (0-IIa + IIc or IIc + IIa) (OR 4.37; 95 % CI 1.88-9.88), and the undifferentiated type (OR 5.93; 95 % CI 1.65-19.41) were identified as independent factors associated with non-curative ESD. The superficial elevated and depressed type in particular was found to be highly related to submucosal and lymphovascular invasion. The rate of non-curative ESD in cases of this macroscopic type occurring together with a tumor size >20 mm was 58.3 %, and the adjusted OR was 16.48 (95 % CI 4.69-62.09). CONCLUSION: The results suggest that the superficial elevated and depressed type is an independent factor associated with non-curative ESD and that the risk of non-curative ESD is increased when this macroscopic type is present along with a large tumor size.

Management of gastroesophageal varices in cirrhotic patients: current status and future directions.

Bleeding from gastroesophageal varices (GEV) is a serious event in cirrhotic patients and can cause death. According to the explosion theory, progressive portal hypertension is the primary mechanism underlying variceal bleeding. There are two approaches for treating GEV: primary prophylaxis to manage bleeding or emergency treatment for bleeding followed by secondary prophylaxis. Treatment methods can be classified into two categories: 1) Those used to decrease portal pressure, such as medication (i.e., nonselective ß-blockers), radiological intervention [transjugular intrahepatic portosystemic shunt (TIPS)] or a surgical approach (i.e., portacaval shunt), and 2) Those used to obstruct GEV, such as endoscopy [endoscopic variceal ligation (EVL), endoscopic injection sclerotherapy (EIS), and tissue adhesive injection] or radiological intervention [balloon-occluded retrograde transvenous obliteration (BRTO)]. Clinicians should choose a treatment method based on an understanding of its efficacy and limitations. Furthermore, elastography techniques and serum biomarkers are noninvasive methods for estimating portal pressure and may be helpful in managing GEV. The impact of these advances in cirrhosis therapy should be evaluated for their effectiveness in treating GEV.

Planning Sonography Using Real-time Virtual Sonography and Contrast-enhanced Sonography for Radiofrequency Ablation of Inconspicuous Hepatocellular Carcinoma Nodules.

BACKGROUND/AIMS: Determining whether planning sonography, using real-time virtual sonography (RVS) and contrast-enhanced sonography (CEUS), enables the identification of inconspicuous HCC nodules on conventional sonography (US), during percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODOLOGY: We examined the factors associated with poor conspicuity, identification rate of inconspicuous HCC nodules in planning US using RVS and CEUS, the success rate of RFA for such nodules and local recurrence rates. RESULTS: Sixty inconspicuous HCC nodules were analyzed. Factors associated with poor conspicuity included location of the nodules for 34 nodules, US findings of HCC nodules for 24 nodules, US findings of surrounding hepatic parenchyma for 26 nodules and local recurrence for 18 nodules. Fifty-five (90.0%) HCC nodules were identified with RVS. Of the remaining five HCC nodules, three were visualized with CEUS. Thus, 96.7% (58/60) of the inconspicuous HCC nodules were identified. Forty-six (79.3%) identified HCC nodules, were treated with RFA; the success rate was 95.7% (44/46). The cumulative local recurrence rates were 0%, 2.7% and 9.4% at 12, 24 and 36 months, respectively. CONCLUSIONS: This study suggested that planning US using RVS and CEUS permits the identification of most inconspicuous HCC nodules, thereby improving the success rate of RFA.

Binge alcohol consumption aggravates oxidative stress and promotes pathogenesis of NASH from obesity-induced simple steatosis.

The pathogenesis of nonalcoholic steatohepatitis (NASH) is a two-stage process in which steatosis is the "first hit" and an unknown "second hit." We hypothesized that "a binge" could be a "second hit" to develop NASH from obesity-induced simple steatosis. Thirty-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) rats were administered 10 mL of 10% ethanol orally for 5, 3, 2, and 1 d/wk for 3 consecutive weeks. As control, male Otsuka Long-Evans Tokushima (OLET) rats were administered the same amount of alcohol. Various biochemical parameters of obesity, steatosis and NASH were monitored in serum and liver specimens in untreated and ethanol-treated rats. The liver sections were evaluated for histopathological alterations of NASH and stained for cytochrome P-4502E1 (CYP2E1) and 4-hydroxy-nonenal (4-HNE). Simple steatosis, hyperinsulinemia, hyperglycemia, insulin resistance, hypertriglycemia and marked increases in hepatic CYP2E1 and 4-HNE were present in 30-wk-old untreated OLETF rats. Massive steatohepatitis with hepatocyte ballooning was observed in the livers of all OLETF rats treated with ethanol. Serum and hepatic triglyceride levels as well as tumor necrosis factor (TNF)-α mRNA were markedly increased in all ethanol-treated OLETF rats. Staining for CYP2E1 and 4-NHE demonstrated marked increases in the hepatic tissue of all the groups of OLETF rats treated with ethanol compared with OLET rats. Our data demonstrated that "a binge" serves as a "second hit" for development of NASH from obesity-induced simple steatosis through aggravation of oxidative stress. The enhanced levels of CYP2E1 and increased oxidative stress in obesity play a significant role in this process.

Measurement of spleen stiffness by acoustic radiation force impulse imaging identifies cirrhotic patients with esophageal varices.

BACKGROUND & AIMS: We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination. METHODS: In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices. RESULTS: Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%). CONCLUSIONS: Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.

Real-time image fusion for successful percutaneous radiofrequency ablation of hepatocellular carcinoma.

Percutaneous radiofrequency ablation (RFA) is an established nonsurgical curative treatment for hepatocellular carcinoma (HCC). Because of its efficiency and safety, sonography is the most commonly used imaging modality when performing RFA. However, the presence of HCC nodules that are inconspicuous when using conventional sonography is a major drawback of RFA and limits its feasibility as a treatment for HCC. However, a new technology has been developed that synthesizes high-resolution multiplanar reconstruction images using 3-dimensional data and is combined with a position-tracking system using magnetic navigation. With this technology, real-time sonograms can be fused with corresponding computed tomographic, magnetic resonance imaging, or even sonographic volume data; this process is known as real-time image fusion. In this article, we describe this novel imaging method as a useful tool for successful RFA treatment of HCC.

Comparison of combined transcatheter arterial chemoembolization and radiofrequency ablation with surgical resection by using propensity score matching in patients with hepatocellular carcinoma within Milan criteria.

PURPOSE: To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching. RESULTS: After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively). CONCLUSION: TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible.

Influence of HRH2 promoter polymorphism on aberrant DNA methylation of DAPK and CDH1 in the gastric epithelium.

BACKGROUND: Aberrant methylation patterns in CpG island are known to be influential in gene silencing. Histamine plays important physiological roles in the upper gastrointestinal tract and acts via the H2 receptor. We report an investigation into the effect of HRH2 promoter polymorphism (rs2607474 G > A) on the methylation of DAPK and CDH1. METHODS: Non cancerous gastric mucosa samples were obtained from 115 subjects with gastric cancer (GC) and 412 non-cancer subjects (non-GC). Methylation status of genes was determined by MSP. The genotyping of rs2607474 was performed by PCR-SSCP. RESULTS: Methylation of DAPK and CDH1 was observed in 296 and 246 subjects, respectively. The frequency of CDH1 methylation in the subjects with GC was significantly lower in cancer lesion than in non cancerous mucosa, whereas that of DAPK methylation was not different. The allelic distribution of rs2607474 was 401GG, 119GA and 7AA. The GG homozygote was associated with a significantly increased risk for methylation of both DAPK and CDH1 (p < 0.0001 and p = 0.0009, respectively). In the non-GC subjects or more than 60 years of age, GG homozygote was more closely associated with both DAPK and CDH1 methylation. However, this genotype did not show an increased risk for the development of methylation of both genes in patients with GC. In H. pylori negative subjects, GG homozygote showed an increased risk for the methylation of both DAPK and CDH1 (p = 0.0074 and p = 0.0016, respectively), whereas this genotype was associated with an increased risk for the development of DAPK methylation in H. pylori positive subjects (p = 0.0018). In addition, in subjects older than 60 years of age, atrophy and metaplasia scores were significantly higher in the GG homozygote (p = 0.011 and p = 0.039, respectively) and a significant correlation was observed between age and atrophy or metaplasia. CONCLUSIONS: Our results suggest that rs2607474 GG homozygote confers a significantly increased risk for age- and inflammation-related DAPK and CDH1 methylation.

Irsogladine maleate for the treatment of recurrent aphthous stomatitis in hepatitis C virus patients on pegylated-interferon and ribavirin: a pilot study.

BACKGROUND AND AIM: Aphthous stomatitis is one of the adverse effects associated with interferon (IFN) that forces dose reduction of IFN and there is no established therapy. This study was aimed to investigate whether irsogladine maleate, which enhances the functions of intercellular communication through the gap junctions, is effective for the treatment of aphthous stomatitis developed in hepatitis C virus (HCV) patients on pegylated-interferon (PEG-IFN) and ribavirin. METHODS: Nineteen patients with HCV were treated with PEG-IFN and ribavirin for 48 weeks. Ten out of 19 patients developed aphthous stomatitis during treatment with PEG-IFN and ribavirin. Within 1-2 weeks after development of aphthous stomatitis, 4 mg irsogladine maleate was orally administered daily to all patients and the therapeutic and adverse effects of irsogladine maleate were examined on every week. The degree of aphthous stomatitis was evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: Out of 10 patients, aphthous stomatitis was evaluated as grade 3 in three patients (30%) and grade 2 in seven patients (70%) by CTCAE. CTCAE grade was improved to 0 after 1 week in six patients, after 2 weeks in two patients, and after 3 weeks in two patients after the start of administration of irsogladine maleate. Aphthous stomatitis has not recurred in patients who had been on irsogladine maleate continuously during treatment of PEG-IFN and ribavirin. CONCLUSIONS: Irsogladine maleate is effective for the treatment of aphthous stomatitis developing during PEG-IFN and ribavirin administration in HCV patients.

Needle electrode position assessed using three-dimensional ultrasonography and outcome of radiofrequency ablation in hepatocellular carcinoma.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is an established curative therapy for early-stage hepatocellular carcinoma (HCC). We assessed the positions of inserted needle electrodes using three-dimensional ultrasonography (3D-US) and examined the association between the electrode position and outcomes of RFA. METHODOLOGY: Forty-seven patients with 49 HCC nodules treated with a cooled-tip RFA system were enrolled. Immediately after the first insertion of electrodes, 3D volume data were acquired. After RFA completion, the electrode position was assessed using the data. RESULTS: There were 18 central and 31 marginal pattern nodules. The total number of electrode insertions was significantly greater for the marginal nodules than for the central nodules (p=0.032). In the first session of RFA, 36 HCC nodules (central, n=14; marginal, n=22) were treated with single insertion of electrodes. The ratio of incompletely ablated nodules after the first session was greater for the marginal nodules than for the central nodules (p=0.025). CONCLUSIONS: Our study demonstrated that inserted electrode positions assessed using 3D-US are closely associated with outcomes of RFA and the number of electrode insertions.

Comparison of the relationships of alcoholic and nonalcoholic fatty liver with hypertension, diabetes mellitus, and dyslipidemia.

We compared the relationships of alcoholic fatty liver and nonalcoholic fatty liver with hypertension, diabetes mellitus, and dyslipidemia. Using a nationwide Japanese survey, we collected data on subjects with biopsy-proven alcoholic fatty liver or nonalcoholic fatty liver. Multiple logistic regression analysis was performed to determine whether alcoholic fatty liver and nonalcoholic fatty liver are associated factors for these diseases. Data on 191 subjects (65, alcoholic fatty liver; 126, nonalcoholic fatty liver) were analyzed. Alcoholic fatty liver (odds ratio, 2.54; 95% confidence interval, 1.06-6.32; p = 0.040), age ≥55 years, and body mass index ≥25 kg/m(2) were correlated with hypertension, whereas nonalcoholic fatty liver (odds ratio, 2.32; 95% confidence interval, 1.08-5.20; p = 0.035) and serum γ-glutamyl transpeptidase levels ≥75 IU/l were correlated with dyslipidemia. Furthermore, we found that there were biological interactions between alcoholic fatty liver and body mass index ≥25 kg/m(2) in ≥55-year-old subjects (attributable proportion due to interaction, 0.68; 95% confidence interval, 0.19-1.17), as well as between alcoholic fatty liver and age ≥55 years in subjects with body mass index ≥25 kg/m(2) (attributable proportion due to interaction, 0.71; 95% confidence interval, 0.24-1.18). Alcoholic fatty liver was more strongly associated with hypertension than nonalcoholic fatty liver and nonalcoholic fatty liver was more strongly associated with dyslipidemia than alcoholic fatty liver. Moreover, alcoholic fatty liver, obesity, and older age may interact to influence hypertension status.

Advanced ultrasonography technologies to assess the effects of radiofrequency ablation on hepatocellular carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) is a curative therapy for hepatocellular carcinoma (HCC). In RFA, ultrasonography (US) is most commonly used to guide tumor puncture, while its effects are assessed using dynamic computed tomography or magnetic resonance. The differences in modalities used for RFA and assessment of its effects complicate RFA. We developed a method for assessing the effects of RFA on HCC by combining contrast-enhanced (CE) US and real-time virtual sonography with three-dimensional US data. PATIENTS AND METHODS: Before RFA, we performed a sweep scan of the target HCC nodule and the surrounding hepatic parenchyma to generate three-dimensional US data. After RFA, we synchronized multi-planar reconstruction images derived from stored three-dimensional US data with real-time US images on the same US monitor and performed CEUS and real-time virtual sonography. Using a marking function, we drew a sphere marker along the target HCC nodule contour on pre-treatment US- multi-planar reconstruction images so that the automatically synchronized sphere marker represented the original HCC nodule contour on post-treatment real-time CEUS images. Ablation was considered sufficient when an avascular area with a margin of several millimeters in all directions surrounded the sphere marker on CEUS. RESULTS: This method was feasible and useful for assessing therapeutic effects in 13 consecutive patients with HCC who underwent RFA. In 2 patients who underwent multiple sessions of RFA, HCC-nodule portions requiring additional RFA were easily identified on US images. CONCLUSIONS: This method using advanced US technologies will facilitate assessment of the effects of RFA on HCC.

[Radiofrequency ablation for hepatocellular carcinoma in elderly patients].

The efficacy and safety of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) were compared between elderly (age≥75 years, n=82) and non-elderly groups (age<75 years, n=158). No significant differences were observed in complications between the two groups. Elderly patients had a lower survival rate compared to the non-elderly patients. Multivariate analysis showed that age was not a significant factor for survival on tumor recurrence. Matching by propensity score revealed no significant differences were observed in survival on tumor recurrence rate. The prognosis of elderly patients undergoing RFA might be considered poorer than that of non-elderly patients. However, when considering the clinical background, RFA might be safe and effective in elderly patients, as well as non-elderly patients.

Prognostic factors in hepatitis C patients with a single small hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND/AIMS: Hepatitis C is a major cause of hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) has been widely performed as a curative treatment for small HCC. The knowledge of prognostic factors in hepatitis C patients with small HCC after RFA is therefore important. METHODOLOGY: One hundred consecutive hepatitis C patients with a single HCC3cm or less treated with RFA were enrolled. The cumulative recurrence and survival rates were calculated using Kaplan-Meier analysis. Prognostic factors were investigated using the Cox proportional hazard mod-el. RESULTS: Five-year local and distant intra hepatic recurrence rates were 10.4% and 70.9%, respectively. Five-year overall survival and recurrence-free survival rates were 60.3% and 15.9%, respectively. Multivarlate analysis revealed that an age of 75 years or more[relative hazard (RH) 1.61, p=0.019] and a serum al-bumin level less than 3.5g/dL (RH 1.61, p=0.016)were significant factors for decreased overall survival. Furthermore, a serum albumin level less than 3.5g/dL (RH 1.50, p=0.003) was the only significant factor for decreased recurrence-free survival. CONCLUSIONS: This study suggests that host-related factors (age and serum albumin level) are important in predicting survival in hepatitis C patients with a single small HCC af-ter RFA.

Influence of high-risk esophageal varices on outcomes in hepatocellular carcinoma patients: benefits of prophylactic endoscopic therapies.

BACKGROUND/AIMS: To clarify whether high-risk esophageal varices (EVs) influence outcomes in hepatocellular carcinoma (HCC) patients and to determine whether prophylactic endoscopic therapies(PETs) provide benefits for such patients. METHODOLOGY: Ninety-six consecutive patients with naive HCC complicated by EVs were analyzed. Patients with low-risk EVs (group A, n=53), those with high-risk EVs not treated with PETs (group B, n=31), and those with high-risk EVs treated with PETs (group C, n=12) were compared with respect to first bleeding and mortality. Furthermore, factors associated with outcomes were examined. RESULTS: The first bleeding rates were higher in group B than in group A; the survival rates were lower in group B than in group A. High-risk EVs and advanced stage HCC were risk factors for both outcomes in groups A and B. By contrast, the first bleeding rates tended to be lower in group C than in group B, while the survival rates did not significantly differ. In groups B and C, advanced stage HCC was a risk factor for both outcomes, whereas PETs significantly decreased first bleeding. CONCLUSIONS: High-risk EVs negatively influence both first bleeding and mortality in HCC patients and PETs may have a preventive effect on bleeding.

Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria.

BACKGROUND AND AIM: The prognosis of cryptogenic cirrhosis-associated hepatocellular carcinoma (CC-HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC-HCC. METHODS: Consecutive 36 curatively treated CC-HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV-associated HCC (HCV-HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed. RESULTS: The size of CC-HCCs was larger than that of HCV-HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC-HCC, and 21%, 59%, and 81% in the HCV-HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC-HCC, and 98%, 81%, and 61% in the HCV-HCC. CC-HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV-HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC-HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV-HCC. The factor for survival was albumin in both groups. CONCLUSION: The size of CC-HCC was larger than that of HCV-HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC-HCC was lower than those with HCV-HCC.