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Objective: The precise relationship between alcohol intake and metabolic syndrome (MetS) is still unclear, and the results from previous studies have been inconclusive. Thus, we examined the effect of alcohol intake on the risk of MetS in men in order to gain more information on a potential relationship., Methods: This study included 22,349 men who were divided into four groups according to their average alcohol intake [non-, light (less than 20 g ethanol/day), heavy (equal or more than 20 g and less than 60 g ethanol/day) and very heavy (equal and greater than 60 g ethanol/day) drinkers]. We measured each subject's body mass index (BMI), waist circumference and blood pressure (BP) and conducted a blood test to obtain a complete blood count and biochemical panel. These results were used to obtain the MetS prevalence. Additionally, fatty liver was diagnosed using abdominal ultrasonography., Results: Light drinkers had smaller waist circumferences. Heavy and very heavy drinkers had larger waist circumferences, a higher BMI, a higher BP, higher fasting plasma glucose levels, higher triglycerides (TG) levels and higher high-density lipoprotein (HDL) cholesterol levels while they had lower low-density lipoprotein cholesterol levels than nondrinkers. The prevalence of high BP, hyperglycemia and high TG was significantly higher in heavy and very heavy drinkers than in nondrinkers. The prevalence of low HDL cholesterol levels decreased with an increase in alcohol consumption. The prevalence of MetS was significantly lower in light drinkers and higher in very heavy drinkers compared with nondrinkers., Conclusion: Alcohol intake significantly influences the risk of MetS in men. A significant association was seen between an alcohol intake of 60 g/day or higher and the prevalence of MetS.

Aim: To evaluate the efficacy of a new ablation procedure for the stepwise hook extension technique using a SuperSlim needle for radiofrequency ablation (RFA) treatment of hepatocellular carcinoma (HCC), a randomized controlled trial was performed., Methods: Thirty patients with HCC measuring 20 mm or less were randomly treated with a conventional four stepwise expansion technique (group 1) and the new stepwise expansion technique (group 2; the electrode was closed in the shaft after the same three steps of the conventional procedure and then fully extended). All patients underwent the RFA procedure using a 10-hook expandable electrode of 17-G diameter (LeVeen SuperSlim 30 mm). We compared the ablation time, required energy and ablated lesions in the two groups., Results: The long and short diameters of RFA-induced necrosis were significantly larger in group 2 (37 and 28 mm) than group 1 (30 and 26 mm, P = 0.001 and =0.045, respectively). Irregular and small needle expansion resulting in the parachute-like or irregularly shaped ablated zone was observed in more cases in group 1 than in group 2. The new technique made all tines expand uniformly and largely, which produced a near-oval ablated zone of which the long axis is perpendicular to the needle shaft., Conclusion: The two kinds of stepwise procedures allow the selection of a more suitable procedure according to the tumor size and shape in each RFA., (© 2013 The Japan Society of Hepatology.)

Aim:   To evaluate the efficacy of reduction therapy of natural human interferon (IFN)-β and ribavirin in elderly patients with hepatitis C virus (HCV) genotype 1b and high viral load who had complications of anemia, low bodyweight (<50 kg), diabetes mellitus and/or hypertension., Methods:   Inclusion criteria were age of 65 years or older, HCV genotype 1b, and serum HCV RNA level of 5.0 logIU/mL or higher. A total of 23 subjects with hemoglobin level of less than 13 g/dL, low bodyweight, diabetes mellitus and/or hypertension were enrolled in this study (reduction-dose group). IFN-β was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 44 weeks. Ribavirin was given daily for 48 weeks at a decreased dose of one tablet per day compared to the ordinary dose described based on bodyweight. As a control, another 22 patients without anemia, low bodyweight and/or complications treated with the standard dose of ribavirin (standard-dose group) were enrolled., Results:   Patients' rates with further dose reduction or discontinuation of treatment was 26.1% (6/23) in the reduction-dose group and 77.3% (17/22) in the standard-dose group. The sustained virological response (SVR) was 39.1% (9/23) in the reduction-dose group and 27.3% (6/22) in the standard-dose group (P = 0.404). Based on genetic variations near the IL28B gene (rs8099917), SVR was 44.1% (15/34) in patients with TT and 0% (0/11) in patients with TG (P = 0.008)., Conclusion:   The reduction therapy of IFN-β and ribavirin in elderly HCV patients with genotype 1b, high viral load, IL28B gene (rs8099917) of TT who had complications of anemia, low bodyweight, diabetes mellitus and/or hypertension is one possible selection of treatment., (© 2012 The Japan Society of Hepatology.)

Objectives: Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the core region of HCV-1b are useful as predictors of treatment efficacy to telaprevir/pegylated interferon (PEG-IFN)/ribavirin, but its impact on viral dynamics is not clear., Methods: This study investigated predictive factors of viral dynamics during 12- or 24-week regimen of triple therapy in 80 Japanese adults infected with HCV-1b., Results: After 24 h of commencement of treatment, the proportion of patients with Arg70 and Leu91 substitutions in the core region who showed ≥3.0 log drop in HCV RNA level was significantly higher than that of patients with Gln70 (His70) and/or Met91. At 8 and 12 weeks, HCV RNA loss rate of patients with rs8099917 genotype TT near IL28B gene was significantly higher than that of patients with non-TT. Multivariate analysis identified substitution of aa 70 and 91 as a predictor of ≥3.0 log fall in HCV RNA level at 24 h (Arg70 and Leu91) and SVR (Arg70), and rs8099917 (TT) as a predictor of HCV RNA loss at 12 weeks and SVR., Conclusions: This study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of viral dynamics during triple therapy., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To evaluate predictive factors of treatment efficacy to interferon (IFN)/ribavirin in patients infected with HCV genotype 1b (HCV-1b)., Methods: This study investigated pretreatment predictors, including viral- (aa substitutions in core aa 70/91 and NS5A-ISDR/IRRDR) and host-related factors (genetic variation near IL28B gene), to 48-week IFN/ribavirin in 490 Japanese adults infected with HCV-1b., Results: The proportion of patients who showed end-of-treatment response (ETR), sustained virological response (SVR), and SVR after ETR was 76, 54, and 76%, respectively. There was a significant positive correlation between the number of aa substitutions in ISDR and those in IRRDR. Concerning the substitution of core aa 91, the number of aa substitutions in ISDR/IRRDR of patients with Leu91 was significantly higher than that of patients with Met91. Furthermore, levels of viremia were influenced by aa substitutions in core aa 91 and ISDR/IRRDR. By multivariate analysis, rs8099917 genotype was an important predictor of ETR and SVR. With regard to viral factors, core aa 70/91 was an important predictor of ETR, and SVR after ETR. ISDR was an important predictor of SVR, and SVR after ETR., Conclusion: aa substitution in core/NS5A region and genetic variation near IL28B were important predictors of treatment efficacy to IFN/ribavirin., (Copyright © 2011 S. Karger AG, Basel.)

Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Stage progression of 374 small hepatocellular carcinomas (HCC) was retrospectively analysed., Patients and Methods: During 8 years, 236 patients with the early stage of HCC received radiofrequency ablation (RFA), and 138 underwent surgery as an initial therapy. More patients of young age and with better liver function tended to undergo surgical treatment. Based on 1892 patient-year data, the Markov model analysed the stepwise progression of early stage (multiple up to three nodules, 3 cm or less each) to intermediate stage (four nodules or more, or larger than 3 cm), to advanced stage (portal invasion, extrahepatic metastasis or Child-Pugh C) and to death., Results: The recurrence rates after RFA and surgery were 53.3 and 40.6% in the third year. The annual progression rates from the early stage to the intermediate stage, advanced stage and death were 5.40, 1.63 and 1.73% in the RFA group and 3.90, 1.87 and 0.62% in the surgery group respectively. The progression rate from the early to the intermediate stage was significantly lower (2.34% annually) in the younger patient group (<60 years) than that in the older group (≥ 60 years, 5.70%, P=0.0053). In contrast, the progression rate from the intermediate to the advanced stage was significantly higher in the younger patient group (<60 years, 37.50% annually) than that in the older groups (60-69 years, 30.30%, 70 years or older 22.09%, P=0.0011). Multivariate hazard analysis showed that initial treatment did not significantly affect the stage progression rate (hazard ratio of RFA 1.09, P=0.70) and the survival rate (hazard ratio of RFA 1.09, P=0.73)., Conclusion: Although the recurrence rate was slightly higher in the RFA group, additional ablation procedures could control the progression of HCC, with a rate comparable to the surgical group., (© 2011 John Wiley & Sons A/S.)

Unlabelled: Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49 patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA) ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1. Decreases in hemoglobin levels were greater in patients with CC than CA/AA genotypes at week 2 (-1.63 ± 0.92 vs. -0.48 ± 0.75 g/dL, P = 0.001) and week 4 (-3.5 ± 1.1 vs. -2.2 ± 0.96, P = 0.001), as well as at the end of treatment (-2.9 ± 1.1 vs. -2.0 ± 0.86, P = 0.013). Risk factors for hemoglobin <11.0 g/dL at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was smaller in patients with CC than CA/AA genotypes (52 ± 14% vs. 65 ± 21% of the target dose, P = 0.039), but the total RBV dose was no different between them (49 ± 17% and 54 ± 18% of the target, P = 0.531). Sustained virological response (SVR) was achieved in 70% and 64% of them, respectively (P = 0.724)., Conclusion: ITPA polymorphism influences hemoglobin levels during triple therapy, particularly during the first 12 weeks while telaprevir is given. With careful monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved comparably frequently between patients with CC and CA/AA genotypes., (Copyright © 2010 American Association for the Study of Liver Diseases.)

Background:   Since hepatocellular carcinoma often recurs after surgical resection or radiofrequency ablation, we analyzed a retrospective large cohort of patients with small hepatocellular carcinoma caused by hepatitis C virus (HCV)., Methods:   Among 379 patients with HCV RNA-positive small hepatocellular carcinoma (multiple up to three nodules, 3 cm or less each), 77 received interferon-alpha injection and 302 received no anti-viral therapy., Results:   Four patients (5.2%) attained sustained virological response (SVR). Cumulative recurrence rates in the treated and untreated groups were 41.1% and 57.5% at the end of the third year, and 63.0% and 74.5% at the fifth year, respectively (P = 0.013). Fifth year-recurrence rates in treated group were 25.0% in SVR, 85.7% in biochemical response, 71.1% in no response, and 46.7% in patients with continuous administration. When four patients with SVR were excluded, recurrence rates in short-term interferon therapy (<2 years) and long-term therapy (≥2 years) were 46.2% and 39.3% at the third year, and 66.2% and 57.4% at the fifth year, respectively (P = 0.012). Multivariate analysis showed that long-term interferon therapy significantly decreased recurrence rate (hazard ratio for interferon <2 years 0.80, interferon ≥2 years 0.60, P = 0.044), after adjustment with background covariates including indocyanine green retention rate (P = 0.018), alpha-fetoprotein (P = 0.051), and tumor treatment (P = 0.066)., Conclusion:   A long-term administration of low-dose interferon significantly decreased recurrence of hepatocellular carcinoma after surgical resection or radiofrequency ablation., (© 2010 The Japan Society of Hepatology.)

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 ≥4.8 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., 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., (© 2010 John Wiley & Sons A/S.)

Aim:   The aim of this study was to elucidate whether the histopathological characteristics of hepatocellular carcinoma (HCC) can be predicted from baseline dynamic computed tomography (CT) images., Methods:   This retrospective study included 86 consecutive patients with HCC who underwent surgical resection between January 2000 and September 2008. The arterial- and portal-phase dynamic CT images obtained preoperatively were classified into four enhancement patterns: Type-1 and Type-2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively; Type-3, heterogeneous enhancement pattern with septum-like structure; and Type-4, heterogeneous enhancement pattern with irregular ring-like structures. We also evaluated the predictive factors for poorly-differentiated HCC, specific macroscopic type of HCC (simple nodular type with extranodular growth [SNEG] and confluent multinodular [CMN]) by univariate and multivariate analyses., Results:   The percentages of poorly-differentiated HCC according to the enhancement pattern were three of 51 nodules (6%) of Type-1 and -2, three of 24 (13%) of Type-3, and eight of 11 (73%) of Type-4. The percentages of SNEG/CMN according to the enhancement pattern were 12 of 51 nodules (24%) of Type-1 and -2, 13 of 24 (54%) of Type-3, and five of 11 (45%) of Type-4. Multivariate analysis identified Type-4 pattern as a significant and independent predictor of poorly-differentiated HCC (P < 0.001) while Type-3 pattern was a significant predictor of SNEG/CMN (P = 0.017)., Conclusion:   Heterogeneity of dynamic CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment., (© 2010 The Japan Society of Hepatology.)

Background: This retrospective cohort study assessed the impact of diabetes mellitus on hepatocarcinogenesis and determined the predictors of hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus infection., Methods: A total of 2058 hepatitis C virus-positive, noncirrhotic patients treated with interferon were enrolled. The median follow-up period was 6.7 years. The primary end point was the onset of hepatocellular carcinoma. The cumulative rate of new hepatocellular carcinoma cases was computed by the Kaplan-Meier method and Cox proportional hazard analysis according to diabetic state and response to interferon therapy., Results: The cumulative rates of hepatocellular carcinoma in diabetic patients (3.2% at 4 years, 8.5% at 8 years, and 24.4% at 12 years) were significantly higher than those of nondiabetic patients (1.3% at 4 years, 2.2% at 8 years, and 5.6% at 12 years, P<.001). In patients with a sustained virologic response, diabetes had no significant effect on the rate of hepatocarcinogenesis. In contrast, the rate in patients with a nonsustained virologic response was significantly higher in diabetic than in nondiabetic patients. Multivariate analysis identified lack of sustained virologic response (hazard ratio [HR] 7.28; 95% confidence interval [CI], 3.28-16.15; P<.001) and diabetes as independent risk factors for hepatocarcinogenesis (HR 2.00; 95% CI, 1.05-3.84; P=.036)., Conclusions: Our results highlight the enhancing effect of diabetes mellitus on hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus. The sustained virologic response induced by interferon therapy eliminates the influence of diabetes and markedly reduces the rate of hepatocarcinogenesis in such patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Unlabelled: Genetic variation near the IL28B gene and substitution of amino acid (aa) 70 and 91 in the core region of hepatitis C virus (HCV) genotype 1b can predict the response to pegylated interferon (PEG-IFN)/ribavirin combination therapy, but its impact on triple therapy of telaprevir/PEG-IFN/ribavirin is not clear. The aims of this study were to investigate the predictive factors of sustained virological response to a 12-week or 24-week regimen of triple therapy in 72 of 81 Japanese adults infected with HCV genotype 1. Overall, sustained virological response and end-of-treatment response were achieved by 61% and 89%, respectively. Especially, the sustained virological response was achieved by 45% and 67% in the 12- and 24-week regimens, respectively. Multivariate analysis identified rs8099917 near the IL28B gene (genotype TT) and substitution at aa 70 (Arg70) as significant determinants of sustained virological response. Prediction of response to therapy based on a combination of these factors had high sensitivity, specificity, and positive and negative predictive values. The efficacy of triple therapy was high in the patients with genotype TT, who accomplished sustained virological response (84%), irrespective of substitution of core aa 70. In the patients having genotype non-TT, those of Arg70 gained high sustained virological response (50%), and sustained virological response (12%) was the worst in patients who possessed both genotype non-TT and Gln70(His70)., Conclusion: This study identified genetic variation near the IL28B gene and aa substitution of the core region as predictors of sustained virological response to a triple therapy of telaprevir/PEG-IFN/ribavirin in Japanese patients infected with HCV genotype 1b.

Background: Influence of human lymphocyte antigen (HLA) on the therapeutic response in autoimmune hepatitis (AIH) is not known., Aims: To evaluate if HLA-DR types influence biological and histological responses to corticosteroids in patients with AIH., Methods: During 28 years from 1979 through 2007, 48 patients with definite diagnosis of AIH received long-term corticosteroid therapy (median 9 years [range: 5-28 years]) in a single Japanese center. They were followed for transaminase levels and received liver biopsy before and after the treatment., Results: DR4 was detected in 32 and DR14 in 11 patients; seven possessed both DR4 and DR14. DR4 was more frequent in AIH patients than in the general population (67% vs. 22%), while DR14 was comparably frequent between them (23% vs. 17%). Overall, biochemical response was achieved in 43 (90%) of the 48 patients. The sustained biochemical response to a maintenance prednisolone dose < 10 mg was gained more frequently in the patients with than without DR14 (10/11 [91%] vs. 10/37 [27%], P < 0.001). Marked histological improvement with a decrease in histology activity index (HAI) score by > 2 points was achieved in 31 of the 32 (97%) biochemical responders. Histological aggravation with an increase in HAI score occurred in 4 of the 16 (25%) patients without biochemical response (non-responders and relapsers combined), but in none of the 32 responders., Conclusion: Long-term immunosuppressive treatment can improve the outcome of Japanese patients with AIH, and DR14 is associated with excellent biochemical response.

Background and Aims: To assess the efficacy of switching Japanese chronic hepatitis B patients from lamivudine monotherapy to entecavir 0.5 mg/day., Methods: A retrospective analysis was conducted on 134 patients switched to entecavir between September 2006 and February 2008 for 6 months or more. Patients were divided into three groups based on viral load at entecavir switching point (baseline < 2.6, 2.6-5.0 and > 5.0 log(10) copies/mL)., Results: At baseline, detection of lamivudine-resistant virus was highest in patients with higher hepatitis B virus (HBV) DNA (76% vs 23% in > or = 2.6 and < 2.6 log(10) copies/mL, respectively), and in patients with longest previous exposure to lamivudine (52%, 28% and 24% for > 3 years, 1-3 years and < 1 year, respectively). Two years after entecavir switching, HBV DNA suppression to less than 2.6 log(10) copies/mL was achieved in 100% (32/32), 92% (12/13) and 44% (4/9) of patients in the less than 2.6, 2.6-5.0 and more than 5.0 log(10) copies/mL baseline groups, respectively. Alanine aminotransferase (ALT) normalization occurred in 76-96% and 90-100% of patients following 1 and 2 years of entecavir treatment, respectively. One patient (2.6-5.0 log(10) copies/mL) with lamivudine-resistant mutants at baseline developed entecavir resistance at week 48 during follow up., Conclusion: Switching to entecavir 0.5 mg/day achieves or maintains undetectable HBV DNA levels and ALT normalization over 2 years, especially in patients with viral load less than 5.0 log(10) copies/mL.

Ideally, long-term lamivudine therapy should not induce tyrosine-methionine-aspartate-aspartate (YMDD) mutants (reverse transcription [rt]; rt M204I/V) in patients with chronic hepatitis B. There is little or no information on the clinical features of patients who do not develop such mutants. We analyzed 368 patients who received lamivudine therapy for more than 6 months between 1995 and 2003. Among them, 98 patients were negative for YMDD mutants during 5-year lamivudine therapy. Multivariate analysis identified hepatitis B e antigen (HBeAg) negativity, lack of cirrhosis, and high gamma glutamyltranspeptidase (GGTP) level as independent factors associated with lack of emergence of YMDD mutants during 5-year treatment. In these 98 patients, 21 patients developed YMDD mutants in the 5-year posttreatment follow-up. Old age was identified as the only factor associated with the emergence of YMDD mutants during that period. For all patients, 53 showed no elevation of alanine aminotransferase (ALT) or viral load after emergence of YMDD mutants during 5 years. Short latency to emergence of YMDD mutants, mixed (tyrosine-isoleucine-aspartate-aspartate (YIDD) [rtM204I] + tyrosine-valine-aspartate-aspartate (YVDD) [rtM204V]) type, and low ALT level were identified as independent factors associated with elevation ALT or viral load. HBeAg negativity, lack of cirrhosis, and high GGTP level were associated with lack of emergence of YMDD mutants during 5-year period. Young age protected against emergence of YMDD mutants over the 5-year period. Moreover, after the emergence of YMDD mutants, short latency to the emergence of YMDD mutant, mixed type mutants, and low baseline ALT level were associated with elevation of ALT or viral load., (2010 Wiley-Liss, Inc.)

Substitution of amino acid (aa) 70 and 91 in the core region of hepatitis C virus (HCV) genotype 1b can predict the response to pegylated interferon (PEG-IFN)/ribavirin combination therapy, but its impact on triple therapy of telaprevir/PEG-IFN/ribavirin is not clear. The aims of this study were to investigate the rate of HCV RNA loss following 12-week triple therapy, and determine the effect of aa substitutions on very early (within 48 hr) viral dynamics. Sixty-seven patients infected with HCV genotype 1b (HCV-1b) and high viral load who received 12-week triple therapy were studied. RNA loss could be achieved in 2%, 34%, 80%, 92%, 95%, 94%, and 90% of the patients after 1, 2, 4, 6, 8, 10, and 12 weeks of triple therapy, respectively. After 24-hr treatment, the proportion of patients with Arg70 and Leu91 substitutions with > or = 3.0 log fall in HCV RNA was significantly higher than those with < 3.0 log fall (P = 0.008). However, the aa substitution patterns in the core region did not influence the fall in HCV RNA after 48-hr treatment. Multivariate analysis identified substitutions of aa 70 and 91 (P = 0.014) and level of viremia at baseline (> or = 7.0 log IU/ml; P = 0.085) as independent parameters that determined the > or = 3.0 log fall in HCV RNA level after 24-hr triple therapy. It is concluded that 12-week triple therapy achieved high rates of loss of HCV RNA in Japanese patients infected with HCV-1b and high viral load, and that the aa substitution pattern in the core region seems to influence very early viral dynamics., (2010 Wiley-Liss, Inc.)

Osteoporosis is often present in postmenopausal women. The aim of this retrospective cohort study was to assess the cumulative incidence and predictive factors for bone fracture after cessation of interferon (IFN) in postmenopausal women with osteoporosis and chronic liver disease caused by hepatitis C virus (HCV). A total of 420 postmenopausal women treated with IFN monotherapy were enrolled. The mean observation period was 7.2 years. The primary goal was the development of bone fracture. Evaluation was carried out by using the Kaplan-Meier method and the Cox proportional hazards analysis. Thirty-one out of 420 patients sustained bone fracture. The cumulative development rate of bone fracture was 3.6% at 5th year, 9.2% at 10th year, and 17.4% at 15th year. Multivariate Cox proportional hazards analysis showed that bone fracture after cessation of IFN therapy occurred when histological staging of the liver was advanced (hazard ratio (HR): 2.54; 95% confidence interval (CI) = 1.21-5.31; P = 0.013), serum albumin level was < 3.5g/dl (HR: 2.25; 95% CI = 1.10-4.59; P = 0.026), and virus clearance was not achieved (HR: 3.65; 95% CI = 1.11-12.05; P = 0.033). The results indicate that virus clearance causes a reduction of two-thirds in the risk of bone fracture after cessation of IFN therapy in postmenopausal women with osteoporosis and chronic liver disease caused by HCV. J. Med. Virol. 82:390-395, 2010. (c) 2010 Wiley-Liss, Inc.

Aim: To identify factors for the development of hepatocellular carcinoma (HCC) in the patients who receive adefovir add-on lamivudine for treatment of lamivudine-resistant hepatitis B virus (HBV) mutants., Methods: A total of 247 patients who developed lamivudine-resistant HBV mutants, with an increase of HBV DNA >/= 1 log copies/mL, received adefovir dipivoxil 10 mg add-on lamivudine 100 mg daily during a median of 115 weeks (range: 25-282 weeks). They were followed for the development of HCC by imaging modalities every 3-6 months., Results: HCC developed in 18 of the 247 (7.3%) patients. Eight factors were in significant association with the development of HCC by the univariate analysis. They included age, cirrhosis, platelet counts, levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase and alpha-fetoprotein, as well as YMDD mutants at the start of adefovir dipivoxil. By the multivariate analysis, AST levels, YIDD mutants, cirrhosis and age were independent factors for the development of HCC. By the Kaplan-Meier analysis, AST levels >/= 70 IU/L, YIDD mutants, cirrhosis and age >/= 50 years increased the risk of HCC (P = 0.018, P = 0.035, P = 0.002 and P = 0.014, respectively). HCC developed more frequently in the patients with than without cirrhosis at the start of adefovir (10/59 [16.9%] vs. 8/188 [4.3%], P = 0.002)., Conclusion: HCC can develop in cirrhotic patients receiving adefovir add-on lamivudine. Hence, the patients with baseline AST >/= 70 IU/L and YIDD mutants would need to be monitored closely for HCC.

Here, we describe for the first time a case of sustained virological response (SVR) achieved in a patient with chronic hepatitis C (CH-C) by monotherapy with a NS3-4A protease inhibitor, telaprevir, without interferon therapy. A 59-year-old treatment-naïve Japanese man was enrolled in a phase II trial of telaprevir by repeat oral administration at a dose of 750mg every 8h for 24 weeks. At the start of treatment, he exhibited a low-level viremia with genotype 1b of the hepatitis C virus (HCV). After the first week of treatment with telaprevir, serum HCV RNA was undetectable, and negativity remained until the end of treatment. Moreover, he was evaluated as having a SVR after the post-treatment 24-week follow-up program. Two characteristics may explain the strong antiviral activity of telaprevir in the present case. First, although pre-treatment PCR-direct sequencing and cloning for the N-terminal in the NS3 region showed a protease inhibitor-resistant variant (T54A) in 1 of 32 independent clones, the T54A substitution has only a low-level resistance to protease inhibitors and his viral load was low. Second, when compared to a consequence sequence of 35 treatment-naïve patients with HCV genotype 1b, R130K and Q195K substitutions were unique to the present case. Although it is presently unknown whether the R130K and Q195K substitutions are related to SVR, this case suggests that long-term telaprevir monotherapy may be effective in CH-C patients with genotype 1 and a low viral load., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the efficacy of combination therapy of natural human interferon-beta and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 and high virus load., Methods: Inclusion criteria were HCV-genotype 2, serum HCV RNA level of >or=100 KIU/mL before combination therapy. A total of 24 were enrolled in this retrospective cohort study. The treatment period of combination therapy was 24 weeks., Results: Of the 24 study patients, no patient stopped the treatment due to treatment-related adverse events. The dose of drugs were reduced in 8 patients. Twenty-one of 24 patients (87.5%) had sustained virological response (SVR) by the intention to treat analysis. The rate of negative HCV RNA at 8 week after the initiation of treatment was 18/21 (86%) in patients with SVR and 1/3 (33%) in patients with non-SVR. Logistic regression analysis showed that SVR occurred when serum HCV RNA at 8 week after the initiation of combination therapy was negative (hazard ratio: 40.0; 95% confidence interval=1.75-914.78; p=0.021), Conclusion: The combination therapy of IFN-beta and ribavirin offers sufficient safety and efficacy in chronic hepatitis C patients with genotype 2 and high virus load.

Objective: The aim of this study was to evaluate the efficacy of combination therapy of natural human interferon-beta and ribavirin in patients infected with hepatitis C virus (HCV) genotype 1b., Methods: Inclusion criteria were HCV-genotype 1b, serum HCV RNA level of >or=100 KIU/ml before the initiation of treatment. A total of 40 patients were enrolled in this retrospective cohort study. The treatment period of combination therapy was 48 weeks. Nonparametric procedures were employed for the analysis of background features of the patients with SVR and without SVR. A p value of <0.05 was considered to indicate a significant difference., Results: Of the 40 study patients, ten had mental disorders before the initiation of combination therapy. One of the patients stopped the treatment due to exacerbation of depression and another patient stopped due to a skin rash. Three patients suspended the therapy due to an insufficient response of positive serum HCV RNA at 24 weeks after the initiation of treatment. Thus, 34 patients completed combination therapy. Fifteen had sustained virological response (SVR). The SVR rate in patients who showed negative HCV RNA 8 weeks after the initiation of combination therapy was 86.7% (13/15). On the other hand, the SVR rate in patients who showed positive HCV RNA at 8 weeks was 8% (2/25) (p<.001). Continuous period of negative serum HCV RNA was 33.1 weeks in SVR groups, and 12.5 weeks in non-SVR groups (p<.001)., Conclusion: The combination therapy of IFN-beta and ribavirin is a possible therapy selection for patients with type C hepatitis of genotype 1b and high virus load.

Objective: In treatment-resistant patients with genotype 2 chronic hepatitis C the suitable treatment duration is still unclear. The aims were to investigate extending combination therapy with peginterferon plus ribavirin for genotype 2., Methods: 7 patients infected with genotype 2 at a high viral load and who did not achieve a sustained virological response (SVR) with the first course of 24-week IFN plus ribavirin were recruited into the study protocol with a total of 48 weeks of peginterferon plus ribavirin therapy., Results: SVR was achieved in 5 of 7 patients (71%). All 4 patients (100%) who were in relapse with the first course achieved SVR. Only 1 of 3 patients (33%) who had a non-virological response (NVR) with the first course achieved SVR. All 4 patients who had an early virological response (EVR) with the first course achieved EVR and SVR. Two of 3 patients who had no EVR with the first course also did not achieve EVR and SVR. One patient who had no EVR or a NVR during the first course achieved EVR and SVR with the second course., Conclusions: Our results suggest that extending combination therapy for genotype 2 chronic hepatitis C might be useful for patients who relapse following 24-week combination therapy., (2010 S. Karger AG, Basel.)

The aim of this retrospective cohort study is to assess the cumulative development incidence and predictive factors for type 2 diabetes (T2DM) in HCV positive and hypertensive patients treated with losartan. Eighty Japanese patients were given 50 mg of losartan per day after diagnosis of hypertension (losartan group). Another 160 treated with spironolactone were selected as control (spironolactone group). Patients in spironolactone group were matched 1:2 with losartan group for age and sex. The mean observation period was 5.2 years in losartan group and 5.4 years in spironolactone group. An overnight (12 hr) fasting blood sample or a casual blood sample was taken for routine analyses during follow-up. The primary goal is the onset of T2DM. Evaluation was performed by using the Kaplan-Meier method and the cox proportional hazards analysis. Three patients in losartan group and 20 in spironolactone group developed T2DM. The 5th year cumulative appearance rates of T2DM were 5.4% in losartan group and 14.4% in spironolactone group. Multivariate cox proportional hazards analysis showed that T2DM development after the initiation of anti-hypertensive drugs occurred when anti-hypertensive drug was spironolactone (hazard ratio: 6.10; 95% confidence interval = 1.78-20.84; P = 0.004), histological staging was advanced (hazard ratio: 4.31; 95% confidence interval = 1.94-9.60; P < 0.001), fatty liver was present (hazard ratio: 3.28; 95% confidence interval = 1.47-7.27; P = 0.004), and patient had pre-diabetes (hazard ratio: 2.47; 95% confidence interval = 1.08-5.63; P = 0.032). Our results indicate losartan causes about 60% reduction of the onset of T2DM compared to patients treated with spironolactone.

Previous studies provided a direct experimental evidence for the contribution of HCV core protein in the development of insulin resistance (IR), but the clinical impact of HCV core region on IR is still not clear. The present study evaluated the impact of Amino acid (aa) substitutions of HCV-1b core region on IR in 123 Japanese patients infected with HCV-1b without cirrhosis and diabetes mellitus, and investigated the treatment efficacy of 48-week pegylated interferon (PEG-IFN) plus ribavirin (RBV) according to HOMA-IR values. Patients with IR (HOMA-IR > or = 2.5) and severe IR (HOMA-IR > or = 3.5) were present in 51.2% and 27.6%, respectively. Multivariate analysis identified body mass index (> or = 25 kg/m(2)) and hepatocyte steatosis (> or = 5%) as significant determinants of IR. Furthermore, multivariate analysis identified hepatocyte steatosis (> or = 5%), aa substitutions of the core region (Gln70 (His70) and/or Met91), and age (> or = 55 years) as significant determinants of severe IR. Especially, significantly lower proportions of patients with Gln70 (His70) and/or Met91 were noted among those without severe IR (59.6%) than those with severe IR (82.4%). The rates of sustained virological response in patients with IR (50.0%) were not significantly different from those without IR (52.9%). Furthermore, the rates of non-virological response in patients with IR (28.9%) were not significantly also different from those without IR (20.6%). In conclusion, the present study indicated that substitutions of HCV-1b core region were the important predictor of severe IR in patients without cirrhosis and diabetes mellitus, but HOMA-IR values might be not useful as predictors of 48-week PEG-IFN plus RBV therapy.

Background: The tumour recurrence rate after resection is still high even in patients with small hepatocellular carcinoma (HCC). The advanced patterns of recurrence occasionally occur after resection. In this study, we analysed the clinical and histological characteristics of small HCC and evaluated the predictive factors of advanced tumour recurrence., Methods: One hundred and sixty-five patients underwent resection of small HCC measuring 3 cm or less in greatest dimension. Patterns of tumour recurrences were classified into advanced recurrence and minor recurrence based on size, number, vascular invasion and extrahepatic metastasis of recurrent tumour. We created a simple index to closely evaluate the malignant potential of small HCC, named alpha-foetoprotein-size ratio index (ASRI)., Results: Overall tumour recurrence was significantly associated with tumour multiplicity (P<0.001) and ASRI (P=0.001). Tumour multiplicity, ASRI and tumour differentiation were independent and significant predictive factors of advanced recurrences. The overall survival rates were lower in the advanced recurrence group than the minor recurrence or the no recurrence group., Conclusions: Patients with advanced recurrences have a poor prognosis, although they have undergone curative resection of small HCC. On the other hand, patients with minor recurrences have a relatively good prognosis. ASRI was a useful index to predict advanced recurrence after curative resection of small HCC. The therapeutic management to prevent advanced recurrences is needed.

Aim: Hepatocellular carcinoma (HCC) often shows resistance to transcatheter arterial chemoembolization (TACE). Such patients often have a poor prognosis and are unresponsive to other forms of therapy. The aim of this retrospective study was to determine the response to TACE using platinum analogues in patients deemed resistant to TACE using epirubicin., Methods: We studied 152 consecutive patients with advanced HCC resistant to TACE using epirubicin. All cases were treated with platinum analogue using transcatheter arterial chemotherapy with or without embolization., Results: Computed tomography at 3 months after therapy showed complete response (CR) in 6 patients (4.0%), partial response (PR) in 28 (18%), stable disease (SD) in 35 (23%), and progressive disease (PD) in 83 (55%). The cumulative survival rates for PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization (81.8% at first year, 53.9% at second year, and 33.1% at third year) were significantly higher than those of SD/PD patients (36.6%, 17.5% and 7.4%, respectively) (P < 0.001). The 50% survival period was extended almost 1.4 year in PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization., Conclusion: Our retrospective study is the first to report the efficacy of platinum analogues for advanced HCC unresponsive to TACE using epirubicin.

Unlabelled: Diabetes is present in patients with chronic hepatitis C virus infection. The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for type 2 diabetes after the termination of interferon therapy in Japanese patients positive for hepatitis C virus (HCV). A total of 2,842 HCV-positive patients treated with interferon (IFN) monotherapy or combination therapy with IFN and ribavirin were enrolled. The mean observation period was 6.4 years. An overnight (12-hour) fasting blood sample or a casual blood sample was taken for routine analyses during follow-up. The primary goal was the onset of type 2 diabetes. Evaluation was performed by using the Kaplan-Meier method and Cox proportional hazard analysis. Of 2,842 HCV patients, 143 patients developed type 2 diabetes. The cumulative development rate of type 2 diabetes was 3.6% at 5 years, 8.0% at 10 years, and 17.0% at 15 years. Multivariate Cox proportional hazard analysis revealed that type 2 diabetes development after the termination of IFN therapy occurred when histological staging was advanced (hazard ratio 3.30; 95% confidence interval [CI] 2.06-5.28; P < 0.001), sustained virological response was not achieved (hazard ratio 2.73; 95% CI 1.77-4.20; P < 0.001), the patient had pre-diabetes (hazard ratio 2.19; 95% CI 1.43-3.37; P < 0.001), and age was >or=50 years (hazard ratio 2.10; 95% CI 1.38-3.18; P < 0.001)., Conclusion: Our results indicate sustained virological response causes a two-thirds reduction in the risk of type 2 diabetes development in HCV-positive patients treated with IFN.

Substitution of amino acid (aa) 70 and 91 in the core region of HCV genotype 1b is a useful pretreatment predictor of efficacy of 48-week peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the efficacy of 72-week PEG-IFN/RBV and the predictive factors to such therapy in a case-control study matched for sex, age, and periods from the start of treatment to initial point of HCV RNA-negative. We compared the treatment efficacy of 72-week regimen in 65 patients with that of 48-week in 130 patients, who were infected with HCV genotype 1b and treated with PEG-IFN/RBV. They consisted mainly of late virological responders (LVR) (HCV RNA-positive at 12 weeks and negative at 24 weeks after start of treatment). Sustained virological response (SVR) was achieved by 61.5% and 32.3% of patients of the 72- and 48-week groups, respectively, while non-virological response was noted in 9.2% and 29.2% of the respective groups. Multivariate analysis identified substitution of aa 70 and 91 (Arg70 and/or Leu91) and duration of treatment (72-week) as independent parameters that significantly influenced SVR. For Arg70 and/or Leu91 of core region, SVR rate was significantly higher in 72- (68.0%) than 48-week group (37.8%). For wild-type of ISDR, SVR rate was significantly higher in 72- (61.2%) than in 48-week group (29.3%). We conclude that 72-week PEG-IFN/RBV improves SVR rate for LVR, especially those with Arg70 and/or Leu91 of core region or wild-type of ISDR. Substitution of aa 70 and 91 is also a useful pretreatment predictor of response to 72-week PEG-IFN/RBV., (Copyright 2009 Wiley-Liss, Inc.)

Objective: The aim of this study was to elucidate the efficacy of interferon (IFN)-beta monotherapy for elderly patients of > or = 70 years with type C hepatitis (HCV) of genotype 2., Methods: The present study was a retrospective cohort study. Inclusion criteria were type C hepatitis patients with HCV genotype 2a or 2b, > or = 70 years, and IFN-beta monotherapy of within 24 weeks. Thirty-one consecutive patients who satisfied the above criteria were enrolled in the present study. Independent factors that might have influenced the sustained virological response (SVR) were studied using logistic regression analysis., Results: Background of clinical profiles was as follows: median (range) age = 71 (70-76) years, male/female = 13/18, and median (range) HCV-RNA = 260 (< 5-3,800) KIU/mL. Out of 31, 16 patients (51.6%) had SVR by the intention-to-treat analysis. The SVR was significantly associated with the serum HCV RNA level. Logistic analysis showed that SVR occurred when HCV RNA level was < 100 KIU/mL (p=0.020). Based on the difference of the serum HCV RNA level, the SVR rate was 81.8% (9/11) in patients with a serum HCV RNA level of < 100 KIU/mL and 35.0% (7/20) in patients with a serum HCV RNA level of > or = 100 KIU/mL., Conclusion: IFN-beta monotherapy of < or = 24 week is a possible therapy selection for elderly patients of > or = 70 years with type C hepatitis of genotype 2.

Background: Substitution of amino acids (aa) 70 and 91 in the core region of HCV genotype 1b is a useful pretreatment predictor of poor response to interferon + ribavirin combination therapy, but the impacts of aa substitutions in the core region of HCV genotype 2a are still not clear., Methods: 154 consecutive Japanese adults with a high viral load (> or =100 kIU/ml) of genotype 2a who could complete combination therapy for 24 weeks were evaluated. To examine the differences in virological characteristics between non-sustained virological response (non-SVR) and rapid responder (SVR patients who could achieve a HCV-RNA-negative status within 8 weeks), 86 patients could be analyzed by pretreatment substitution patterns of the core region., Results: SVR was achieved in 127 of 154 patients (83%), and rapid response in 113 of 127 (90%). In all 154 patients, multivariate analysis identified younger age, lower level of viremia, and higher level of albumin as significant determinants of SVR. As significant determinants of rapid response in 86 patients, multivariate analysis identified substitution of aa 4 (non-asparagine) in addition to the significant determinants of SVR., Conclusions: Our results suggest that the aa substitution pattern of the core region in patients with a high titer of genotype 2a may partly affect the virological response to combination therapy., (Copyright 2009 S. Karger AG, Basel.)

Aims: We showed previously that amino acid (aa) substitutions in HCV genotype 1b (HCV-1b) core region are negative predictors of virological response to peginterferon + ribavirin therapy, and also risk factors of hepatocarcinogenesis. The aim of this study was to evaluate the impact of core aa substitutions on mortality in elderly patients., Methods: We compared the characteristics and survival of 92 elderly (> or =75 years) patients with HCV-related hepatocellular carcinoma (HCC) (including 62 patients with HCV-1b) with those of 44 younger patients (<50 years, 34 patients with HCV-1b)., Results: For all patients, univariate analysis identified female sex, history of blood transfusion, preserved liver function and glucose metabolism as significant variables in the elderly patients. In patients with HCV-1b-related HCC, univariate analysis identified preserved lipid metabolism as significant variable in addition to significant variables in overall patients. In elderly patients with HCV-1b-related HCC, multivariate analysis identified male sex, methionine of core aa91, and non-radical therapy as factors that influenced mortality after first treatment for HCC., Conclusions: Our results characterized elderly patients who develop HCC after HCV-1b infection, and suggested that aa substitutions of HCV-1b core region correlate with mortality of patients after first treatment for HCC., (Copyright 2009 S. Karger AG, Basel.)

Objective: The aim of this study was to evaluate the efficacy of combination therapy of peginterferon and ribavirin in patients infected with hepatitis C virus (HCV) genotype 1b and low virus load., Methods: Inclusion criteria were HCV-genotype 1b, serum HCV RNA level of < 100 KIU/mL at the initiation time of treatment. A total of 60 were enrolled in this retrospective cohort study. The treatment period of combination therapy was 39.8+/-16.1 weeks., Results: Of the 60 study patients, 47 had sustained virological response (SVR) by the intention to treat analysis. SVR occurred when serum HCV RNA was negative 8 weeks after the initiation of the treatment (p=0.004) and continuance of negative HCV RNA during treatment was > or = 30 week (p=0.016). In rapid virological response, all of seven patients with continuance of negative HCV RNA 20 to 29 weeks during treatment had SVR. In early virological response nine of 10 patients with continuance of negative HCV RNA of 30 to 39 week during treatment had SVR., Conclusion: The duration of combination therapy for chronic hepatitis C should be determined based on the time of attainment of negative HCV RNA in patients with genotype 1b and low-virus load.

Aim: To investigate the cumulative development incidence and predictive factors for idiopathic pulmonary fibrosis in hepatitis C virus (HCV) positive patients., Methods: We studied 6150 HCV infected patients who were between 40-70 years old (HCV-group). Another 2050 patients with hepatitis B virus (HBV) were selected as control (HBV-group). The mean observation period was 8.0 +/- 5.9 years in HCV-group and 6.3 +/- 5.5 years in HBV-group. The primary goal is the development ofidiopathic pulmonary fibrosis (IPF) in both groups. The cumulative appearance rate of IPF and independent factors associated with the incidence rate of IPF were calculated using the Kaplan-Meier method and the Cox proportional hazard model. All of the studies were performed retrospectively by collecting and analyzing data from the patient records in our hospital., Results: Fifteen patients in HCV-group developed IPF. On the other hand, none of the patients developed IPF in HBV-group. In HCV-group, the cumulative rates of IPF development were 0.3% at 10th year and 0.9% at 20th year. The IPF development rate in HCV-group was higher than that in HBV-group (P = 0.021). The IPF development rate in patients with HCV or HBV was high with statistical significance in the following cases: (1) patients > or = 55 years (P < 0.001); (2) patients who had smoking index (package per day multiply year) of > or = 20 (P = 0.002); (3) patients with liver cirrhosis (P = 0.042)., Conclusion: Our results indicate that age, smoking and liver cirrhosis enhance the development of IPF in HCV positive patients.

Objective: The stepwise hook extension technique for an expandable needle, which we reported previously, allowed roll-off in short time with low power. The aim of this study was to investigate experimentally the efficacy of a modified extension procedure., Methods: Three pigs underwent 10 radiofrequency ablation (RFA) procedures using the 10-hook electrode of LeVeen needle. The conventional technique was used in five RFA (group 1; the electrode was deployed in four steps to full extension), while the new technique was used in the other five RFA (group 2; the electrode was closed after the same three steps as group 1 and then fully extended)., Results: The shape of the RFA-induced zone was cone-like or irregular in group 1 and oval-like in group 2. The diameter vertical to the shaft was larger in group 2 (37, range 33-42 mm) than in group 1 (23, range 20-29 mm). The median ablation time was longer in group 2 (10 min 13 s) than in group 1 (3 min 56 s). Although the required energy was higher in group 2 than in group 1, that per volume was comparable between the groups (median 0.9 vs. 1.4 kJ/mm(3))., Conclusions: Our new procedure requires a longer session but produces larger necrosis of a uniform ellipsoid volume, making it potentially suitable for tumours more than 3 cm in diameter.

Objective: Interferon (IFN) therapy reduces the incidence of hepatocarcinogenesis in patients with hepatitis C viral (HCV) infection who achieve a sustained virological response (SVR). The aim of the present study was to determine the rate of hepatocarcinogenesis and the risk factor in sustained virological responders., Patients and Method: The study subjects were 1,193 patients with HCV-related chronic liver disease and IFN- or IFN plus ribavirin-induced SVR. The age, male/female ratio, and liver fibrosis stage [(F0-F3)/LC] were 15-83 years, 808/385, and 1106/41, respectively. Patients were followed-up for 8.3 years (range, 0 to 19.0 years) and the incidence of hepatocellular carcinoma was recorded., Results: Hepatocellular carcinogenesis was detected in 23 patients during the follow-up. The crude rates of hepatocarcinogenesis at 5, 10, and 15 years were 1.5%, 2.4% and 4.1%, respectively. Multivariate analysis identified cirrhosis, male sex and age older than 50 years as determinants of hepatocarcinogenesis with hazard ratios of 12.9 (p<0.001), 6.45 (p=0.012), and 20.2 (p=0.004), respectively., Conclusion: Long-term follow-up of patients with chronic HCV infection is necessary even in those who show SVR, especially in male elderly patients with cirrhosis.

Objective: The aim of this study was to elucidate efficacy after dose reduction in combination therapy of peginterferon and ribavirin for chronic hepatitis C., Methods: Inclusion criteria were hepatitis C virus (HCV) genotype 1b, serum HCV RNA level of >/=100 KIU/ml, dose reduction of peginterferon and/or ribavirin between the first 4 weeks and 20 weeks after the initiation of treatment. 164 patients were enrolled in this retrospective cohort study. Predictive factors for sustained viral response (SVR) after dose reduction were examined., Results: Out of the 146 patients treated with dose reduction, 57 had SVR. Multivariate analysis showed that SVR occurred when serum HCV RNA at the time of dose reduction was negative (p < 0.001) and total ribavirin dose was >/=100% of the anticipated total dose (p < 0.001). 57% (55/97) of patients with undetectable serum HCV RNA at the time of dose reduction had SVR. In contrast, only 4% (2/49) of patients with detectable serum HCV RNA at the time of dose reduction had SVR., Conclusions: On dose reduction of combination therapy for chronic hepatitis C, undetectable serum HCV RNA at the time of dose reduction and attainment of the total ribavirin dose of >/=100% enhance SVR., (Copyright (c) 2008 S. Karger AG, Basel.)

Objectives: The aim of this study was to elucidate the efficacy of interferon (IFN) therapy in liver cirrhosis Japanese patients with genotype 1b and low virus load., Methods: The present study was a retrospective cohort study. Inclusion criteria were liver cirrhosis, HCV genotype 1b, HCV RNA of <100 KIU/ml, and natural IFN-alpha monotherapy for 24 weeks. In 23 consecutive patients who satisfied the above criteria the efficacy and side effects of IFN were examined. Independent factors that might have influenced a sustained virologic response (SVR) were studied using logistic regression analysis., Results: The clinical patient profiles were as follows: median (range) age 52 (37-69) years; male/female 18/5, and median (range) HCV RNA 52 (<5-92) KIU/ml. Eight of the 23 patients (34.8%) had SVR by intention-to-treat analysis. Logistic analysis indicated that an HCV RNA level of <50 KIU/ml was associated with SVR (p = 0.049). The median (range) HCV RNA levels were 28 (<5-68) KIU/ml in patients with SVR and 60 (6-92) KIU/ml in patients without SVR., Conclusions: 24-week IFN monotherapy is a suitable therapy for type C cirrhotic patients with genotype 1b and an HCV RNA level of <50 KIU/ml., (Copyright 2008 S. Karger AG, Basel.)

Objectives: Intrahepatic metastasis is one of the serious complications of radiofrequency ablation (RFA) therapy for hepatocellular carcinoma. The aim of this study was to investigate how liver tissue could be disseminated during the RFA procedure with different devices and protocols in an in vivo porcine model., Methods: Three pigs underwent RFA procedures using 2 different devices: needles that could be expanded (LeVeen needle) and those that could not (cool-tip needle). A LeVeen needle was used with a single-step full extension method or a stepwise extension method. Before RFA, a mixture of lipiodol and blue dye was injected intrahepatically into a precoagulated area. After the ablation procedure, the specimen was cut to evaluate the amount of dye remaining in the ablated region and the distribution of the dye outside the ablated area., Results: The stepwise extension method resulted in the disappearance of the smallest amount of the dye and lipiodol at the ablation site, compared with the full extension method and cool-tip needle. Dye was found at sites distant from the ablated area in all cases using the cool-tip needle, but in none with the stepwise extension method., Conclusions: The stepwise procedure using the expandable needle can reduce tumor cell scattering, which can cause intrahepatic metastasis, compared with other methods., (2009 S. Karger AG, Basel.)