Yuya Seko

Kyoto Prefectural University of Medicine, Kioto, Kyōto, Japan

Are you Yuya Seko?

Claim your profile

Publications (37)107.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background & AimsSome cases with nonalcoholic fatty liver disease (NAFLD), particularly nonalcoholic steatohepatitis (NASH), can ultimately progress to liver cirrhosis. However, studies to clarify factors predictive of histological change in patients with NASH remain scarce. Our aim is to determine predictors of histological progression in Japanese patients with biopsy-proven NASH.Methods This retrospective cohort study enrolled 52 patients with NASH who underwent serial liver biopsies. Histological evaluation included NAFLD activity score (NAS) and liver fibrosis. The median interval between initial and second liver biopsies was 968 days. An ALT response was defined as a decrease of 30% or more from baseline.ResultsOf 52 patients, NAS was ameliorated in 30.8%, deteriorated in 30.8%, and remained unchanged in 38.4%. Liver fibrosis was improved in 25.0% of patients, progressed in 25.0%, and remained stable in 50.0%. Multivariate analysis identified ALT non-response as a predictor of deterioration of NAS (hazard ratio [HR], 5.85; p=0.031) and progression of liver fibrosis (HR, 4.50; p=0.029). The mean annual rate of fibrosis was 0.002 stages/year overall, increasing to 0.15 stages/year in ALT non-responders.ConclusionsA lack of reduction in serum ALT level by at least 30% from baseline was a predictor for histological progression in patients with NASH. Serum ALT level is a better predictor of histological change than insulin resistance or body weight and can be a valid index in treatment. Serum ALT should be strictly controlled to prevent liver histological progression in patients with NASH.
    Hepatology Research 11/2014; · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Some patients with nonalcoholic fatty liver disease develop hepatocellular carcinoma and have higher mortality than others. The evidence causally linking nonalcoholic fatty liver disease to extrahepatic malignancies is scarce. Our aim was to determine the incidence of and risk factors for hepatocellular carcinoma, extrahepatic cancer, and mortality in Japanese patients with biopsy-proven nonalcoholic fatty liver disease.Methods This retrospective cohort study analyzed outcomes including onset of malignant tumors and death in 312 patients with nonalcoholic fatty liver disease diagnosed by liver biopsy.ResultsOf 312 patients, 176 (56.4%) were diagnosed with nonalcoholic steatohepatitis. During a median follow-up period of 4.8 years (range, 0.3–15.8 years), six patients (1.9%) developed hepatocellular carcinoma, and twenty (6.4%) developed extrahepatic cancer. Multivariate analysis identified fibrosis stage (≥3; hazard ratio, 12.3; 95% confidence interval, 1.11-136.0; p=0.041) as a predictor for hepatocellular carcinoma and type IV collagen 7s (>5 ng/ml; hazard ratio, 1.74; 95% confidence interval, 1.08-2.79; p=0.022) as a predictor for extrahepatic cancer. Eight patients (2.6%) died during the follow-up period. The most common cause of death was extrahepatic malignancy. None died of cardiovascular disease. Multivariate analysis identified type IV collagen 7s (>5 ng/ml; hazard ratio, 3.38; 95% confidence interval, 1.17-9.76; p=0.024) as a predictor for mortality.Conclusions The incidence of extrahepatic cancer was higher than that of hepatocellular carcinoma. Severe fibrosis was a predictor for hepatocellular carcinoma. Patients with nonalcoholic fatty liver disease and elevated type IV collagen 7s levels are at increased risk for extrahepatic cancer and overall mortality.
    Hepatology Research 08/2014; · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimGrowth hormone (GH) deficiency may be associated with histological progression of nonalcoholic fatty liver disease (NAFLD) which includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Insulin-like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion is stimulated by GH. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of IGF-1 in Japanese patients.Methods Serum samples were obtained in 199 Japanese patients with biopsy-proven NAFLD and in 2,911 sex- and age-matched healthy people undergoing health checkups. The serum levels of IGF-1 were measured using a commercially available immunoradiometric assay. The standard deviation scores (SDS) of IGF-1 according to age and gender were also calculated in NAFLD patients.ResultThe serum IGF-1 levels in NAFLD patients were significantly lower (median, 112 ng/ml) compared with the control population (median, 121 ng/mL, p<0.0001). IGF-1 SDS less than -2.0 SD from median were found in 11.6% of 199 patients. NASH patients exhibited significantly lower levels of IGF-1 SDS (n=130, median, -0.7) compared with NAFL patients (n=69: median, -0.3, p =0.026). The IGF-1 SDS values decreased significantly with increasing lobular inflammation (p <0.001) and fibrosis (p <0.001). In multiple regressions, the association between the IGF-1 SDS values and the severity of NAFLD persisted after adjusting for age, gender, and insulin resistance.Conclusion Low levels of circulating IGF-1 might have a role in the development of advanced NAFLD, independent of insulin resistance. Supplementation with GH/IGF-1 may be a candidate for the treatment of NASH.
    Hepatology Research 08/2014; · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/AimsMice fed high-fat diet (HFD) demonstrate obesity-related systemic insulin resistance (IR). Aim of this study is to clarify the role of interleukin (IL)-6 in IR in vivo focusing on skeletal muscle, adipose tissue and liver.Methods Plasma markers of IR and hepatic IL-6 signaling were examined in eight-week HFD feeding C57/BL6 mice. Furthermore, IR-related molecules in skeletal muscles, adipose tissues and livers were investigated following a single injection of anti- IL-6 receptor neutralizing antibody (MR16-1) in two-week-HFD feeding mice. To investigate the role of IL-6 in hepatic steatosis by prolonged HFD, hepatic triglyceride accumulation was assessed in eight-week HFD-feeding mice with continuous MR16-1 treatment.ResultsHFD for both two and eight weeks elevated plasma IL-6, insulin, and leptin, which were decreased by MR16-1 treatment. A single injection of MR16-1 ameliorated IR as assessed by glucose and insulin tolerance test, which may be attributable to upregulation of glucose transporter type 4 via phosphorylation of AMP-activated protein kinase as well as upregulation of peroxisome proliferator-activated receptor alpha in livers and, particularly, in skeletal muscles. MR16-1 also decreased mRNA expression of leptin and tumor necrosis factor-alpha and increased that of adiponectin in adipose tissue. HFD for eight weeks, not two weeks, induced hepatic steatosis and increased hepatic triglyceride content, all of which were ameliorated by MR16-1 treatment.Conclusions Blockade of excessive IL-6 stimulus ameliorated HFD-induced IR in a skeletal muscle and modulated the production of adipokines from an early stage of NAFLD, leading to prevention of liver steatosis for a long term.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 07/2014; · 3.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion therapy for hepatocellular carcinoma (HCC). We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gelatin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. The mean free cisplatin concentrations were as follows. For group A, the mean was 48.58 µg/mL at 0 minute, 7.31 µg/mL at 5 minutes, 5.70 µg/mL at 10 minutes, and 7.15 µg/mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 µg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 µg/mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver.
    Gut and liver 09/2013; 7(5):576-84. · 1.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Using ultra-deep sequencing technology, the present was designed to investigate whether the emergence of telaprevir-resistant variants (amino acid substitutions of aa36, aa54, aa155, aa156, and aa170 positions in HCV NS3 region) after commencement of triple therapy of telaprevir/peginterferon (PEG-IFN)/ribavirin could be predicted at baseline in previous non-responders to dual therapy. Fourteen patients infected with HCV genotype 1 who did not respond to previous PEG-IFN/ribavirin, received a 24-week regimen of triple therapy, and were evaluated for appearance of telaprevir-resistant variants (amino acid substitutions of more than 0.2% among the total coverage) by ultra-deep sequencing. The sustained virological response rate was 28.6% (4 of 14 patients), which was significantly higher in patients with Arg70 (substitution at core aa70) and partial response (type of previous response to PEG-IFN/ribavirin) than in other patients. Telaprevir-resistant variants at baseline were detected in 7.1% (1 of 14 patients) by direct sequencing and in 21.4% (3 of 14 patients) by ultra-deep sequencing. The appearance of telaprevir-resistant variants was examined by ultra-deep sequencing in 10 who did not show sustained virological responders. De novo variants emerged at re-elevation of viral load, regardless of variant frequencies at baseline (one patient with very high frequency variants [T54S: 99.9%], two patients with very low frequency variants [V36A: 0.2%; and V170A: 0.4%], and seven patients of undetectable variants). It is concluded that it is difficult to predict at baseline the emergence of telaprevir-resistant variants after commencement of triple therapy in prior non-responders of HCV genotype 1, even with the use of ultra-deep sequencing. J. Med. Virol. 85: 1028-1036, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2013; 85(6):1028-36. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Renal dysfunction and Fanconi's syndrome associated with hypophosphatemia caused by long-term administration of low-dose adefovir dipivoxil (ADV) has been reported in recent years. The aim of this retrospective study was to determine the incidence and factors associated with renal dysfunction and hypophosphatemia in patients with hepatitis B infection on long-term treatment with ADV and lamivudine (LAM). METHODS: The study subjects were 292 patients treated with 10 mg/day ADV and 100 mg/day LAM for more than 6 months. We evaluated estimated glomerular filtration rate (eGFR), serum creatinine and serum phosphate level at the start of ADV and every 6 months. RESULT: During a median treatment duration of 64 months, 28 (9.6 %) patients developed renal impairment (defined as eGFR < 50 ml/min/1.73 m(2)), and 73 (27.1 %) developed hypophosphatemia, including 14 with persistent hypophosphatemia. The cumulative incidences of renal impairment at 1, 3, and 5 years were 1.4, 7.5, 10.5 %, respectively, and those of hypophosphatemia were 6.8, 20.6, 26.7 %, respectively. Multivariate analysis identified old age, liver cirrhosis and hypertension as determinants of renal impairment, and male sex, HCC, low baseline serum phosphate as determinants of hypophosphatemia. Three of the 14 patients with persistent hypophosphatemia developed Fanconi's syndrome; their serum creatinine level remained normal, but eGFR was lower than at baseline. CONCLUSION: Long-term treatment of hepatitis B with low-dose (10 mg/day) ADV and LAM can potentially cause renal impairment and hypophosphatemia. We advocate regular monitoring of serum phosphate and evaluation of eGFR, in addition to serum creatinine, in such patients.
    Journal of Gastroenterology 03/2013; · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: The aim of this case-control study was to assess the efficacy and safety of dipeptidyl peptidase-4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD). METHODS: Twenty NAFLD patients with T2DM treated by sitagliptin were retrospectively enrolled as the sitagliptin group. These patients were given sitagliptin between January 2010 and July 2011. Another 20 NAFLD patients with T2DM treated only with diet and exercise for 48 weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48 weeks after the initiation of treatment. RESULTS: In the sitagliptin group, average HbA1c levels decreased approximately 0.7% at 48 weeks after the initiation of sitagliptin. Next, average FPG levels decreased approximately 15 mg/dL at 48 weeks after the initiation of sitagliptin. The serum levels of HbA1c and FPG in the sitagliptin group decreased with statistical significance compared to those in the control group (P < 0.05). All the patients could take sitagliptin of 50 mg/day without reduction necessitated by sitagliptin-related side-effects. There were no significant changes of average AST and ALT levels during follow up of 48 weeks in both sitagliptin and control groups. CONCLUSION: Our results indicate sitagliptin is effective and safe for the treatment of T2DM complicated with NAFLD.
    Hepatology Research 03/2013; · 2.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Miriplatin is a novel lipophilic platinum complex that was developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, little prospective data are available regarding the clinical toxicity of chemotherapeutic agents used to treat HCC patients with chronic renal failure. In a phase II study, the plasma concentration of total platinum in patients who received miriplatin was very low, and no severe renal toxicity caused by miriplatin injection was reported. Here, we present three cases of HCC with stage 4 chronic renal failure who received transcatheter arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83 years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively. Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min, respectively. All cases were treated for unresectable HCC with transcatheter arterial chemotherapy with miriplatin. No serious adverse events were observed, and serum creatinine levels did not elevate, even in the patient who experienced renal failure caused by cisplatin administration. These results might suggest that transcatheter arterial chemotherapy with miriplatin can be safely used in HCC patients with chronic renal failure.
    Gut and liver 03/2013; 7(2):246-51. · 1.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The definitive diagnosis of nonalcoholic steatohepatitis (NASH) is currently based on histopathological assessment. This study aimed to elucidate the utility of a novel noninvasive method, three-dimensional magnetic resonance imaging (3D-MRI), for diagnosing advanced fibrosis in patients with NASH, using histopathological diagnosis as the reference standard. Methods This retrospective study included 30 consecutive patients who had been diagnosed with NASH by histopathology and had undergone 3D-MRI before biopsy. 3D-MRI provided a three-dimensional reconstruction of the liver from contrast-enhanced hepatobiliary phase MR images. In the present study, histopathological advanced fibrosis was defined as stage 3 and 4 NASH. Advanced fibrosis, diagnosed by 3D-MRI, was considered to be diffuse irregularity of the entire surface of the liver. The diagnostic features of 3D-MRI and the noninvasive evaluation systems (APRI, FIB-4 index, and BARD score) for identifying advanced and nonadvanced fibrosis of NASH were determined and compared. Results Nine (30 %) of the 30 study patients were diagnosed histopathologically with advanced fibrosis, and 11 (37 %) of 30 patients were diagnosed with advanced fibrosis using 3D-MRI. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 3D-MRI for diagnosing advanced fibrosis were 100, 90, 82, and 100 %, respectively. The sensitivities of APRI, the FIB-4 index, and BARD score ranged from 78 to 89 %, the specificities from 71 to 90 %, the PPVs from 54 to 78 %, and the NPVs from 88 to 94 %. Conclusion Compared with the common noninvasive methods for diagnosing advanced fibrosis associated with NASH, 3D-MRI was more accurate.
    Hepatology International 01/2013; · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: Patients with unresectable hepatocellular carcinoma (HCC) often undergo transcatheter arterial chemoembolization (TACE). Miriplatin is a lipophilic cisplatin derivative used in TACE that is effective in HCC. However, the difference in antitumor efficacy between warmed versus room temperature miriplatin is unclear. METHODS: Chemotherapy efficacy was evaluated by dynamic computed tomography 1-3 months after TACE, according to the Modified Response Evaluation Criteria in Solid Tumors. A total of 203 patients with HCC who received TACE with miriplatin for the first time were included in a follow-up study to retrospectively investigate its efficacy and safety. Overall, 45 patients underwent TACE with warmed (40°C) miriplatin and 158 patients received TACE with room temperature miriplatin. RESULTS: Seventy patients (44.3%) treated with room temperature miriplatin and 32 patients (71.1%) who received warmed miriplatin experienced complete or partial responses. Multivariate analysis identified miriplatin temperature (warmed miriplatin, risk ratio (RR) = 2.26, P = 0.047), tumor number (solitary, RR = 3.48, P = 0.007), α-fetoprotein (AFP) level (<50 ng/mL, RR = 2.35, P = 0.012) and history of TACE (no history, RR = 2.22, P = 0.041) as predictors of objective response following TACE with miriplatin, and no serious complications were observed. CONCLUSION: Warm temperature, solitary tumors, low AFP level and first TACE are significant and independent predictors of objective response after TACE using miriplatin. These results suggest that warmed miriplatin can be considered as one of the standard treatments for unresectable HCC.
    Hepatology Research 12/2012; · 2.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic hepatitis B virus (HBV) infection leads to cirrhosis and hepatocellular carcinoma (HCC). Antiviral agents are thought to reduce HCC development, but agent such as lamivudine (LAM) has a high rate of drug resistance. We compared the incidence of HCC in 472 entecavir (ETV)-treated patients and 1143 non-treated HBV patients (control group). Propensity score matching eliminated the baseline differences, resulting in a sample size of 316 patients per cohort. The drug mutation resistance was 0.8% (4/472) in the ETV group. The cumulative HCC incidence rates at 5-year were 3.7% and 13.7% for the ETV, and control groups, respectively (P < 0.001). Cox proportional hazard regression analysis, adjusted for a number of known HCC risk factors, showed that patients in the ETV group were less likely to develop HCC than those in the control group (hazard ratio: 0.37; 95% CI: 0.15 to 0.91; P = 0.030). Both cohorts were applied into 3 previously reported risk scales and risk scores were generated based on age, gender, cirrhosis status, levels of ALT, HBeAg, baseline HBV DNA, albumin, and bilirubin. The greatest HCC risk reduction occurred in high-risk patients who scored higher on respective risk scales. In a group analysis, we compared treatment effect between nucleos(t)ide analogues (NAs) which included matched LAM-treated patients without rescue therapy (n = 182). We found HCC suppression effect greater in etv-treated (P < 0.001) than non-rescued LAM-treated (P = 0.019) cirrhotic patients when they were compared with the control group. Conclusion: Long-term entecavir treatment may reduce the incidence of HCC in HBV-infected patients. The treatment effect was greater in patients at higher risk of HCC. (HEPATOLOGY 2012.).
    Hepatology 12/2012; · 12.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver-related death in patients of hepatitis C virus (HCV) genotype 1b (HCV-1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV-infected patients, who had not received antiviral therapy, were included in a follow-up study to determine predictive factors of hepatocarcinogenesis and survival for liver-related death. The cumulative hepatocarcinogenesis rates in HCV-1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV-1b of Arg70 (arginine at aa 70) and HCV-2a/2b. The cumulative survival rates for liver-related death in HCV-1b of Gln70(His70) were significantly lower than those in HCV-1b of Arg70 and HCV-2a/2b. Multivariate analysis identified gender (male), age (≥60 years), albumin (<3.9 g/dL), platelet count (<15.0 × 104/mm3), aspartate aminotransferase (≥67 IU/L), and HCV subgroup (HCV-1b of Gln70(His70)) as determinants of both hepatocarcinogenesis and survival rates for liver-related death. In HCV-1b patients, the cumulative change rates from Arg70 to Gln70(His70) by direct sequencing were significantly higher than those from Gln70(His70) to Arg70. In patients of Arg70 at the initial visit, the cumulative change rates from Arg70 to Gln70(His70) in IL28B rs8099917 non-TT genotype were significantly higher than those in the TT genotype. Conclusion: Substitution of aa 70 in the core region of HCV-1b is an important predictor of hepatocarcinogenesis and survival for liver-related death in HCV patients who had not received antiviral therapy. The IL28B genotype might partly affect changes over time of dominant amino acid in core aa 70 of HCV-1b. (HEPATOLOGY 2012;56:2134–2141)
    Hepatology 12/2012; 56(6). · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: The aims of this study are to assess the antiviral effects, safety and telaprevir (TVR) pharmacokinetics in two cohorts given TVR every 8 h (q8h) at doses of 500 mg and 750 mg with peginterferon-α-2b and ribavirin in chronic hepatitis C patients. METHODS: Twenty chronic hepatitis C (HCV) patients with genotype 1b in high viral loads were randomly assigned to two TVR-based regimens of 750 mg q8h (group A) and 500 mg q8h (group B) in combination with peginterferon-α-2b and ribavirin for 12 weeks. RESULTS: Although the difference was not statistically significant other than trough concentration (C(trough) ) at week 4, the parameters of maximum concentration (C(max) ), the area under the concentration time curve (AUC(0-∞) ) and C(trough) tended to be higher in group A than those in group B. The antiviral effects were similar in the two groups (sustained virological response rates [SVR], 40% in group A, 50% in group B). The discontinuation rates by anemia were 30% in group A and 20% in group B. Serum creatinine concentrations were lower in group B than those in group A. CONCLUSION: Although the exposure to TVR tended to be lower in 500 mg q8h than that in 750 mg q8h, the SVR rates in both groups were similar. The result suggests that the 500 mg q8h dose may be one option for treatment. In addition, the present findings indicate that the development of adverse events which increase with a TVR-based regimen, specifically anemia and creatinine, could be avoided by dose adjustment of TVR.
    Hepatology Research 11/2012; · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Clearance of hepatitis B surface antigen (HBsAg) is considered the ultimate goal in chronic hepatitis B treatment. One treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this treatment in promoting clearance and longitudinal declines of HBsAg. METHOD: The study included 791 NA therapy patients who received lamivudine as their first drug. At the baseline, 442 patients were hepatitis B e antigen (HBeAg)+ and 349 were HBeAg-. All analyses were performed after separating the HBeAg+ and HBeAg- cohorts. Cox proportional hazards models were used to determine which factors were associated with HBsAg clearance. RESULTS: HBsAg clearance was observed in 18 (4.1 %) of the HBeAg+ patients and 20 (5.7 %) of the HBeAg- patients at baseline, giving seroclearance rates of 6.4 and 6.9 %, respectively, over the nine-year study period. HBsAg clearance was influenced by several independent factors that varied according to HBeAg cohort. For HBeAg+ patients, these included previous interferon therapy, infection with hepatitis B virus (HBV) genotype A, a ≥0.5 log IU/mL decline in HBsAg level within six months, and clearance of HBeAg at six months. For HBeAg- patients, these included infection with HBV genotype A, decline in HBsAg at six months, and a baseline HBsAg level of <730 IU/mL. CONCLUSION: This study suggests that both direct antiviral potential and host immune response are needed to achieve HBsAg clearance by NA therapy. Viral genotype strongly influenced HBsAg clearance during NA therapy.
    Journal of Gastroenterology 10/2012; · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Anticarcinogenic activity of ribavirin combination therapy for hepatitis C virus (HCV)-related compensated cirrhosis is still unclear. Methods: In study 1, in 157 consecutive patients with HCV-related compensated cirrhosis, treatment efficacy with interferon plus ribavirin therapy was evaluated for 48 weeks of HCV genotype 1b (HCV-1b) or 24 weeks of HCV-2a/2b. In study 2, in 185 consecutive patients with HCV-related compensated cirrhosis, who showed no sustained virological response following the first course of interferon monotherapy, hepatocarcinogenesis rates were evaluated according to the additional treatment, and they were classified into three groups: no treatment, interferon monotherapy, and ribavirin combination therapy. Results: In study 1, in HCV-1b, rates of sustained virological response and sustained biochemical response were 21 and 56%, respectively. In HCV-2a/2b, rates of sustained virological response and sustained biochemical response were 70 and 78%, respectively. In HCV-1b, sustained biochemical response rates were significantly higher than those of sustained virological response. In study 2, the hepatocarcinogenesis rates in ribavirin combination therapy were significantly lower than those in interferon monotherapy and no treatment, respectively. Conclusion: Ribavirin combination therapy for HCV-related compensated cirrhosis reduces the risk of hepatocarcinogenesis in comparison with interferon monotherapy, and higher rates of sustained biochemical response might be associated with lower hepatocarcinogenesis rates.
    Intervirology 10/2012; · 1.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The impacts of IL28B genotype to treatment response of hepatitis C virus (HCV) genotype 2 are still not clear. A total of 381 consecutive Japanese patients infected with HCV genotype 2, who could complete combination therapy with interferon (IFN) plus ribavirin for 24 weeks, were evaluated to investigate pretreatment predictors. Patients, who could not achieve sustained virological response at the first course of 24-week IFN plus ribavirin, were recruited into the study protocol of total 48-week IFN plus ribavirin. In 24-week regimen, rates of sustained virological response and rapid virological response were 82% and 50%, respectively. There were no significant differences in rates of sustained virological response and rapid virological response, according to IL28B genotype. Multivariate analysis identified younger age, higher level of albumin, absence of past history of IFN, and lower level of viremia as significant determinants of sustained virological response. As significant or marginal significant determinants of non-sustained virological response regardless of rapid virological response, multivariate analysis identified IL28B rs8099917 genotype TG + GG and lower level of albumin. In 48-week regimen to 10 patients of non-sustained virological response at the first course of 24-week regimen, sustained virological response rates were 70%. All of six patients, with IL28B TT and relapse at the first course of 24-week regimen, could achieve sustained virological response, but two patients with IL28B TG could not achieve sustained virological response. In conclusion, the present results suggest that IL28B genotype might partly affect viral response of HCV genotype 2 to combination therapy.
    Journal of Medical Virology 10/2012; 84(10):1593-9. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Substitution of amino acid 70 and/or 91 in the core region of hepatitis C virus (HCV) genotype 1b (HCV-1b) is an important predictor of hepatocellular carcinoma (HCC), but its impact on HCC in nonresponders to interferon (IFN) and ribavirin (RIB) combination therapy is not clear. Methods: A total of 292 patients with HCV-1b-related chronic liver disease who did not achieve a sustained virological response to 24-48 weeks of IFN+RIB combination therapy were included in a follow-up study to investigate the risk factors for HCC. Results: Sixteen patients developed HCC during the follow-up. The cumulative HCC rates were 5.0, 13.1 and 16.9% at the end of 3, 5 and 7 years, respectively. Multivariate analysis identified substitution of core amino acid 70 (Gln70/His70; hazard ratio 4.64, p = 0.018) and low serum levels of high-density lipoprotein cholesterol (<50 mg/dl; hazard ratio 9.35, p = 0.041) as determinants of HCC. Gender, stage of fibrosis and interleukin-28B showed no such relationship. Conclusions: Amino acid substitution in the core region of HCV-1b and low serum levels of high-density lipoprotein cholesterol are significant and independent predictors of HCC in nonresponders to IFN+RIB combination therapy. These results emphasize the importance of viral and lipid metabolic factors in the development of HCC after combination therapy.
    Intervirology 08/2012; · 1.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims of this study were to evaluate the efficacy of long-term interferon (IFN) monotherapy on hepatocellular carcinoma (HCC) in patients who showed no virological response to the first course of IFN therapy, define predictive factors for HCC in patients on long-term IFN monotherapy, and evaluate the clinical impact of amino acid (aa) substitutions in the hepatitis C virus (HCV)-1b core region on HCC rate. This retrospective study included 494 consecutive treatment-naive patients infected with HCV-1b who failed to achieve sustained virological response after ≥24-week IFN monotherapy. Of 494 patients, 113 (22.9%) received another course of ≥48-week IFN monotherapy (additional-IFN group), while the remaining 381 (77.1%) received no such therapy (no-additional-IFN group), and 10 years have elapsed since the end of the first IFN monotherapy. The cumulative HCC rate was significantly higher in the no-additional-IFN group than additional-IFN group, and in those with aa substitutions in the core region of Gln70(His 70) and Met 91 than those with Arg 70 and/or Leu 91. Multivariate analysis identified stage of liver fibrosis, liver enzymes, age, treatment group, aa substitution in the core region, low-density lipoprotein cholesterol (LDL-cholesterol), and gender as determinants of HCC, and that additional IFN treatment significantly lowered the cumulative rate of HCC, even in patients with cirrhosis. In conclusion, long-term IFN monotherapy reduces the risk of HCC, even in patients with cirrhosis. Substitution of aa at position 70 and/or 91 in the core region and lipid metabolism are important predictors of HCC in long-term IFN monotherapy.
    Journal of Medical Virology 08/2012; 84(8):1199-207. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim:  To evaluate the efficacy of natural human interferon (IFN)-β and ribavirin in elderly patients infected with hepatitis C virus (HCV) genotype 2 and high virus load. Methods:  Inclusion criteria were age of 65 years or older, HCV genotype 2 and serum HCV RNA level of 5.0 logIU/mL or more. A total of 33 were enrolled in this retrospective cohort study. 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 20 weeks. Ribavirin was given daily for 24 weeks at the dose described based on bodyweight. Fifteen patients were given a standard dose of ribavirin (standard group). Eighteen patients were given a reduction dose of ribavirin that decreased by one tablet per day compared to the standard group (reduction group). Results:  Of the 33 study patients, no patient stopped the treatment due to treatment-related adverse events. The dose of IFN-β was reduced in three patients: Two patients belonged to the standard group and one patient belonged to the reduction group. The dose of ribavirin was reduced in 11 patients during combination therapy: nine patients belonged to the standard group and two patients belonged to the reduction group. The sustained virological response (SVR) was 72.2% (13/18) in the reduction group and 80.0% (12/15) in the standard group. There was no significant difference in SVR rate between the reduction and standard groups (P = 0.699). Conclusion:  The reduction therapy of IFN-β and ribavirin in elderly chronic hepatitis C patients with genotype 2 and high virus load is one selection of treatment.
    Hepatology Research 08/2012; 42(8):750-6. · 2.07 Impact Factor