Amino acid substitution in HCV core region and genetic variation near the IL28B gene affect viral dynamics during telaprevir, peginterferon and ribavirin treatment.

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.

Diabetes enhances hepatocarcinogenesis in noncirrhotic, interferon-treated hepatitis C patients.

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.

New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma.

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.

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

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.

Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin.

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.

Efficacy and safety of combination therapy of natural human interferon beta and ribavirin in chronic hepatitis C patients with genotype 1b 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.

Efficacy and safety of combination therapy of natural human interferon beta and ribavirin 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 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.

Efficacy of switching to entecavir monotherapy in Japanese lamivudine-pretreated patients.

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.

Extending combination therapy with peginterferon plus ribavirin for genotype 2 chronic hepatitis C virological responders: a pilot study of 7 cases.

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.

Clinical and virological effects of long-term (over 5 years) lamivudine therapy.

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.

Amino acid substitutions in the hepatitis C virus core region of genotype 1b affect very early viral dynamics during treatment with telaprevir, peginterferon, and ribavirin.

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.

Association of HLA-DR14 with the treatment response in Japanese patients with autoimmune hepatitis.

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.

Virus clearance reduces bone fracture in postmenopausal women with osteoporosis and chronic liver disease caused by hepatitis C virus.

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.

Correlation of YMDD mutation and breakthrough hepatitis with hepatitis B virus DNA and serum ALT during lamivudine treatment.

AIM: Continuous lamivudine treatment is associated with high frequency of drug resistance. We analyzed the incidence of tyrosine-methionine-aspartate-aspartate (YMDD) motif mutant and breakthrough hepatitis (BTH) in hepatitis B virus (HBV) DNA positive patients receiving lamivudine for > 1 year and correlated it with HBV DNA and alanine aminotransferase (ALT) levels to evaluate if these measurements can provide a practical option for monitoring patients in clinical practice and define early switch from lamivudine therapy. METHODS: Of the 929 patients receiving lamivudine for > 1 year, 359 patients who maintained an ALT level of /= 3 years. RESULTS: The incidence of YMDD motif in patients receiving lamivudine for < 3 years was 27% in patients with ALT

Sustained virological response in a patient with chronic hepatitis C treated by monotherapy with the NS3-4A protease inhibitor telaprevir.

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.

Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 2a high viral load and virological response to interferon-ribavirin combination therapy.

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.

The efficacy of interferon-beta monotherapy for elderly patients with type C hepatitis of genotype 2.

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.

Losartan reduces the onset of type 2 diabetes in hypertensive Japanese patients with chronic hepatitis C.

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.

Rapid loss of hepatitis C virus genotype 1b from serum in patients receiving a triple treatment with telaprevir (MP-424), pegylated interferon and ribavirin for 12 weeks.

AIM: To evaluate the efficacy and safety of the triple treatment with telaprevir (MP-424), pegylated interferon (PEG-IFN) and ribavirin during 12 weeks on-treatment. METHODS: The triple treatment was given to 20 patients with chronic hepatitis C who had been infected with hepatitis C virus (HCV)-1b in high viral load (median: 6.8 log IU/mL [range: 5.5-7.2]), with a median age of 54 years (range: 36-65 years). They were followed for early dynamics of HCV RNA in serum during 12 weeks and side-effects. RESULTS: HCV RNA levels decreased by 4.8 logs by 7 days and 5.5 logs by 14 days. HCV RNA disappeared in 50% (10/20) at 2 weeks, 79% (15/19) at 4 weeks, 88% (14/16) at 6 weeks, 94% (15/16) at 8 weeks and 100% (13/13) at 12 weeks. HCV RNA disappeared equally frequently in 10 treatment-naive patients, six non-responders to IFN monotherapy and four non-responders to PEG-IFN and ribavirin. It was no different in the patients with and without amino acid substitutions reducing the response to IFN. The treatment was withdrawn in seven (35%) patients, mostly due to reduced hemoglobin of less than 8.5 g/dL, of whom six (86%) remained clear of HCV RNA at 12 weeks. CONCLUSION: HCV RNA was lost from serum rapidly and universally in patients infected with HCV-1b in high viral loads by the triple treatment. Because an early loss of HCV RNA correlates with high rates of sustained virological response (SVR), it would increase SVR substantially, and merit the patients who have not responded to previous therapies.

Development of hepatocellular carcinoma in elderly patients with chronic hepatitis C with or without elevated aspartate and alanine aminotransferase levels.

OBJECTIVE: Hepatocellular carcinoma (HCC) in the elderly infected with hepatitis C virus (HCV) is expected to increase globally within the next two decades. The purpose of the study was to define the natural history of elderly patients with chronic hepatitis C needs in order to prevent HCC from arising in these patients. MATERIAL AND METHODS: Treatment-naive patients aged >or=65 years with platelet counts >120 x 10(3)/mm(3) were classified as 120 with aspartate and alanine aminotransferase (ASAT and ALAT) levels or=41 (group B) and followed-up for 3 years or longer without antiviral treatment. RESULTS: Cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 for both). In particular, of the patients aged 65-69 years at entry, cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 and p=0.001, respectively). Liver-related causes of death were more common in group B than in group A (20/34 (59%) versus 1/9 (11%), p=0.021). HCC developed more frequently in men than in women (p=0.033). CONCLUSIONS: In elderly patients with chronic hepatitis C, cirrhosis and HCC develop more frequently in those with elevated transaminase levels than in those without elevated transaminase levels. Therefore, transaminase levels need to be suppressed below