Entecavir administration to pregnant Japanese woman with chronic hepatitis B and hepatocellular carcinoma: A case report.

Women taking entecavir hydrate (ETV) may not need to consider abortion in the event of an unexpected pregnancy. If a woman with renal dysfunction and taking ETV for chronic hepatitis B becomes pregnant, continuous use of ETV may also be tolerated.

FIB-4 index-based surveillance for advanced liver fibrosis in diabetes patients.

Liver fibrosis is associated with lifestyle-related diseases, including diabetes. The identification of diabetic patients with severe liver fibrosis is important, but a simple and reliable diagnostic procedure remains to be determined. We conducted an observational study to evaluate the performance of a FIB-4 index-based screening strategy for the diagnosis of advanced liver fibrosis in patients with diabetes or prediabetes. Two hundred and forty-two patients underwent abdominal imaging in our Study. According to the abdominal imaging findings, fatty liver, liver cirrhosis, and hepatocellular carcinoma were defined, and their association with FIB-4 index evaluated. The prevalences of liver cirrhosis and hepatocellular carcinoma in patients with a high (≥ 2.67; liver cirrhosis: 42.9%, hepatocellular carcinoma: 14.3%) FIB-4 index were significantly higher than in those with an intermediate (1.3 ≤ FIB-4 < 2.67; liver cirrhosis: 1.6%, hepatocellular carcinoma: 0.8%) or low FIB-4 index (< 1.3; liver cirrhosis: 1.2%, hepatocellular carcinoma: 0%). The diagnostic accuracy, specificity, and sensitivity of the FIB-4 index for the diagnosis of liver cirrhosis or hepatocellular carcinoma were 84.3%, 85.5%, and 89.3%, respectively, with an optimized cut-off value of 2.96 (sensitivity = 0.86, specificity = 0.98). Using an optimized cut-off value, FIB-4 index might be useful to identify liver cirrhosis or hepatocellular carcinoma in diabetes patients with high diagnostic accuracy.

Management of Hepatitis B Surface Antigen and Hepatitis C Antibody-Positive Patients by Departments Not Specializing in Hepatology at a Suburban University Hospital in Japan: A Single-Center Observational Study.

OBJECTIVE: To investigate effects of an altered medical environment between 2010 and 2015 on viral hepatitis treatment behaviors of doctors who were not hepatology specialists. METHODS: Charts of patients who were identified as hepatitis B surface antigen (HBs-Ag)-positive or hepatitis C virus antibody (HCV-Ab)-positive by university hospital departments not specializing in hepatology from January to December 2015 were retrospectively reviewed. Patients were assigned to a "referred" group or a "non-referred" group based on whether they were subsequently referred to the Hepatology Department. Age, sex, type of department visited (one of various internal medicine departments, or a different department), and blood test results were compared in the two groups. RESULTS: Among 7,824 patients screened for HBs-Ag, 82 were positive. Twenty-nine (35.4%) had subsequently been referred to the Hepatology Department, which was higher than the 2010 referral rate (20.6%). In multivariate analysis, patients in the referred group were significantly more likely to have visited one of various internal medicine departments, and they had higher levels of platelet count and γ-glutamyl transpeptidase. Among 7,778 patients screened for HCV-Ab, 279 were positive. Only 33 (11.8%) had subsequently been referred to the Hepatology Department, which was lower than the 2010 referral rate (18.7%). In multivariate analysis, patients in the referred group were significantly more likely to have visited an internal medicine department. CONCLUSION: HCV-antibody-positive patients screened by departments not specializing in hepatology were not managed adequately in 2015. This suggests a need for education of doctors not specializing in hepatology, particularly those not working in internal medicine departments.

Recommendations from primary care physicians, family, friends and work colleagues influence patients' decisions related to hepatitis screening, medical examinations and antiviral treatment.

Identification and screening of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) is important to prevent liver cancer. Comprehensive antiviral treatments should follow three sequential steps: Hepatitis screening (step 1; examination of HB surface antigen and HCV antibody), medical examination (step 2; examination of HBV-DNA and/or HCV-RNA and performance of abdominal ultrasonography) and antiviral treatment (step 3). Patients who underwent these three steps were studied to determine effective information sources (factors) for raising awareness of comprehensive treatments. A total of 182 patients from 11 medical institutions were who were undergoing antiviral treatment were investigated. The number of patients who accessed each of the 18 information sources in each of the three steps and the percentage of these information sources that directly influenced the participants to make treatment-related decisions were calculated. 'Recommendation from a primary care physician' was the most common information source (64.3, 77.5, and 75.8% at steps 1, 2, and 3, respectively). 'Recommendation from a public health nurse (PHN),' 'recommendation from friends or family,' and 'recommendation from work colleagues' were the next most common human factors (3.3-19.8%). 'Recommendation from a primary care physician' had the greatest influence (76.9, 73.0, and 77.5% at steps 1, 2, and 3, respectively). 'Recommendation from a PHN' (50.0, 26.3 and 64.3%), 'recommendations from friends and family' (58.3, 38.9 and 58.3%), and 'recommendations from work colleagues' (33.3, 33.3 and 42.9%) were highly influential factors. Media such as TV commercial messages and programs also had high recognition, but were not directly influential. The findings of the present study indicated that recommendations from primary care physicians, friends, family and work colleagues influenced patients' decision-making regarding hepatitis screening, examination and treatment.

Estimating the cost-effectiveness of screening for hepatitis C virus infection in Japan.

AIM: The management of hepatitis C virus (HCV) has changed with the advent of interferon (IFN)-free treatment and the declining prevalence of HCV infection, which may impact the cost-effectiveness of the screening. We aimed to compare the cost-effectiveness and clinical outcomes of three screening strategies in the Japanese general population: no screening, screening plus IFN-based therapy, and screening plus IFN-free therapy. METHODS: We developed a decision analytic Markov model for screening intervention and natural history of HCV. Model parameters were derived from published literature. A lifetime horizon and the healthcare payer perspective were taken. Subanalyses included high screening scenario with improved rates of screening and attending referral, in addition to heterogeneity analysis by age subgroup. RESULTS: In the base case, the incremental cost-effectiveness ratio in the Japanese general population aged 40-89 years was ¥1 124 482 and ¥1 085 183 per quality-adjusted life year gained for screening plus IFN-free therapy compared with no screening and screening plus IFN-based therapy, respectively. Screening plus IFN-free therapy remained cost-effective below ¥5 000 000 per quality-adjusted life year gained in sensitivity analyses. Incremental cost-effectiveness ratios were lower in the younger population. Nearly 0.2% of HCV-related deaths were avoided by 1.5% of the general population screened followed by IFN-free therapy relative to no screening; the impact was greater with improved rates of screening and attending referral. CONCLUSIONS: Screening and subsequent IFN-free therapy for HCV appears to be cost-effective. Early diagnosis and treatment would produce a favorable incremental cost-effectiveness ratio. Improved rates of screening and attending referral would result in further reduction of disease progression.

Real-World Effectiveness From the Asia Pacific Rim Liver Consortium for HBV Risk Score for the Prediction of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated With Oral Antiviral Therapy.

BACKGROUND: Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort. METHODS: Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score. RESULTS: A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001). CONCLUSIONS: The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.

Generation Gap for Screening and Treatment of Hepatitis C Virus in Saga Prefecture, Japan: An Administrative Database Study of 35,625 Subjects.

Objective Despite recent advances in hepatitis C virus (HCV) treatment, some HCV-positive individuals are unaware of their infection. The present study aimed to assess the rate and age distribution in Saga Prefecture regarding i) HCV infection and HCV screening and ii) direct acting anti-viral (DAA) treatment. Methods HCV screening data collected at a medical institution or in the workplace were obtained from the administrative database in Saga Prefecture between April 1, 2008 and March 31, 2014. DAA treatment data from Saga Prefecture were obtained from the DAA treatment reimbursement recipient database between October 2014 and March 2017. Results There were 35,625 individuals who underwent HCV screening, and the HCV positive rate was 1.18% (421 individuals), which increased in an age-related manner. The screening rate in the screened populations peaked at 45-74 years of age (approximately 6%) and decreased in the younger and older generations. The estimated percentage of DAA treatment peaked at 65-74 years old (65.8%) and significantly decreased inversely with age in the younger generations; only 9.4% of HCV carriers received DAA treatment in the 20- to 34-year age group. The proportion of subjects who received a complete physical examination for DAA treatment was higher in the subjects who were screened at a medical institution than in those screened at the workplace. Conclusion The rate of subjects who underwent HCV screening and DAA treatment was not high, especially in the younger generation, in Saga Prefecture. This group should be targeted for HCV screening and treatment.

Hepatitis C Virus Cure Rates Are Reduced in Patients With Active but Not Inactive Hepatocellular Carcinoma: A Practice Implication.

BACKGROUND: Cure rates of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared with HCV/non-HCC patients. METHODS: Using data from the Real-World Evidence from the Asia Liver Consortium (REAL-C) registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin levels to evaluate DAA treatment outcomes in a large population of HCV/HCC compared with HCV/non-HCC patients. RESULTS: We included 6081 patients (HCC, n = 465; non-HCC, n = 5 616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs 93.7%; P = .03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR, 0.28; P = .01) when compared with non-HCC. CONCLUSIONS: Active HCC but not inactive HCC was independently associated with lower SVR compared with non-HCC patients undergoing DAA therapy, although cure rate was still relatively high (85%) in active HCC patients.

Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium.

BACKGROUND AND AIMS: One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. METHODS: Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25 IU/mL 12 week post-therapy). RESULTS: A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, p < 0.0001), had lower body mass indices (22.9 kg/m2 vs. 24.6 kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes. CONCLUSIONS: In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

Categorization and Characterization of Activities Designed to Help Health-care Professionals Involved in Hepatitis Care Increase Their Awareness of the Disease: The Classification of Hepatitis Medical Care Coordinators.

Objective This study aimed to investigate the current state of the activities performed by hepatitis medical care coordinators, categorize coordinators according to the activities they perform, and determine the backgrounds of these coordinators. Methods A self-administered questionnaire survey was completed by 414 coordinators. The surveyed items included gender, occupation, activity items performed, and barriers that inhibited the performance of these activities. A hierarchical cluster analysis was applied, and cases were classified based on the contents of the activities in question. Results The coordinators were classified into four groups (A-D). Group A, consisting primarily of public health nurses, was classified as "the type that conducted activities aimed at providing information and recommendations." Group B, which included registered dieticians and clerks, was classified as "the type that uses multidisciplinary collaboration to perform their tasks." Group C, which included clinical nurses, was classified as "the type that was more likely to perform activities as leaders in an organization." Group D, consisting primarily of pharmacists, was classified as "the type that promoted activities centered on providing instructions regarding medication dosage and administration." Conclusion Our study showed that coordinators' professional skills and abilities are reflected in the contents of the activities they conduct, and that, to adequately perform their roles, they must acquire skills in addition to those required in their original occupations. To implement high-quality hepatitis countermeasures, there is a need to foster an environment that facilitates cooperation between coordinators, as well as relationship-building.

Regulation of interferon signaling and HCV­RNA replication by extracellular matrix.

Although interferon (IFN)­based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH­7 human hepatoma cell line and HuH­7 cells were stably transfected with full­length HCV­RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM­coated dishes or non­coated plastic dishes (NDs), and treated with human IFN­α. In Huh­7 cells cultured on coated dishes, the IFN­stimulated response element (ISRE) luciferase activity was measured following ISRE plasmid transfection and the expression of IFN­stimulated genes (ISG) were significantly lower than those in cells cultured on NDs. In addition, after IFN­α treatment, the amount of HCV­RNA and viral protein produced by OR6 cells cultured on coated dishes was higher than that produced by cells cultured on NDs. When cells were treated with ß1­integrin­blocking antibody to disrupt the cell­matrix interaction, the ISRE luciferase activity was restored, and the protein expression of ISG was increased, while that of HCV proteins was suppressed. Treatment of cells with integrin­linked kinase (ILK) inhibitor or focal adhesion kinase (FAK) inhibitor restored the ISRE luciferase activity and expression of ISG proteins. These results suggested that ß1­integrin­mediated signals affected the IFN signaling and promoted HCV replication. Therefore, the accumulation of ECM in liver fibrosis may impair IFN signaling through ß1­integrin­mediated signaling involving ILK and FAK.

Chronic Hepatitis C Treatment with Daclatasvir Plus Asunaprevir Does Not Lead to a Decreased Quality of Life.

Objective The aim of this study was to determine if direct-acting antiviral (DAA) treatment with daclatasvir (DCV) plus asunaprevir (ASV) for 24 weeks influenced the health-related quality of life (HRQOL) at 12 and 24 weeks after treatment initiation [end of treatment (EOT)]. Methods This was a prospective, longitudinal study comparing the HRQOL of patients receiving DAA treatment at 12 weeks after treatment initiation and EOT with the HRQOL at baseline. We used a Japanese-validated version of the 8-item Short Form Health Survey (SF-8) to assess the HRQOL of patients. This score can be compared to the Japanese normative sample scores of SF-8. Wilcoxon signed-rank tests were used to compare the HRQOL before treatment, 12 weeks after treatment initiation, and at EOT. Patients We enrolled patients who received 24-week combination therapy using DCV and ASV for HCV at Saga University Hospital between November 2014 and July 2015. Those who discontinued treatment due to relapse or adverse reactions during the treatment period were excluded from the study. Results There were no significant changes in any of the SF-8 subscales, Physical component scores (PCS) or mental component scores (MCS) during the treatment period for both males and females. Conclusion Our study makes a significant contribution to the literature because 24-week DAA treatment with DCV plus ASV did not decrease the HRQOL at 12 or 24 weeks after treatment initiation.

Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis. METHODS: Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography. RESULTS: After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P < 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P < 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC. CONCLUSIONS: Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.

Reducing the mortality rate of hepatitis and liver cancer in Japan.

The Basic Act on Hepatitis Countermeasures issued in 2009 states the comprehensive measures that can be taken against viral hepatitis as well as the responsibility that the national government, local governments, health insurance provides, physicians, and citizens should take in these measures, thereby organically facilitating the construction of a hepatitis management system in Japan. In addition, the Committee for the Clinical Management of Hepatitis has established branches in each prefecture to create a hepatitis management network for public hepatitis screening facilities, primary care physicians, medical institutions specializing in hepatitis, and primary hospitals for cooperative medical care of liver diseases to address regional hepatitis-related issues.

"Weariness" and "unpleasantness" reduce adherence to branched-chain amino acid granules among Japanese patients with liver cirrhosis: results of a single-center cross-sectional survey.

AIM: Branched-chain amino acids (BCAA) are valuable in the treatment of liver cirrhosis because they increase serum albumin levels. Poor adherence to BCAA may adversely affect prognosis, but little is known about factors predicting adherence. We undertook a survey of patients prescribed BCAA for the treatment of cirrhosis. METHODS: Pharmacists carried out face-to-face interviews with patients (or their representatives) prescribed any of nine BCAA formulations. Question categories included patient characteristics, prescription of BCAA granules, and perceptions of BCAA administration, including adherence and possible factors that might impact adherence. "Poor adherence" was defined as "not taking the medication appropriately" or "forgetting to take the medication". RESULTS: Overall, 253 patients (or representatives) completed the survey, of whom 135 were men, 114 were women, and 148 were ≥70 years old. Most patients (163) were prescribed BCAA for ≥2 years and were using three packs per day. Thirty-two patients did not take their medication appropriately and 69 sometimes forgot to administer it. Weariness of taking the medication (P < 0.001) and the perceived unpleasantness (P = 0.023) of the medication in terms of its taste and volume were significantly associated with poor adherence. The patients reported that the most influential educators were general practitioners, followed by certified hepatologists, then pharmacists. CONCLUSION: Most patients had good adherence to BCAA in clinical practice. Poor adherence was associated with weariness with taking medication, and the unpleasantness of the medication itself. Patient education from general practitioners and hepatologists combined with adherence counseling from pharmacists may help improve adherence.

Optimal Follow-up of Patients with Viral Hepatitis Improves the Detection of Early-stage Hepatocellular Carcinoma and the Prognosis of Survival.

Objective To manage patients with viral hepatitis, it is important to screen for hepatitis, conduct a comprehensive examination if such screening is positive, administer antiviral treatment, and conduct surveillance for hepatocellular carcinoma (HCC). The proper execution of this strategy is expected to effectively reduce the number of deaths from viral hepatitis. Such an "optimal" follow-up for HCC surveillance is therefore important. This study aimed to determine the benefits of performing an optimal follow-up of patients with viral hepatitis. Methods The subjects were infected with the hepatitis virus and were initially diagnosed with or treated for HCC from 2004-2012. We retrospectively analyzed the history of a patient's current illness using the hospital discharge summary. To minimize any lead-time bias, we calculated the corrected survival for patients who received an optimal follow-up. Results Of 333 patients, 107 (32.1%) did not receive an optimal follow-up and thus had low cumulative survival rates in comparison to those who did. The median corrected survival was 51.5 months for patients with an optimal follow-up compared with 31.4 months for those without (p=0.011). A multivariate analysis revealed that AFP <35 [odds ratio (OR), 2.054], Child-Pugh A (OR, 2.488), and an optimal follow-up (OR, 4.539) were independent factors associated with the detection of early-stage HCC. Age (OR, 0.939), tumor stage I/II (OR, 6.918), and an optimal follow-up (OR, 3.213) were found to be independent factors associated with receiving curative treatment. Conclusion An optimal follow-up of patients with viral hepatitis independently increased the detection of early-stage HCC and the administration of curative treatment. Patients with an optimal follow-up survived longer than those without.

Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1.

BACKGROUND: The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants. METHODS: A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated. RESULTS: Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR. CONCLUSION: NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

Clinical course of hepatitis B surface antigen positive subjects following screening: A retrospective observational study from April 2008 to January 2013.

AIM: Determination of the percentage of hepatitis B surface antigen (HBsAg) positive participants who undergo screening and treatment may reduce the development of hepatocellular carcinoma. This study assessed the percentages of HBsAg positive participants detected by free screening at medical institutions in Saga Prefecture who underwent detailed examinations and antiviral treatment. METHODS: Participants were screened for HBsAg positivity at medical institutions in Saga Prefecture from April 2008 to January 2013, with some visiting physicians for detailed examinations and applying for reimbursement. Participants in the database of the Health Promotion Division of Saga Prefecture and results of detailed examinations were analyzed retrospectively. RESULTS: Screening revealed 193 eligible participants, 105 men (54%) and 88 women (46%), of a mean age of 55.5 ± 14.9 years. Of these 193 participants, 147 (76%) visited physicians for detailed examinations, 24 (16%) were regarded as needing treatment and seven (3.6%) were reimbursed for antiviral treatments. The 46 participants who did not undergo detailed examinations were significantly younger than the 147 examined participants (50.9 ± 13.2 vs 56.9 ± 15.2 years, P = 0.018). Of the 110 participants thought to require observation, 68 (62%) were assigned to this group without determination of alanine aminotransferase or hepatitis B virus DNA concentration, and 15 (14%) had indications for antiviral treatment according to the 2014 guidelines of the Japanese Society of Hepatology. CONCLUSION: The proportion of HBsAg positive participants receiving antiviral treatment was lower than that of participants undergoing detailed examinations.

Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial.

OBJECTIVE: Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC. METHODS: The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by ≥5% before starting treatment with PEG-IFN plus RBV. RESULTS: Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of ≥5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a ≥5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar. CONCLUSION: Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate.

Efficacy and safety of telaprevir, pegylated interferon α-2b and ribavirin triple therapy in Japanese patients infected with hepatitis C virus genotype 1b.

Objective This study evaluated the efficacy and safety of triple therapy with telaprevir (TVR), pegylated interferon α-2b (PegIFN-α-2b) and ribavirin (RBV) in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1b in real-world clinical practice. Methods A total of 106 consecutive patients with HCV genotype 1b were treated with triple therapy for 12 weeks followed by dual therapy with PegIFN-α-2b and RBV for 12 weeks. The primary end point was sustained virological response (SVR), defined as undetectable serum HCV RNA at 24 weeks after the end of treatment. Results The overall SVR rate was 87.7% (93/106 patients). Age and body weight (BW) differed significantly between patients with and patients without SVR. Multivariate analysis showed that age <67 years [odds ratio (OR) 5.03, p=0.014] and BW ≥55 kg (OR 5.87, p=0.008) were independent pretreatment factors predictive of SVR. When posttreatment factors were included, age <67 years (OR 7.30, p=0.041), rapid virological response (OR 10.60, p=0.019) and continuation of therapy (OR 14.45, p=0.012) were each independently associated with SVR. Body weight <55 kg (OR 5.96, p=0.015) and TVR initial dose ≥41 mg/kg/day (OR 5.19, p=0.017) were each independently associated with discontinuation of therapy. Discontinuation rates decreased in inverse proportion to the percentage of patients with an initial TVR dose of 1,500 mg/day. Conclusion For TVR-based triple therapy, continuation of therapy is the most important predictor of SVR. Patients who are likely intolerant of standard-dose TVR should receive reduced initial doses of TVR to avoid discontinuation of therapy.