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Nakamoto D, Piao Y, Mizutani H, LoPresti M, Chikamura Y, Makhija D, Kwon KM, Zagorski J, Jinushi M, Eguchi Y. Patient and physician preferences for treatment of hepatitis C virus infection in Japan: a discrete choice experiment. J Med Econ 2025; 28:524-534. [PMID: 40126410 DOI: 10.1080/13696998.2025.2483572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 03/18/2025] [Accepted: 03/20/2025] [Indexed: 03/25/2025]
Abstract
AIMS This study was performed to evaluate patients' and physicians' preferences regarding hepatitis C virus (HCV) treatment in Japan, particularly focusing on direct-acting antivirals. Understanding these preferences is important for maintaining adherence to treatment necessary for achieving HCV elimination. METHODS A discrete choice experiment was conducted to identify patients' and physicians' preferences for HCV treatment in Japan. Eligible participants completed a preference survey via an online questionnaire. Eight attributes and their respective levels - pertaining to dosing regimen/schedule, safety, and out-of-pocket costs - were identified. The primary and secondary endpoints were the relative attribute importance (RAI) and utility value of attribute levels, which were compared between patients and physicians to highlight differences. RESULTS Both patients (n = 95) and physicians (n = 118) showed the greatest concern for total out-of-pocket treatment costs, followed by safety risks. While patients and physicians generally shared similar treatment preferences, patients placed a higher RAI on total out-of-pocket costs than did physicians (50.4% vs. 39.4%). Conversely, patients assigned lower RAI values to the risks of nasopharyngitis and pruritus (15.2% vs. 17.9% and 11.7% vs. 16.2%, respectively). The RAI for the number of tablets taken daily was higher than that for treatment duration among patients (11.6% vs. 0.2%), but nearly equal among physicians. LIMITATIONS The study had potential non-response bias, physicians not being actual care providers for surveyed patients, a small sample size, reliance on predefined DCE attributes, and limited participant diversity from online panels. CONCLUSIONS This study highlights the importance of patient-centered care in HCV treatment and the need to raise awareness of the public subsidy for hepatitis, and to ensure an effective access scheme for the patients. Simplifying regimens like once-daily pills and minimal monitoring may enhance treatment convenience. Improved patient-physician communication supports optimized strategies, aiding Japan's goal of HCV elimination by 2030.
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Affiliation(s)
| | - Yi Piao
- Gilead Sciences K.K, Tokyo, Japan
| | | | | | | | | | | | | | | | - Yuichiro Eguchi
- Locomedical General Institute, Locomedical Medical Cooperation, Saga, Japan
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Ikeda Y, Nago H, Yamaguchi M, Om R, Terai Y, Kita Y, Sato S, Murata A, Sato S, Shimada Y, Nagahara A, Genda T. Serum pro-inflammatory cytokine interleukin-6 level is predictive of further decompensation and mortality in liver cirrhosis. Hepatol Res 2025; 55:696-706. [PMID: 40317675 DOI: 10.1111/hepr.14175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 01/27/2025] [Accepted: 02/02/2025] [Indexed: 05/07/2025]
Abstract
AIM Systemic inflammation drives the progression of portal hypertension in patients with liver cirrhosis. Interleukin-6 is a key mediator of the cytokine network in acute inflammation that stimulates the production of many acute phase reactants. In this study, we investigated the association between serum interleukin-6 and acute phase reactant levels and the disease stage and prognosis of patients with liver cirrhosis. METHODS A single-center retrospective cohort of 359 patients with liver cirrhosis was staged according to the symptomatic decompensation. Baseline serum C-reactive protein , interleukin-6, procalcitonin, and serum amyloid A protein levels were measured. The outcomes of further decompensation, hepatocellular carcinoma development, and mortality were identified during a 3.3-year median follow-up period. RESULTS Serum C-reactive protein , interleukin-6, and procalcitonin levels were significantly different across the stages. The multivariate Cox proportional hazards model identified serum interleukin-6 as an independent predictor of further decompensation in patients with compensated and the first single decompensated cirrhosis. Kaplan-Meier analyses showed that the probability of further decompensation was stratified by serum interleukin-6 level in a dose-dependent manner. In the entire cohort, serum interleukin-6 level also showed a significant association with liver-related and all-cause mortalities, but not with hepatocellular carcinoma development, independent of stage and liver disease severity indices. CONCLUSIONS Elevated levels of serum markers of systemic inflammation were associated with symptomatic decompensation, and serum interleukin-6 level is a predictor of further decompensation and mortality in patients with liver cirrhosis.
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Affiliation(s)
- Yuji Ikeda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Hiroki Nago
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Masahiro Yamaguchi
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Rihwa Om
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Yuichiro Terai
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Yuji Kita
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Sho Sato
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Ayato Murata
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Shunsuke Sato
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Yuji Shimada
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
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Nakazawa S, Fukai K, Sano K, Furuya Y, Hoshi K, Kojimahara N, Toyota A, Korenaga M, Tatemichi M. Association of occupational physical activity and sedentary behaviour with the risk of hepatocellular carcinoma: a case-control study based on the Inpatient Clinico-Occupational Database of Rosai Hospital Group. BMJ Open 2025; 15:e092020. [PMID: 40074261 PMCID: PMC11904348 DOI: 10.1136/bmjopen-2024-092020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
OBJECTIVES While there is growing evidence that physical activity reduces the risk of hepatocellular carcinoma (HCC), the impact of occupational physical activity and sedentary behaviour remains unclear. This study aimed to investigate the associations between occupational physical activity and sedentary behaviour and HCC risk. DESIGN Matched case-control study. SETTING Nationwide multicentre, hospital-inpatient data set in Japan, from 2005 to 2021. PARTICIPANTS The study included 5625 inpatients diagnosed with HCC and 27 792 matched controls without liver disease or neoplasms. Participants were matched based on sex, age, admission date, and hospital. PRIMARY MEASURES The association between levels of occupational physical activity (low, medium, high) and sedentary time (short, medium, long) with the risk of HCC. SECONDARY MEASURES Stratification of HCC risk by viral infection status (hepatitis B/C virus), alcohol consumption levels and the presence of metabolic diseases (hypertension, diabetes, dyslipidaemia, obesity). RESULTS High occupational physical activity was not associated with HCC caused by hepatitis B/C virus infection in men. In women, high occupational physical activity was associated with a reduced risk of non-viral HCC, with ORs (95% CIs) of 0.65 (0.45-0.93). Among patients with non-viral HCC, medium occupational physical activity combined with medium alcohol intake further decreased the HCC risk in men with an OR of 0.70 (0.50-0.97), while high occupational physical activity combined with lowest alcohol intake decreased the HCC risk in women with an OR of 0.69 (0.48-0.99). Men and women with medium sedentary time had a lower HCC risk compared with those with long sedentary time, with ORs of 0.88 (0.79-0.98) in men and 0.77 (0.62-0.97) in women, respectively. In patients without viral infection or alcohol use, medium sedentary time reduced the HCC risk associated with fatty liver disease without comorbid metabolic diseases in women. CONCLUSIONS High levels of occupational physical activity and/or medium periods of sedentary time are associated with a reduced risk of HCC, particularly non-alcoholic steatohepatitis.
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Affiliation(s)
- Shoko Nakazawa
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Kota Fukai
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Kei Sano
- Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan
| | - Yuko Furuya
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Keika Hoshi
- Center for Health Informatics Policy, National Institute of Public Health, Wako, Japan
- Department of Hygiene, Kitasato University School of Medicine, Sagamihara, Japan
| | - Noriko Kojimahara
- Department of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
| | - Akihiro Toyota
- Chugoku Rosai Hospital Research Center for the Promotion of Health and Employment Support, Japan Organization of Occupational Health and Safety, Hiroshima, Japan
| | - Masaaki Korenaga
- Hepatitis Information Centre, Research Centre for Hepatitis and Immunology, National Centre for Global Health and Medicine, Ichikawa, Japan
| | - Masayuki Tatemichi
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
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Sugiyama A, Kagaya A, Ko K, Phyo Z, Akuffo GA, Akita T, Takahashi K, Tsukue R, Shimohara C, Tanaka J. Prevalence of hepatitis B and C, and their linkage to care among drug abusers attending psychiatric hospital in Hiroshima, Japan. GHM OPEN 2024; 4:1-10. [PMID: 40144738 PMCID: PMC11933930 DOI: 10.35772/ghmo.2023.01017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/13/2024] [Accepted: 01/17/2024] [Indexed: 03/28/2025]
Abstract
Towards the WHO goal for hepatitis elimination, understanding the prevalence and management of hepatitis B and C viruses (HBV, HCV) among drug abusers is crucial. However, in Japan, where drug abuse is less prevalent than in other countries, there is a dearth of epidemiological studies on this topic. This study aimed to fill this gap by investigating virus prevalence and the testing and treatment landscape for drug abusers in Japan. We conducted a cross-sectional sero-epidemiological study at a psychiatric hospital in Hiroshima where approaching drug abusers was feasible. Blood samples and questionnaire on HBV/HCV testing and treatment were collected from drug abusers (n = 35, 85.7% male, mean age 55.4 years) and control group (n = 45, 71.1%, 48.2 years). Prevalence of HCV-Ab and HCV RNA in drug abusers was 60.0% (95% CI: 43.8-76.2%) and 28.6% (13.6-43.5%), respectively, which was significantly higher than in the control group (2.2%, 0.0%, respectively). All HCV-Ab positive drug abusers had undergone prior hepatitis virus testing, but only 42.9% of those eligible for HCV treatment were connected to it. For HBV, while prevalence of HBsAg was similar between groups (2.9% vs. 2.2%), prevalence of HBc-Ab was higher in drug abusers (34.3% vs. 17.8%), indicating a greater likelihood of exposure to HBV infection. In conclusion, HCV prevalence among drug abusers in psychiatric care is notably high. Although testing is accessible, a recognized challenge is the insufficient connection to treatment. Enhancing collaboration between psychiatric hospitals and hepatologists is crucial. Disregarding this issue is not an option for hepatitis elimination.
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Affiliation(s)
- Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Ariyuki Kagaya
- Senogawa Hospital, Hiroshima, Japan
- KONUMA Memorial Institute of Addiction and Mental Health, Senogawa Hospital, Hiroshima, Japan
| | - Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Zayar Phyo
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Golda Ataa Akuffo
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Takahashi
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
| | | | | | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of viral hepatitis and hepatocellular carcinoma, Hiroshima University, Hiroshima, Japan
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Mori K, Akiyama Y, Tanaka M, Sato T, Endo K, Hosaka I, Hanawa N, Sakamoto N, Furuhashi M. Deciphering metabolic dysfunction-associated steatotic liver disease: insights from predictive modeling and clustering analysis. J Gastroenterol Hepatol 2024; 39:1382-1393. [PMID: 38629681 DOI: 10.1111/jgh.16552] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/12/2024] [Accepted: 03/20/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND AND AIM New nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS Japanese individuals who received annual health checkups including abdominal ultrasonography (n = 15 788, men/women: 10 250/5538, mean age: 49 years) were recruited. RESULTS The numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t-distributed stochastic neighbor embedding and K-means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low-grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning-based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides, was selected as a useful feature for SLDs. CONCLUSIONS The new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs.
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Affiliation(s)
- Kazuma Mori
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Japan
| | - Yukinori Akiyama
- Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Marenao Tanaka
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tatsuya Sato
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuke Endo
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Itaru Hosaka
- Department of Cardiovascular Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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Satake M, Sugiyama M, Mizokami M, Tanaka J. Incidences of new hepatitis B infection and anti-hepatitis B core-negative occult hepatitis B infection among Japanese blood donors in relation to anti-hepatitis B surface antigen levels. J Med Virol 2024; 96:e29823. [PMID: 39039862 DOI: 10.1002/jmv.29823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/05/2024] [Accepted: 07/15/2024] [Indexed: 07/24/2024]
Abstract
A transfusion-transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti-hepatitis B surface antigen (anti-HBs) was reported. Occult HBV infection (OBI) with sole anti-HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti-HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA-only conversions, and 15 DNA plus anti-hepatitis B core (anti-HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti-HBc. Total incidence was 2.38/100 000 person-years (PY). None of these 202 new HBV infections arose in the group with anti-HBs titer ≥ 10 mIU/mL. In total, 30 anti-HBc-negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti-HBs response, and 23 showed stable anti-HBc and anti-HBs levels at DNA conversion. The HBV infection-protective ability of anti-HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti-HBc-positive- and negative OBI with immune reactions or abortive HBV infection.
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Affiliation(s)
- Masahiro Satake
- Blood Service Headquarters, Japanese Red Cross, Tokyo, Japan
| | - Masaya Sugiyama
- Department of Viral Pathogenesis and Controls, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Tokyo, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Chen PJ. Challenges for hepatitis B control in Asia-Pacific areas: Consolidating vaccination and rolling-out antiviral therapies. J Gastroenterol Hepatol 2024; 39:1033-1039. [PMID: 38413195 DOI: 10.1111/jgh.16528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 02/07/2024] [Indexed: 02/29/2024]
Abstract
Chronic hepatitis B (CHB) was, and still is, a prevalent liver disease in the world, especially high in the Asia-Pacific areas. With the advent of preventive vaccines and effective viral suppression drugs and active implementations, CHB has gradually become under control. The world-wide prevalence reduces from 4.2% in 1980 to 3.2% in 2020 study. CHB patients receiving long-term antiviral therapies significantly improve the clinical outcomes, saving from end-stage liver diseases. Despite of these impressive progresses, to meet the WHO sustained development goals (SDG) for CHB control, a 90% reduction of incidence and a 65% reduction of mortality in year 2030, there is still a long way to go. In this review, four ongoing approaches have been proposed: (i) A continuous monitoring of long-term vaccine efficacy in vaccinated populations; (ii) consolidating the hepatitis B virus vaccination program against vaccine hesitancy and limited resources; (iii) rolling-out current oral antivirals to more CHB patients not only for diseases treatment but also for infection preventions; and (iv) development of curative therapies, both friendly-to-dispense and affordable. A coherent and persevere efforts by the society may succeed and achieve the SDG for CHB in the future.
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Affiliation(s)
- Pei-Jer Chen
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Taiwan University College of Medicine, Taipei, Taiwan
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Tada T, Kumada T, Hiraoka A, Kariyama K, Yasuda S, Tada F, Ohama H, Nouso K, Matono T, Nakamura S, Toyoda H. mADRES predicts hepatocellular carcinoma development in patients with hepatitis C virus who achieved sustained virological response. J Gastroenterol Hepatol 2024; 39:1164-1171. [PMID: 38403468 DOI: 10.1111/jgh.16512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/30/2023] [Accepted: 01/31/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND AND AIM The study aims to develop a novel predictive model including the fibrosis (FIB)-3 index for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) who achieved sustained virological response (SVR) with direct-acting antiviral (DAA) therapy. METHODS This study included 2529 patients in whom HCV was eradicated with DAA therapy. The after DAA recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used to predict HCC development. We developed a modified ADRES (mADRES) score, in which the FIB-4 index was replaced by the FIB-3 index, and evaluated its usefulness in predicting HCC development compared with the ADRES score. RESULTS In the training set (n = 1770), multivariate analysis with Cox proportional hazards modeling showed that male sex (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.48-3.01), FIB-3 index (HR, 1.36; 95% CI, 1.28-1.45), and α-fetoprotein (HR, 1.05; 95% CI, 1.03-1.07) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES or mADRES score in multiple comparisons. Univariate Cox proportional hazards models showed that compared with the mADRES score 0 group, the HR for HCC development was 2.07 (95% CI, 1.02-4.19) for the mADRES score 1 group, 11.37 (95% CI, 5.80-22.27) for the mADRES score 2 group, and 21.95 (95% CI, 10.17-47.38) for the mADRES score 3 group. Similar results were obtained for mADRES score but not for ADRES score in the validation set (n = 759). CONCLUSION The mADRES score is useful for predicting HCC development after SVR.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Tomomitsu Matono
- Department of Internal Medicine, Himeji St. Mary's Hospital, Himeji, Japan
- Department of Gastroenterology, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
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Lewin A, McGowan E, Ou-Yang J, Boateng LA, Dinardo CL, Mandal S, Almozain N, Ribeiro J, Sasongko SL. The future of blood services amid a tight balance between the supply and demand of blood products: Perspectives from the ISBT Young Professional Council. Vox Sang 2024; 119:505-513. [PMID: 38272856 DOI: 10.1111/vox.13590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 12/07/2023] [Accepted: 12/29/2023] [Indexed: 01/27/2024]
Abstract
BACKGROUND AND OBJECTIVES Blood services manage the increasingly tight balance between the supply and demand of blood products, and their role in health research is expanding. This review explores the themes that may define the future of blood banking. MATERIALS AND METHODS We reviewed the PubMed database for articles on emerging/new blood-derived products and the utilization of blood donors in health research. RESULTS In high-income countries (HICs), blood services may consider offering these products: whole blood, cold-stored platelets, synthetic blood components, convalescent plasma, lyophilized plasma and cryopreserved/lyophilized platelets. Many low- and middle-income countries (LMICs) aim to establish a pool of volunteer, non-remunerated blood donors and wean themselves off family replacement donors; and many HICs are relaxing the deferral criteria targeting racial and sexual minorities. Blood services in HICs could achieve plasma self-sufficiency by building plasma-dedicated centres, in collaboration with the private sector. Lastly, blood services should expand their involvement in health research by establishing donor cohorts, conducting serosurveys, studying non-infectious diseases and participating in clinical trials. CONCLUSION This article provides a vision of the future for blood services. The introduction of some of these changes will be slower in LMICs, where addressing key operational challenges will likely be prioritized.
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Affiliation(s)
- Antoine Lewin
- Medical Affairs and Innovation, Héma-Québec, Montreal, Quebec, Canada
- Medicine faculty and health science, Sherbrooke University, Sherbrooke, Quebec, Canada
| | - Eunike McGowan
- Research and Development, Australian Red Cross Lifeblood, Brisbane, Australia
- Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | | | - Lilian Antwi Boateng
- Department of Medical Diagnostics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- Immunohaematology laboratory, University Health Services, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | - Saikat Mandal
- Medical Oncology, Hull York Medical School, University of Hull, Hull, UK
| | - Nour Almozain
- Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia
- Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Jannison Ribeiro
- Centro de Hematologia e Hemoterapia do Ceará - Hemoce, Fortaleza, Brazil
- Instituto Pró-Hemo Saúde - IPH, Fortaleza, Brazil
| | - Syeldy Langi Sasongko
- Department of Public and Occupational Health, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
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Tanaka M, Mori K, Takahashi S, Higashiura Y, Ohnishi H, Hanawa N, Furuhashi M. Metabolic dysfunction-associated fatty liver disease predicts new onset of chronic kidney disease better than fatty liver or nonalcoholic fatty liver disease. Nephrol Dial Transplant 2023; 38:700-711. [PMID: 35612975 DOI: 10.1093/ndt/gfac188] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed. METHODS We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or positive for urinary protein, over a 10-year period in 28 890 Japanese subjects who received annual health examinations. After exclusion of subjects with no data for abdominal ultrasonography and subjects with CKD at baseline, a total of 13 159 subjects (men 8581, women 4578; mean age 48 years) were recruited. RESULTS The prevalence of FL, NAFLD and MAFLD was 34.6% (men 45.1%, women 15.1%), 32.8% (men 42.7%, women 14.5%) and 32.3% (men 42.4%, women 13.4%), respectively. During the 10-year follow-up period, 2163 subjects (men 1475, women 688) had new onset of CKD. Multivariable Cox proportional hazards model analyses showed that MAFLD [hazard ratio 1.12 (95% confidence interval 1.02-1.26); P = .027] but not FL or NAFLD was an independent risk factor for new onset of CKD after adjustment of age, sex, eGFR, current smoking habit, ischemic heart disease, diabetes mellitus, overweight/obesity, hypertension and dyslipidemia. The addition of MAFLD [continuous net reclassification improvement (NRI) 0.154, integrated discrimination improvement (IDI) 0.0024] to traditional risk factors without metabolic abnormalities significantly improved the discriminatory capacity better than did the addition of FL (NRI 0.138, IDI 0.0018) or NAFLD (NRI 0.132, IDI 0.0017). CONCLUSIONS MAFLD is modestly and independently associated with new onset of CKD and predicts the risk for development of CKD better than FL or NAFLD.
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Affiliation(s)
- Marenao Tanaka
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.,Tanaka Medical Clinic, Yoichi, Japan
| | - Kazuma Mori
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Satoko Takahashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yukimura Higashiura
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hirofumi Ohnishi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.,Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, Sapporo, Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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Metabolic dysfunction-associated fatty liver disease is associated with an increase in systolic blood pressure over time: linear mixed-effects model analyses. Hypertens Res 2023; 46:1110-1121. [PMID: 36717630 DOI: 10.1038/s41440-023-01179-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/24/2022] [Accepted: 12/24/2022] [Indexed: 02/01/2023]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD), a new feature of fatty liver (FL) disease that is defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic dysregulation, has been reported to be associated with the development of diabetes mellitus, chronic kidney disease and cardiovascular disease. However, the association between MAFLD and hypertension remains unclear. We investigated the association between MAFLD and systolic blood pressure (SBP) over a 10-year period in 28,990 Japanese subjects who received annual health examinations. After exclusion of subjects without data for SBP and abdominal ultrasonography at baseline, a total of 17,021 subjects (men/women: 10,973/6048; mean age: 49 years) were recruited. Linear mixed-effects model analyses using diagnoses of FL, nonalcoholic fatty liver disease (NAFLD) or MAFLD and age, sex, SBP, use of anti-hypertensive drugs, levels of uric acid and estimated glomerular filtration rate, family history of hypertension and habits of current smoking and alcohol drinking at baseline as well as the duration of the observation period and the interaction between each covariate and the duration of the observation period showed that the significant association of change in SBP over time with diagnosis of MAFLD (estimate: 0.223 mmHg/year, P < 0.001) was greater than that with diagnoses of FL (estimate: 0.196 mmHg/year, P < 0.001) and NAFLD (estimate: 0.203 mmHg/year, P < 0.001). Furthermore, the rate of increase in SBP over time was higher in subjects with MAFLD than in subjects without FL and subjects with FL who had no MAFLD. In conclusion, MAFLD is significantly associated with an increase in SBP over time. The presence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significantly associated with an increase in systolic blood pressure over time.
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12
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Nakazawa S, Fukai K, Furuya Y, Hoshi K, Kojimahara N, Toyota A, Korenaga M, Tatemichi M. Occupational class and risk of hepatitis B and C viral infections: A case-control study-based data from a nationwide hospital group in Japan. J Infect Public Health 2022; 15:1415-1426. [PMID: 36395666 DOI: 10.1016/j.jiph.2022.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 10/26/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Occupational class, a proxy for socio-economic status, is a known factor for health disparities. However, no study has reported the association between occupational class and the risk of viral hepatitis B and C (HBV/HCV) infections. We investigated the effects of occupational class on the prevalence of HBV/HCV infections. METHODS This is an unmatched hospital-based case-control study that included 12,101 patients who were diagnosed with HBV infection (ICD-10, B16.0, B16.1, B16.2, B16.9, B17.0, B18.0, B18.1) or HCV infection (ICD-10, B17.1, B18.2) and 698,168 controls (those with non-HBV/HCV-related diseases) aged ≥ 20 years who were initially hospitalized between 2005 and 2019. Patients were categorized according to occupational class (blue-collar, service, professional, and manager) and industrial sector (blue-collar, service, and white-collar). Managers in the blue-collar industry were set as the reference group, and the odds ratios (ORs) for the risk of HBV and HCV infections were calculated. RESULTS Occupational class was significantly associated with only HCV infection risk. Professionals in all industrial sectors showed the lowest risk for HCV (OR (95% confidence intervals [CIs]) = 0.69 [0.58-0.82] in the blue-collar industry, 0.52 [0.38-0.73] in the service industry, and 0.60 [0.52-0.70] in the white-collar industry). Further, after adjusting for sex, age, and region of admitting hospital, all occupational classes in the white-collar industry showed lower risks of HCV than those in the other industries (ORs= 0.58 [0.47-0.71] in blue-collar workers, 0.74 [0.64-0.84] in service workers, 0.60 [0.52-0.70] in professionals, and 0.81 [0.64-1.02] in managers in white-collar industry). CONCLUSIONS Occupational class was closely associated with HCV infection risk only. Considering that blue-collar workers in the white-collar industry also showed a low risk, adequate measures should be taken against hepatitis, possibly because of the screening tests and cure implemented in that population.
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Affiliation(s)
- Shoko Nakazawa
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Kota Fukai
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan.
| | - Yuko Furuya
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Keika Hoshi
- Center for Public Health Informatics, National Institute of Public Health, Wako, Japan; Department of Hygiene, School of Medicine, Kitasato University, Sagamihara, Japan
| | - Noriko Kojimahara
- Department of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
| | - Akihiro Toyota
- Chugoku Rosai Hospital Research Center for the Promotion of Health and Employment Support, Japan Organization of Occupational Health and Safety, Hiroshima, Japan
| | - Masaaki Korenaga
- Hepatitis Information Centre, Research Centre for Hepatitis and Immunology, National Centre for Global Health and Medicine, Ichikawa, Japan
| | - Masayuki Tatemichi
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
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Okamoto C, Tsukamoto O, Hasegawa T, Hitsumoto T, Matsuoka K, Amaki M, Kanzaki H, Izumi C, Takashima S, Ito S, Kitakaze M. Candidate Screening for Heart Failure With Preserved Ejection Fraction Clinic by Fib-4 Index From Subclinical Subjects. GASTRO HEP ADVANCES 2022; 2:170-181. [PMID: 39132617 PMCID: PMC11307393 DOI: 10.1016/j.gastha.2022.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/14/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Recognition of heart failure with preserved ejection fraction (HFpEF) at an early stage in mass screening is desirable, but difficult to achieve. We examined whether the fibrosis (Fib)-4 index, a simple index of liver stiffness/fibrosis, could be used as a screening tool to select candidates requiring expert diagnostics. Methods Individuals who participated in annual health checks between 2006 and 2007 in Arita-cho, Saga, Japan, with no history of cardiovascular disease and EF ≥ 50% were enrolled (total 710; 258 men; median age, 59 years). Results Participants were divided into 5 groups according to HFpEF risk: 215 (30%), 100 (14%), 171 (24%), 163 (23%), and 61 (9%) with Heart Failure Association (HFA)-PEFF scores of 0, 1, 2, 3, and 4-6 points, respectively. The highest HFpEF risk group (HFA-PEFF score, 4-6 points) showed poor prognosis for the clinical events of all-cause mortality and hospitalization for HF (log-rank test, P = .002). The Fib-4 index was correlated with HFpEF risk stratification (rs = 0.526), and increment in the Fib-4 index was independently linked to high HFpEF risk by multiple logistic regression analysis (adjusted odds ratio, 1.311; 95% confidence interval, 1.078-1.595; P = .007). The Fib-4 index stratified clinical prognosis (log-rank test, P < .001) was an independent predictor of all-cause mortality and hospitalization for HF (hazard ratio, 1.305; 95% confidence interval, 1.139-1.495; P < .001). Conclusion The Fib-4 index can be used to select appropriate candidates for a detailed examination of HFpEF in a subclinical population.
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Affiliation(s)
- Chisato Okamoto
- Department of Medical Biochemistry, Osaka University Graduate School of Medicine/Frontier Biosciences, Suita, Osaka, Japan
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Osamu Tsukamoto
- Department of Medical Biochemistry, Osaka University Graduate School of Medicine/Frontier Biosciences, Suita, Osaka, Japan
| | - Takuya Hasegawa
- Department of Cardiovascular Medicine, Garatia Hospital, Mino, Osaka, Japan
| | - Tatsuro Hitsumoto
- Department of Medical Biochemistry, Osaka University Graduate School of Medicine/Frontier Biosciences, Suita, Osaka, Japan
| | - Ken Matsuoka
- Department of Medical Biochemistry, Osaka University Graduate School of Medicine/Frontier Biosciences, Suita, Osaka, Japan
| | - Makoto Amaki
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Hideaki Kanzaki
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Chisato Izumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Seiji Takashima
- Department of Medical Biochemistry, Osaka University Graduate School of Medicine/Frontier Biosciences, Suita, Osaka, Japan
| | - Shin Ito
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Masafumi Kitakaze
- Department of Medical Biochemistry, Osaka University Graduate School of Medicine/Frontier Biosciences, Suita, Osaka, Japan
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
- Department of Cardiovascular Medicine, Hanwa Memorial Hospital, Osaka, Osaka, Japan
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Preoperative inflammatory markers as prognostic predictors after hepatocellular carcinoma resection: data from a western referral center. BMC Surg 2022; 22:329. [PMID: 36056350 PMCID: PMC9440527 DOI: 10.1186/s12893-022-01779-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 08/26/2022] [Indexed: 12/23/2022] Open
Abstract
Background Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown. Aim To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5–10 cm, > 10 cm) in patients undergoing HCC resection with curative intent.
Methods Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free survival (DFS) curves were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox method was used to identify independent predictors of OS and DFS. Results In total, 161 consecutive adult patients were included. A high NLR (> 1.715) was associated with worse OS (P = 0.018). High NLR (> 2.475; P = 0.047) and PLR (> 100.25; P = 0.028) were predictors of short DFS. In HCC < 5 cm, MLR (> 1.715) was associated with worse OS (P = 0.047). In the multivariate analysis, high PLR was an independent predictor of worse DFS [hazard ratio (HR) 3.029; 95%CI 1.499–6.121; P = 0.002]. Conclusion Inflammatory markers are useful tools to predict long-term outcomes after liver resection in western patients, high NLR was able to stratify subgroups of patients with short OS and DFS, an increased PLR was an independent predictor of short DFS, while high MLR was associated with short OS in patients with early HCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12893-022-01779-6.
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15
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Kaya M, Nakamura K, Sugiyama K, Kinae A, Yamaguchi H, Ukita H, Odagiri K, Ujiie C, Kato J, Kageyama F, Nagura M, Matsushita K, Sugiue K, Ishida H, Endo S, Suzuki T. Retrospective multicentre study on the effectiveness of first-line direct-acting antivirals against hepatitis C virus genotype-1. J Clin Pharm Ther 2022; 47:940-947. [PMID: 35229326 PMCID: PMC9543670 DOI: 10.1111/jcpt.13624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 02/02/2022] [Accepted: 02/09/2022] [Indexed: 11/29/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE In Japan, ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir are recommended as first-line treatments for patients with untreated hepatitis C virus genotype 1. Although they have demonstrated a high efficacy in clinical trials, there are no direct comparative studies. Clarification of their effectiveness and safety in real-world clinical practice is required. Therefore, we conducted a retrospective multicentre study on the effectiveness of these direct-acting antivirals in real-world clinical practice. METHODS We retrospectively evaluated the clinical data of untreated patients with persistent HCV genotype 1 infection who started first-line treatment with ledipasvir/sofosbuvir, elbasvir/grazoprevir or glecaprevir/pibrentasvir between September 2015 and January 2019 at 11 medical institutions in Japan. The primary efficacy endpoint was a sustained virologic response after 12 weeks of treatment. The secondary endpoints included sustained virologic response after 24 weeks of treatment and end of treatment response. The safety endpoint was treatment completion rate. RESULTS AND DISCUSSION During the study, 420 patients (median age, 70 years; 181 males) received ledipasvir/sofosbuvir, 48 (median age 72, years; 29 males) received elbasvir/grazoprevir and 63 (median age 66, years; 35 males) received glecaprevir/pibrentasvir. For ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir, the sustained virologic response after 12 weeks of treatment was 98.6%, 97.9% and 100%; the sustained virologic response after 24 weeks of treatment was 99.0%, 97.7% and 100%; the end of treatment response was 99.8%, 97.9% and 98.4%; and the treatment completion rate was 98.3%, 91.7% and 100% respectively. WHAT IS NEW AND CONCLUSION In real-world clinical practice, hepatitis C virus treatment with ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir was effective with safety.
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Affiliation(s)
- Michihiro Kaya
- Department of PharmacyShizuoka General HospitalShizuoka CityShizuokaJapan
| | - Kazuyo Nakamura
- Department of PharmacyShizuoka General HospitalShizuoka CityShizuokaJapan
| | - Kyohei Sugiyama
- Department of PharmacyShizuoka General HospitalShizuoka CityShizuokaJapan
| | - Ayumi Kinae
- Department of PharmacyShizuoka General HospitalShizuoka CityShizuokaJapan
| | - Hiromi Yamaguchi
- Department of PharmacyShizuoka City Shimizu HospitalShizuoka CityShizuokaJapan
| | - Hirotoshi Ukita
- Clinical Study Management OfficeIwata City HospitalIwata CityShizuokaJapan
| | - Keiichi Odagiri
- Center for Clinical ResearchHamamatsu University School of MedicineHamamatsu CityShizuokaJapan
| | - Chika Ujiie
- Department of PharmacySeirei Mikatahara General HospitalHamamatsu CityShizuokaJapan
| | - Jun Kato
- Department of PharmacyYaizu City HospitalYaizu CityShizuokaJapan
| | - Fujito Kageyama
- Department of Gastroenterology and HepatologyHamamatsu Medical CenterHamamatsu CityShizuokaJapan
| | - Mariko Nagura
- Clinical Research CenterChutoen General Medical CenterKakegawa CityShizuokaJapan
| | - Kumi Matsushita
- Department of PharmacyKikugawa General HospitalKikugawa CityShizuokaJapan
| | - Kaori Sugiue
- Department of PharmacyJapan Japanese Red Cross Shizuoka HospitalShizuoka CityShizuokaJapan
| | - Hiroki Ishida
- Department of PharmacyJA Shizuoka Kohseiren Enshu HospitalHamamatsu CityShizuokaJapan
| | - Shinya Endo
- Department of GastroenterologyShizuoka General HospitalShizuoka CityShizuokaJapan
| | - Takaya Suzuki
- Department of PharmacyShizuoka General HospitalShizuoka CityShizuokaJapan
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Yoshitani H, Ito J, Kozono H. Post-Marketing Surveillance Study of the Safety and Efficacy of Nalfurafine (Capsules 2.5 μg, Oral Dispersing Tablets 2.5 μg) in 1186 Patients with Chronic Liver Disease and Intractable Pruritus. Hepat Med 2022; 14:37-66. [PMID: 35530746 PMCID: PMC9075016 DOI: 10.2147/hmer.s352775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 03/08/2022] [Indexed: 11/23/2022] Open
Abstract
Background Nalfurafine (Remitch®, Toray Industries, Inc.) is a selective κ-receptor agonist approved in Japan for the improvement of pruritus in patients with chronic liver diseases (only when existing treatments bring insufficient efficacy) in May 2015. Methods A post-marketing Specific Drug Use Survey was conducted in Japan (March 1, 2016 to June 30, 2020) of the safety and efficacy of nalfurafine for the improvement of pruritus in patients with chronic liver disease. Results Among 1186 cases analyzed for safety, the incidence of adverse drug reactions was 9.4% (112/1186 cases), lower than 61.4% reported in pre-marketing surveillance (297/484 cases). No specific safety issues were found and no cases of concern for drug dependence identified. Efficacy (itch improvement) was demonstrated in 73.16% (815/1114 cases; 12-week analysis set) and in 85.67% (520/607; general assessment of itch improvement at 1-year analysis set). A significant difference was found in 4 items of itch improvement at 12 weeks and 8 items of itch improvement at 1 year. No noteworthy issues were identified. Mean Visual Analog Scale (VAS) values after 12 weeks and 1 year after the first dose were significantly lower than the baseline (p < 0.0001 for both treatment durations). Mean severity scores (Kawashima’s classification scheme) were significantly lower than the pretreatment score at 12 weeks and 1 year after the first dose (both p < 0.0001). No concerns were identified in the efficacy and safety of nalfurafine in patients with specific background, ie, the elderly (aged ≥ 65 years), those with renal impairment, and those on long-term treatment (≥ 365 days) compared with patients without corresponding background. Conclusion No new safety issues of concern or cases of insufficient efficacy were identified in this Specific Drug Use Survey of the safety and efficacy of nalfurafine for the improvement of pruritus in patients with chronic liver diseases.
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Affiliation(s)
- Hiroshi Yoshitani
- Pharmaceutical & Medical Device Vigilance Department, Toray Industries, Inc., Tokyo, Japan
| | - Junko Ito
- Pharmaceutical & Medical Device Vigilance Department, Toray Industries, Inc., Tokyo, Japan
| | - Hideki Kozono
- Pharmaceutical & Medical Device Vigilance Department, Toray Industries, Inc., Tokyo, Japan
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17
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Takahashi S, Tanaka M, Higashiura Y, Mori K, Hanawa N, Ohnishi H, Furuhashi M. Prediction and validation of nonalcoholic fatty liver disease by fatty liver index in a Japanese population. Endocr J 2022; 69:463-471. [PMID: 34803123 DOI: 10.1507/endocrj.ej21-0563] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Fatty liver index (FLI) calculated by using body mass index (BMI), waist circumference and levels of γ-glutamyl transferase and triglycerides is a non-invasive predictor of nonalcoholic fatty liver disease (NAFLD). The original study in Italy showed that the cutoff level for prediction of NAFLD was FLI ≥60. However, the sex difference in FLI was not taken into consideration, and it is unclear whether the cutoff value can be applied to other races. We investigated the cutoff value of FLI for prediction of NAFLD determined by abdominal ultrasonography using receiver operating characteristic curve analyses in 14,471 Japanese subjects (men/women: 9,240/5,231; mean age: 48 ± 9 years). There was a significant interaction between sex and FLI for detection of NAFLD (p < 0.001). The cutoff values of FLI in men and women were 35.1 (area under the curve [AUC]: 0.82) and 15.6 (AUC: 0.91), respectively. When the subjects were divided by the absence and presence of obesity (BMI ≥25), there was a significant interaction between FLI and obesity for detection of NAFLD in women (p < 0.001) but not in men (p = 0.679). The cutoff values of FLI in non-obese/obese men and women were 22.6/52.6 and 11.2/33.2, respectively. In conclusion, the cutoff value of FLI for prediction of NAFLD in Japanese individuals was lower than that in the original study, and there is a significant sex difference. The simple and useful cutoff values in Japanese men and women are FLI ≥35 (non-obese/obese: 23/53) and FLI ≥16 (non-obese/obese: 11/33), respectively.
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Affiliation(s)
- Satoko Takahashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Marenao Tanaka
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yukimura Higashiura
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Kazuma Mori
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Internal Medicine, Japan Self-Defense Forces Sapporo Hospital, Sapporo, Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, Sapporo, Japan
| | - Hirofumi Ohnishi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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18
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Komaki Y, Ozono Y, Nakamura K, Iwakiri H, Hasuike S, Sueta M, Miike T, Yamamoto S, Uto H, Kusumoto K, Ochiai T, Kato J, Komada N, Kuroki K, Eto T, Shigehira M, Hirono S, Nagata K, Kawakami H. Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C virus infection aged 75 years or older. BMC Gastroenterol 2022; 22:210. [PMID: 35484503 PMCID: PMC9052496 DOI: 10.1186/s12876-022-02284-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/14/2022] [Indexed: 12/31/2022] Open
Abstract
Background It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. Methods This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group. Results In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups. Conclusions Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.
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Affiliation(s)
- Yuri Komaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Yoshinori Ozono
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kenichi Nakamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hisayoshi Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Satoru Hasuike
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Mitsue Sueta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Tadashi Miike
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Shojiro Yamamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hirofumi Uto
- Department of Gastroenterology, Miyazaki Medical Center Hospital, Miyazaki, Japan
| | - Kazunori Kusumoto
- Department of Internal Medicine, Koga General Hospital, Miyazaki, Japan
| | - Toshimasa Ochiai
- Department of Internal Medicine, Koga General Hospital, Miyazaki, Japan
| | - Junya Kato
- Department of Internal Medicine, National Hospital Organization Miyakonojo Medical Center, Miyazaki, Japan
| | - Naoto Komada
- Department of Internal Medicine, National Hospital Organization Miyakonojo Medical Center, Miyazaki, Japan
| | - Kazuo Kuroki
- Department of Internal Medicine, Kushima Municipal Hospital, Miyazaki, Japan
| | - Toshiharu Eto
- Department of Internal Medicine, Kushima Municipal Hospital, Miyazaki, Japan
| | | | - Shuichi Hirono
- Department of Internal Medicine, Hirono Naika Clinic, Miyazaki, Japan
| | - Kenji Nagata
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hiroshi Kawakami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
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19
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Nakajima K, Yuno M, Tanaka K, Nakamura T. High Aspartate Aminotransferase/Alanine Aminotransferase Ratio May Be Associated with All-Cause Mortality in the Elderly: A Retrospective Cohort Study Using Artificial Intelligence and Conventional Analysis. Healthcare (Basel) 2022; 10:674. [PMID: 35455851 PMCID: PMC9029370 DOI: 10.3390/healthcare10040674] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/25/2022] [Accepted: 03/29/2022] [Indexed: 02/05/2023] Open
Abstract
Low serum alanine aminotransferase (ALT) activity and high aspartate aminotransferase (AST)/ALT ratio may be associated with high mortality in the elderly. We aimed to confirm this in an 8-year retrospective cohort study. Clinical data for 5958 people living in a city aged 67−104 years were analyzed for their relationships with all-cause mortality using artificial intelligence (AI) and conventional statistical analysis. In total, 1413 (23.7%) participants died during the study. Auto-AI analysis with five rounds of cross-validation showed that AST/ALT ratio was the third-largest contributor to mortality, following age and sex. Serum albumin concentration and body mass index were the fourth- and fifth-largest contributors. However, when serum ALT and AST were individually considered in the same model, the individual serum ALT and AST activities were the seventh- and tenth-largest contributors. Conventional survival analysis showed that ALT, AST, and AST/ALT ratio as continuous variables were all associated with mortality (adjusted hazard ratios (95% confidence intervals): 0.98 (0.97−0.99), 1.02 (1.02−1.03), and 1.46 (1.32−1.62), respectively; all p < 0.0001). In conclusion, both AI and conventional analysis suggest that of the conventional biochemical markers, high AST/ALT ratio is most closely associated with all-cause mortality in the elderly.
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Affiliation(s)
- Kei Nakajima
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka 238-8522, Japan; (M.Y.); (K.T.); (T.N.)
- Saitama Medical Center, Department of Endocrinology and Diabetes, Saitama Medical University, 1981 Kamoda, Kawagoe 350-8550, Japan
| | - Mariko Yuno
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka 238-8522, Japan; (M.Y.); (K.T.); (T.N.)
| | - Kazumi Tanaka
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka 238-8522, Japan; (M.Y.); (K.T.); (T.N.)
| | - Teiji Nakamura
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka 238-8522, Japan; (M.Y.); (K.T.); (T.N.)
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20
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Nakajima T, Karino Y, Hige S, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y, Toyota J. Aging impairs fibrosis-4 index after sustained virologic response by direct-acting antivirals in chronic hepatitis C infection. Ann Hepatol 2022; 27:100566. [PMID: 34688887 DOI: 10.1016/j.aohep.2021.100566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 09/18/2021] [Accepted: 09/27/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVES Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index. MATERIAL AND METHODS Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis. RESULTS Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index. CONCLUSIONS Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.
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Affiliation(s)
- Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan; Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan.
| | - Shuhei Hige
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | | | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Joji Toyota
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
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21
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Tanaka J, Kurisu A, Ohara M, Ouoba S, Ohisa M, Sugiyama A, Wang ML, Hiebert L, Kanto T, Akita T. Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: A simulation study. THE LANCET REGIONAL HEALTH - WESTERN PACIFIC 2022; 22:100428. [PMID: 35637862 PMCID: PMC9142742 DOI: 10.1016/j.lanwpc.2022.100428] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Background Determining the number of chronic hepatitis B (HBV) and C virus (HCV) infections is essential to assess the progress towards the World Health Organization 2030 viral hepatitis elimination goals. Using data from the Japanese National Database (NDB), we calculated the number of chronic HBV and HCV infections in 2015 and predicted the trend until 2035. Methods NDB and first-time blood donors data were used to calculate the number of chronic HBV and HCV infections in 2015. A Markov simulation was applied to predict chronic infections until 2035 using transition probabilities calculated from NDB data. Findings The total number of chronic HBV and HCV infections in 2015 in Japan was 1,905,187–2,490,873 (HCV:877,841–1,302,179, HBV:1,027,346–1,188,694), of which 923,661–1,509,347 were undiagnosed or diagnosed but not linked to care (“not engaged in care”), and 981,526 were engaged in care. Chronic HBV and HCV infections are expected to be 923,313–1,304,598 in 2030, and 739,118–1,045,884 in 2035. Compared to 2015, by 2035, the number of persons with HCV not engaged in care will decline by 59·8 – 76·1% and 86·5% for patients in care. For HBV, a 47·3 – 49·3% decrease is expected for persons not engaged in care and a decline of 26·0% for patients engaged in care. Interpretation Although the burden of HBV and HCV is expected to decrease by 2035, challenges in controlling hepatitis remain. Improved and innovative screening strategies with linkage to care for HCV cases, and a functional cure for HBV are needed. Funding Japan Ministry of Health, Labour and Welfare.
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Affiliation(s)
- Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
- Corresponding authors at: Department of Epidemiology, Infectious Disease Control and Prevention, Graduate school of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima-shi 734-8551, Japan.
| | - Akemi Kurisu
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan
- Department of Gastroenterology and Hepatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Serge Ouoba
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Masayuki Ohisa
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Michelle L. Wang
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA
| | - Lindsey Hiebert
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Coalition for Global Hepatitis Elimination, The Task Force for Global Health, Decatur, GA, USA
| | - Tatsuya Kanto
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
- Corresponding authors at: Department of Epidemiology, Infectious Disease Control and Prevention, Graduate school of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima-shi 734-8551, Japan.
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22
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Kondou H. Current management of children with hepatitis C virus mother-to-child transmission. Pediatr Int 2022; 64:e15053. [PMID: 35175674 DOI: 10.1111/ped.15053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 11/04/2021] [Indexed: 01/18/2023]
Affiliation(s)
- Hiroki Kondou
- Department of Pediatrics, Kindai University Nara Hospital, Nara, Japan
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23
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Effects of Hepatitis C Virus Elimination by Direct-Acting Antiviral Agents on the Occurrence of Oral Lichen Planus and Periodontal Pathogen Load: A Preliminary Report. Int J Dent 2021; 2021:8925879. [PMID: 34804168 PMCID: PMC8601815 DOI: 10.1155/2021/8925879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 09/21/2021] [Accepted: 10/25/2021] [Indexed: 11/18/2022] Open
Abstract
Objective The association between hepatitis C virus (HCV) and oral lichen planus (OLP) is well known, but the association with periodontal disease has been reported less often. The purpose of this study was to investigate the effects of periodontal bacteria and OLP lesions before and after HCV elimination. Subjects and Methods. The subjects were four OLP patients (mean age 72.5 years) with HCV infection. Six types of periodontal bacteria (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum) were quantified in saliva, and changes in OLP were examined before and after elimination of HCV by antiviral therapy. Biochemical blood tests also were performed. Results The total number of periodontal bacteria, the numbers of P. gingivalis, T. forsythia, T. denticola, and F. nucleatum, and the risk of presenting with the red-complex bacteria (P. gingivalis, T. forsythia, and T.denticola), leading to periodontal disease progression, decreased after HCV elimination. OLP disappeared in three of the four patients and decreased in the other after sustained virological responses (SVRs). Conclusion HCV elimination not only improved OLP lesions but also reduced the number of periodontal pathogens and the amount of red-complex periodontal pathogens.
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24
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Ko K, Akita T, Satake M, Tanaka J. Epidemiology of viral hepatitis C: Road to elimination in Japan. Glob Health Med 2021; 3:262-269. [PMID: 34782867 DOI: 10.35772/ghm.2021.01069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 06/26/2021] [Accepted: 07/26/2021] [Indexed: 12/30/2022]
Abstract
Although HCV infection was the main cause of HCC in Japan contributing 70% over two decades after its first cloning in 1989, it was markedly decreased to 49% in 2013 and expected to decrease continuously. Based on blood donor national database, the new incident cases were 0.4/100,000 person-years, the prevalence was 0.13% and the total number was 890,902-1,302,179 in 2015. Establishment of blood donor screening with anti-HCV measurement and nucleic acid test introduced by Japanese Red Cross as pioneer, high-level medical and surgical care, and the government's policy under the Basic Act on Hepatitis Control have changed its epidemiology and outbreak trend and also enforced the disruption of potential transmission cascades. HCV prevalence among the younger generation was extremely low in all regions, and the predominant age for HCC has shifted to over 60 years old population. Considering such changes, HCV induced HCC occurrence is supposed to be ultimately suppressed in the near future. However, taking into account society changes, regulating intravenous drugs users and monitoring high-risk groups such as tattoos, and men who have sex with men are indeed required in Japan. Understanding the epidemiological changes in HCV is important in assigning, modifying, and designating effective response systems. Selective or national action plans, strategic approaches, and cooperation between government sectors have a positive impact on HCV prevention and control. A dramatic decrease in total number of HCV carriers, increase in number of people treated with highly effective DAA, and subsequent high SVR indicates Japan might achieve WHO's target of HCV elimination by 2030.
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Affiliation(s)
- Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Satake
- Central Blood Institute, Japanese Red Cross Society, Tokyo, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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25
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Mizuno S, Ono S, Yasunaga H, Iwase H. Factors associated with methamphetamine use in Japanese people who died of unnatural causes: Analysis using forensic autopsy reports. Forensic Sci Int 2021; 327:110946. [PMID: 34464922 DOI: 10.1016/j.forsciint.2021.110946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 07/02/2021] [Accepted: 08/15/2021] [Indexed: 11/27/2022]
Abstract
This study aimed to examine factors related to methamphetamine use in Japanese people who died of unnatural causes. This study used a cross-sectional design. A total of 3343 forensic autopsy reports were obtained from two forensic medicine departments in the Kanto region of Japan. We classified the decedents who underwent forensic autopsies into methamphetamine/amphetamine (MA) and undetected (comparison) groups based on toxicological examination. We matched the decedents in the MA group with those in the comparison group at a 1:4 ratio based on sex and age. The variables, including gang members, criminal records, tattoos, body mass index, infections, concurrent psychotropic drug use, and cause of death, were compared between the groups. Of the 3343 decedents, we matched 109 in the MA group with 436 in the comparison group. Methamphetamine use was significantly associated with gang membership (13.8% vs. 3%, p < 0.001), criminal records unrelated to methamphetamine (47.7% vs. 13.8%, p < 0.001), tattoos (29.2% vs. 6.4%, p < 0.001), and hepatitis C virus infection (48.0% vs. 3.6%, p < 0.001). One-third of the patients in the MA group died from poisoning. This is the first study to show the physical and social characteristics associated with methamphetamine use in Japanese people who died of unnatural causes. Our results could be extended to people with methamphetamine use disorder at risk of death and enable the development of policies and practices to provide necessary intervention in a timely manner.
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Affiliation(s)
- Satomi Mizuno
- Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.
| | - Sachiko Ono
- Department of Eat-loss Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.
| | - Hirotaro Iwase
- Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan; Department of Legal Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, Chiba Prefecture 260-8670, Japan.
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26
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Doi H, Kanto T. Factors influencing the durability of hepatitis B vaccine responses. Vaccine 2021; 39:5224-5230. [PMID: 34340855 DOI: 10.1016/j.vaccine.2021.07.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 11/20/2020] [Accepted: 07/05/2021] [Indexed: 12/15/2022]
Abstract
The World Health Organization recommends the implementation of universal hepatitis B (HB) vaccination, and global coverage for this vaccine reached 84% in 2015. In Japan, the policy aimed at preventing mother-to-child transmission of HB virus (HBV) initially commenced as a specific vaccination program for infants born to mothers who were positive for HB surface antigen. In 2016, universal HB vaccination was implemented in this country to cover unvaccinated individuals at risk of horizontal HBV transmission. Although HB vaccination has been shown to be highly efficacious and safe, the issues of vaccine non-responders and of the loss of antibodies directed against HB surface antigen (anti-HBs) in HB vaccine recipients remain. To gain better insight into these problems, we previously performed an immunological analysis on adult vaccine recipients after they received an initial HB vaccination. We found that the course of successful HB vaccination is composed of the following distinct phases: 1) acquisition of anti-HBs antibody, 2) attainment of high anti-HBs antibody titers, and 3) maintenance of acquired anti-HBs antibody levels. In this review, we describe the significance of HB vaccination and suggest a potential means of improving the impact of HB vaccination based on our immunological analysis.
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Affiliation(s)
- Hiroyoshi Doi
- Department of Gastroenterology and Hepatology, Shin-yurigaoka General Hospital, 255 Furusawa Asao-ku, Kawasaki, Kanagawa 215-0026, Japan; The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Konodai, Ichikawa, Chiba 272-8516, Japan; Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
| | - Tatsuya Kanto
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Konodai, Ichikawa, Chiba 272-8516, Japan.
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27
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Higashiura Y, Furuhashi M, Tanaka M, Takahashi S, Mori K, Miyamori D, Koyama M, Ohnishi H, Moniwa N, Numata K, Hisasue T, Hanawa N, Miura T. Elevated Fatty Liver Index Is Independently Associated With New Onset of Hypertension During a 10-Year Period in Both Male and Female Subjects. J Am Heart Assoc 2021; 10:e021430. [PMID: 34259033 PMCID: PMC8483452 DOI: 10.1161/jaha.121.021430] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. Because of a sex difference in FLI level, we hypothesized that FLI is associated with development of hypertension to a greater extent in men or women. Methods and Results We investigated the relationship between FLI and development of hypertension during a 10‐year period in a general population of subjects who received annual health examinations (n=28 990). After exclusion (44.9%) of subjects with missing data and those with hypertension at baseline, a total of 15 965 subjects (men/women: 9466/6499) were included. FLI level was significantly higher in men than in women. During the 10‐year period, 2304 men (24.3%) and 745 women (11.5%) had new onset of hypertension. Multivariable Cox proportional hazard models with a restricted cubic spline showed that the hazard ratios (HRs) for development of hypertension after adjustment of age, systolic blood pressure, estimated glomerular filtration rate, habits of smoking and alcohol drinking, family history of hypertension, and diagnosis of diabetes mellitus and dyslipidemia increased gradually with increase in FLI in men and increased rapidly and then slowly with increase in FLI in women. There was a significant interaction between FLI and sex for the risk of hypertension in all of the subjects (P=0.049). The addition of FLI to traditional risk factors significantly improved the discriminatory capability. Conclusions A high level of FLI predicts the development of hypertension in both men and women, although distribution patterns of HRs were different between sexes.
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Affiliation(s)
- Yukimura Higashiura
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Marenao Tanaka
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Satoko Takahashi
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Kazuma Mori
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Daisuke Miyamori
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Masayuki Koyama
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan.,Department of Public Health Sapporo Medical University School of Medicine Sapporo Japan
| | - Hirofumi Ohnishi
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan.,Department of Public Health Sapporo Medical University School of Medicine Sapporo Japan
| | - Norihito Moniwa
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Keita Numata
- Department of Health Checkup and Promotion Keijinkai Maruyama Clinic Sapporo Japan
| | - Takashi Hisasue
- Department of Health Checkup and Promotion Keijinkai Maruyama Clinic Sapporo Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion Keijinkai Maruyama Clinic Sapporo Japan
| | - Tetsuji Miura
- Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine Sapporo Japan
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28
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Sato S, Amano N, Sato S, Kita Y, Ikeda Y, Kabemura D, Murata A, Yatagai N, Tsuzura H, Shimada Y, Genda T. Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis. Hepatol Res 2021; 51:786-795. [PMID: 33964118 DOI: 10.1111/hepr.13651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/23/2021] [Accepted: 05/03/2021] [Indexed: 12/14/2022]
Abstract
AIM Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. METHODS This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation. RESULTS Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA-to-tyrosine ratio for 114 patients (72.2%). During a median follow-up period of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis showed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110 µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15-3.11, p = 0.012). Kaplan-Meier analysis showed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p < 0.001). CONCLUSIONS Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA-to-tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.
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Affiliation(s)
- Sho Sato
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Nozomi Amano
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Shunsuke Sato
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Yuji Kita
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Yuji Ikeda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Daishi Kabemura
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Ayato Murata
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Noboru Yatagai
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Hironori Tsuzura
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Yuji Shimada
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
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High level of fatty liver index predicts new onset of diabetes mellitus during a 10-year period in healthy subjects. Sci Rep 2021; 11:12830. [PMID: 34145341 PMCID: PMC8213804 DOI: 10.1038/s41598-021-92292-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023] Open
Abstract
Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. This study aimed to evaluate the relationship between FLI and new onset of diabetes mellitus (DM). We investigated the association of FLI with new onset of DM during a 10-year period in subjects who received annual health examinations (n = 28,990). After exclusion of subjects with DM at baseline and those with missing data, a total of 12,290 subjects (male/female: 7925/4365) who received health examinations were recruited. FLI was significantly higher in males than in females. During the 10-year period, DM was developed in 533 males (6.7%) and 128 females (2.9%). Multivariable Cox proportional hazard models with a restricted cubic spline showed that the risk of new onset of DM increased with a higher FLI at baseline in both sexes after adjustment of age, fasting plasma glucose, habits of alcohol drinking and current smoking, family history of DM and diagnosis of hypertension and dyslipidemia at baseline. When the subjects were divided into subgroups according to tertiles of FLI level at baseline (T1–T3) in the absence and presence of impaired fasting glucose (IFG), hazard ratios after adjustment of the confounders gradually increased from T1 to T3 and from the absence to presence of IFG in both male and female subjects. In conclusion, a high level of FLI predicts new onset of DM in a general population of both male and female individuals.
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Miyoshi T, Hamaguchi M, Kitagawa N, Hashimoto Y, Fukui M. Correlation between Liver Stiffness by Two-Dimensional Shear Wave Elastography and Waist Circumference in Japanese Local Citizens with Abdominal Obesity. J Clin Med 2021; 10:jcm10091971. [PMID: 34064337 PMCID: PMC8125660 DOI: 10.3390/jcm10091971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/23/2021] [Accepted: 04/30/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Various factors other than fibrosis could affect liver stiffness (LS), measured by two-dimensional shear wave elastography (2D-SWE). We aimed to clarify the factors affecting LS in local citizens. Methods: We performed a cross-sectional study among local citizens of a health checkup program. Abdominal obesity was defined as waist circumference ≥85 cm for men and ≥90 cm for women. We evaluated the correlation between LS by 2D-SWE (Aplio 500) and waist circumference with linear regression analyses. We selected the following items as variables in the multivariate analysis: waist circumference, sex, hypertension, diabetes, diagnostic components of metabolic syndrome, γ−glutamyl transpeptidase, total bilirubin, NAFLD fibrosis score, and an indicator of a fatty liver, evaluated ultrasonographically. Results: Overall, 345 individuals were included; 318 (181 men and 137 women; age, 63.4 years; waist circumference, 84.0 cm; LS, 5.79 kPa) were analyzed, 128 of whom had abdominal obesity and significantly higher LS than non-abdominally obese individuals. In the multivariate analysis, waist circumference was positively, independently, and significantly correlated with LS only in abdominally obese individuals. Conclusions: Liver stiffness by 2D-SWE could increase with increases in waist circumference in local citizens with abdominal obesity. Physicians should pay attention when assessing the LS of abdominally obese individuals.
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Affiliation(s)
- Tomoki Miyoshi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
- Correspondence: ; Tel.: +81-75-251-5506
| | - Noriyuki Kitagawa
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka 621-8585, Japan;
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
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31
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Okushin K, Suzuki R, Tsutsumi T, Okamoto K, Ikeuchi K, Kado A, Minatsuki C, Minami-Kobayashi Y, Satoh N, Ikeda M, Harada S, Enooku K, Fujinaga H, Yotsuyanagi H, Koike K, Moriya K. Change in hepatitis C virus positivity among needle-stick injury source patients: a 10-year experience in a Japanese tertiary hospital. BMC Infect Dis 2021; 21:399. [PMID: 33931015 PMCID: PMC8086119 DOI: 10.1186/s12879-021-06117-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/23/2021] [Indexed: 12/03/2022] Open
Abstract
Background As a blood-borne pathogen, hepatitis C virus (HCV) has long been a major threat associated with needle-stick injuries (NSIs) mainly because no vaccine is available for HCV. Following an NSI, we usually test the source patient for HCV antibody (HCV-Ab). Since HCV-Ab positivity does not necessarily indicate current infection, HCV RNA is further examined in patients positive for HCV-Ab. Direct-acting antivirals (DAAs) have enabled us to treat most HCV-infected patients; therefore, we speculate that the rate of HCV RNA positivity among HCV-Ab-positive patients decreased after the emergence of DAAs. This cross-sectional study was performed to investigate the change in the actual HCV RNA positivity rate in source patients before and after the interferon (IFN)-free DAA era. Methods This was a cross-sectional study of NSI source patients at a tertiary academic hospital in Japan from 2009 to 2019. IFN-free DAA regimens were first introduced in Japan in 2014. Accordingly, we compared HCV status of NSI source patients that occurred between 2009 and 2014 (the era before IFN-free DAAs) with those that occurred between 2015 and 2019 (the era of IFN-free DAAs) in a tertiary care hospital in Japan. Results In total, 1435 NSIs occurred, and 150 HCV-Ab-positive patients were analyzed. The proportion of HCV RNA-positive patients significantly changed from 2009 through 2019 (p = 0.005, Cochran–Armitage test). Between 2009 and 2014, 102 source patients were HCV-Ab-positive, 78 of whom were also positive for HCV RNA (76.5%; 95%CI, 67.4–83.6%). Between 2015 and 2019, 48 patients were HCV-Ab-positive, 23 of whom were also positive for HCV RNA (47.9%; 95%CI, 34.5–61.7%; p = 0.0007 compared with 2009–2014). In the era of IFN-free DAAs, 9 of 23 HCV RNA-negative patients (39.1%) and 2 of 22 HCV RNA-positive patients (9.1%) were treated with an IFN-free combination of DAAs (p = 0.0351). Regarding the departments where NSIs occurred, HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs (p = 0.0078, compared with 2009–2014). Conclusions Actual HCV RNA positivity in source patients of NSIs decreased after the emergence of IFN-free DAAs. IFN-free DAAs might have contributed to this reduction, and HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06117-4.
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Affiliation(s)
- Kazuya Okushin
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Rie Suzuki
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Koh Okamoto
- Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Ikeuchi
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.,Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Akira Kado
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Chihiro Minatsuki
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuka Minami-Kobayashi
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhiko Satoh
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Mahoko Ikeda
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.,Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sohei Harada
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.,Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kyoji Moriya
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. .,Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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Kuroda R, Nogawa K, Watanabe Y, Morimoto H, Sakata K, Suwazono Y. Association between High-Sensitive C-Reactive Protein and the Development of Liver Damage in Japanese Male Workers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18062985. [PMID: 33799436 PMCID: PMC7998110 DOI: 10.3390/ijerph18062985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND The aim of this study was to determine whether a causative relationship exists between the development of liver damage and increased high-sensitivity C-reactive protein (HsCRP) levels by long-term follow-up in Japanese workers. METHODS The target participants comprised 7830 male workers in a Japanese steel company. The prospective cohort study was performed over a 6-year period, and annual health screening information was analyzed by pooled logistic regression. The endpoint, regarded as the development of liver damage, was defined as aspartate aminotransferase (AST) ≥ 40 IU/L. RESULTS A significant relationship between the development of liver damage and increased HsCRP levels was observed after adjusting for confounding factors such as various physiological and blood chemistry parameters and lifestyle factors. The odds ratio of a 1.5-fold increase in HsCRP was 1.07 (95% confidence interval: 1.03-1.10, p < 0.001). CONCLUSIONS The results suggested that an increase of HsCRP is associated with the development of liver damage.
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Affiliation(s)
- Reiko Kuroda
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
- Division for Environment, Health and Safety, The University of Tokyo, Tokyo 113-8654, Japan
| | - Kazuhiro Nogawa
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Yuuka Watanabe
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Hideki Morimoto
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Kouichi Sakata
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Yasushi Suwazono
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
- Correspondence: ; Tel.: +81-43-226-2065
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Kanbe A, Ishikawa T, Hara A, Suemizu H, Nanizawa E, Tamaki Y, Ito H. Novel hepatitis B virus infection mouse model using herpes simplex virus type 1 thymidine kinase transgenic mice. J Gastroenterol Hepatol 2021; 36:782-789. [PMID: 32515517 DOI: 10.1111/jgh.15142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 04/24/2020] [Accepted: 06/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV-specific immune responses that cannot eliminate or cure the infected hepatocytes efficiently. Previous studies have used immunodeficient mice such as herpes simplex virus type 1 thymidine kinase NOD/Scid/IL2Rrnull (HSV-TK-NOG) mice. However, it is difficult to analyze the immune response in the previous models. In the present study, we established a novel HBV infection model using herpes simplex virus type 1 thymidine kinase (HSV-TK) mice in which the host immune system was not impaired. METHODS Herpes simplex virus type 1 thymidine kinase mice were injected intraperitoneally with ganciclovir (GCV). Seven days after GCV injection, GCV-treated mice were transplanted with 1 × 106 hepatocytes from HBV-transgenic (HBV-Tg) mice. RESULTS Serum alanine aminotransferase levels in HSV-TK mice increased 1 and 2 weeks after GCV injection. The number and viability of hepatocytes from the whole liver of HBV-Tg mice significantly increased using digestion medium containing liberase. Hepatitis B surface antigen (HBsAg)-positive areas in the liver tissue were observed for at least 20 weeks after HBsAg-positive hepatocyte transplantation. In addition, we measured HBsAg in the serum after transplantation. HBsAg levels in HBV-Tg hepatocyte-replaced mice increased 4 weeks after transplantation. Furthermore, we examined the immune response in HSV-TK mice. The increase in hepatitis B surface antibody levels in replaced mice was maintained for 20 weeks. Also, interferon-γ-producing cells were increased in non-replaced mice. CONCLUSIONS A novel HBV infection mouse model will help to understand the mechanisms of HBV tolerance similar to human chronic HBV-infected patients and can be used to develop a new strategy to treat chronic HBV infection.
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Affiliation(s)
- Ayumu Kanbe
- Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Tetsuya Ishikawa
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akira Hara
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Hiroshi Suemizu
- Department of Laboratory Animal Research, Central Institute for Experimental Animals, Kawasaki, Japan
| | - Eri Nanizawa
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuki Tamaki
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroyasu Ito
- Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu City, Japan
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Nakajima T, Karino Y, Hige S, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y, Hasegawa T, Toyota J. Factors affecting the recovery of hepatic reserve after sustained virologic response by direct-acting antiviral agents in chronic hepatitis C virus-infected patients. J Gastroenterol Hepatol 2021; 36:367-375. [PMID: 32991760 DOI: 10.1111/jgh.15280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 09/12/2020] [Accepted: 09/21/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve. METHODS We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69 years) for at least 3 years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin-bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography. RESULTS At the start of treatment, the albumin-bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3 years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P < 0.0138), male sex (HR: 3.45, P = 0.0143), hemoglobin level of <11.5 g/dL (HR: 4.19, P = 0.0157), the presence of a portosystemic shunt (HR: 3.07, P = 0.0349), and alanine aminotransferase levels <45 U/L (HR: 2.67, P = 0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor. CONCLUSION Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time.
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Affiliation(s)
- Tomoaki Nakajima
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan.,Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan
| | - Shuhei Hige
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | | | - Tomohiro Arakawa
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Ysuaki Kuwata
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Takashi Hasegawa
- Department of Radiology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Joji Toyota
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
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Taniguchi H, Iwasaki Y, Aimi M, Shimazaki G, Moriya A. Clinical features of chronic hepatitis B patients with low hepatitis B surface antigen levels and determinants of hepatitis B surface antigen seroclearance. JGH Open 2020; 4:698-706. [PMID: 32782959 PMCID: PMC7411555 DOI: 10.1002/jgh3.12321] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 02/22/2020] [Accepted: 02/25/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM A low hepatitis B surface antigen (HBsAg) level is reported to be predictive of future HBsAg seroclearance. A hospital-based cohort study was conducted to clarify the clinical features of patients with low HBsAg levels and to demonstrate the usefulness of low HBsAg levels for predicting HBsAg seroclearance. METHODS A total of 1459 patients with chronic hepatitis B were included in the study. Of these, 587 had repeated measurements for HBsAg levels and two or more records of HBsAg-positive results. HBsAg levels were measured with a commercially available HBsAg assay. Based on a cut-off index (COI) of 2000, a high HBsAg level was defined as HBsAg ≥2000 COI, and a low HBsAg level was defined as HBsAg <2000 COI. RESULTS The proportion of patients with low HBsAg levels at baseline tended to increase with age. Patients with low HBsAg levels at baseline had significantly older age, lower transaminase levels, and lower hepatitis B virus (HBV) DNA levels than those with high HBsAg levels. The annual HBsAg seroclearance rate was 1.30%/year. The cumulative incidences of HBsAg seroclearance differed significantly by HBsAg level at baseline (<2000 vs ≥2000 COI), age (≥50 vs <50 years), and HBV DNA level (<4.0 vs ≥4.0 log copies/mL). Cox proportional hazards regression analyses showed that low HBsAg level (<2000 COI) and low HBV DNA level (<4.0 log copies/mL) were significantly associated with HBsAg seroclearance. CONCLUSION Aging was one of the factors affecting HBsAg level. HBsAg seroclearance was significantly associated with low HBsAg level and low HBV DNA level at baseline.
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Affiliation(s)
| | | | - Masahito Aimi
- Internal MedicineTottori Municipal HospitalTottoriJapan
| | | | - Akio Moriya
- GastroenterologyMitoyo General HospitalJapan
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Nagai K, Ide K, Kawasaki Y, Tanaka-Mizuno S, Seto K, Iwane S, Eguchi Y, Kawakami K. Estimating the cost-effectiveness of screening for hepatitis C virus infection in Japan. Hepatol Res 2020; 50:542-556. [PMID: 31899841 DOI: 10.1111/hepr.13478] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 11/28/2019] [Accepted: 12/04/2019] [Indexed: 01/15/2023]
Abstract
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.
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Affiliation(s)
- Kota Nagai
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.,Eisai Co., Ltd., Tokyo, Japan
| | - Kazuki Ide
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.,Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
| | - Yohei Kawasaki
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | | | - Kahori Seto
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan
| | - Shinji Iwane
- Liver Center, Saga University Hospital, Saga, Japan
| | | | - Koji Kawakami
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.,Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
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Hamaguchi M, Obora A, Okamura T, Hashimoto Y, Kojima T, Fukui M. Changes in metabolic complications in patients with alcoholic fatty liver disease monitored over two decades: NAGALA study. BMJ Open Gastroenterol 2020; 7:e000359. [PMID: 32337056 PMCID: PMC7170409 DOI: 10.1136/bmjgast-2019-000359] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 03/05/2020] [Accepted: 03/12/2020] [Indexed: 12/17/2022] Open
Abstract
Objective The social conditions are changing in the world, which may contribute to the change in lifestyle, including alcohol consumption and dietary intake; however, changes in metabolic complications in patients with alcoholic fatty liver disease (AFLD) have never been reported. Therefore, here we compare the metabolic complications in current AFLD with those of two decades ago. Methods We performed this cross-sectional study in a Japanese health check-up centre. Consecutive participants who visited the facilities between June 1994 and December 1997 or between January 2014 and December 2017 were enrolled. A total of 7499 participants (4804 men, 2695 women) in the past cohort and 20 029 participants (11 676 men, 8353 women) in the current cohort were entered to this study. Results The prevalence of drinkers in the current cohort was significantly lower (4.7%) than that in the past cohort in men (5.9%, p<0.001) but significantly higher in women (1.9% in the current vs 1.1% in the past, p<0.001). The prevalence of fatty liver in drinkers has increased in men (22.3% in the past cohort, 36.6% in the current cohort; p<0.001) but not in women (13.3% in the past cohort, 14.7% in the current cohort; p=1.0), while the prevalence of all fatty liver has increased in men and women (men: 24.0% in the past cohort, 36.2% in the current cohort, p<0.001; women: 9.3% in the past cohort, 12.8% in the current cohort, p<0.001). Regarding metabolic abnormalities, the prevalence of hyperglycaemia increased from 25.4% to 43.0% in men with AFLD (p<0.001) and from 25.1% to 39.1% in women with AFLD (p=1.0). Conclusions AFLD currently tends to be accompanied by hyperglycaemia. The prevalence of fatty liver in drinkers increased in men, although alcoholic consumptions did not increase. We should pay attention to fatty liver combined with hyperglycaemia for individuals who consume alcohol today.
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Affiliation(s)
- Masahide Hamaguchi
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akihiro Obora
- Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Takuro Okamura
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshitaka Hashimoto
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takao Kojima
- Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Michiaki Fukui
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Ujiie I, Ujiie H, Yoshimoto N, Iwata H, Shimizu H. Prevalence of infectious diseases in patients with autoimmune blistering diseases. J Dermatol 2020; 47:378-384. [PMID: 32043652 DOI: 10.1111/1346-8138.15244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/05/2020] [Indexed: 01/10/2023]
Abstract
A long-term immunosuppressive treatment can provoke latent infections. Autoimmune blistering diseases (AIBD) are mostly treated with systemic immunosuppressive agents. To prevent the reactivation or exacerbation of existing latent infections, patients must be screened for infectious diseases before immunosuppressive treatments are initiated. However, the prevalence of infectious diseases in AIBD remains to be elucidated. To evaluate the necessity of screening infectious diseases in AIBD, we retrospectively reviewed the clinical records of 215 patients at a single center with AIBD for hepatitis B virus (HBV), hepatitis C virus (HCV), Mycobacterium tuberculosis, Treponema pallidum, human T-cell leukemia virus type 1 (HTLV-1) and HIV infections. Approximately 40% of patients were infected with HBV. During systemic corticosteroid treatment, HBV DNA became positive in 3.4% of cases. Antibodies to HCV, interferon-γ release assays for M. tuberculosis and the T. pallidum latex agglutination test were positive in 0.6%, 6.6% and 1.2% cases, respectively. Neither HTLV-1 nor HIV infections were detected. In conclusion, checks for HBV and M. tuberculosis infections should be made before immunosuppressive treatments are started, because of the high prevalence of these potentially life-threatening infections. Other infections should be tested for depending on the patient's risk factors.
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Affiliation(s)
- Inkin Ujiie
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hideyuki Ujiie
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Norihiro Yoshimoto
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hiroaki Iwata
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hiroshi Shimizu
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Sarin SK, Kumar M, Eslam M, George J, Al Mahtab M, Akbar SMF, Jia J, Tian Q, Aggarwal R, Muljono DH, Omata M, Ooka Y, Han KH, Lee HW, Jafri W, Butt AS, Chong CH, Lim SG, Pwu RF, Chen DS. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol 2020; 5:167-228. [PMID: 31852635 PMCID: PMC7164809 DOI: 10.1016/s2468-1253(19)30342-5] [Citation(s) in RCA: 363] [Impact Index Per Article: 72.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 07/20/2019] [Accepted: 08/02/2019] [Indexed: 02/06/2023]
Abstract
The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.
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Affiliation(s)
- Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Mohammed Eslam
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, Australia
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sheikh M Fazle Akbar
- Department of Pathology, Ehime University Proteo-Science Center, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Qiuju Tian
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | | | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan; University of Tokyo, Tokyo, Japan
| | - Yoshihiko Ooka
- Department of Gastroenterology, Chiba University Hospital, Chiba, Japan
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Wasim Jafri
- Department of Medicine, Section of Gastroenterology, The Aga Khan University, Karachi, Pakistan
| | - Amna S Butt
- Department of Medicine, Section of Gastroenterology, The Aga Khan University, Karachi, Pakistan
| | - Chern H Chong
- Division of Gastroenterology & Hepatology, National University Health System, Singapore; Division of General Medicine, Woodlands Health Campus, Singapore
| | - Seng G Lim
- Division of Gastroenterology & Hepatology, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Raoh-Fang Pwu
- National Hepatitis C Program Office, Ministry of Health and Welfare, Taipei, Taiwan
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
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Isoda H, Oeda S, Takamori A, Sato K, Okada M, Iwane S, Takahashi H, Anzai K, Eguchi Y, Fujimoto K. Generation Gap for Screening and Treatment of Hepatitis C Virus in Saga Prefecture, Japan: An Administrative Database Study of 35,625 Subjects. Intern Med 2020; 59:169-174. [PMID: 31534084 PMCID: PMC7008045 DOI: 10.2169/internalmedicine.3248-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
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.
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Affiliation(s)
- Hiroshi Isoda
- Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
- Liver Center, Saga University Hospital, Japan
| | | | - Ayako Takamori
- Division of Clinical Research Center, Saga University Hospital, Japan
| | - Keiko Sato
- Division of Clinical Research Center, Saga University Hospital, Japan
| | - Michiaki Okada
- Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | | | - Hirokazu Takahashi
- Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Keizo Anzai
- Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | | | - Kazuma Fujimoto
- International University of Health and Welfare, Faculty of Medicine, Japan
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A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan. Adv Ther 2020; 37:457-476. [PMID: 31808054 DOI: 10.1007/s12325-019-01166-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The objective of the study was to evaluate the cost-effectiveness of glecaprevir/pibrentasvir versus other direct-acting antivirals (DAAs) for treating chronic hepatitis C virus (HCV) infections in Japan. METHODS We developed a health state transition model to capture the natural history of HCV. A cost-effectiveness analysis of DAAs from the perspective of a public healthcare payer in Japan with a lifetime horizon over annual cycles was performed. Treatment attributes, baseline demographics, transition probabilities, health-state utilities, and costs data were extracted from publications. Costs and outcomes were discounted at 2% per annum. In the base case we focused on genotype 1 (GT1) treatment-naïve patients without cirrhosis. The scenario analysis examined a pan-genotype treatment in GT1-3 (i.e., portfolio), treatment-naïve, and treatment-experienced patients. The portfolio cost-effectiveness of DAAs was derived by calculating a weighted average of patient segments defined by treatment history, cirrhosis status, and genotype. RESULTS The base case results indicated that glecaprevir/pibrentasvir was dominant (i.e., generating higher quality-adjusted life years [QALYs] and lower lifetime costs) compared to all other DAAs. The predicted lifetime risk of hepatocellular carcinoma was 3.66% for glecaprevir/pibrentasvir and sofosbuvir/ledipasvir, 4.99% for elbasvir/grazoprevir, and 5.27% for daclatasvir/asunaprevir/beclabuvir. In scenario analysis the glecaprevir/pibrentasvir (GLE/PIB) portfolio dominated the sofosbuvir (SOF)-based portfolio (namely sofosbuvir/ledipasvir in GT1-2 and sofosbuvir + ribavirin in GT3). The base case probabilistic sensitivity analysis (PSA) showed that glecaprevir/pibrentasvir was cost-effective in 93.4% of the simulations for a willingness-to-pay/QALY range of Japanese yen (JPY) 1.6-20 million. The PSA for the portfolio scenario indicated that the GLE/PIB portfolio was cost-effective in 100% of simulations until the willingness-to-pay/QALY reached JPY 5.2 million; this proportion decreased to 69.4% at a willingness-to-pay/QALY of JPY 20 million. Results were also robust in deterministic sensitivity analyses. CONCLUSION In GT1 treatment-naïve non-cirrhotic patients GLE/PIB was a cost-effective strategy compared to other DAAs. When a pan-genotypic framework was used, the GLE/PIB portfolio dominated the SOF-based portfolio.
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Kunishima H, Yoshida E, Caputo J, Mikamo H. Estimating the national cost burden of in-hospital needlestick injuries among healthcare workers in Japan. PLoS One 2019; 14:e0224142. [PMID: 31697746 PMCID: PMC6837393 DOI: 10.1371/journal.pone.0224142] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 10/07/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Needlestick injury (NSI) is one of the most burdensome professional hazards in any medical setting; it can lead to transmission of fatal infectious diseases, such as hepatitis B, hepatitis C and human immunodeficiency virus. In the United States, the annual cost burden was estimated as somewhere between $118 million to $591 million; in the United Kingdom it is approximated to be £500,000 (US$919,117.65) per the National Health Service. METHOD This is the first published paper on the national cost burden of NSIs in Japan. A systematic literature review was conducted to review previous study design in global studies and to extract parameter values from Japanese studies. We conducted abstract searches through PubMed and the Japan Medical Abstracts Society (Ichushi), together with grey literature and snowball searches. A simple economic model was developed to calculate cost burden of NSIs from a societal perspective over a one-year time horizon. We assumed all NSIs are reported and perfect adherence in post NSI management that presented in the labour compensation scheme. Local guidelines were also referenced to extract resource utilization. Lastly, a deterministic sensitivity analysis was conducted and a scenario analysis which considered a payer perspective was also included. RESULT AND CONCLUSION The national cost burden of in-hospital NSIs is estimated as ¥33.4 billion (US$302 million) annually, based on an average cost per NSI of ¥63,711 (US$577) and number of NSIs at 525,000/year. 70% of the cost is due to initial laboratory tests, followed by productivity loss, estimated at 20% of the total cost. Cost of contaminated NSIs remains at 5% of the total cost. Change in number of NSIs significantly influences outcomes. Variation in post-exposure management practices suggests a need for NSI specific National guidelines and holistic labour compensation scheme development in Japan.
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Affiliation(s)
- Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University, Kanagawa, Japan
| | | | - Joe Caputo
- Vista Health Pte. Ltd., Singapore, Singapore
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University, Aichi, Japan
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Nagao Y, Tanigawa T. Red complex periodontal pathogens are risk factors for liver cirrhosis. Biomed Rep 2019; 11:199-206. [PMID: 31632667 PMCID: PMC6792321 DOI: 10.3892/br.2019.1245] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 09/23/2019] [Indexed: 12/13/2022] Open
Abstract
Periodontal disease has been associated with liver disease; however, the identities of the periodontal disease-causing bacteria in patients with viral liver disease remain unknown. The aim of the present study was to determine the counts of the 3 periodontal pathogens that form the red complex in chronic periodontitis (Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and 3 other bacteria (Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Fusobacterium necrophorum) in patients with liver disease. A total of 47 patients with liver disease were divided into two groups based on the counts of the red complex bacteria: group A (high counts of red complex bacteria) and group B (low counts of red complex bacteria). The counts of the 6 types of bacteria in saliva and the prevalence of P. gingivalis-specific fimA genotype were determined. In addition, salivary occult blood tests and serological assays were performed. Univariate and multivariate logistic regression analyses were used to analyze the risk factors between the two groups of patients. Hepatitis C virus-related liver disease was the most frequent (41/47; 87.2%) occurrence followed by liver cirrhosis (LC; 12/47; 25.5%) and oral lichen planus (32/47; 68.1%). The significant risk factors between the two groups were LC, albumin (Alb) level, ratios of each bacteria and prevalence of the fimA II genotype. The 3 factors identified in the multivariate analysis to be associated with the red complex bacteria count were low Alb level (<3.7 g/dl), LC and fimA II genotype, with adjusted odds ratios of 6.93, 4.72 and 4.08, respectively (P<0.05). These data indicated that patients with LC were at increased risk of presenting with the red complex bacteria leading to periodontal disease progression. Therefore, these patients may need to take additional care of their oral health compared with patients without LC, which may prove beneficial for the maintenance of their general health.
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Affiliation(s)
- Yumiko Nagao
- Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan.,Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan
| | - Takeshi Tanigawa
- Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
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Kumagi T, Terao T, Yokota T, Azemoto N, Kuroda T, Imamura Y, Uesugi K, Kisaka Y, Tanaka Y, Shibata N, Koizumi M, Ohno Y, Yukimoto A, Tange K, Nishiyama M, Kanemitsu K, Miyake T, Miyata H, Ishii H, Hiasa Y. Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance. Mayo Clin Proc 2019; 94:2004-2010. [PMID: 31262521 DOI: 10.1016/j.mayocp.2018.12.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 12/06/2018] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To evaluate whether patients with hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC). PATIENTS AND METHODS We retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ2 test. RESULTS The UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease. CONCLUSION Patients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.
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Affiliation(s)
- Teru Kumagi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
| | - Takashi Terao
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan; Department of Gastroenterology, Shikoku National Cancer Center, Matsuyama, Japan
| | - Tomoyuki Yokota
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Nobuaki Azemoto
- Department of Gastroenterology, Shikoku National Cancer Center, Matsuyama, Japan; Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Taira Kuroda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoshiki Imamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kazuhiro Uesugi
- Department of Gastroenterology, Shikoku National Cancer Center, Matsuyama, Japan; Department of Gastroenterology, Uwajima Municipal Hospital, Uwajima, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima Municipal Hospital, Uwajima, Japan; Department of Gastroenterology, Matsuyama Shimin Hospital, Matsuyama, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, Matsuyama, Japan
| | - Naozumi Shibata
- Department of Internal Medicine, Niihama Prefectural Hospital, Niihama, Japan
| | - Mitsuhito Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoshinori Ohno
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan; Department of Gastroenterology, Uwajima Municipal Hospital, Uwajima, Japan
| | - Kazuhiro Tange
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan; Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Mari Nishiyama
- Department of Gastroenterology, Matsuyama Shimin Hospital, Matsuyama, Japan
| | - Kozue Kanemitsu
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan; Department of Gastroenterology, Uwajima Municipal Hospital, Uwajima, Japan
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hideki Miyata
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Hiroshi Ishii
- Department of Gastroenterology, Shikoku National Cancer Center, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
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Tanaka J, Akita T, Ko K, Miura Y, Satake M, Epidemiological Research Group on Viral Hepatitis and its Long ‐term Course, Ministry of Health, Labour and Welfare of Japan. Countermeasures against viral hepatitis B and C in Japan: An epidemiological point of view. Hepatol Res 2019; 49:990-1002. [PMID: 31364248 PMCID: PMC6852166 DOI: 10.1111/hepr.13417] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 07/01/2019] [Accepted: 07/23/2019] [Indexed: 12/12/2022]
Abstract
Although the mortality rate due to hepatocellular carcinoma (HCC) has been gradually decreasing in Japan, approximately 30 000 people died of HCC in 2016. In 2007, the dominant etiology was persistent hepatitis C virus (HCV) infection, which accounted for 65% of total HCC deaths, and 15% of cases were due to chronic hepatitis B virus (HBV) infection. In managing chronic HBV and HCV infection, it is critically important to know the exact number of infected individuals in a particular country, which then assists in evaluating medical and financial needs in the foreseeable future. Therefore, from an epidemiological perspective, we estimated the numbers of HBV and HCV carriers in four categories: (i) undiagnosed carriers; (ii) carriers who were already hospitalized as patients or were receiving outpatient medical attention; (iii) diagnosed carriers who had not consulted any medical facility, or had discontinued consultation; and (iv) newly infected carriers. From these estimates we determined the current HBV and HCV burden and then reviewed the existing countermeasures for their prevention and control in Japan. While continuing the surveillance on the dynamics of hepatitis virus infections linked with preventive measures against hepatitis virus infection, it is crucially important to promote appropriate measures for each of the four groups of hepatitis virus carriers in society.
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Affiliation(s)
- Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health SciencesHiroshima UniversityJapan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health SciencesHiroshima UniversityJapan
| | - Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health SciencesHiroshima UniversityJapan
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The course of elderly patients with persistent hepatitis C virus infection without hepatocellular carcinoma. J Gastroenterol 2019; 54:829-836. [PMID: 31161311 DOI: 10.1007/s00535-019-01595-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/27/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Little is known about the course of elderly patients with persistent hepatitis C virus (HCV) infection. We investigated the course of HCV infection in this patient population. METHODS Among 9,126 HCV antibody-positive patients who visited our hospital between 1995 and 2015, there were 453 patients with continuous follow-up who survived to age 80. They were included in the study following the inclusion criteria: confirmed persistent detection of HCV RNA, no HCV eradication if anti-HCV therapy occurred before enrollment, and no development of hepatocellular carcinoma (HCC) before enrollment. For all study patients, baseline was defined as the date when they turned 80. Mortality rates after the age of 80 years and cause of death were analyzed. RESULTS During the study period, 155 patients (34.2%) died. Median survival time (MST) after age 80 was 8.8 years, which was comparable to that of the general population (10.1 years). Among 155 deceased patients, the majority (115 patients, 74.2%) died due to non-liver-related disease, followed by HCC (28 patients, 18.1%) and liver-related disease other than HCC (12 patients, 7.7%). Patients with advanced liver fibrosis (FIB-4 index > 3.25, n = 245) had shorter MST than patients with mild liver fibrosis (FIB-4 index ≤ 3.25, n = 208) (7.1 vs. 10.2 years; p = 0.020) due to a higher mortality rate from liver-related complications, including HCC. CONCLUSION Most elderly HCV patients die from non-liver-related disease, especially those with less advanced liver fibrosis.
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Akita T, Tanaka J, Satake M, Lin Y, Wada T, Kato K, Inoue M. Meta-regression Analysis of Sex- and Birth Year-Specific Prevalence of HBsAg and Anti-HCV Among Un-diagnosed Japanese: Data From the First-time Blood Donors, Periodical Health Checkup, and the Comprehensive Health Checkup With Lifestyle Education (Ningen Dock). J Epidemiol 2019; 30:420-425. [PMID: 31447462 PMCID: PMC7429148 DOI: 10.2188/jea.je20190055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background This study was aimed to precisely estimate the prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV) stratified by sex and birth year in Japan. Methods Three large-scaled cohorts: first-time blood donors, periodic health check-up, and comprehensive health check-up with lifestyle education (Ningen dock) were used for pooled prevalence of HBsAg and anti-HCV using meta-regression. Results Trends of birth year-specific prevalence of HBsAg and anti-HCV among the three cohorts were similar to one another, while birth year-specific pooled prevalence of HBsAg peaked in the 1941–1950 birth cohort. Prevalence of anti-HCV showed a decreasing trend by birth year. Conclusion We could estimate the pooled prevalence of HBsAg and anti-HCV based on nationwide data. The results can be used as reference data for various countermeasures for hepatitis eradication.
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Affiliation(s)
- Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | | | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine
| | - Takashi Wada
- The Large-scale Research Committee on the Usefulness of Ningen Dock Health Evaluation, Japan Society of Ningen Dock
| | - Kiminori Kato
- The Large-scale Research Committee on the Usefulness of Ningen Dock Health Evaluation, Japan Society of Ningen Dock
| | - Manami Inoue
- Division of Prevention, Center for Public Health Sciences, National Cancer Center
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Kanzaki N, Iwane S, Oeda S, Okada M, Kimura H, Eguchi Y, Fujimoto K. 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. Intern Med 2019; 58:1825-1834. [PMID: 30799338 PMCID: PMC6663536 DOI: 10.2169/internalmedicine.1755-18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
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.
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Affiliation(s)
- Naruyo Kanzaki
- Department of Medicine Sciences, Graduate School of Medicine, Saga University, Japan
| | | | | | | | - Hiromi Kimura
- Department of Nursing, Faculty of Medicine, Fukuoka University, Japan
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The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan. Orphanet J Rare Dis 2019; 14:155. [PMID: 31242950 PMCID: PMC6595668 DOI: 10.1186/s13023-019-1122-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Accepted: 06/10/2019] [Indexed: 12/31/2022] Open
Abstract
Background Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was partly covered by the government. This study aimed to examine the changes in the number of patients with sIBM over the last 10 years and to elucidate the cross-sectional profile of Japanese patients with sIBM. Methods The number of sIBM patients was estimated through a reply-paid postcard questionnaire for attending physicians. Only patients diagnosed as “definite” or “probable” sIBM by clinical and biopsy sIBM criteria were included in this study (Lancet Neurol 6:620-631, 2007, Neuromuscul Disord 23:1044-1055, 2013). Additionally, a registered self-administered questionnaire was also sent to 106 patients who agreed to reply via their attending physician, between November 2016 and March 2017. Results The number of patients diagnosed with sIBM for each 5-year period was 286 and 384 in 2011 and 2016, respectively. Inability to stand-up, cane-dependent gait, inability to open a plastic bottle, choking on food ingestion, and being wheelchair-bound should be included as sIBM milestones. Eight patients were positive for anti-hepatitis C virus antibody; three of them were administered interferon before sIBM onset. Steroids were administered to 33 patients (31.1%) and intravenous immunoglobulin to 46 patients (43.4%). From 2016 to 2017, total of 70 patients applied for the designated incurable disease medical expenses subsidy program. Although the treatment cost was partly covered by the government, many patients expressed psychological/mental and financial anxieties. Conclusions We determined the cross-sectional profile of Japanese patients with sIBM. Continuous support and prospective surveys are warranted.
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Toyoda H, Atsukawa M, Uojima H, Nozaki A, Tamai H, Takaguchi K, Fujioka S, Nakamuta M, Tada T, Yasuda S, Chuma M, Senoh T, Tsutsui A, Yamashita N, Hiraoka A, Michitaka K, Shima T, Akahane T, Itobayashi E, Watanabe T, Ikeda H, Iio E, Fukunishi S, Asano T, Tachi Y, Ikegami T, Tsuji K, Abe H, Kato K, Mikami S, Okubo H, Shimada N, Ishikawa T, Matsumoto Y, Itokawa N, Arai T, Tsubota A, Iwakiri K, Tanaka Y, Kumada T. Trends and Efficacy of Interferon-Free Anti-hepatitis C Virus Therapy in the Region of High Prevalence of Elderly Patients, Cirrhosis, and Hepatocellular Carcinoma: A Real-World, Nationwide, Multicenter Study of 10 688 Patients in Japan. Open Forum Infect Dis 2019; 6:ofz185. [PMID: 31123693 PMCID: PMC6524830 DOI: 10.1093/ofid/ofz185] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/10/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND We investigated changes in patient characteristics, rate of sustained virologic response (SVR), and factors associated with SVR after anti-hepatitis C virus (HCV) therapy with direct-acting antiviral (DAA) regimens in real-world practice in Japan, where patients with HCV are characterized by older age and high prevalence of cirrhosis and hepatocellular carcinoma (HCC). METHODS Changes in patient characteristics and SVR rates were evaluated from medical records among 10 688 patients who started interferon (IFN)-free DAA therapy between September 2014 and June 2018 in a nationwide, multicenter study. Factors associated with failure of SVR were analyzed. In particular, effects of cirrhosis or history of HCC on SVR were assessed by exact matching. RESULTS Patient age was becoming younger and baseline liver fibrosis was becoming milder over time. Overall SVR rate was 95.4%. The SVR rates increased over time in patients without a history of IFN-free DAA therapy. Multivariate analysis revealed that cirrhosis was unfavorably associated with achievement of SVR in both patients with genotype 1 (odds ratio, 1.68; 95% confidence interval [CI], 1.27-2.21) and genotype 2 (odds ratio, 1.69; 95% CI, 1.01-2.78). Comparisons after exact matching showed that the SVR rate was significantly lower in patients with cirrhosis than without it, whereas patients with and without a history of HCC had similar SVR rates. CONCLUSIONS Background characteristics of patients who undergo IFN-free DAA therapy are changing in Japan. Patients without a history of IFN-free DAA therapy have high SVR rates. Exact matching confirmed that cirrhosis significantly influences the achievement of SVR in real-world settings.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
| | - Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akito Nozaki
- Gastroenterology Center, Yokohama City University Medical Center, Japan
| | - Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Japan
| | - Makoto Nakamuta
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
| | - Makoto Chuma
- Gastroenterology Center, Yokohama City University Medical Center, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Naoki Yamashita
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hiroki Ikeda
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | - Toru Asano
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tokyo Metropolitan Bokuto Hospital, Japan
| | - Yoshihiko Tachi
- Department of Gastroenterology and Hepatology, Komaki City Hospital, Japan
| | | | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Noritomo Shimada
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Yoshihiro Matsumoto
- Department of Gastroenterology and Hepatology, Jikei University School of Medicine Kashiwa Hospital, Japan
| | - Norio Itokawa
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Jikei University School of Medicine, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
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