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Ohama H, Hiraoka A, Tada T, Kariyama K, Itobayashi E, Tsuji K, Ishikawa T, Toyoda H, Hatanaka T, Kakizaki S, Naganuma A, Tada F, Tanaka H, Nakamura S, Nouso K, Tanaka K, Kumada T. Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents. J Gastroenterol Hepatol 2024; 39:1394-1402. [PMID: 38602340 DOI: 10.1111/jgh.16553] [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: 12/26/2023] [Revised: 03/11/2024] [Accepted: 03/20/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND AND AIM Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. METHODS A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. RESULTS Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 104/μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0). CONCLUSION The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.
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Affiliation(s)
- Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
- Department of Gastroenterology, Takarazuka City Hospital, Hyogo, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Kazuya Kariyama
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hironori Tanaka
- Department of Gastroenterology, Takarazuka City Hospital, Hyogo, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Kazuhiro Nouso
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Kazunari Tanaka
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Masaoka R, Gyotoku Y, Shirahashi R, Suda T, Tamano M. Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance. World J Clin Cases 2023; 11:5204-5214. [PMID: 37621583 PMCID: PMC10445062 DOI: 10.12998/wjcc.v11.i22.5204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/23/2023] [Accepted: 07/07/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND The treatment of hepatitis C with direct-acting antiviral agents (DAAs) produces a high rate of sustained virological response (SVR) with fewer adverse events than interferon (IFN) therapy with a similar effect in inhibiting carcinogenesis as IFN therapy. The age-male-albumin-bilirubin-platelets (aMAP) score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients, and the velocity of shear waves (Vs) measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk. Combining these two may improve the prediction of carcinogenic risk. AIM To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients. METHODS This retrospective, observational study involved hepatitis C patients treated with DAAs who achieved SVR. Vs was measured before treatment (baseline), at the end of treatment (EOT), and 12 wk (follow-up 12) and 24 wk (follow-up 24) after treatment. The patients were followed for at least six months after EOT to determine whether cancer developed. Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis. The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic (ROC) curve analyses. RESULTS A total of 279 patients (mean age 65.9 years, 118 males, 161 females) were included in the analysis. Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase, platelets, α-fetoprotein, Vs, and the Fib-4 index as explanatory variables; only Vs was found to be significant (P = 0.0296). The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s. Carcinoma developed in 2.0% (3/151) of those with Vs < 1.53 m/s and in 10.5% (9/86) of those with Vs ≥ 1.53 m/s. CONCLUSION In hepatitis C patients after SVR, combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.
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Affiliation(s)
- Rion Masaoka
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Yoshinori Gyotoku
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Ryosaku Shirahashi
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Toshikuni Suda
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Masaya Tamano
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful. J Viral Hepat 2023; 30:148-159. [PMID: 36461645 DOI: 10.1111/jvh.13778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/07/2022] [Accepted: 11/26/2022] [Indexed: 12/04/2022]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is one of the most serious complications of hepatitis C virus (HCV) infection. Recently, effective antiviral medications have made sustained viral response (SVR) or cure a realistic therapeutic goal for most chronic HCV patients. Given HCV's tumorigenic propensity, it is not surprising that achieving SVR is helpful in preventing HCC. This review briefly summarizes and discusses the existing evidence on the relationship between hepatic carcinogenesis and viral eradication by antivirals, which is mainly divided into interferon-based and direct-acting antivirals (DAAs) based therapy. DAAs have changed the treatment landscape of chronic HCV, reaching high rates of SVR even in patients with advanced cirrhosis, with few contraindications and little side effects. Although some early reports suggested that DAA treatment increased the chance of HCC occurrence, more subsequent observational studies have refuted this theory. The probability of HCC recurrence after HCV eradication appears to be decreasing over time following SVR. Despite virological suppression/cure, individuals with liver cirrhosis are still at risk of HCC and should be monitored. There is a considerable need for markers/scores to predict the long-term risk of HCC in patients with HCV-related liver disease who attain SVR with direct-acting antivirals.
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Affiliation(s)
- Walaa Abdelhamed
- Endemic Medicine Department, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Enomoto H, Takashima T, Nishimura T, Aizawa N, Ikeda N, Yuri Y, Okamoto M, Yoshihara K, Yoshioka R, Kawata S, Ota S, Nakano R, Shiomi H, Iijima H. Liver cirrhosis in Japan: Future global trends in the era of progressive antiviral therapy. PORTAL HYPERTENSION & CIRRHOSIS 2022; 1:178-183. [DOI: 10.1002/poh2.30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/04/2022] [Indexed: 01/03/2025]
Abstract
AbstractIn Japan, viral hepatitis is the main cause of chronic liver diseases, including liver cirrhosis. Due to the availability of highly effective antiviral drugs in combination with antihepatitis measures, Japan has become one of the most successful countries in the world with regard to hepatitis virus elimination. In Japan, there are many elderly patients who have been infected with hepatitis C virus for a long time, and antihepatitis measures have been in place since the 2000s. Thus, the medical situation in Japan is expected to reflect the future situation in other countries where hepatitis countermeasures have been recently initiated and the infected population is aging. Our nationwide survey clarified the changes in the etiologies of liver cirrhosis in Japan. Although viral hepatitis remains a major cause of liver cirrhosis in Japan, nonviral cirrhosis is suggested to increasingly contribute to the etiologies of liver cirrhosis, as opposed to viral hepatitis‐related liver cirrhosis. The changing etiology of liver cirrhosis in Japan may help to predict future global trends in chronic liver diseases.
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Affiliation(s)
- Hirayuki Enomoto
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Tomoyuki Takashima
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Nobuhiro Aizawa
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Naoto Ikeda
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Yukihisa Yuri
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Mamiko Okamoto
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Kohei Yoshihara
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Ryota Yoshioka
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Shoki Kawata
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Shogo Ota
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Ryota Nakano
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Hideyuki Shiomi
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
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Hagiwara H, Ito Y, Ohta T, Nozaki Y, Iwamoto T, Hosui A, Hiramatsu N, Tahata Y, Sakamori R, Hikita H, Hayashi N. Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C who achieved a sustained virological response through direct‐acting antiviral agents among the working population in Japan. JGH Open 2022; 6:395-401. [PMID: 35774345 PMCID: PMC9218520 DOI: 10.1002/jgh3.12745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 11/18/2022]
Abstract
Background and Aim The development of hepatocarcinogenesis after a sustained virological response (SVR) remains an important issue affecting the balance between treatment and occupational life of workers with chronic hepatitis C virus (HCV) infection in Japan. Here, we aimed to evaluate the hepatocellular carcinoma (HCC) reducing effect and risk factors for developing HCC after SVR in patients treated with direct‐acting antiviral agents (DAAs) among the working population. Methods We studied 2579 working patients with chronic HCV infection who achieved SVR after antiviral treatment. We compared the difference in the cumulative incidence of post‐SVR HCC between the interferon (IFN)‐based n = 1615 and DAA (n = 964) groups. The risk factors for post‐SVR HCC development were determined in the DAA group. Results After propensity score matching (n = 644 in each group), the HCC development rates were not significantly different between the groups (P = 0.186). Multivariate Cox regression and the cutoff values determined by the receiver operating characteristic curve analyses revealed that age ≥61 years, diabetes, lower serum albumin levels <4.0 g/dL at 24 weeks after the end of treatment (EOT), and higher serum α‐fetoprotein levels ≥4.1 ng/mL at 24 weeks after the EOT were associated with the development of HCC. Conclusion The HCC suppressing effect after SVR through DAA treatment is equivalent to that of IFN treatment in patients in the working population. Intensive follow‐up is required after SVR with DAA treatment in Japanese workers with these risk factors to ensure the promotion of health and employment support.
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Affiliation(s)
- Hideki Hagiwara
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Yoshiki Ito
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Takashi Ohta
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Yasutoshi Nozaki
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Takayuki Iwamoto
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Atsushi Hosui
- Department of Gastroenterology and Hepatology Osaka Rosai Hospital Sakai Osaka Japan
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology Osaka Rosai Hospital Sakai Osaka Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan
| | - Norio Hayashi
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
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Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus. J Med Ultrason (2001) 2022; 49:253-259. [PMID: 35129720 PMCID: PMC9038899 DOI: 10.1007/s10396-021-01188-x] [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: 11/02/2021] [Accepted: 11/28/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE). METHODS Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma. RESULTS The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis. CONCLUSION In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.
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Yugawa K, Maeda T, Nagata S, Sakai A, Edagawa M, Omine T, Kometani T, Yamaguchi S, Konishi K, Hashimoto K. Mac-2-Binding Protein Glycosylation Isomer as a Novel Predictor of Hepatocellular Carcinoma Recurrence in Patients with Hepatitis C Virus Eradication. Ann Surg Oncol 2021; 29:2711-2719. [PMID: 34729653 DOI: 10.1245/s10434-021-11011-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/11/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. METHODS This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. RESULTS Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006, log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. CONCLUSIONS Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.
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Affiliation(s)
- Kyohei Yugawa
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Takashi Maeda
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
| | - Shigeyuki Nagata
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Akihiro Sakai
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Makoto Edagawa
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Takahiro Omine
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Takuro Kometani
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Shohei Yamaguchi
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Kozo Konishi
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Kenkichi Hashimoto
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
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Tada T, Kurosaki M, Nakamura S, Hasebe C, Kojima Y, Furuta K, Kobashi H, Kimura H, Ogawa C, Yagisawa H, Uchida Y, Joko K, Akahane T, Arai H, Marusawa H, Narita R, Ide Y, Sato T, Kusakabe A, Tsuji K, Mori N, Kondo M, Mitsuda A, Izumi N. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Med Virol 2021; 93:6247-6256. [PMID: 34170517 DOI: 10.1002/jmv.27157] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 06/22/2021] [Indexed: 11/12/2022]
Abstract
The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5-89.9) (52/64), 98.4% (95% CI, 91.2-100.0) (60/61), and 98.5% (95% CI, 91.7-100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0-97.5) (60/65). Albumin-bilirubin (ALBI) scores decreased during and after treatment (p < 0.001), and there were significant differences between baseline and end of treatment and between baseline and SVR12. Subgroup analyses showed no significant differences in SVR rates according to patient age, sex, HCV genotype (subtype), Child-Pugh classification, modified ALBI grade, presence of ascites, presence of hepatic coma, or history of hepatocellular carcinoma. In all subpopulations, the SVR rates were higher than 80%. There were no severe adverse events associated with the treatment. The SOF/VEL regimen showed good virological efficacy and acceptable safety even in patients with HCV-related decompensated cirrhosis.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
| | - Shinichiro Nakamura
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Mie, Japan
| | - Koichiro Furuta
- Department of Gastroenterology, Japanese Red Cross Masuda Hospital, Shimane, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Kagawa, Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Shimane, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan
| | - Hirotaka Arai
- Department of Gastroenterology, Japanese Red Cross Maebashi Hospital,, Gunma, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Ryoichi Narita
- Department of Gastroenterology, Japanese Red Cross Oita Hospital, Oita, Japan
| | - Yasushi Ide
- Department of Gastroenterology, Japanese Red Cross Karatsu Hospital, Saga, Japan
| | - Takashi Sato
- Department of Gastroenterology, Japanese Red Cross Nasu Hospital, Tochigi, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Shiga, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
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Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Tada F, Kisaka Y, Nakanishi S, Yamauchi K, Ochi H, Hiraoka A, Yagi S, Yukimoto A, Hirooka M, Abe M, Hiasa Y. AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy. BMC Cancer 2021; 21:699. [PMID: 34126947 PMCID: PMC8201700 DOI: 10.1186/s12885-021-08401-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 05/24/2021] [Indexed: 01/05/2023] Open
Abstract
Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08401-7.
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Affiliation(s)
- Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Norio Horiike
- Department of Gastroenterology, Saiseikai Imabari Hospital, 7-1-6 Kitamura, Imabari, Ehime, 799-1502, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, 2-6-5 Ootemachi, Matsuyama, Ehime, 790-0067, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima City Hospital, 1-1 Gotenmachi, Uwajima, Ehime, 798-8510, Japan
| | - Seiji Nakanishi
- Department of Gastroenterology, Ehime Prefectural Imabari Hospital, 4-5-5 Ishiicho, Imabari, Ehime, 794-0006, Japan
| | - Kazuhiko Yamauchi
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, 366 Yokogawara, Toon, Ehime, 791-0203, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Atsushi Hiraoka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Sen Yagi
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
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Toyoda H, Tada T, Yasuda S, Mizuno K, Ito T, Kumada T. Dynamic Evaluation of Liver Fibrosis to Assess the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Who Achieved Sustained Virologic Response. Clin Infect Dis 2021; 70:1208-1214. [PMID: 31056696 DOI: 10.1093/cid/ciz359] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 04/30/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Liver fibrosis is an important risk factor for the development of hepatocellular carcinoma (HCC) after sustained virologic response (SVR) in patients with persistent hepatitis C virus (HCV) infection. However, as the degree of liver fibrosis changes following the eradication of HCV after SVR, it is unclear whether the prediction of HCC development based on liver fibrosis at baseline remains valid. METHODS In 522 patients who achieved SVR by interferon-based anti-HCV therapy, the Fibrosis-4 Index for Liver Fibrosis (FIB-4 index) was updated annually by recalculation based on laboratory values after SVR. The incidence of HCC was reassessed annually based on the updated FIB-4 index. RESULTS The percentage of patients with mild liver fibrosis (FIB-4 index <1.45) increased annually after SVR, whereas the percentage of patients with advanced liver fibrosis (FIB-4 index ≥3.25) decreased. The incidences of HCC based on the FIB-4 index remained constant between the time of SVR and subsequent annual updates. No patients developed HCC after SVR if the FIB-4 index decreased to <1.45. CONCLUSIONS The FIB-4 index retained its predictive ability for the risk of HCC when recalculated after SVR, despite the decrease in patients with high FIB-4 index values. Dynamic assessment of the FIB-4 index can be useful in the surveillance of HCC after SVR. Patients with a FIB-4 index <1.45 did not develop HCC even by the regression from advanced fibrosis after SVR. Further studies will be necessary to confirm these findings, which may result in a decrease in the number of patients in whom surveillance is required.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takanori Ito
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Tada F, Kisaka Y, Nakanishi S, Yamauchi K, Yukimoto A, Nakamura Y, Hirooka M, Abe M, Hiasa Y. Sex difference in the development of hepatocellular carcinoma after direct-acting antiviral therapy in patients with HCV infection. J Med Virol 2020; 92:3507-3515. [PMID: 32374470 DOI: 10.1002/jmv.25984] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/02/2020] [Accepted: 04/30/2020] [Indexed: 12/27/2022]
Abstract
Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct-acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log-rank test, P = .007). On multivariate analysis, the fibrosis-4 index (HR = 1.11; 95%CI, 1.042-1.202, P = .002) and posttreatment α-fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046-1.197, P = .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR = 1.090; 95%CI, 1.024-1.160, P = .007) was an independent factor in male patients. The optimal posttreatment AFP cut-off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut-off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut-off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.
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Affiliation(s)
- Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan
| | - Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
| | - Norio Horiike
- Department of Gastroenterology, Saiseikai Imabari Hospital, Imabari, Ehime, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, Matsuyama, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, Matsuyama, Ehime, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima City Hospital, Uwajima, Ehime, Japan
| | - Seiji Nakanishi
- Department of Gastroenterology, Ehime Prefectural Imabari Hospital, Imabari, Ehime, Japan
| | - Kazuhiko Yamauchi
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, Toon, Ehime, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshiko Nakamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
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Real-World Virological Efficacy and Safety of Ledipasvir and Sofosbuvir in Patients with Chronic Hepatitis C Virus Genotype 2 Infection: A Multicenter Study. Infect Dis Ther 2020; 10:269-280. [PMID: 33141401 PMCID: PMC7954884 DOI: 10.1007/s40121-020-00364-9] [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: 09/26/2020] [Accepted: 10/20/2020] [Indexed: 10/26/2022] Open
Abstract
INTRODUCTION The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with ledipasvir (LDV) plus sofosbuvir (SOF) were assessed in patients who were chronically infected with hepatitis C virus (HCV) genotype 2. METHODS A total of 126 patients with chronic hepatitis C due to HCV genotype 2 infection who were treated with the LDV/SOF regimen were enrolled. The sustained virological response (SVR) rate and safety were analyzed. SVR was assessed in the intention-to-treat (ITT) population as well as in the modified intention-to-treat (mITT) population, which excluded patients with non-virological failure, including those who dropped out before the SVR assessment. RESULTS The overall SVR rates of the ITT and mITT populations were 87.3% (95% confidence interval [CI] 80.2-92.6) (110/126) and 97.3% (95% CI 92.4-99.4) (110/113), respectively. In the mITT population, the percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 92.9% (95% CI 86.5-96.9) (105/113), 99.1% (95% CI 95.2-100.0) (112/113), and 100.0% (95% CI 97.4-100.0) (113/113), respectively. Subgroup analyses of the mITT population showed no significant differences in SVR rates according to age, sex, HCV genotype (subtype), history of interferon-based therapy, baseline FIB-4 index, or baseline estimated glomerular filtration rate. In all subpopulations, the SVR rates were > 90%. There were no severe adverse events associated with the treatment. CONCLUSION The LDV/SOF regimen showed high virological efficacy and acceptable safety in patients with HCV genotype 2 infection. TRIAL REGISTRATION UMIN registration no. 000038604.
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Li CF, Tsao SM, Liao HH, Chen SC, Lee YT. Treatment of chronic hepatitis C regiments containing with recombinant interferon in patients with sustained virological response predicts risk of hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2020; 99:e22435. [PMID: 33019424 PMCID: PMC7535677 DOI: 10.1097/md.0000000000022435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.
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Affiliation(s)
- Chien-Feng Li
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
| | - Shih-Ming Tsao
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
| | - Hsien-Hua Liao
- School of Medicine, Chung Shan Medical University
- Department of Plastic Surgery
| | - Shiuan-Chih Chen
- School of Medicine, Chung Shan Medical University
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yuan-Ti Lee
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
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Recommendations from primary care physicians, family, friends and work colleagues influence patients' decisions related to hepatitis screening, medical examinations and antiviral treatment. Exp Ther Med 2020; 19:2973-2982. [PMID: 32256783 PMCID: PMC7086226 DOI: 10.3892/etm.2020.8533] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 01/22/2018] [Indexed: 12/22/2022] Open
Abstract
Identification and screening of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) is important to prevent liver cancer. Comprehensive antiviral treatments should follow three sequential steps: Hepatitis screening (step 1; examination of HB surface antigen and HCV antibody), medical examination (step 2; examination of HBV-DNA and/or HCV-RNA and performance of abdominal ultrasonography) and antiviral treatment (step 3). Patients who underwent these three steps were studied to determine effective information sources (factors) for raising awareness of comprehensive treatments. A total of 182 patients from 11 medical institutions were who were undergoing antiviral treatment were investigated. The number of patients who accessed each of the 18 information sources in each of the three steps and the percentage of these information sources that directly influenced the participants to make treatment-related decisions were calculated. 'Recommendation from a primary care physician' was the most common information source (64.3, 77.5, and 75.8% at steps 1, 2, and 3, respectively). 'Recommendation from a public health nurse (PHN),' 'recommendation from friends or family,' and 'recommendation from work colleagues' were the next most common human factors (3.3-19.8%). 'Recommendation from a primary care physician' had the greatest influence (76.9, 73.0, and 77.5% at steps 1, 2, and 3, respectively). 'Recommendation from a PHN' (50.0, 26.3 and 64.3%), 'recommendations from friends and family' (58.3, 38.9 and 58.3%), and 'recommendations from work colleagues' (33.3, 33.3 and 42.9%) were highly influential factors. Media such as TV commercial messages and programs also had high recognition, but were not directly influential. The findings of the present study indicated that recommendations from primary care physicians, friends, family and work colleagues influenced patients' decision-making regarding hepatitis screening, examination and treatment.
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Joko K, Mashiba T, Ochi H, Yano R, Sato K, Okujima Y, Aono M, Azemoto N, Takechi S, Yokota T, Jinoka R, Moriyama Y, Nishiyama M. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepatogastroenterol 2020; 9:78-83. [PMID: 32117695 PMCID: PMC7047307 DOI: 10.5005/jp-journals-10018-1305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. Materials and methods The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. Results Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. Conclusion The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future. How to cite this article Joko K, Mashiba T, Ochi H, et al. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepato-Gastroenterol 2019;9(2):78–83.
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Affiliation(s)
- Kouji Joko
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan; Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Toshie Mashiba
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Hironori Ochi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryo Yano
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Kaori Sato
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yusuke Okujima
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Michiko Aono
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Nobuaki Azemoto
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Shunji Takechi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Tomoyuki Yokota
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryosuke Jinoka
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yasunori Moriyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Masataka Nishiyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
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Mashiba T, Joko K, Kurosaki M, Ochi H, Hasebe C, Akahane T, Sohda T, Tsuji K, Mitsuda A, Kimura H, Narita R, Ogawa C, Furuta K, Shigeno M, Okushin H, Ito H, Kusakabe A, Satou T, Kawanami C, Nakata R, Kobashi H, Tamada T, Ide Y, Yagisawa H, Morita A, Matsushita T, Okada K, Izumi N. Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group. Hepatol Res 2019; 49:1114-1120. [PMID: 31077527 PMCID: PMC6899599 DOI: 10.1111/hepr.13362] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 04/23/2019] [Accepted: 05/04/2019] [Indexed: 12/13/2022]
Abstract
AIM The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naïve patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P < 0.0001) was identified as an independent predictor of treatment failure. No serious adverse events were observed with EBR/GZR therapy. CONCLUSIONS The SVR rate of EBR/GZR would have been 100% in patients without either a history of DAA therapy or double mutation. This combination of drugs could be safely given and is, thus, considered a highly useful first-line treatment for DAA-naïve patients with HCV.
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Affiliation(s)
- Toshie Mashiba
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalEhimeJapan
| | - Kouji Joko
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalEhimeJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Hironori Ochi
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalEhimeJapan
| | - Chitomi Hasebe
- Department of GastroenterologyJapanese Red Cross Asahikawa HospitalHokkaidoJapan
| | - Takehiro Akahane
- Department of GastroenterologyIshinomaki Red Cross HospitalMiyagiJapan
| | - Tetsuro Sohda
- Hepatology DivisionJapanese Red Cross Fukuoka HospitalFukuokaJapan
| | - Keiji Tsuji
- Department of GastroenterologyHiroshima Red Cross Hospital and Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Akeri Mitsuda
- Department of Internal MedicineJapanese Red Cross Tottori HospitalTottoriJapan
| | - Hiroyuki Kimura
- Department of GastroenterologyJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Ryoichi Narita
- Department of GastroenterologyOita Red Cross HospitalOitaJapan
| | - Chikara Ogawa
- Department of GastroenterologyTakamatsu Red Cross HospitalKagawaJapan
| | - Koichiro Furuta
- Department of Internal MedicineMasuda Red Cross HospitalShimaneJapan
| | - Masaya Shigeno
- Department of GastroenterologyJapanese Red Cross Nagasaki Genbaku HospitalNagasakiJapan
| | - Hiroaki Okushin
- Department of GastroenterologyJapanese Red Cross Society Himeji HospitalHyogoJapan
| | - Hiroshi Ito
- Department of GastroenterologyFukaya Red Cross HospitalSaitamaJapan
| | - Atsunori Kusakabe
- Department of GastroenterologyJapanese Red Cross Nagoya Daini HospitalNagoyaAichiJapan
| | - Takashi Satou
- Department of GastroenterologyNasu Red Cross HospitalTochigiJapan
| | | | - Ryo Nakata
- Department of GastroenterologyJapanese Red Cross Medical CenterTokyoJapan
| | - Haruhiko Kobashi
- Department of GastroenterologyJapanese Red Cross Okayama HospitalOkayamaJapan
| | - Takashi Tamada
- Department of GastroenterologyTakatsuki Red Cross HospitalTakatsukiJapan
| | - Yasushi Ide
- Department of Internal MedicineKaratsu Red Cross HospitalSagaJapan
| | - Hitoshi Yagisawa
- Department of GastroenterologyJapanese Red Cross Akita HospitalAkitaJapan
| | - Atsuhiro Morita
- Department of GastroenterologyJapanese Red Cross Kyoto Daini HospitalKyotoJapan
| | | | - Kazuhiko Okada
- Department of GastroenterologyToyama Red Cross HospitalToyamaJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
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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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Nagaoki Y, Imamura M, Nishida Y, Daijo K, Teraoka Y, Honda F, Nakamura Y, Morio K, Fujino H, Nakahara T, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Miki D, Hiyama Y, Ochi H, Chayama K, Aikata H. The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy. J Med Virol 2019; 91:650-658. [PMID: 30381831 DOI: 10.1002/jmv.25352] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 10/23/2018] [Indexed: 01/04/2025]
Abstract
BACKGROUND AND AIM To examine the effect on recurrence and survival of treatment by interferon (IFN)-free direct-acting antivirals (DAA) for patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. METHODS This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti-HCV treatment after HCC treatment, 38 patients received IFN-free DAA therapy (DAA patients) and 94 received IFN-based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case-control study. RESULTS The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P < 0.001) as independent predictors of overall survival. Propensity score matching analysis showed no significant difference in HCC development rates and overall survival rates in the two groups. CONCLUSIONS We found that SVR obtained after curative treatment for primary HCC suppressed recurrence and improved overall survival. And, IFN-free DAA therapy after curative treatment for primary HCC could predict improving overall survival and suppressed HCC recurrence.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Yuno Nishida
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kana Daijo
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Fumi Honda
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Nakamura
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Yuichi Hiyama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Hidenori Ochi
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
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19
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Nakano M, Koga H, Ide T, Kuromatsu R, Hashimoto S, Yatsuhashi H, Seike M, Higuchi N, Nakamuta M, Shakado S, Sakisaka S, Miuma S, Nakao K, Yoshimaru Y, Sasaki Y, Oeda S, Eguchi Y, Honma Y, Harada M, Nagata K, Mawatari S, Ido A, Maeshiro T, Matsumoto S, Takami Y, Sohda T, Torimura T. Predictors of hepatocellular carcinoma recurrence associated with the use of direct-acting antiviral agent therapy for hepatitis C virus after curative treatment: A prospective multicenter cohort study. Cancer Med 2019; 8:2646-2653. [PMID: 30900818 PMCID: PMC6536965 DOI: 10.1002/cam4.2061] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 12/23/2018] [Accepted: 02/11/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Previous studies have suggested an association between the use of direct-acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection and the resulting decrease in the incidence of hepatocellular carcinoma (HCC); however, it is unclear whether DAAs prevent the recurrence of HCC after curative treatment for HCC. This study aimed to prospectively investigate HCC recurrence and its predictors after curative treatment for HCC. METHODS A total of 3012 patients with chronic HCV infection, with or without cirrhosis, who were treated with DAAs were enrolled between January 1, 2015 and January 31, 2017 as per the institutional review board approved study protocol at 15 institutions, including 10 university hospitals and five high-volume centers in the Kyusyu area of Japan. Of the 3012 patients, 459 patients who had HCC but were cured with surgery or ablation therapy (curative treatment) before the use of DAAs were included in the analysis. RESULTS During a mean follow-up period of 29.4 months, 217 (47.2%) patients developed HCC recurrence. The median time to recurrence was 34.0 months, and the 1-, 2-, and 3-year cumulative HCC recurrence rates were 27.1%, 43.4%, and 50.8%, respectively. The risk factors for HCC recurrence were the α-fetoprotein (AFP) level before DAA therapy (P = 0.0047) and the number of curative treatments for HCC before DAA therapy (P < 0.0001). CONCLUSIONS A high AFP level and multiple occurrences of HCC before DAA therapy are associated with a high risk for HCC recurrence after curative treatment. Follow-up after DAA therapy should include special attention to the abovementioned risk factors.
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Affiliation(s)
- Masahito Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Hironori Koga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Ryoko Kuromatsu
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Satoru Hashimoto
- Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
| | - Hiroshi Yatsuhashi
- Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
| | - Masataka Seike
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Nobito Higuchi
- Division of Gastroenterology, National Kyusyu Medical Center Hospital, Fukuoka, Japan
| | - Makoto Nakamuta
- Division of Gastroenterology, National Kyusyu Medical Center Hospital, Fukuoka, Japan
| | - Satoshi Shakado
- Department of Gastroenterology and Medicine, Fukuoka University, Faculty of Medicine, Fukuoka, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology and Medicine, Fukuoka University, Faculty of Medicine, Fukuoka, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
| | - Yoko Yoshimaru
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yutaka Sasaki
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Satoshi Oeda
- Liver Center, Saga University Hospital, Saga, Japan
| | | | - Yuichi Honma
- Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Kenji Nagata
- Department of Liver Disease, University of Miyazaki Hospital, Miyazaki, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Tatsuji Maeshiro
- First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
| | | | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery and Clinical Research Institute, National Kyushu Medical Center Hospital, Fukuoka, Japan
| | - Tetsuo Sohda
- Hepatology Division, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
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Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study. Hepatol Int 2019; 13:293-301. [PMID: 30820753 DOI: 10.1007/s12072-019-09939-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 02/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan. METHODS Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6 months. A total of 2552 patients were enrolled. RESULTS Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment. CONCLUSION Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.
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21
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Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Tada F, Kisaka Y, Nakanishi S, Yamauchi K, Yukimoto A, Hirooka M, Abe M, Hiasa Y. Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection. Hepatol Res 2019; 49:136-146. [PMID: 30335208 DOI: 10.1111/hepr.13278] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 10/13/2018] [Accepted: 10/13/2018] [Indexed: 12/17/2022]
Abstract
AIM The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated. METHODS A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed. RESULTS During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre- and post-treatment factors identified the Fibrosis-4 (FIB-4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021-1.178; P = 0.011) and post-treatment α-fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054-1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high-score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1- and 2-year cumulative incidence rates of HCC were 6.1% and 14.4%. CONCLUSIONS A high FIB-4 index and a high post-treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.
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Affiliation(s)
- Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Norio Horiike
- Department of Gastroenterology, Saiseikai Imabari Hospital, Imabari, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, Matsuyama, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, Matsuyama, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima City Hospital, Uwajima, Japan
| | - Seiji Nakanishi
- Department of Gastroenterology, Ehime Prefectural Imabari Hospital, Imabari, Japan
| | - Kazuhiko Yamauchi
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, Toon, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
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22
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Toyoda H, Atsukawa M, Takaguchi K, Senoh T, Michitaka K, Hiraoka A, Fujioka S, Kondo C, Okubo T, Uojima H, Tada T, Yoneyama H, Watanabe T, Asano T, Ishikawa T, Tamai H, Abe H, Kato K, Tsuji K, Ogawa C, Shimada N, Iio E, Deguchi A, Itobayashi E, Mikami S, Moriya A, Okubo H, Tani J, Tsubota A, Tanaka Y, Masaki T, Iwakiri K, Kumada T. Real-world virological efficacy and safety of elbasvir and grazoprevir in patients with chronic hepatitis C virus genotype 1 infection in Japan. J Gastroenterol 2018; 53:1276-1284. [PMID: 29740665 DOI: 10.1007/s00535-018-1473-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 04/30/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics. RESULTS Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment. CONCLUSIONS The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan.
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kida, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Toru Asano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Otakanomori Hospital, Kashiwa, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Akihiro Deguchi
- Department of Gastroenterology, Kagawa Rosai Hospital, Marugame, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Shigeru Mikami
- Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Joji Tani
- Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kida, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
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Kogiso T, Sagawa T, Kodama K, Taniai M, Katagiri S, Egawa H, Yamamoto M, Tokushige K. Hepatocellular carcinoma after direct-acting antiviral drug treatment in patients with hepatitis C virus. JGH OPEN 2018; 3:52-60. [PMID: 30834341 PMCID: PMC6386743 DOI: 10.1002/jgh3.12105] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 08/26/2018] [Accepted: 10/09/2018] [Indexed: 01/05/2023]
Abstract
Background and Aim Given the use of direct‐acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined. Methods This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir‐boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients’ histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases. Results Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed de novo HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134–2.441, P < 0.01). Surgical resection or LT reduced the risk of HCC. Conclusions DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow‐up for HCC recurrence is required in previously treated cases.
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Affiliation(s)
- Tomomi Kogiso
- Department of Internal Medicine, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Takaomi Sagawa
- Department of Internal Medicine, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Kazuhisa Kodama
- Department of Internal Medicine, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Makiko Taniai
- Department of Internal Medicine, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Satoshi Katagiri
- Department of Surgery Tokyo Women's Medical University, Yachiyo Medical Center Yachiyo Japan.,Department of Surgery, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology Tokyo Women's Medical University Tokyo Japan
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Dong J, Olaleye OE, Jiang R, Li J, Lu C, Du F, Xu F, Yang J, Wang F, Jia W, Li C. Glycyrrhizin has a high likelihood to be a victim of drug-drug interactions mediated by hepatic organic anion-transporting polypeptide 1B1/1B3. Br J Pharmacol 2018; 175:3486-3503. [PMID: 29908072 DOI: 10.1111/bph.14393] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 05/11/2018] [Accepted: 05/30/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND PURPOSE Intravenous glycyrrhizin, having anti-inflammatory and hepatoprotective properties, is incorporated into the management of liver diseases in China. This investigation was designed to elucidate the molecular mechanism underlying hepatobiliary excretion of glycyrrhizin and to investigate its potential for drug-drug interactions on organic anion-transporting polypeptide (OATP)1B. EXPERIMENTAL APPROACH Human transporters mediating hepatobiliary excretion of glycyrrhizin were characterized at the cellular and vesicular levels and compared with rat hepatic transporters. The role of Oatp1b2 in glycyrrhizin's elimination and pharmacokinetics was evaluated in rats using the inhibitor rifampin. A physiologically based pharmacokinetic (PBPK) model for glycyrrhizin, incorporating transporter-mediated hepatobiliary excretion, was established and applied to predict potential drug-drug interactions related to glycyrrhizin in humans. KEY RESULTS Hepatobiliary excretion of glycyrrhizin involved human OATP1B1/1B3 (Oatp1b2 in rats)-mediated hepatic uptake from blood and human multidrug resistance-associated protein (MRP)2/breast cancer resistance protein (ABCP)/bile salt export pump (BSEP)/multidrug resistance protein 1 (Mrp2/Abcp/Bsep in rats)-mediated hepatic efflux into bile. In rats, rifampin impaired hepatic uptake of glycyrrhizin significantly increasing its systemic exposure. Glomerular-filtration-based renal excretion of glycyrrhizin was slow due to extensive protein binding in plasma. Quantitative analysis using the PBPK model demonstrated that OATP1B1/1B3 have critical roles in the pharmacokinetics of glycyrrhizin, which is highly likely to be a victim of drug-drug interactions when co-administered with potent dual inhibitors of these transporters. CONCLUSIONS AND IMPLICATIONS Transporter-mediated hepatobiliary excretion governs glycyrrhizin's elimination and pharmacokinetics. Understanding glycyrrhizin's potential drug-drug interactions on OATP1B1/1B3 should enhance the therapeutic outcome of glycyrrhizin-containing drug combinations on liver diseases.
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Affiliation(s)
- Jiajia Dong
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.,University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China
| | - Olajide E Olaleye
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Rongrong Jiang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Jing Li
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Chuang Lu
- Department of DMPK, Sanofi, Cambridge, MA, USA
| | - Feifei Du
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Fang Xu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Junling Yang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Fengqing Wang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Weiwei Jia
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Chuan Li
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.,University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China
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Hu H, Yang L, Li L, Zeng C. Long non-coding RNA KCNQ1OT1 modulates oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ ABCC1 axis. Biochem Biophys Res Commun 2018; 503:2400-2406. [PMID: 29966655 DOI: 10.1016/j.bbrc.2018.06.168] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 06/29/2018] [Indexed: 12/20/2022]
Abstract
The underlying functions of long non-coding RNAs (lncRNAs) on chemoresistance in multiple cancers have been testified. However, the function and mechanism of lncRNAs on chemoresistance in hepatocellular carcinoma are still confused. In this study, we concentrated on the function and mechanism of KCNQ1OT1 on oxaliplatin resistance in hepatocellular carcinoma. Results showed that KCNQ1OT1 was significantly up-regulated in oxaliplatin-resistant HepG2 and Huh7 cells. Moreover, knockdown of KCNQ1OT1 inhibited the cell proliferation, migration, invasion and reduced the expression of drug-resistant gene (MRP5, MDR1, LRP1). Additionally, bioinformatics analysis and dual-luciferase reporter assay showed that miR-7-5p directly targeted the 3'-UTR of miR-7-5p and ABCC1 mRNA, indicating that KCNQ1OT1 regulated the expression of ABCC1 via endogenous sponging miR-7-5p. Conclusively, KCNQ1OT1 modulated oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ABCC1 axis, indicating a novel approach for the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Huiqin Hu
- Department of Chinese Medicine, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, Guangdong, China.
| | - Li Yang
- Department of Chinese Medicine, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, Guangdong, China.
| | - Lijun Li
- Department of Quality Control, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, Guangdong, China.
| | - Changchun Zeng
- Department of Medical Laboratory, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, Guangdong, China.
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Tachi Y, Hirai T, Kojima Y, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. Liver stiffness reduction correlates with histological characteristics of hepatitis C patients with sustained virological response. Liver Int 2018; 38:59-67. [PMID: 28557143 DOI: 10.1111/liv.13486] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Accepted: 05/23/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS We investigated the correlation between histological characteristics and changes in liver stiffness (LS) in patients with sustained virological response (SVR) using acoustic radiation force impulse (ARFI) elastography. METHODS In this prospective study, we enrolled 176 hepatitis C patients with SVR who underwent ARFI elastography and liver biopsy before antiviral treatment, and serial ARFI elastography at the end of treatment (EOT) and at 24 weeks after the EOT. To compare the long-term changes in LS in patients with SVR using ARFI elastography, another group of 140 patients who had undergone paired biopsy after achieving SVR was included. RESULTS Mean LS values were 1.60±0.63 m/s, 1.48±0.56 m/s and 1.37±0.62 m/s at baseline, EOT and 24 weeks after EOT, respectively, P<.001. Higher inflammatory activity at baseline was associated with an improvement in LS at the EOT, with an odds ratio of 1.940. Significant fibrosis at baseline was associated with an improvement in LS at 24 weeks after the EOT, with an odds ratio of 2.617. Among patients in the paired biopsy group with baseline fibrosis stage identical to the ARFI group, LS values at 24 weeks after the EOT did not show any difference with values at 5 years after EOT. CONCLUSIONS Pre-treatment histological characteristics influence LS reduction after SVR is achieved.
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Affiliation(s)
- Yoshihiko Tachi
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Takanori Hirai
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Yuko Kojima
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
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Okimoto S, Kobayashi T, Kuroda S, Ishiyama K, Ide K, Ohira M, Tahara H, Shimizu S, Iwako H, Hamaoka M, Honmyo N, Yamaguchi M, Ohdan H. Prediction of recurrence following hepatectomy in patients with hepatitis C virus infection-related hepatocellular carcinoma who achieved a sustained virological response. Hepatol Res 2017; 47:1186-1195. [PMID: 28326662 DOI: 10.1111/hepr.12896] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 03/10/2017] [Accepted: 03/17/2017] [Indexed: 12/22/2022]
Abstract
AIM The risk of hepatitis C virus infection-related hepatocellular carcinoma (HCC) is lower, with a better prognosis, in patients who achieve a sustained virological response (SVR) than in those who do not. We aimed to identify risk factors of post-hepatectomy HCC recurrence in patients who achieved a SVR. METHODS This retrospective study included 349 HCC patients who underwent an initial radical hepatectomy at our institution between January 2005 and December 2014. Sixty-eight patients had achieved a SVR (the SVR group) and 281 patients had not (the non-SVR group). Clinical characteristics and long-term outcomes were compared between the two groups. Univariate and multivariate analyses identified variables associated with recurrence-free survival in the SVR group. RESULTS Post-hepatectomy overall and recurrence-free survival rates were significantly higher in the SVR group than the non-SVR group (P < 0.01 and <0.05, respectively). Univariate analysis of post-hepatectomy recurrence-free survival in the SVR group revealed multiple significant factors: aspartate aminotransferase, 25 IU/L or more (P = 0.01); indocyanine green retention rate at 15 min, 20.0% or less (P < 0.05); hepatic vascular invasion (P < 0.05); and an interval of months or less between achieving a SVR and hepatectomy (P < 0.01). Multivariate analysis confirmed an interval of 30 months or less between achieving a SVR and hepatectomy as an independent prognostic factor of recurrence-free survival (hazard ratio, 2.30; 95.0% confidence interval, 1.04-5.13; P < 0.05). CONCLUSION The interval between achieving a SVR and hepatectomy is an important predictor of recurrence in hepatitis C virus infection-related HCC patients who achieved a SVR.
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Affiliation(s)
- Sho Okimoto
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Seiichi Shimizu
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Iwako
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Michinori Hamaoka
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Megumi Yamaguchi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Direct-Acting Antivirals Decreased Tumor Recurrence After Initial Treatment of Hepatitis C Virus-Related Hepatocellular Carcinoma. Dig Dis Sci 2017; 62:2932-2942. [PMID: 28884320 DOI: 10.1007/s10620-017-4739-z] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 08/24/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2-10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy. RESULTS HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2-3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively (P < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively (P = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191-0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time. CONCLUSIONS DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.
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Ogasawara N, Kobayashi M, Akuta N, Kominami Y, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Suzuki F, Saitoh S, Suzuki Y, Arase Y, Ikeda K, Kobayashi M, Kumada H. Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b. J Med Virol 2017; 90:313-319. [DOI: 10.1002/jmv.24950] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 09/07/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Nobuhiko Ogasawara
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Masahiro Kobayashi
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Norio Akuta
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Yoko Kominami
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Shunichiro Fujiyama
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Yusuke Kawamura
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Hitomi Sezaki
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Tetsuya Hosaka
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Fumitaka Suzuki
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Satoshi Saitoh
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Yasuji Arase
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | - Kenji Ikeda
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
| | | | - Hiromitsu Kumada
- Department of Hepatology and Okinaka Memorial Institute for Medical Research; Toranomon Hospital; Tokyo Japan
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Elsharkawy A, Alem SA, Fouad R, El Raziky M, El Akel W, Abdo M, Tantawi O, AbdAllah M, Bourliere M, Esmat G. Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon. J Gastroenterol Hepatol 2017; 32:1624-1630. [PMID: 28177543 DOI: 10.1111/jgh.13758] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Revised: 01/07/2017] [Accepted: 01/30/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen. METHODS This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. RESULTS There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. CONCLUSION Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.
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Affiliation(s)
- Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Maissa El Raziky
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Wafaa El Akel
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Abdo
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Omnia Tantawi
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Centre, Giza, Egypt
| | - Marc Bourliere
- Department of Hepato-Gastroenterology, Hospital Saint Joseph, Marseille, France
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
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Nagaoki Y, Imamura M, Aikata H, Daijo K, Teraoka Y, Honda F, Nakamura Y, Hatooka M, Morio R, Morio K, Kan H, Fujino H, Kobayashi T, Masaki K, Ono A, Nakahara T, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Hayes CN, Miki D, Ochi H, Chayama K. The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy. PLoS One 2017; 12:e0182710. [PMID: 28797106 PMCID: PMC5552231 DOI: 10.1371/journal.pone.0182710] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Accepted: 07/24/2017] [Indexed: 02/06/2023] Open
Abstract
The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10–196) and 23 (range 4–78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Kana Daijo
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Fumi Honda
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Yuki Nakamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Masahiro Hatooka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Reona Morio
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiromi Kan
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Tomoki Kobayashi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Keiichi Masaki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - C. Nelson Hayes
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Hidenori Ochi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
- * E-mail:
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Morishita N, Hiramatsu N, Oze T, Urabe A, Tahata Y, Yamada R, Yakushijin T, Hosui A, Iio S, Yamada A, Hagiwara H, Mita E, Yamada Y, Ito T, Inada M, Katayama K, Yabuuchi I, Imai Y, Hikita H, Sakamori R, Yoshida Y, Tatsumi T, Hayashi N, Takehara T. Ultra-deep sequencing analysis of resistance-associated variants during retreatment with simeprevir-based triple therapy after failure of telaprevir-based triple therapy in patients with genotype 1 hepatitis C virus infection. Hepatol Res 2017; 47:773-782. [PMID: 27593967 DOI: 10.1111/hepr.12817] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 07/15/2016] [Accepted: 08/31/2016] [Indexed: 01/13/2023]
Abstract
AIM Simeprevir (SMV)-based triple therapy is an effective retreatment option following failure of telaprevir (TVR)-based triple therapy. However, it is unclear whether the persistence of resistance-associated variants (RAVs) induced by TVR-based therapy may reduce the treatment effect of SMV-based therapy. METHODS The factors associated with the treatment effect, including RAVs in the NS3 region, were examined in 21 patients with genotype 1b HCV infection who were treated with SMV-based therapy after failure of TVR-based therapy. Ultra-deep sequencing was carried out to detect RAVs. RESULTS With the exception of one patient who discontinued treatment owing to adverse events, the sustained virologic response (SVR) rate was 50% (10/20). Ultra-deep sequencing at the start of SMV-based therapy revealed that TVR-resistant variants were detected in six patients (29%), and no variants were observed at position 168. Cross-resistance between TVR and SMV with low frequency was detected in only one patient, and this patient achieved SVR. Higher SVRs for SMV-based therapy were attained in patients who discontinued treatment owing to the adverse effects of prior TVR-based therapy (discontinuation 100% vs. non-discontinuation 29%, P = 0.005), and patients who relapsed following prior pegylated interferon plus ribavirin therapy (relapse 100% vs. non-response 20%, P = 0.007). CONCLUSIONS In this study, ultra-deep sequencing analysis revealed that TVR and/or SMV-resistant variants may have no influence on the effect of SMV-based therapy after failure of TVR-based therapy. Patients who discontinued treatment owing to adverse effects of TVR-based therapy and relapsers to previous pegylated interferon/ribavirin therapy would be good candidates for retreatment with SMV-based therapy.
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Affiliation(s)
- Naoki Morishita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tsugiko Oze
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ayako Urabe
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takayuki Yakushijin
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | | | - Sadaharu Iio
- Higashiosaka City General Hospital, Higashiosaka, Japan
| | | | | | - Eiji Mita
- National Hospital Organization Osaka National Hospital, Osaka, Japan
| | | | - Toshifumi Ito
- Japan Community Health Care Organization Osaka Hospital, Osaka, Japan
| | | | - Kazuhiro Katayama
- Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | - Iwao Yabuuchi
- National Hospital Organization Minami Wakayama Medical Center, Tanabe, Japan
| | | | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | | | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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Abstract
There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.
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Matsuura K, Sawai H, Ikeo K, Ogawa S, Iio E, Isogawa M, Shimada N, Komori A, Toyoda H, Kumada T, Namisaki T, Yoshiji H, Sakamoto N, Nakagawa M, Asahina Y, Kurosaki M, Izumi N, Enomoto N, Kusakabe A, Kajiwara E, Itoh Y, Ide T, Tamori A, Matsubara M, Kawada N, Shirabe K, Tomita E, Honda M, Kaneko S, Nishina S, Suetsugu A, Hiasa Y, Watanabe H, Genda T, Sakaida I, Nishiguchi S, Takaguchi K, Tanaka E, Sugihara J, Shimada M, Kondo Y, Kawai Y, Kojima K, Nagasaki M, Tokunaga K, Tanaka Y. Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection. Gastroenterology 2017; 152:1383-1394. [PMID: 28163062 DOI: 10.1053/j.gastro.2017.01.041] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Revised: 01/17/2017] [Accepted: 01/23/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS There is still a risk for hepatocellular carcinoma (HCC) development after eradication of hepatitis C virus (HCV) infection with antiviral agents. We investigated genetic factors associated with the development of HCC in patients with a sustained virologic response (SVR) to treatment for chronic HCV infection. METHODS We obtained genomic DNA from 457 patients in Japan with a SVR to interferon-based treatment for chronic HCV infection from 2007 through 2015. We conducted a genome-wide association study (GWAS), followed by a replication analysis of 79 candidate single nucleotide polymorphisms (SNPs) in an independent set of 486 patients in Japan. The study end point was HCC diagnosis or confirmation of lack of HCC (at follow-up examinations until December 2014 in the GWAS cohort, and until January 2016 in the replication cohort). We collected clinical and laboratory data from all patients. We analyzed expression levels of candidate gene variants in human hepatic stellate cells, rats with steatohepatitis caused by a choline-deficient L-amino acid-defined diet, and a mouse model of liver injury caused by administration of carbon tetrachloride. We also analyzed expression levels in liver tissues of patients with chronic HCV infection with different stages of fibrosis or tumors vs patients without HCV infection (controls). RESULTS We found a strong association between the SNP rs17047200, located within the intron of the tolloid like 1 gene (TLL1) on chromosome 4, and development of HCC; there was a genome-wide level of significance when the results of the GWAS and replication study were combined (odds ratio, 2.37; P = 2.66 × 10-8). Multivariate analysis showed rs17047200 AT/TT to be an independent risk factor for HCC (hazard ratio, 1.78; P = .008), along with male sex, older age, lower level of albumin, advanced stage of hepatic fibrosis, presence of diabetes, and higher post-treatment level of α-fetoprotein. Combining the rs17047200 genotype with other factors, we developed prediction models for HCC development in patients with mild or advanced hepatic fibrosis. Levels of TLL1 messenger RNA (mRNA) in human hepatic stellate cells increased with activation. Levels of Tll1 mRNA increased in liver tissues of rodents with hepatic fibrogenesis compared with controls. Levels of TLL1 mRNA increased in liver tissues of patients with progression of fibrosis. Gene expression levels of TLL1 short variants, including isoform 2, were higher in patients with rs17047200 AT/TT. CONCLUSIONS In a GWAS, we identified the association between the SNP rs17047200, within the intron of TLL1, and development of HCC in patients who achieved an SVR to treatment for chronic HCV infection. We found levels of Tll1/TLL1 mRNA to be increased in rodent models of liver injury and liver tissues of patients with fibrosis, compared with controls. We propose that this SNP might affect splicing of TLL1 mRNA, yielding short variants with high catalytic activity that accelerates hepatic fibrogenesis and carcinogenesis. Further studies are needed to determine how rs17047200 affects TLL1 mRNA levels, splicing, and translation, as well as the prevalence of this variant among other patients with HCC. Tests for the TLL1 SNP might be used to identify patients at risk for HCC after an SVR to treatment of HCV infection.
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Affiliation(s)
- Kentaro Matsuura
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromi Sawai
- Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuho Ikeo
- Center for Information Biology, National Institute of Genetics, Mishima, Japan
| | - Shintaro Ogawa
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masanori Isogawa
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Atsumasa Komori
- Clinical Research Center, National Nagasaki Medical Center, Omura, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tadashi Namisaki
- Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan
| | - Hitoshi Yoshiji
- Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan
| | - Naoya Sakamoto
- Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Center for Interprofessional Education, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masayuki Kurosaki
- Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Namiki Izumi
- Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, University of Yamanashi, Chuo, Japan
| | - Atsunori Kusakabe
- Division of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Eiji Kajiwara
- Department of Hepatology, Steel Memorial Yahata Hospital, Kitakyushu, Japan
| | - Yoshito Itoh
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University, Kurume, Japan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Misako Matsubara
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Ken Shirabe
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiichi Tomita
- Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan
| | - Masao Honda
- Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Sohji Nishina
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hisayoshi Watanabe
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shuhei Nishiguchi
- Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Eiji Tanaka
- Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Junichi Sugihara
- Department of Gastroenterology, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Mitsuo Shimada
- Department of Surgery, The University of Tokushima, Tokushima, Japan
| | - Yasuteru Kondo
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yosuke Kawai
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Kaname Kojima
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Masao Nagasaki
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Katsushi Tokunaga
- Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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Fraenkel L, Lim J, Garcia-Tsao G, Reyna V, Monto A, Bridges JFP. Variation in Treatment Priorities for Chronic Hepatitis C: A Latent Class Analysis. PATIENT-PATIENT CENTERED OUTCOMES RESEARCH 2017; 9:241-9. [PMID: 26518200 DOI: 10.1007/s40271-015-0147-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Data describing patients' priorities, or main concerns, are essential to inform important decisions in healthcare, including treatment planning, diagnostic testing, and the development of programs to improve access and delivery of care. To date, the majority of studies performed does not account for variability in patients' priorities, and as a consequence may not effectively inform end users. The objective of this study was to examine the value of segmentation analysis as a method to illustrate variability in priorities for treatment of chronic hepatitis C (HCV). METHODS We elicited patients' main concerns when considering antiviral therapy for HCV using a Best-Worst Scaling experiment (Case 1) with ten objects. Latent class analysis was used to estimate part-worth utilities and the probability that each respondent belongs to each segment. RESULTS In the aggregate, subjects (N = 162) had three main concerns: (1) not being cured; (2) experiencing a lot of side effects; and (3) developing viral resistance to therapy. Segmentation into two groups demonstrated that both groups prioritized the likelihood of cure and coping with side effects, but that only one group (n = 78) was concerned about developing viral resistance to therapy, while subjects in the second group (n = 84) prioritized being able to keep up with their responsibilities. Further segmentation revealed distinct clusters of patients with unique priorities. CONCLUSIONS Patients' priorities vary significantly. Preference studies should consider including methods to determine whether distinct clusters of priorities and/or concerns exist in order to accurately inform end users' decision making.
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Affiliation(s)
- Liana Fraenkel
- VA Connecticut Health Care System, Yale University School of Medicine, 300 Cedar ST, TAC Bldg, RM #525, PO Box 208031, New Haven, CT, USA.
| | - Joseph Lim
- VA Connecticut Health Care System, Yale University School of Medicine, 300 Cedar ST, TAC Bldg, RM #525, PO Box 208031, New Haven, CT, USA
| | - Guadalupe Garcia-Tsao
- VA Connecticut Health Care System, Yale University School of Medicine, 300 Cedar ST, TAC Bldg, RM #525, PO Box 208031, New Haven, CT, USA
| | - Valerie Reyna
- Department of Human Development and Psychology, Cornell University, Ithaca, NY, USA
| | - Alexander Monto
- Section of Digestive Diseases, University of California, San Francisco, San Francisco, CA, USA
| | - John F P Bridges
- Department of Health Policy and Management, John Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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Hirohata Y, Yoh T, Nakamura Y, Kato T, Okamura R. Surgical Treatment for Hepatocellular Carcinoma in a Chronic Hepatitis C Patient 20 Years after Achieving a Sustained Virological Response. ACTA ACUST UNITED AC 2017. [DOI: 10.5833/jjgs.2016.0117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
| | - Tomoaki Yoh
- Department of Surgery, Graduate School of Medicine, Kyoto University
| | - Yuya Nakamura
- Department of Surgery, Yamatotakada Municipal Hospital
| | - Tatsushi Kato
- Department of Surgery, Yamatotakada Municipal Hospital
| | - Ryuji Okamura
- Department of Surgery, Yamatotakada Municipal Hospital
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Lee SH, Jin YJ, Shin JY, Lee JW. Assessment of hepatocellular carcinoma risk based on peg-interferon plus ribavirin treatment experience in this new era of highly effective oral antiviral drugs. Medicine (Baltimore) 2017; 96:e5321. [PMID: 28072684 PMCID: PMC5228644 DOI: 10.1097/md.0000000000005321] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Revised: 10/12/2016] [Accepted: 10/12/2016] [Indexed: 12/27/2022] Open
Abstract
In this new era of highly effective oral antiviral drugs for chronic hepatitis C virus (HCV), indications for antiviral treatment may be extendable. This study undertaken to identify suitable candidates for peg-interferon plus ribavirin (PEG-IFN/RBV) treatment by evaluating hepatocellular carcinoma (HCC) risk in patients with chronic HCV treated or not with PEG-IFN/RBV.This large-scale retrospective study was conducted on 1176 patients with chronic HCV without a history of HCC (treatment group [n = 489] and no-treatment group [n = 687]). In the treatment group, patients treated with PEG-IFN/RBV were dichotomized based on the achievement of sustained virologic response (SVR) into SVR (+) and SVR (-) groups.Median follow-up for all study subjects was 31 months (range 6-144 months). Three-year cumulative HCC development rates in the SVR (+) (1.1%) and SVR (-) (8.6%) subgroups were significantly lower than in the no-treatment group (13.5%) (P < 0.01 and P < 0.01, respectively). In all study subjects, presence of cirrhosis (hazard ratio [HR], 9.92, P < 0.01), age (HR 1.03, P < 0.01), SVR (-) (HR 7.02, P < 0.01), and no-treatment (HR 6.76, P < 0.01) were found to be independent risk factors of HCC development. In the treatment group, age, the presence of cirrhosis, and SVR (-) were predictors of HCC development. In the no-treatment group, age, male, and the presence of cirrhosis were independent predictors for HCC development.HCC risk increased in patients with chronic HCV with older age, cirrhosis, SVR (-) after PEG-IFN/RBV treatment, and no PEG-IFN/RBV treatment. Active antiviral therapy based on highly effective oral drugs needs to be considered in these patients.
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Maida M, Malizia G, Affronti A, Virdone R, Maida C, Margherita V, D’amico G. Screening and surveillance for hepatocellular carcinoma: perspective of a new era? Expert Rev Anticancer Ther 2016; 16:1291-1302. [PMID: 27730841 DOI: 10.1080/14737140.2016.1246965] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Marcello Maida
- Section of Gastroenterology, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Giuseppe Malizia
- Section of Gastroenterology, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Andrea Affronti
- Section of Internal Medicine, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Roberto Virdone
- Section of Internal Medicine, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Carlo Maida
- Section of Internal Medicine, DIBIMIS, University of Palermo, Palermo, Italy
| | - Vito Margherita
- Department of Medical Sciences, Surgical and Advanced Technologies, University of Catania, Catania, Italy
| | - Gennaro D’amico
- Section of Gastroenterology, Villa Sofia, V. Cervello Hospital, Palermo, Italy
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Toyoda H, Tada T, Tachi Y, Hirai T, Yasuda S, Honda T, Hayashi K, Ishigami M, Goto H, Kumada T. Liver fibrosis indices for identifying patients at low risk of developing hepatocellular carcinoma after eradication of HCV. Antivir Ther 2016; 22:185-193. [PMID: 27586087 DOI: 10.3851/imp3081] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2016] [Indexed: 12/28/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) in patients with chronic hepatitis C can develop after sustained virological response (SVR) to antiviral therapy for HCV, that is, the eradication of HCV, and effective surveillance systems for HCC should be established for this population. We retrospectively evaluated the utility of three laboratory liver fibrosis indices (aspartate aminotransferase-platelet ratio index [APRI], FIB-4 index and Forns index) for identifying patients at low risk of HCC development after SVR, for whom the termination of surveillance for HCC can be considered. METHODS APRI, FIB-4 index and Forns index scores were calculated based on laboratory data prior to anti-HCV therapy and at 24 weeks after the end of anti-HCV therapy (SVR24) in 522 patients with SVR who continued surveillance for HCC after SVR. The associations between HCC development and laboratory indices at both points were analysed. RESULTS Twenty-one patients developed HCC after SVR during 2.3-24.4 years follow-up. Whereas HCC developed even in patients with low APRI or FIB-4 index scores, no patients with low Forns index scores developed HCC after SVR. These results were confirmed in a separate cohort of 309 patients who achieved SVR (HCC developed in 17 patients during 1.7-21.6 years follow-up). CONCLUSIONS Forns index, especially assessed prior to anti-HCV therapy, was a useful laboratory liver fibrosis index for identifying patients at low likelihood of HCC after SVR. This index may be used as one of indicators to consider the termination of surveillance for HCC after the eradication of HCV.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yoshihiko Tachi
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - Takanori Hirai
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
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Velosa J. Why is viral eradication so important in patients with HCV-related cirrhosis? Antivir Ther 2016; 22:1-12. [PMID: 27553973 DOI: 10.3851/imp3077] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2016] [Indexed: 02/07/2023]
Abstract
Approximately one-third of patients infected with chronic HCV have cirrhosis, and this is likely to increase in the near future. The risk of complications, mainly the development of hepatocellular carcinoma, depends on the presence of cirrhosis, and a significant increase in the incidence of cirrhosis-related events, including mortality, is likely in the following years. All-oral therapy with direct-acting antivirals (DAAs) offers a safe and short treatment, with cure rates over 90% in compensated cirrhosis. Cirrhotic patients should be given high priority for treatment because viral clearance has a significant impact on the natural history of HCV infection, halting the progression of the disease and inducing the regression of fibrosis, as well as reducing the need for liver transplantation and improving survival. The benefit of DAAs is great in patients with decompensated cirrhosis, up until recently a population for whom no alternative therapy was available. The efficacy of all-oral therapy has been reported to improve liver function in about 50% of Child-Pugh class C patients. The regression of cirrhosis observed in more than half of patients achieving viral eradication on prior interferon-based regimens still has to be demonstrated in patients treated with DAAs, although there is reason to believe that this will happen. Advanced cirrhosis will eventually become the last boundary of antiviral therapy that will soon be conquered with new drugs currently pending approval.
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Affiliation(s)
- José Velosa
- Hospital de Santa Maria - Gastroenterology and Hepatology, Lisbon, Portugal
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Tachi Y, Hirai T, Kojima Y, Miyata A, Ohara K, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. Liver stiffness measurement using acoustic radiation force impulse elastography in hepatitis C virus-infected patients with a sustained virological response. Aliment Pharmacol Ther 2016; 44:346-55. [PMID: 27291657 DOI: 10.1111/apt.13695] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Revised: 03/11/2016] [Accepted: 05/21/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND Acoustic radiation force impulse (ARFI) elastography is a non-invasive method for measuring liver stiffness. However, there are no reports evaluating the value of ARFI elastography for liver fibrosis in chronic hepatitis C patients with a sustained virological response (SVR). AIM To investigate the diagnostic performance of ARFI elastography for the assessment of liver fibrosis in hepatitis C virus (HCV) infected patients with an SVR. METHODS In this prospective study, we enrolled 336 patients: 121 HCV patients with an SVR (44.6% women) and 215 patients with HCV (47.9% women). ARFI elastography measurements of all patients were performed on the same day of liver biopsy. RESULTS The diagnostic accuracies, expressed as areas under the receiver operating characteristic curves for ARFI elastography, in HCV patients with an SVR and those in patients with HCV were 0.818 and 0.875 for the diagnosis of significant fibrosis (≥F2), 0.909 and 0.888 for the diagnosis of severe fibrosis (≥F3), and 0.981 and 0.890 for the diagnosis of liver cirrhosis (F4), respectively. The optimum cut-off values for ARFI elastography were 1.26 m/s for ≥F2, 1.31 m/s for ≥F3 and 1.49 m/s for F4 in HCV patients with an SVR. The liver stiffness values were lower in patients with SVR compared with those in patients with HCV at the same stage of fibrosis. The liver stiffness values were affected by the necroinflammatory activity and the time after SVR. CONCLUSION Acoustic radiation force impulse elastography is an acceptable method for predicting the severity of fibrosis in patients with hepatitis C virus and a sustained viral response.
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Affiliation(s)
- Y Tachi
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - T Hirai
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - Y Kojima
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - A Miyata
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - K Ohara
- Department of Gastroenterology, Komaki City Hospital, Komaki, Japan
| | - Y Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - T Honda
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - T Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - K Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - M Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - H Goto
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
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Okamura Y, Ashida R, Yamamoto Y, Ito T, Sugiura T, Uesaka K. FIB-4 Index is a Predictor of Background Liver Fibrosis and Long-Term Outcomes After Curative Resection of Hepatocellular Carcinoma. Ann Surg Oncol 2016; 23:467-474. [DOI: 10.1245/s10434-016-5377-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Fujita K, Iwama H, Miyoshi H, Tani J, Oura K, Tadokoro T, Sakamoto T, Nomura T, Morishita A, Yoneyama H, Masaki T. Diabetes mellitus and metformin in hepatocellular carcinoma. World J Gastroenterol 2016; 22:6100-13. [PMID: 27468203 PMCID: PMC4945972 DOI: 10.3748/wjg.v22.i27.6100] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 05/25/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments.
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Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol 2016; 51:741-7. [PMID: 26872889 DOI: 10.1007/s00535-016-1174-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 01/18/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis. METHODS The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction. RESULTS The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups. CONCLUSIONS The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.
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Kudo M. Risk of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Who Achieved Sustained Virological Response. Liver Cancer 2016; 5:155-61. [PMID: 27493891 PMCID: PMC4960361 DOI: 10.1159/000443563] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Toyoda H, Tada T, Tsuji K, Hiraoka A, Tachi Y, Itobayashi E, Takaguchi K, Senoh T, Takizawa D, Ishikawa T, Kumada T. Characteristics and prognosis of hepatocellular carcinoma detected in patients with chronic hepatitis C after the eradication of hepatitis C virus: A multicenter study from Japan. Hepatol Res 2016; 46:734-42. [PMID: 26508201 DOI: 10.1111/hepr.12613] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 09/29/2015] [Accepted: 10/21/2015] [Indexed: 02/08/2023]
Abstract
AIM We investigated the characteristics and prognosis of patients with hepatocellular carcinoma (HCC) diagnosed after sustained virological response (SVR) to antiviral therapy for chronic hepatitis C virus (HCV) infection, namely, the eradication of HCV, according to surveillance status after SVR. METHODS In this multicenter study, liver function at HCC diagnosis and progression of HCC among patients with HCC diagnosed after SVR were compared. Outcomes were also investigated. RESULTS In patients not under surveillance after SVR, HCC was significantly more advanced at diagnosis, with tumors that were larger in size and of higher stage than in patients who continued under surveillance after SVR. Survival rates were significantly lower in patients not under surveillance (P < 0.0001). Among patients who were under surveillance, those with a 6-month surveillance interval had larger and higher stage HCC than patients with a 3-month interval. Recurrence rates in patients with a 6-month surveillance interval were significantly higher than in patients with a 3-month surveillance interval (P = 0.0417). CONCLUSION Lack of surveillance after SVR was obviously associated with more advanced HCC at detection, resulting in poor prognosis. More importantly, there may be a difference in the severity of HCC at diagnosis and prognosis based on the surveillance interval after SVR. Establishing guidelines how to survey patients with chronic hepatitis C after SVR is necessary.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Atsushi Hiraoka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Yoshihiko Tachi
- Department of Gastroenterology and Hepatology, Komaki City Hospital, Komaki, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Daichi Takizawa
- Department of Hepatology, Isesaki Municipal Hospital, Isesaki, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
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Tachi Y, Hirai T, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. α-fetoprotein levels after interferon therapy predict regression of liver fibrosis in patients with sustained virological response. J Gastroenterol Hepatol 2016; 31:1001-8. [PMID: 27123974 DOI: 10.1111/jgh.13245] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 11/06/2015] [Accepted: 11/06/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Eradicating chronic hepatitis C virus (HCV) infection improves liver fibrosis and reduces hepatocellular carcinoma (HCC) incidence in chronic HCV patients. We evaluated the relationship between fibrosis regression, as assessed by sequential biopsies, and clinical factors of patients with sustained virological response (SVR). METHODS We retrospectively enrolled 130 patients (74 men; 60.1 ± 8.1 years) with chronic HCV treated with interferon and ribavirin therapy who achieved SVR. To evaluate the change in fibrosis stage over time, all patients underwent a pre-therapy initial biopsy and a second biopsy after achieving SVR. RESULTS The mean time between biopsies was 5.5 ± 1.2 years. Fibrosis stage regressed in 55 patients (42.3%), remained stable in 69 (53.1%), and progressed in 6 (4.6%). The mean fibrosis stage significantly decreased, from 2.01 ± 0.99 units to 1.61 ± 1.24 units (P < 0.001). Aspartate aminotransferase, γ-glutamyltransferase, and α-fetoprotein (AFP) levels at 24 weeks after the end of treatment (EOT) were significantly lower, and the platelet count at 24 weeks after the EOT was significantly higher in patients with fibrosis regression than in those without. Logistic regression analysis confirmed that lower AFP levels (< 5.4 ng/mL) at 24 weeks after the EOT (odds ratio [OR], 4.626; 95% confidence interval [CI], 1.557-13.153; P = 0.006) and HCV genotype 2 (OR, 2.198; 95% CI, 1.010-4.786; P = 0.047) were significant independent predictive factors for regressed fibrosis after SVR. CONCLUSIONS Lower post-treatment AFP levels and HCV genotype 2 significantly correlated with liver fibrosis regression after SVR.
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Affiliation(s)
- Yoshihiko Tachi
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Takanori Hirai
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Youji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
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Nagaoki Y, Aikata H, Nakano N, Shinohara F, Nakamura Y, Hatooka M, Morio K, Kan H, Fujino H, Kobayashi T, Fukuhara T, Masaki K, Ono A, Nakahara T, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Imamura M, Takahashi S, Kawakami Y, Ochi H, Chayama K. Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large-scale, long-term cohort study. J Gastroenterol Hepatol 2016; 31:1009-15. [PMID: 26584407 DOI: 10.1111/jgh.13236] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 10/01/2015] [Accepted: 11/08/2015] [Indexed: 12/30/2022]
Abstract
BACKGROUND We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study. METHODS We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013. RESULTS During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P < 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P < 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P < 0.0001) as significant and independent risk factors for post-SVR HCC. CONCLUSIONS Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Norihito Nakano
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Fumi Shinohara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Yuki Nakamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Masahiro Hatooka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiromi Kan
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Tomoki Kobayashi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Takayuki Fukuhara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Keiichi Masaki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Shoichi Takahashi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hidenori Ochi
- Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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Examining Hepatitis C Virus Treatment Preference Heterogeneity Using Segmentation Analysis: Treat Now or Defer? J Clin Gastroenterol 2016; 50:252-7. [PMID: 26166145 PMCID: PMC4811360 DOI: 10.1097/mcg.0000000000000380] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE To improve our understanding of patients' treatment preferences for chronic hepatitis C (HCV). METHODS Subjects with HCV were recruited from 2 VA medical centers. Preferences were ascertained using conjoint analysis. We used segmentation analysis to examine whether there were groups of respondents with similar preferences that were systematically different from the preferences of others. We then measured the associations between treatment preference with subjects' characteristics and their gist principles related to living with HCV and the burden of therapy. RESULTS A total of 199 subjects participated in this study. The segmentation analysis demonstrated that subjects could be classified into 2 distinct groups. The larger group [group 1, n=118 (59%)] opted for current treatment and the other [group 2, n=81 (41%)] preferred to defer. Patients with cirrhosis were less likely to belong to group 2 (prefer to defer) compared with those without cirrhosis (40.5% vs. 21.3%), whereas subjects self-identifying as African American were more likely to belong to group 2 than white subjects (51.3% vs. 30.5%). Members of group 1 had a more positive overall gist principles related to HCV compared with members of group 2 [mean (SD) score=28.63 (3.06) vs. 26.46 (2.79), P<0.0001]. These gist principles mediated the relationship between race and treatment preference (Sobel test statistic=-2.68, 2-tailed P=0.007). CONCLUSIONS Our findings indicate that there are groups of HCV patients with similar preferences that are distinct from other groups' preferences. Patients' gist principles related to the significance of having a chronic viral infection and the burdens of therapy are strongly related to their current treatment decisions. These findings help inform how best to initiate and deliver treatment for patients with HCV.
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Asahina Y, Izumi N, Hiromitsu K, Kurosaki M, Koike K, Suzuki F, Takikawa H, Tanaka A, Tanaka E, Tanaka Y, Tsubouchi H, Hayashi N, Hiramatsu N, Yotsuyanagi H. JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2. Hepatol Res 2016; 46:129-65. [PMID: 26876581 DOI: 10.1111/hepr.12645] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital
| | | | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo
| | | | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine
| | - Eiji Tanaka
- The Second Department of Internal Medicine, Shinshu University School of Medicine
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science
| | | | | | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
| | - Hiroshi Yotsuyanagi
- Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo
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