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Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR. J Gastroenterol 2022; 58:299-310. [PMID: 36585501 DOI: 10.1007/s00535-022-01940-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/05/2022] [Indexed: 12/31/2022]
Abstract
Hepatitis C virus infection is characterized by chronic liver inflammation and fibrogenesis, leading to end-stage liver failure and hepatocellular carcinoma over the course of 20 to 30 years. It seems not only the chronicity of hepatitis C but also the presence of the virus in non-hepatic tissues creates a favorable environment for the potential development of pathogenic impacts on extrahepatic systems and organs. Numerous extra-hepatic manifestations have been reported in association with HCV infection, all of which can substantially affect morbidity, mortality, and quality of life. With the recent development of DAAs, antiviral treatment can cure almost all patients with HCV infection, even those intolerant of or unresponsive to IFN treatment, and several large multicenter studies have confirmed the association of DAA-induced SVR with reductions in liver-related and liver-unrelated complications, such as cardiovascular events, end stage renal disease, and so on. Because, in addition to liver-related diseases, extrahepatic lesions are threatening for patients, it is important to eradicate the virus before these progress and affect life prognosis; in other words, patients should be treated before reaching the point of no return. Tailored surveillance with biomarkers such as M2BPGi and Ang-2, which can be used to identify patients with an elevated risk of EHM, and early prevention or treatment for these patients could improve the morbidity, mortality and QOL. Advancement of both basic and clinical research in this field including the development of more precise biomarkers is highly anticipated.
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Nakagawa M, Nawa N, Takeichi E, Shimizu T, Tsuchiya J, Sato A, Miyoshi M, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Azuma S, Kakinuma S, Fujiwara T, Watanabe M, Tanaka Y, Asahina Y. Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs. J Gastroenterol 2020; 55:990-999. [PMID: 32770465 DOI: 10.1007/s00535-020-01715-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/28/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND It is crucial to identify risk factors for life prognosis after hepatitis C virus (HCV) eradication among patients with or without a high risk of liver cancer or complications. METHODS This is a prospective, multicenter and observational study using the database of 1031 patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the development of hepatocellular carcinoma (HCC) and patients' survival after a sustained virological response (SVR). The Cox proportional hazards regression model was used to estimate hazard ratios associated with HCC development and survival. RESULTS AFP at SVR was significantly associated with HCC recurrence in the adjusted model. Liver fibrosis, Mac-2 binding protein glycosylation isomer (M2BPGi) at SVR and smoking status before treatment were positively associated with the development of HCC and M2BPGi was positively associated with HCC recurrence, although not reaching statistical significance. Among patients without a history of HCC, M2BPGi and estimated glomerular filtration rate (eGFR) at SVR were significantly associated with death after viral eradication [M2BPGi (HR 4.07, 95% CI 1.22, 13.57), eGFR (HR 0.97, 95% CI 0.94, 0.99)]. Strikingly, of 16 patients who died, among participants without a history of HCC, only two died of liver cancer associated with HCV, whereas 11 died of non-HCV- related cancer or cardiovascular diseases. CONCLUSION M2BPGi at SVR is a potential predictor for patients' survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancer-related and unrelated to HCV, as well as cardiovascular diseases, after viral eradication.
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Affiliation(s)
- Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.,Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobutoshi Nawa
- Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Medical Education Research and Development, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
| | - Eiko Takeichi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Taro Shimizu
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.,Department of Clinical Laboratory, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Yasuhiro Itsui
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.,Department of General Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Takeo Fujiwara
- Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.,Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yujiro Tanaka
- Department of Medical Education Research and Development, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. .,Department of Liver Disease Control, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
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Kurokawa K, Ohki T, Kato J, Fukumura Y, Imai M, Shibata C, Arai J, Kondo M, Takagi K, Kojima K, Seki M, Mori M, Toda N, Tagawa K. Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report. J Med Case Rep 2020; 14:62. [PMID: 32456712 PMCID: PMC7251811 DOI: 10.1186/s13256-020-02392-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 04/28/2020] [Indexed: 12/16/2022] Open
Abstract
Background Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion. Case presentation A 74-year-old Japanese man who had hepatitis C virus–related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy. Conclusions Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.
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Affiliation(s)
- Ken Kurokawa
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan.
| | - Takamasa Ohki
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Jun Kato
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Yukiyo Fukumura
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Makoto Imai
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Chikako Shibata
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Junya Arai
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Mayuko Kondo
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Kaoru Takagi
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Kentaro Kojima
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Michiharu Seki
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Masaya Mori
- Department of Pathology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Nobuo Toda
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Kazumi Tagawa
- Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumi-cho Chiyoda-ku, Tokyo, 101-8643, Japan
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Saleh MI, Bani Melhim S. A time-to-event analysis describing virologic response in patients with chronic hepatitis C infection. J Chemother 2019; 31:274-283. [PMID: 31070545 DOI: 10.1080/1120009x.2019.1609739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The objective of this project was to describe longitudinal change in chronic hepatitis C virologic reponse using time-to-event (TTE) analysis and to identify patient characteristics that determine the dynamics of this change. We compiled demographic, clinical, and genetic data from 715 chronic hepatitis C virus (HCV) patients treated with pegylated interferon (PEG-IFN) alfa-2a and ribavirin. TTE modelling described the time between antiviral treatment initiation and the first observation of undetectable HCV RNA. A lognormal TTE model was selected to describe time to first undetectable HCV RNA. The identified predictors of prolonged time to achieve undetectable HCV RNA include HCV genotype 1, low pre-treatment ALT level, older age, or with elevated baseline haemoglobin level. In conclusion, a cohort of patients with low probability of achieving SVR can be identified. This project identifies patients with a low risk of responding to PEG-IFN alfa-2a and ribavirin combination.
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Xing J, Spradling PR, Moorman AC, Holmberg SD, Teshale EH, Rupp LB, Gordon SC, Lu M, Boscarino JA, Schmidt MA, Trinacty CM, Xu F. A Point System to Forecast Hepatocellular Carcinoma Risk Before and After Treatment Among Persons with Chronic Hepatitis C. Dig Dis Sci 2017; 62:3221-3234. [PMID: 28965221 DOI: 10.1007/s10620-017-4762-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 09/11/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. AIM Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. METHODS Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. RESULTS Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87). CONCLUSION This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR.
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Affiliation(s)
- Jian Xing
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Mailstop G37, 1600 Clifton Road NE, Atlanta, GA, 30333, USA
| | - Philip R Spradling
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Mailstop G37, 1600 Clifton Road NE, Atlanta, GA, 30333, USA.
| | - Anne C Moorman
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Mailstop G37, 1600 Clifton Road NE, Atlanta, GA, 30333, USA
| | - Scott D Holmberg
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Mailstop G37, 1600 Clifton Road NE, Atlanta, GA, 30333, USA
| | - Eyasu H Teshale
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Mailstop G37, 1600 Clifton Road NE, Atlanta, GA, 30333, USA
| | | | | | - Mei Lu
- Henry Ford Health System, Detroit, MI, USA
| | | | - Mark A Schmidt
- The Center for Health Research, Kaiser Permanente-Northwest, Portland, OR, USA
| | - Connie M Trinacty
- The Center for Health Research, Kaiser Permanente-Hawaii, Honolulu, HI, USA
| | - Fujie Xu
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC), Mailstop G37, 1600 Clifton Road NE, Atlanta, GA, 30333, USA
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Ok KS, Jeong SH, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, Bae SH, Lee HC. The clinical outcomes of chronic hepatitis C in South Korea: A prospective, multicenter cohort study. Medicine (Baltimore) 2016; 95:e4594. [PMID: 27583874 PMCID: PMC5008558 DOI: 10.1097/md.0000000000004594] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region.From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival.During the median follow-up of 39.0 months (range 18.0-81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150 × 10/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002).The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy.
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Affiliation(s)
- Kyeong Sam Ok
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
- Correspondence: Sook-Hyang Jeong, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea (e-mail: )
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan
| | - In Hee Kim
- Departement of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University College of Medicine, Jeonju
| | - Sung Bum Cho
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun
| | - Si Hyun Bae
- Department of Internal Medicine, The Catholic University of Korea, Seoul Saint Mary's Hospital
| | - Han Chu Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Nakayama M, Kobayashi H, Fukushima K, Ishido M, Komada Y, Yoshizawa K. Predictive factors for 24 weeks sustained virologic response (SVR24) and viral relapse in patients treated with simeprevir plus peginterferon and ribavirin. Hepatol Int 2016; 10:158-68. [PMID: 26264253 PMCID: PMC4722076 DOI: 10.1007/s12072-015-9654-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 07/15/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Simeprevir with peginterferon and ribavirin has been used for the treatment of chronic hepatitis caused by genotype 1 hepatitis C virus (HCV). We explored the predictive factors for sustained virological response (SVR) and viral relapse using datasets from four Japanese phase 3 studies (CONCERTO). METHODS We used a multiple logistic regression model. First, an integrated dataset comprising 357 patients was analyzed. Subsequently, prior treatment-naïve and relapser (223 patients) and nonresponder (134 patients) of interferon-based treatment subsets were analyzed to identify predictors of SVR. A subset of nonresponders (106 patients) who were treated ≥24 weeks was also analyzed to identify predictors for viral relapse. RESULTS In the integrated dataset, prior treatment response was significantly associated with SVR. In subset analyses, interleukin-28B (IL28B) TT genotype and undetectable plasma HCV RNA level at week 4 were associated in treatment-naïve patients and relapsers [odds ratio (OR); 4.106 and 3.701, respectively]. In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively). Furthermore, ribavirin dose intensity (RBV-DI) and detectable plasma HCV RNA at week 4 were significantly associated with viral relapse (OR; 0.327 and 2.922, respectively). CONCLUSION IL28B and plasma HCV RNA level at week 4 were clinically relevant predictive factors for SVR in treatment-naïve patients and relapsers. Moreover, RBV-DI and plasma HCV level at week 4 were identified as relevant predictive factors for viral relapse in nonresponders.
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Affiliation(s)
- Masahiko Nakayama
- Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
| | - Hisanori Kobayashi
- Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan
| | - Koji Fukushima
- Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan
| | - Miwako Ishido
- Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan
| | - Yuji Komada
- Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan
- Research and Development Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan
| | - Kazutake Yoshizawa
- Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan
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Hiramatsu N, Oze T, Takehara T. Suppression of hepatocellular carcinoma development in hepatitis C patients given interferon-based antiviral therapy. Hepatol Res 2015; 45:152-61. [PMID: 25052449 DOI: 10.1111/hepr.12393] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Revised: 07/15/2014] [Accepted: 07/17/2014] [Indexed: 12/17/2022]
Abstract
The advance of antiviral treatment for chronic hepatitis C has brought a high sustained virological response (SVR) rate. In this review article, the suppressive effect of interferon (IFN)-based therapy on the development of hepatocellular carcinoma (HCC), risk factors for developing HCC and the characteristics of HCC development after SVR among chronic hepatitis C patients given IFN-based therapy were studied. The HCC incidence has been revealed to decrease with IFN-based antiviral therapy, especially in SVR, and the risk factors for developing HCC were older age, advanced liver fibrosis and male sex. α-Fetoprotein levels at 24 weeks after the end of IFN-based treatment was associated strongly with HCC incidence irrespective of virological response. In patients with SVR, other risk factors were glucose metabolism disorders, lipid metabolism disorders and alcohol intake. Extra attention to the possibility of HCC incidence should be required for these SVR patients. Antiviral therapy with a combination of HCV-specific direct-acting antivirals (DAA) is expected to be utilized in the future. However, it is not known whether DAA-based treatment can suppress HCC to the level of IFN-based treatment. Further research is required to clarify this.
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Affiliation(s)
- Naoki Hiramatsu
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
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Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes. J Gastroenterol 2014; 49:1504-13. [PMID: 24317936 DOI: 10.1007/s00535-013-0921-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 11/22/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Due to advances in interferon (IFN) therapy for chronic hepatitis C, most elderly patients, and even many of those with advanced hepatic fibrosis, now achieve a sustained virological response (SVR). However, carcinogenesis remains problematic in these patients. Hence, we aimed to elucidate risk factors for hepatocarcinogenesis in SVR patients and to present an appropriate follow-up protocol for improving outcomes. METHODS We retrospectively studied 562 consecutive SVR patients for a median observation period of 4.8 years. RESULTS Hepatocellular carcinoma was diagnosed in 31 patients (5.5%). Respective cumulative incidences were 3.1, 10.1, and 15.9% at 5, 10, and 15 years after completion of IFN therapy. The proportional hazards model identified moderate or advanced fibrosis stage, advanced age, habitual alcohol consumption, and alpha-fetoprotein elevation as determinants of carcinogenesis, with hazard ratios of 10.7 (p < 0.001), 4.1 (p < 0.01), 3.9 (p < 0.01), and 2.6 (p < 0.05), respectively. Carcinoma was diagnosed in 26% of patients more than 10 years after completion of IFN therapy. Unexpectedly, F2 fibrosis was detected in 42% of these patients. The 5-year survival rate was 93% in the patients who had received periodic cancer screening but only 60% in those who had not. CONCLUSION We recommend that SVR patients be observed at 6-month intervals, at a minimum, to facilitate diagnosis at an early stage, for as long as possible after completion of therapy even if not at an advanced stage of fibrosis.
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Yang Z, Zhuang L, Yang L, Liu C, Lu Y, Xu Q, Chen X, Chen L. Efficacy and safety of peginterferon plus ribavirin for patients aged ≥ 65 years with chronic hepatitis C: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2014; 38:440-50. [PMID: 24176812 DOI: 10.1016/j.clinre.2013.08.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Revised: 08/04/2013] [Accepted: 08/29/2013] [Indexed: 02/08/2023]
Abstract
METHODS Studies up to August 30, 2012 of the efficacy and safety of peginterferon plus ribavirin therapy in CHC patients aged≥65 years were systematically identified in PubMed, Ovid, Web of Knowledge and Cochrane Library databases. A meta-analysis was performed using both fixed- and random-effects models based on heterogeneity across studies. RESULTS The overall sustained virological response (SVR) in CHC patients aged≥65 years was significantly lower than in patients aged<65 years on both intention-to-treat (ITT; 42.0% vs. 60.1%, respectively; P<0.00001) and per-protocol (PP; 54.4% vs. 67.4%, respectively; P=0.002) analyses, including treatment-naïve patients. Subgroup analysis showed that patients≥65 years with either hepatitis C virus (HCV) genotype 1/4 or 2/3 had lower SVR rates than younger patients. No statistically significant differences were observed between the two groups in terms of rapid virological response (RVR) and early virological response (EVR) rates (both P≥0.05). However, the end-of-treatment virological response (ETR) rate was lower in patients≥65 years, who also had a significantly higher risk of relapse than those aged<65 years (39.8% vs. 26.9%, respectively; P<0.00001). The discontinuation rate in the older patients was also significantly higher than in the younger patients (25.5% vs. 14.8%, respectively; P<0.00001). Ribavirin dose reduction in the older patients treated with peginterferon plus ribavirin was also significantly higher than in younger patients (44.5% vs. 32.8%, respectively; P<0.00001). CONCLUSION Peginterferon plus ribavirin therapy was effective for older patients with CHC, particularly those with HCV genotype 2/3. Response-guided therapy can be used for older patients with genotype 1/4, but such patients had poorer treatment adherence, leading to poorer treatment efficacy.
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Affiliation(s)
- Zongguo Yang
- Shanghai Public Health Clinical Center Affiliated to Fudan University, No. 2901, Caolang Rd, Jinshan District, 201508 Shanghai, PR China
| | - Liping Zhuang
- Shanghai Medical College, Fudan University, Department of Oncology, 200032 Shanghai, PR China; Shanghai Cancer Center, Department of Integrative Medicine, 200032 Shanghai, PR China
| | - Lei Yang
- The Central Hospital of China Aerospace Corporation, 100049 Beijing, PR China
| | - Cheng Liu
- Shanghai Public Health Clinical Center Affiliated to Fudan University, No. 2901, Caolang Rd, Jinshan District, 201508 Shanghai, PR China
| | - Yunfei Lu
- Shanghai Public Health Clinical Center Affiliated to Fudan University, No. 2901, Caolang Rd, Jinshan District, 201508 Shanghai, PR China
| | - Qingnian Xu
- Shanghai Public Health Clinical Center Affiliated to Fudan University, No. 2901, Caolang Rd, Jinshan District, 201508 Shanghai, PR China
| | - Xiaorong Chen
- Shanghai Public Health Clinical Center Affiliated to Fudan University, No. 2901, Caolang Rd, Jinshan District, 201508 Shanghai, PR China.
| | - Liang Chen
- Shanghai Public Health Clinical Center Affiliated to Fudan University, No. 2901, Caolang Rd, Jinshan District, 201508 Shanghai, PR China.
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Zavaglia C, Silini E, Mangia A, Airoldi A, Piazzolla V, Vangeli M, Stigliano R, Foschi A, Mazzarelli C, Tinelli C. Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion-acquired HCV infection. Liver Int 2014; 34:e308-16. [PMID: 24529078 DOI: 10.1111/liv.12502] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 02/08/2014] [Indexed: 12/20/2022]
Abstract
AIMS Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. METHODS Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. RESULTS The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. CONCLUSIONS In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.
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Affiliation(s)
- Claudio Zavaglia
- Struttura Complessa di Gastroenterologia ed Epatologia 'Crespi', Ospedale Niguarda, piazza Ospedale Maggiore 3, 20162, Milano, Italy
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12
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Tajiri K, Shimizu Y. Liver physiology and liver diseases in the elderly. World J Gastroenterol 2013; 19:8459-8467. [PMID: 24379563 PMCID: PMC3870491 DOI: 10.3748/wjg.v19.i46.8459] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Revised: 08/02/2013] [Accepted: 09/13/2013] [Indexed: 02/06/2023] Open
Abstract
The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Moreover, elderly patients have significantly decreased reserve functions of various organs, reducing their tolerability to treatments for liver diseases. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients.
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Abstract
Worldwide, an estimated 130-170 million people have HCV infection. HCV prevalence is highest in Egypt at >10% of the general population and China has the most people with HCV (29.8 million). Differences in past HCV incidence and current HCV prevalence, together with the generally protracted nature of HCV disease progression, has led to considerable diversity in the burden of advanced liver disease in different countries. Countries with a high incidence of HCV or peak incidence in the recent past will have further escalations in HCV-related cirrhosis and hepatocellular carcinoma (HCC) over the next two decades. Acute HCV infection is difficult to detect because of the generally asymptomatic nature of the disease and the marginalization of at-risk populations. Around 25% of patients with acute HCV infection undergo spontaneous clearance, with increased rates among those with favourable IL28B genotypes, acute symptoms and in women. The remaining 75% of patients progress to chronic HCV infection and are subsequently at risk of progression to hepatic fibrosis, cirrhosis and HCC. Chronic hepatitis C generally progresses slowly in the initial two decades, but can be accelerated during this time as a result of advancing age and co-factors such as heavy alcohol intake and HIV co-infection.
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14
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Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Tada T, Tanaka J. Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients. J Gastroenterol Hepatol 2013. [PMID: 23190084 DOI: 10.1111/jgh.12057] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM The average age of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients has been rising in Japan. We evaluate characteristics of HCV-positive patients who develop HCC in older age to determine an optimal surveillance strategy. METHODS A total of 323 patients with three or more years of follow-up before HCC diagnosis and 323 propensity-matched controls without HCC were studied. HCC patients were classified into four groups according to age at the time of HCC diagnosis: group A (≤ 60 years, n = 36), group B (61-70 years, n = 115), group C (71-80 years, n = 143), and group D (> 80 years, n = 29). Clinical and laboratory data were compared. RESULTS Platelet counts were significantly higher in the older groups at HCC diagnosis (P < 0.0001). The rate of platelet counts decline was lower in older groups (P = 0.0107). The average integration value of serum alanine aminotransferase (ALT) in groups A, B, C, and D were 80.9 IU/L, 62.3 IU/L, 59.0 IU/L, and 44.9 IU/L, respectively (P < 0.0001). In older patients (≥ 65 years old), cirrhosis and average integration value of ALT were significantly associated with hepatocarcinogenesis, but platelet count was not. CONCLUSION Elderly HCV-positive patients (≥ 65 years old) with low ALT values developed HCC regardless of their platelet counts. These findings should be taken into account when designing the most suitable HCC surveillance protocol for this population.
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Affiliation(s)
- Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
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15
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Masuzaki R, Tateishi R, Yoshida H, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Asaoka Y, Kondo Y, Goto T, Ikeda H, Shiina S, Omata M, Koike K. Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography. World J Gastroenterol 2012; 18:1385-90. [PMID: 22493553 PMCID: PMC3319966 DOI: 10.3748/wjg.v18.i12.1385] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2011] [Revised: 08/01/2011] [Accepted: 01/22/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC). METHODS Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness. RESULTS A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043). CONCLUSION Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.
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16
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Nishikawa H, Iguchi E, Koshikawa Y, Ako S, Inuzuka T, Takeda H, Nakajima J, Matsuda F, Sakamoto A, Henmi S, Hatamaru K, Ishikawa T, Saito S, Kita R, Kimura T, Osaki Y. The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients. BMC Res Notes 2012; 5:135. [PMID: 22405406 PMCID: PMC3317866 DOI: 10.1186/1756-0500-5-135] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Accepted: 03/10/2012] [Indexed: 02/08/2023] Open
Abstract
Background The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108 elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response. Results There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, P < 0.001). Conclusions The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
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Kawai T. Experience of long-term low dose pegylated interferon therapy for chronic hepatitis C patients who cannot treat with standard of care therapy. KANZO 2012; 53:699-706. [DOI: 10.2957/kanzo.53.699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Huang CF, Chuang WL, Yu ML. Chronic hepatitis C infection in the elderly. Kaohsiung J Med Sci 2011; 27:533-7. [PMID: 22208535 DOI: 10.1016/j.kjms.2011.10.020] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Accepted: 03/19/2011] [Indexed: 01/14/2023] Open
Abstract
The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly in many countries. Aging is regarded as an unfavorable factor for liver disease progression and treatment outcome in HCV infection. The efficacy and safety of treating elderly patients remain a source of significant debate. Discrepancies in results may be attributed to dissimilarities in study design and treatment regimens. The long-term benefits of administering interferon-based therapy to elderly patients with HCV infection is a critical issue when taking the patient's remaining life expectancy into consideration. Rapid virological response is the most notable on-treatment response factor that is predictive of treatment success in elderly patients. A shortened treatment course may reduce drug-related side effects and promote treatment adherence, especially in the elderly. A regimen tailored towards super-responders might provide insights for treatment strategies in elderly patients.
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Affiliation(s)
- Chung-Feng Huang
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
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Watanabe S, Enomoto N, Koike K, Izumi N, Takikawa H, Hashimoto E, Moriyasu F, Kumada H, Imawari M. Cancer preventive effect of pegylated interferon α-2b plus ribavirin in a real-life clinical setting in Japan: PERFECT interim analysis. Hepatol Res 2011; 41:955-64. [PMID: 21707888 DOI: 10.1111/j.1872-034x.2011.00847.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AIM This study was conducted to clarify the incidence of hepatocellular carcinoma (HCC) and the factors contributing to its occurrence by following chronic hepatitis C patients who received pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) combination therapy. METHODS Patients who received PEG-IFN α-2b and RBV combination therapy with no history of HCC or HCC within 3 months after the start of treatment were observed for the onset of HCC at 67 centers. RESULTS Sustained virological response (SVR) was observed in 999 (53.5%) of 1865 patients eligible for analysis. During the observation period (median duration: 4 years and 3 months), HCC developed in 59 patients (3.1%). A significant difference was observed in the 5-year cumulative incidence of HCC between SVR and non-SVR patients (1.1% vs. 7.1%). Factors contributing to HCC selected in multivariate analysis were therapeutic efficacy, sex, age, alanine aminotransferase (ALT) level at 24 weeks after the end of treatment, and platelet count. Non-SVR patients with ALT improvement after the end of treatment had a significantly lower 5-year cumulative incidence of HCC than those without (3.4% vs. 11.0%). HCC developed in 10 patients who achieved SVR, and multivariate analysis indicated that ALT level at 24 weeks after the end of treatment was the only significant factor contributing to HCC. CONCLUSION Several known risk factors for HCC contributed to HCC in patients who received PEG-IFN α-2b and RBV combination therapy, and ALT abnormality after the end of treatment contributes to the onset of HCC in both non-SVR and SVR patients.
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Affiliation(s)
- Sumio Watanabe
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanash Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, Tokyo Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo Department of Medicine, Teikyo University School of Medicine, Tokyo Department of Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo Department of Hepatology, Toranomon Hospital, Tokyo Department of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
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Honda T, Miyaaki H, Ichikawa T, Taura N, Miuma S, Shibata H, Isomoto H, Takeshima F, Nakao K. Clinical characteristics of hepatocellular carcinoma in elderly patients. Oncol Lett 2011; 2:851-854. [PMID: 22866139 DOI: 10.3892/ol.2011.359] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Accepted: 06/03/2011] [Indexed: 01/07/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) in elderly patients in Japan has been on the increase. The aim of the present study was to evaluate the impact of aging on the clinicopathological findings and the survival of HCC patients. A total of 624 patients with HCC were examined in this study. The patients were classified according to their age at the time of diagnosis: one group comprised younger patients (<75 years; n=544) and the second comprised elderly patients [(≥75 years; n=80, (12%)]. Results showed that there were significantly more female patients (younger:elderly, 22:36; p=0.005), normal livers (younger:elderly, 0.3:6%; p=0.0002), non-viral HCC (younger:elderly, 11:31%; p<0.001) and solitary tumors (younger:elderly, 53:76%; p=0.0008) in the elderly group. Five out of seven (71%) non-B non-C (NBNC) HCC patients who developed HCC in the normal liver were elderly patients. Survival between the younger and elderly HCC groups was not significantly different (younger:elderly, 4.38:3.45 years; p=0.665). Additionally, elderly HCC patients had fewer tumors, more mild underlying liver damage, and more frequent NBNC HCC. Their prognosis was not necessarily poorer than that of the younger HCC patients. Additionally, it appears that elderly patients develop HCC even without fibrosis. Therefore, aging may be a factor affecting hepatocarcinogenesis.
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Affiliation(s)
- Takuya Honda
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan
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Oze T, Hiramatsu N, Yakushijin T, Mochizuki K, Oshita M, Hagiwara H, Mita E, Ito T, Fukui H, Inui Y, Hijioka T, Inada M, Kaytayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Kato M, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N. Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy. J Hepatol 2011; 54:604-11. [PMID: 21145907 DOI: 10.1016/j.jhep.2010.07.043] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2010] [Revised: 07/28/2010] [Accepted: 07/28/2010] [Indexed: 01/06/2023]
Abstract
BACKGROUND & AIMS This study investigated the efficacy and adverse effects of pegylated interferon (Peg-IFN) plus ribavirin therapy in aged patients with chronic hepatitis C (CH-C). METHODS A total of 1040 naïve patients with CH-C (genotype 1, n=759; genotype 2, n=281), of whom 240 (23%) over 65 years old (y.o.), were treated with Peg-IFN alfa-2b plus ribavirin and assessed after being classified into five categories, according to age. RESULTS The discontinuance rate was higher for patients over 70 y.o. (36%), the most common reason being anemia. In the presence of genotype 1, the SVR rate was similar (42-46%) among patients under 65 y.o. and declined (26-29%) among patients over 65 y.o. For patients over 65 y.o., being male (Odds ratio, OR, 3.5, p=0.035) and EVR (OR, 83.3, p<0.001) were significant factors for SVR, in multivariate analysis. The Peg-IFN dose was related to EVR, and when EVR was attained, 76-86% of patients over 65 y.o. achieved SVR. SVR was not achieved (0/35, 0/38, respectively) if a 1-log decrease and a 2-log decrease were not attained at week 4 and week 8, respectively. In the presence of genotype 2, the SVR rate was similar (70-71%) among patients under 70 y.o. and declined among patients over 70 y.o. (43%). CONCLUSIONS Aged patients up to 65 y.o. with genotype 1 and 70 y.o. with genotype 2 can be candidates for Peg-IFN plus ribavirin therapy. The response-guided therapy can be applied for aged patients with genotype 1.
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Affiliation(s)
- Tsugiko Oze
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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Akiyama T, Mizuta T, Kawazoe S, Eguchi Y, Kawaguchi Y, Takahashi H, Ozaki I, Fujimoto K. Body mass index is associated with age-at-onset of HCV-infected hepatocellular carcinoma patients. World J Gastroenterol 2011; 17:914-21. [PMID: 21412500 PMCID: PMC3051141 DOI: 10.3748/wjg.v17.i7.914] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 09/29/2010] [Accepted: 10/06/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To identify factors associated with the age at onset of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS Five hundred and fifty-six consecutive patients positive for HCV antibody and treatment-naïve HCC diagnosed between 1995 and 2004 were analyzed. Patients were classified into three groups according to age at HCC onset: < 60 years (n = 79), 60-79 years (n = 439), or ≥ 80 years (n = 38). Differences among groups in terms of sex, body mass index (BMI), lifestyle characteristics, and liver function were assessed. Factors associated with HCC onset in patients < 60 or ≥ 80 years were analyzed by logistic regression analysis. RESULTS Significant differences emerged for sex, BMI, degree of smoking and alcohol consumption, mean bilirubin, alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGT) levels, prothrombin activity, and platelet counts. The mean BMI values of male patients > 60 years old were lower and mean BMI values of female patients < 60 years old were higher than those of the general Japanese population. BMI > 25 kg/m² [hazard ratio (HR), 1.8, P = 0.045], excessive alcohol consumption (HR, 2.5, P = 0.024), male sex (HR, 3.6, P = 0.002), and GGT levels > 50 IU/L (HR, 2.4, P = 0.014) were independently associated with HCC onset in patients < 60 years. Low ALT level was the only factor associated with HCC onset in patients aged ≥ 80 years. CONCLUSION Increased BMI is associated with increased risk for early HCC development in HCV-infected patients. Achieving recommended BMI and reducing alcohol intake could help prevent hepatic carcinogenesis.
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Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, Yasui Y, Hosokawa T, Ueda K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Izumi N. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52:518-27. [PMID: 20683951 DOI: 10.1002/hep.23691] [Citation(s) in RCA: 227] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
UNLABELLED An increase in the aging population is an impending problem. A large cohort study was carried out to determine the influence of aging and other factors on hepatocarcinogenesis in patients treated with interferon. Biopsy-proven 2547 chronic hepatitis C patients registered at our referral center since 1992 were included. Of these, 2166 were treated with interferon-based therapy. Incidences of hepatocellular carcinoma (HCC) associated with interferon were analyzed by Kaplan-Meier and person-years methods for an average follow-up of 7.5 years. Factors associated with HCC risk were determined by Cox proportional hazard analysis. HCC developed in 177 interferon-treated patients. The risk for HCC depended on age at primary biopsy and increased more than 15-fold after 65 years of age. Even when stratified by stage of fibrosis, the cumulative and annual incidences of HCC were significantly higher in older patients than in younger patients (P < 0.001) at the same stage of fibrosis, except for cirrhosis. Progression of fibrosis over time was significantly accelerated in older patients. The impact of viral eradication on HCC prevention was less significant in older patients than in younger patients. Multivariate analysis confirmed that age, gender, liver fibrosis, liver steatosis, total cholesterol level, fasting blood sugar level, baseline and postinterferon alpha-fetoprotein level, and virological response to interferon were independent risk factors associated with HCC. Aging was the strongest risk factor for a nonvirological response to interferon-based antiviral therapy. CONCLUSION Elderly patients are at a higher risk for HCC. Hepatitis C viral eradication had a smaller effect on hepatocarcinogenesis in older patients. Patients should therefore be identified at an earlier age and treatment should be initiated.
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Affiliation(s)
- Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Thein HH, Yi Q, Heathcote EJ, Krahn MD. Prognosis of hepatitis C virus-infected Canadian post-transfusion compensation claimant cohort. J Viral Hepat 2009; 16:802-13. [PMID: 19413692 DOI: 10.1111/j.1365-2893.2009.01136.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Accurate prognostic estimates were required to ensure the sufficiency of the $1.1 billion compensation fund established in 1998 to compensate Canadians who acquired hepatitis C virus (HCV) infection through blood transfusion between 1986 and 1990. This article reports the application of Markov modelling and epidemiological methods to estimate the prognosis of individuals who have claimed compensation. Clinical characteristics of the claimant cohort (n = 5004) were used to define the starting distribution. Annual stage-specific transition probabilities (F0-->F1, . . ., F3-->F4) were derived from the claimants, using the Markov maximum likelihood estimation method. HCV treatment efficacy was derived from the literature and practice patterns were estimated from a national survey. The estimated stage-specific transition probabilities of the cohort between F0-->F1, F1-->F2, F2-->F3 and F3-->F4 were 0.032, 0.137, 0.150 and 0.097 respectively. At 20 years after the index transfusion, approximately 10% of all living claimants (n = 3773) had cirrhosis and 0.5% developed hepatocellular carcinoma (HCC). For nonhaemophilic patients, the predicted 20-year (2030) risk of HCV-related cirrhosis was 23%, and the risk of HCC and liver-related death was 7% and 11% respectively. Haemophilic patients who are younger and are frequently co-infected with human immunodeficiency virus would have higher 20-year risks of cirrhosis (37%), HCC (12%) and liver-related death (19%). Our results indicate that rates of progression to advanced liver disease in post-transfusion cohorts may be lower than previously reported. The Canadian post-transfusion cohort offers new and relevant prognostic information for post-transfusion HCV patients in Canada and is an invaluable resource to study the natural history and resource utilization of HCV-infected individuals in future studies.
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Affiliation(s)
- H-H Thein
- Toronto General Research Institute, University Health Network, Toronto, ON, Canada
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Uto H, Stuver SO, Hayashi K, Kumagai K, Sasaki F, Kanmura S, Numata M, Moriuchi A, Hasegawa S, Oketani M, Ido A, Kusumoto K, Hasuike S, Nagata K, Kohara M, Tsubouchi H. Increased rate of death related to presence of viremia among hepatitis C virus antibody-positive subjects in a community-based cohort study. Hepatology 2009; 50:393-9. [PMID: 19585614 PMCID: PMC4551403 DOI: 10.1002/hep.23002] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
UNLABELLED The overall mortality of patients infected with hepatitis C virus (HCV) has not been fully elucidated. This study analyzed mortality in subjects positive for antibody to HCV (anti-HCV) in a community-based, prospective cohort study conducted in an HCV hyperendemic area of Japan. During a 10-year period beginning in 1995, 1125 anti-HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005. Cause of death was assessed by death certificates. Subjects with detectable HCV core antigen (HCVcAg) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers; subjects who were negative for both HCVcAg and HCV RNA (i.e., viremia-negative) were considered as having had a prior HCV infection and were classified as HCV noncarriers. Among the anti-HCV-positive subjects included in the analysis, 758 (67.4%) were HCV carriers, and 367 were noncarriers. A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years: 176 deaths in the HCV carrier group and 55 in the noncarrier group. The overall mortality rate was higher in HCV carriers than in noncarriers, adjusted for age and sex (hazard ratio, 1.53; 95% confidence interval, 1.13-2.07). Although liver-related deaths occurred more frequently among the HCV carriers (hazard ratio, 5.94; 95% confidence interval, 2.58-13.7), the rates of other causes of death did not differ between HCV carriers and noncarriers. Among HCV carriers, a higher level of HCVcAg (>or=100 pg/mL) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality. CONCLUSION The presence of viremia increases the rate of mortality, primarily due to liver-related death, among anti-HCV-seropositive persons in Japan.
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Affiliation(s)
- Hirofumi Uto
- Department of Digestive and Life-style related Disease, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
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Saneto H, Kobayashi M, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Akuta N, Suzuki F, Suzuki Y, Arase Y, Ikeda K, Kumada H. Clinicopathological features, background liver disease, and survival analysis of HCV-positive patients with hepatocellular carcinoma: differences between young and elderly patients. J Gastroenterol 2009; 43:975-81. [PMID: 19107342 DOI: 10.1007/s00535-008-2268-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2007] [Accepted: 07/21/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this retrospective study was to determine the incidence and characteristics of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) antibody-positive elderly patients with chronic hepatitis without cirrhosis. METHODS The study included 65 patients who developed HCC at >or=75 years of age and who received their first HCC therapy at Toranomon Hospital between 1985 and 2005. Their clinicopathological and laboratory data were analyzed and compared with those of 33 patients who developed HCC at <or=50 years of age during the same period. RESULTS The ratio of women patients in the elderly group (M: F = 1.1: 1) was higher than in the younger group (M: F = 5.6: 1). Also, patients in the elderly group had better liver function and prothrombin activity (P = 0.001), and lower total bilirubin (P = 0.002) than the young group. Only 11 of 65 elderly patients were diagnosed with liver cirrhosis by biopsy or peritoneoscopy before or at the time of development of HCC. Based on a discriminate score using gamma-globulin, hyaluronate level, platelet count, and sex, 27 (41.5%) elderly patients were considered to have chronic hepatitis, compared with six of 33 (18.1%) patients in the young group (P = 0.025). There were no differences in tumor number or size or tumor markers between the two groups. Survival rate was higher in the younger patients (P = 0.002), who were more likely to receive radical treatment. CONCLUSIONS Our results showed distinct differences in HCV-related HCC between elderly and young patients and suggested that elderly patients (especially women) could develop HCC even when liver histology shows chronic hepatitis and lack of cirrhosis.
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Affiliation(s)
- Hiromi Saneto
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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Clinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma. J Gastroenterol 2008; 43:550-7. [PMID: 18648742 DOI: 10.1007/s00535-008-2194-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2007] [Accepted: 03/20/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND It is well known that the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) correlates with progression of liver fibrosis. However, there is little information on the impact of aging on hepatocarcinogenesis. The aim of this study was to elucidate the clinicopathological features of elderly patients with HCV-related HCC. METHODS The study subjects were 693 consecutive patients newly diagnosed with HCC with anti-HCV. First, we divided them into a younger group (<70 years) and an elderly group (> or =70 years) and compared clinicopathological features between the two groups. Next, we selected pure HCV-related HCC patients by excluding the patients with other probable factors for hepatocarcinogenesis (anti-HBc, interferon therapy, and alcohol) and compared the two groups again. RESULTS Higher platelet count, lower male/female ratio, lower rate of habitual alcohol consumption, and better Child-Pugh class were recognized in the elderly group thant the younger group, statistically. In 133 cases of hepatic resection, fibrosis stage was lower in the elderly than the younger group. After selection of pure HCV-related HCC patients, in a stepwise multi variate analysis, male sex and platelet count <10 x 10(4)/mm3 were significant variables associated with age <70. Regarding the latency period to HCC development, the patients who received a blood transfusion at an older age developed HCC sooner despite their lower grade of fibrosis. CONCLUSIONS The elderly patients developed HCC more often, despite their lower grade of fibrosis, compared with the younger patients. In addition to fibrosis, aging could be a factor affecting HCV-related hepatocarcinogenesis.
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Tanaka K, Tsuji I, Wakai K, Nagata C, Mizoue T, Inoue M, Tsugane S. Alcohol drinking and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 2008; 38:816-38. [PMID: 18945722 DOI: 10.1093/jjco/hyn108] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Although alcohol consumption has been recognized as a risk factor for primary liver cancer, it will be informative to summarize relevant epidemiologic data in the Japanese who have characteristic environmental determinants (e.g. hepatitis C virus infection) and genetic traits (e.g. presence of poor acetaldehyde metabolizers). METHODS We systematically reviewed epidemiologic studies on alcohol drinking and liver cancer among Japanese populations. Original data were obtained through searches of the MEDLINE (PubMed) and Ichushi databases, complemented with manual searches. The evaluation was performed in terms of the magnitude of association ('strong', 'moderate', 'weak' or 'no association') in each study and the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient'), together with biological plausibility as previously assessed by the International Agency for Research on Cancer. RESULTS Among 22 cohort studies identified, 14 (64%) reported weak to strong positive associations between alcohol and liver cancer risk, 3 (14%) reported no association and five (23%) reported weak to moderate inverse associations; such inverse associations were found mostly in follow-up studies of patients with chronic liver disease (particularly, cirrhotic patients), yet recent studies on patients with chronic hepatitis C presented fairly consistent positive associations. Of 24 case-control studies identified, 19 (79%) showed weak to strong positive associations, whereas the remainder demonstrated no association (n = 4) or a moderate inverse association (n = 1). CONCLUSION We conclude that there is 'convincing' evidence that alcohol drinking increases the risk of primary liver cancer among the Japanese population.
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Affiliation(s)
- Keitaro Tanaka
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
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Thein HH, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology 2008; 48:418-31. [PMID: 18563841 DOI: 10.1002/hep.22375] [Citation(s) in RCA: 615] [Impact Index Per Article: 36.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
UNLABELLED Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F0-->F1, ... , F3-->F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F0-->F1 0.117 (0.104-0.130); F1-->F2 0.085 (0.075-0.096); F2-->F3 0.120 (0.109-0.133); and F3-->F4 0.116 (0.104-0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%-19%) for all studies, 18% (15%-21%) for cross-sectional/retrospective studies, 7% (4%-14%) for retrospective-prospective studies, 18% (16%-21%) for studies conducted in clinical settings, and 7% (4%-12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. CONCLUSION Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates.
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Affiliation(s)
- Hla-Hla Thein
- University Health Network, Division of Clinical Decision-Making and Health Care Research, Toronto, Ontario, Canada.
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30
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Kim SR, Imoto S, Fuki S, Kim KI, Taniguchi M, Nagano M, Hotta H, Shouji I, Kanbara Y, Maekawa Y, Kudo M, Hayashi Y. Pegylated interferon α-2b/ribavirin combination therapy for elderly patients with chronic hepatitis C with high viral load of HCV genotype 1b. KANZO 2008; 49:145-152. [DOI: 10.2957/kanzo.49.145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Yamada G, Iino S, Okuno T, Omata M, Kiyosawa K, Kumada H, Hayashi N, Sakai T. Virological Response in Patients with??Hepatitis C Virus Genotype 1b and??a??High Viral Load. Clin Drug Investig 2008; 28:9-16. [DOI: 10.2165/00044011-200828010-00002] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Nomura H, Kashiwagi Y, Hirano R, Tanimoto H, Tsutsumi N, Higashi M, Ishibashi H. Efficacy of low dose long-term interferon monotherapy in aged patients with chronic hepatitis C genotype 1 and its relation to alpha-fetoprotein: A pilot study. Hepatol Res 2007; 37:490-7. [PMID: 17539990 DOI: 10.1111/j.1872-034x.2007.00073.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
AIM The objective of this study was to examine the efficacy and safety of low dose long-term interferon (IFN) therapy in aged patients with chronic hepatitis C genotype 1. METHODS The IFN therapy was performed in Shin-Kokura Hospital on 44 patients aged 60 or older with chronic hepatitis C. All patients had high viral loads of genotype 1. Three million units of natural IFN-alpha was administered intramuscularly or intrasubcutaneously, three times a week for three years. A control group of 44 subjects not treated with IFN, matched for age, gender and hepatic histology, was formed. RESULTS Two of the 44 patients showed a sustained virological response. Alanine aminotransferase was below the upper limit of normal in 59% (23/39) of the patients and alpha-fetoprotein was less than 40 ng/mL in 97% (38/39) on the completion of treatment. Sustained biochemical response was observed in 53% (19/36) of the patients. In the liver cirrhosis group, serum albumin values and platelet counts increased in 38% (6/16) and 33% (6/18) of patients, respectively. Hepatocellular carcinoma (HCC) appeared in three patients by 13 months after the start of treatment, but no cases were reported thereafter. The cumulative non-carcinogenesis rate of HCC in the liver cirrhosis group was significantly higher in the IFN treatment group compared to the control group (log-rank test, P = 0.046). CONCLUSION Low dose long-term interferon monotherapy to prevent carcinogenesis of HCC was considered useful in aged patients for whom peg-interferon and ribavirin combination therapy is difficult.
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Affiliation(s)
- Hideyuki Nomura
- The Center for Liver Diseases, Shin-Kokura Hospital, Kitakyushu City, Japan
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Kim SR. Is long-term interferon monotherapy welcome news for older patients with chronic hepatitis C genotype 1? Hepatol Res 2007; 37:487-9. [PMID: 17539989 DOI: 10.1111/j.1872-034x.2007.00111.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Soo R Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan
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Oze T, Hiramatsu N, Kurashige N, Tsuda N, Yakushijin T, Kanto T, Takehara T, Kasahara A, Kato M, Yoshihara H, Katayama K, Kubota S, Hijioka T, Ishibashi K, Oshita M, Hagiwara H, Haruna Y, Mita E, Tamura S, Hayashi N. Early decline of hemoglobin correlates with progression of ribavirin-induced hemolytic anemia during interferon plus ribavirin combination therapy in patients with chronic hepatitis C. J Gastroenterol 2006; 41:862-72. [PMID: 17048050 DOI: 10.1007/s00535-006-1858-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2006] [Accepted: 06/12/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to examine the factors correlated with the progression of ribavirin-induced hemolytic anemia in patients with chronic hepatitis C treated by interferon and ribavirin combination therapy. METHODS This study was conducted on 505 patients by the Osaka Liver Disease Study Group. A decline of hemoglobin (Hb) concentration by 2 g/dl at the end of 2 weeks from the start of the treatment ("2 by 2" standard) was adopted as a predictive factor for progression to severe anemia. The ribavirin apparent clearance (CL/F) was also examined. RESULTS Of 482 patients whose Hb value was more than 12 g/dl before the treatment, 68 patients (14%) had to discontinue ribavirin owing to severe anemia. Patients in the "2 by 2"-positive group (Hb decline over 2 g/dl) and the group with lower CL/F were significantly more likely to discontinue ribavirin owing to severe anemia. Discontinuation was more common among patients aged 60 years or older than for those under 60 years old (21% vs. 9%, P < 0.001). Among patients aged 60 years or older, only the "2 by 2" standard was significantly associated with the discontinuance of ribavirin owing to severe anemia in a multivariate analysis (odds ratio, 4.18; P < 0.001). CONCLUSIONS The "2 by 2" standard of Hb decline can be used to identify patients likely to develop severe anemia. The early reduction of ribavirin can help prevent progression to severe anemia, thus allowing ribavirin therapy to be completed even in older patients.
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Affiliation(s)
- Tsugiko Oze
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan
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Yoshizawa H, Tanaka J, Miyakawa Y. National prevention of hepatocellular carcinoma in Japan based on epidemiology of hepatitis C virus infection in the general population. Intervirology 2005; 49:7-17. [PMID: 16166783 DOI: 10.1159/000087257] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
During the past 30 years, hepatocellular carcinoma (HCC) in Japan has kept linearly increasing from 10 to 30 per 100,000 population per year and is expected to grow further. The increment is attributed to infection with hepatitis C virus (HCV). Hence, there is a pressing need to find subjects with persistent HCV infection in the general population of Japan and take necessary measures to prevent HCC developing in them. As a first approach toward this goal, the sex- and age-specific prevalence of ongoing HCV infection was surveyed in 3,485,648 first-time blood donors during 1995-2000. Taking into account the size of subpopulations with different sex and age in Japan registered at the Census 2000, there are an estimated 884,954 HCV carriers aged from 16 to 69 years, and 759,316 (86%) of them are older than 40 years, with an increased risk for HCC; they are hidden in the society, without overt liver disease. The national 5-year project searching for HCV carriers in the general population was started in April 2002. Subjects are examinees of health check-ups, which they receive every 5 years when reaching the age of 40, as well as those at increased risk for HCV infection. The project detected HCV RNA in 14,672 of the 1,298,746 (1.1%) health check examinees and in 16,721 of the 624,734 (2.7%) high-risk individuals during the first fiscal year. Subjects found with HCV RNA have been referred to clinics and hospitals with expert hepatologists. Hopefully, this project will decrease HCC development in HCV carriers in Japan and be considered in other countries where increases in HCC are predicted from the current age-specific prevalence of anti-HCV.
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Affiliation(s)
- Hiroshi Yoshizawa
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan
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Mizokami M, Tanaka Y, Miyakawa Y. Spread Times of Hepatitis C Virus Estimated by the Molecular Clock Differ among Japan, the United States and Egypt in Reflection of Their Distinct Socioeconomic Backgrounds. Intervirology 2005; 49:28-36. [PMID: 16166786 DOI: 10.1159/000087260] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Infection with hepatitis C virus (HCV) is taking an ever increasing role in the development of hepatocellular carcinoma (HCC) over the world. Dynamics of HCV infection were determined by the molecular clock, estimating the dissemination time when HCV entered the country and the "spread time" when it started to grow exponentially on a national scale. A comparison of HCV dynamics in Japan, the United States and Egypt has disclosed different dissemination and spread times among the three countries. Furthermore, they faithfully mirror socioeconomic as well as medical and paramedical events inherent to each country responsible for the wide spread of HCV infection during the past. Epidemic histories of HCV would enable us to predict what is going to happen in the future for HCV infection, in special reference to HCC associated with it. Population dynamics of HCV need to be determined in other countries where HCV prevails and compared with those in the three countries described. These studies should help foresee what will happen in the near future for HCV infection in a given country, time the future development of HCC and take measures for preventing it.
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Affiliation(s)
- Masashi Mizokami
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
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Kamitsukasa H, Harada H, Tanaka H, Yagura M, Tokita H, Ohbayashi A. Late liver-related mortality from complications of transfusion-acquired hepatitis C. Hepatology 2005; 41:819-25. [PMID: 15793849 DOI: 10.1002/hep.20648] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Although several cohort studies have been reported in individuals with chronic hepatitis C virus (HCV) infection, little is known about liver-related mortality among the elderly. We conducted a cohort study in 302 patients with tuberculosis sequelae who had received a blood transfusion at a young age and had subsequently been treated at a chest clinic. The cohort consisted of 147 patients with antibody to HCV (anti-HCV), of whom 81% were positive for HCV RNA, and 155 without anti-HCV. The cohort was followed for a mean duration of 5.7 years. There were no differences between the two groups in the mean age of the patients at the time of transfusion (31 vs. 34 years) or at the time of entry into the study (65 vs. 66 years). The outcome of 143 patients with, and 145 without, anti-HCV could be traced; 92 (64%) and 82 (57%) had died, respectively. The main cause of death was tuberculosis sequelae in 61 (42%) and 66 (46%) patients, respectively. Eight (6%) of the 143 patients with anti-HCV died of liver disease (hepatocellular carcinoma: seven; rupture of varices: one). The average annual mortality from liver disease from study entry in the patients with anti-HCV was 9.8 per 1,000 person-years. The patients with anti-HCV had a significantly lower cause-specific survival probability for liver disease (92% vs. 100% at 10 years, P < .005). In conclusion, in our study, liver-related mortality appeared to be high among elderly HCV-infected individuals.
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Markowitz JS, Gutterman EM, Hodes D, Klaskala W. Factors associated with the initiation of alpha-interferon treatment in Medicaid patients diagnosed with hepatitis C. J Viral Hepat 2005; 12:176-85. [PMID: 15720533 DOI: 10.1111/j.1365-2893.2005.00607.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
We aimed to determine rates of treatment with alpha-interferon medication in patients diagnosed with hepatitis C virus (HCV), to ascertain the prevalence of selected conditions that could influence initiation of interferon treatment, and to examine the association between the presence of these conditions and interferon treatment. A nested case-control design was used in California Medicaid (Medi-Cal) claims data covering the period from 1 January 1996 to 30 June 2002. Interferon-treated cases and non-treated controls were selected in a 1 : 2 ratio that matched the length of the observation period and year of index HCV diagnosis. Predictor variables examined in bivariate and multivariate analyses included demographics, substance abuse and dependence, psychotropic drug use, selected chronic conditions and medical utilization. The proportion of eligible subjects diagnosed with HCV and treated with interferon ranged from 10.7 to 13.9%. There were 529 treated cases that met the eligibility criteria and 1058 non-treated HCV patients selected as controls. Multivariate factors that increased the likelihood of treatment were a liver biopsy, a diagnosis of mild liver disease, a diagnosis of psoriasis, antidepressant use and classification of race/ethnicity as 'other'. A decreased likelihood of treatment was linked to age > or =65 years, a diagnosis of kidney disease, one to four emergency visits and five or more emergency visits. The proportion of patients receiving interferon treatment in the Medi-Cal-insured population was low compared with published rates in HCV patients in other general medical settings. The diverse factors linked to initiation of HCV therapy raise compelling questions for further research.
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Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, Tanaka E. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology 2004; 127:S17-26. [PMID: 15508082 DOI: 10.1053/j.gastro.2004.09.012] [Citation(s) in RCA: 223] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
During the past 20 years, primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. The numbers of deaths and death rate from HCC showed a sharp increase beginning in 1975. Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes, HCV-related HCC has accounted for most of the recent increase and now represents 75% of all HCC in Japan. Geographically, HCC is more frequent in western than eastern Japan, and the death rate of HCC in each prefecture correlates with prevalence of anti-HCV. Among patients with HCV-related HCC, a history of blood transfusion was a relatively important source of infection in the 1990s, whereas community-acquired infections increased after 2000. There was a negative correlation between the duration from onset of infection to development of HCC and the age at onset. Interferon therapy for chronic hepatitis C has reduced the risk for HCC, indicating that early detection of HCV carriers and better treatment will contribute to improved outcomes. Nationwide screening for HCV and HBV began in 2002 in Japan, and reduction of HCC is anticipated. Further research should focus on mechanisms of carcinogenesis by HCV and HBV, development of more effective treatments, and establishment of early detection and treatment approaches. Better understanding of HCC unrelated to HCV and HBV and possibly because of steatohepatitis and diabetes should also be a major concern in future studies.
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Affiliation(s)
- Kendo Kiyosawa
- Department of Internal Medicine, Gastroenterology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano-Prefecture 390-8621, Japan.
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Abstract
Hepatitis C virus (HCV) infection is now a global public health issue. However, the global burden of disease attributable to HCV infection is unknown. The objectives of this WHO informal consultation included the following: (1) defining a strategy to estimate the global burden of disease (GBD) associated with HCV infection in terms of morbidity and mortality, (2) describing the natural history of HCV infection in terms of morbidity and mortality, and (3) identifying areas for which more research is needed. The GBD project is an attempt to examine all causes of morbidity and mortality using an approach common to all conditions. The World Health Organization (WHO) already has estimated the burden of disease associated with hepatitis B virus (HBV) infection and is now about to conduct the same analysis for HCV infection. A review has been conducted to estimate the prevalence of HCV infection by age, gender, and region. These figures can be used to estimate incidence, although there are a number of areas of uncertainty. Combined with natural history parameters, incidence estimates could be used to estimate the future burden due to current infections. However, the present model is not validated and requires calibration before it can be used. A consensus was reached over the strategies to be used to (1) estimate the current burden due to past infections and (2) estimate the future burden due to current infections. Provisional expert consensus was reached over natural history parameters and cofactors that influence them. However, systematic literature reviews and meta-analysis are preferable for obtaining estimates to be included in models. Areas deserving future research include (1) obtaining a better estimate of HCV infection prevalence by age groups, (2) characterizing the various morbidity states associated with HCV infection and their disability weights, (3) understanding the long-term natural history of HCV infection beyond 20 years after infection, and (4) estimating the prevalence (and numbers of) of HCV infection among the drug-using population worldwide. A working group was created to address unmet needs and to assist the WHO in estimating the GBD associated with HCV infection.
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Tsai JF, Jeng JE, Chuang LY, Ho MS, Ko YC, Lin ZY, Hsieh MY, Chen SC, Chuang WL, Wang LY, Yu ML, Dai CY. Habitual betel quid chewing and risk for hepatocellular carcinoma complicating cirrhosis. Medicine (Baltimore) 2004; 83:176-187. [PMID: 15118544 DOI: 10.1097/01.md.0000126971.80227.a4] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
This case-control study aimed to assess the independent and interactive role of habitual betel quid chewing and known risk factors for hepatocellular carcinoma (HCC). Subjects enrolled included 210 pairs of sex- and age-matched cirrhotic patients with HCC, patients with cirrhosis alone, and healthy controls. Information on risk factors was obtained through serologic examination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and a standardized personal interview with a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio [OR], 5.81; 95% confidence interval [CI], 2.26-14.94); HBsAg (OR, 37.98; 95% CI, 19.65-73.42); and anti-HCV (OR, 47.23; 95% CI, 18.86-118.25) were independent risk factors for HCC when HCC patients were compared with healthy controls. Using patients with cirrhosis alone as a reference group, multivariate analysis indicated that only betel quid chewing (OR, 1.69; 95% CI, 1.04-2.76) and HBsAg (OR, 1.54; 95% CI, l.01-2.37) were independent risk factors for HCC. There was an additive interaction between betel quid chewing and the presence of either HBsAg (synergy index, 5.22) or anti-HCV (synergy index, 1.35). Moreover, a higher risk of HCC was associated with a longer duration of betel quid chewing and a larger amount of betel quid consumed (each p(for trend) < 0.0001). In conclusion, betel quid chewing is an independent risk factor for cirrhotic HCC. There is an additive interaction between betel quid chewing and chronic hepatitis B and/or hepatitis C virus infection.
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Affiliation(s)
- Jung-Fa Tsai
- From the Department of Internal Medicine, Clinical Laboratory, Biochemistry, and Public Health, Kaohsiung Medical University College of Medicine; the National Health Research Institutes, and the Institute of Biomedical Sciences, Academia Sinica, Taiwan
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Abstract
Nearly three million persons in the United States are viremic with hepatitis C (HCV). Despite a decreasing incidence of HCV in this country, the prevalence of HCV-related chronic liver disease is increasing. Most infections in the United States are acquired by intravenous drug use. The chronicity rate of HCV is high, reaching 85% in some populations, and the risk of progression to advanced liver disease is as high as 20% within twenty years of infection. Host factors like alcohol use accelerate the rate of progression. The enzyme immunoassay is the preferred initial test for diagnosis; the third generation assay has greater than a 99% specificity in immunocompetent patients. Barring contraindications, the standard of care for treatment of chronic HCV has become pegylated interferon and ribavirin. With this therapy, the cure rate for treatment-naïve patients is about 55%, but rates are higher in certain groups. Common side effects of therapy include neuropsychiatric symptoms, influenza-like symptoms and hematological abnormalities.
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Affiliation(s)
- Brian L Pearlman
- Center for Hepatitis C, Atlanta Medical Center, Atlanta, GA 30312, USA.
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Kaplan DE, Reddy KR. Rising incidence of hepatocellular carcinoma: the role of hepatitis B and C; the impact on transplantation and outcomes. Clin Liver Dis 2003; 7:683-714. [PMID: 14509534 DOI: 10.1016/s1089-3261(03)00060-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma caused by hepatitis B and hepatitis C are global scourges but are likely to peak in incidence in the next 2 decades and then decline. Universal vaccination has been effective in stemming the incidence of chronic hepatitis B and early-onset HCC in regions of high endemicity where implemented, but preventive measures in HCV are not yet available. After the attrition of older affected generations, the incidence of HCC will likely decline rapidly. While no vaccine is currently available for hepatitis C, cases are projected to peak and decline because of a marked reduction in transmission as a result of behavioral modification and safeguarding of blood supplies. Until these epidemiologic projections come to pass, management of hepatocellular carcinoma will continue to become a progressively more frequently encountered clinical challenge. Therapy for chronic hepatitis may ameliorate but will not eliminate the development of tumors. The demand for orthotopic liver transplantation will continue to climb, and palliative therapies for non-resectable cases will require studies aimed at optimization of benefit. LDLT may remain an option for high-risk patients affording tumor-free survival for some otherwise terminal patients.
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Affiliation(s)
- David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, 3 Raydin, 3400 Spruce Street, Philadelphia, PA 19104, USA
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Hao CQ, Feng ZH, Zhou YX, Nie QH, Li JG, Jia ZS, Liang XS, Xie YM, Cao YZ, Kang WZ. Construction, package and identification of replication-deficient recombinant adenovirus expression vector of HCV C. Shijie Huaren Xiaohua Zazhi 2003; 11:144-147. [DOI: 10.11569/wcjd.v11.i2.144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To construct a replication-deficient recombinant adenovirus expression vector of HCV C.
METHODS: The HCV core gene was cloned at the downstream of CMV promoter of the adenoviral shuttle plasmid pAd. CMV-link. 1, and the resultant recombinant plasmid pAd. HCV-C was cotransfected into 293 cell together with plasmid pJM17 containing adenoviral genome, then the adenovirus expression vector was obtained, and identified by infecting test, electronic microscope observation and PCR co-amplification. The plasmid pAd. HCV-C was identified by endonuclease, PCR and sequencing. The expressive activity of adenovirus vector was identified by immunofluorescence and Western blot.
RESULTS: HCV core gene in the inserted DNA of pAd. HCV-C was confirmed by endonuclease, PCR and sequencing. Results of infecting test, electronic microscopic observation and PCR co-amplification showed that the adenovirus vector had been constructed successfully. Expression of HCV core antigen was proved in the HepG2 cells by immunofluorescence and Western blot.
CONCLUSION: The replication-deficient recombinant adenovirus vector can express HCV core antigen in HepG2 cells. This study established a foundation for further study on HCV vaccines and gene therapy for hepatitis C.
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