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Liu CH, Cheng PN, Fang YJ, Chen CY, Kao WY, Lin CL, Yang SS, Shih YL, Peng CY, Chang YP, Huang SC, Su TH, Tseng TC, Liu CJ, Chen PJ, Kao JH. Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection. J Hepatol 2025; 82:582-593. [PMID: 39368711 DOI: 10.1016/j.jhep.2024.09.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 09/12/2024] [Accepted: 09/20/2024] [Indexed: 10/07/2024]
Abstract
BACKGROUND & AIMS Data are limited on the risk of de novo hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) who have achieved sustained virologic response at off-treatment week 12 (SVR12) using direct-acting antivirals (DAAs) for HCV. METHODS A total of 1,598 eligible patients received biannual alpha-fetoprotein (AFP) and liver imaging surveillance to detect de novo HCC after achieving SVR12. MASLD was defined as presence of controlled attenuation parameter (CAP) ≥248 dB/m and ≥1 cardiometabolic risk factor (CMRF). Cumulative HCC incidence was compared between patients with/without MASLD. We built univariable and multivariable Cox proportional hazards models to evaluate factors associated with HCC. Sensitivity analysis was performed using the Fine-Gray subdistribution hazards model. Additionally, we evaluated the mediation effect of MASLD on CMRFs and of CMRFs on MASLD for HCC using mediation analysis with bootstrapping. RESULTS The incidence rate of HCC was 1.44 per 100 person-years of follow-up (95% CI 1.19-1.74). Patients with MASLD had a higher cumulative HCC incidence than those without MASLD (log-rank test, p <0.001). Multivariable Cox regression analysis revealed that in addition to age, sex, liver stiffness measurement, platelet count, and AFP, MASLD (adjusted hazard ratio 2.07; 95% CI 1.36-3.16; p <0.001) was independently associated with HCC. This finding was confirmed by the Fine-Gray model, which showed a subdistribution hazard ratio of 2.07 (95% CI 1.34-3.19, p <0.001) for MASLD. MASLD significantly mediated CMRFs for HCC development. CONCLUSION After achieving SVR12, patients with MASLD exhibited an increased HCC risk compared to those without MASLD. Vigilant HCC surveillance and control of CMRFs to mitigate the effect of MASLD on HCC remain crucial for this population. IMPACT AND IMPLICATIONS The risk of de novo hepatocellular carcinoma (HCC) among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) who have attained a sustained virologic response to direct-acting antivirals remains to be confirmed. In this study, recruiting 1,598 patients in Taiwan, individuals with MASLD had an approximately two-fold increased risk of de novo HCC compared to those without MASLD after achieving a sustained virologic response. MASLD significantly mediated cardiometabolic risk factors for HCC development. Our findings underscore the critical importance of pharmacological interventions and proactive lifestyle modifications to control cardiometabolic risk factors in patients with MASLD, as well as the need for vigilant HCC surveillance to ensure favorable outcomes following HCV eradication.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
| | - Yu-Ping Chang
- Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu, Taiwan
| | - Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Huang JF, Chang TJ, Yeh ML, Shen FC, Tai CM, Chen JF, Huang YH, Hsu CY, Cheng PN, Lin CL, Hung CH, Chen CC, Lee MH, Lee CC, Lin CW, Liu SC, Yang HI, Chien RN, Kuo CS, Peng CY, Chang ML, Huang CF, Yang YS, Yang HC, Lin HC, Ou HY, Liu CJ, Tseng CH, Kao JH, Chuang WL, Huang CN, Chen PJ, Wang CY, Yu ML. Clinical care guidance in patients with diabetes and metabolic dysfunction-associated steatotic liver disease: A joint consensus. Hepatol Commun 2024; 8:e0571. [PMID: 39470335 PMCID: PMC11524742 DOI: 10.1097/hc9.0000000000000571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 08/05/2024] [Indexed: 10/30/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting >30% of the global population. Metabolic dysregulation, particularly insulin resistance and its subsequent manifestation as type 2 diabetes mellitus, serves as the fundamental pathogenesis of metabolic liver disease. Clinical evidence of the recent nomenclature evolution is accumulating. The interaction and impacts are bidirectional between MASLD and diabetes in terms of disease course, risk, and prognosis. Therefore, there is an urgent need to highlight the multifaceted links between MASLD and diabetes for both hepatologists and diabetologists. The surveillance strategy, risk stratification of management, and current therapeutic achievements of metabolic liver disease remain the major pillars in a clinical care setting. Therefore, the Taiwan Association for the Study of the Liver (TASL), Taiwanese Association of Diabetes Educators, and Diabetes Association of the Republic of China (Taiwan) collaboratively completed the first guidance in patients with diabetes and MASLD, which provides practical recommendations for patient care.
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Affiliation(s)
- Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tien-Jyun Chang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Feng-Chih Shen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jung-Fu Chen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University Faculty of Medicine, Taipei, Taiwan
- Healthcare and Services Center and Therapeutic and Research Center of Liver Cancer, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chih-Yao Hsu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei City Hospital Renai Branch, Taipei, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ching-Ling Lin
- Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan
| | - Chao-Hung Hung
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ching-Chu Chen
- Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University Faculty of Medicine, Taipei, Taiwan
| | - Chun-Chuan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, Mackay Medical College, Taipei, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Sung-Chen Liu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, Mackay Medical College, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Rong-Nan Chien
- Department of Gastroenterology and Hepatobiliary Disease, Linkou Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chin-Sung Kuo
- Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Ling Chang
- Department of Gastroenterology and Hepatobiliary Disease, Linkou Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Sun Yang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Shan Medical University Hospital, Taichung, Taiwan
| | - Hung-Chih Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department and Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology & Hepatology, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chien-Ning Huang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Shan Medical University Hospital, Taichung, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine, Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
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Yeh ML, Huang JF, Dai CY, Huang CF, Yu ML, Chuang WL. Metabolic dysfunction-associated steatotic liver disease and diabetes: the cross-talk between hepatologist and diabetologist. Expert Rev Gastroenterol Hepatol 2024; 18:431-439. [PMID: 39099428 DOI: 10.1080/17474124.2024.2388790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/30/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (DM) are the most prevalent metabolic disorders globally. The numbers affected in both disorders are also rapidly increasing with alarming trends in children and young adults. AREAS COVERED Insulin resistance (IR) and the subsequent metabolic dysregulation are the fundamental pathogenesis pathways of the prevalent metabolic disorders. The interaction and impacts are bidirectional between MASLD and DM in terms of disease mechanisms, disease course, risks, and prognosis. There's a pressing issue for highlighting the links between MASLD and DM for both care specialists and primary care providers. The review collected the scientific evidence addressing the mutual interactions between the two disorders. The strategies for surveillance, risk stratification, and management are discussed in a practical manner. It also provides individualized viewpoints of patient care in hepatology and diabetology. EXPERT OPINION Both MASLD and DM shared similar disease mechanisms, and affected the disease development and progression in a bidirectional manner. The high prevalence and the cross-link between the two disorders raise clinical issues from awareness, screening, risk stratification, optimal referral, to appropriate management for primary care providers.
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Affiliation(s)
- Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Ohama H, Hiraoka A, Tada T, Kariyama K, Itobayashi E, Tsuji K, Ishikawa T, Toyoda H, Hatanaka T, Kakizaki S, Naganuma A, Tada F, Tanaka H, Nakamura S, Nouso K, Tanaka K, Kumada T. Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents. J Gastroenterol Hepatol 2024; 39:1394-1402. [PMID: 38602340 DOI: 10.1111/jgh.16553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/11/2024] [Accepted: 03/20/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND AND AIM Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. METHODS A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. RESULTS Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 104/μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0). CONCLUSION The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.
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Affiliation(s)
- Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
- Department of Gastroenterology, Takarazuka City Hospital, Hyogo, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Kazuya Kariyama
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hironori Tanaka
- Department of Gastroenterology, Takarazuka City Hospital, Hyogo, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Kazuhiro Nouso
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Kazunari Tanaka
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Sacco M, Ribaldone DG, Saracco GM. Metformin and Hepatocellular Carcinoma Risk Reduction in Diabetic Patients with Chronic Hepatitis C: Fact or Fiction? Viruses 2023; 15:2451. [PMID: 38140692 PMCID: PMC10748230 DOI: 10.3390/v15122451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/07/2023] [Accepted: 12/15/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. AIM the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. METHODS A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. RESULTS Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. CONCLUSION according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.
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Affiliation(s)
| | | | - Giorgio Maria Saracco
- Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.S.); (D.G.R.)
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Yang LS, Yan LJ, Yan YC, Ding ZN, Liu H, Tan SY, Dong ZR, Wang DX, Li T. Regional and sex differences in the mortality risk associated with primary liver cancer in obesity: A systematic review and meta-analysis. Nutrition 2023; 113:112097. [PMID: 37406391 DOI: 10.1016/j.nut.2023.112097] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 07/07/2023]
Abstract
OBJECTIVE Obesity has increasingly become a prominent public health problem. Although some studies have shown that obesity is associated with the risk for primary liver cancer (PLC)-related mortality, the regional and sex differences are not clear. The aim of this meta-analysis was to further elucidate the influence of obesity on PLC prognosis from multiple aspects. METHODS This study used a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, Sinomed, and CNKI for eligible studies evaluating the effects of obesity on the prognosis of PLC. Data on PLC-related mortality, all-cause mortality, or recurrence should be available to obtain, and studies providing regional, or sex specificity are of concern. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. RESULTS Obesity is strongly associated with an increased risk for PLC-related mortality. A significant regional difference was observed (North America: HR, 1.57; 95% CI, 1.06-2.34; Europe: HR, 1.53; 95% CI, 1.08-2.16; Asia: HR, 1.05; 95% CI, 0.92-1.19; Oceania: HR, 1.13; 95% CI, 0.76-1.67). A stronger association between excess body mass index (BMI) and an increased risk for PLC-related mortality was demonstrated in men compared with women (men: HR, 1.87; 95% CI, 1.25-2.77; women: HR, 1.22; 95% CI, 1.00-1.47). No association was observed in the analysis between obesity and all-cause mortality and recurrence risk in PLC (all-cause mortality: HR, 1.01; 95% CI, 0.96-1.06; recurrence risk: HR, 1.00; 95% CI, 0.88-1.15). CONCLUSION This study demonstrated a stronger association between obesity and PLC-related mortality in North America and Europe and among men.
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Affiliation(s)
- Long-Shan Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Tao Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
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Rocha C, Doyle EH, Bowman CA, Fiel M, Stueck AE, Goossens N, Bichoupan K, Patel N, Crismale JF, Makkar J, Lewis S, Perumalswami PV, Schiano TD, Hoshida Y, Schwartz M, Branch AD. Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis. Cancer Med 2023; 12:10175-10186. [PMID: 37078924 PMCID: PMC10225173 DOI: 10.1002/cam4.5711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 01/06/2023] [Accepted: 02/07/2023] [Indexed: 04/21/2023] Open
Abstract
BACKGROUND Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). AIMS To identify risk factors for new-onset HCC in patients cured of hepatitis C. METHODS Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post-SVR HCC were identified by comparison with HALT-C participants who did not develop post-SVR HCC. RESULTS Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post-SVR [interquartile range (IQR) =1.4-10y] at a median age of 61 years (IQR, 59-67). Approximately one-third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25-4), indicating mild necroinflammation. In a multivariable logistic regression model, post-SVR HCC was positively associated with non-Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/μL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. CONCLUSIONS One-third of patients with post-SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post-SVR HCC risk.
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Affiliation(s)
- Chiara Rocha
- Department of Surgery—Transplant DivisionIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Erin H. Doyle
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount Sinai SchoolNew YorkNew YorkUSA
| | - Chip A. Bowman
- Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - M‐Isabel Fiel
- Department of PathologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Ashley E. Stueck
- Department of PathologyDalhousie UniversityHalifaxNova ScotiaCanada
| | - Nicolas Goossens
- Division of Liver Diseases, Department of MedicineTisch Cancer Institute, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Kian Bichoupan
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Neal Patel
- Division of GastroenterologyDepartment of Medicine, Nuvance Health Danbury HospitalDanburyCTUSA
| | - James F. Crismale
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Jasnit Makkar
- Department of RadiologyColumbia UniversityNew YorkNew YorkUSA
| | - Sara Lewis
- Department of RadiologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | | | - Thomas D. Schiano
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Yujin Hoshida
- Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTexasUSA
| | - Myron Schwartz
- Department of SurgeryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Andrea D. Branch
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
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8
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Yan LJ, Yang LS, Yan YC, Tan SY, Ding ZN, Liu H, Wang DX, Dong ZR, Li T. Anthropometric indicators of adiposity and risk of primary liver cancer: A systematic review and dose-response meta-analysis. Eur J Cancer 2023; 185:150-163. [PMID: 36996625 DOI: 10.1016/j.ejca.2023.03.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/29/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND AND AIMS Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. METHODS Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. RESULTS Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33-55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26-40.75). CONCLUSION Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Long-Shan Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China.
| | - Tao Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China; Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan 250012, PR China.
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9
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Kozuka R, Tamori A, Enomoto M, Muto-Yukawa Y, Odagiri N, Kotani K, Motoyama H, Kawamura E, Hagihara A, Fujii H, Uchida-Kobayashi S, Kawada N. Risk factors for liver-related and non-liver-related mortality following a sustained virological response after direct-acting antiviral treatment for hepatitis C virus infection in a real-world cohort. J Viral Hepat 2023; 30:374-385. [PMID: 36583600 DOI: 10.1111/jvh.13795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 12/15/2022] [Accepted: 12/17/2022] [Indexed: 12/31/2022]
Abstract
A direct-acting antiviral (DAA)-induced sustained virological response (SVR) reduces the risk of mortality. However, the risk factors associated with liver-related and non-liver-related mortality following a SVR after DAA treatment are unclear. We assessed the incidence and risk factors of liver-related and non-liver-related mortality in 1180 patients who achieved a SVR after DAA treatment. During the follow-up period after DAA treatment (median duration, 1099 [range: 84-2345] days), 53 (4.5%) patients died: 15 due to liver-related mortality, 25 due to non-liver-related mortality and 13 due to unknown causes. The all-cause, liver-related and non-liver-related mortality rates were 14.9, 4.2 and 7.0/1000 person-years, respectively. In a multivariate analysis, the development of hepatocellular carcinoma (HCC) after DAA treatment (p = .009; hazard ratio [HR], 31.484), an estimated glomerular filtration rate (eGFR) at baseline ≤61.68 ml/min/1.73 m2 (p = .015; HR, 6.607), and an α-fetoprotein level post-treatment ≥7.6 ng/ml (p = .041; HR, 18.490) were significantly associated with liver-related mortality. Furthermore, eGFR ≤67.94 ml/min/1.73 m2 at baseline (p = .012; HR, 3.407) and albumin-bilirubin (ALBI) grade ≥ 2 at SVR (p = .024; HR, 3.449) were significantly associated with non-liver-related mortality. Early diagnosis and therapeutic interventions for HCC development after DAA treatment are important to reduce liver-related mortality. The ALBI grade, which reflects the hepatic functional reserve, is a useful predictor of non-liver-related mortality after a SVR induced by DAA treatment. Furthermore, the renal dysfunction caused by metabolic syndrome may affect prognosis even after eliminating hepatitis C virus.
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Affiliation(s)
- Ritsuzo Kozuka
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Kashiwara Municipal Hospital, Osaka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yoshimi Muto-Yukawa
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Naoshi Odagiri
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Kohei Kotani
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Hiroyuki Motoyama
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Etsushi Kawamura
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Atsushi Hagihara
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Sawako Uchida-Kobayashi
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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10
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful. J Viral Hepat 2023; 30:148-159. [PMID: 36461645 DOI: 10.1111/jvh.13778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/07/2022] [Accepted: 11/26/2022] [Indexed: 12/04/2022]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is one of the most serious complications of hepatitis C virus (HCV) infection. Recently, effective antiviral medications have made sustained viral response (SVR) or cure a realistic therapeutic goal for most chronic HCV patients. Given HCV's tumorigenic propensity, it is not surprising that achieving SVR is helpful in preventing HCC. This review briefly summarizes and discusses the existing evidence on the relationship between hepatic carcinogenesis and viral eradication by antivirals, which is mainly divided into interferon-based and direct-acting antivirals (DAAs) based therapy. DAAs have changed the treatment landscape of chronic HCV, reaching high rates of SVR even in patients with advanced cirrhosis, with few contraindications and little side effects. Although some early reports suggested that DAA treatment increased the chance of HCC occurrence, more subsequent observational studies have refuted this theory. The probability of HCC recurrence after HCV eradication appears to be decreasing over time following SVR. Despite virological suppression/cure, individuals with liver cirrhosis are still at risk of HCC and should be monitored. There is a considerable need for markers/scores to predict the long-term risk of HCC in patients with HCV-related liver disease who attain SVR with direct-acting antivirals.
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Affiliation(s)
- Walaa Abdelhamed
- Endemic Medicine Department, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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11
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Hsu PY, Liang PC, Huang CI, Hsieh MH, Tsai YS, Lin TC, Yeh ML, Huang CF, Wang CW, Jang TY, Lin YH, Lin ZY, Chuang WL, Dai CY. Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR. Viruses 2022; 14:2412. [PMID: 36366510 PMCID: PMC9693099 DOI: 10.3390/v14112412] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR.
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Affiliation(s)
- Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- College of Medicine, National Sun Yat-sen University, Kaohsiung 807, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tzu-Chun Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
- Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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12
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Shin HS, Jun BG, Yi SW. Impact of diabetes, obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases. Clin Mol Hepatol 2022; 28:773-789. [PMID: 35934813 PMCID: PMC9597232 DOI: 10.3350/cmh.2021.0383] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/20/2022] [Indexed: 01/05/2023] Open
Abstract
Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.
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Affiliation(s)
- Hwang Sik Shin
- Department of Family Medicine, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea,Corresponding author : Baek Gyu Jun Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea Tel: +82-2-950-8889, Fax: +82-2-950-1955, E-mail:
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, Gangneung, Korea,Sang-Wook Yi Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, 24 Beomil-ro 579beon-gil, Gangneung 25601, Korea Tel: +82-33-649-7468, Fax: +82-33-641-1074, E-mail:
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13
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Yang C, Wan M, Lu Y, Yang X, Yang L, Wang S, Sun G. Associations between diabetes mellitus and the risk of hepatocellular carcinoma in Asian individuals with hepatitis B and C infection: systematic review and a meta-analysis of cohort studies. Eur J Cancer Prev 2022; 31:107-116. [PMID: 35103624 DOI: 10.1097/cej.0000000000000669] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We aim to further analyze and compare associations between diabetes mellitus and the risk of hepatocellular carcinoma (HCC) in Asian individuals with hepatitis B or C virus infection by conducting an updated meta-analysis of cohort studies. Literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library from the beginning of indexing for each database to January 1, 2020. A total of 22 articles met the inclusion criteria, in which 18 were cohort studies and 4 were case-control studies. We identified eight cohort studies and three case-control studies that presented results on diabetes mellitus and the risk of HCC in Asian subjects with hepatitis B virus (HBV) infection: the cumulative relative risk (RR) with 95% confidence interval (CI) was 1.37 (95% CI: 1.24 to 1.51; I2 = 27.8%) for cohort studies and cumulative odds ratio (OR) with 95% CI was 1.99 (95% CI: 0.73 to 5.48; I2 = 88.4%) for case-control studies. Thirteen cohort studies and two case-control studies presented results on the association between diabetes mellitus and the risk of HCC in Asian subjects with hepatitis C virus (HCV) infection: the RR with 95% CI was 1.76 (95% CI: 1.42 to 2.17; I2 = 62.8%) for cohort studies and OR with 95% CI was 1.77 (95% CI: 1.18 to 2.64; I2 = 0.0%) for case-control studies. In summary, our meta-analysis strongly supports the association between coexistent HCV and diabetes with the increasing risk of HCC; although the results equally support diabetes mellitus being significantly associated with increased risk of HCC among patients with HBV infection, this correlation is weaker than the former.
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Affiliation(s)
- Chao Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
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14
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Nakai M, Yamamoto Y, Baba M, Suda G, Kubo A, Tokuchi Y, Kitagataya T, Yamada R, Shigesawa T, Suzuki K, Nakamura A, Sho T, Morikawa K, Ogawa K, Furuya K, Sakamoto N. Prediction of hepatocellular carcinoma using age and liver stiffness on transient elastography after hepatitis C virus eradication. Sci Rep 2022; 12:1449. [PMID: 35087141 PMCID: PMC8795443 DOI: 10.1038/s41598-022-05492-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 01/12/2022] [Indexed: 12/27/2022] Open
Abstract
Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age < 71 years and LSM < 8.4 kPa at the time of SVR24, the 4-year cumulative incidence of HCC was as low as 1.1%. Both pre-treatment LSM (≥ 9.2 kPa) and SVR24 LSM (≥ 8.4 kPa) and age (≥ 71 years) are useful in predicting the risk of HCC after SVR with IFN-free treatment. Identification of low-risk individuals may improve the efficiency of follow-up.
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Affiliation(s)
- Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yoshiya Yamamoto
- Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Masaru Baba
- Department of Gastroenterology, JCHO Hokkaido Hospital, Sapporo, Hokkaido, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kazuharu Suzuki
- Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Ken Furuya
- Department of Gastroenterology, JCHO Hokkaido Hospital, Sapporo, Hokkaido, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
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15
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Benhammou JN, Moon AM, Pisegna JR, Su F, Vutien P, Moylan CA, Ioannou GN. Nonalcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After Direct-Acting Antiviral Treatment for Hepatitis C. Dig Dis Sci 2021; 66:2394-2406. [PMID: 32654086 PMCID: PMC7854862 DOI: 10.1007/s10620-020-06457-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/28/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION In hepatitis C (HCV) patients, obesity and/or diabetes may increase the risk of liver-related outcomes. We aimed to determine whether diabetes and/or obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-treated HCV patients. METHODS We conducted a retrospective study of 33,003 HCV-infected, DAA-treated Veterans between 2013 and 2015. Body mass index was used to categorize patients into underweight (< 18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), obesity I (30 to < 35 kg/m2), and obesity II-III (> 35 kg/m2). Diabetes was defined by ICD-9/10 codes in association with hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180 days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis, decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox proportional hazards regression models were used to determine the association between diabetes and/or obesity and outcomes. RESULTS During a mean follow-up of 3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a decompensation and 4.0% developed HCC. Diabetes was associated with an increased risk of mortality (AHR = 1.25, 95% CI 1.10-1.42), cirrhosis (AHR = 1.31, 95% CI 1.16-1.48), decompensation (AHR = 1.74, 95% CI 1.31-2.31), and HCC (AHR = 1.32, 95% CI 1.01-1.72) among patients without baseline cirrhosis. Compared to normal-weight persons, obese persons had a higher risk of cirrhosis, but overweight and obese persons had lower risk of mortality and HCC. CONCLUSIONS In this large DAA-treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related events independent of SVR. Continued vigilance is warranted in patients with diabetes despite SVR. Elevated BMI categories appear to have improved outcomes, although further studies are needed to understand those associations.
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Affiliation(s)
- Jihane N Benhammou
- Pfleger Liver Institute, University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA, 90095, USA.
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA.
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 130 Mason Farm Road, Bioinformatics Building CB#7080, Chapel Hill, NC, 27599-7080, USA
| | - Joseph R Pisegna
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA
| | - Feng Su
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Cynthia A Moylan
- Division of Gastroenterology, Veterans Affairs Health System, Durham, NC, USA
- Division of Gastroenterology, Duke University Health System, 905 Lasalle St., Gsrb 1 DUMC 3256, Durham, NC, 27710, USA
| | - George N Ioannou
- Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 130 Mason Farm Road, Bioinformatics Building CB#7080, Chapel Hill, NC, 27599-7080, USA
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA, 98108, USA
- Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA, 98108, USA
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16
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Sacco M, Saracco GM. The impact of direct-acting antiviral treatment on glycemic homeostasis in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:264-272. [PMID: 33856147 DOI: 10.23736/s2724-5985.21.02835-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND there is robust epidemiological evidence suggesting the link of chronic Hepatitis C Virus (HCV) infection with type 2 diabetes mellitus (DM). Viral clearance achieved by Direct Acting Antiviral Agents (DAAs) has been associated to significant improvements in glycometabolic control but data on the long-term effect of Sustained Virological Response on diabetic disease are limited. AIM the aim of this review is to evaluate the influence of SVR after DAA-based therapy on Insulin Resistance (IR) and DM incidence in non-diabetic patients, on the glycemic homeostasis in diabetic patients and on their long-term hepatic and metabolic outcomes. METHODS an electronic search of Embase, PubMed, MEDLINE, Ovid and the Cochrane Database of Systematic Reviews was performed for papers regarding the effect of DAAinduced SVR on the glycometabolic control and clinical outcomes of HCV-positive diabetic patients up to September 30, 2020. RESULTS among non-diabetic patients, a significant reduction in the risk of IR and DM was reported by the vast majority of the studies; the glycometabolic control significantly improved in diabetic patients during and immediately after the end of antiviral treatment. However, whether this beneficial effect is long lasting is still matter of debate. Furthermore, at variance with data obtained during the Interferon (IFN) era, DM does not seem to be an unfavourable predictive factor of Hepatocellular Carcinoma (HCC) in cured patients. CONCLUSIONS a favourable influence of DAA-induced SVR on IR and DM incidence and on glycemic control is reported by several studies. However, the long-term biochemical, metabolic and clinical impact of this endocrine benefit remains largely unknown.
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Affiliation(s)
- Marco Sacco
- Gastro-hepatoloy Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giorgio M Saracco
- Gastro-hepatoloy Unit, Department of Medical Sciences, University of Turin, Turin, Italy -
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17
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Yoshio S, Kanto T. Macrophages as a source of fibrosis biomarkers for non-alcoholic fatty liver disease. Immunol Med 2021; 44:175-186. [PMID: 33444517 DOI: 10.1080/25785826.2020.1868664] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) are becoming major liver diseases worldwide. Liver fibrosis and cirrhosis are among the most significant risk factors of hepatocellular carcinoma (HCC) and associated with the long-term prognosis of NAFLD patients. To stratify the risk of HCC in NAFLD patients clinically, the discovery of non-invasive fibrosis markers is needed urgently. Liver macrophages play critical roles in the regulation of inflammation and fibrosis by interacting with hepatic stellate cells (HSCs) and other immune cells. Thus, it is rational to explore feasible biomarkers for liver fibrosis by focusing on macrophage-related factors. We examined serum factors comprehensively in multiple cohorts of NAFLD/NASH patients to determine whether they were correlated with the biopsy-proven fibrosis stage. We found that the serum levels of interleukin (IL)-34, YKL-40 and soluble Siglec-7 (sSiglec7) were closely associated with liver fibrosis and served as diagnostic biomarkers in patients with NAFLD/NASH. In the NAFLD liver, IL-34 was produced by activated fibroblasts, and YKL-40 and sSiglec-7 were secreted from macrophages. The sensitivity and specificity of these markers to detect advanced liver fibrosis varied, supporting the notion that the combination of these markers with other modalities is an option for clinical application.
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Affiliation(s)
- Sachiyo Yoshio
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Tatsuya Kanto
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
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18
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Abe K, Wakabayashi H, Nakayama H, Suzuki T, Kuroda M, Yoshida N, Tojo J, Kogure A, Rai T, Saito H, Mukai S, Fujita M, Hayashi M, Takahashi A, Ohira H. Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis. PLoS One 2020; 15:e0243473. [PMID: 33284844 PMCID: PMC7721183 DOI: 10.1371/journal.pone.0243473] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 11/21/2020] [Indexed: 02/08/2023] Open
Abstract
The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.
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Affiliation(s)
- Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
- Department of Internal Medicine, Hanawa Kosei Hospital, Higashishirakawa, Japan
- * E-mail:
| | - Hiroto Wakabayashi
- Department of Gastroenterology, Takeda General Hospital, Aizuwakamatsu, Japan
| | - Haruo Nakayama
- Department of Gastroenterology, Iwaki City Medical Center, Iwaki, Japan
| | - Tomohiro Suzuki
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Masahito Kuroda
- Department of Gastroenterology, Fukushima Red Cross Hospital, Fukushima, Japan
| | - Naoe Yoshida
- Department of Internal Medicine, Iwase General Hospital, Sukagawa, Japan
| | | | - Atsuko Kogure
- Department of Gastroenterology, Fujita General Hospital, Date, Japan
| | | | | | - Shinji Mukai
- Department of Gastroenterology, Ohta Nishinouchi Hospital, Koriyama, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
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19
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Sohn W, Lee HW, Lee S, Lim JH, Lee MW, Park CH, Yoon SK. Obesity and the risk of primary liver cancer: A systematic review and meta-analysis. Clin Mol Hepatol 2020; 27:157-174. [PMID: 33238333 PMCID: PMC7820201 DOI: 10.3350/cmh.2020.0176] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022] Open
Abstract
Background/Aims In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer. Methods This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included. Results A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancer-related mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I2=80%). Conclusions High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.
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Affiliation(s)
- Won Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sangheun Lee
- Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Jin Hong Lim
- Department of General Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University College of Medicine, Seoul, Korea
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20
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Liver abscess caused by Cutibacterium namnetense after transarterial chemoembolization for hepatocellular carcinoma. Clin J Gastroenterol 2020; 14:246-250. [DOI: 10.1007/s12328-020-01283-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022]
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21
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Asahina Y. JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update; Protective Effect of Antiviral Therapy against Hepatocarcinogenesis. Hepatol Res 2020; 50:775-790. [PMID: 32298527 DOI: 10.1111/hepr.13501] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/04/2020] [Accepted: 04/05/2020] [Indexed: 02/08/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.
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22
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Chen Y, Ji H, Shao J, Jia Y, Bao Q, Zhu J, Zhang L, Shen Y. Different Hepatitis C Virus Infection Statuses Show a Significant Risk of Developing Type 2 Diabetes Mellitus: A Network Meta-Analysis. Dig Dis Sci 2020; 65:1940-1950. [PMID: 31758432 DOI: 10.1007/s10620-019-05918-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 10/22/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of hepatitis C virus (HCV) infection statuses in the development of type 2 diabetes mellitus (T2DM) has not been completely understood. AIM To evaluate the prevalence of T2DM in patients with different HCV infection statuses. METHODS We conducted a systematic study on T2DM risk in five types of individuals with different HCV infection statuses: non-HCV controls, HCV-cleared patients, chronic HCV patients without cirrhosis, patients with HCV cirrhosis and patients with decompensated HCV cirrhosis. Studies published from 2010 to 2019 were selected. Both pairwise and network meta-analyses were employed to compare the T2DM risk among patients with different HCV infection statuses. RESULTS The pairwise meta-analysis showed that non-HCV (OR = 0.60, 95% CI [0.47-0.78]) had a lower risk of T2DM compared with CHC, while cirrhosis had a significant higher risk (OR = 1.90, 95% CI [1.60-2.26]). Network meta-analysis further demonstrated patients with HCV infection were at a significantly higher risk of T2DM than those without HCV infection or with HCV clearance, while decompensated cirrhosis had a significant higher T2DM risk than non-HCV (OR = 3.84, 95% CI [2.01-7.34]), patients with HCV clearance (OR = 3.17, 95% CI [1.49-6.73]), and CHC patients (OR = 2.21, 95% CI [1.24-3.94]). CONCLUSIONS HCV infection is a significant risk factor for developing T2DM. CHC, cirrhosis, and decompensated cirrhosis contribute to an increasingly greater risk of T2DM, but HCV clearance spontaneously or through clinical treatment may immediately reduce the risk of the onset and development of T2DM.
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Affiliation(s)
- Ying Chen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Hanzhen Ji
- Centre for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Jianguo Shao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
- Centre for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Yulong Jia
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Qi Bao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Jianan Zhu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Lei Zhang
- Research Centre for Public Health, School of Medicine, Tsinghua University, Beijing, China
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia
- Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Australia
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China.
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23
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: part (I) general population. J Formos Med Assoc 2020; 119:1019-1040. [PMID: 32359879 DOI: 10.1016/j.jfma.2020.04.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) infection remains a major public health issue with high prevalence in Taiwan. Recently, the advent of direct-acting antiviral (DAA) agents, with higher efficacy, excellent safety profile, and truncated treatment duration, has revolutionized the paradigm of hepatitis C treatment and made HCV elimination possible. To provide timely guidance for optimal hepatitis C management, the Taiwan Association for the Study of the Liver (TASL) established an expert panel to publish a 2-part consensus statement on the management of hepatitis C in the DAA era. After comprehensive literature review and a consensus meeting, patient-oriented, genotype-guided recommendations on hepatitis C treatment for the general and special populations have been provided based on the latest indications and scientific evidence. In the first part of this consensus, we present the epidemiology and treatment situation of hepatitis C in Taiwan, the development of DAA, pre-treatment evaluation, post sustained virologic response (SVR) monitoring, and most importantly the treatment recommendations for the general population with compensated liver disease. The second part will focus on the treatment recommendations for the special populations.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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24
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Tahata Y, Sakamori R, Urabe A, Yamada R, Ohkawa K, Hiramatsu N, Hagiwara H, Oshita M, Hijioka T, Tamura S, Imai Y, Kodama T, Hikita H, Tatsumi T, Takehara T. Hepatocellular carcinoma occurrence does not differ between interferon-based and interferon-free treatment with liver histological assessment. Hepatol Res 2020; 50:313-320. [PMID: 31747479 DOI: 10.1111/hepr.13454] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 10/10/2019] [Accepted: 11/01/2019] [Indexed: 02/08/2023]
Abstract
AIM Several studies have recently reported that hepatocellular carcinoma (HCC) occurrence does not differ between hepatitis C virus patients receiving interferon (IFN)-based and IFN-free treatments considering the patients' backgrounds. However, liver fibrosis was not directly considered in these studies. METHODS In total, 3972 patients without a history of HCC who started IFN-based or IFN-free treatment between August 2002 and April 2017 at 30 Japanese hospitals and achieved a sustained virologic response were included. Propensity score matching considering liver histology was performed. RESULTS The median age and percentage of patients with advanced liver fibrosis (F3/4) were 58 years and 11.4% in the IFN-based group, and 68 years and 18.9% in the IFN-free group, respectively. The HCC occurrence rates at 1 year and 2 years were 0.4% and 1.1% in the IFN-based group, and 1.6% and 4.1% in the IFN-free group, respectively, and HCC occurrence in the IFN-free group was significantly higher than that in the IFN-based group (P < 0.001). The characteristics of the HCC occurrence patterns did not differ between the two groups. After propensity score matching, among 764 patients, the HCC occurrence rates at 1 year and 2 years were 0.5% and 1.9% in the IFN-based group and 1.1% and 3.0% in the IFN-free group, respectively, and no significant difference was observed between the two groups (P = 0.489). CONCLUSIONS HCC occurrence in sustained virologic response patients does not differ between IFN-based and IFN-free treatment considering liver fibrosis stage. The degree of its progress at diagnosis does not differ between the two groups.
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Affiliation(s)
- Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ayako Urabe
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | | | | | | | | | - Taizo Hijioka
- National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan
| | | | | | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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The Effect of Viral Clearance Achieved by Direct-Acting Antiviral Agents on Hepatitis C Virus Positive Patients with Type 2 Diabetes Mellitus: A Word of Caution after the Initial Enthusiasm. J Clin Med 2020; 9:jcm9020563. [PMID: 32092892 PMCID: PMC7074145 DOI: 10.3390/jcm9020563] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 02/11/2020] [Accepted: 02/17/2020] [Indexed: 02/07/2023] Open
Abstract
The causal link between chronic hepatitis C and glycometabolic alterations has been confirmed by much biochemical, clinical, and epidemiological research work, but what is still controversial is the long-term clinical impact of sustained virologic response (SVR) achieved by direct-acting antiviral agents (DAAs) on patients with type 2 diabetes mellitus (DM). The aim of this paper is to summarize the biochemical and clinical consequences to DM of DAA-based therapy for hepatitis C virus (HCV) infection. An electronic search of Embase, PubMed, MEDLINE, Ovid, and the Cochrane Database of Systematic Reviews was conducted for publications assessing whether clearance of HCV achieved by interferon (IFN)-free antiviral therapy determines significant changes in glycometabolic control and clinical outcomes of diabetic patients. A beneficial effect of SVR obtained by DAA therapy on DM prevention and the short-term outcome of glycometabolic alterations are acknowledged by most of the studies. Whether this effect is maintained over the long term with a significant clinical impact on diabetic and liver disease is still a matter of debate.
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Yang C, Lu Y, Xia H, Liu H, Pan D, Yang X, Sun G. Excess Body Weight and the Risk of Liver Cancer: Systematic Review and a Meta-Analysis of Cohort Studies. Nutr Cancer 2019; 72:1085-1097. [PMID: 31544511 DOI: 10.1080/01635581.2019.1664602] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Revised: 08/21/2019] [Accepted: 09/01/2019] [Indexed: 12/24/2022]
Abstract
Objective: To update and expand the previous meta-analysis including all prospective studies on the issue of the associations between overweight, obesity, and liver cancer risk. We also performed a meta-regression to investigate a potential nonlinear and/or linear association between body mass index (BMI) and liver cancer risk.Methods: Literature search was conducted in four libraries from the beginning of indexing for each database to 1st September, 2018.Results: The summary risk estimate was statistically significant on the association between overweight and the risk of liver cancer incidence (relative ratio [RR] = 1.19). The RRs were significantly stronger in people with known liver disease with overweight than in the general population with overweight (RR = 1.50 vs. RR = 1.10; Pdifference = .02). The meta-analysis showed an increase by 87% on the risk of liver cancer incidence in obesity categories, relative to categories of normal BMI (RR = 1.87, P < .01). Moreover, the results showed that, overweight was associated with 9% increased and obesity with 66% increased for risk of liver cancer mortality. In linear model, the relative risks of liver cancer were 1.32 for continuous BMI per 5 kg/m2 increase.Conclusion: This meta-analysis supports the hypothesis that overweight, obesity may significantly increase liver cancer risk.
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Affiliation(s)
- Chao Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Yifei Lu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Hui Xia
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Hechun Liu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Xian Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Guiju Sun
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
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Tan Y, Zhang X, Zhang W, Tang L, Yang H, Yan K, Jiang L, Yang J, Li C, Yang J, Wen T, Tang H, Yan L. The Influence of Metabolic Syndrome on the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Mainland China. Cancer Epidemiol Biomarkers Prev 2019; 28:2038-2046. [PMID: 31533942 DOI: 10.1158/1055-9965.epi-19-0303] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/15/2019] [Accepted: 09/12/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The association between metabolic syndrome (MS), both in terms of its components and as a whole, and the risk of hepatocellular carcinoma (HCC) in subjects with hepatitis B virus (HBV) infection remains unclear, especially in mainland China. METHODS We prospectively included 6,564 individuals with HBV infection from an initial cohort of 105,397 civil servants. The multivariate-adjusted HR and 95% confidence interval (95% CI) were evaluated using Cox proportional hazards models to explore the potential connection between HCC risk and MS. Cumulative incidences were plotted using Kaplan-Meier curves. RESULTS After a 45,668.0 person-year follow-up (76.0 ± 30.8 months) of 6,564 subjects who were seropositive for hepatitis B surface antigen, 89 incident HCC cases were identified. MS as a whole was independently associated with a 2-fold increased HCC risk (HR, 2.25; 95% CI, 1.41-3.60) after adjusting for age (in 1-year increments), gender, cigarette smoking, alcohol consumption, liver cirrhosis, and elevated aspartate aminotransferase levels (≥40 U/L). Subjects with three or more factors and those with one or two factors had adjusted increased HCC risks of 2.12-fold (95% CI, 1.16-3.89) and 1.28-fold (95% CI, 0.74-2.22), respectively, in comparison with those without any metabolic factors. Central obesity and type 2 diabetes were associated with significantly increased HCC risk, whereas this association was not observed in obese subjects (body mass index ≥30 kg/m2; 95% CI, 0.73-3.44). CONCLUSIONS MS as a whole, central obesity, and type 2 diabetes were independently associated with increased HCC risk in a population with HBV infection in mainland China. IMPACT MS may be a risk factor for HCC.
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Affiliation(s)
- Yifei Tan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoyun Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Wei Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Li Tang
- Department of Intense Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hanwei Yang
- Physical Examination Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Ke Yan
- West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China
| | - Li Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jian Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Chuan Li
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jiayin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Tianfu Wen
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Huairong Tang
- Physical Examination Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Lunan Yan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
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Diabetes mellitus as a risk factor of hepatocellular carcinoma in patients with chronic hepatitis B on nucleot(s)ide analogues. J Hepatol 2019; 70:795-796. [PMID: 30630598 DOI: 10.1016/j.jhep.2018.11.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 11/16/2018] [Indexed: 12/04/2022]
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Nishijima N, Nasu A, Kimura T, Osaki Y. Two Cases of Hepatocellular Carcinoma Occurring Immediately after Direct-acting Antiviral Agents against Hepatitis C Virus. Intern Med 2019; 58:225-231. [PMID: 30146562 PMCID: PMC6378164 DOI: 10.2169/internalmedicine.0712-17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
We experienced two cases of hepatocellular carcinoma (HCC) occurring immediately after treatment with direct-acting antiviral agents (DAAs). Case 1 was a 75-year-old woman in whom HCC was detected immediately after completion of DAA treatment. Case 2 was a 75-year-old woman who had a hypovascular nodule in liver. The hypovascular nodule became hypervascular without enlargement of the nodule size immediately after DAA treatment completion. Although the association between DAA treatment and hepatocarcinogenesis is unknown, sufficient surveillance after achieving a sustained viral response is required, as a large number of patients at a high risk of hepatocarcinogenesis are treated with DAAs.
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Affiliation(s)
- Norihiro Nishijima
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Japan
| | - Akihiro Nasu
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Japan
| | - Toru Kimura
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Japan
| | - Yukio Osaki
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Japan
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Tan Y, Wei S, Zhang W, Yang J, Yang J, Yan L. Type 2 diabetes mellitus increases the risk of hepatocellular carcinoma in subjects with chronic hepatitis B virus infection: a meta-analysis and systematic review. Cancer Manag Res 2019; 11:705-713. [PMID: 30679924 PMCID: PMC6338123 DOI: 10.2147/cmar.s188238] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background Type 2 diabetes mellitus has been proved to be a risk factor of hepatocellular carcinoma, but how diabetes affects incidence of hepatocellular carcinoma among patients with chronic hepatitis B virus infection remains controversial. Methods A comprehensive search of Medline and Embase was performed. Incidence of hepatocellular carcinoma in chronic hepatitis B patients was the primary outcome. Pooled HRs and 95% CIs were calculated to assess the correlation between diabetes and incidence of hepatocellular carcinoma. Results Five cohort studies and two case–control studies were identified, with a total of 21,842 chronic hepatitis B patients. The diabetes mellitus cohort was found to have increased incidence of hepatocellular carcinoma (pooled HR 1.77, 95% CI 1.28–2.47; fixed effect) and worse overall mortality (pooled RR 1.93, 95% CI 1.64–2.27; fixed effect) in comparison with those without diabetes. In case–control studies, hepatocellular carcinoma cases were found to have an insignificantly elevated diabetes mellitus rate in comparison with the control group. Conclusion Type 2 diabetes mellitus is significantly associated with increased risk of hepatocellular carcinoma among patients with chronic hepatitis B virus infection, and aggressive management of diabetes mellitus is strongly suggested.
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Affiliation(s)
- Yifei Tan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Shiyou Wei
- Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Wei Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Jian Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Jiayin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Lunan Yan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
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Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
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Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
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Hu CC, Weng CH, Chang LC, Lin CL, Chen YT, Hu CF, Hua MC, Chen LW, Chien RN. Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy. Ther Clin Risk Manag 2018; 14:783-791. [PMID: 29750037 PMCID: PMC5933468 DOI: 10.2147/tcrm.s158424] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Purpose Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. Patients and methods We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9–12.6 years). Results The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390–4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420–4.871, P=0.002), pretreatment platelet counts <146.5 × 103/μL (HR: 2.751, 95% CI: 1.373–5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277–4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283–7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). Conclusion The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.
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Affiliation(s)
- Ching-Chih Hu
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Cheng-Hao Weng
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Nephrology and Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Liang-Che Chang
- Department of Pathology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Yen-Ting Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Fang Hu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Man-Chin Hua
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Li-Wei Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan
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Yeh ML, Huang CI, Huang CF, Hsieh MH, Hsieh MY, Lin ZY, Chen SC, Huang JF, Kuo PL, Kuo HT, Dai CY, Yu ML, Chuang WL. Post-treatment alpha fetoprotein and platelets predict hepatocellular carcinoma development in dual-infected hepatitis B and C patients after eradication of hepatitis C. Oncotarget 2018; 9:12240-12249. [PMID: 29552306 PMCID: PMC5844742 DOI: 10.18632/oncotarget.24219] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 09/21/2017] [Indexed: 02/06/2023] Open
Abstract
We investigated the long-term risk of hepatocellular carcinoma (HCC) in dual-infected hepatitis B and C patients after eradication of hepatitis C virus (HCV). A total of 164 (62% male, median age, 50.5 years) hepatitis B and C dual-infected patients who achieved HCV sustained virological response were recruited. Half the patients were HCV genotype 1 with a median viral load of 5.5 log10 IU/mL, and 22.6%had an HBV DNA level ≥ 2000 IU/mL before therapy. HCC developed in 14 patients (8.5%), with an annual incidence of 1.38% per person-year. The 3-year, 5-year, 10-year, and 15-year cumulative probabilities were 2.5%, 5.1%, 12.6%, and 22.7%, respectively. Six months after treatment, a Cox regression hazard analysis revealed platelet level (HR: 0.98, 95% CI: 0.957-0.999, P = 0.038) and AFP level (HR: 1.20, 95% CI: 1.031-1.400, P = 0.019) to be independent factors in HCC. A higher 10-year cumulative risk of HCC was detected in patients with 6-month post-treatment AFP levels > 5.0 ng/mL and platelet levels < 130 x1000/µL (54.9%), compared to patients with neither (8.6%). Although the risk of HCC is low, surveillance of HCC is encouraged in dual-infected patients after eradication of HCV. Post-treatment AFP and platelet levels predict HCC development.
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Affiliation(s)
- Ming-Lun Yeh
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Lin Kuo
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
- Department of Senior Citizen Service Management Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Chia-Yen Dai
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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Adinolfi LE, Jacobson I, Bondin M, Cacoub P. Expert opinion on managing chronic HCV infection in patients with type 2 diabetes mellitus. Antivir Ther 2018; 23:11-21. [PMID: 30451154 DOI: 10.3851/imp3255] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2018] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes mellitus (T2DM) has been identified as an extrahepatic manifestation of chronic HCV infection. Conversely, in the context of chronic HCV infection, T2DM can accelerate the course of HCV-induced liver disease leading to increased risk of fibrosis, cirrhosis and hepatocellular carcinoma. The presence of T2DM negatively impacts the efficacy of interferon-based antiviral therapy, but real-world data with high-efficacy direct-acting antiviral therapies suggest high viral clearance rates in T2DM patients. In HCV-infected individuals, viral eradication is associated with a reduced risk of de novo T2DM in non-diabetic patients and beneficial metabolic changes in patients with T2DM, highlighting the importance of antiviral treatment and physician awareness of this association.
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MESH Headings
- Antiviral Agents/therapeutic use
- Blood Glucose/drug effects
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/virology
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/prevention & control
- Diabetes Mellitus, Type 2/virology
- Disease Management
- Drug Combinations
- Glycated Hemoglobin/antagonists & inhibitors
- Glycated Hemoglobin/metabolism
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Humans
- Insulin Resistance
- Liver/drug effects
- Liver/metabolism
- Liver/pathology
- Liver/virology
- Liver Cirrhosis/drug therapy
- Liver Cirrhosis/etiology
- Liver Cirrhosis/pathology
- Liver Cirrhosis/virology
- Liver Neoplasms/drug therapy
- Liver Neoplasms/etiology
- Liver Neoplasms/pathology
- Liver Neoplasms/virology
- Risk Factors
- Treatment Outcome
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Affiliation(s)
- Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | | | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, Paris, France
- CNRS, FRE3632, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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35
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Ciancio A, Bosio R, Bo S, Pellegrini M, Sacco M, Vogliotti E, Fassio G, Bianco Mauthe Degerfeld AGF, Gallo M, Giordanino C, Terzi di Bergamo L, Ribaldone D, Bugianesi E, Smedile A, Rizzetto M, Saracco GM. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol 2017; 90:320-327. [DOI: 10.1002/jmv.24954] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Alessia Ciancio
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Roberta Bosio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Simona Bo
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marianna Pellegrini
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marco Sacco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Edoardo Vogliotti
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giulia Fassio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | | | - Monica Gallo
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Chiara Giordanino
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Lodovico Terzi di Bergamo
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Davide Ribaldone
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Elisabetta Bugianesi
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Antonina Smedile
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Mario Rizzetto
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giorgio Maria Saracco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
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36
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Kawaguchi T, Ide T, Koga H, Kondo R, Miyajima I, Arinaga-Hino T, Kuwahara R, Amano K, Niizeki T, Nakano M, Kuromatsu R, Torimura T. Rapidly growing hepatocellular carcinoma after direct-acting antiviral treatment of chronic hepatitis C. Clin J Gastroenterol 2017; 11:69-74. [PMID: 29082453 DOI: 10.1007/s12328-017-0789-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 10/12/2017] [Indexed: 12/29/2022]
Abstract
We report on a 62-year-old man with chronic hepatitis C who developed rapidly growing hepatocellular carcinoma (HCC) after achieving sustained virological response at post-treatment week 24 (SVR 24) by direct-acting antiviral (DAA) treatment. In 2008, he failed interferon therapy at 56 years of age. He received daclatasvir plus asunaprevir for 24 weeks after confirmation of no liver tumor by abdominal ultrasonography. He had no advanced liver fibrosis. Three months after initiation of DAA treatment, a liver tumor measuring 6 mm in diameter was detected by ultrasonography and confirmed with magnetic resonance imaging. After achieving SVR 24, the tumor increased in size to 16 mm. Two months later, a tumor biopsy was performed, and histology revealed moderately to poorly differentiated HCC. The patient's alpha-fetoprotein (AFP) level was within the normal range, but the Lens culinaris agglutinin-reactive fraction of AFP level was elevated. The diameter of the tumor increased to 32 mm at 2 months after diagnosis. Lymph node metastasis in porta hepatis was found by positron emission tomography at 4 months after diagnosis. The patient received hepatic arterial infusion chemotherapy and radiation therapy, but died later. Careful monitoring is required during and after DAA treatment because HCC can grow fast even in patients with normal AFP and no advanced liver fibrosis.
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Affiliation(s)
- Toshihiro Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Hironori Koga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Reiichiro Kondo
- Department of Pathology, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Ichiro Miyajima
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Teruko Arinaga-Hino
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Reiichiro Kuwahara
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Takashi Niizeki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Masahito Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Ryoko Kuromatsu
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
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37
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Management consensus guideline for hepatocellular carcinoma: 2016 updated by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. J Formos Med Assoc 2017; 117:381-403. [PMID: 29074347 DOI: 10.1016/j.jfma.2017.09.007] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/16/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Taiwan. To help clinical physicians to manage patients with HCC, the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan produced the management consensus guideline for HCC. METHODS The recommendations focus on nine important issues on management of HCC, including surveillance, diagnosis, staging, surgery, local ablation, transarterial chemoembolization/transarterial radioembolization/hepatic arterial infusion chemotherapy, systemic therapy, radiotherapy, and prevention. RESULTS The consensus statements were discussed, debated and got consensus in each expert team. And then the statements were sent to all of the experts for further discussion and refinement. Finally, all of the experts were invited to vote for the statements, including the level of evidence and recommendation. CONCLUSION With the development of the management consensus guideline, HCC patients could benefit from the optimal therapeutic modality.
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38
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Cacoub P, Comarmond C, Desbois AC, Saadoun D. Rheumatologic Manifestations of Hepatitis C Virus Infection. Clin Liver Dis 2017; 21:455-464. [PMID: 28689585 DOI: 10.1016/j.cld.2017.03.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatitis C virus (HCV) infection is associated with a morbidity and mortality due to liver complications. HCV infection is also frequently associated with rheumatic disorders, such as arthralgia, myalgia, cryoglobulinemia vasculitis, and sicca syndrome, as well as the production of autoantibodies. The treatment of HCV infection with interferon alpha (IFN) has been contraindicated for a long time in many rheumatologic autoimmune/inflammatory disorders. New oral IFN-free combinations offer an opportunity for HCV-infected patients with extrahepatic manifestations, including rheumatologic autoimmune/inflammatory disorders, to be cured with a short treatment duration and a low risk of side effects.
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Affiliation(s)
- Patrice Cacoub
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), UMR 7211, UPMC Université Paris 06, Sorbonne Universités, Paris F-75005, France; INSERM, UMR_S 959, Paris F-75013, France; CNRS, FRE3632, Paris F-75005, France; Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 83 boulevard de l'hô pital, Paris F-75013, France.
| | - Cloé Comarmond
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), UMR 7211, UPMC Université Paris 06, Sorbonne Universités, Paris F-75005, France; INSERM, UMR_S 959, Paris F-75013, France; CNRS, FRE3632, Paris F-75005, France; Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 83 boulevard de l'hô pital, Paris F-75013, France
| | - Anne Claire Desbois
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), UMR 7211, UPMC Université Paris 06, Sorbonne Universités, Paris F-75005, France; INSERM, UMR_S 959, Paris F-75013, France; CNRS, FRE3632, Paris F-75005, France; Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 83 boulevard de l'hô pital, Paris F-75013, France
| | - David Saadoun
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), UMR 7211, UPMC Université Paris 06, Sorbonne Universités, Paris F-75005, France; INSERM, UMR_S 959, Paris F-75013, France; CNRS, FRE3632, Paris F-75005, France; Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 83 boulevard de l'hô pital, Paris F-75013, France
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39
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Bang CS, Song IH. Impact of antiviral therapy on hepatocellular carcinoma and mortality in patients with chronic hepatitis C: systematic review and meta-analysis. BMC Gastroenterol 2017; 17:46. [PMID: 28376711 PMCID: PMC5379714 DOI: 10.1186/s12876-017-0606-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 03/28/2017] [Indexed: 12/17/2022] Open
Abstract
Background The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy. This study aimed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection. Methods A systematic review was conducted for studies that evaluated the antiviral efficacy for patients with chronic hepatitis C or assessed the development of HCC or mortality between SVR (sustained virologic response) and non-SVR patients. The methodological quality of the enrolled publications was evaluated using Risk of Bias table or Newcastle-Ottawa scale. Random-effect model meta-analyses and meta-regression were performed. Publication bias was assessed. Results In total, 59 studies (4 RCTs, 15 prospective and 40 retrospective cohort studies) were included. Antiviral treatment was associated with reduced development of HCC (vs. no treatment; OR 0.392, 95% CI 0.275–0.557), and this effect was intensified when SVR was achieved (vs. no SVR, OR: 0.203, 95% CI 0.164–0.251). Antiviral treatment was associated with lower all-cause mortality (vs. no treatment; OR 0.380, 95% CI 0.295–0.489) and liver-specific mortality (OR 0.363, 95% CI 0.260–0.508). This rate was also intensified when SVR was achieved [all-cause mortality (vs. no SVR, OR 0.255, 95% CI 0.199–0.326), liver-specific mortality (OR 0.126, 95% CI 0.094–0.169)]. Sensitivity analyses revealed robust results, and a small study effect was minimal. Conclusions In patients with chronic hepatitis C, antiviral therapy can reduce the development of HCC and mortality, especially when SVR is achieved. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0606-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Il Han Song
- Division of Hepatology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea, Republic of Korea.
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40
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Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
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41
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Cacoub P, Commarmond C, Sadoun D, Desbois AC. Hepatitis C Virus Infection and Rheumatic Diseases. Rheum Dis Clin North Am 2017; 43:123-132. [PMID: 27890169 DOI: 10.1016/j.rdc.2016.09.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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42
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Zhao Y, Xing H. A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases. J Diabetes Res 2017; 2017:5625371. [PMID: 28352640 PMCID: PMC5352886 DOI: 10.1155/2017/5625371] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 01/21/2017] [Accepted: 01/30/2017] [Indexed: 02/07/2023] Open
Abstract
Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.
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Affiliation(s)
- Yingying Zhao
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Huichun Xing
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
- *Huichun Xing:
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43
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Wang JH, Yen YH, Yao CC, Hung CH, Chen CH, Hu TH, Lee CM, Lu SN. Liver stiffness-based score in hepatoma risk assessment for chronic hepatitis C patients after successful antiviral therapy. Liver Int 2016; 36:1793-1799. [PMID: 27254286 DOI: 10.1111/liv.13179] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 05/31/2016] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Patients with chronic hepatitis C (CHC) after successful antiviral therapy remain at risk of hepatocellular carcinoma (HCC). This study was to determine whether liver stiffness measurement (LSM) was useful in HCC risk assessment and to develop a risk-score system for clinical use. METHODS This retrospective study enrolled patients with CHC achieving sustained virological response (SVR) after interferon-based therapy with LSM at/after SVR determination. The demographics, clinical characteristics and HCC development were obtained from medical chart reviews. The diagnosis of HCC was based on recommended criteria. RESULTS A total of 376 (M/F: 185/191, mean age: 54.1 years) patients, including 278 with pretreatment liver biopsy specimens, with a median follow-up period of 7.6 years were enrolled. Twenty-one patients developed HCC. The 5- and 10-year cumulative HCC incidences were 1.4% and 7.8%, respectively. Multivariate analysis showed advanced fibrosis/cirrhosis, diabetes and LSM were associated with HCC developments with odds ratio (OR) of 12.38, 2.80 and 1.01, respectively. For LSM in HCC prediction, the performance and cut-off were 0.783 and 12 kilopascal (kPa), respectively. For 278 patients with pretreatment biopsy, a risk-score system (score 0-4) combining advanced fibrosis/cirrhosis, diabetes and LSM >12 kPa was developed. With the low-risk group as a reference, patients in intermediate- (OR: 12.57) and high-risk (OR: 197.33) groups carried higher risk of HCC development. CONCLUSIONS For patients with CHC achieving SVR, liver stiffness value at/after SVR determination was associated with HCC development independently. Patients with pretreatment advanced fibrosis/cirrhosis, diabetes and LSM >12 kPa after SVR were at high risk of HCC development.
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Affiliation(s)
- Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chuan-Mo Lee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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44
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Al-Mahtab M, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing. Hepatol Int 2016; 10:681-701. [PMID: 27229718 PMCID: PMC5003900 DOI: 10.1007/s12072-016-9736-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023]
Abstract
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on "APASL consensus statements and recommendations for management of hepatitis C" in March 2015 to revise the "APASL consensus statements and management algorithms for hepatitis C virus infection" (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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45
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Carrilho FJ, Mattos AAD, Vianey AF, Vezozzo DCP, Marinho F, Souto FJ, Cotrim HP, Coelho HSM, Silva I, Garcia JHP, Kikuchi L, Lofego P, Andraus W, Strauss E, Silva G, Altikes I, Medeiros JE, Bittencourt PL, Parise ER. Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma. ARQUIVOS DE GASTROENTEROLOGIA 2016; 52 Suppl 1:2-14. [PMID: 26959803 DOI: 10.1590/s0004-28032015000500001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.
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Affiliation(s)
| | | | | | | | - Fábio Marinho
- Hospital Português de Beneficiência, Recife, PE, Brazil
| | | | | | | | - Ivonete Silva
- Faculdade de Medicina, Universidade Federal de São Paulo, SP, Brazil
| | | | - Luciana Kikuchi
- Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Patricia Lofego
- Faculdade de Medicina, Universidade Federal do Espírito Santo, ES, Brazil
| | | | - Edna Strauss
- Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | | | | | | | - Edison R Parise
- Faculdade de Medicina, Universidade Federal de São Paulo, SP, Brazil
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Ng KJ, Tseng CW, Chang TT, Tzeng SJ, Hsieh YH, Hung TH, Huang HT, Wu SF, Tseng KC. Aspartate aminotransferase to platelet ratio index and sustained virologic response are associated with progression from hepatitis C associated liver cirrhosis to hepatocellular carcinoma after treatment with pegylated interferon plus ribavirin. Clin Interv Aging 2016; 11:1035-41. [PMID: 27536084 PMCID: PMC4976814 DOI: 10.2147/cia.s108589] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate the clinically significant predictors of hepatocellular carcinoma (HCC) development among hepatitis C virus (HCV) cirrhotic patients receiving combination therapy. PATIENTS AND METHODS One hundred and five compensated cirrhosis patients who received pegylated interferon plus ribavirin between January 2005 and December 2011 were enrolled. All the patients were examined with abdominal sonography and liver biochemistry at baseline, end of treatment, and every 3-6 months posttreatment. The occurrence of HCC was evaluated every 3-6 months posttreatment. RESULTS A total of 105 patients were enrolled (mean age 58.3±10.4 years). The average follow-up time for each patient was 4.38 years (standard deviation 1.73 years; range 1.13-9.27 years). Fifteen (14.3%) patients developed HCC during follow-up period. Thirteen of them had high baseline aspartate aminotransferase to platelet ratio index (APRI) (ie, an APRI >2.0). Multivariate analysis showed that those without sustained virologic response (SVR) (hazard ratio [HR] 5.795; 95% confidence interval [CI] 1.370-24.5; P=0.017) and high APRI (HR 5.548; 95% CI 1.191-25.86; P=0.029) had a significantly higher risk of HCC occurrence. The cumulative incidence of HCC was significantly higher (P=0.009) in patients without SVR (3-year cumulative incidence 21.4%; 95% CI 7.4%-35.5%; 5-year cumulative incidence 31.1%; 95% CI 11.2%-51.1%) compared to those with SVR (3- and 5-year cumulative incidence 6.2%; 95% CI 0%-1.3%). Further, the cumulative incidence of HCC was significantly higher (P=0.006) in patients with high APRI (3-year cumulative incidence 21.8%; 95% CI 8.2%-35.3%; 5-year cumulative incidence 30.5%, 95% CI 11.8%-49.3%) compared to those with low APRI (3- and 5-year cumulative incidence 4.2%, 95% CI 0%-1.0%). CONCLUSION In HCV-infected cirrhotic patients who received combination therapy, APRI and SVR are the two major predictors of HCC development.
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Affiliation(s)
- Khai-Jing Ng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien
| | - Chih-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei; School of Medicine, National Yang-Ming University, Taipei
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan; Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan
| | | | - Yu-Hsi Hsieh
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien
| | - Tsung-Hsing Hung
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien
| | - Hsiang-Ting Huang
- Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi
| | - Shu-Fen Wu
- Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien
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Huang CF, Yeh ML, Huang CY, Tsai PC, Ko YM, Chen KY, Lin ZY, Chen SC, Dai CY, Chuang WL, Huang JF, Yu ML. Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy. Medicine (Baltimore) 2016; 95:e4157. [PMID: 27399135 PMCID: PMC5058864 DOI: 10.1097/md.0000000000004157] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 06/03/2016] [Accepted: 06/14/2016] [Indexed: 12/15/2022] Open
Abstract
Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979-1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cing-Yi Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuan-Yu Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University
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Macaluso FS, Calvaruso V, Craxì A. Residual risk of hepatocellular carcinoma after HCV eradication: more than meets the eye. Future Microbiol 2016; 10:977-88. [PMID: 26059621 DOI: 10.2217/fmb.15.31] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Eradication of HCV in patients with advanced liver fibrosis or cirrhosis reduces, but does not altogether abolish, the risk of development of hepatocellular carcinoma. The reasons underlying this residual risk remain elusive. Even if HCV clearance eliminates its direct and indirect carcinogenic effects, the persistence of cirrhosis and the possible coexistence of metabolic factors (diabetes, obesity and insulin resistance) and of alcohol abuse can promote the development of hepatocellular carcinoma acting as autonomous, nonviral carcinogenic factors. Lessons learned in the IFN era may still assist in predicting the forthcoming scenario, when IFN-free regimens will obtain high rates of viral clearance even at the most advanced stages of liver disease.
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Affiliation(s)
| | - Vincenza Calvaruso
- Sezione di Gastroenterologia & Epatologia, DiBiMIS, University of Palermo, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia & Epatologia, DiBiMIS, University of Palermo, Italy
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Influence of insulin resistance on the development of hepatocellular carcinoma after antiviral treatment for non-cirrhotic patients with chronic hepatitis C. Infect Agent Cancer 2016; 11:9. [PMID: 26913058 PMCID: PMC4765113 DOI: 10.1186/s13027-016-0056-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Accepted: 02/04/2016] [Indexed: 02/07/2023] Open
Abstract
Background Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin. Methods This retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome. Results The overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR. Conclusions Insulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure.
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