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Li H, Jiao J, Gu Y, Zeng Y, Sheng Y. Risk factors and clinical outcomes in patients with HCV eradication by direct-acting antivirals: a systematic review and meta-analysis. Infect Dis (Lond) 2025:1-31. [PMID: 40333300 DOI: 10.1080/23744235.2025.2493370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/09/2025] [Accepted: 04/07/2025] [Indexed: 05/09/2025] Open
Abstract
BACKGROUND In hepatitis C patients with sustained virologic response (SVR) achieved after direct-acting antivirals (DAAs), the incidence of adverse clinical outcomes can be reduced but not completely eliminated. This meta-analysis aims at estimating the incidence of clinical outcomes in hepatitis C patients after achieving SVR with DAAs. METHODS Literature search was carried out in PubMed, Cochrane Library database, Web of Science, and Embase. The primary endpoint was the incidence of hepatocellular carcinoma (HCC) occurrence, HCC recurrence, decompensated cirrhosis, and liver-related mortality, following DAA-induced elimination of hepatitis C virus (HCV). Subgroup analyses were performed according to age, gender, comorbidities, region, fibrosis stage, presence of decompensation, duration of follow-up, start point of follow-up, and HCC treatment modality. Furthermore, meta-regression was performed to explore sources of high heterogeneity. RESULTS Finally, 132 articles were included in our study. The pooled HCC occurrence rate was 1.50/100 person-years (95% CI, 1.35-1.65), HCC recurrence rate was 17.00/100 person-years (95% CI, 13.83-20.42), decompensation rate was 0.30/100 person-years (95% CI, 0.16-0.48), and liver-related mortality was 0.32/100 person-years (95% CI, 0.14-0.56). Meta-regression showed that duration of follow-up and fibrosis grade were important contributors to HCC occurrence. Age, start point of follow-up, and duration of follow-up were important contributors to HCC recurrence rate. CONCLUSION Patients with DAA-induced HCV elimination remain at risk for adverse outcomes, particularly those with cirrhosis and HCC history. The exposure to adverse outcomes tended to decrease over time, and the frequency and intensity of follow-up might be reduced in the future, which will require new scoring models to identify these individuals.
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Affiliation(s)
- Hualing Li
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jiahuan Jiao
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yuyi Gu
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yu Zeng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yunjian Sheng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Chang SH, Cabrera R, Heo J, Park C, Guo J, Park H. Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC. Clin Pharmacol Ther 2025; 117:1030-1038. [PMID: 39489881 DOI: 10.1002/cpt.3481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/08/2024] [Indexed: 11/05/2024]
Abstract
The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.
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Affiliation(s)
- Shao-Hsuan Chang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Roniel Cabrera
- Division of Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Jihaeng Heo
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Chanhyun Park
- Health Outcomes Division, College of Pharmacy, University of Texas at Austin, Austin, Texas, USA
| | - Jingchuan Guo
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Haesuk Park
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Chang CW, Hsu WF, Tseng KC, Chen CY, Cheng PN, Hung CH, Lo CC, Bair MJ, Chen CH, Lee PL, Lin CY, Kuo HT, Chen CT, Yang CC, Huang JF, Tai CM, Hu JT, Lin CL, Su WW, Tsai WL, Huang YH, Cheng CY, Lin CL, Wang CC, Yang SS, Mo LR, Chen GY, Chang CC, Wang SJ, Huang CS, Hsieh TY, Lin CW, Lee TH, Chong LW, Huang CW, Chang SN, Tsai MC, Hsu SJ, Kao JH, Liu CJ, Liu CH, Lin HC, Tsai PC, Yeh ML, Huang CF, Dai CY, Chuang WL, Yu ML, Peng CY. Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan. Dig Dis Sci 2024; 69:3501-3512. [PMID: 38965159 DOI: 10.1007/s10620-024-08512-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/25/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.
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Affiliation(s)
- Chin-Wei Chang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
| | - Wei-Fan Hsu
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St Martin De Porres Hospital, Chiayi, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, New Taipei City, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chi-Ming Tai
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Magong City, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Chia-Sheng Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yang Ming Hospital, Chiayi, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Wen Lin
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | | | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.
- School of Medicine, China Medical University, Taichung, Taiwan.
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Sahakyan Y, Erman A, Wong WWL, Greenaway C, Janjua N, Kwong JC, Sander B. Bridging Hepatitis C Care Gaps: A Modeling Approach for Achieving the WHO's Targets in Ontario, Canada. Viruses 2024; 16:1224. [PMID: 39205198 PMCID: PMC11359558 DOI: 10.3390/v16081224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND The World Health Organization (WHO) has set hepatitis C (HCV) elimination targets for 2030. Understanding existing gaps in the "HCV care-cascade" is essential for meeting these targets. We aimed to identify the level of service scale-up needed along the "HCV care-cascade" to achieve the WHO's HCV elimination targets in Ontario, Canada. METHODS By employing a decision analytic model, we projected the quality-adjusted life years (QALYs) and healthcare costs for individuals with HCV in Ontario. We increased RNA testing and treatment rates to 98%, followed by increasing antibody testing uptake until we achieved the WHO's mortality target (i.e., a 65% reduction in liver-related mortality by 2030 vs. 2015). RESULTS Without scaling up by 2030, the expected QALYs and costs per person were 9.156 and CAD 48,996, respectively. Improved RNA testing and treatment rates reduced liver-related deaths to 3.3/100,000, a 57% reduction from 2015. Further doubling the antibody testing rates can achieve the WHO's mortality target in 2035, but not in 2030. Compared to the status quo, such program would be cost-effective considering a 50,000 CAD/QALY gained threshold if annual implementation costs stayed under 2.3 M CAD/100,000 people. CONCLUSIONS Doubling the antibody testing rates, along with increased RNA testing and treatment rates, showed promise in meeting the WHO's goals by 2035.
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Affiliation(s)
- Yeva Sahakyan
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University Health Network, Toronto, ON M5G 2C4, Canada; (Y.S.); (A.E.)
| | - Aysegul Erman
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University Health Network, Toronto, ON M5G 2C4, Canada; (Y.S.); (A.E.)
- ICES, Toronto, ON M4N 3M5, Canada
| | - William W. L. Wong
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University Health Network, Toronto, ON M5G 2C4, Canada; (Y.S.); (A.E.)
- ICES, Toronto, ON M4N 3M5, Canada
- School of Pharmacy, University of Waterloo, Kitchener, ON N2G 1C5, Canada;
| | - Christina Greenaway
- Division of Infectious Diseases, Jewish General Hospital, McGill University, Montreal, QC H3A 0G4, Canada;
| | - Naveed Janjua
- British Columbia Centre for Disease Control (BCDC), Vancouver, BC V5Z 4R4, Canada;
| | - Jeffrey C. Kwong
- ICES, Toronto, ON M4N 3M5, Canada
- Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada;
- Public Health Ontario, Toronto, ON M5G 1M1, Canada
| | - Beate Sander
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University Health Network, Toronto, ON M5G 2C4, Canada; (Y.S.); (A.E.)
- ICES, Toronto, ON M4N 3M5, Canada
- Public Health Ontario, Toronto, ON M5G 1M1, Canada
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON M5T 3M6, Canada
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Sohn W, Park SY, Lee TH, Chon YE, Kim IH, Lee BS, Yoon KT, Jang JY, Lee YR, Yu SJ, Choi WM, Kim SG, Jun DW, Jeong J, Kim JH, Jang ES, Kim HY, Cho SB, Jang BK, Park JG, Lee JW, Seo YS, Lee JI, Song DS, Kim MY, Yim HJ, Sinn DH, Ahn SH, Kim YS, Jang H, Kim W, Han S, Kim SU. Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study. EClinicalMedicine 2024; 73:102671. [PMID: 38881570 PMCID: PMC11176940 DOI: 10.1016/j.eclinm.2024.102671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 05/10/2024] [Accepted: 05/16/2024] [Indexed: 06/18/2024] Open
Abstract
BACKGROUND It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. METHODS This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. FINDINGS Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). INTERPRETATION Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. FUNDING The Korea Disease Control and Prevention Agency.
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Affiliation(s)
- Won Sohn
- Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea
| | - Soo Young Park
- Kyungpook National University Hospital, Kyungpook National University, Daegu, South Korea
| | - Tae Hee Lee
- Konyang University College of Medicine, Daejeon, South Korea
| | - Young Eun Chon
- CHA Bundang Medical Centre, CHA University, Seongnam, South Korea
| | - In Hee Kim
- Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, South Korea
| | - Byung-Seok Lee
- Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, South Korea
| | - Ki Tae Yoon
- Pusan National University Yangsan Hospital, Pusan National University College of Medicine, Yangsan, South Korea
| | - Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Yu Rim Lee
- Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, South Korea
| | - Su Jong Yu
- Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Won-Mook Choi
- Liver Centre, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang Gyune Kim
- Soonchunhyang University Hospital Bucheon, Soonchunhyang University College of Medicine, Bucheon, South Korea
| | - Dae Won Jun
- Hanyang University Hospital, Hanyang University College of Medicine, Seoul, South Korea
| | - Joonho Jeong
- Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, South Korea
| | - Ji Hoon Kim
- Guro Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Eun Sun Jang
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Hwi Young Kim
- College of Medicine, Ewha Womans University, Seoul, South Korea
| | - Sung Bum Cho
- Chonnam National University Hospital, Chonnam National University, Hwasun, South Korea
| | | | - Jung Gil Park
- Yeungnam University College of Medicine, Daegu, South Korea
| | - Jin-Woo Lee
- Inha University Hospital, Inha University School of Medicine, Incheon, South Korea
| | - Yeon Seok Seo
- Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Jung Il Lee
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Do Seon Song
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea
| | - Moon Young Kim
- Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Hyung Joon Yim
- Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea
| | - Dong Hyun Sinn
- Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Hoon Ahn
- Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Centre, Severance Hospital, Seoul, South Korea
| | - Young Seok Kim
- Soonchunhyang University Hospital Bucheon, Soonchunhyang University College of Medicine, Bucheon, South Korea
| | - Heejoon Jang
- Seoul Metropolitan Government Seoul National University Boramae Medical Centre, Seoul National University College of Medicine, Seoul, South Korea
| | - Won Kim
- Seoul Metropolitan Government Seoul National University Boramae Medical Centre, Seoul National University College of Medicine, Seoul, South Korea
| | - Seungbong Han
- Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea
| | - Seung Up Kim
- Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Centre, Severance Hospital, Seoul, South Korea
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Pearlman BL. Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis. Dig Dis Sci 2024; 69:1551-1561. [PMID: 38580885 DOI: 10.1007/s10620-024-08393-x] [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: 12/11/2023] [Accepted: 03/16/2024] [Indexed: 04/07/2024]
Abstract
Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.
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Affiliation(s)
- Brian L Pearlman
- Center for Hepatitis C, Wellstar Atlanta Medical Center, 285 Boulevard NE, Suite 525, Atlanta, GA, 30312, USA.
- Medical College of Georgia, Augusta, GA, USA.
- Emory School of Medicine, Atlanta, GA, USA.
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Fatima I, Parikh ND, Likhitsup A. Controversies of Direct-Acting Antivirals in Hepatocellular Carcinoma. Surg Oncol Clin N Am 2024; 33:43-58. [PMID: 37945144 DOI: 10.1016/j.soc.2023.06.007] [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] [Indexed: 11/12/2023]
Abstract
Therapy for chronic hepatitis C virus infection with direct-acting antiviral agents (DAAs) has been highly successful in achieving sustained virological response (SVR) with associated improvements in liver dysfunction, liver-related mortality, and transplant-free survival. There is a high risk of hepatocellular carcinoma (HCC) with an annual incidence of 2% to 4% in patients with cirrhosis. Following DAAs treatment and achievement of SVR, the risk of incident and recurrent HCC drops significantly over time, with risk associated with demographic and liver disease-related factors. Several risk factors have been described including age, male, diabetes comorbidities, alcohol abuse, hepatitis B virus or human immunodeficiency virus-coinfection, and advanced liver disease or increased liver fibrosis. Recurrence risk after DAA therapy has been associated with baseline tumor burden, with increased risk with larger lesion(s), multifocal disease, elevated alpha-fetoprotein level, treatment type (curative vs palliative), and shorter interval between HCC complete response and DAA initiation. Overall, due to the heterogeneity among individual patient data and lack of adequately controlled data, there are no conclusive statements that can be drawn that DAAs exposure is directly associated with HCC occurrence or recurrence. However, the best available data suggest a decreased risk of incident HCC with DAA therapy and no increased risk of recurrence with DAAs after complete tumor response.
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Affiliation(s)
- Ifrah Fatima
- University of Missouri-Kansas City, 2301 Holmes Street, Kansas City, MO 64108, USA
| | - Neehar D Parikh
- University of Michigan, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
| | - Alisa Likhitsup
- University of Michigan, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
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STOKES CALEB, J. MELVIN ANN. Viral Infections of the Fetus and Newborn. AVERY'S DISEASES OF THE NEWBORN 2024:450-486.e24. [DOI: 10.1016/b978-0-323-82823-9.00034-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abu-Freha N, Abu-Kosh O, Yardeni D, Ashur Y, Abu-Arar M, Yousef B, Monitin S, Weissmann S, Etzion O. Liver Fibrosis Regression and Associated Factors in HCV Patients Treated with Direct-Acting Antiviral Agents. Life (Basel) 2023; 13:1872. [PMID: 37763276 PMCID: PMC10533124 DOI: 10.3390/life13091872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open
Abstract
There is accumulating evidence that treatment of chronic hepatitis C (HCV) leads to improvements in liver fibrosis. We aimed to investigate the improvement in fibrosis stage following treatment with direct-acting antivirals (DAAs) and factors associated with fibrosis regression. Fibroscan® was performed for patients treated with DAAs, at least 3 years post-HCV eradication. The fibrosis stage at the onset of treatment was compared with the current fibrosis stage. A total of 209 patients were enrolled in this study (56% males; age 58.8 ± 13.3 years; age at treatment 54 ± 10.9 years). Genotype subgrouping was as follows: 1a (16%), 1b (58%), 2a (4%), 3 (18%), and 4a (2%). Overall, 71% of patients were considered treatment-naïve, with a mean follow-up time of 4.5 ± 1.3 years. Fibrosis improvement was observed among 57% of patients; fibrosis progression was seen among 7% of patients and no change was seen in 36% of patients. Moreover, 28% of these patients regressed from F3/F4 to F2 or less. In our multivariable analysis, the age at treatment and advanced fibrosis stage were found to be factors significantly associated with fibrosis regression. In conclusion, fibrosis improvement was observed among 57% of HCV patients after treatment with DAAs. Age and advanced fibrosis at baseline were found to be factors associated with fibrosis regression.
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Affiliation(s)
- Naim Abu-Freha
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; (D.Y.); (B.Y.); (S.M.); (O.E.)
| | - Osama Abu-Kosh
- Division of Internal Medicine, Soroka University Medical Center, Beer-Sheva 84101, Israel (M.A.-A.)
| | - David Yardeni
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; (D.Y.); (B.Y.); (S.M.); (O.E.)
| | - Yaffa Ashur
- Medical Management Unit, Soroka University Medical Center, Beer-Sheva 84101, Israel
| | - Muhammad Abu-Arar
- Division of Internal Medicine, Soroka University Medical Center, Beer-Sheva 84101, Israel (M.A.-A.)
| | - Baha Yousef
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; (D.Y.); (B.Y.); (S.M.); (O.E.)
| | - Shulamit Monitin
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; (D.Y.); (B.Y.); (S.M.); (O.E.)
| | - Sarah Weissmann
- Soroka Clinical Research Center, Soroka University Medical Center, Beer-Sheva 84101, Israel;
| | - Ohad Etzion
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; (D.Y.); (B.Y.); (S.M.); (O.E.)
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11
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Jiang X, Song HJ, Chang CY, Wilson DL, Lo-Ciganic WH, Park H. Impact of Direct-acting Antivirals on Hepatocellular Carcinoma and Mortality Among Medicaid Beneficiaries With Hepatitis C. Med Care 2023; 61:505-513. [PMID: 37223993 PMCID: PMC10330248 DOI: 10.1097/mlr.0000000000001870] [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] [Indexed: 05/26/2023]
Abstract
OBJECTIVE The effects of all-oral direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) and liver-related and all-cause mortality were assessed among Medicaid beneficiaries with hepatitis C virus (HCV). SUBJECTS This cohort study used 2013-2019 Arizona Medicaid data from beneficiaries with HCV aged 18-64 years. METHODS Risks of HCC and liver-related and all-cause mortality were compared between patients with or without DAA treatment, stratified by liver disease severity, using inverse probability of treatment weighted multivariable Cox proportional hazards regression models. RESULTS Of 29,289 patients, 13.3% received DAAs. Among patients with compensated cirrhosis (CC), DAA treatment was associated with a lower risk of HCC [adjusted hazard ratio (aHR), 0.57; 95% CI, 0.37-0.88] compared with untreated patients although this association was not statistically significant for patients without cirrhosis or with decompensated cirrhosis (DCC). Compared with untreated patients, DAA treatment was associated with decreased risk of liver-related mortality for patients without cirrhosis (aHR: 0.02; 95% CI: 0.004-0.11), with CC (aHR: 0.09; 95% CI: 0.06-0.13), or with DCC (aHR: 0.20; 95% CI: 0.14-0.27). Similarly, compared with untreated patients, DAA treatment was associated with lower all-cause mortality for patients without cirrhosis (aHR: 0.10; 95% CI: 0.08-0.14), with CC (aHR: 0.07; 95% CI: 0.05-0.10), or with DCC (aHR: 0.15; 95% CI: 0.11-0.20). CONCLUSIONS Among Arizona Medicaid beneficiaries with HCV, DAA treatment was associated with decreased risk of HCC for patients with CC but not for patients without cirrhosis or with DCC. However, DAA treatment was associated with decreased risk of liver-related and all-cause mortality.
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Affiliation(s)
- Xinyi Jiang
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Hyun Jin Song
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Ching-Yuan Chang
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Debbie L. Wilson
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Wei-Hsuan Lo-Ciganic
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
- Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL
| | - Haesuk Park
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
- Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL
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Moreau C, Roux M, Riou J, Canivet CM, Audureau E, Lusivika-Nzinga C, Nahon P, Carrat F, Boursier J. Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients. J Viral Hepat 2023; 30:567-577. [PMID: 36891763 DOI: 10.1111/jvh.13830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/22/2023] [Accepted: 03/03/2023] [Indexed: 03/10/2023]
Abstract
Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver-related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono-infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow-up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n = 695; 50 LRC during the median 3.8 [1.6-7.5] years follow-up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n = 7064; 273 LRC during the median 3.6 [2.5-4.9] years follow-up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time-dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow-up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.
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Affiliation(s)
- Clémence Moreau
- Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d'Angers, Angers, France
| | - Marine Roux
- Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d'Angers, Angers, France
| | - Jérémie Riou
- Centre Hospitalier Universitaire d'Angers, Délégation à la recherche clinique et à l'innovation, Angers, France
- Inserm, UMR 1066, Micro et Nanomédecines translationnelles, Université d'Angers, Angers, France
| | - Clémence M Canivet
- Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d'Angers, Angers, France
- Centre Hospitalier Universitaire d'Angers, Service d'Hépato-Gastroentérologie et Oncologie Digestive, Angers, France
| | - Etienne Audureau
- AP-HP, Hôpital Henri Mondor, Département de Santé Publique, and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Ageing) Unit EA7376, UPEC, Créteil, France
| | - Clovis Lusivika-Nzinga
- Sorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Pierre Nahon
- APHP, Liver Unit, Bobigny, Université Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Centre de recherche des Cordeliers, Université de Paris, Paris, France
| | - Fabrice Carrat
- Sorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, France
- AP-HP, Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France
| | - Jérôme Boursier
- Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d'Angers, Angers, France
- Centre Hospitalier Universitaire d'Angers, Service d'Hépato-Gastroentérologie et Oncologie Digestive, Angers, France
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Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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Elbahrawy A, Atalla H, Alboraie M, Alwassief A, Madian A, El Fayoumie M, Tabll AA, Aly HH. Recent Advances in Protective Vaccines against Hepatitis Viruses: A Narrative Review. Viruses 2023; 15:214. [PMID: 36680254 PMCID: PMC9862019 DOI: 10.3390/v15010214] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/03/2023] [Accepted: 01/07/2023] [Indexed: 01/15/2023] Open
Abstract
Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.
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Affiliation(s)
- Ashraf Elbahrawy
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Hassan Atalla
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mohamed Alboraie
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed Alwassief
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
- Gastroenterology Unit, Department of Internal Medicine, Sultan Qaboos University Hospital, P.O. Box 50, Muscat 123, Oman
| | - Ali Madian
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt
| | - Mohammed El Fayoumie
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Center, Giza 12622, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt
| | - Hussein H. Aly
- Department of Virology II, National Institute of Infectious Diseases, Toyama1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
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Clinical and economic value of sofosbuvir-based regimens in the treatment of chronic hepatitis C in Spain. PLoS One 2022; 17:e0278544. [PMID: 36454996 PMCID: PMC9714855 DOI: 10.1371/journal.pone.0278544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 11/18/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND The treatment of chronic hepatitis C virus (HCV) with direct-acting antivirals has undergone a spectacular revolution and added significant value to healthcare systems and patients. The aim of the study was to evaluate the efficiency and value of Sofosbuvir (SOF)-based regimens for a target population of 85,959 chronic HCV patients treated in Spain during 2015-2019, compared to previous therapeutic strategies (peginterferon/ and ribavirin in double/triple therapy with telaprevir or boceprevir). METHODS A previously developed lifetime Markov model was adapted to simulate the disease HCV evolution. In SOF-based regimens, all patients (100%) were treated regardless with sustained virological response (SVR) of 93-98%, obtained from real-world data. In previous therapeutic, only ≥F2 patients were treated according to clinical practice (38%) with an average SVR of 61% taken from published literature. The value was measured as clinical and economic impact in terms of avoided HCV-related mortality and liver complications; total costs and quality-adjusted life years (QALYs) applying an annual 3% discount rate. RESULTS Compared to previous therapeutic, during lifetime, SOF-based regimens reduced decompensated cirrhosis by 89%, hepatocellular carcinoma by 77% and liver transplant by 84%, decreasing the cost associated to liver complications management in €770 million. SOF-based regimens also decreased liver-related mortality by 82%. Besides, SOF-based regimens gained 310,765/QALYs, saving €274 million (considering drugs, monitoring, and HCV management). CONCLUSION For Spain, SOF-based regimens offer value for HCV patients in terms of lowering HCV-related liver disease burden and generating significant cost savings for the health system, contributing to the WHO goal.
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Rolland B, Lions C, Di Beo V, Carrieri P, Authier N, Barré T, Delorme J, Mathurin P, Bailly F, Protopopescu C, Marcellin F. Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study). Harm Reduct J 2022; 19:119. [PMID: 36303159 PMCID: PMC9615191 DOI: 10.1186/s12954-022-00702-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 09/29/2022] [Indexed: 11/17/2022] Open
Abstract
Background Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection. Methods Using the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014–2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity. Results Among the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18–1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status. Conclusions Adherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals. Supplementary Information The online version contains supplementary material available at 10.1186/s12954-022-00702-9.
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Affiliation(s)
- Benjamin Rolland
- Service Universitaire d'Addictologie de Lyon (SUAL), Hospices Civils de Lyon, CH Le Vinatier, Lyon, France.,PsyR2 CRNL, UCBL1, INSERM U1028, CNRS UMR5292, Bron, France
| | - Caroline Lions
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Vincent Di Beo
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Patrizia Carrieri
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France.
| | - Nicolas Authier
- CHU Clermont-Ferrand, Neuro-Dol, Service de Pharmacologie Médicale, Centres Addictovigilance et Pharmacovigilance, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Tangui Barré
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Jessica Delorme
- CHU Clermont-Ferrand, Neuro-Dol, Service de Pharmacologie Médicale, Centres Addictovigilance et Pharmacovigilance, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Philippe Mathurin
- Service Des Maladies de L'appareil Digestif, CHU Lille, Université de Lille, Lille, France
| | - François Bailly
- Service d'hépatologie et d'addictologie, Groupe Hospitalier Nord, Hôpital de La Croix-Rousse, Lyon, France
| | - Camelia Protopopescu
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Fabienne Marcellin
- Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Choi GH, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, Lee HC, Jang JW, Ki M, Choi HY, Baik D, Jeong SH. Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study. World J Gastroenterol 2022; 28:4182-4200. [PMID: 36157119 PMCID: PMC9403421 DOI: 10.3748/wjg.v28.i30.4182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/24/2022] [Accepted: 07/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries. AIM To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR. METHODS This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. RESULTS During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.
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Affiliation(s)
- Gwang Hyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, South Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 47392, South Korea
| | - In Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Jeonju 54907, Jeonbuk, South Korea
| | - Sung Bum Cho
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, South Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Moran Ki
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Hwa Young Choi
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Dahye Baik
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
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Pipitone RM, Calvaruso V, Di Marco L, Di Salvo F, Gaggianesi M, Lupo G, Zito R, La Mantia C, Ramazzotti M, Petta S, Di Marco V, Craxì A, Grimaudo S. Mer Tyrosine Kinase (MERTK) modulates liver fibrosis progression and hepatocellular carcinoma development. Front Immunol 2022; 13:926236. [PMID: 36003399 PMCID: PMC9394453 DOI: 10.3389/fimmu.2022.926236] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 07/05/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundMerTK is a tyrosine kinase receptor that belongs to the TAM (Tyro3/Axl/Mer) receptor family. It is involved in different processes including cellular proliferation/survival, cellular adhesion/migration, and release of the inflammatory/anti-inflammatory cytokines. Although it is reported that MERTK polymorphisms affect the severity of viral and metabolic liver diseases, being able to influence fibrosis progression and hepatocellular carcinoma development, the mechanisms remain unknown. Methods: using a microarray approach, we evaluated the liver expression of genes involved in fibrogenesis and hepatocarcinogenesis in patient with chronic hepatitis C (CHC), stratified for MERTK genotype and MERTK expression. Results: we found that the rs 4374383 AA homozygosity is associated with lower MERTK expression in CHC patients and that, depending on MERTK genotype, Matrix Metallopeptidase 9 (MMP9), Matrix Metallopeptidase 7 (MMP7), Secreted Frizzled Related Protein 1 (SFRP1) and WNT gene family 11(WNT11) show differential expression in patients with CHC with or without neoplastic progression. Conclusions: our results confirm that MERTK represents a genetic biomarker for progression of liver disease and are suggestive of translational relevance for the study of downstream pathways involved in fibrogenesis and hepatocarcinogenesis.
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Affiliation(s)
- Rosaria Maria Pipitone
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
- *Correspondence: Rosaria Maria Pipitone, ; Stefania Grimaudo,
| | - Vincenza Calvaruso
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Lorenza Di Marco
- Gastroenterology Unit, Department of Medical Specialties, University of Modena e Reggio Emilia, Modena, Italy
| | - Francesca Di Salvo
- Department of Agricultural, Food and Forest Sciences, University of Palermo, Palermo, Italy
| | - Miriam Gaggianesi
- Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Giulia Lupo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Rossella Zito
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Claudia La Mantia
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Matteo Ramazzotti
- Department of Biochemical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Salvatore Petta
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Stefania Grimaudo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
- *Correspondence: Rosaria Maria Pipitone, ; Stefania Grimaudo,
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Lockart I, Yeo MGH, Hajarizadeh B, Dore G, Danta M. HCC incidence after hepatitis C cure among patients with advanced fibrosis or cirrhosis: A meta-analysis. Hepatology 2022; 76:139-154. [PMID: 35030279 PMCID: PMC9303770 DOI: 10.1002/hep.32341] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/28/2021] [Accepted: 01/04/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS HCV cure reduces but does not eliminate the risk of HCC. HCC surveillance is recommended in populations where the incidence exceeds 1.5% per year. In cirrhosis, HCC surveillance should continue after HCV cure, although it is uncertain if this should be indefinite. For patients with advanced fibrosis (F3), guidelines are inconsistent in their recommendations. We evaluated the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. APPROACH AND RESULTS This systematic review and meta-analysis identified 44 studies (107,548 person-years of follow-up) assessing the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. The incidence of HCC was 2.1 per 100 person-years (95% CI, 1.9-2.4) among patients with cirrhosis and 0.5 per 100 person-years (95% CI, 0.3-0.7) among patients with F3 fibrosis. In a meta-regression analysis among patients with cirrhosis, older age (adjusted rate ratio [aRR] per 10-year increase in mean/median age, 1.32; 95% CI, 1.00-1.73) and prior decompensation (aRR per 10% increase in the proportion of patients with prior decompensation, 1.06; 95% CI, 1.01-1.12) were associated with an increased incidence of HCC. Longer follow-up after HCV cure was associated with a decreased incidence of HCC (aRR per year increase in mean/median follow-up, 0.87; 95% CI, 0.79-0.96). CONCLUSIONS Among patients with cirrhosis, the incidence of HCC decreases over time after HCV cure and is lowest in patients with younger age and compensated cirrhosis. The substantially lower incidence in F3 fibrosis is below the recommended threshold for cost-effective screening. The results should encourage the development of validated predictive models that better identify at-risk individuals, especially among patients with F3 fibrosis.
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Affiliation(s)
- Ian Lockart
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
- St. Vincent’s HospitalSydneyNew South WalesAustralia
| | - Malcolm G. H. Yeo
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
| | - Behzad Hajarizadeh
- The Kirby InstituteUniversity of New South WalesSydneyNew South WalesAustralia
| | - Gregory J. Dore
- St. Vincent’s HospitalSydneyNew South WalesAustralia
- The Kirby InstituteUniversity of New South WalesSydneyNew South WalesAustralia
| | - Mark Danta
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
- St. Vincent’s HospitalSydneyNew South WalesAustralia
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Nakamura Y, Miyaaki H, Miuma S, Akazawa Y, Fukusima M, Sasaki R, Haraguchi M, Soyama A, Hidaka M, Eguchi S, Nakao K. Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease. Hepatol Int 2022; 16:555-561. [PMID: 35553006 DOI: 10.1007/s12072-022-10340-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/09/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Fibrosis is the most important pathological feature in predicting development of Hepatocellular carcinoma (HCC). However, the incidence rate of HCC in patients with non-alcoholic fatty liver disease (NAFLD) is relatively low. We evaluated phenotypic histological features to differentiate HCC from non-HCC in patients with non-tumor lesions of cirrhotic livers. METHODS Seventeen patients with NAFLD who underwent liver transplantation were enrolled. FibroNest was used to quantify histological phenotypes of non-tumor fibrosis lesions. Quantification included collagen content and structure traits, fiber morphometric traits, and fibrosis architecture traits. Each trait was described by up to seven quantitative fibrosis traits (qFTs). Among the qFTs measured in each specimen, those that described most of the variability between consecutive groups were automatically detected and combined into a normalized Phenotypic Composite Fibrosis Score (Ph-CFS). We trained FibroNest to identify the principal traits that differentiate HCC from non-HCC. RESULTS HCC was found in 8 cases and non-HCC in 9 cases. The Ph-CFS significantly differentiated HCC from non-HCC (4.6 vs. 5.9, p < 0.05). Individual qFTs for morphometric features including collagen fiber length, width, perimeter, and area denoted significant differences between HCC and non-HCC. The Ph-CFS could be used to distinguish HCC (Ph-FCS < 5.0) from non-HCC (Ph-FCS ≥ 5.0) with 75% sensitivity and 100% specificity. CONCLUSION In patients who underwent liver transplantation, fibrotic histological phenotypes in non-tumor lesions appeared to be different between HCC and non-HCC. Phenotypic analysis of collagen in non-tumor lesions might be an effective and automated method to distinguish HCC from non-HCC on histopathology imaging.
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Affiliation(s)
- Yutaka Nakamura
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Yuko Akazawa
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masanori Fukusima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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Sakamaki A, Takamura M, Sakai N, Watanabe Y, Arao Y, Kimura N, Setsu T, Abe H, Yokoo T, Kamimura H, Tsubata S, Waguri N, Ishikawa T, Kawai H, Sugitani S, Sato T, Funakoshi K, Watanabe M, Igarashi K, Kamimura K, Tsuchiya A, Aoyagi Y, Terai S. Longitudinal increase in albumin-bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis. PLoS One 2022; 17:e0263464. [PMID: 35113969 PMCID: PMC8812983 DOI: 10.1371/journal.pone.0263464] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/19/2022] [Indexed: 02/08/2023] Open
Abstract
Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Division of Gastroenterology and Hepatology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Niigata, Japan
| | - Norihiro Sakai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yusuke Watanabe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan
| | - Yoshihisa Arao
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Naruhiro Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shunsuke Tsubata
- Department of Gastroenterology and Hepatology, Tachikawa General Hospital, Niigata, Japan
| | - Nobuo Waguri
- Department Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
| | - Toru Ishikawa
- Division of Gastroenterology and Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of Internal Medicine, Niigata Prefectural Shibata Hospital, Niigata, Japan
| | - Soichi Sugitani
- Department of Gastroenterology and Hepatology, Tachikawa General Hospital, Niigata, Japan
- Department of Internal Medicine, Murakami General Hospital, Niigata, Japan
| | - Tomomi Sato
- Division of Gastroenterology and Hepatology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Niigata, Japan
- Department of Internal Medicine, Joetsu General Hospital, Niigata, Japan
| | - Kazuhiro Funakoshi
- Division of Gastroenterology and Hepatology, Niigata Prefectural Hospital, Niigata, Japan
| | - Masashi Watanabe
- Department of Internal Medicine, Niigata Prefectural Shibata Hospital, Niigata, Japan
| | - Kentarou Igarashi
- Department Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
- Division of Gastroenterology and Hepatology, Mitsuke City Hospital, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of General Medicine, School of Medicine, Niigata University, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yutaka Aoyagi
- Division of Gastroenterology and Hepatology, JA Niigata Medical Center, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure. Am J Gastroenterol 2022; 117:138-146. [PMID: 34817975 DOI: 10.14309/ajg.0000000000001503] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 08/03/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR. METHODS Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months). RESULTS Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007). DISCUSSION We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.
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25
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Wedemeyer H, Herzer K, Serfert Y, Taubert R, Trautwein C, Eurich D, P. Strassburg C, Lang M, Heinz Weiss K, Berg T, R. Galle P, Heinzow H, Zeuzem S, Willuweit K, Kirchner T, Sahin C, Plewe J, Spengler U, Welker MW, Sterneck M, Mehrabi A, Herber A, Zimmermann T, Schmidt H. Declining Numbers of Hepatitis C Virus-Associated Liver Transplantations in Germany. DEUTSCHES ARZTEBLATT INTERNATIONAL 2021; 118:797-798. [PMID: 35129433 PMCID: PMC8864669 DOI: 10.3238/arztebl.m2021.0318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 05/31/2021] [Accepted: 08/12/2021] [Indexed: 06/14/2023]
Affiliation(s)
- Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover
- Leberstiftungs-GmbH Deutschland, Hannover (Wedemeyer, Serfert)
| | - Kerstin Herzer
- Department of Gastroenterology and Hepatology, Essen University Hospital, Duisburg-Essen University, Essen
- Knappschafts-Klinik, Bad Neuenahr, Germany
| | - Yvonne Serfert
- Leberstiftungs-GmbH Deutschland, Hannover (Wedemeyer, Serfert)
| | - Richard Taubert
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover
| | - Christian Trautwein
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen
| | - Dennis Eurich
- Department of Surgery Charité-Universitätsmedizin Berlin, Berlin
| | - Christian P. Strassburg
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen
- Department of Internal Medicine I, University Hospital Bonn (UKB), Bonn
| | - Melanie Lang
- Department of Medicine I, University Medical Center Hamburg-Eppendorf (UKE)
| | - Karl Heinz Weiss
- Department for General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg
- Dept. of Internal Medicine, Salem Medical Center Heidelberg, Heidelberg
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig
| | - Peter R. Galle
- I. Department of Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz
| | - Hauke Heinzow
- Department of Medicine B, Münster University Hospital (UKM), Münster
- Medical Department 1, Merciful Brothers Hospital Trier, Trier, Germany
| | - Stefan Zeuzem
- Medical Department 1, Goethe University Hospital, Frankfurt am Main
| | - Katharina Willuweit
- Department of Gastroenterology and Hepatology, Essen University Hospital, Duisburg-Essen University, Essen
| | - Theresa Kirchner
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover
| | - Cennet Sahin
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen
| | - Julius Plewe
- Department of Surgery Charité-Universitätsmedizin Berlin, Berlin
| | - Ulrich Spengler
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen
- Department of Internal Medicine I, University Hospital Bonn (UKB), Bonn
| | - Martin-Walter Welker
- Medical Department 1, Goethe University Hospital, Frankfurt am Main
- Klinik für Innere Medizin I, Kreisklinik Groß-Umstadt, Groß-Umstadt
| | - Martina Sterneck
- Department of Medicine I, University Medical Center Hamburg-Eppendorf (UKE)
| | - Arianeb Mehrabi
- Department for General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg
| | - Adam Herber
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig
| | - Tim Zimmermann
- I. Department of Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz
- Medizinische Klinik II, Klinikum Worms, Worms
| | - Hartmut Schmidt
- Department of Gastroenterology and Hepatology, Essen University Hospital, Duisburg-Essen University, Essen
- Department of Medicine B, Münster University Hospital (UKM), Münster
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Cachay ER, Hadigan C, Mathews WC. Clinical guidelines for screening of liver cirrhosis complications remain, and clinical judgement must prevail. AIDS 2021; 35:2211-2213. [PMID: 34602589 PMCID: PMC8493806 DOI: 10.1097/qad.0000000000003022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Edward R Cachay
- Department of Medicine, Division of Infectious Diseases and Global Public Health, UC San Diego, San Diego, California
| | - Colleen Hadigan
- National Institute of Allergy and Infectious Diseases. Bethesda, Maryland, USA
| | - Wm Christopher Mathews
- Department of Medicine, Division of Infectious Diseases and Global Public Health, UC San Diego, San Diego, California
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Blach S, Blomé M, Duberg A, Jerkeman A, Kåberg M, Klasa P, Lagging M, Razavi‐Shearer D, Razavi H, Aleman S. Hepatitis C elimination in Sweden: Progress, challenges and opportunities for growth in the time of COVID-19. Liver Int 2021; 41:2024-2031. [PMID: 34051065 PMCID: PMC8242794 DOI: 10.1111/liv.14978] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/20/2021] [Accepted: 05/23/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers. METHODS The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios ('2019 Base' and 'WHO Targets') were developed to evaluate Sweden's progress towards HCV elimination. RESULTS At the beginning of 2019, there were 29 700 (95% uncertainty interval: 19 300-33 700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment and liver-related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025. CONCLUSIONS It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.
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Affiliation(s)
- Sarah Blach
- Department of EpidemiologyCenter for Disease Analysis FoundationLafayetteCOUSA
| | - Marianne Blomé
- Faculty of MedicineDepartment of Translational MedicineClinical Infection MedicineLund UniversityMalmöSweden
| | - Ann‐Sofi Duberg
- Faculty of Medicine and HealthDepartment of Infectious DiseasesÖrebro UniversityÖrebroSweden
| | - Anna Jerkeman
- Faculty of MedicineDepartment of Translational MedicineClinical Infection MedicineLund UniversityMalmöSweden
| | - Martin Kåberg
- Stockholm Needle ExchangeStockholm Centre for Dependency DisordersStockholmSweden,Division of Infection and DermatologyDepartment of Medicine HuddingeKarolinska InstituteKarolinska University Hospital HuddingeStockholmSweden
| | | | - Martin Lagging
- Department of Infectious Diseases/VirologyInstitute of BiomedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden,Department of Clinical MicrobiologyRegion Västra GötalandSahlgrenska University HospitalGothenburgSweden
| | | | - Homie Razavi
- Department of EpidemiologyCenter for Disease Analysis FoundationLafayetteCOUSA
| | - Soo Aleman
- Department of Medicine HuddingeKarolinska InstituteStockholmSweden,Department of Infectious DiseasesKarolinska University HospitalStockholmSweden
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