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1
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D’Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K.C. S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, BR VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK. Acute-on-chronic liver failure (ACLF): the ‘Kyoto Consensus’—steps from Asia. Hepatol Int 2025; 19:1-69. [DOI: https:/doi.org/10.1007/s12072-024-10773-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 04/16/2025]
Abstract
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the “APASL ACLF Research Consortium (AARC)” was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia–Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the ‘Golden Therapeutic Window’, the ‘transplant window’, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The ‘Kyoto APASL Consensus’ presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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2
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Gujarathi R, Klein JA, Liao CY, Pillai A. The Changing Demographics and Epidemiology of Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:1-15. [PMID: 39608950 DOI: 10.1016/j.cld.2024.08.001] [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: 11/30/2024]
Abstract
The epidemiology of hepatocellular carcinoma (HCC) has shifted significantly in the last 2 decades with non-viral etiologies such as metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease on the rise. Key factors include the global obesity epidemic and the resurgence of alcohol use disorder, both of which were exacerbated by the coronavirus disease 2019 pandemic. While these non-viral etiologies of HCC are becoming the leading cause in developed countries, the potential impact of immigration patterns on Hepatitis B virus epidemiology cannot be ignored. The risk of HCC remains significant in individuals with cirrhosis and viral hepatitis after curative treatments.
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Affiliation(s)
- Rushabh Gujarathi
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Jeremy A Klein
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Chih-Yi Liao
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Anjana Pillai
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA.
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3
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D'Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K C S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, Br VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK. Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia. Hepatol Int 2025; 19:1-69. [PMID: 39961976 PMCID: PMC11846769 DOI: 10.1007/s12072-024-10773-4] [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: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 02/23/2025]
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - A S Soin
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | | | - Abhijeet Chowdhury
- Institute of Post-Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India
| | - Abraham Koshy
- VPS Lakeshore Hospital and Research Center Ltd, Kochi, Kerala, India
| | - Ajay Duseja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ajay Kumar
- Govind Ballabh Pant Hospital, New Delhi, India
| | - Ajay Kumar Mishra
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | - Ajit Sood
- Dayanand Medical College, Ludhiana, India
| | - Akash Roy
- Apollo Multispeciality Hospital, Kolkata, India
| | - Akash Shukla
- Seth G S Medical College and K E M Hospital, Mumbai, Maharashtra, India
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Albert Chan
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Amar Mukund
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Amit Goel
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | | | | | - Andrés Cárdenas
- Univerity of Barcelona Institut d'Investigacions Biomèdiques August Pi-Sunyer, Barcelona, Spain
| | | | - Anil Arora
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Anil Chandra Anand
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | | | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anoop Saraya
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anshu Srivastava
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Anupam Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Apurva Pande
- Fortis Hospital, Greater Noida, Uttar Pradesh, India
| | - Archana Rastogi
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Arun Valsan
- Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India
| | - Ashish Goel
- Christian Medical College (CMC), Vellore, India
| | - Ashish Kumar
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Ashwani K Singal
- University of Louisville School of Medicine, Trager Transplant Center and Jewish Hospital, Louisville, KY, USA
| | | | - Audrey Coilly
- Centre Hepato-Biliaire, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Ayaskanta Singh
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Babu Lal Meena
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Bikrant Bihari Lal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - C E Eapen
- Christian Medical College (CMC), Vellore, India
| | - Cesar Yaghi
- Saint Joseph University, Hôtel-Dieu de France University Medical Center, Beirut, Lebanon
| | | | | | | | - Chen Yu
- Capital Medical University, Beijing, China
| | - Chetan R Kalal
- Nanavati Max Super Specialty Hospital, Mumbai, Maharashtra, India
| | - Chhagan Bihari
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Chitranshu Vasishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Christian Jansen
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Chun Yen Lin
- Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
| | | | - Cosmas Rinaldi Adithya Lesmana
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
- Medistra Hospital, Jakarta, Indonesia
| | | | | | | | | | | | | | | | | | | | - Dong-Sik Kim
- Korea University College of Medicine, Seoul, Republic of Korea
| | | | - Fazal Karim
- Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh
| | - Francois Durand
- Université de Paris, AP-HP, C, DMU DIGEST, Centre de Référence Des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de Recherche Sur L'inflammation, Inserm, Paris, France
| | | | - Gennaro D'Amico
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
- Clinica La Maddalena, Palermo, Italy
| | - George K Lau
- Humanity and Health Medical Center, Hongkong, SAR, China
| | | | - Graciela Elia Castro Narro
- Hospital Médica Sur, Mexico City, Mexico
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran",, Mexico City, Mexico
- Latin-American Association for the Study of the Liver (ALEH), Santiago de Chile, Chile
| | - Guan-Huei Lee
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Gupse Adali
- University of Health Sciences, Ümraniye, Istanbul, Turkey
| | | | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - H C Lin
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hai Li
- School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Hari Kumar Nair
- Ernakulam Medical Center (EMC), Kinder Multispeciality Hospital, Kochi, Kerala, India
| | | | - Harshvardhan Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | | | - Irsan Hasan
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - J Fernandez
- University of Barcelona, IDIBAPS and CIBEREHD, Barcelona, Spain
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Jaideep Behari
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James Fung
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Jaya Benjamin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Jennifer C Lai
- University of California, San Francisco, San Francisco, CA, USA
| | - Jidong Jia
- Capital Medical University, Beijing, China
| | - Jin Hua Hu
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Jin Jun Chen
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Lin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Mo Yang
- The Catholic University of Korea, Seoul, Korea
| | - Johannes Chang
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jonel Trebicka
- Medizinische Klinik B, Universitätsklinikum Münster, Münster, Germany
| | - Jörg C Kalf
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jose D Sollano
- Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines
| | - Joy Varghese
- Gleneagles Global Hospital, Chennai, Tamil Nadu, India
| | - Juan Pablo Arab
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Schulich School of Medicine, Western University, London, ON, Canada
| | - Jun Li
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | | | - Kaiser Raja
- King's College Hospital London, Dubai, United Arab Emirates
| | - Kalpana Panda
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Kamal Kajal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Karan Kumar
- Mahatma Gandhi Medical College, Jaipur, Rajasthan, India
| | - Kaushal Madan
- Max Super Specialty Hospital Saket, New Delhi, India
| | - Kemal Fariz Kalista
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | | | - Khin Maung Win
- University of Medicine, Yangon Ministry of Health, Yangon, Myanmar
| | - Ki Tae Suk
- Hallym University, Chuncheon, Republic of Korea
| | | | | | - Lubna Kamani
- Liaquat National Hospital, Karachi, Sindh, Pakistan
| | - Madhumita Premkumar
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Mamun Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Man Fung Yuen
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Manasa Alla
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manoj Sahu
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Manya Prasad
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Mark Dhinesh Muthiah
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Martin Schulz
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Meenu Bajpai
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Ming Lung Yu
- Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine, National Sun Yet-Sen University, Kaohsiung, Taiwan
| | | | - Mithun Sharma
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Mohd Golam Azam
- Endocrine and Metabolic Disorder (BIRDEM) Shahbad, Bangladesh Institute of Research and Rehabilitation in Diabetes, Dhaka, Bangladesh
| | - Mohd Rela
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Moreshwar S Desai
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | - Mukul Vij
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Nadim Mahmud
- University of Pennsylvania, Philadelphia, PA, USA
| | | | | | - Necati Ormeci
- İstanbul Health and Technology University, Istanbul, Turkey
| | - Neeraj Saraf
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | - Nipun Verma
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Norifumi Kawada
- Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Oidov Baatarkhuu
- Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | | | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chuo-Ku, Chiba, Japan
| | - P N Rao
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Paolo Angeli
- Department of Medicine (DIMED), University of Padova, Padua, Italy
| | | | | | | | - Philipp Lingohr
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Piyush Ranjan
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Pravin Rathi
- Topi Wala National (TN) Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | | | - Puneet Puri
- Virginia Commonwealth University, Richmond, VA, USA
| | - Qin Ning
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - R K Dhiman
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Rahul Kumar
- Changi General Hospital, Singapore, Singapore
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- Centre de Recherche Sur L'Inflammation (CRI), INSERM and Université Paris-Cité, Paris, France
- Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Beaujon, Service d'Hépatologie, Clichy, France
| | - Rino Alvani Gani
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - Rohit Loomba
- University of California, San Diego, La Jolla, CA, USA
| | - Rohit Mehtani
- Amrita Institute of Medical Sciences and Research Centre, Faridabad, Haryana, India
| | | | - S S Hamid
- Aga Khan University Hospital, Karachi, Pakistan
| | | | - Sadhna Lal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sagnik Biswas
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Samagra Agarwal
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Sanjiv Saigal
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | | | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Saurabh Mukewar
- Midas Multispeciality Hospital Pvt. Ltd, Nagpur, Maharashtra, India
| | - Seema Alam
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seng Gee Lim
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Shahinul Alam
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shalimar
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | | | - Shiran Shetty
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shobna Bhatia
- National Institute of Medical Sciences, Jaipur, India
| | | | - Shyam Kottilil
- University of Maryland School of Medicine, Baltimore, USA
| | | | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Soek Siam Tan
- Selayang Hospital, University of Malaysia, Batu Caves, Selangor, Malaysia
| | | | | | | | - Subhash Gupta
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | - Sudhamshu K C
- Bir Hospital, National Academy of Medical Sciences, Kathmandu, Nepal
| | - Sudhir Maharshi
- Sawai Man Singh (SMS) Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sumeet Asrani
- Baylor Simmons Transplant Institute, Dallas, TX, USA
| | - Sunil Dadhich
- Dr Sampuranand Medical College (SNMC), Jodhpur, Rajasthan, India
| | - Sunil Taneja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Suprabhat Giri
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Surender Singh
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Tao Chen
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tarana Gupta
- Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
| | - Tatsuo Kanda
- Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | | | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - V G Mohan Prasad
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | | | | | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Vikrant Sood
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vinay Kumar Br
- Mazumdar Shaw Medical Centre, Bangalore, Karnataka, India
| | | | - Viniyendra Pamecha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Virendra Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India
| | - Vishwa Mohan Dayal
- Indira Gandhi Institute of Medical Sciences, (IGIMS), Bely Road Patna, Bihar, India
| | | | - WRay Kim
- Stanford University, Stanford, CA, USA
| | - Wasim Jafri
- Aga Khan University Hospital, Karachi, Pakistan
| | - Wenyi Gu
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Wong Yu Jun
- Changi General Hospital, Singapore, Singapore
| | - Xiaolong Qi
- Medical School, Zhongda Hospital, Southeast University, Nanjing, China
| | - Yogesh K Chawla
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Yoon Jun Kim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yu Shi
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Zaigham Abbas
- Ziauddin University Hospital Karachi, Karachi, Pakistan
| | - Guresh Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Lai Wei
- Changgung Hospital, Tsinghua University, Beijing, China
| | - Masao Omata
- Yamanashi Central Hospital, Yamanashi, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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Olivas P, Soler-Perromat A, Tellez L, Carrión JA, Alvarado-Tapias E, Ferrusquía-Acosta J, Lens S, Guerrero A, Falgà Á, Vizcarra P, Orts L, Perez-Campuzano V, Shalaby S, Torres S, Baiges A, Turon F, García-Pagán JC, García-Criado Á, Hernández-Gea V. Persistent varices in cured patients: Understanding the role of hepatic venous pressure gradient. JHEP Rep 2024; 6:101170. [PMID: 39430576 PMCID: PMC11489337 DOI: 10.1016/j.jhepr.2024.101170] [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: 03/26/2024] [Revised: 07/04/2024] [Accepted: 07/15/2024] [Indexed: 10/22/2024] Open
Abstract
Background & Aims Etiologic factor removal (ER) drives recompensation and improves portal hypertension in cirrhosis. Esophageal varices (EV) and portosystemic shunts (PSS) have been found in patients despite hepatic venous pressure gradient (HVPG) dropping below 10 mmHg after ER, questioning HVPG accuracy in reflecting true portal pressure in the setting of ER. We aim to evaluate the correlation of HVPG with direct portal pressure (DPP) in patients with persistence of EV after ER despite HVPG <10 mmHg. Methods This is a bicentric 'proof of concept' study evaluating HVPG and ultrasound-guided percutaneous DPP in patients with HCV or alcohol-related cirrhosis with persistent varices and HVPG <10 mmHg after at least 5 years of ER. Results Seven patients with HCV and three with alcohol-related cirrhosis with persistent varices and HVPG <10 mmHg after at least 5 years of ER were included. At evaluation, all patients had a patent portal vein and were compensated. The median platelet count was 129.5 (IQR 95-145) × 109/ml, and the median liver stiffness measurement was 16.15 (IQR 14.4-22.3) kPa. In five patients, EV remained the same size (two large and three small), and five downsized to small after ER. Wedge hepatic vein pressure (median 19 [IQR 16.5-20] mmHg) and portal pressure (median 18 [IQR 15-19.5] mmHg) had an excellent correlation (R = 0.93, p <0.0001). Portal pressure gradient (PPG) confirmed the absence of clinically significant portal hypertension as identified by HVPG across all the patients. Conclusions HVPG accurately reflects PPG in the context of HCV and alcohol-related cirrhosis regression. After ER, EV may persist despite HVPG <10 mmHg. The benefit of prophylaxis in patients with EV and HVPG <10 mmHg is unknown. Future studies with clinical endpoints are needed to validate our findings. Impact and implications Despite a favorable evolution after the removal of the etiologic factor, varices persist in some patients, and there is a lack of concise guidelines for the evaluation and management of portal hypertension in this population. Our research underscores the persistence of varices in the absence of clinically significant portal hypertension and significantly demonstrates the accuracy of hepatic venous pressure gradient (HVPG) in reflecting portal vein pressure in this specific patient group. These findings emphasize the crucial role of HVPG in the assessment of portal hypertension after etiologic factor removal and lay the groundwork for further investigation into clinical outcomes and the necessity of non-selective beta-blockers in individuals with persistent varices after the removal of etiologic factor.
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Affiliation(s)
- Pol Olivas
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
- Depertament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Alexandre Soler-Perromat
- Radiology Department, CDI, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Luis Tellez
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain
| | - José Antonio Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, Institut Hospital del mar D’Investigacions Mèdiques, PSMAR, Universitat Pompeu Fabra, Facultat de ciències de la Salut i de la Vida, Barcelona, Spain
| | - Edilmar Alvarado-Tapias
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Gastroenterology Department, Hospital de la Santa Creu I Sant Pau, Institut d’Investigacions Biomèdiques Sant Pau, Barcelona, Spain
| | - José Ferrusquía-Acosta
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Unitat Hepatologia, Servei Aparell Digestiu, Hospital Universitari Parc Taulí, Institut d’Investigació i Innovació Parc Taulí (I3PT), Sabadell, Spain
| | - Sabela Lens
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Depertament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Antonio Guerrero
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain
| | - Ángeles Falgà
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
| | - Pamela Vizcarra
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
| | - Lara Orts
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
| | - Valeria Perez-Campuzano
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
| | - Sarah Shalaby
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
| | - Sonia Torres
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
| | - Anna Baiges
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
| | - Juan Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
- Depertament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Ángeles García-Criado
- Radiology Department, CDI, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Fundacióde Recerca Clínic Barcelona - Institut de Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver)
- Depertament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
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5
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Ferraioli G, Barr RG, Berzigotti A, Sporea I, Wong VWS, Reiberger T, Karlas T, Thiele M, Cardoso AC, Ayonrinde OT, Castera L, Dietrich CF, Iijima H, Lee DH, Kemp W, Oliveira CP, Sarin SK. WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:1071-1087. [PMID: 38762390 DOI: 10.1016/j.ultrasmedbio.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 03/20/2024] [Accepted: 03/25/2024] [Indexed: 05/20/2024]
Abstract
The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.
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Affiliation(s)
- Giovanna Ferraioli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
| | - Richard Gary Barr
- Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio, USA; Southwoods Imaging, Youngstown, Ohio, USA
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Ioan Sporea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Center for Advanced Research in Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong, China
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Thomas Karlas
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Maja Thiele
- Center for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department for Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Ana Carolina Cardoso
- Hepatology Division, School of Medicine, Federal University of Rio de Janeiro, Clementino, Fraga Filho Hospital, Rua Prof. Rodolpho Paulo Rocco, Cidade Universitária da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Oyekoya Taiwo Ayonrinde
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia; Medical School, University of Western Australia, Crawley, Western Australia, Australia; Curtin Medical School, Curtin University, Kent Street, Bentley, Western Australia, Australia
| | - Laurent Castera
- Université Paris-Cité, Inserm UMR1149, Centre de Recherche sur l'Inflammation, Paris, France; Service d'Hépatologie, Hôpital Beaujon, Assistance-Publique Hôpitaux de Paris, Clichy, France
| | - Christoph Frank Dietrich
- Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem and Permancence, Bern, Switzerland
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Hyogo, Japan; Ultrasound Imaging Center, Hyogo Medical University, Nishinomiya, Hyogo, Japan
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - William Kemp
- Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | - Claudia P Oliveira
- Gastroenterology Department, Laboratório de Investigação (LIM07), Hospital das Clínicas de São Paulo, HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
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Abstract
Chronic liver disease (CLD) is a persistent public health burden, with over one billion cases reported worldwide. In most cases, the progression of CLD is slow and undulating with end-stage liver disease developing at variable time points depending on the underlying etiology of the disease. The concept of reversibility or halting progression to end stage liver disease is recent and various medications are in the pipeline which influence the progression of CLD. Non-invasive tests for monitoring of CLD may have the potential to avoid the morbidity and mortality related to invasive procedures. However, their applicability and validation in pediatrics requires further development and a coordinated effort by large pediatric liver centres. Recent advances in metabolomics and modern molecular technologies have led to an understanding of the interaction between gut microbiome liver axis and gut dysbiosis contributing to liver diseases. In the future, modifying the gut microbiome has the potential to change the outcome and significantly reduce the morbidity associated with CLD. This article focuses on newer modalities and concepts in the management of CLD, which may help develop strategies to prevent its progression to end-stage liver disease and associated morbidity/mortality.
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Affiliation(s)
- Ezyana Effandie
- Liver Unit (Including Small Bowel Transplantation), Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK
| | - Girish L Gupte
- Liver Unit (Including Small Bowel Transplantation), Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
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7
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Hofmeister MG, Zhong Y, Moorman AC, Samuel CR, Teshale EH, Spradling PR. Temporal Trends in Hepatitis C-Related Hospitalizations, United States, 2000-2019. Clin Infect Dis 2023; 77:1668-1675. [PMID: 37463305 PMCID: PMC11017377 DOI: 10.1093/cid/ciad425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/06/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Hospitalization burden related to hepatitis C virus (HCV) infection is substantial. We sought to describe temporal trends in hospitalization rates before and after release of direct-acting antiviral (DAA) agents. METHODS We analyzed 2000-2019 data from adults aged ≥18 years in the National Inpatient Sample. Hospitalizations were HCV-related if (1) hepatitis C was the primary diagnosis, or (2) hepatitis C was any secondary diagnosis with a liver-related primary diagnosis. We analyzed characteristics of HCV-related hospitalizations nationally and examined trends in age-adjusted hospitalization rates. RESULTS During 2000-2019, there were an estimated 1 286 397 HCV-related hospitalizations in the United States. The annual age-adjusted hospitalization rate was lowest in 2019 (18.7/100 000 population) and highest in 2012 (29.6/100 000 population). Most hospitalizations occurred among persons aged 45-64 years (71.8%), males (67.1%), White non-Hispanic persons (60.5%), and Medicaid/Medicare recipients (64.0%). The national age-adjusted hospitalization rate increased during 2000-2003 (annual percentage change [APC], 9.4%; P < .001) and 2003-2013 (APC, 1.8%; P < .001) before decreasing during 2013-2019 (APC, -7.6%; P < .001). Comparing 2000 to 2019, the largest increases in hospitalization rates occurred among persons aged 55-64 years (132.9%), Medicaid recipients (41.6%), and Black non-Hispanic persons (22.3%). CONCLUSIONS Although multiple factors likely contributed, overall HCV-related hospitalization rates declined steadily after 2013, coinciding with the release of DAAs. However, the declines were not observed equally among age, race/ethnicity, or insurance categories. Expanded access to DAA treatment is needed, particularly among Medicaid and Medicare recipients, to reduce disparities and morbidity and eliminate hepatitis C as a public health threat.
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Affiliation(s)
- Megan G Hofmeister
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Yuna Zhong
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Anne C Moorman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Christina R Samuel
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Eyasu H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Philip R Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
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8
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Choi WT, Gill RM. Pathologic features and differential diagnosis of chronic hepatitis. DIAGNOSTIC HISTOPATHOLOGY 2023; 29:12-22. [DOI: 10.1016/j.mpdhp.2022.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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9
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Orr CE, Wang PL, Chen L, Wang T. Features of fibrosis regression abound in “non-cirrhotic” patients with resected hepatocellular carcinoma. PLoS One 2022; 17:e0267474. [PMID: 35552548 PMCID: PMC9098014 DOI: 10.1371/journal.pone.0267474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 04/08/2022] [Indexed: 11/18/2022] Open
Abstract
Cirrhosis is a major risk factor for developing hepatocellular carcinoma (HCC). However, many surgically resected HCCs are presumably non-cirrhotic. The dynamic nature of chronic liver disease leads to periods of hepatic repair and fibrosis regression. We hypothesize that most resected HCCs, including those from non-cirrhotic patients, exhibit features of fibrosis regression in their background liver, suggesting previously more advanced liver disease. We reviewed the histology of 37 HCC resections performed between 2005–2020, including 30 from non-cirrhotic patients. The non-neoplastic liver was evaluated for features of liver disease and of the hepatic repair complex (HRC). CD34 immunohistochemistry was performed as a marker of sinusoidal capillarization. CD34 staining was evaluated manually and also by a digital image classifier algorithm. Overall, 28 cases (76%) had a high number of fibrosis regression and hepatic repair features (≥4 out of 8 features). Amongst the 30 non-cirrhotic patients, 21 (70%) showed a high number of repair features. Relative CD34 expression was increased in cases with a high number (≥4) of HRC features versus a low number (≤3) of features (p = 0.019). High HRC cases were more likely to exhibit nodular circumferential CD34 staining (p = 0.019). Our findings suggest that most resected HCC from non-cirrhotic patients display features of fibrosis regression in their background liver. Thus many, if not most, HCC patients who are “non-cirrhotic” may in fact have regressed cirrhosis. This finding reinforces that patients with regressed cirrhosis continue to be at high risk for HCC.
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Affiliation(s)
- Christine E. Orr
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
| | - Peter L. Wang
- Department of Medicine, Division of Gastroenterology, Queen’s University, Kingston, Ontario, Canada
| | - Lina Chen
- Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Tao Wang
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
- * E-mail:
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10
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Kim HN, Nance RM, Lo Re V, Silverberg MJ, Franco R, Sterling TR, Cachay ER, Horberg MA, Althoff KN, Justice AC, Moore RD, Klein M, Crane HM, Delaney JA, Kitahata MM. Development and Validation of a Model for Prediction of End-Stage Liver Disease in People With HIV. J Acquir Immune Defic Syndr 2022; 89:396-404. [PMID: 35202048 PMCID: PMC8887786 DOI: 10.1097/qai.0000000000002886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/06/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND End-stage liver disease (ESLD) is a leading cause of non-AIDS-related death among people with HIV (PWH). Factors that increase the progression of liver disease include comorbidities and HIV-specific factors, but we currently lack a tool to apply this evidence into clinical practice. METHODS We developed and validated a risk prediction model for ESLD among PWH who received care in 12 cohorts of the North American AIDS Cohort Collaboration on Research and Design between 2000 and 2016 and had fibrosis-4 index > 1.45. The first occurrence of ascites, variceal bleed, spontaneous bacterial peritonitis, or hepatic encephalopathy was verified by standardized medical record review. The Bayesian model averaging was used to select predictors among biomarkers and diagnoses and the Harrell C statistic to assess model discrimination. RESULTS Among 13,787 PWH in the training set, 82% were men and 54% were Black with a mean age of 48 years. Three hundred ninety ESLD events occurred over a mean 5.4 years. Among the ESLD cases, 52% had hepatitis C virus, 15% hepatitis B virus, and 31% alcohol use disorder. Twelve factors together predicted ESLD risk moderately well (C statistic 0.79, 95% confidence interval: 0.76 to 0.81): age, sex, race/ethnicity, chronic hepatitis B or C, and routinely collected laboratory values reflecting hepatic impairment (serum albumin, aspartate aminotransferase, total bilirubin, and platelets) and lipid metabolism (triglycerides, high-density lipoprotein, and total cholesterol). Our model performed well in the test set (C statistic 0.81, 95% confidence interval: 0.76 to 0.86). CONCLUSION This model of readily accessible clinical parameters predicted ESLD in a large diverse population of PWH.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Amy C. Justice
- Yale University Schools of Medicine and Public Health, New Haven, CT, USA and Veterans Administration Connecticut Healthcare System, USA
| | | | - Marina Klein
- McGill University Health Centre, Montreal, Quebec, Canada
| | | | - Joseph A. Delaney
- University of Washington, Seattle, WA, USA
- University of Manitoba, Winnipeg, Manitoba, Canada
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Alswat K, Al-Sohaibani F, Khathlan A, Bashmail A, Alanazi M, Kurdi A, Almakadma AH, Al-Hamoudi W. Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals. Ann Saudi Med 2022; 42:89-95. [PMID: 35380056 PMCID: PMC8981998 DOI: 10.5144/0256-4947.2022.89] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited. OBJECTIVES We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders. DESIGN Retrospective cohort study. SETTING Tertiary care centers. PATIENTS AND METHODS This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up. MAIN OUTCOME MEASURES Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up. SAMPLE SIZE AND CHARACTERISTICS 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females. RESULTS Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%). CONCLUSIONS Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality. LIMITATIONS Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen. CONFLICT OF INTEREST None.
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Affiliation(s)
- Khalid Alswat
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
| | - Fahad Al-Sohaibani
- From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Khathlan
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia.,From the Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ahmad Bashmail
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
| | - Mohammed Alanazi
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
| | - Amr Kurdi
- From the Department of Medicine, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia
| | | | - Waleed Al-Hamoudi
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
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12
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Cuesta-Sancho S, Márquez-Coello M, Illanes-Álvarez F, Márquez-Ruiz D, Arizcorreta A, Galán-Sánchez F, Montiel N, Rodriguez-Iglesias M, Girón-González JA. Hepatitis C: Problems to extinction and residual hepatic and extrahepatic lesions after sustained virological response. World J Hepatol 2022; 14:62-79. [PMID: 35126840 PMCID: PMC8790402 DOI: 10.4254/wjh.v14.i1.62] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 08/02/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Loss of follow-up or reinfections hinder the expectations of hepatitis C eradication despite the existence of highly effective treatments. Moreover, the elimination of the infection does not imply the reversion of those chronic alterations derived from the previous infection by hepatitis C virus (HCV). This review analyzes the risk factors associated with loss to follow-up in diagnosis or treatment, and the possibility of reinfection. Likewise, it assesses the residual alterations induced by chronic HCV infection considering the liver alterations (inflammation, fibrosis, risk of decompensation, hepatocellular carcinoma, liver transplantation) and, on the other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia, non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, bone and cognitive alterations). Peculiarities present in subjects coinfected with human immunodeficiency virus are analyzed in each section.
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Affiliation(s)
- Sara Cuesta-Sancho
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Mercedes Márquez-Coello
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Francisco Illanes-Álvarez
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Denisse Márquez-Ruiz
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Ana Arizcorreta
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Fátima Galán-Sánchez
- Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Natalia Montiel
- Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - Manuel Rodriguez-Iglesias
- Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
| | - José-Antonio Girón-González
- Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz 11009, Spain
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13
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Modifications of liver stiffness and CXCL4, TGF-β1 and HGF are similar in HCV- and HIV/HCV-infected patients after DAAs. Sci Rep 2021; 11:9824. [PMID: 33972651 PMCID: PMC8110591 DOI: 10.1038/s41598-021-89370-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 04/26/2021] [Indexed: 01/11/2023] Open
Abstract
The objective of this work was to identify predictive factors of fibrosis regression after direct antiviral agents (DAAs) in HCV-monoinfected and HIV/HCV-coinfected patients. This was a prospective study of HCV-monoinfected (n = 20), HIV/HCV-co-infected (n = 66) patients and healthy controls (n = 15). Patients had started DAAs and achieved sustained virological response. Liver stiffness (LS) and serum concentrations of profibrotic transforming growth factor (TGF)-β1 and CXC chemokine ligand 4 (CXCL4) and antifibrotic HGF hepatocyte growth factor (HGF) were analyzed at baseline (M0) and 12 months after starting DAAs (M12). A M12 LS achievement of ≤ 9.5 kPa was considered the cutoff point to discharge from a liver clinic. The LS decrease from M0 to M12 was 34%. No significant differences were observed in LS decline between HCV- and HIV/HCV-infected individuals. Changes of serum CXCL4, TGF-β1 and HGF levels did not correlate with LS improvement. 16 out from 56 patients (28%) with a baseline LS > 9.5 achieved a M12 LS ≤ 9.5. HCV-monoinfected and HIV/HCV coinfected patients experienced a significant reduction of LS after sustained virological response. This improvement did not correlate with changes in serum profibrotic or antifibrotic markers. A 29% of those with a baseline LS > 9.5 achieved a LS under this cutoff point.
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14
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The Impact of Markers of HIV Infection on Change in Liver Stiffness in People With HIV and Hepatitis C Virus Co-infection After Treatment and Cure of Hepatitis C. J Acquir Immune Defic Syndr 2021; 85:e81-e89. [PMID: 32842055 DOI: 10.1097/qai.0000000000002487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Markers of HIV disease severity are associated with increased liver fibrosis in HIV/Hepatitis C virus (HCV) co-infected individuals. HCV treatment may reverse liver fibrosis, but evidence among HIV/HCV-co-infected populations and the impact of HIV parameters on fibrosis regression is limited. We aimed to assess the influence of surrogate markers of HIV-infection and other determinants of liver stiffness before HCV treatment and changes after HCV cure in people living with HIV. METHODS We used data from an HCV treatment implementation study aiming for HCV micro-elimination among gay and bisexual men with HIV in Melbourne, Australia (co-EC Study). We obtained liver stiffness measurements (LSM) before and after direct-acting antiviral treatment using transient elastography (FibroScan). Linear mixed models were used to evaluate determinants of pretreatment LSM and changes in LSM following cure with duration in years between pre- and post-LSM assessment as main exposure variable. RESULTS At least one LSM was available in 173 participants, and 98 participants had 2 LSMs. Median pre- and post-treatment LSMs were 5.7 and 5.1 kPa, respectively. Median time between transient elastography measurements was 1.3 years (interquartile range = 0.9-2.1). In multivariable analysis, longer duration of known HIV infection, a lower CD4 and CD8 T-cell count and hazardous alcohol consumption were associated with higher LSM values before treatment initiation. Successfully treated patients had a 6% (95% confidence interval = -10% to -2%) annual decrease (0.34 kPa predicted decrease) in LSM following cure. Changes in LSM values did not depend on any of the pretreatment HIV markers or other factors. CONCLUSION Low levels of liver stiffness were observed before treatment initiation and a small decrease (6%) in LSM following HCV cure in people living with HIV. No clear predictors affecting change in LSM following cure were found in this study, including markers of HIV infection. However, markers of advanced HIV immunodeficiency and hazardous alcohol consumption remained associated with higher LSM values even after HCV cure.
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15
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Yuen MF, Liu SH, Seto WK, Mak LY, Corman SL, Hsu DC, Lee MYK, Khan TK, Puenpatom A. Cost-Utility of All-Oral Direct-Acting Antiviral Regimens for the Treatment of Genotype 1 Chronic Hepatitis C Virus-Infected Patients in Hong Kong. Dig Dis Sci 2021; 66:1315-1326. [PMID: 32385703 PMCID: PMC7990846 DOI: 10.1007/s10620-020-06281-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 04/16/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) are entering the hepatitis C virus (HCV) treatment landscape in Hong Kong, prompting the need for cost-effectiveness evaluations of these interventions to enable optimal use of healthcare resources. AIMS This study aimed to compare the cost-effectiveness of DAAs to standard-of-care pegylated interferon plus ribavirin (RBV) in treatment-naïve patients without significant liver fibrosis and to compare different DAAs in patients who are treatment-experienced and/or have advanced liver disease. METHODS A Markov model was constructed to evaluate cost-effectiveness over a lifetime time horizon from the payer perspective. The target population was treatment-naïve and treatment-experienced HCV genotype 1 patients, stratified by degree of liver fibrosis. The model consists of 16 health states encompassing METAVIR fibrosis score (F0-F4), treatment success or failure, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death. The proportions of patients achieving sustained virologic response were obtained from clinical trials. Other inputs were obtained from published and local data. The primary outcome was incremental cost-utility ratio for each DAA versus pegylated interferon + ribavirin and among different DAAs. RESULTS In treatment-naïve F0-2 HCV patients, all DAAs were cost-effective in genotype 1a and daclatasvir + asunaprevir, elbasvir/grazoprevir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir were cost-effective compared to pegylated interferon + ribavirin in genotype 1b. In genotypes 1a and 1b, treatment-experienced patients, and F3-4 patients, elbasvir/grazoprevir was the least costly DAA and economically dominant over most other DAAs. CONCLUSIONS DAAs can be a cost-effective option for the treatment of genotype 1 HCV patients in Hong Kong, and elbasvir/grazoprevir is cost-effective.
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Affiliation(s)
- Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
- State Key Laboratory of Liver Disease, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Sze-Hang Liu
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
- State Key Laboratory of Liver Disease, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Lung-Yi Mak
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Shelby L Corman
- Pharmerit International, 4350 East-West Highway Suite 1100, Bethesda, MD, 20814, USA.
| | - Danny C Hsu
- Merck Sharp & Dohme (Asia) Ltd., Hong Kong, Hong Kong
| | - Mary Y K Lee
- Merck Sharp & Dohme (Asia) Ltd., Hong Kong, Hong Kong
| | - Tsz K Khan
- Merck Sharp & Dohme (Asia) Ltd., Hong Kong, Hong Kong
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16
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Sepulveda-Crespo D, Resino S, Martinez I. Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis. Drugs 2021; 81:419-443. [PMID: 33400242 DOI: 10.1007/s40265-020-01458-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Direct-acting antivirals eliminate hepatitis C virus (HCV) in more than 95% of treated individuals and may abolish liver injury, arrest fibrogenesis, and reverse fibrosis and cirrhosis. However, liver regeneration is usually a slow process that is less effective in the late stages of fibrosis. What is more, fibrogenesis may prevail in patients with advanced cirrhosis, where it can progress to liver failure and hepatocellular carcinoma. Therefore, the development of antifibrotic drugs that halt and reverse fibrosis progression is urgently needed. Fibrosis occurs due to the repair process of damaged hepatic tissue, which eventually leads to scarring. The innate immune response against HCV is essential in the initiation and progression of liver fibrosis. HCV-infected hepatocytes and liver macrophages secrete proinflammatory cytokines and chemokines that promote the activation and differentiation of hepatic stellate cells (HSCs) to myofibroblasts that produce extracellular matrix (ECM) components. Prolonged ECM production by myofibroblasts due to chronic inflammation is essential to the development of fibrosis. While no antifibrotic therapy is approved to date, several drugs are being tested in phase 2 and phase 3 trials with promising results. This review discusses current state-of-the-art knowledge on treatments targeting the innate immune system to revert chronic hepatitis C-associated liver fibrosis. Agents that cause liver damage may vary (alcohol, virus infection, etc.), but fibrosis progression shows common patterns among them, including chronic inflammation and immune dysregulation, hepatocyte injury, HSC activation, and excessive ECM deposition. Therefore, mechanisms underlying these processes are promising targets for general antifibrotic therapies.
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Affiliation(s)
- Daniel Sepulveda-Crespo
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
| | - Isidoro Martinez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
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17
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Odagiri N, Matsubara T, Sato-Matsubara M, Fujii H, Enomoto M, Kawada N. Anti-fibrotic treatments for chronic liver diseases: The present and the future. Clin Mol Hepatol 2020; 27:413-424. [PMID: 33317250 PMCID: PMC8273638 DOI: 10.3350/cmh.2020.0187] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 11/07/2020] [Indexed: 12/12/2022] Open
Abstract
Liver fibrosis reflects tissue scarring in the liver due to the accumulation of excessive extracellular matrix in response to chronically persistent liver injury. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells including macrophages and Kupffer cells, and activation of hepatic stellate cells (HSCs), resulting in progression of liver fibrosis. Liver cirrhosis is the terminal state of liver fibrosis and is associated with severe complications, such as liver failure, portal hypertension, and liver cancer. Nevertheless, effective therapy for cirrhosis has not yet been established, and liver transplantation is the only radical treatment for severe cases. Studies investigating HSC activation and regulation of collagen production in the liver have made breakthroughs in recent decades that have advanced the knowledge regarding liver fibrosis pathophysiology. In this review, we summarize molecular mechanisms of liver fibrosis and discuss the development of novel anti-fibrotic therapies.
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Affiliation(s)
- Naoshi Odagiri
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Tsutomu Matsubara
- Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Misako Sato-Matsubara
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.,Department of Endowed Laboratory of Synthetic Biology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Hideki Fujii
- Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
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18
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Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2020. [DOI: 10.1016/j.cegh.2020.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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19
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Majumdar A, Tsochatzis EA. Changing trends of liver transplantation and mortality from non-alcoholic fatty liver disease. Metabolism 2020; 111S:154291. [PMID: 32531295 DOI: 10.1016/j.metabol.2020.154291] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 05/18/2020] [Accepted: 06/08/2020] [Indexed: 02/06/2023]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major international health concern. NAFLD is the leading global cause of liver disease with an estimated prevalence of 25% and is the fastest growing indication for liver transplantation (LT). The presence and severity of liver fibrosis is the only histologic predictor of clinical outcomes in this group. NAFLD poses several challenges in the peri-transplant setting including the management of multiple metabolic co-morbidities, post-transplant obesity and cardiovascular risk. However, post-LT outcomes in well-selected NAFLD patients appear similar to non-NAFLD indications, including in the setting of hepatocellular carcinoma (HCC). The rising prevalence of NAFLD may impact potential liver graft donors, which may in-turn adversely affect post-LT outcomes. This review outlines the current epidemiology, natural history and outcomes of NAFLD with a focus on pre- and post-liver transplant settings.
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Affiliation(s)
- Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia; Central Clinical School, The University of Sydney, Australia
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.
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Akiyama MJ, Lipsey D, Heo M, Agyemang L, Norton BL, Hidalgo J, Lora K, Litwin AH. Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy. Clin Infect Dis 2020; 70:2695-2702. [PMID: 31346609 PMCID: PMC7456350 DOI: 10.1093/cid/ciz693] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 07/19/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. METHODS PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. RESULTS Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). CONCLUSIONS HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.
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Affiliation(s)
- Matthew J Akiyama
- Divisions of General Internal Medicine, Bronx, New York
- Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
| | - Daniel Lipsey
- Divisions of General Internal Medicine, Bronx, New York
| | - Moonseong Heo
- Department of Public Health Sciences, College of Behavioral, Social, and Health Sciences, Clemson University, South Carolina
| | | | - Brianna L Norton
- Divisions of General Internal Medicine, Bronx, New York
- Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
| | | | - Kiara Lora
- Divisions of General Internal Medicine, Bronx, New York
| | - Alain H Litwin
- Department of Medicine, University of South Carolina School of Medicine–Greenville, Greenville
- Department of Medicine, Prisma Health-Upstate, Greenville
- Clemson University School of Health Research, South Carolina
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21
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Hepatitis C: Does Successful Treatment Alter the Natural History and Quality of Life? Gastroenterol Clin North Am 2020; 49:301-314. [PMID: 32389364 DOI: 10.1016/j.gtc.2020.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The cure of chronic hepatitis C infection has a major impact on the morbidity and mortality of infected patients. It is now clear that sustained virologic response improves overall survival and significantly reduces the risk of liver failure, fibrosis progression, need of liver transplantation, and incidence of hepatocellular carcinoma. Moreover, hepatitis C eradication improves a broad range of extrahepatic manifestations, such as dermatologic, neoplastic, cardiovascular, and endocrine, and improves quality of life.
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22
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Dash S, Aydin Y, Widmer KE, Nayak L. Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment. J Hepatocell Carcinoma 2020; 7:45-76. [PMID: 32346535 PMCID: PMC7167284 DOI: 10.2147/jhc.s221187] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 03/06/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.
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Affiliation(s)
- Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
- Department of Medicine, Division of Gastroenterology, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Kyle E Widmer
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
| | - Leela Nayak
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
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23
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Trivella JP, Martin P, Carrion AF. Novel targeted therapies for the management of liver fibrosis. Expert Opin Emerg Drugs 2020; 25:59-70. [PMID: 32098512 DOI: 10.1080/14728214.2020.1735350] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Juan P. Trivella
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Paul Martin
- Division of Gastroenterology and Hepatology, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Andres F. Carrion
- Division of Gastroenterology and Hepatology, University of Miami, Miller School of Medicine, Miami, FL, USA
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24
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Does fibrosis really regress in HIV/hepatitis C virus co-infected patients after treatment with direct antiviral agents? AIDS 2020; 34:427-432. [PMID: 31996593 DOI: 10.1097/qad.0000000000002433] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the progression of liver stiffness after treatment with direct antiviral agents (DAAs), to identify predictive factors of fibrosis regression and to analyze the changes of scores AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) after treatment. DESIGN Multicenter prospective cohort study of HIV/HCV co-infected patients conducted within the GECMEI cohort, Spain. METHODS Individuals were eligible if they were willing to start DAAs and underwent two transient elastographies: at baseline and after the end of treatment (EOT). All patients with detectable HCV RNA naïve to DAAs were consecutively enrolled from nine medical hospitals. Liver stiffness results were categorized in four Metavir stages (F1: <7.1; F2 : 7.1--9.5; F3 : 9.5--2.4; F4: >12.4 kPa). The APRI and FIB-4 scores were calculated at baseline, EOT and 12 weeks after EOT. RESULTS One hundred and seventy-eight patients were examined throughout a follow-up of 16.3 months (IQR: 12.5-25). The median of liver stiffness decrease was 2.6 kPa (IQR: 0-6.3). A greater improvement was observed in F3-F4 compared with F1-F2, (6.4 vs. 0.91 kPa, P < 0.001; P = 0.001, respectively). A decline between baseline and EOT measures was observed in APRI and FIB-4 (P < 0.001). Sustained virological response (SVR12) achievement was the only predictor of fibrosis regression [OR:17.4 (95% CI: 1.8-164.6; P = 0.013)]. CONCLUSION Most patients experienced a significant reduction of liver stiffness and APRI and FIB-4 scores. This improvement was greater in those with advanced liver disease. SVR12 was the only predictor of fibrosis regression. The significance of this reduction is unclear and could reflect a decline in inflammation rather than true fibrosis regression.
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25
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Tanwar S, Rhodes F, Srivastava A, Trembling PM, Rosenberg WM. Inflammation and fibrosis in chronic liver diseases including non-alcoholic fatty liver disease and hepatitis C. World J Gastroenterol 2020; 26:109-133. [PMID: 31969775 PMCID: PMC6962431 DOI: 10.3748/wjg.v26.i2.109] [Citation(s) in RCA: 127] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 12/18/2019] [Accepted: 01/01/2020] [Indexed: 02/06/2023] Open
Abstract
At present chronic liver disease (CLD), the third commonest cause of premature death in the United Kingdom is detected late, when interventions are ineffective, resulting in considerable morbidity and mortality. Injury to the liver, the largest solid organ in the body, leads to a cascade of inflammatory events. Chronic inflammation leads to the activation of hepatic stellate cells that undergo trans-differentiation to become myofibroblasts, the main extra-cellular matrix producing cells in the liver; over time increased extra-cellular matrix production results in the formation of liver fibrosis. Although fibrogenesis may be viewed as having evolved as a “wound healing” process that preserves tissue integrity, sustained chronic fibrosis can become pathogenic culminating in CLD, cirrhosis and its associated complications. As the reference standard for detecting liver fibrosis, liver biopsy, is invasive and has an associated morbidity, the diagnostic assessment of CLD by non-invasive testing is attractive. Accordingly, in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice. Due to differing disease prevalence and treatment efficacy, disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection. To facilitate this, a review of the pathogenesis of both conditions is also conducted. Finally, the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed, including the current use of antifibrotic therapy.
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Affiliation(s)
- Sudeep Tanwar
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Campus, Hampstead, London NW3 2PF United Kingdom
- Department of Gastroenterology, Whipps Cross University Hospital, Barts Health NHS Trust, Leytonstone, London E11 1NR, United Kingdom
| | - Freya Rhodes
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Campus, Hampstead, London NW3 2PF United Kingdom
| | - Ankur Srivastava
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Campus, Hampstead, London NW3 2PF United Kingdom
| | - Paul M Trembling
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Campus, Hampstead, London NW3 2PF United Kingdom
| | - William M Rosenberg
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Campus, Hampstead, London NW3 2PF United Kingdom
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26
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Nahon P, Ganne-Carrié N. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication. JHEP Rep 2019; 1:480-489. [PMID: 32039400 PMCID: PMC7005771 DOI: 10.1016/j.jhepr.2019.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/30/2019] [Accepted: 11/06/2019] [Indexed: 12/19/2022] Open
Abstract
Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population.
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Key Words
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, AST-to-platelet ratio index
- AST, aspartate aminotransferase
- DAAs, direct-acting antivirals
- EHC, extrahepatic cancer
- FIB-4, fibrosis-4
- HCC, hepatocellular carcinoma
- HCV
- HR, hazard ratio
- Hepatocellular carcinoma
- LSM, liver stiffness measurement
- Liver failure
- MACEs, major adverse cardiovascular events
- PHT, portal hypertension
- Portal hypertension
- SMR, standardised mortality ratio
- SVR
- SVR, sustained virological response
- surveillance
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Affiliation(s)
- Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
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27
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Meissner EG. The Gut-Liver Axis in Hepatitis C Virus Infection: A Path Towards Altering the Natural History of Fibrosis Progression? Clin Infect Dis 2019; 67:878-880. [PMID: 29718134 DOI: 10.1093/cid/ciy208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 03/08/2018] [Indexed: 12/23/2022] Open
Affiliation(s)
- Eric G Meissner
- Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston
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28
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DeCarolis DD, Chen YC, Westanmo AD, Conley C, Gravely AA, Khan FB. Decreased warfarin sensitivity among patients treated with elbasvir and grazoprevir for hepatitis C infection. Am J Health Syst Pharm 2019; 76:1273-1280. [PMID: 31418789 DOI: 10.1093/ajhp/zxz127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
PURPOSE We previously reported an interaction with warfarin anticoagulation when initiating treatment with direct-acting antiviral agents for hepatitis C infection. A decreased warfarin sensitivity led to subtherapeutic anticoagulation. To study this interaction further, we expanded our research to include patients treated with the combination of elbasvir and grazoprevir concurrent with warfarin anticoagulation and investigated changes in warfarin sensitivity during and after treatment. METHODS Using electronic health records of the Veterans Health Administration, patients starting treatment with elbasvir-grazoprevir for hepatitis C infection concurrent with warfarin anticoagulation were identified. Inclusion required stable warfarin anticoagulation prior to 12 weeks of treatment with elbasvir-grazoprevir. A warfarin sensitivity index (WSI) was calculated at the start of treatment, after 12 weeks after treatment, and at the end of treatment. The primary endpoint was the difference in WSI from pre- to end-treatment. The secondary endpoint was the WSI difference from before treatment to Changes in International Normalized Ratio, warfarin doses, and time in therapeutic range were measured. RESULTS In the final sample of 43 patients, the mean WSI decreased during treatment from 0.53 to 0.40, or 25.2%. After treatment, the mean WSI rose to 0.51. Although the mean weekly warfarin dose increased from 40.3 to 44.6 mg during treatment, the mean International Normalized Ratio decreased from 2.40 to 1.96, recovering to 2.59 after treatment. The time spent in therapeutic range decreased from 74.1% before treatment to 39.8% during treatment and back to 64.9% 12 weeks posttreatment. CONCLUSION When elbasvir-grazoprevir was added to stable warfarin anticoagulation, warfarin sensitivity decreased significantly during treatment and returned to baseline after treatment.
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Affiliation(s)
| | - Yi-Chieh Chen
- Pharmacy, Mayo Clinic Health System-Austin, Austin, MN
| | | | | | - Amy A Gravely
- Research Service, Minneapolis VA Health Care System, Minneapolis, MN
| | - Fatima B Khan
- Department of Hematology/Oncology, Minneapolis VA Health Care System, Minneapolis, MN
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29
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Effect of sofosbuvir plus daclatasvir for treatment of chronic hepatitis C on patients with psoriasis. Eur J Gastroenterol Hepatol 2019; 31:1025-1029. [PMID: 30702448 DOI: 10.1097/meg.0000000000001370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIM Until recently, clinicians caring for patients with psoriasis who were infected with hepatitis C virus (HCV) were concerned that treating one condition could exacerbate the other. We evaluated the outcome of treatment with direct-acting antiviral agents (DAAs) on patients with psoriasis having chronic hepatitis C (CHC) infection. PATIENTS AND METHODS This was an observational prospective cross-sectional study. It included CHC-naive patients with plaque psoriasis. All patients received sofosbuvir plus daclatasvir once daily for 12 weeks for treatment of CHC. Psoriasis area severity index (PASI) scores and the dermatology quality-of-life index were evaluated at the start of treatment with DAAs and then at 12 and 24 weeks after the end of HCV treatment. The primary end point was sustained virological response 12 weeks after treatment (SVR12). RESULTS A total of 34 CHC-naive patients were enrolled in this study. Most of them were of male sex (76.5%), and most of them had severe psoriasis, as the mean PASI score was 32. The primary and secondary end points (SVR12 and SVR24) for our patients were 100%. Regarding PASI and dermatology quality-of-life index scores, there was a highly significant difference before start of treatment and after treatment at 12 and 24 weeks. The most common adverse events are fatigue and headache. CONCLUSION Sofosbuvir plus daclatasvir is effective in the eradication of HCV and improvement of symptoms in patients with psoriasis having CHC infection. Future large series studies are needed to evaluate this promising effect of DAAs.
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30
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El-Garem H, AbdAllah M, Omar H, Cordie A, Abdel Alem S, Mohey Eldin Elzahry MA, Ghaith D, Abou El-Soud NH, Kamal W, Elsharkawy A, Esmat G. DAAs therapy associated with improved hepatic fibrosis in HCV-GT4 patients co-infected with HIV. Expert Rev Gastroenterol Hepatol 2019; 13:693-698. [PMID: 31043104 DOI: 10.1080/17474124.2019.1614441] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: The present work aimed at evaluation of the potential dynamic changes in hepatic fibrosis following treatment of chronic HCV using DAAs in patients coinfected with HIV. Patients and methods: In total, 50 HCV/HIV coinfected patients [age; 34.68 ± 10.38 years, 82% men] were included. For all included patients, liver stiffness measured using transient elastography as well as serum liver fibrosis scores; [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were calculated at baseline and at 12 and 24-weeks following 12 weeks therapy of HCV with once daily sofosbuvir 400 mg plus daclatasvir 60 mg. Results: Most of the included patients (70%, n = 35) were on anti-retroviral therapy. SVR24 was achieved by 93.48% of the patients. There was significant serial improvement in baseline liver stiffness measurement (LSM), FIB-4 and APRI among responders; [LSM: baseline, 7.05 ± 4.84 kPa vs. 5.66 ± 2.63 kPa at SVR24, p < 0.001], [FIB-4: baseline, 1.24 ± 1.08 vs. 0.93 ± 0.64 at SVR24, p 0.001) and (APRI: baseline, 0.725 ± 0.66 vs. 0.36 ± 0.19at SVR24, p 0.001) respectively. Conclusion: Treatment of HCV patients coinfected with HIV using DAAs is associated with a rapid significant regression in hepatic fibrosis, as evaluated by FibroScan, FIB-4, and APRI scores.
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Affiliation(s)
- Hassan El-Garem
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Mohamed AbdAllah
- b Medical Research Division , National Research Center , Giza , Egypt
| | - Heba Omar
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Ahmed Cordie
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Shereen Abdel Alem
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | | | - Doaa Ghaith
- c Clinical and Chemical Pathology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | | | - Walid Kamal
- d Preventive sector , Ministry of Health , Cairo , Egypt
| | - Aisha Elsharkawy
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Gamal Esmat
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt.,e Badr University , Cairo , Egypt
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31
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Anand L, Bihari C, Kedarisetty CK, Rooge SB, Kumar D, Shubham S, Kumar G, Sahney A, Sharma MK, Maiwall R, Kumar A, Sarin SK. Early cirrhosis and a preserved bone marrow niche favour regenerative response to growth factors in decompensated cirrhosis. Liver Int 2019; 39:115-126. [PMID: 29962032 DOI: 10.1111/liv.13923] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 06/12/2018] [Accepted: 06/28/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Exogenous growth factor-mobilized bone marrow (BM) stem cells have shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in granulocyte-colony stimulating factor (G-CSF)-mobilized stem cell therapy, possible mechanisms of regeneration and predictive factors of regenerative response. METHODS Sixty consecutive DC patients received either G-CSF with EPO (Group A; n = 30) or G-CSF and placebo (Group B; n = 30) for 2 months and were carefully followed up for 1 year. Baseline and post-treatment liver biopsy, BM biopsy and BM aspirate were analysed for fibro-inflammatory and regenerative response and BM hematopoietic reservoir. RESULTS Addition of EPO to G-CSF showed a significant improvement in Child-Pugh score (P = 0.03) and MELD score (P = 0.003) as compared to G-CSF alone, with reduction in mortality (16.6% vs 36.7%, P = 0.09). The combination arm also demonstrated a decreased incidence of acute kidney injury (P < 0.001), encephalopathy (P = 0.005) and refilling of ascites (P = 0.03). Compared to monotherapy, it increased CD163+ macrophages (P = 0.013), Ki67+ index (P < 0.001) with decrease in α-SMA levels (P < 0.001) in liver tissue. The response was better with grade 1 and 2 than with grade 3 ascites; Child B cirrhosis and MELD < 16. Non-responders had lower hematopoietic stem cells (HSCs) at baseline. On multivariate analysis, the liver disease severity (MELD < 16) and a relatively preserved BM (BM-HSCs > 0.4) predicted therapeutic response (AUROC = 0.82). CONCLUSIONS Early DC (MELD < 16) patients with mild-moderate ascites and those with a healthy cellular baseline BM respond better to growth factor therapy. Addition of EPO to G-CSF provides better regenerative response than G-CSF monotherapy.
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Affiliation(s)
- Lovkesh Anand
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Sheetalnath B Rooge
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Dhananjay Kumar
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Smriti Shubham
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amrish Sahney
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj K Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Anupam Kumar
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.,Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
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32
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Ioannou GN, Feld JJ. What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection? Gastroenterology 2019; 156:446-460.e2. [PMID: 30367836 DOI: 10.1053/j.gastro.2018.10.033] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 09/26/2018] [Accepted: 10/03/2018] [Indexed: 02/06/2023]
Abstract
Direct-acting antiviral (DAA) regimens are safe and effective at eradicating hepatitis C virus (HCV) infection. Unfortunately, DAAs remain expensive, so treatment of all HCV-infected patients would substantially affect health care costs. It is therefore important to continue to assess the hepatic and extrahepatic benefits of a DAA-induced sustained virologic response (SVR). A DAA-induced SVR reduces a patient's risk of cirrhosis and hepatocellular carcinoma and extrahepatic manifestations of HCV infection; there are also data to indicate that an SVR can reduce mortality. SVR is a relevant clinical end point, but further analyses are required to confirm its importance among diverse HCV-infected populations and to document the public health benefits of HCV elimination at the population level. We review the evidence for the benefits associated with SVRs in different clinical settings and challenges to data collection.
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Affiliation(s)
- George N Ioannou
- Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington.
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
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33
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Yanny B, Saab S, Durazo F, Latt N, Mitry A, Mikhail MM, Hanna RM, Aziz A, Sahota A. Eight-Week Hepatitis C Treatment with New Direct Acting Antivirals Has a Better Safety Profile While Being Effective in the Treatment-Naïve Geriatric Population Without Liver Cirrhosis and Hepatitis C Virus-RNA < 6 Million IU/mL. Dig Dis Sci 2018; 63:3480-3486. [PMID: 30259281 DOI: 10.1007/s10620-018-5283-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 09/11/2018] [Indexed: 01/19/2023]
Abstract
AIM Results of recent studies have confirmed the efficacy of an 8-week course of ledipasvir/sofosbuvir (LDV/SOF) in patients who are non-cirrhotics, native to treatment, are infected with hepatitis C (HCV) genotype 1, and have HCV viral load < 6 million IU/mL. However, there are limited data on a shortened treatment course in patients who are over the age of 65. METHODS A retrospective study was performed to examine the safety, tolerability, and sustained viral response rates (SVR) of the 8-week LDV/SOF therapy compared to the 12-week LDV/SOF therapy among non-cirrhotic, treatment-naïve, genotype 1 HCV patients with viral load < 6 million IU/mL who are 65 years of age or older. RESULTS A total of 454 patients were identified of which 182 non-cirrhotic, genotype 1 HCV-RNA < 6 million IU/mL patients received the 8-week LDV/SOF treatment and 272 received the 12-week LDV/SOF treatment. Mean [± standard deviation (SD)] aspartate aminotransferase to platelet ratio index score for the entire cohort was 0.45 ± 0.03. The mean (± SD) age for the 8-week treatment was 69.7 (± 7) years, 54.7% male and 45.3% female. The mean (± SD) age of the 12-week treatment was 71.7 (± 3) years, 56.4% male and 43.6% female. Overall, SVR-12 for the 8-week regimen was 93% and SVR-12 for the 12-week regimen was 95%. For the 182 treated with the 8-week LDV/SOF treatment, there were no serious adverse events requiring hospitalization or signs of liver failure requiring transplantation. Overall, the 8-week treatment patient cohort experienced less fatigue, headache, dry mouth, and diarrhea. This finding was statistically significant with a P value < 0.001. CONCLUSION Eight-week LDV/SOF therapy in treatment-naive, non-cirrhotic, genotype 1 HCV patients with RNA < 6 million IU/mL was found safe, better tolerated, effective, and required less upfront cost when compared with the 12-week LDV/SOF treatment regimen in properly selected geriatric population.
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Affiliation(s)
- Beshoy Yanny
- Department of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA. .,Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA.
| | - Sammy Saab
- Department of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.,Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
| | - Francisco Durazo
- Department of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.,Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
| | - Nyan Latt
- Ochsner Clinic Foundation, Jefferson, USA
| | | | - Mira Moris Mikhail
- Department of Nephrology, University of California Los Angeles, Los Angeles, CA, USA.,Biological Science, Biola University, La Mirada, USA
| | - Ramy M Hanna
- Department of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.,Department of Nephrology, University of California Los Angeles, Los Angeles, CA, USA.,Biological Science, Biola University, La Mirada, USA
| | - Antony Aziz
- Department of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.,Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
| | - Amandeep Sahota
- Department of Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, USA.,Department of Gastroenterology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, USA.,Department of Transplant Hepatology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, USA
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34
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Wirth S, Zhang H, Hardikar W, Schwarz KB, Sokal E, Yang W, Fan H, Morozov V, Mao Q, Deng H, Huang Y, Yang L, Frey N, Nasmyth-Miller C, Pavlovic V, Wat C. Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study. Hepatology 2018; 68:1681-1694. [PMID: 29689122 DOI: 10.1002/hep.30050] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 03/07/2018] [Accepted: 04/18/2018] [Indexed: 02/06/2023]
Abstract
Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 μg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.
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Affiliation(s)
- Stefan Wirth
- Department of Pediatrics, Helios Medical Center Wuppertal, Witten-Herdecke University, Germany
| | | | | | | | - Etienne Sokal
- Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Weibo Yang
- First Affiliated Hospital of Kunming Medical College, Kunming, China
| | - Huimin Fan
- Eighth People's Hospital of Guangzhou, Guangzhou, China
| | | | - Qing Mao
- SouthWest Hospital, Third Military Medical University, Chongqing, China
| | - Hong Deng
- Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yang Huang
- Roche (China) Holding Ltd, Shanghai, China
| | - Lei Yang
- Roche (China) Holding Ltd, Shanghai, China
| | - Nicolas Frey
- Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland
| | | | | | - Cynthia Wat
- Roche Products Limited, Welwyn Garden City, United Kingdom
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Fabbri G, Mastrorosa I, Vergori A, Timelli L, Lorenzini P, Zaccarelli M, Cicalini S, Bellagamba R, Plazzi MM, Mazzotta V, Antinori A, Ammassari A. Liver stiffness reduction and serum fibrosis score improvement in HIV/hepatitis C virus-coinfected patients treated with direct-acting antivirals. HIV Med 2018; 19:578-584. [PMID: 29953713 DOI: 10.1111/hiv.12632] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2018] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver stiffness and in serum liver fibrosis scores in HIV/HCV-coinfected patients before and after treatment with direct-acting antivirals (DAAs). METHODS Liver stiffness measured using transient elastography as well as serum liver fibrosis scores [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated before and at 6-12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used. RESULTS A total of 78 HIV/HCV-coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline [16.8 (interquartile range (IQR) 10.2-27.0) kPa at baseline vs. 9.4 (IQR 6.7-15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB-4 score [2.8 (IQR 1.5-4.8) vs. 2.0 (IQR 1.3-3.2), respectively; P < 0.01] and APRI [0.9 (IQR 0.5-2.2) vs. 0.4 (IQR 0.2-0.7), respectively; P < 0.01] was found. In univariate analysis, liver stiffness decrease was associated with increasing age, 'other' HCV genotype (vs. G1), the presence of cirrhosis, higher pre-DAA liver stiffness, sofosbuvir-based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB-4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA. CONCLUSIONS A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV-coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow-up.
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Affiliation(s)
- G Fabbri
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - I Mastrorosa
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - A Vergori
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - L Timelli
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - P Lorenzini
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - M Zaccarelli
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - S Cicalini
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - R Bellagamba
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - M M Plazzi
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - V Mazzotta
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - A Antinori
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
| | - A Ammassari
- Clinical Department, HIV/AIDS Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy
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Cirrhosis regression: extrahepatic angiogenesis and liver hyperarterialization persist. Clin Sci (Lond) 2018; 132:1341-1343. [PMID: 29954952 DOI: 10.1042/cs20180129] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 05/19/2018] [Accepted: 05/22/2018] [Indexed: 12/21/2022]
Abstract
Data on the consequences of cirrhosis regression on portal hypertension and on splanchnic and systemic hemodynamic are scarce. Previous studies have reported a decrease in hepatic venous pressure gradient following antiviral treatment in patients with hepatitis B or C related cirrhosis. However, these studies did not investigate splanchnic and systemic hemodynamic changes associated with virus control. To fill this gap in knowledge, in a recent issue of Clinical Science, Hsu et al. (vol. 132, issue 6, 669-683) used rat models of cirrhosis induced by thioacetamide and by bile duct ligation and provided a comprehensive analysis of the effects of cirrhosis regression on splanchnic and systemic hemodynamics. They observed a significant reduction in portal pressure accompanied by a normalization of systemic hemodynamic (normal cardiac index and systemic vascular resistance) and a decrease in intrahepatic vascular resistance. No change in extrahepatic vascular structures were observed despite normalization of collateral shunting, meaning that portosystemic collaterals persist but are not perfused. One intriguing part of their results is the only marginal effect of cirrhosis regression on liver hyperarterialisation. This result suggests that changes in splanchnic hemodynamic features induced by cirrhosis remain when hepatic vascular resistance decreases, raising the hypothesis of an autonomous mechanism persisting despite regression of intrahepatic vascular resistance. Microbiota changes and bacterial translocation might account for this effect. In conclusion cirrhosis regression normalizes systemic hemodynamics, but some splanchnic hemodynamic changes persist including extrahepatic angiogenesis and liver hyperarterialization.
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Mauro E, Crespo G, Montironi C, Londoño MC, Hernández-Gea V, Ruiz P, Sastre L, Lombardo J, Mariño Z, Díaz A, Colmenero J, Rimola A, Garcia-Pagán JC, Brunet M, Forns X, Navasa M. Portal pressure and liver stiffness measurements in the prediction of fibrosis regression after sustained virological response in recurrent hepatitis C. Hepatology 2018; 67:1683-1694. [PMID: 28960366 DOI: 10.1002/hep.29557] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 08/21/2017] [Accepted: 09/25/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Sustained virological response (SVR) improves survival in post-liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension (PH) post-SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after-SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and PH after viral clearance. We evaluated 112 hepatitis C virus-infected LT recipients who achieved SVR between 2001 and 2015. A liver biopsy was performed before treatment and 12 months post-SVR. Hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and Enhanced Liver Fibrosis (ELF) score were also determined at the same time points. Sixty-seven percent of the cohort presented fibrosis regression: 43% in recipients with cirrhosis and 72%-85% in the remaining stages (P = 0.002). HVPG, LSM, and ELF significantly decreased post-SVR. Liver function significantly improved, and survival was significantly better in patients achieving fibrosis regression. Baseline HVPG and LSM as well as decompensations before therapy were independent predictors of fibrosis regression. One year post-SVR, LSM had a high diagnostic accuracy to discard the presence of advanced fibrosis (AF) and clinically significant PH (AUROC, 0.902 and 0.888). CONCLUSION In conclusion, SVR post-LT induces fibrosis regression in most patients, leading to significant clinical benefits. Pretreatment HVPG and LSM are significant determinants of the likelihood of fibrosis regression. Finally, LSM accurately predicts the presence of AF and PH 1 year after SVR and thus can be used to determine monitoring strategies. (Hepatology 2018;67:1683-1694).
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Affiliation(s)
- Ezequiel Mauro
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain.,Liver Unit, Hospital Italiano, Buenos Aires, Argentina
| | - Gonzalo Crespo
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | | | | | - Virginia Hernández-Gea
- Barcelona Hemodynamics Laboratory, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Pablo Ruiz
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Lydia Sastre
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Julissa Lombardo
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Alba Díaz
- Pathology Department, Hospital Clínic, Barcelona, Spain
| | - Jordi Colmenero
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Antoni Rimola
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Juan Carlos Garcia-Pagán
- Barcelona Hemodynamics Laboratory, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Mercé Brunet
- Pharmacology and Toxicology, IDIBAPS, CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Miquel Navasa
- Liver Transplant Unit, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, Barcelona, Spain
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Waziry R, Gomaa A, Waked I, Dore GJ. Determinants of survival following hepatocellular carcinoma in Egyptian patients with untreated chronic HCV infection in the pre-DAA era. Arab J Gastroenterol 2018; 19:26-32. [PMID: 29506913 DOI: 10.1016/j.ajg.2018.02.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 12/09/2017] [Accepted: 02/04/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND STUDY AIMS In this study we assessed rates and determinants of survival in people with untreated chronic HCV infection and hepatocellular carcinoma (HCC) in an Egyptian liver clinic setting. PATIENTS AND METHODS This is a prospective cohort study of patients diagnosed with HCV-related HCC and undergoing HCC management at a national liver centre in Egypt in 2013-2014 and with a follow-up through 2016. RESULTS A total of 345 patients diagnosed with HCV-related liver cirrhosis complicated by HCC were included. Median age at diagnosis was 57 years (IQR = 52, 62), the majority were male (78%) and Child-Turcotte-Pugh (CTP) class A (64%). At diagnosis Barcelona Clinic Liver Cancer staging (BCLC) was 0 (8%), A (48%), B (20%), C (17%), and D (7%). Most common HCC management modalities were transarterial chemoembolization (TACE) (42%), and radiofrequency ablation (RFA) (21%). Median survival following HCC was 22.8 months. Factors associated with poorer survival in adjusted analyses were INR (HR = 1.81, p = 0.01), alpha-foeto protein (AFP) ≥200 (HR = 1.41, p = 0.02), higher CTP score (HR = 2.48, p < 0.01), and advanced BCLC stage (HR = 1.85, p < 0.01). One year survival in patients with CTP A, B, and C was 85%, 71% and 32%, respectively. One year survival following RFA, TACE, combination RFA/TACE, and sorafenib was 93%, 79%, 80% and 60%, respectively. CONCLUSION Survival following HCV-HCC in Egyptian patients undergoing HCC management in a specialised clinic setting is poor, although similar to high income country settings. CTP score is a key determinant of survival, even following adjustment for BCLC stage and HCC management.
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Affiliation(s)
- Reem Waziry
- The Kirby Institute, UNSW Sydney, Sydney, Australia.
| | - Asmaa Gomaa
- Hepatology Department, National Liver Institute, Menoufiya University, Shebeen Elkom, Menoufiya, Egypt
| | - Imam Waked
- Hepatology Department, National Liver Institute, Menoufiya University, Shebeen Elkom, Menoufiya, Egypt
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Pascual-Argente N, Puig-Junoy J, Llagostera-Punzano A. Non-healthcare costs of hepatitis C: a systematic review. Expert Rev Gastroenterol Hepatol 2018; 12:19-30. [PMID: 28844170 DOI: 10.1080/17474124.2017.1373016] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
There is an increasing interest in the indirect (or non-healthcare) costs of hepatitis C virus (HCV). Areas covered: Systematic review of original studies on the non-healthcare costs of HCV published in English or Spanish between January 2000 and March 2017. 19 studies addressing non-healthcare cost of HCV were included in the analysis. All studies but one contain treatments with monotherapy or dual therapy prior to the recent introduction of innovative and highly effective direct acting antivirals (DAAs). Five studies estimate the incremental non-healthcare cost of HCV with a control group, which is regarded as high-quality methodology. The incremental annual non-healthcare costs of HCV in untreated patients compared with non-HCV patients are €4,209 in the US, and taking data from 5 European countries costs range from €280 in the UK to €659 in France. Expert commentary: Available studies may be underestimating the true burden of non-healthcare costs for HCV as they are all partial studies, mainly including absenteeism and premature mortality estimates. Moreover, there is a need for studies addressing non-healthcare costs of HCV in settings where new treatments with DAAs have been implemented, as they are probably changing the current and future burden of the disease.
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Affiliation(s)
- Natàlia Pascual-Argente
- a UPF Barcelona School of Management, Pompeu Fabra University , Barcelona , Spain.,b Department of Economics and Business. Center for Research in Health and Economics (CRES-UPF) , Pompeu Fabra University , Barcelona , Spain
| | - Jaume Puig-Junoy
- a UPF Barcelona School of Management, Pompeu Fabra University , Barcelona , Spain.,b Department of Economics and Business. Center for Research in Health and Economics (CRES-UPF) , Pompeu Fabra University , Barcelona , Spain
| | - Anna Llagostera-Punzano
- b Department of Economics and Business. Center for Research in Health and Economics (CRES-UPF) , Pompeu Fabra University , Barcelona , Spain
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Grgurevic I, Bozin T, Madir A. Hepatitis C is now curable, but what happens with cirrhosis and portal hypertension afterwards? Clin Exp Hepatol 2017; 3:181-186. [PMID: 29255805 PMCID: PMC5731432 DOI: 10.5114/ceh.2017.71491] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Accepted: 09/03/2017] [Indexed: 02/06/2023] Open
Abstract
Results from the interferon era have demonstrated reversibility of cirrhosis following viral eradication, but only for patients in the initial stage of cirrhosis. Although direct-acting antivirals (DAA) represent revolutionary treatment of hepatitis C, there are currently no studies showing histological effects of therapy on a large number of cirrhotic patients. However, studies involving transient elastography demonstrated a rapid decrease in liver stiffness after successful DAA therapy, probably due to resolution of inflammation, rather than fibrosis regression, as the latter requires a longer period of time. Reversal of fibrosis and cirrhosis upon viral eradication is a prerequisite for the reduction of portal pressure, but this effect has only been observed for the subclinical stage of portal hypertension (PH). On the other hand, the majority of patients with clinically significant PH remain at risk of decompensation and death, despite hepatitis C virus cure, as PH remains high in this setting. This calls for novel therapeutic approaches.
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Affiliation(s)
- Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
- University of Zagreb School of Medicine, Zagreb, Croatia
| | - Tonci Bozin
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
| | - Anita Madir
- University of Zagreb School of Medicine, Zagreb, Croatia
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Bennett H, Gordon J, Jones B, Ward T, Webster S, Kalsekar A, Yuan Y, Brenner M, McEwan P. Hepatitis C disease transmission and treatment uptake: impact on the cost-effectiveness of new direct-acting antiviral therapies. THE EUROPEAN JOURNAL OF HEALTH ECONOMICS : HEPAC : HEALTH ECONOMICS IN PREVENTION AND CARE 2017; 18:1001-1011. [PMID: 27803989 DOI: 10.1007/s10198-016-0844-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 10/18/2016] [Indexed: 05/23/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) treatment can reduce the incidence of future infections through removing opportunities for onward transmission. This benefit is not captured in conventional cost-effectiveness evaluations of treatment and is particularly relevant in patient groups with a high risk of transmission, such as those people who inject drugs (PWID), where the treatment rates have been historically low. This study aimed to quantify how reduced HCV transmission changes the cost-effectiveness of new direct-acting antiviral (DAA) regimens as a function of treatment uptake rates. METHODS An established model of HCV disease transmission and progression was used to quantify the impact of treatment uptake (10-100%), within the PWID population, on the cost-effectiveness of a DAA regimen versus pre-DAA standard of care, conducted using daclatasvir plus sofosbuvir in the UK setting as an illustrative example. RESULTS The consequences of reduced disease transmission due to treatment were associated with additional net monetary benefit of £24,304-£90,559 per patient treated at £20,000/QALY, when 10-100% of eligible patients receive treatment with 100% efficacy. Dependent on patient genotype, the cost-effectiveness of HCV treatment using daclatasvir plus sofosbuvir improved by 36-79% versus conventional analysis, at 10-100% treatment uptake in the PWID population. CONCLUSIONS The estimated cost-effectiveness of HCV treatment was shown to improve as more patients are treated, suggesting that the value of DAA regimens to the NHS could be enhanced by improved treatment uptake rates among PWID. However, the challenge for the future will lie in achieving increased rates of treatment uptake, particularly in the PWID population.
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Affiliation(s)
- Hayley Bennett
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK.
| | - Jason Gordon
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
- Department of Public Health, University of Adelaide, Adelaide, Australia
| | - Beverley Jones
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
| | - Thomas Ward
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
| | - Samantha Webster
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
| | - Anupama Kalsekar
- World Wide Health Economics and Outcomes Research, Bristol-Myers Squibb Pharmaceuticals Ltd, Princeton, USA
| | - Yong Yuan
- World Wide Health Economics and Outcomes Research, Bristol-Myers Squibb Pharmaceuticals Ltd, Princeton, USA
| | - Michael Brenner
- UK HEOR, Bristol-Myers Squibb Pharmaceuticals Ltd, Uxbridge, UK
| | - Phil McEwan
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
- School of Human and Health Sciences, Swansea University, Swansea, UK
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Corman S, Elbasha EH, Michalopoulos SN, Nwankwo C. Cost-Utility of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1 Infection. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2017; 20:1110-1120. [PMID: 28964443 DOI: 10.1016/j.jval.2017.05.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 04/24/2017] [Accepted: 05/03/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVE To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. METHODS A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA (< or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients. CONCLUSIONS Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations.
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Elsharkawy A, Eletreby R, Fouad R, Soliman Z, Abdallah M, Negm M, Mohey M, Esmat G. Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients. Expert Rev Gastroenterol Hepatol 2017; 11:773-778. [PMID: 28480808 DOI: 10.1080/17474124.2017.1326816] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment. METHODS 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment. RESULTS Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL. CONCLUSION DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.
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Affiliation(s)
- Aisha Elsharkawy
- a Endemic Medicine and Hepatogastroentrology Department, Faculty of medicine , Cairo University , Cairo , Egypt
| | - Rasha Eletreby
- a Endemic Medicine and Hepatogastroentrology Department, Faculty of medicine , Cairo University , Cairo , Egypt
| | - Rabab Fouad
- a Endemic Medicine and Hepatogastroentrology Department, Faculty of medicine , Cairo University , Cairo , Egypt
| | - Zeinab Soliman
- a Endemic Medicine and Hepatogastroentrology Department, Faculty of medicine , Cairo University , Cairo , Egypt
| | - Mohamed Abdallah
- b Medical research division , National research Centre , Cairo , Egypt
| | - Mohamed Negm
- c Kasr Al-Ainy Viral Hepatitis Center, Faculty of medicine , Cairo University , Cairo , Egypt
| | - Mohammad Mohey
- a Endemic Medicine and Hepatogastroentrology Department, Faculty of medicine , Cairo University , Cairo , Egypt
| | - Gamal Esmat
- a Endemic Medicine and Hepatogastroentrology Department, Faculty of medicine , Cairo University , Cairo , Egypt
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Jeffrey AW, Huang Y, de Boer WB, Adams LA, MacQuillan G, Speers D, Joseph J, Jeffrey GP. Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome. World J Hepatol 2017; 9:850-856. [PMID: 28740596 PMCID: PMC5504360 DOI: 10.4254/wjh.v9.i19.850] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 04/30/2017] [Accepted: 05/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish if serial Hepascore tests (referred to as delta Hepascore) in those with chronic hepatitis C (CHC) correlate with the increase and/or decrease in risk of liver related complications.
METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28 (8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis and subsequent clinical outcomes in chronic liver disease.
RESULTS Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation (P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint (P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year (P = 0.03).
CONCLUSION In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.
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Gupta V, Kumar A, Sharma P, Arora A. Newer direct-acting antivirals for hepatitis C virus infection: Perspectives for India. Indian J Med Res 2017; 146:23-33. [PMID: 29168457 PMCID: PMC5719604 DOI: 10.4103/ijmr.ijmr_679_15] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Indexed: 12/20/2022] Open
Abstract
Approximately three per cent of the world's population (170-200 million people) is chronically infected with hepatitis C virus (HCV) and almost 500,000 people die each year (mostly in lower middle-income countries) from complications secondary to HCV infection. In India, HCV infection imposes a considerable burden of mortality, morbidity and healthcare costs. In the last two decades, the treatment of HCV has evolved from interferon (IFN)-based therapies with or without ribavirin (RBV) to pegylated-IFN (PEG-IFN) and RBV-based therapies that were better tolerated by patients. However, the introduction of oral drugs, which specifically target virus-specific proteins, has now revolutionized the treatment of chronic HCV. These agents are known as direct-acting antivirals (DAAs). These drugs have resulted in very high HCV cure rates even with reduced treatment duration and an excellent tolerability by the patients compared to PEG-IFN- and RBV-based therapies. In India, sofosbuvir (SOF), one of the most effective DAAs, has been made available at a compassionate price; thus only those DAA-based management strategies, which contain SOF are adopted in India. Here, we review different DAAs and their possible roles in different genotypes and stages of liver disease, stressing upon the role of SOF. An attempt has also been made to devise strategies using SOF for the most prevalent genotypes in our country (genotypes 3 and 1) and cirrhosis.
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Affiliation(s)
- Varun Gupta
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
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Anand AC. Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation? J Clin Exp Hepatol 2017; 7:42-54. [PMID: 28348470 PMCID: PMC5357718 DOI: 10.1016/j.jceh.2017.01.116] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 01/31/2017] [Indexed: 12/12/2022] Open
Abstract
Treatment of hepatitis C virus (HCV) with newer directly acting antivirals (DAAs) and lead to sustained viral response (SVR) in majority of patients and SVR has been documented to be associated with reversal of liver cirrhosis. The improved SVR rates and safety profiles of DAAs have led to the treatment of patients with decompensated cirrhosis awaiting liver transplantation (LT). Several clinical trials of DAAs in decompensated HCV patients have recently demonstrated SVR rates above 80%, which have been associated with significant improvements, in the Child-Pugh-Turcotte scores/or model for end-stage liver disease scores in a proportion of patients. Moreover, it has been shown that HCV RNA becomes negative after 2-4 weeks of treatment, and those who are transplanted after becoming HCV RNA negative will be have very low the risk of HCV recurrence after transplantation. Some of the patients may have reached the "point of no return" and may proceed to worsening of decomposition over time. To avoid the risk of worsening, there is an additional option of treating these patients after LT should they develop recurrent HCV infection. Currently there are no guidelines as to select patients who would benefit from treatment prior to LT as opposed to those who will be better off being treated after the transplant surgery. The article discusses a possible approach for such selection.
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Key Words
- CSA, cyclosporine A
- CTP, Child–Turcotte–Pugh staging
- DAA, directly acting antivirals
- DCV, daclatasvir
- DDLT, deceased donor liver transplant
- DSB, dasabuvir
- EBV, elbasvir
- FCH, fibrosing cholestatic hepatitis
- GRZ, grazoprevir
- GT, genotype
- HCV, hepatitis C virus
- IU, international units
- LDLT, living donor liver transplant
- LDV, ledipasvir
- LT, liver transplantation
- MELD, model for end-stage liver disease RNA
- OMB, ombitasvir
- PTV, paritaprevir
- Peg-IFN, pegylated interferon alfa
- RBV, ribavirin
- SMV, simeprevir
- SOF, sofosbuvir
- SVR, sustained virological response, (SVR 12 signifies SVR at 12 weeks)
- TAC, tacrolimus
- VLP, velpatasvir
- decompensated cirrhosis
- directly acting antivirals
- hepatitis C virus infection
- liver transplantation
- rt, ritonavir
- sustained virological response
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Affiliation(s)
- Anil C. Anand
- Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
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Liu Z, Wei X, Chen T, Huang C, Liu H, Wang Y. Characterization of fibrosis changes in chronic hepatitis C patients after virological cure: A systematic review with meta-analysis. J Gastroenterol Hepatol 2017; 32:548-557. [PMID: 27503423 DOI: 10.1111/jgh.13500] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/20/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Virological cure becomes available for most patients with chronic hepatitis C (CHC), but residual fibrosis can be an independent risk factor for liver-related complications. We aimed to characterize fibrosis change in CHC patients achieved virological cure. METHODS We did a systematic literature search for studies that had pre and post-treatment evaluations of histologic fibrosis in CHC patients with sustained virological response (SVR). We identified the association of SVR with the incidence, extent, and velocity of fibrosis change. RESULTS Overall, 3243 patients were included. Interferon-based regimens were used for all the patients, achieving a median SVR prevalence of 36.2%. Biopsy interval ranged from 1 to 10 years. Mean baseline fibrosis score (METAVIR) was 2.3 points. Compared with non-SVR patients, SVR patients could have higher incidence of fibrosis regression (35.1% vs 17.0%; OR: 3.3; P < 0.001), regardless of baseline fibrosis severity, way of biopsy evaluation, treatment regimen, or study design, and could have more extent of reduction (-0.31 points vs -0.00 points; P = 0.004). Baseline advanced fibrosis (F > 2) was associated with more rapid regression in both SVR and non-SVR patients (P < 0.05 for both). SVR patients could have lower incidence of fibrosis progression and maintenance than non-SVR patients by 4.8% versus 23.1% (OR: 0.20; P = 0.008) and 42.9% versus 55.2% (OR: 0.53; P < 0.001), respectively. CONCLUSIONS There could be a favorable characteristic of fibrosis regression in SVR patients. However, residential fibrosis may remain an issue because of a non-ignorable prevalence of fibrosis maintenance among these patients.
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Affiliation(s)
- Zhipeng Liu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China.,Department of Hepatobiliary Surgery, Zhujiang Hospital, Guangzhou, China
| | - Xuewu Wei
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China.,Department of Hepatobiliary Surgery, Zhujiang Hospital, Guangzhou, China
| | - Ting Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China.,Department of Hepatobiliary Surgery, Zhujiang Hospital, Guangzhou, China
| | - Chuhong Huang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China.,Department of Hepatobiliary Surgery, Zhujiang Hospital, Guangzhou, China
| | - Haiyan Liu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Guangzhou, China
| | - Yan Wang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China.,Southern Medical University Biomedical Research Center, Southern Medical University, Guangzhou, China
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Britnell SR, Willets AE, Vanderman AJ, Woodard CL, Britt RB. Influence of Successful Chronic Hepatitis C Virus Treatment with Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans. Pharmacotherapy 2016; 36:1173-1179. [PMID: 27716978 DOI: 10.1002/phar.1845] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
STUDY OBJECTIVE To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin. DESIGN Case series. SETTING Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System. PATIENTS Four patients aged 59-66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection. MEASUREMENTS AND MAIN RESULTS All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14-67% was required, with changes in warfarin doses starting 2-3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment. CONCLUSION To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes.
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Affiliation(s)
- Sara R Britnell
- Pharmacy Department, Durham Veterans Affairs Health Care System, Durham, North Carolina
| | - Amy E Willets
- Pharmacy Department, Durham Veterans Affairs Health Care System, Durham, North Carolina
| | - Adam J Vanderman
- Pharmacy Department, Durham Veterans Affairs Health Care System, Durham, North Carolina
| | - Catherine L Woodard
- Pharmacy Department, Durham Veterans Affairs Health Care System, Durham, North Carolina
| | - Rachel B Britt
- Pharmacy Department, Durham Veterans Affairs Health Care System, Durham, North Carolina
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