Fanpu Ji1, Yee Hui Yeo2, Mike Tzuhen Wei2, Eiichi Ogawa3, Masaru Enomoto4, Dong Hyun Lee5, Etsuko Iio6, John Lubel7, Wenjun Wang8, Bin Wei2, Tatsuya Ide9, Carmen Monica Preda10, Fabio Conti11, Tatsuya Minami12, Rob Bielen13, Hitomi Sezaki14, Michele Barone15, Philippe Kolly16, Po-Sung Chu17, Victor Virlogeux18, Dennis Eurich19, Linda Henry2, Michelle B Bass20, Takanori Kanai17, Shuangsuo Dang8, Zongfang Li21, Jean-François Dufour16, Fabien Zoulim22, Pietro Andreone11, Ramsey C Cheung23, Yasuhito Tanaka6, Norihiro Furusyo24, Hidenori Toyoda25, Akihiro Tamori4, Mindie H Nguyen26. 1. Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. 2. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. 3. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 4. Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 5. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology, Department of Internal Medicine, Good Gang-An Hospital, Busan, Republic of Korea. 6. Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan. 7. Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia. 8. Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. 9. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan. 10. University of Medicine and Pharmacy "Carol Davila", Department of Gastroenterology and Hepatology, Clinical Institute Fundeni, Bucharest, Romania. 11. Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 12. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan. 13. Faculty of Medicine and Life Sciences, Hasselt University, Belgium. 14. Department of Hepatology, Toranomon Hospital, Tokyo, Japan. 15. Gastroenterology Unit, Department of Emergency and Organ Transplantation, Azienda Universitario-Ospedaliera Policlinico, University of Bari, Bari, Italy. 16. Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland. 17. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. 18. Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France. 19. Department of Surgery Campus Charité Mitte / Campus Virchow-Klinikum, Berlin, Germany. 20. Lane Medical Library & Knowledge Management Center, Stanford University, Palo Alto, CA, USA. 21. National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. 22. Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Cancer Research Center of Lyon (CRCL-INSERM U1052), Lyon University, Lyon, France. 23. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. 24. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 25. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. 26. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. Electronic address: mindiehn@stanford.edu.
Abstract
BACKGROUND & AIMS: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY: There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
BACKGROUND & AIMS: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY: There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
Authors: Michael K Turgeon; Shimul A Shah; Aaron M Delman; Benjamin V Tran; Vatche G Agopian; Joel P Wedd; Joseph F Magliocca; Ahyoung Kim; Andrew Cameron; Ali Olyaei; Susan L Orloff; Matthew P Anderson; Chandrashekhar A Kubal; Robert M Cannon; Jayme E Locke; Mary A Simpson; Mohamed E Akoad; Chelsey P Wongjirad; Juliet Emamaullee; Amika Moro; Federico Aucejo; Cyrus A Feizpour; Parsia A Vagefi; Mindie H Nguyen; Carlos O Esquivel; Kiran Dhanireddy; Vijay Subramanian; Alejandro Chavarriaga; Marwan M Kazimi; Maia S Anderson; Christopher J Sonnenday; Steven C Kim; David P Foley; Marwan Abdouljoud; Reena J Salgia; Dimitrios Moris; Debra L Sudan; Swaytha R Ganesh; Abhinav Humar; Majella Doyle; William C Chapman; Shishir K Maithel Journal: Ann Surg Date: 2021-10-01 Impact factor: 13.787