Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma

A systematic review and meta-analysis

F. Ji, Yee Hui Yeo, Mike Tzuhen Wei, Eiichi Ogawa, Masaru Enomoto, Dong Hyun Lee, Etsuko Iio, John Lubel, Wenjun Wang, Bin Wei, Tatsuya Ide, Carmen Monica Preda, F. Conti, Tatsuya Minami, Rob Bielen, Hitomi Sezaki, Michele Barone, Philippe Kolly, Po sung Chu, Victor Virlogeux & 15 others Dennis Eurich, L. Henry, Michelle B. Bass, Takanori Kanai, Shuangsuo Dang, Zongfang Li, Jean François Dufour, Fabien Zoulim, Pietro Andreone, Ramsey C. Cheung, Yasuhito Tanaka, Norihiro Furusyo, Hidenori Toyoda, Akihiro Tamori, Mindie H. Nguyen

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)473-485
Number of pages13
JournalJournal of Hepatology
Volume71
Issue number3
DOIs
Publication statusPublished - Sep 1 2019

Fingerprint

Chronic Hepatitis C
Antiviral Agents
Meta-Analysis
Hepatocellular Carcinoma
Therapeutics
Liver Neoplasms
Sustained Virologic Response
Ritonavir
Hepatitis C
PubMed
Hepacivirus
Interferons
Liver Diseases

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma : A systematic review and meta-analysis. / Ji, F.; Yeo, Yee Hui; Wei, Mike Tzuhen; Ogawa, Eiichi; Enomoto, Masaru; Lee, Dong Hyun; Iio, Etsuko; Lubel, John; Wang, Wenjun; Wei, Bin; Ide, Tatsuya; Preda, Carmen Monica; Conti, F.; Minami, Tatsuya; Bielen, Rob; Sezaki, Hitomi; Barone, Michele; Kolly, Philippe; Chu, Po sung; Virlogeux, Victor; Eurich, Dennis; Henry, L.; Bass, Michelle B.; Kanai, Takanori; Dang, Shuangsuo; Li, Zongfang; Dufour, Jean François; Zoulim, Fabien; Andreone, Pietro; Cheung, Ramsey C.; Tanaka, Yasuhito; Furusyo, Norihiro; Toyoda, Hidenori; Tamori, Akihiro; Nguyen, Mindie H.

In: Journal of Hepatology, Vol. 71, No. 3, 01.09.2019, p. 473-485.

Research output: Contribution to journalArticle

Ji, F, Yeo, YH, Wei, MT, Ogawa, E, Enomoto, M, Lee, DH, Iio, E, Lubel, J, Wang, W, Wei, B, Ide, T, Preda, CM, Conti, F, Minami, T, Bielen, R, Sezaki, H, Barone, M, Kolly, P, Chu, PS, Virlogeux, V, Eurich, D, Henry, L, Bass, MB, Kanai, T, Dang, S, Li, Z, Dufour, JF, Zoulim, F, Andreone, P, Cheung, RC, Tanaka, Y, Furusyo, N, Toyoda, H, Tamori, A & Nguyen, MH 2019, 'Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis', Journal of Hepatology, vol. 71, no. 3, pp. 473-485. https://doi.org/10.1016/j.jhep.2019.04.017
Ji, F. ; Yeo, Yee Hui ; Wei, Mike Tzuhen ; Ogawa, Eiichi ; Enomoto, Masaru ; Lee, Dong Hyun ; Iio, Etsuko ; Lubel, John ; Wang, Wenjun ; Wei, Bin ; Ide, Tatsuya ; Preda, Carmen Monica ; Conti, F. ; Minami, Tatsuya ; Bielen, Rob ; Sezaki, Hitomi ; Barone, Michele ; Kolly, Philippe ; Chu, Po sung ; Virlogeux, Victor ; Eurich, Dennis ; Henry, L. ; Bass, Michelle B. ; Kanai, Takanori ; Dang, Shuangsuo ; Li, Zongfang ; Dufour, Jean François ; Zoulim, Fabien ; Andreone, Pietro ; Cheung, Ramsey C. ; Tanaka, Yasuhito ; Furusyo, Norihiro ; Toyoda, Hidenori ; Tamori, Akihiro ; Nguyen, Mindie H. / Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma : A systematic review and meta-analysis. In: Journal of Hepatology. 2019 ; Vol. 71, No. 3. pp. 473-485.
@article{e579347ebeb8455c99e879b3589e82c3,
title = "Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis",
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.",
author = "F. Ji and Yeo, {Yee Hui} and Wei, {Mike Tzuhen} and Eiichi Ogawa and Masaru Enomoto and Lee, {Dong Hyun} and Etsuko Iio and John Lubel and Wenjun Wang and Bin Wei and Tatsuya Ide and Preda, {Carmen Monica} and F. Conti and Tatsuya Minami and Rob Bielen and Hitomi Sezaki and Michele Barone and Philippe Kolly and Chu, {Po sung} and Victor Virlogeux and Dennis Eurich and L. Henry and Bass, {Michelle B.} and Takanori Kanai and Shuangsuo Dang and Zongfang Li and Dufour, {Jean Fran{\cc}ois} and Fabien Zoulim and Pietro Andreone and Cheung, {Ramsey C.} and Yasuhito Tanaka and Norihiro Furusyo and Hidenori Toyoda and Akihiro Tamori and Nguyen, {Mindie H.}",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.jhep.2019.04.017",
language = "English",
volume = "71",
pages = "473--485",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma

T2 - A systematic review and meta-analysis

AU - Ji, F.

AU - Yeo, Yee Hui

AU - Wei, Mike Tzuhen

AU - Ogawa, Eiichi

AU - Enomoto, Masaru

AU - Lee, Dong Hyun

AU - Iio, Etsuko

AU - Lubel, John

AU - Wang, Wenjun

AU - Wei, Bin

AU - Ide, Tatsuya

AU - Preda, Carmen Monica

AU - Conti, F.

AU - Minami, Tatsuya

AU - Bielen, Rob

AU - Sezaki, Hitomi

AU - Barone, Michele

AU - Kolly, Philippe

AU - Chu, Po sung

AU - Virlogeux, Victor

AU - Eurich, Dennis

AU - Henry, L.

AU - Bass, Michelle B.

AU - Kanai, Takanori

AU - Dang, Shuangsuo

AU - Li, Zongfang

AU - Dufour, Jean François

AU - Zoulim, Fabien

AU - Andreone, Pietro

AU - Cheung, Ramsey C.

AU - Tanaka, Yasuhito

AU - Furusyo, Norihiro

AU - Toyoda, Hidenori

AU - Tamori, Akihiro

AU - Nguyen, Mindie H.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85067690668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067690668&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2019.04.017

DO - 10.1016/j.jhep.2019.04.017

M3 - Article

VL - 71

SP - 473

EP - 485

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 3

ER -