Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma

Hidenori Toyoda; Mounika Kanneganti; Jonathan Melendez-Torres; Neehar D. Parikh; Prasun K. Jalal; Federico Piñero; Manuel Mendizabal; Ezequiel Ridruejo; Hugo Cheinquer; Andrea Casadei-Gardini; Arndt Weinmann; Markus Peck-Radosavljevic; Jean Francois Dufour; Pompilia Radu; Gamal Shiha; Riham Soliman; Shiv K. Sarin; Manoj Kumar; Jing Houng Wang; Pisit Tangkijvanich; Wattana Sukeepaisarnjaroen; Masanori Atsukawa; Haruki Uojima; Akito Nozaki; Makoto Nakamuta; Koichi Takaguchi; Atsushi Hiraoka; Hiroshi Abe; Kentaro Matsuura; Tsunamasa Watanabe; Noritomo Shimada; Kunihiko Tsuji; Toru Ishikawa; Shigeru Mikami; Ei Itobayashi; Amit G. Singal; Philip J. Johnson

doi:10.1016/j.cgh.2023.06.026

Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma

Hidenori Toyoda, Mounika Kanneganti, Jonathan Melendez-Torres, Neehar D. Parikh, Prasun K. Jalal, Federico Piñero, Manuel Mendizabal, Ezequiel Ridruejo, Hugo Cheinquer, Andrea Casadei-Gardini, Arndt Weinmann, Markus Peck-Radosavljevic, Jean Francois Dufour, Pompilia Radu, Gamal Shiha, Riham Soliman, Shiv K. Sarin, Manoj Kumar, Jing Houng Wang, Pisit TangkijvanichWattana Sukeepaisarnjaroen, Masanori Atsukawa, Haruki Uojima, Akito Nozaki, Makoto Nakamuta, Koichi Takaguchi, Atsushi Hiraoka, Hiroshi Abe, Kentaro Matsuura, Tsunamasa Watanabe, Noritomo Shimada, Kunihiko Tsuji, Toru Ishikawa, Shigeru Mikami, Ei Itobayashi, Amit G. Singal, Philip J. Johnson

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background & Aims: Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. Methods: We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan–Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. Results: Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%–100%), median maximum tumor diameter (range, 1.8–5.0 cm), and the proportion with multinodular HCC (range, 15.4%–60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82–9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P <.0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18–0.46). Conclusions: Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.

Original language	English (US)
Pages (from-to)	72-80.e4
Journal	Clinical Gastroenterology and Hepatology
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.cgh.2023.06.026
State	Published - Jan 2024

Keywords

Hepatitis C Virus Infection
Hepatocellular Carcinoma
Prognosis
Surveillance
Sustained Virologic Response

ASJC Scopus subject areas

Hepatology
Gastroenterology

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10.1016/j.cgh.2023.06.026

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Toyoda, H., Kanneganti, M., Melendez-Torres, J., Parikh, N. D., Jalal, P. K., Piñero, F., Mendizabal, M., Ridruejo, E., Cheinquer, H., Casadei-Gardini, A., Weinmann, A., Peck-Radosavljevic, M., Dufour, J. F., Radu, P., Shiha, G., Soliman, R., Sarin, S. K., Kumar, M., Wang, J. H., ... Johnson, P. J. (2024). Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma. Clinical Gastroenterology and Hepatology, 22(1), 72-80.e4. https://doi.org/10.1016/j.cgh.2023.06.026

Toyoda, H, Kanneganti, M, Melendez-Torres, J, Parikh, ND, Jalal, PK, Piñero, F, Mendizabal, M, Ridruejo, E, Cheinquer, H, Casadei-Gardini, A, Weinmann, A, Peck-Radosavljevic, M, Dufour, JF, Radu, P, Shiha, G, Soliman, R, Sarin, SK, Kumar, M, Wang, JH, Tangkijvanich, P, Sukeepaisarnjaroen, W, Atsukawa, M, Uojima, H, Nozaki, A, Nakamuta, M, Takaguchi, K, Hiraoka, A, Abe, H, Matsuura, K, Watanabe, T, Shimada, N, Tsuji, K, Ishikawa, T, Mikami, S, Itobayashi, E, Singal, AG & Johnson, PJ 2024, 'Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma', Clinical Gastroenterology and Hepatology, vol. 22, no. 1, pp. 72-80.e4. https://doi.org/10.1016/j.cgh.2023.06.026

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title = "Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma",

abstract = "Background & Aims: Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. Methods: We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan–Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. Results: Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%–100%), median maximum tumor diameter (range, 1.8–5.0 cm), and the proportion with multinodular HCC (range, 15.4%–60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82–9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P <.0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18–0.46). Conclusions: Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.",

keywords = "Hepatitis C Virus Infection, Hepatocellular Carcinoma, Prognosis, Surveillance, Sustained Virologic Response",

author = "Hidenori Toyoda and Mounika Kanneganti and Jonathan Melendez-Torres and Parikh, {Neehar D.} and Jalal, {Prasun K.} and Federico Pi{\~n}ero and Manuel Mendizabal and Ezequiel Ridruejo and Hugo Cheinquer and Andrea Casadei-Gardini and Arndt Weinmann and Markus Peck-Radosavljevic and Dufour, {Jean Francois} and Pompilia Radu and Gamal Shiha and Riham Soliman and Sarin, {Shiv K.} and Manoj Kumar and Wang, {Jing Houng} and Pisit Tangkijvanich and Wattana Sukeepaisarnjaroen and Masanori Atsukawa and Haruki Uojima and Akito Nozaki and Makoto Nakamuta and Koichi Takaguchi and Atsushi Hiraoka and Hiroshi Abe and Kentaro Matsuura and Tsunamasa Watanabe and Noritomo Shimada and Kunihiko Tsuji and Toru Ishikawa and Shigeru Mikami and Ei Itobayashi and Singal, {Amit G.} and Johnson, {Philip J.}",

note = "Publisher Copyright: {\textcopyright} 2024 AGA Institute",

year = "2024",

month = jan,

doi = "10.1016/j.cgh.2023.06.026",

language = "English (US)",

volume = "22",

pages = "72--80.e4",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

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number = "1",

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TY - JOUR

T1 - Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma

AU - Toyoda, Hidenori

AU - Kanneganti, Mounika

AU - Melendez-Torres, Jonathan

AU - Parikh, Neehar D.

AU - Jalal, Prasun K.

AU - Piñero, Federico

AU - Mendizabal, Manuel

AU - Ridruejo, Ezequiel

AU - Cheinquer, Hugo

AU - Casadei-Gardini, Andrea

AU - Weinmann, Arndt

AU - Peck-Radosavljevic, Markus

AU - Dufour, Jean Francois

AU - Radu, Pompilia

AU - Shiha, Gamal

AU - Soliman, Riham

AU - Sarin, Shiv K.

AU - Kumar, Manoj

AU - Wang, Jing Houng

AU - Tangkijvanich, Pisit

AU - Sukeepaisarnjaroen, Wattana

AU - Atsukawa, Masanori

AU - Uojima, Haruki

AU - Nozaki, Akito

AU - Nakamuta, Makoto

AU - Takaguchi, Koichi

AU - Hiraoka, Atsushi

AU - Abe, Hiroshi

AU - Matsuura, Kentaro

AU - Watanabe, Tsunamasa

AU - Shimada, Noritomo

AU - Tsuji, Kunihiko

AU - Ishikawa, Toru

AU - Mikami, Shigeru

AU - Itobayashi, Ei

AU - Singal, Amit G.

AU - Johnson, Philip J.

PY - 2024/1

Y1 - 2024/1

N2 - Background & Aims: Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. Methods: We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan–Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. Results: Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%–100%), median maximum tumor diameter (range, 1.8–5.0 cm), and the proportion with multinodular HCC (range, 15.4%–60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82–9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P <.0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18–0.46). Conclusions: Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.

AB - Background & Aims: Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. Methods: We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan–Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. Results: Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%–100%), median maximum tumor diameter (range, 1.8–5.0 cm), and the proportion with multinodular HCC (range, 15.4%–60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82–9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P <.0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18–0.46). Conclusions: Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.

KW - Hepatitis C Virus Infection

KW - Hepatocellular Carcinoma

KW - Prognosis

KW - Surveillance

KW - Sustained Virologic Response

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AN - SCOPUS:85171686442

SN - 1542-3565

VL - 22

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JO - Clinical Gastroenterology and Hepatology

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ER -

Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma

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