Disease trajectory and competing risks of patients with cirrhosis in the US

Mohsen Mohammadi; Bima J. Hasjim; Salva N. Balbale; Praneet Polineni; Alexander A. Huang; Mitchell Paukner; Therese Banea; Oriana Dentici; Dominic J. Vitello; Joy E. Obayemi; Andrés Duarte-Rojo; Satish N. Nadig; Lisa B. Vanwagner; Lihui Zhao; Sanjay Mehrotra; Daniela P. Ladner

doi:10.1371/journal.pone.0313152

Disease trajectory and competing risks of patients with cirrhosis in the US

Mohsen Mohammadi, Bima J. Hasjim, Salva N. Balbale, Praneet Polineni, Alexander A. Huang, Mitchell Paukner, Therese Banea, Oriana Dentici, Dominic J. Vitello, Joy E. Obayemi, Andrés Duarte-Rojo, Satish N. Nadig, Lisa B. Vanwagner, Lihui Zhao, Sanjay Mehrotra, Daniela P. Ladner^*

^*Corresponding author for this work

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

Abstract

Background Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting. Methods A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006–2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates. Results Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36–2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23–1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71–2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified. Conclusion Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.

Original language	English (US)
Article number	e0313152
Journal	PloS one
Volume	20
Issue number	2 February
DOIs	https://doi.org/10.1371/journal.pone.0313152
State	Published - Feb 2025

Funding

This study was supported by R01AG070194 [Ladner/Mehrotra]. Dr. Hasjim and Dr. Obayemi were supported by NIH grant T32DK077662-15 (PD: Ladner/Green). Dr. VanWagner was supported by the National Heart, Lung, and Blood Institute K23 HL136891 and R56 HL155093 grant. Praneet Polineni and Dr. Vitello were supported by the Steven J. Stryker Gastrointestinal Research and Endowment Grant. There was no additional external funding received for this study. We would like to acknowledge the Northwestern University Transplant Outcomes Research Collaborative (NUTORC), which provided IRB support and coordination. Presented at the American College of Surgeons 109th Annual Clinical Congress, ScientificForum, Boston, MA, October 2023

ASJC Scopus subject areas

General

Access to Document

10.1371/journal.pone.0313152

Cite this

Mohammadi, M., Hasjim, B. J., Balbale, S. N., Polineni, P., Huang, A. A., Paukner, M., Banea, T., Dentici, O., Vitello, D. J., Obayemi, J. E., Duarte-Rojo, A., Nadig, S. N., Vanwagner, L. B., Zhao, L., Mehrotra, S., & Ladner, D. P. (2025). Disease trajectory and competing risks of patients with cirrhosis in the US. PloS one, 20(2 February), Article e0313152. https://doi.org/10.1371/journal.pone.0313152

@article{cac3ed597d19489e845cb5ea38c45b15,

title = "Disease trajectory and competing risks of patients with cirrhosis in the US",

abstract = "Background Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting. Methods A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006–2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates. Results Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36–2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23–1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71–2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified. Conclusion Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.",

author = "Mohsen Mohammadi and Hasjim, {Bima J.} and Balbale, {Salva N.} and Praneet Polineni and Huang, {Alexander A.} and Mitchell Paukner and Therese Banea and Oriana Dentici and Vitello, {Dominic J.} and Obayemi, {Joy E.} and Andr{\'e}s Duarte-Rojo and Nadig, {Satish N.} and Vanwagner, {Lisa B.} and Lihui Zhao and Sanjay Mehrotra and Ladner, {Daniela P.}",

note = "Publisher Copyright: {\textcopyright} 2025 Mohammadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2025",

month = feb,

doi = "10.1371/journal.pone.0313152",

language = "English (US)",

volume = "20",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "2 February",

}

Mohammadi, M, Hasjim, BJ, Balbale, SN, Polineni, P, Huang, AA, Paukner, M, Banea, T, Dentici, O, Vitello, DJ, Obayemi, JE, Duarte-Rojo, A , Nadig, SN, Vanwagner, LB, Zhao, L , Mehrotra, S & Ladner, DP 2025, 'Disease trajectory and competing risks of patients with cirrhosis in the US', PloS one, vol. 20, no. 2 February, e0313152. https://doi.org/10.1371/journal.pone.0313152

TY - JOUR

T1 - Disease trajectory and competing risks of patients with cirrhosis in the US

AU - Mohammadi, Mohsen

AU - Hasjim, Bima J.

AU - Balbale, Salva N.

AU - Polineni, Praneet

AU - Huang, Alexander A.

AU - Paukner, Mitchell

AU - Banea, Therese

AU - Dentici, Oriana

AU - Vitello, Dominic J.

AU - Obayemi, Joy E.

AU - Duarte-Rojo, Andrés

AU - Nadig, Satish N.

AU - Vanwagner, Lisa B.

AU - Zhao, Lihui

AU - Mehrotra, Sanjay

AU - Ladner, Daniela P.

N1 - Publisher Copyright: © 2025 Mohammadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2025/2

Y1 - 2025/2

N2 - Background Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting. Methods A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006–2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates. Results Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36–2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23–1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71–2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified. Conclusion Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.

AB - Background Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting. Methods A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006–2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates. Results Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36–2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23–1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71–2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified. Conclusion Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.

UR - http://www.scopus.com/inward/record.url?scp=85218111901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85218111901&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0313152

DO - 10.1371/journal.pone.0313152

M3 - Article

C2 - 39951428

AN - SCOPUS:85218111901

SN - 1932-6203

VL - 20

JO - PloS one

JF - PloS one

IS - 2 February

M1 - e0313152

ER -

Disease trajectory and competing risks of patients with cirrhosis in the US

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this