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Alsaqa M, Sierra L, Marenco-Flores A, Parraga X, Barba R, Goyes D, Ozturk NB, Curry MP, Bonder A, Saberi B. Metabolic dysfunction-associated steatotic liver disease correlates with higher lower graft survival in liver transplant recipients with hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2025; 37:497-504. [PMID: 39976068 DOI: 10.1097/meg.0000000000002914] [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] [Indexed: 02/21/2025]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment. The changing landscape of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients lacks a thorough description of the outcomes of HCC based on etiology. OBJECTIVE To assess the waitlist (WL) dropout and graft survival in HCC LT candidates based on the etiology of HCC in the post-DAA era. METHODS This retrospective cohort study analyzed United Network Organ Sharing/Organ Procurement Transplant Network data from 2015 to 2022. Graft survival was analyzed using Kaplan-Meier curves, and predictors of WL dropout and graft failure were assessed using multivariate analysis. RESULTS Among LT recipients, etiologies were HCV (53.6%), alcohol-associated liver disease (ALD) (12.0%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.6%), hepatitis B virus (HBV) (5.6%), and other (12.1%). MASLD and ALD had the highest dropout rates (1-year: 20.4%, 21.7%; 3-year: 58.2%, 51.1%; P < 0.001). Dropout was linked to diabetes, low albumin, high Model of End-Stage Liver Disease, high alpha-fetoprotein, tumor number, and size. MASLD had the worst 1-, 3-, and 5-year graft survival (89.8%, 81.8%, and 74.1%) and higher failure risk than HCV (hazard ratio: 1.143, 95% CI: 1.021-1.281). Diabetes negated MASLD's impact on graft failure but worsened survival for MASLD-HCC compared with HBV and ALD, matching HCV. CONCLUSION MASLD has the highest WL dropout and post-LT graft failure among HCC LT candidates, surpassing HCV in the post-DAA era. The worst graft survival in MASLD-HCC is associated with pre-LT diabetes.
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Affiliation(s)
- Marwan Alsaqa
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Leandro Sierra
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Ana Marenco-Flores
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Ximena Parraga
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Romelia Barba
- Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Daniela Goyes
- Division of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - N Begum Ozturk
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, Michigan, USA
| | - Michael P Curry
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Behnam Saberi
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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Younossi ZM, Stepanova M, Al Shabeeb R, Eberly KE, Shah D, Nguyen V, Ong J, Henry L, Alqahtani SA. The changing epidemiology of adult liver transplantation in the United States in 2013-2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease. Hepatol Commun 2024; 8:e0352. [PMID: 38126928 PMCID: PMC10749707 DOI: 10.1097/hc9.0000000000000352] [Citation(s) in RCA: 47] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 10/04/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States. METHODS The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant. RESULTS There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes. CONCLUSIONS Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC.
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Affiliation(s)
- Zobair M. Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- The Global NASH Council, Washington, District of Columbia, USA
| | - Maria Stepanova
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- The Global NASH Council, Washington, District of Columbia, USA
| | - Reem Al Shabeeb
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Katherine E. Eberly
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Dipam Shah
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Veronica Nguyen
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Janus Ong
- The Global NASH Council, Washington, District of Columbia, USA
- Department of Internal Medicine, College of Medicine, University of the Philippines, Manila, Philippines
| | - Linda Henry
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- The Global NASH Council, Washington, District of Columbia, USA
- Center for Outcomes Research in Liver Diseases, Washington, District of Columbia, USA
| | - Saleh A. Alqahtani
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Outcomes Research in Liver Diseases, Washington, District of Columbia, USA
- Epidemiology & Scientific Computing Department, Liver Transplant Center and Biostatistics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
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Lee HA, Lee S, Lee HL, Song JE, Lee DH, Han S, Shim JH, Kim BH, Choi JY, Rhim H, Kim DY. The efficacy of treatment for hepatocellular carcinoma in elderly patients. JOURNAL OF LIVER CANCER 2023; 23:362-376. [PMID: 37705145 PMCID: PMC10565541 DOI: 10.17998/jlc.2023.08.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/22/2023] [Accepted: 08/03/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND/AIM Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. METHODS Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. RESULTS Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P<0.001). In early-stage HCC, surgery yielded significantly lower OS in elderly patients compared to non-elderly patients (median, 97.4 vs. 138.0 months; P<0.001), however, local ablation (median, 82.2 vs. 105.5 months) and transarterial therapy (median, 42.6 vs. 56.9 months) each provided comparable OS between the two groups after inverse probability of treatment weighting (IPTW) analysis (all P>0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). CONCLUSIONS Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Sangheun Lee
- Department of Internal Medicine, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Hae Lim Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Eun Song
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Sojung Han
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University, Eulji University School of Medicine, Uijeongbu, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyunchul Rhim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Cancer Center, Severance Hospital, Seoul, Korea
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Rajendran L, Choi WJ, Muaddi H, Ivanics T, Feld JJ, Claasen MPAW, Castelo M, Sapisochin G. Association of Viral Hepatitis Status and Post-hepatectomy Outcomes in the Era of Direct-Acting Antivirals. Ann Surg Oncol 2023; 30:2793-2802. [PMID: 36515750 DOI: 10.1245/s10434-022-12937-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/21/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of viral hepatitis status in post-hepatectomy outcomes has yet to be delineated. This large, multicentred contemporary study aimed to evaluate the effect of viral hepatitis status on 30-day post-hepatectomy complications in patients treated for hepatocellular carcinoma (HCC). METHODS Patients from the National Surgical Quality Improvement Program (NSQIP) database with known viral hepatitis status, who underwent hepatectomy for HCC between 2014 and 2018, were included. Patients were classified as HBV-only, HCV-only, HBV and HCV co-infection (HBV/HCV), or no viral hepatitis (NV). Multivariable models were used to assess outcomes of interest. The primary outcome was any 30-day post-hepatectomy complication. The secondary outcomes were major complications and post-hepatectomy liver failure (PHLF). Subgroup analyses were performed for cirrhotic and noncirrhotic patients. RESULTS A total of 3234 patients were included. The 30-day complication rate was 207/663 (31.2%) HBV, 356/1077 (33.1%) HCV, 29/81 (35.8%) HBV/HCV, and 534/1413 (37.8%) NV (p = 0.01). On adjusted analysis, viral hepatitis status was not associated with occurrence of any 30-day post-hepatectomy complications (ref: NV, HBV odds ratio (OR) 0.89 [95% confidence interval (CI): 0.71-1.12]; HCV OR 0.91 [95% CI: 0.75-1.10]; HBV/HCV OR 1.17 [95% CI: 0.71-1.93]). Similar results were found in cirrhotic and noncirrhotic subgroups, and for secondary outcomes: occurrence of any major complications and PHLF. CONCLUSIONS In patients with HCC managed with resection, viral hepatitis status is not associated with 30-day post-hepatectomy complications, major complications, or PHLF compared with NV. This suggests that clinical decisions and prognostication of 30-day outcomes in this population likely should not be made based on viral hepatitis status.
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Affiliation(s)
- Luckshi Rajendran
- Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Woo Jin Choi
- Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Hala Muaddi
- Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Henry Ford Hospital, Detroit, Michigan, USA
- Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Matthew Castelo
- Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
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Zhao Y, Jia Y, Qi S, Wu C, Wu J, Zhang R, Li J, Guo Z. Comparison of Postoperative Prognosis Among HBV-Related, HCV-Related, and Non-HBV Non-HCV Hepatocellular Carcinomas: A Systematic Review and Meta-analysis. HEPATITIS MONTHLY 2022; 22. [DOI: 10.5812/hepatmon-121820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 06/22/2022] [Accepted: 06/23/2022] [Indexed: 01/03/2025]
Abstract
Context: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and different hepatitis viruses might affect the prognosis of patients with HCC. Objectives: This study aimed to reveal the differences in the postoperative prognosis of patients with hepatitis B virus-related HCC (HBV-HCC), hepatitis C virus-related HCC (HCV-HCC), and non-HBV non-HCV hepatocellular carcinoma (NBNC-HCC). Methods: The databases PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for articles published until April 2022. Stata software version 12 and Review Manager version 5.4 were used to conduct the meta-analysis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was adopted in this study. Results: In the present study, 26 papers on a total of 20381 participants who met the inclusion criteria were analyzed. The 5-year overall survival in the HBV-HCC and HCV-HCC groups was lower than in the NBNC-HCC group (HBV-HCC vs. NBNC-HCC, P = 0.005; HCV-HCC vs. NBNC-HCC, P = 0.001). Patients with HBV-HCC and HCV-HCC had worse 5-year recurrence-free survival than patients with NBNC-HCC (HBV-HCC vs. NBNC-HCC, P = 0; HCV-HCC vs. NBNC-HCC, P = 0). In addition, the 5-year recurrence-free rate in the HCV-HCC group was lower than in the HBV-HCC group (P = 0). The observed association between serum alpha-fetoprotein levels and the postoperative prognosis was inconsistent in different subgroups. Conclusions: Patients with NBNC-HCC had a significantly better postoperative prognosis than those with virus-related HCC. The alpha-fetoprotein levels significantly correlated with the postoperative prognosis of patients with HCC.
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Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses 2022; 14:v14050986. [PMID: 35632728 PMCID: PMC9146458 DOI: 10.3390/v14050986] [Citation(s) in RCA: 95] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.
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