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Hirode G, Kilany M, Pi S, Kim A, Bhat M, Van Uum R, Lilly LB, Hansen BE, Feld JJ, Selzner N, Janssen HLA. Chronic Hepatitis B Patients Referred for Liver Transplantation After Nucleos(t)ide Analog Cessation. J Viral Hepat 2025; 32:e70031. [PMID: 40372086 PMCID: PMC12080295 DOI: 10.1111/jvh.70031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2025] [Revised: 04/22/2025] [Accepted: 04/30/2025] [Indexed: 05/16/2025]
Abstract
Nucleos(t)ide analogs (NAs) provide prolonged viral suppression with favourable clinical outcomes in chronic hepatitis B (CHB) patients. Characterisation of adverse hepatic events after NA cessation leading to liver transplantation (LT) is vital to the improvement of patient management and safety considerations. This is a retrospective case series of CHB patients who developed hepatic decompensation due to NA discontinuation and were referred for LT. Patients with hepatocellular carcinoma or coinfection were excluded. Of 11 CHB patients included (81.8% clinical jaundice, 63.6% ascites, 54.5% hepatic encephalopathy and 18.2% variceal bleeding), 45.5% underwent LT, 36.4% were waitlisted (1 active, 1 died, 2 delisted of whom 1 died), and 18.2% died after referral during the assessment period. Median age was 55.1 years, 81.8% were male, and 72.7% had cirrhosis at NA cessation. Reasons for NA withdrawal included nonadherence (81.8%) and physician discretion (18.2%). Median time from NA cessation to a decompensating event was 3.2 months, and from the decompensating event to referral was 16.0 days. This study shows that most patients experience decompensations soon after NA cessation and reinforces that patients should not discontinue treatment themselves. Physicians should very carefully select non-cirrhotic, adherent patients for NA withdrawal, after which close monitoring and timely retreatment are crucial.
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Affiliation(s)
- Grishma Hirode
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Mai Kilany
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Steven Pi
- Division of GastroenterologyUniversity of British ColumbiaVancouverBritish ColumbiaCanada
| | - Audrey Kim
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Mamatha Bhat
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Rafique Van Uum
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Leslie B. Lilly
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Bettina E. Hansen
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
- Department of Epidemiology and BiostatisticsErasmus MC University Medical CenterRotterdamthe Netherlands
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Nazia Selzner
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Harry L. A. Janssen
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamthe Netherlands
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Tigano S, Casolaro G, Bianchini A, Bernardi E, Laici C, Ramahi L, Vitale G, Siniscalchi A. Hemodynamic Monitoring During Liver Transplantation for Patients on Perioperative Extracorporeal Membrane Oxygenation (ECMO) Support: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:768. [PMID: 40283059 PMCID: PMC12028808 DOI: 10.3390/medicina61040768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/04/2025] [Accepted: 04/16/2025] [Indexed: 04/29/2025]
Abstract
Background and Objectives: Indications for liver transplants are increasing worldwide due to the growing number of transplants performed on patients with significant cardiovascular and respiratory risk factors. Additional support for this trend comes from the growing use of marginal organs, which is made possible by donations made after circulatory death (DCD). Liver transplantation (LT) in such high-risk patients may be challenging and may require perioperative Extracorporeal Membrane Oxygenation (ECMO). There is a lack of evidence on the best hemodynamic monitoring techniques for patients undergoing ECMO support during the perioperative period of LT. This review aims to provide a comprehensive overview of the hemodynamic monitoring standards of patients supported by ECMO before, during, and after LT. Materials and Methods: Comprehensive research was conducted through the PubMed database, and 153 articles regarding patients who needed perioperative ECMO support were found. Among these, 18 articles were finally included in our analysis as the authors specified hemodynamic monitoring techniques and data. The articles included case reports, letters to the editor, and correspondence. Results: We identified 20 cases of patients supported by ECMO as a planned preoperative strategy (9 patients), as a rescue therapy during surgery (7 patients), and as a postoperative support (4 patients). Cardiac catheterism and echocardiography (transthoracic and transesophageal) were the authors' most cited hemodynamic monitoring techniques. Conclusions: Data on hemodynamic monitoring methods used to manage patients supported by ECMO during the whole perioperative period of LT are poor and derived from descriptive low-quality studies. However, a multimodal approach that includes continuous monitoring of pulmonary pressures and echocardiography can increase diagnostic accuracy and improve the decision-making process to manage this complex patient population.
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Affiliation(s)
- Stefano Tigano
- Postoperative and Abdominal Organ Transplant Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.T.); (A.B.); (E.B.); (C.L.); (L.R.); (A.S.)
| | - Giulio Casolaro
- Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Università di Bologna, 40126 Bologna, Italy;
| | - Amedeo Bianchini
- Postoperative and Abdominal Organ Transplant Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.T.); (A.B.); (E.B.); (C.L.); (L.R.); (A.S.)
| | - Enrico Bernardi
- Postoperative and Abdominal Organ Transplant Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.T.); (A.B.); (E.B.); (C.L.); (L.R.); (A.S.)
| | - Cristiana Laici
- Postoperative and Abdominal Organ Transplant Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.T.); (A.B.); (E.B.); (C.L.); (L.R.); (A.S.)
| | - Linda Ramahi
- Postoperative and Abdominal Organ Transplant Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.T.); (A.B.); (E.B.); (C.L.); (L.R.); (A.S.)
| | - Giovanni Vitale
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Antonio Siniscalchi
- Postoperative and Abdominal Organ Transplant Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.T.); (A.B.); (E.B.); (C.L.); (L.R.); (A.S.)
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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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Fassio E, Colombato L, Gualano G, Perez S, Puga-Tejada M, Landeira G. Hepatocellular Carcinoma After HCV Eradication with Direct-Acting Antivirals: A Reappraisal Based on New Parameters to Assess the Persistence of Risk. Cancers (Basel) 2025; 17:1018. [PMID: 40149352 PMCID: PMC11940336 DOI: 10.3390/cancers17061018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/12/2025] [Accepted: 03/16/2025] [Indexed: 03/29/2025] Open
Abstract
Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk.
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Affiliation(s)
- Eduardo Fassio
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
| | - Luis Colombato
- Hospital Británico de Buenos Aires, Buenos Aires 1280, Argentina;
| | - Gisela Gualano
- Hospital Regional Dr. Ramón Carrillo, Santiago del Estero 4200, Argentina;
| | - Soledad Perez
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
| | - Miguel Puga-Tejada
- Instituto Ecuatoriano de Enfermedades Digestivas, Guayaquil 090505, Ecuador;
| | - Graciela Landeira
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
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Hassanain H, Connor AA, Brombosz EW, Patel K, Elaileh A, Basra T, Kodali S, Victor DW, Simon CJ, Cheah YL, Hobeika MJ, Mobley CM, Saharia A, Dhingra S, Schwartz M, Maqsood A, Heyne K, Kaseb AO, Vauthey JN, Gaber AO, Abdelrahim M, Ghobrial RM. Sorafenib as Adjuvant Therapy Post-Liver Transplant: A Single-center Experience. Transplant Direct 2025; 11:e1746. [PMID: 39866680 PMCID: PMC11759322 DOI: 10.1097/txd.0000000000001746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/11/2024] [Accepted: 10/31/2024] [Indexed: 01/28/2025] Open
Abstract
Background Hepatocellular carcinoma (HCC) has a rising incidence and mortality in North America. Liver transplantation (LT) with adjunctive therapies offers excellent outcomes. However, HCC recurrences are associated with high mortality. We investigate whether adjuvant systemic therapy can reduce recurrence, as shown with other malignancies. Methods Medical records of patients undergoing LT for HCC at a single center between January 2016 and December 2022 were retrospectively reviewed. Patients were stratified into 3 groups: (1) recipients of adjuvant sorafenib, (2) nonrecipients at high recurrence risk, and (3) nonrecipients at low risk by explant pathology features. The outcomes were overall survival (OS) and recurrence-free survival (RFS). Adjuvant sorafenib recipients were also propensity score matched 1:2 to nonadjuvant recipients based on recurrence risk features. Results During the study period, 273 patients with HCC underwent LT and 16 (5.9%) received adjuvant sorafenib therapy. Adjuvant sorafenib recipients were demographically similar to nonrecipients and, on explant pathology, had greater tumor burden, lymphovascular invasion, and poorer differentiation (all P < 0.001). Adverse events were observed in 12 adjuvant sorafenib recipients (75%). OS was similar among the 3 groups (P = 0.2), and adjuvant sorafenib was not associated with OS in multivariable analysis (hazard ratio, 1.31; 95% confidence interval, 0.45-3.78; P = 0.62). RFS was significantly lower in sorafenib patients (hazard ratio, 6.99; 95% confidence interval, 2.12-23.05; P = 0.001). Following propensity matching, adjuvant sorafenib use was not associated with either OS (P = 0.24) or RFS rates (P = 0.65). Conclusions In this single-center analysis, adjuvant sorafenib was not associated with OS. Recipients were observed to have shorter RFS, likely due to the increased prevalence of high-risk features, and sorafenib use was associated with high frequencies of adverse events.
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Affiliation(s)
- Hala Hassanain
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ashton A. Connor
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | | | - Khush Patel
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ahmed Elaileh
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Tamneet Basra
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Sudha Kodali
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - David W. Victor
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | | | - Yee Lee Cheah
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Mark J. Hobeika
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | | | - Ashish Saharia
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Sadhna Dhingra
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Mary Schwartz
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Anaum Maqsood
- Dr. Mary and Ron Neal Cancer Center, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Kirk Heyne
- Dr. Mary and Ron Neal Cancer Center, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Ahmed O. Kaseb
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX
| | - A. Osama Gaber
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Maen Abdelrahim
- Dr. Mary and Ron Neal Cancer Center, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - R. Mark Ghobrial
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
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Protopapas AA, Tsankof A, Papagiouvanni I, Kaiafa G, Skoura L, Savopoulos C, Goulis I. Outpatient management after hospitalisation for acute decompensation of cirrhosis: A practical guide. World J Hepatol 2024; 16:1377-1394. [PMID: 39744202 PMCID: PMC11686542 DOI: 10.4254/wjh.v16.i12.1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/24/2024] [Accepted: 11/20/2024] [Indexed: 11/29/2024] Open
Abstract
Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension. The transition from compensated to decompensated cirrhosis involves hemodynamic changes leading to multiorgan dysfunction, managed predominantly in outpatient settings with regular monitoring. The mortality risk is elevated in decompensated patients. Therefore, diligent outpatient management should focus on regular medical follow-ups, medication adjustments, patient education, addressing emergent issues and evaluation for liver transplantation. The ultimate goal is to improve quality of life, prevent disease progression, reduce complications, and assess possible recompensation. This guide provides valuable recommendations for medical experts managing decompensated cirrhotic patients post-hospitalization.
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Affiliation(s)
- Adonis A Protopapas
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece.
| | - Alexandra Tsankof
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Ioanna Papagiouvanni
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki 54642, Greece
| | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Lemonia Skoura
- Department of Microbiology, Aristotle University οf Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki 54642, Greece
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Al-Naamani KM, Omar H, Al Busafi SA, Al Shuaili HH, Al-Naamani Z, Al-Khabori M, Said EA, AlKalbani AH, Kamath BR, Emad B, Daar S, Alhajri L, AlKalbani A, AlFarsi Z, Alzuhaibi H. Real-World Experience, Effectiveness, and Safety of Direct-Acting Antivirals for the Treatment of Hepatitis C in Oman: A Cross-Sectional, Multicenter Study. J Clin Med 2024; 13:7411. [PMID: 39685869 DOI: 10.3390/jcm13237411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 11/20/2024] [Accepted: 11/30/2024] [Indexed: 12/18/2024] Open
Abstract
Background: The advent of direct-acting antiviral (DAA) therapy has revolutionized the treatment landscape of the hepatitis C virus (HCV) infection. This study aimed to provide a comprehensive research study of the real-world effectiveness and safety of DAA treatment, representing the first study conducted in the Omani population. Methods: A cross-sectional study was conducted including 375 HCV patients with different genotypes, treated using different DAA regimens, with or without ribavirin, between January 2012 and December 2020 at the Sultan Qaboos University Hospital and the medical city for military and security services, two tertiary hospitals in Muscat, Oman. The rate of sustained virologic response 12 weeks after completing the regimen (SVR-12) was analyzed as the primary outcome. Secondary outcomes included treatment safety and adverse events related to DAA therapy, as reported by patients and treating physicians. Results: A total of 375 patients were included in the study, with a mean age of 47.3 ± 15.4 years. Most were male (59.2%) and treatment-naïve (71.7%). The prevalence of liver cirrhosis was 19.7%, while 4.0% had hepatocellular carcinoma (HCC). The SVR-12 rate among treatment-naïve and treatment-experienced patients was 95.0% and 93.4%, respectively. Several parameters were associated with DAA treatment failure, including liver cirrhosis (p = 0.004) and active HCC (p = 0.009). Following SVR-12, significant improvements were observed in alanine transaminase, bilirubin, and albumin levels, Fibrosis-4 Index, and liver stiffness measurements compared to baseline (p <0.001 each). No significant adverse effects were reported. Conclusions: Based on our real-world experience, DAAs are highly effective in treating patients with HCV infection in Oman, with an excellent tolerability and safety profile.
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Affiliation(s)
- Khalid M Al-Naamani
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Heba Omar
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11652, Egypt
| | - Said A Al Busafi
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Halima H Al Shuaili
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Zakariya Al-Naamani
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Murtadha Al-Khabori
- Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Elias A Said
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Abdullah H AlKalbani
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - B R Kamath
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Bashar Emad
- Department of Medicine, Jordan University of Science and Technology, Ar-Ramtha 22110, Jordan
| | - Shahina Daar
- Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Lolo Alhajri
- Department of Nursing, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Alya AlKalbani
- Department of Nursing, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Zainab AlFarsi
- Department of Nursing, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman
| | - Haifa Alzuhaibi
- Department of Nursing, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman
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Akabane M, Imaoka Y, Esquivel CO, Kim WR, Sasaki K. The suggestion of mitigating disparity in the liver transplantation field among ABO blood type. Am J Transplant 2024; 24:2235-2245. [PMID: 38866110 DOI: 10.1016/j.ajt.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 05/07/2024] [Accepted: 06/07/2024] [Indexed: 06/14/2024]
Abstract
Medical literature highlights differences in liver transplantation (LT) waitlist experiences among ABO blood types. Type AB candidates reportedly have higher LT rates and reduced mortality. Despite liver offering guidelines, ABO disparities persist. This study examines LT access discrepancies among blood types, focusing on type AB, and seeks equitable strategies. Using the United Network for Organ Sharing database (2003-2022), 170 276 waitlist candidates were retrospectively analyzed. Dual predictive analyses (LT opportunity and survival studies) evaluated 1-year recipient pool survival, considering waitlist and post-LT survival, alongside anticipated allocation value per recipient, under 6 scenarios. Of the cohort, 97 670 patients (57.2%) underwent LT. Type AB recipients had the highest LT rate (73.7% vs 55.2% for O), shortest median waiting time (90 vs 198 days for A), and lowest waitlist mortality (12.9% vs 23.9% for O), with the lowest median model for end-stage liver disease-sodium (MELD-Na) score (20 vs 25 for A/O). The LT opportunity study revealed that reallocating type A (or A and O) donors originally for AB recipients to A recipients yielded the greatest reduction in disparities in anticipated value per recipient, from 0.19 (before modification) to 0.08. Meanwhile, the survival study showed that ABO-identical LTs reduced disparity the most (3.5% to 2.8%). Sensitivity analysis confirmed these findings were specific to the MELD-Na score < 30 population, indicating current LT allocation may favor certain blood types. Prioritizing ABO-identical LTs for MELD-Na score < 30 recipients could ensure uniform survival outcomes and mitigate disparities.
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Affiliation(s)
- Miho Akabane
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, California, USA
| | - Yuki Imaoka
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, California, USA
| | - Carlos O Esquivel
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, California, USA
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Kazunari Sasaki
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, California, USA.
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9
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Akabane M, Kwong A, Imaoka Y, Esquivel CO, Kim WR, Melcher ML, Sasaki K. Beyond 75: Graft Allocation and Organ Utility Implications in Liver Transplantation. Transplant Direct 2024; 10:e1661. [PMID: 39359941 PMCID: PMC11446594 DOI: 10.1097/txd.0000000000001661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 03/05/2024] [Accepted: 03/07/2024] [Indexed: 10/04/2024] Open
Abstract
Background The global surge in aging has intensified debates on liver transplantation (LT) for candidates aged 75 y and older, given the prevalent donor scarcity. This study examined both the survival benefits and organ utility of LT for this age group. Methods A total of 178 469 adult LT candidates from the United Network for Organ Sharing database (2003-2022) were analyzed, with 112 266 undergoing LT. Post-LT survival outcomes and waitlist dropout rates were monitored across varying age brackets. Multivariable Cox regression analysis determined prognostic indicators. The 5-y survival benefit was assessed by comparing LT recipients to waitlist candidates using hazard ratios. Organ utility was evaluated through a simulation model across various donor classifications. Results Among candidates aged 75 y and older, 343 received LT. The 90-d graft and patient survival rates for these patients were comparable with those in other age categories; however, differences emerged at 1 and 3 y. Age of 75 y or older was identified as a significant negative prognostic indicator for 3-y graft survival (hazard ratio: 1.72 [1.20-2.42], P < 0.01). Dropout rates for the 75 y and older age category were 12.0%, 24.1%, and 35.1% at 90 d, 1 y, and 3 y, respectively. The survival benefit of LT for the 75 y and older cohort was clear when comparing outcomes between LT recipients and those on waitlists. However, organ utility considerations did not favor allocating livers to this age group, regardless of donor type. Comparing 3-y patient survival between LT using donors aged 60 y and younger and older than 60 y showed no significant difference (P = 0.50) in the 75 y or older cohort. Conclusions Although LT offers survival benefits to individuals aged 75 y and older, the system may need rethinking to optimize the use of scarce donor livers, perhaps by matching older donors with older recipients.
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Affiliation(s)
- Miho Akabane
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA
| | - Yuki Imaoka
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Carlos O Esquivel
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA
| | - Marc L Melcher
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Kazunari Sasaki
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
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10
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Alnagar A, Zakeri N, Koilias K, Faulkes RE, Brown R, Cain O, Perera MTPR, Roberts KJ, Sanabria-Mateos R, Bartlett DC, Ma YT, Sivakumar S, Shetty S, Shah T, Dasari BVM. SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation. World J Transplant 2024; 14:95849. [PMID: 39295983 PMCID: PMC11317860 DOI: 10.5500/wjt.v14.i3.95849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/28/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.
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Affiliation(s)
- Amr Alnagar
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nekisa Zakeri
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Konstantinos Koilias
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rosemary E Faulkes
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rachel Brown
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Owen Cain
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - M Thamara P R Perera
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith J Roberts
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rebeca Sanabria-Mateos
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Yuk Ting Ma
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shivan Sivakumar
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shishir Shetty
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Bobby V M Dasari
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
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11
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Badwei N. Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope? World J Transplant 2024; 14:96637. [PMID: 39295978 PMCID: PMC11317853 DOI: 10.5500/wjt.v14.i3.96637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 06/08/2024] [Accepted: 06/24/2024] [Indexed: 07/31/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common liver malignancy and represents a serious cause of cancer-related mortality and morbidity. One of the favourable curative surgical therapeutic options for HCC is liver transplantation (LT) in selected patients fulfilling the known standard Milan/University of California San Francisco criteria which have shown better outcomes and longer-term survival. Despite careful adherence to the strict HCC selection criteria for LT in different transplant centres, the recurrence rate still occurs which could negatively affect HCC patients' survival. Hence HCC recurrence post-LT could predict patients' survival and prognosis, depending on the exact timing of recurrence after LT (early or late), and whether intra/extrahepatic HCC recurrence. Several factors may aid in such a complication, particularly tumour-related criteria including larger sizes, higher grades or poor tumour differentiation, microvascular invasion, and elevated serum alpha-fetoprotein. Therefore, managing such cases is challenging, different therapeutic options have been proposed, including curative surgical and ablative treatments that have shown better outcomes, compared to the palliative locoregional and systemic therapies, which may be helpful in those with unresectable tumour burden. To handle all these issues in our review.
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Affiliation(s)
- Nourhan Badwei
- Department of Tropical Medicine, Gastroenterology and Hepatology, Hepatoma Group, Ain Shams University, Cairo 11517, Egypt
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12
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Awad SM, El Batanony EH, Elmahdy SK, Allam ET, Rizk SK, Zaid AB, Taha M, Salem RH. Interleukin 6 and interleukin 17A serum levels and gene- polymorphisms in the development of early allograft rejection in living donor liver transplant recipients. Sci Rep 2024; 14:21687. [PMID: 39289412 PMCID: PMC11408691 DOI: 10.1038/s41598-024-71102-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 08/26/2024] [Indexed: 09/19/2024] Open
Abstract
The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.
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Affiliation(s)
- Samah Mohammed Awad
- Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shibin Elkom, 32511, Egypt
| | - Eman Helmy El Batanony
- Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shibin Elkom, 32511, Egypt
| | - Shaimaa K Elmahdy
- Gastroenterology and Hepatology Department, National Liver Institute, Menoufia University, Shibin Elkom, 32511, Egypt
| | - Esraa Tawfik Allam
- Departments of Clinical Pathology, National Liver Institute, Menoufia University, Shibin Elkom, 32511, Egypt
| | - Sara Kamal Rizk
- Biochemistry department, Faculty of Medicine, Menoufia University, Shibin Elkom, 32511, Egypt
| | - Ahmed B Zaid
- Departments of Clinical Pathology, National Liver Institute, Menoufia University, Shibin Elkom, 32511, Egypt.
| | - Mohammad Taha
- Hepatopancreatobiliary and Liver Transplant Surgery, National Liver Institute, Shibin Elkom, 32511, Egypt
| | - Radwa H Salem
- Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shibin Elkom, 32511, Egypt
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13
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To J, Ghosh S, Zhao X, Pasini E, Fischer S, Sapisochin G, Ghanekar A, Jaeckel E, Bhat M. Deep learning-based pathway-centric approach to characterize recurrent hepatocellular carcinoma after liver transplantation. Hum Genomics 2024; 18:58. [PMID: 38840185 PMCID: PMC11151487 DOI: 10.1186/s40246-024-00624-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 05/23/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) is offered as a cure for Hepatocellular carcinoma (HCC), however 15-20% develop recurrence post-transplant which tends to be aggressive. In this study, we examined the transcriptome profiles of patients with recurrent HCC to identify differentially expressed genes (DEGs), the involved pathways, biological functions, and potential gene signatures of recurrent HCC post-transplant using deep machine learning (ML) methodology. MATERIALS AND METHODS We analyzed the transcriptomic profiles of primary and recurrent tumor samples from 7 pairs of patients who underwent LT. Following differential gene expression analysis, we performed pathway enrichment, gene ontology (GO) analyses and protein-protein interactions (PPIs) with top 10 hub gene networks. We also predicted the landscape of infiltrating immune cells using Cibersortx. We next develop pathway and GO term-based deep learning models leveraging primary tissue gene expression data from The Cancer Genome Atlas (TCGA) to identify gene signatures in recurrent HCC. RESULTS The PI3K/Akt signaling pathway and cytokine-mediated signaling pathway were particularly activated in HCC recurrence. The recurrent tumors exhibited upregulation of an immune-escape related gene, CD274, in the top 10 hub gene analysis. Significantly higher infiltration of monocytes and lower M1 macrophages were found in recurrent HCC tumors. Our deep learning approach identified a 20-gene signature in recurrent HCC. Amongst the 20 genes, through multiple analysis, IL6 was found to be significantly associated with HCC recurrence. CONCLUSION Our deep learning approach identified PI3K/Akt signaling as potentially regulating cytokine-mediated functions and the expression of immune escape genes, leading to alterations in the pattern of immune cell infiltration. In conclusion, IL6 was identified to play an important role in HCC recurrence.
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Affiliation(s)
- Jeffrey To
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Soumita Ghosh
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Xun Zhao
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Elisa Pasini
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Sandra Fischer
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Anand Ghanekar
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada.
- Division of Gastroenterology & Hepatology, University of Toronto, Toronto, ON, Canada.
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
- Department of Medicine, University of Toronto, Toronto, ON, Canada.
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14
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Faleiro MD, Mir ZM, Azizieh Y, Hiebert SE, Livingstone SM, Walsh MJ, Gala-Lopez BL. Oncologic Outcomes of Interventions to Decrease Allograft Ischemia-Reperfusion Injury within Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review. Curr Oncol 2024; 31:2895-2906. [PMID: 38920705 PMCID: PMC11202749 DOI: 10.3390/curroncol31060221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/12/2024] [Accepted: 05/17/2024] [Indexed: 06/27/2024] Open
Abstract
Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to evaluate interventions to reduce IRI during liver transplantation for HCC and their impact on oncologic outcomes. A comprehensive literature search retrieved four retrospective studies involving 938 HCC patients, utilising interventions such as post-operative prostaglandin administration, hypothermic machine perfusion, and normothermic machine perfusion. Overall, treated patients exhibited reduced post-operative hepatocellular injury and inflammation and significantly enhanced recurrence-free survival. Despite these promising results, the impact of these interventions on overall survival remains unclear. This underscores the imperative for further prospective research to comprehensively understand the efficacy of these interventions in HCC patients undergoing transplantation. The findings highlight the potential benefits of these strategies while emphasising the need for continued investigation into their overall impact.
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Affiliation(s)
- Matheus D. Faleiro
- Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
| | - Zuhaib M. Mir
- Department of Surgery, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - Yara Azizieh
- Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | | | | | - Mark J. Walsh
- Department of Surgery, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - Boris L. Gala-Lopez
- Department of Surgery, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Beatrice Hunter Cancer Research Institute, Halifax, NS B3H 0A2, Canada
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15
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Ivanics T, Claasen MPAW, Samstein B, Emond JC, Fox AN, Pomfret E, Pomposelli J, Tabrizian P, Florman SS, Mehta N, Roberts JP, Emamaullee JA, Genyk Y, Hernandez-Alejandro R, Tomiyama K, Sasaki K, Hashimoto K, Nagai S, Abouljoud M, Olthoff KM, Hoteit MA, Heimbach J, Taner T, Liapakis AH, Mulligan DC, Sapisochin G, Halazun KJ. Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience. Ann Surg 2024; 279:104-111. [PMID: 37522174 DOI: 10.1097/sla.0000000000006049] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023]
Abstract
OBJECTIVE To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, Department of Surgery, University Health Network, Toronto, Canada
- Department of Surgery, Henry Ford Hospital, Detroit, MI
- Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, Department of Surgery, University Health Network, Toronto, Canada
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Benjamin Samstein
- Department of Surgery, Division of Liver Transplantation and Hepatobiliary Surgery, Weill Cornell Medicine, New York, NY
| | - Jean C Emond
- Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York Presbyterian Hospital, NY
| | - Alyson N Fox
- Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York Presbyterian Hospital, NY
| | - Elizabeth Pomfret
- Department of Surgery, Division of Transplant Surgery, University of Colorado School of Medicine, Aurora, CO
| | - James Pomposelli
- Department of Surgery, Division of Transplant Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Parissa Tabrizian
- Recanati/Miller Transplantation Institute, Division of Abdominal Transplantation, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Sander S Florman
- Recanati/Miller Transplantation Institute, Division of Abdominal Transplantation, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - John P Roberts
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | | | - Yuri Genyk
- Department of Surgery, University of Southern California, Los Angeles, CA
| | | | - Koji Tomiyama
- Department of Surgery, Division of Transplantation/Hepatobiliary Surgery, University of Rochester, NY
| | - Kazunari Sasaki
- Department of Surgery-Abdominal Transplantation, Stanford Hospital and Clinics, Palo Alto, CA
| | - Koji Hashimoto
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Henry Ford Hospital, Detroit
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Henry Ford Hospital, Detroit
| | - Kim M Olthoff
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Maarouf A Hoteit
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Julie Heimbach
- Division of Transplantation Surgery, Department of Surgery, Mayo Clinic, Rochester, MN
| | - Timucin Taner
- Division of Transplantation Surgery, Department of Surgery, Mayo Clinic, Rochester, MN
| | | | | | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, Department of Surgery, University Health Network, Toronto, Canada
| | - Karim J Halazun
- NYU Langone Transplant Institute, NYU Langone Health, New York, NY
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16
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Giannini EG. Proper assessment and prognostication of patients with hepatocellular carcinoma. Clin Liver Dis (Hoboken) 2024; 23:e0129. [PMID: 38455237 PMCID: PMC10919536 DOI: 10.1097/cld.0000000000000129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 01/09/2024] [Indexed: 03/09/2024] Open
Affiliation(s)
- Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Department of Internal Medicine, Digestive Diseases Section, Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA
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17
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ZHANG LINGLI, LI YAN, MAO JINGXIN. Research progress on natural products against hepatocellular carcinoma. BIOCELL 2024; 48:905-922. [DOI: 10.32604/biocell.2024.050396] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/24/2024] [Indexed: 11/26/2024]
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18
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Mazur RD, Cron DC, Chang DC, Yeh H, Dageforde LAD. Impact of Median MELD at Transplant Minus 3 National Policy on Quality of Transplanted Livers for Patients With and Without Hepatocellular Carcinoma. Transplantation 2024; 108:204-214. [PMID: 37189232 PMCID: PMC10651798 DOI: 10.1097/tp.0000000000004621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) have been overprioritized in the deceased donor liver allocation system. The United Network for Organ Sharing adopted a policy in May 2019 that limited HCC exception points to the median Model for End-Stage Liver Disease at transplant in the listing region minus 3. We hypothesized this policy change would increase the likelihood to transplant marginal quality livers into HCC patients. METHODS This was a retrospective cohort study of a national transplant registry, including adult deceased donor liver transplant recipients with and without HCC from May 18, 2017, to May 18, 2019 (prepolicy) to May 19, 2019, to March 1, 2021 (postpolicy). Transplanted livers were considered of marginal quality if they met ≥1 of the following: (1) donation after circulatory death, (2) donor age ≥70, (3) macrosteatosis ≥30% and (4) donor risk index ≥95th percentile. We compared characteristics across policy periods and by HCC status. RESULTS A total of 23 164 patients were included (11 339 prepolicy and 11 825 postpolicy), 22.7% of whom received HCC exception points (prepolicy versus postpolicy: 26.1% versus 19.4%; P = 0.03). The percentage of transplanted donor livers meeting marginal quality criteria decreased for non-HCC (17.3% versus 16.0%; P < 0.001) but increased for HCC (17.7% versus 19.4%; P < 0.001) prepolicy versus postpolicy. After adjusting for recipient characteristics, HCC recipients had 28% higher odds of being transplanted with marginal quality liver independent of policy period (odds ratio: 1.28; confidence interval, 1.09-1.50; P < 0.01). CONCLUSIONS The median Model for End-Stage Liver Disease at transplant in the listing region minus 3 policy limited exception points and decreased the quality of livers received by HCC patients.
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Affiliation(s)
| | - David C Cron
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - David C Chang
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Heidi Yeh
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Leigh Anne D Dageforde
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA
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19
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Wang K, Gao F, Dong S, Ding J, Dong L, Shao C, Wang Z, Qiu X, Wei X, Wang Z, Yang J, Xia Q, Zheng S, Xu X. A novel nomogram for prognosis stratification in salvage liver transplantation: a national-wide study with propensity score matching analysis in China. Hepatobiliary Surg Nutr 2023; 12:854-867. [PMID: 38115922 PMCID: PMC10727818 DOI: 10.21037/hbsn-22-304] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 12/21/2022] [Indexed: 12/21/2023]
Abstract
Background Salvage liver transplantation (SLT) has been reported to be an efficient treatment option for patients with recurrent hepatocellular carcinoma (HCC) after liver resection (LR). However, for recipients who underwent liver transplantation (LT) due to recurrent HCC after LR in China, the selection criteria are not well established. Methods In this study, data from the China Liver Transplant Registry (CLTR) of 4,244 LT performed from January 2015 to December 2019 were examined, including 3,498 primary liver transplantation (PLT) and 746 SLT recipients. Propensity score matching (PSM) analysis was used to minimize between-group imbalances. The overall survival (OS) and disease-free survival (DFS) between PLT and SLT in recipients fulfilling the Milan or Hangzhou criteria were compared based on the multivariate analysis, nomograms were plotted to further classify the SLT group into low- and high-risk groups. Results In this study, the 1-, 3- and 5-year OS and DFS of SLT recipients fulfilling Milan criteria (OS, P=0.01; DFS, P<0.001) or Hangzhou criteria (OS, P=0.03; DFS, P=0.003) were significantly reduced when compared to that of PLT group after PSM analysis. Independent risk factors, including preoperative transarterial chemoembolization (TACE), alpha fetoprotein (AFP) level, tumor maximum size and tumor total diameter were selected to draw a prognostic nomogram. The low-risk SLT recipients (1-year, 95.34%; 3-year, 84.26%; 5-year, 77.20%) showed a comparable OS with PLT recipients fulfilling Hangzhou criteria (P=0.107). Conclusions An optimal nomogram model for prognosis stratification and clinical decision guidance of SLT was established. The low-risk SLT recipients based on the nomograms showed comparable survival with those fulfilling Hangzhou criteria in PLT group.
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Affiliation(s)
- Kai Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Fengqiang Gao
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Siyi Dong
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China
| | - Jialu Ding
- Graduate School, Nanjing University of Chinese Medicine, Nanjing, China
| | - Libin Dong
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Chuxiao Shao
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Zhoucheng Wang
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Xun Qiu
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Zhengxin Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiayin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Qiang Xia
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shusen Zheng
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Shulan Hospital of Hangzhou, Hangzhou, China
| | - Xiao Xu
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China
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20
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Nasser A, Smith V, Campbell N, Rivers-Bowerman MD, Stueck AE, Costa AF, Arseneau R, Westhaver L, Gala-Lopez BL. Is hepatocellular carcinoma viability important when using intraoperative blood salvage during liver transplantation? INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2023; 12:145-151. [DOI: 10.18528/ijgii230020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/09/2023] [Accepted: 06/16/2023] [Indexed: 01/03/2025] Open
Affiliation(s)
- Ahmed Nasser
- Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Victoria Smith
- Department of Surgery, Dalhousie University, Halifax, NS, Canada
| | - Niamh Campbell
- Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| | | | | | - Andreu Francesc Costa
- Department of Radiology, Dalhousie University, Halifax, NS, Canada
- Department of Microbiology & Immunology and Pathology, Beatrice Hunter Cancer Research Institute, QEII Health Science Centre, Dalhousie University, Halifax, NS, Canada
| | - Riley Arseneau
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
| | - Lauren Westhaver
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
| | - Boris Luis Gala-Lopez
- Department of Surgery, Dalhousie University, Halifax, NS, Canada
- Department of Microbiology & Immunology and Pathology, Beatrice Hunter Cancer Research Institute, QEII Health Science Centre, Dalhousie University, Halifax, NS, Canada
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21
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Abdelmalak J, Tan N, Con D, Eslick G, Majeed A, Kemp W, Roberts SK. The Effect of Aspirin Use on Incident Hepatocellular Carcinoma-An Updated Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:3518. [PMID: 37444628 PMCID: PMC10341252 DOI: 10.3390/cancers15133518] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/02/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
An increasing number of observational studies have described an association between aspirin use and a reduced risk of incident hepatocellular carcinoma. We performed this meta-analysis to provide a comprehensive and updated aggregate assessment of the effect of aspirin on HCC incidence. Two independent authors performed a systematic search of the literature, utilising the Medline, Embase, Scopus, and PubMed databases. A total of 16 studies (12 cohort studies, and 4 case-control studies) were selected for inclusion, with a large number of studies excluded, due to an overlapping study population. The pooled analysis of cohort studies involving a total population of approximately 2.5 million subjects, 822,680 aspirin users, and 20,626 HCC cases demonstrated a 30% reduced risk of HCC associated with aspirin use (adjusted HR 0.70, 95%CI 0.60-0.81). There was a similar but non-significant association observed across the case-control studies (adjusted OR 0.60, 95%CI 0.32-1.15, p = 0.13), which involved a total of 1961 HCC cases. In a subgroup meta-analysis of patients with cirrhosis, the relationship between aspirin use and incident HCC diminished to non-significance (adjusted HR 0.96, 95%CI 0.84-1.09). Aspirin use was associated with a statistically significant increase in bleeding events when all relevant studies were pooled together (adjusted HR 1.11, 95%CI 1.02-1.22). Prospectively collected data should be sought, to define the optimal patient group in which aspirin is safe and effective for the chemoprophylaxis of HCC.
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Affiliation(s)
- Jonathan Abdelmalak
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - Natassia Tan
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - Danny Con
- Department of Gastroenterology, Austin Health, Heidelberg, VIC 3084, Australia;
| | - Guy Eslick
- Clinical Links Using Evidence-Based Data (CLUED) Pty. Ltd., Sydney, NSW 2060, Australia;
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - Stuart K. Roberts
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
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22
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Durkin C, Schaubel DE, Xu Y, Mahmud N, Kaplan DE, Abt PL, Bittermann T. Induction Immunosuppression Does Not Worsen Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma. Transplantation 2023; 107:1524-1534. [PMID: 36695564 PMCID: PMC11972139 DOI: 10.1097/tp.0000000000004487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated. RESULTS Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [ P < 0.001]; HR 0.64 in the explant model [ P = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P = 0.019; versus no induction plus 3-drug therapy). CONCLUSIONS In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI.
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Affiliation(s)
- Claire Durkin
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Douglas E. Schaubel
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Yuwen Xu
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
- Section of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Section of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Peter L. Abt
- Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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23
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Bixler D, Roberts H, Panagiotakopoulos L, Nelson NP, Spradling PR, Teshale EH. Progress and Unfinished Business: Hepatitis B in the United States, 1980-2019. Public Health Rep 2023:333549231175548. [PMID: 37300309 DOI: 10.1177/00333549231175548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023] Open
Abstract
During 1990-2019, universal infant and childhood vaccination for hepatitis B resulted in a 99% decline in reported cases of acute hepatitis B among children, adolescents, and young adults aged <19 years in the United States; however, during 2010-2019, cases of acute hepatitis B plateaued or increased among adults aged ≥40 years. We conducted a topical review of surveillance strategies that will be critical to support the elimination of hepatitis B as a public health threat in the United States. In 2019, notifiable disease surveillance for acute hepatitis B showed continued transmission, especially among people who inject drugs and people with multiple sexual partners; rates were highest among people who were aged 30-59 years, non-Hispanic White, and living in rural areas. In contrast, newly reported cases of chronic hepatitis B (CHB) were highest among people who were aged 30-49 years, Asian or Pacific Islander, and living in urban areas. The National Health and Nutrition Examination Survey documented the highest CHB prevalence among non-US-born, non-Hispanic Asian people during 2013-2018; only one-third of people with CHB were aware of their infection. In the context of universal adult vaccination (2022) and screening (2023) recommendations for hepatitis B, better data are needed to support programmatic strategies to improve (1) vaccination rates among people with behaviors that put them at risk for transmission and (2) screening and linkage to care among non-US-born people. Surveillance for hepatitis B needs to be strengthened throughout the health care and public health systems.
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Affiliation(s)
- Danae Bixler
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Henry Roberts
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Lakshmi Panagiotakopoulos
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Noele P Nelson
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Philip R Spradling
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Eyasu H Teshale
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
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24
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Zhou J, Yang D. Prognostic Significance of Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:821-831. [PMID: 37288141 PMCID: PMC10243610 DOI: 10.2147/jhc.s411521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 05/24/2023] [Indexed: 06/09/2023] Open
Abstract
Purpose HALP score consisting of hemoglobin content, albumin content, lymphocyte count, and platelet count can comprehensively evaluate the inflammatory response and nutritional status. Many researchers have indicated that the HALP score is an effective predictor of the overall prognosis of various tumors. However, there is no relevant research to suggest whether the HALP score can predict the prognosis of patients with hepatocellular carcinoma (HCC). Patients and Methods We retrospectively analyzed 273 HCC patients who underwent surgical resection. Hemoglobin content, albumin content, lymphocyte count, and platelet count in peripheral blood were measured for each patient. The relationship between the HALP score and overall survival (OS) was investigated. Results With a mean of 56.69 ± 1.25 months follow-up, the 1-, 3-, and 5-year OS was 98.9%, 76.9%, and 55.3% for all patients, respectively. HALP scores (HR=1.708, 95% CI=1.192-2.448, P=0.004) were significant independent risk factors of OS. The 1-, 3-, and 5-year OS were 99.3%, 84.3%, and 63.4% for patients with high HALP scores; and 98.6%, 69.8%, and 47.5% for patients with low HALP scores, respectively (P=0.018). In TNM I-II stage patients, compared with high HALP scores, low HALP scores have worse OS (P=0.039). In AFP positive patients, compared with high HALP scores, low HALP scores have worse OS (P=0.042). Conclusion Our research showed the preoperative HALP score is an independent predictive factor of overall prognosis, and a low HALP score indicates a worse prognosis in HCC patients who underwent surgical resection.
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Affiliation(s)
- Jing Zhou
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Daofeng Yang
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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25
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Zhang SS, Zhang JF, Wang JQ, Tang J, Wu ZL, Huang J, Xue J. Liver Transplantation Outcomes of HBV-, HCV-, and Alcohol-induced Hepatocellular Carcinoma in the United States: Analysis of National Inpatient Samples. Curr Med Sci 2023:10.1007/s11596-023-2718-5. [PMID: 37115395 DOI: 10.1007/s11596-023-2718-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 02/09/2023] [Indexed: 04/29/2023]
Abstract
OBJECTIVE Liver transplantation is a current treatment option for hepatocellular carcinoma (HCC). The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation, including locoregional recurrence, distant metastasis, and in-hospital mortality, in HCC patients with concurrent hepatitis B infection, hepatitis C infection, or alcoholic cirrhosis. METHODS This retrospective cohort study included HCC patients (n=2391) from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection, co-infection with hepatitis B and C, or alcoholic cirrhosis of the liver between 2005 and 2014. Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models. RESULTS Liver cirrhosis was due to alcohol in 10.5% of patients, hepatitis B in 6.6%, hepatitis C in 10.8%, and combined hepatitis B and C infection in 24.3%. Distant metastasis was found in 16.7% of patients infected with hepatitis B and 9% of hepatitis C patients. Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease. CONCLUSION After liver transplantation, patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis. Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.
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Affiliation(s)
- Si-Si Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jin-Feng Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jing-Qiong Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jing Tang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zi-Long Wu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jing Huang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Jun Xue
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Kramer J, Singh S, Janardhan S. PRO: Is liver organ allocation with MMaT-3 appropriate prioritization for patients with liver cancer? Clin Liver Dis (Hoboken) 2023; 21:76-78. [PMID: 37095776 PMCID: PMC10121439 DOI: 10.1097/cld.0000000000000023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 09/08/2022] [Indexed: 04/26/2023] Open
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Shah RH, Chyou D, Goldberg DS. Impact of major hepatocellular carcinoma policy changes on liver transplantation for hepatocellular carcinoma in the United States. Liver Transpl 2022; 28:1857-1864. [PMID: 35585774 DOI: 10.1002/lt.26509] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 04/26/2022] [Accepted: 05/12/2022] [Indexed: 01/13/2023]
Abstract
Since its inception in 2002, Model for End-Stage Liver Disease (MELD)-based allocation has undergone a series of revisions, especially with respect to exception points. Hepatocellular carcinoma (HCC) is the most common indication for MELD exceptions, and as a result of higher transplant proportions and lower waitlist mortality, a series of policy changes have been implemented to deprioritize HCC transplants. We examined the impact of HCC exception policy changes on transplant and waitlist mortality rates. We evaluated Organ Procurement and Transplantation Network/United Network for Organ Sharing data on adult patients from January 1, 2005, to June 4, 2021, focusing on waitlist mortality and deceased donor liver transplantation (DDLT) proportions. The data were divided into four policy eras: (1) MELD 22 points at waitlisting with an increase in points every 3 months (i.e., elevator) (January 2005-October 2015), (2) delay and cap at MELD 34 points (October 2015-May 2019), (3) delay and fixed exceptions based on donor service area (DSA) median MELD at transplantation minus three (MMaT-3; May 2019-February 2020), and (4) delay and fixed exceptions based on the MMaT-3 of centers within 250 nautical miles (i.e., acuity circles; February 2020-June 2021). We evaluated (a) changes in the proportions of DDLTs for patients with HCC exceptions within each era nationally and by DSA and (b) waitlist mortality in the three recent policy eras, focusing on mortality in the 6 months after the 6-month delay period. The percentage of adult DDLT with HCC exceptions decreased through the four eras: 22.9% (n = 14,049), 17.9% (n = 4598), 14.3% (n = 851), and 12.4% (n = 1425), respectively. Of the 51 DSAs analyzed, the annual percent change in DDLTs for patients with HCC exceptions was negative (i.e., decreased) in 47 (92.2%). Waitlist mortality remained stable. All HCC policy implementations led to a decrease in the percentage of transplants for HCC without an increase in waitlist mortality. The impact is not uniform across geographic areas.
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Affiliation(s)
- Rahil H Shah
- Department of Internal Medicine, Jackson Memorial Hospital/University of Miami, Miami, Florida, USA
| | - Darius Chyou
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
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28
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Plaz Torres MC, Jaffe A, Perry R, Marabotto E, Strazzabosco M, Giannini EG. Diabetes medications and risk of HCC. Hepatology 2022; 76:1880-1897. [PMID: 35239194 PMCID: PMC9790535 DOI: 10.1002/hep.32439] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 02/06/2023]
Abstract
Type 2 diabetes mellitus is a recognized risk factor for HCC in patients with liver disease, independent from the etiology of their liver disease. Hence, prevention and treatment of type 2 diabetes mellitus and its underlying cause, insulin resistance, should be considered a treatment target for patients with liver disease. The drug armamentarium for diabetes is wide and consists of agents with insulin-sensitizing activity, agents that stimulate insulin secretion, insulin itself, and agents that reduce gastrointestinal and urinary glucose absorption. From an endocrinology perspective, the main goal of treatment is the achievement of euglycemia; however, in patients at risk of, or with known underlying liver disease, the choice of diabetic medication as it relates to potential hepatic carcinogenesis remains complex and should be carefully considered. In the last decade, increasing evidence has suggested that metformin may reduce the risk of HCC, whereas evidence for other classes of diabetic medications, particularly some of the newer agents including the sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, is fewer and often inconsistent. In this review, we aim to summarize the current evidence on the potential effects of the most widely used diabetic agents on liver cancer tumorigenesis.
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Affiliation(s)
- Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal MedicineIRCCS—Ospedale Policlinico San Martino, University of GenoaGenoaItaly
| | - Ariel Jaffe
- Liver CenterDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
| | - Rachel Perry
- Liver CenterDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
- Section of EndocrinologyDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
- Department of Cellular and Molecular PhysiologyYale University School of MedicineNew HavenConnecticutUSA
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal MedicineIRCCS—Ospedale Policlinico San Martino, University of GenoaGenoaItaly
| | - Mario Strazzabosco
- Liver CenterDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal MedicineIRCCS—Ospedale Policlinico San Martino, University of GenoaGenoaItaly
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Aghemo A, Lai Q. Waiting list trends for liver transplantation in Italy: A snapshot from the future. Dig Liver Dis 2022; 54:1662-1663. [PMID: 36241534 DOI: 10.1016/j.dld.2022.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022]
Affiliation(s)
- Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, Italy.
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Saghafian Larijani R, Shabani Ravari N, Goodarzi N, Akhlaghpour S, Saghafian Larijani S, Rouini MR, Dinarvand R. Current status of transarterial chemoembolization (TACE) agents in hepatocellular carcinoma treatment. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Sposito C, Citterio D, Virdis M, Battiston C, Droz Dit Busset M, Flores M, Mazzaferro V. Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma. World J Gastroenterol 2022; 28:4929-4942. [PMID: 36160651 PMCID: PMC9494935 DOI: 10.3748/wjg.v28.i34.4929] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/05/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Matteo Virdis
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Carlo Battiston
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
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Au KP, Fung JYY, Dai WC, Chan ACY, Lo CM, Chok KSH. Impact of Tumour Biology on Outcomes of Radical Therapy for Hepatocellular Carcinoma Oligo-Recurrence after Liver Transplantation. J Clin Med 2022; 11:4389. [PMID: 35956006 PMCID: PMC9368948 DOI: 10.3390/jcm11154389] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/20/2022] [Accepted: 07/24/2022] [Indexed: 02/05/2023] Open
Abstract
It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy. We conducted a retrospective study on 144 patients with post-transplant HCC recurrence. Early recurrence within one year after transplant (HR 2.53, 95% CI 1.65−3.88, p < 0.001), liver recurrence (HR 1.74, 95% CI 1.12−2.68, p = 0.01) and AFP > 200 ng/mL upon recurrence (HR 1.62, 95% CI 1.04−2.52, p = 0.03) predicted mortality following recurrence. In patients with early recurrence and liver recurrence, radical treatment was associated with improved post-recurrence survival (early recurrence: median 18.2 ± 1.5 vs. 9.2 ± 1.5 months, p < 0.001; liver recurrence: median 28.0 ± 4.5 vs. 11.6 ± 2.0, p < 0.001). In patients with AFP > 200 ng/mL, improvement in survival did not reach statistical significance (median 18.2 ± 6.5 vs. 8.8 ± 2.2 months, p = 0.13). Survival benefits associated with radical therapy were reduced in early recurrence (13.6 vs. 9.0 months) and recurrence with high AFP (15.4 vs. 9.3 months) but were similar among patients with and without liver recurrence (16.9 vs. 16.4 months). They were also diminished in patients with multiple biological risk factors (0 risk factor: 29.0 months; 1 risk factor: 19.7 months; 2−3 risk factors: 3.4 months): The survival benefit following radical therapy was superior in patients with favourable biological recurrence but was also observed in patients with poor tumour biology. Treatment decisions should be individualised considering the oncological benefits, quality of life gain and procedural morbidity.
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Affiliation(s)
- Kin-Pan Au
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (K.-P.A.); (W.-C.D.); (A.C.-Y.C.); (C.-M.L.)
| | | | - Wing-Chiu Dai
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (K.-P.A.); (W.-C.D.); (A.C.-Y.C.); (C.-M.L.)
| | - Albert Chi-Yan Chan
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (K.-P.A.); (W.-C.D.); (A.C.-Y.C.); (C.-M.L.)
| | - Chung-Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (K.-P.A.); (W.-C.D.); (A.C.-Y.C.); (C.-M.L.)
| | - Kenneth Siu-Ho Chok
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (K.-P.A.); (W.-C.D.); (A.C.-Y.C.); (C.-M.L.)
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MELD-GRAIL and MELD-GRAIL-Na Are Not Superior to MELD or MELD-Na in Predicting Liver Transplant Waiting List Mortality at a Single-center Level. Transplant Direct 2022; 8:e1346. [PMID: 35706607 PMCID: PMC9191558 DOI: 10.1097/txd.0000000000001346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/10/2022] [Indexed: 11/27/2022] Open
Abstract
Controversy exists regarding the best predictive model of liver transplant waiting list (WL) mortality. Models for end-stage liver disease–glomerular filtration rate assessment in liver disease (MELD-GRAIL) and MELD-GRAIL-Na were recently described to provide better prognostication, particularly in females. We evaluated the performance of these scores compared to MELD and MELD-Na.
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Petrara MR, Shalaby S, Ruffoni E, Taborelli M, Carmona F, Giunco S, Del Bianco P, Piselli P, Serraino D, Cillo U, Dolcetti R, Burra P, De Rossi A. Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients. Front Oncol 2022; 12:899170. [PMID: 35769714 PMCID: PMC9235349 DOI: 10.3389/fonc.2022.899170] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/16/2022] [Indexed: 11/22/2022] Open
Abstract
Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.
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Affiliation(s)
- Maria Raffaella Petrara
- Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Elena Ruffoni
- Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Martina Taborelli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Francesco Carmona
- Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Silvia Giunco
- Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Paola Del Bianco
- Clinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Pierluca Piselli
- Clinical Epidemiology Unit, Istituto Nazionale per le Malattie Infettive (INMI) “L. Spallanzani” IRCCS, Rome, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Riccardo Dolcetti
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
- Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Anita De Rossi
- Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
- *Correspondence: Anita De Rossi,
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Bezinover D, Geyer NR, Dahmus J, Chinchilli VM, Stine JG. A decline in functional status while awaiting liver transplantation is predictive of increased post-transplantation mortality. HPB (Oxford) 2022; 24:825-832. [PMID: 34772623 PMCID: PMC10691403 DOI: 10.1016/j.hpb.2021.10.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 08/27/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Functional status (FS) is dynamic and changes over time. We examined how changes in FS while awaiting liver transplantation influence post-transplant outcomes. METHODS Data on adult liver transplants performed in the United States during the MELD era were obtained through September 2020. Patient and graft survival were compared between groups with no change or improved FS, and those with worsening FS. RESULTS Of the 90,210 transplant recipients included in the analysis, 39,193 (43%) had worsening FS, which was associated with longer waiting-list time (187 vs. 329 days, p < 0.001) and worse patient survival after liver transplant (1858 vs. 1727 days, p < 0.001). A consistent and dose-dependent relationship was observed for each 10-point decrease in Karnofsky Performance Score and post-transplant survival. Multivariable regression analysis confirmed that a decline in FS was associated with worse patient survival (HR 1.15, p < 0.001). Similar findings were observed for graft survival. CONCLUSION A decline in FS on the waiting-list is associated with significantly greater post-liver transplant mortality in recipients. These results should be taken into consideration when allocating organs and determining transplant candidacy. Strategies to optimize FS prior to transplantation should be prioritized as even subtle decreases in FS are associated with inferior post-transplantation outcomes.
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Affiliation(s)
- Dmitri Bezinover
- Division of Transplant Anesthesia, Department of Anesthesia and Perioperative Medicine, 500 University Drive, Hershey, PA, 17033, USA; Liver Center, The Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA
| | - Nathaniel R Geyer
- Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Jessica Dahmus
- Division of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA
| | - Vernon M Chinchilli
- Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Jonathan G Stine
- Liver Center, The Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA; Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA, 17033, USA; Division of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA; Cancer Institute, The Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
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Shaikh A, Goli K, Rich NE, Benhammou JN, Khaderi S, Hernaez R, Agopian VG, Vierling JM, Kim D, Ahmed A, Goss JA, Rana A, Kanwal F, Cholankeril G. Early Impact of MMaT-3 Policy on Liver Transplant Waitlist Outcomes for Hepatocellular Carcinoma. Transplant Direct 2022; 8:e1313. [PMID: 35434283 PMCID: PMC9005245 DOI: 10.1097/txd.0000000000001313] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 02/09/2022] [Accepted: 02/11/2022] [Indexed: 12/24/2022] Open
Abstract
UNLABELLED To reduce the disparity in access to liver transplant (LT), United Network for Organ Sharing implemented an exception policy in May 2019, which capped hepatocellular carcinoma (HCC) exception score to the median Model for End-Stage Liver Disease (MELD) at transplant within the donor service area minus 3 points (MMaT-3) after the 6-mo wait period. We aimed to evaluate how this policy affected HCC waitlist outcomes. METHODS Using United Network for Organ Sharing data, we analyzed waitlist outcomes in HCC patients at the time they received exception points from in the pre-MMaT era (August 15, 2017, to November 15, 2018) and MMaT era (June 1, 2019, to August 30, 2020). Comparisons were made within the HCC group and HCC versus non-HCC (at time of listing) groups in the pre-MMaT and MMaT eras and regions were grouped as low, medium, and high MELD based on MMaT. RESULTS HCC group: LT probability within HCC patients decreased by 20% (subhazard ratio [sHR], 0.78; 95% confidence interval [CI], 0.74-0.85) between the eras and decreased by 41% in low MELD regions (sHR, 0.59; 95% CI, 0.52-0.66). Waitlist dropout was unchanged. Matched HCC versus non-HCC groups: HCC patients had 80% higher LT probability (sHR, 1.84; 95% CI, 1.71-1.99) than non-HCC patients in the pre-MMaT era; which decreased to a 14% higher LT probability in MMaT era. In low and medium regions, HCC patients had over twofold higher LT probability in the pre-MMaT era, which decreased to a ~20% higher probability (sHR, 1.14; 95% CI, 1.06-1.23) in the MMaT era. After implementation of the acuity circle policy, HCC patients had lower LT probability (sHR, 0.84; 95% CI, 0.74-0.94) than non-HCC patients. CONCLUSIONS The geographic disparity between HCC and non-HCC patients has improved with the MMaT-3 policy. Despite lower LT probability for HCC patients, waitlist dropout was not adversely impacted.
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Affiliation(s)
- Anjiya Shaikh
- Department of Medicine, University of Connecticut School of Medicine, Farmington, CT
| | - Karthik Goli
- Department of Student Affairs, Baylor College of Medicine, Houston, TX
| | - Nicole E. Rich
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX
| | - Jihane N. Benhammou
- Pfleger Liver Institute, The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles, Los Angeles, CA
| | - Saira Khaderi
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Ruben Hernaez
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Vatche G. Agopian
- Pfleger Liver Institute, The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles, Los Angeles, CA
| | - John M. Vierling
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
| | - John A. Goss
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
| | - Abbas Rana
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
| | - Fasiha Kanwal
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - George Cholankeril
- Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX
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Losurdo G, Gravina AG, Maroni L, Gabrieletto EM, Ianiro G, Ferrarese A. Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective. Dig Liver Dis 2022; 54:583-597. [PMID: 34509394 DOI: 10.1016/j.dld.2021.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 02/08/2023]
Abstract
Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.
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Affiliation(s)
- Giuseppe Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari; PhD Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari.
| | - Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luca Maroni
- Department of Gastroenterology, Marche Polytechnic University, Ancona, Italy
| | | | - Gianluca Ianiro
- Digestive Disease Center, Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Alberto Ferrarese
- Gastroenterology and Hepatology, Azienda Ospedaliera Universitaria Integrata, Ospedale Borgo Trento, Verona, Italy
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Reddy T, Esmail A, Chang JC, Ghobrial RM, Abdelrahim M. Utility of Cell-Free DNA Detection in Transplant Oncology. Cancers (Basel) 2022; 14:cancers14030743. [PMID: 35159010 PMCID: PMC8833373 DOI: 10.3390/cancers14030743] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/20/2022] [Accepted: 01/29/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Transplant oncology is an emerging field in cancer treatment that applies transplant medicine, surgery, and oncology to improve cancer patient survival and quality of life. This review aims to provide a comprehensive overview of the history and emergence of cfDNA technology, its applications to specifically monitor tumor burden at pre-and post-liver transplant stages, and evaluate transplant rejection. The use of ctDNA to evaluate transplant rejection has been extensively studied in non-hepatocellular carcinoma (HCC) diseases. Emerging studies have also investigated the use of ctDNA detection in evaluating HCC tumor burden pre-and post-surgery as well as transplant rejection. However, extensive studies still need to be conducted to evaluate the role of ctDNA detection in the medical management of transplant oncology patients. Abstract Transplant oncology is an emerging field in cancer treatment that applies transplant medicine, surgery, and oncology to improve cancer patient survival and quality of life. A critical concept that must be addressed to ensure the successful application of transplant oncology to patient care is efficient monitoring of tumor burden pre-and post-transplant and transplant rejection. Cell-free DNA (cfDNA) detection has emerged as a vital tool in revolutionizing the management of cancer patients who undergo organ transplantation. The advances in cfDNA technology have provided options to perform a pre-transplant evaluation of minimal residual disease (MRD) and post-transplant evaluation of cancer recurrence and transplant rejection. This review aims to provide a comprehensive overview of the history and emergence of cfDNA technology, its applications to specifically monitor tumor burden at pre-and post-transplant stages, and evaluate transplant rejection.
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Affiliation(s)
- Tejaswini Reddy
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (T.R.); (A.E.)
- Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA
- Houston Methodist Research Institute, Houston, TX 77030, USA;
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (T.R.); (A.E.)
- Houston Methodist Research Institute, Houston, TX 77030, USA;
| | - Jenny C. Chang
- Houston Methodist Research Institute, Houston, TX 77030, USA;
- Section of Breast, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA;
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr Center for Transplantation, Houston, TX 77030, USA
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (T.R.); (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA;
- Cockrell Center of Advanced Therapeutics Phase I program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Correspondence:
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Pan L, Feng F, Wu J, Li L, Xu H, Yang L, Xu K, Wang C. Diosmetin inhibits cell growth and proliferation by regulating the cell cycle and lipid metabolism pathway in hepatocellular carcinoma. Food Funct 2021; 12:12036-12046. [PMID: 34755740 DOI: 10.1039/d1fo02111g] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Diosmetin (DSM), a newly discovered natural flavonoid, found in citrus plants and olive leaves, has been reported to inhibit the progression of cancer when used as a food supplement. This study aimed to investigate DSM's anti-hepatocellular carcinoma (HCC) properties and possible molecular mechanisms. Hep3B and HCCLM3 cells were selected to evaluate the anti-HCC properties of DSM in vitro. RNA sequencing (RNA-seq) was used to identify the possible molecular targets and pathways. Gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of DSM treatment on the primary metabolites of HCCLM3 cells. Tumor xenograft was performed in nude mice to examine the anti-HCC properties of DSM in vivo. The results showed that DSM inhibited the proliferation and migration of HCC cells in vitro in a dose-dependent manner. RNA-seq identified 4459 differentially expressed genes (DEGs) that were highly enriched in the cell cycle pathway. In addition, DSM regulated cell growth by arresting the cell cycle in the G1 phase by decreasing the expression of BCL2, CDK1, and CCND1. Furthermore, metabolomics analysis revealed that DSM interfered with the lipid metabolism pathway of HCC cells by significantly inhibiting the synthesis of metabolites, such as acetic acid, decanoic acid, glycerol, and L-proline. Subcutaneous tumor formation experiments revealed that DSM significantly reduced the tumor volume and weight when compared to the control. Immunohistochemical analysis further revealed that DSM treatment significantly decreased the expression of the proliferative marker KI67. Our findings demonstrated that DSM exhibited antitumor effects on HCC cells by inhibiting cell proliferation via cell cycle arrest and interfering with lipid metabolism.
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Affiliation(s)
- Lianhong Pan
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China. .,Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, Chongqing 400030, China
| | - Fan Feng
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
| | - Jiaqin Wu
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
| | - Lanqing Li
- Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
| | - Haiying Xu
- Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
| | - Li Yang
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
| | - Kang Xu
- Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
| | - Chunli Wang
- National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
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Bhat M, Clotet-Freixas S, Baciu C, Pasini E, Hammad A, Ivanics T, Reid S, Azhie A, Angeli M, Ghanekar A, Fischer S, Sapisochin G, Konvalinka A. Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan. Clin Proteomics 2021; 18:27. [PMID: 34794390 PMCID: PMC8600773 DOI: 10.1186/s12014-021-09333-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 11/03/2021] [Indexed: 02/07/2023] Open
Abstract
Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples. Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance. Supplementary Information The online version contains supplementary material available at 10.1186/s12014-021-09333-x.
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Affiliation(s)
- Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, Canada. .,Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Canada. .,Toronto General Hospital Research Institute, Toronto, Canada. .,Institute of Medical Science, University of Toronto, Toronto, Canada.
| | - Sergi Clotet-Freixas
- Ajmera Transplant Program, University Health Network, Toronto, Canada.,Toronto General Hospital Research Institute, Toronto, Canada
| | - Cristina Baciu
- Ajmera Transplant Program, University Health Network, Toronto, Canada
| | - Elisa Pasini
- Ajmera Transplant Program, University Health Network, Toronto, Canada
| | - Ahmed Hammad
- Ajmera Transplant Program, University Health Network, Toronto, Canada.,Department of General Surgery, Mansoura University, Mansoura, Egypt
| | - Tommy Ivanics
- Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Canada
| | - Shelby Reid
- Institute of Medical Science, University of Toronto, Toronto, Canada
| | - Amirhossein Azhie
- Ajmera Transplant Program, University Health Network, Toronto, Canada
| | - Marc Angeli
- Ajmera Transplant Program, University Health Network, Toronto, Canada
| | - Anand Ghanekar
- Ajmera Transplant Program, University Health Network, Toronto, Canada.,Toronto General Hospital Research Institute, Toronto, Canada.,Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Canada
| | - Sandra Fischer
- Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Canada
| | - Gonzalo Sapisochin
- Ajmera Transplant Program, University Health Network, Toronto, Canada.,Division of Multi-Organ Transplant and HPB Surgical Oncology, Department of General Surgery, University Health Network, Toronto, Canada
| | - Ana Konvalinka
- Ajmera Transplant Program, University Health Network, Toronto, Canada. .,Toronto General Hospital Research Institute, Toronto, Canada. .,Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Canada. .,Institute of Medical Science, University of Toronto, Toronto, Canada. .,Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada. .,University Health Network, 585 University Avenue, Room 11-PMB-189, Toronto, ON, M5G 2N2, Canada.
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Cullaro G, Rubin J, Mehta N, Yao F, Verna EC, Lai JC. Sex-based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation. Transplantation 2021; 105:2420-2426. [PMID: 33323764 PMCID: PMC8200371 DOI: 10.1097/tp.0000000000003575] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence postliver transplant. METHODS We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017. RESULTS A total of 12 711 patients underwent liver transplant for HCC: 2909 (23%) women and 9802 (73%) men. Women had significantly lower rates of postliver transplant HCC recurrence than men (4.0% versus 5.4%, P = 0.002). A cox-regression analysis for postliver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of postliver transplant HCC recurrence (95% confidence interval: 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, alpha-fetoprotein, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (P > 0.05 for each). CONCLUSIONS This study demonstrates an independent effect of sex on risk for HCC recurrence postliver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.
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Affiliation(s)
- Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Jessica Rubin
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Francis Yao
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia
University, College of Physicians and Surgeons, New York, NY, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of California-San Francisco, San Francisco, CA
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L R, T I, Mpaw C, H M, G S. THE MANAGEMENT OF POST-TRANSPLANTATION RECURRENCE OF HEPATOCELLULAR CARCINOMA. Clin Mol Hepatol 2021; 28:1-16. [PMID: 34610652 PMCID: PMC8755475 DOI: 10.3350/cmh.2021.0217] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/03/2021] [Indexed: 11/15/2022] Open
Abstract
The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.
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Affiliation(s)
- Rajendran L
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Ivanics T
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.,Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Claasen Mpaw
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands
| | - Muaddi H
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Sapisochin G
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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Patel YA, Yao J, Proeschold-Bell RJ, Niedzwiecki D, Goacher E, Muir AJ. Reduced Alcohol Use Is Sustained in Patients Provided Alcohol-Related Counseling During Direct-Acting Antiviral Therapy for Hepatitis C. Dig Dis Sci 2021; 66:2956-2963. [PMID: 32968965 PMCID: PMC10245073 DOI: 10.1007/s10620-020-06616-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 09/14/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Patients with chronic hepatitis C and risky/harmful alcohol use experience poor outcomes. Granular data evaluating whether alcohol counseling during hepatitis C treatment impacts longitudinal alcohol consumption are lacking. AIMS To evaluate whether provider-delivered counseling in the context of direct-acting antiviral hepatitis C treatment associates with decreased longitudinal alcohol consumption. METHODS We performed secondary data analysis from the Hep ART study including adults with hepatitis C who underwent provider-delivered counseling during direct-acting antiviral treatment between October 2014 and September 2017. Demographics and disease characteristics were summarized. Alcohol consumption, abstinence, and heavy drinking were evaluated in periods before, during, and after direct-acting antiviral treatment. Multivariate regression analyses were performed to evaluate the association of alcohol consumption with each 12-week time period for all patients and a subsample with cirrhosis. RESULTS One hundred twenty-three patients were included; 41 had cirrhosis. Most patients were male (74.0%) and Black (58.5%). Alcohol consumption improved during direct-acting antiviral treatment and was notably sustained (< 12 weeks before treatment 32.5 g/day; during treatment 20.0 g/day; and 12-24 weeks after treatment 23.7 g/day). Multivariable analyses showed significantly improved alcohol consumption metrics during and after antiviral treatment compared to < 12 weeks before treatment (during treatment 13.04 g/day less, p = 0.0001; > 24 weeks after treatment 15.29 g/day less, p = 0.0001). The subsample with cirrhosis showed similar results (during treatment 13.21 g/day less, p = 0.0001; > 24 weeks after treatment 7.69 g/day less, p = 0.0001). CONCLUSIONS Patients with chronic HCV and risky/harmful alcohol use given provider-delivered alcohol-related counseling during HCV treatment sustain decreased alcohol consumption patterns during and after treatment.
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Affiliation(s)
- Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
| | - Jia Yao
- Duke Center for Health Policy and Inequalities Research, Duke University, Durham, NC, USA
| | - Rae Jean Proeschold-Bell
- Duke Center for Health Policy and Inequalities Research, Duke University, Durham, NC, USA
- Duke Global Health Institute, Duke University, Durham, NC, USA
| | - Donna Niedzwiecki
- Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA
| | - Elizabeth Goacher
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
- Duke Clinical Research Institute, Duke University, Durham, NC, USA
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Claasen MPAW, Ivanics T, Gravely A, Sapisochin G. Prognostic risk scores for liver transplantation: game changers or statistical artworks? Hepatobiliary Surg Nutr 2021; 10:553-557. [PMID: 34430542 DOI: 10.21037/hbsn-21-258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 07/18/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Marco P A W Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.,Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Annabel Gravely
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Division of General Surgery, University Health Network, Toronto, ON, Canada
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Ivanics T, Shwaartz C, Claasen MPAW, Patel MS, Yoon P, Raschzok N, Wallace D, Muaddi H, Murillo Perez CF, Hansen BE, Selzner N, Sapisochin G. Trends in indications and outcomes of liver transplantation in Canada: A multicenter retrospective study. Transpl Int 2021; 34:1444-1454. [PMID: 33977568 DOI: 10.1111/tri.13903] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/12/2021] [Accepted: 05/05/2021] [Indexed: 12/30/2022]
Abstract
The liver transplantation (LT) landscape is continuously evolving. We sought to evaluate trends in indications for LT in Canada and the impact of primary liver disease on post-LT outcomes using a national transplant registry. Adult patients who underwent a primary LT between 2000 and 2018 were retrospectively identified in the Canadian Organ Replacement Registry. Outcomes included post-LT patient and graft survival. A total of 5,722 LTs were identified. The number of LT per year increased from 251 in 2000 to 349 in 2018. The proportion of patients transplanted for HCV decreased from 31.5% in 2000 to 3.4% in 2018. In contrast, the percentage of transplants for HCC increased from 2.3% in 2000 to 32.4% in 2018, and those performed for NASH increased from 0.4% in 2005 to 12.6% in 2018. Year of transplant (per 1 year) was protective for both patient (HR:0.96,95%CI:0.94-0.97; P < 0.001) and graft survival (HR:0.97, 95%CI: 0.96-0.99; P = 0.001). Post-LT outcomes have improved over time in this nationwide analysis spanning 18 years. Moreover, trends in the indications for LT have changed, with HCC becoming the leading etiology. The decrease in the proportion of HCV patients and increase in those with NASH has implications on the evolving management of LT patients.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Chaya Shwaartz
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Madhukar S Patel
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Peter Yoon
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Nathanael Raschzok
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - David Wallace
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.,Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Hala Muaddi
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Carla Fiorella Murillo Perez
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, ON, Canada
| | - Bettina E Hansen
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, ON, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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Pamecha V, Sinha PK, Rajendran V, Patil NS, Mohapatra N, Rastogi A, Patidar Y, Choudhury A. Living donor liver transplantation for hepatocellular carcinoma in Indian patients- Is the scenario different? Indian J Gastroenterol 2021; 40:295-302. [PMID: 34019241 DOI: 10.1007/s12664-020-01138-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 12/11/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Living donor liver transplant (LDLT) for hepatocellular carcinoma (HCC) has been controversial in terms of selection and outcome. We share our experience of LDLT for HCC in Indian patients. METHODS Retrospective analysis of patients undergoing LDLT for HCC discovered either preoperatively or incidentally on explant pathology was done. Preoperative characteristics and explant histopathology findings were recorded. Overall, recurrence-free survival and factors predicting recurrence were analyzed. RESULTS Six hundred and eleven LDLT were performed between June 2011 and October 2019. HCC constituted 6.5% (n = 53) of transplant activity. Forty had preoperative diagnosis, while 13 were detected incidentally. The median model for end-stage liver disease (MELD) score was 18 for patients with HCC. Only in 10 patients (19%), HCC was the primary indication for liver transplant (LT), and the rest had undergone transplant for progressive decompensation. Thirty-two patients were within up-to-7, while 21 were outside up-to-7 criteria. Overall 5-year survival was 85.4% and recurrence-free survival was 83.3% after a median follow-up of 35 months (13-59). This was similar to LDLT for other indications (81.2% at 5 years). Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score was best able to predict recurrence (p = 0.03) with odds ratio of 6.8. CONCLUSION Patients with HCC in India present late for liver transplant. Most patients have some form of decompensation before they undergo LT. In selected patients, overall survival was comparable with other indications for LDLT with acceptable recurrence rates. RETREAT score was best to predict recurrence.
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Affiliation(s)
- Viniyendra Pamecha
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India.
| | - Piyush K Sinha
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
| | - Vivek Rajendran
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
| | - Nilesh S Patil
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
| | - Nihar Mohapatra
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
| | - Yashwant Patidar
- Department of Intervention Radiology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110 070, India
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Fang C, Su B, Jiang T, Li C, Tan Y, Wang Q, Dong L, Liu X, Lin X, Xu G. Prognosis prediction of hepatocellular carcinoma after surgical resection based on serum metabolic profiling from gas chromatography-mass spectrometry. Anal Bioanal Chem 2021; 413:3153-3165. [PMID: 33796932 DOI: 10.1007/s00216-021-03281-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/26/2021] [Accepted: 03/08/2021] [Indexed: 01/27/2023]
Abstract
Comprehensive prognostic risk prediction of hepatocellular carcinoma (HCC) after surgical treatment is particularly important for guiding clinical decision-making and improving postoperative survival. Hence, we aimed to build prognostic models based on serum metabolomics data, and assess the prognostic risk of HCC within 5 years after surgical resection. A pseudotargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomics method was applied to analyze serum profiling of 78 HCC patients. Important metabolic features with discriminant ability were identified by a novel network-based metabolic feature selection method based on combinational significance index (N-CSI). Subsequently, phenylalanine and galactose were further identified to be relevant with mortality by the Cox regression analysis, while galactose and tyrosine were associated with recurrence and metastasis. Two models to predict risk of mortality (risk score of overall survival, RSOS) and risk of recurrence and metastasis (risk score of disease-free survival, RSDFS) were generated based on two panels of metabolites, respectively, which present favorable ability to predict prognosis of HCC, especially when combined with clinical staging system. The performance of models was further validated in an external independent cohort from 91 HCC patients. This study demonstrated that metabolomics is a powerful tool for risk screening of HCC prognosis.
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Affiliation(s)
- Chengnan Fang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Benzhe Su
- School of Computer Science & Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
| | - Tianyi Jiang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, 200438, China
| | - Chao Li
- School of Computer Science & Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
| | - Yexiong Tan
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, 200438, China
| | - Qingqing Wang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
| | - Liwei Dong
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, 200438, China.
| | - Xinyu Liu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China.
| | - Xiaohui Lin
- School of Computer Science & Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China.
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
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49
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Shalaby S, Taborelli M, Zanetto A, Ferrarese A, D'Arcangelo F, Gambato M, Senzolo M, Russo FP, Germani G, Boccagni P, Ettorre GM, Baccarani U, Lauro A, Galatioto L, Rendina M, Petrara R, De Rossi A, Nudo F, Toti L, Fantola G, Vennarecci G, Risaliti A, Pinna AD, Gruttadauria S, Di Leo A, Rossi M, Tisone G, Zamboni F, Cillo U, Piselli P, Serraino D, Burra P. Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study. Transpl Int 2021; 34:743-753. [PMID: 33492715 DOI: 10.1111/tri.13831] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 09/22/2020] [Accepted: 01/20/2021] [Indexed: 02/05/2023]
Abstract
Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.
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Affiliation(s)
- Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Taborelli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesca D'Arcangelo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Patrizia Boccagni
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | | | - Augusto Lauro
- Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Laura Galatioto
- Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
| | - Maria Rendina
- Department of Emergency and Organ Transplantation, Gastroenterology Section, University Hospital, Bari, Italy
| | - Raffaella Petrara
- Oncology and Immunology Section, AIDS Reference Center, Department of Oncology and Immunology, University of Padua, Padua, Italy
| | - Anita De Rossi
- Oncology and Immunology Section, AIDS Reference Center, Department of Oncology and Immunology, University of Padua, Padua, Italy
| | - Francesco Nudo
- Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
| | - Luca Toti
- UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
| | - Giovanni Fantola
- Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
| | - Giovanni Vennarecci
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy
| | | | - Antonio Daniele Pinna
- Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Salvatore Gruttadauria
- Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
| | - Alfredo Di Leo
- Department of Emergency and Organ Transplantation, Gastroenterology Section, University Hospital, Bari, Italy
| | - Massimo Rossi
- Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
| | - Giuseppe Tisone
- UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
| | - Fausto Zamboni
- Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Pierluca Piselli
- Department of Epidemiology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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50
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Romano DN, Mokuolu DC, Katz DJ, DeMaria S. Orthotopic liver transplant in the pregnant recipient: A systematic review of preoperative management and maternal and fetal outcomes. Clin Transplant 2021; 35:e14269. [PMID: 33615548 DOI: 10.1111/ctr.14269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/01/2021] [Accepted: 02/13/2021] [Indexed: 11/27/2022]
Abstract
Severe liver dysfunction requiring transplantation is a major event at any stage of life, but for those requiring liver transplantation while pregnant, two lives hang in the balance. Available evidence on this relatively rare event consists solely of case reports and have yet to be reviewed or synthesized. We performed a systematic literature review and analyzed reports of 22 patients who underwent liver transplantation during pregnancy. This review describes the reported etiologies of hepatic failure in pregnant patients requiring transplantation, perioperative anesthetic management techniques, and the maternal and fetal clinical outcomes.
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Affiliation(s)
- Diana N Romano
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Liver Transplant Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Debbie C Mokuolu
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Daniel J Katz
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Obstetric Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Samuel DeMaria
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Liver Transplant Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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