Liver transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades

Puigvehí, Marc; Hashim, Dana; Haber, Philipp K.; Dinani, Amreen; Schiano, Thomas D.; Asgharpour, Amon; Kushner, Tatyana; Kakked, Gaurav; Tabrizian, Parissa; Schwartz, Myron; Gürakar, Ahmet; Dieterich, Douglas T.; Boffetta, Paolo; Friedman, Scott L.; Llovet, Josep M.; Saberi, Behnam

doi:10.1111/ajt.15576

Cited by 36 publications

(30 citation statements)

References 30 publications

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“… 21 , 28 , 29 A recent study showed that diabetes was a predictor of decreased survival in the interferon era but not the direct-acting antiviral era, but the reasons for this are unclear. 30 Finally, it also appears that BCLC stage is important, as Su et al reported lower survival rates in HCC patients with diabetes and BCLC stage 0, A, and B, but no difference in survival seen in stages C and D. 31 , 32 …”

Section: Discussionmentioning

confidence: 99%

Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma

Weinfurtner

Dodge

Yao

et al. 2020

Transplantation Direct

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Background. Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown. Methods. We conducted a retrospective study of 631 HCC patients listed for LT at a large academic center from 2004 to 2013. Waitlist dropout and LT were analyzed using competing risk regression. Results. Compared with other-HCC patients (n = 589), NAFLD-HCC patients (n = 42, 6.7%) were older (65 versus 58, P < 0.001) with more women (50.0 versus 23.6%, P < 0.001), Hispanic ethnicity (40.5 versus 17.7%, P = 0.001), obesity (69.0 versus 29.9%, P < 0.001), diabetes mellitus (59.5 versus 27.8%, P < 0.01), insulin-dependence (23.8 versus 10.2%, P = 0.007), hyperlipidemia (40.5 versus 10.5, P < 0.001), and statin use (33.3 versus 5.3%, P < 0.001). Cumulative incidence of waitlist dropout at 2 y was 17.4% (95% confidence intervals, 7.7-30.4) for NAFLD HCC and 25.4% (95% confidence intervals, 21.9-29.0) for other HCC (P = 0.28). No difference in waitlist dropout or receipt of LT between NAFLD HCC and other HCC was found on regression analysis. Similarly, NAFLD and obesity, obesity alone, diabetes mellitus, insulin-dependence, hyperlipidemia, and statin use were not associated with waitlist outcomes. Finally, we observed no statistically significant difference in 5-y survival from HCC diagnosis between NAFLD HCC and other HCC (78.5% versus 66.9%, P = 0.9). Conclusions. In our single-center cohort, we observed no difference in waitlist outcomes or survival in NAFLD HCC, although conclusions are limited by the small number of NAFLD-HCC patients. Notably, the inclusion of patients with obesity in the NAFLD-HCC group and stratification by individual metabolic factors also showed no difference in waitlist outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma

Weinfurtner

Dodge

Yao

et al. 2020

Transplantation Direct

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“…( 36 ) Despite this, the proportion of LT due to HCC has steadily increased. ( 37 ) It remains a common indication for LT both in terms of wait‐list registrants and recipients (24% and 27% in 2015, respectively). ( 38 ) Considering the discrepancy between the number of recipients with HCC and the number of available organs and our lack of tools to accurately monitor tumor aggressiveness, it is imperative to develop new methods and better match patients with organs on an individual basis.…”

Section: Clinical Selection Criteria For Patients With Hccmentioning

confidence: 99%

Role of Molecular Biomarkers in Liver Transplantation for Hepatocellular Carcinoma

Felden¹,

Villanueva

2020

Liver Transpl

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Patient selection and organ allocation for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) relies predominantly on clinical parameters, such as tumor burden (ie, radiological imaging). Patients transplanted withinMilan criteria have outstanding outcomes with a 5-and 10-year survival of 70% and 55%, respectively. Tumor recurrence after transplantion is rare in these patients (10%); however, treatment options upon recurrence are generally limited, and outcomes are poor. There are also several studies showing how a subgroup of patients with tumors outside the Milan criteria might achieve comparable outcomes to patients within Milan criteria. In other words, the size and number of tumor nodules does not always reflect tumor biology, which could be better captured using molecular proxies for cancer aggressiveness. Over the last decade, we have significantly improved our understanding of the molecular landscape of early stage HCC. This includes the development of molecular classification, identification of prognostic and mutational signatures, and potential mechanisms of hepatocarcinogenesis. Some molecular markers have already proven useful to predict tumor-related outcomes in HCC patients after LT. Most of these analyses are limited to tissue-derived biomarkers, which limits their implementation in clinical practice because tissue biopsy is not required for HCC diagnosis. Minimally invasive alternative tools, such as liquid biopsy, are being increasingly explored and could help to individualize risk stratification for patients with HCC who will benefit from LT despite being outside the accepted clinical criteria.Liver Transplantation 26 823-831 2020 AASLD.

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“…The proposed mechanism of action of HBIg includes binding to the viral particles and HBsAg, resulting in neutralization and The viral envelope proteins, such as HBsAg, bind to host cell surface receptors, resulting in endocytosis of the hepatitis B virion into the host cell. 1 The nucleocapsid releases relaxed circular HBV DNA (rcDNA) into the nucleus,2 which is converted into covalently closed circular double stranded DNA (cccDNA). 3 The cccDNA is a template for transcription of viral RNA.…”

Section: Hbig Monotherapymentioning

confidence: 99%

“…In the USA, hepatocellular carcinoma (HCC) and liver failure due to hepatitis C are the most common indications for liver transplant (LT). 1 However, worldwide, hepatitis B virus (HBV) infection is the major risk factor for development of HCC, and has remained the leading indication for LT in Asian countries. 2 Until the 1990s, HBV infection was considered a relative contraindication to LT, due to high risk of graft infection and subsequent liver failure as a result of post-transplant immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Prevention of HBV Recurrence after Liver Transplant: A Review

Nasir

2020

Journal of Clinical and Translational Hepatology

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Globally, hepatitis B virus (HBV) infection is recognized as a major risk factor for the development of hepatocellular carcinoma, and HBV-induced liver failure is one of the leading indications for liver transplantation. Until about two decades ago, liver transplantation in patients with chronic HBV infection was a relative contraindication, due to high risk of viral replication with the use of immunosuppressants which could result in graft infection. In the 1990s, hepatitis B immunoglobulin (HBIg) use significantly reduced the risk of graft infection, improving outcomes of liver transplant in patients with chronic HBV infection. However, very high costs, especially with the need for long-term use, became a major concern. With the advent of nucleos(t)ide analogs (NAs), there was less need for high-dose, long-term HBIg use to prevent HBV recurrence. Lamivudine was initially used but resistance soon became a major issue. This was followed by more potent NAs, such as entecavir and tenofovir, emerging as the more preferred agents. Additionally, the use of these antiviral agents (HBIg and/or NAs) have made it possible to use the grafts from donors with positivity for hepatitis B core antibody, allowing for expansion of the donor pool. Nevertheless, there is no consensus on management protocols, which vary significantly amongst centers. In this review, we appraise studies on management strategies used and the role of active vaccination in the prevention of HBV recurrence in post-liver transplant patients.

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Liver transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 36 publications

References 30 publications

Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma

Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma

Role of Molecular Biomarkers in Liver Transplantation for Hepatocellular Carcinoma

Prevention of HBV Recurrence after Liver Transplant: A Review

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