NASH is the Leading Cause of Hepatocellular Carcinoma in Liver Transplant Candidates.
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ABSTRACT:
SUBMITTER: Koh JH
PROVIDER: S-EPMC10939135 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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NASH is the Leading Cause of Hepatocellular Carcinoma in Liver Transplant Candidates.
Koh Jia Hong JH Ng Cheng Han CH Nah Benjamin B Tan Darren Jun Hao DJH Loomba Rohit R Huang Daniel Q DQ
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20230526 1
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Project description:ObjectivesChronic infection with hepatitis C virus (HCV) was previously the leading indication for liver transplant (LT) in the United States. However, since 2014 the use of direct-acting antivirals (DAAs) has decreased the chronic HCV burden, while the prevalence of nonalcoholic steatohepatitis (NASH) has risen substantially through the last decade. Both gender and ethnic disparities in indications for LT have been shown in the past but no data on this have been reported since the implementation of DAAs.MethodsWe assessed changes in etiologies for LT listing and in gender and ethnic differences in those listed for LT. Adult patients registered for LT in the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between January 1, 2004 and December 31, 2016 were included. Multinomial logistic regression modeling was used to test for changes in waitlist or liver transplant rates.ResultsThe study included 127,164 adult patients registered for LT. By 2016, alcoholic liver disease (ALD) was the leading etiology for waitlisting and LT; NASH was second; hepatocellular carcinoma (HCC) due to chronic HCV and chronic HCV alone were 3rd and 4th. NASH was the leading cause for LT for women and the 2nd leading cause for men (following ALD). NASH increased as the cause in all ethnic subgroups and was the leading cause in 2016 among Asian, Hispanic, and non-Hispanic white females. We also found that although the indication for liver transplant for hepatocellular carcinoma (HCC) due to HCV has increased over the years, this indication decreased for the first time between 2015 and 2016 in both males and females.ConclusionsNASH is currently the second leading cause for LT waitlist registration/liver transplantation overall, and in females, the leading cause. Given the rate of increase, NASH will likely rise to become the leading indication for LT in males as well.
| S-EPMC9083888 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) mainly stems from liver cirrhosis and its genetic predisposition is believed to be rare. However, two recent studies describe pathogenic/likely pathogenic germline variants (PV) in cancer-predisposition genes (CPG). As the risk of de novo tumors might be increased in PV carriers, especially in immunosuppressed patients after a liver transplantation, we analyzed the prevalence of germline CPG variants in HCC patients considered for liver transplantation. Using the panel NGS targeting 226 CPGs, we analyzed germline DNA from 334 Czech HCC patients and 1662 population-matched controls. We identified 48 PVs in 35 genes in 47/334 patients (14.1%). However, only 7/334 (2.1%) patients carried a PV in an established CPG (PMS2, 4×NBN, FH or RET). Only the PV carriers in two MRN complex genes (NBN and RAD50) were significantly more frequent among patients over controls. We found no differences in clinicopathological characteristics between carriers and non-carriers. Our study indicated that the genetic component of HCC is rare. The HCC diagnosis itself does not meet criteria for routine germline CPG genetic testing. However, a low proportion of PV carriers may benefit from a tailored follow-up or targeted therapy and germline testing could be considered in liver transplant recipients.
| S-EPMC9818325 | biostudies-literature
Project description:ImportanceRacial disparities in liver transplant (LT) for hepatocellular carcinoma (HCC) may be associated with unequal access to life-saving treatment.ObjectiveTo quantify racial disparities in LT for HCC and mortality after LT, adjusting for demographic, clinical, and socioeconomic factors.Design, setting, and participantsThis cohort study was a retrospective analysis of United Network Organ Sharing/Organ Procurement Transplant Network (OPTN) data from 2003 to 2021. Participants were adult patients with HCC on the LT waiting list and those who received LT. Data were analyzed from March 2022 to September 2023.ExposuresRace and time before and after the 2015 OPTN policy change.Main outcomes and measuresProportion of LT from wait-listed candidates, the proportion of waiting list removals, and mortality after LT.ResultsAmong 12 031 patients wait-listed for LT with HCC (mean [SD] age, 60.8 [7.4] years; 9054 [75.3%] male; 7234 [60.1%] White, 2590 [21.5%] Latinx/o/a, and 1172 [9.7%] Black or African American), this study found that after the 2015 model of end-stage liver disease (MELD) exception policy changes for HCC (era 2), the overall proportion of LT for HCC across all races decreased while the proportion of dropouts on the LT waiting list remained steady compared with patients who did not have HCC. In Kaplan-Meier analysis, Asian patients demonstrated the lowest dropout rates in both era 1 and era 2 (1-year dropout, 16% and 17%, respectively; P < .001). In contrast, Black or African American patients had the highest dropout rates in era 1 (1-year dropout, 24%), but comparable dropout rates (23%) with White patients (23%) and Latinx/o/a patients in era 2 (23%). In both eras, Asian patients had the highest survival after LT (5-year survival, 82% for era 1 and 86% for era 2), while Black or African American patients had the worst survival after LT (5-year survival, 71% for era 1 and 79% for era 2). In the multivariable analysis for HCC LT recipients, Black or African American race was associated with increased risk of mortality in both eras, compared with White race (HR for era 1, 1.17; 95% CI, 1.05-1.35; and HR for era 2, 1.31; 95% CI, 1.10-1.56).Conclusions and relevanceThis cohort study of LT candidates in the US found that after the 2015 MELD exception policy change for HCC, the proportion of LT for HCC had decreased for all races. Black or African American patients had worse outcomes after LT than other races. Further research is needed to identify the underlying causes of this disparity and develop strategies to improve outcomes for HCC LT candidates.
| S-EPMC10623194 | biostudies-literature
Project description:BackgroundNon-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) has been emerging a predominant reason for liver transplantation (LT). The complexity of comorbidities in this population increases the possibility of poor transplant outcomes. The purpose of this study was to evaluate the differences in survival after transplantation among patients with NASH HCC and those with non-NASH HCC.MethodWe conducted systematic searches of the PubMed, Embase, Web of Science, and Cochrane Library databases. To analyze the data, both fixed and random-effects models were employed to aggregate hazard ratios (HRs) along with 95% confidence intervals (CIs) for recurrence-free survival (RFS) and overall survival (OS) outcomes. This study is registered with PROSPERO as CRD42024578441.ResultsA total of seven studies were included in this study. This study revealed that there was no significant difference in OS between liver transplant recipients with NASH HCC and those with non-NASH HCC. The RFS of NASH HCC patients were significantly longer. The HRs were 0.70 (95% CI: 0.51-0.97, P = 0.03) for RFS and 0.88 (95% CI: 0.72-1.07, P = 0.21) for OS, respectively.ConclusionThis study indicates that patients with NASH HCC who undergo LT have comparable OS as those with non-NASH HCC, while NASH HCC was associated with increased RFS. However, further research in randomized trials is necessary to verify these results and address potential selection biases.
| S-EPMC11922278 | biostudies-literature
Project description:Background & aimsPolicy changes in the United States have lengthened overall waiting times for patients with hepatocellular carcinoma (HCC). We investigated temporal trends in utilization of locoregional therapy (LRT) and associated waitlist outcomes among liver transplant (LT) candidates in the United States.MethodsData for primary adult LT candidates listed from 2003 to 2018 who received HCC exception were extracted from the Organ Procurement and Transplantation Network database. Explant histology was examined, and multivariable competing risk analysis was used to evaluate the association between LRT type and waitlist dropout.ResultsThere were 31,609 eligible patients with at least 1 approved HCC exception, and 34,610 treatments among 24,145 LT candidates. The proportion with at least 1 LRT recorded increased from 42.3% in 2003 to 92.4% in 2018. Chemoembolization remains the most frequent type, followed by thermal ablation, with a notable increase in radioembolization from 3% in 2013 to 19% in 2018. An increased incidence of LRT was observed among patients with tumor burden beyond Milan criteria, higher α-fetoprotein level, and more compensated liver disease. Receipt of any type of LRT was associated with a lower risk of waitlist dropout; there was no significant difference by number of LRTs. In inverse probability of treatment weighting-adjusted analysis, radioembolization or ablation as the first LRT was associated with a reduced risk of waitlist dropout compared with chemoembolization.ConclusionsIn a large nationwide cohort of LT candidates with HCC, LRT, and in particular radioembolization, increasingly was used to bridge to LT. Patients with greater tumor burden and those with more compensated liver disease received more treatments while awaiting LT. Bridging LRT was associated with a lower risk of waitlist dropout.
| S-EPMC10306121 | biostudies-literature
Project description:In cirrhotic patients listed for liver transplantation (LT) with a history of hepatic encephalopathy (HE), rifaximin reduces the number of hospitalizations, but whether it influences the time to first hospitalization is unknown.Aimsto evaluate the time-dependent impact of rifaximin on the risk of all-cause hospitalization and dropout in patients on the LT waiting list.MethodsConsecutive patients listed for LT were retrospectively enrolled. After balancing populations with and without rifaximin treatment using the inverse probability therapy weighting analysis, Fine-Gray multivariable competing risk analyses were run to explore risk factors for the first episode of hospitalization and dropout.ResultsWhen comparing 92 patients taking rifaximin to the untreated group of 152, rifaximin treatment was not associated with any of the study outcomes. In the subset of patients with a history of HE at waitlist entry (N = 81 rifaximin-treated and N = 39 untreated), rifaximin intake was independently associated with a lower risk of hospitalization for all causes (SHR 0.638; 95.0% CI 0.418-0.973; p = 0.037) and for HE (SHR 0.379; 95.0% CI 0.207-0.693; p = 0.002).Conclusionscirrhotic LT candidates with a prior history of HE rifaximin treatment are associated with a lower risk of time-dependent all-cause hospitalization, likely due to its unique effect on gut microbiome composition/function.
| S-EPMC10647372 | biostudies-literature
Project description:Candidates with hepatocellular carcinoma (HCC) within the Milan criteria (MC) receive standardized Model for End-Stage LIver Disease (MELD) exception points because of the projected risk of tumor expansion beyond the MC. Exception points at listing are meant to be equivalent to a 15% rusj if 90-day mortality, with additional points granted every 3 months, equivalent to a 10% increased morality risk. We analyzed the United Network for Organ Sharing database (January 1, 2005 to May 31, 2009) to compare the 90-day waitlist outcomes of HCC candidates and non-HCC candidates with similar MELD scores. Two hundred fifty-nine HCC candidates (4.1%) who were initially listed with 22 MELD exception points were removed because of death or clinical deterioration within 90 days of listing, whereas 283 non-HCC candidates (11.0%) with initial laboratory MELD scores of 21 to 23 were removed. Ninety-three HCC candidates (4.6%) with 25 exception points (after 3-6 months of waiting) were removed because of death or clinical deterioration within 90 days, whereas 805 non-HCC candidates (17.3%) with laboratory MELD scores of 24 to 26 were removed. Twenty HCC candidates (3.0%) with 28 exception points (after 6-9 months of waiting) were removed for death or clinical deterioration within 90 days, whereas 646 non-HCC candidates (23.6%) with laboratory MELD scores of 27 to 29 were removed. In multivariate logistic regression models, HCC candidates had significantly lower 90-day odds of waitlist removal for death or clinical deterioration (P < 0.001). Over time, the risk of waitlist removal for death or clinical deterioration was unchanged for HCC candidates (P = 0.17), whereas it increased significantly for non-HCC candidates. The current allotment of HCC exception points should be re-evaluated because of the stable risk of waitlist dropout for these candidates.
| S-EPMC3319293 | biostudies-literature
Project description:The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)-a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk, and ultimately increase survival of patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC.
| S-EPMC9890137 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.
| S-EPMC9777129 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a leading cause of global cancer mortality, with liver transplantation as the sole curative treatment. For advanced disease, first-line systemic therapies including immune checkpoint inhibitors (ICIs) have shown a survival benefit, but there is scarce data on clinical outcomes when used prior to transplantation. We present three case studies of patients who received immunotherapy with atezolizumab/bevacizumab or ipilimumab/nivolumab before liver transplant. We reviewed clinical outcomes including disease response, adverse events related to systemic therapy, as well as graft function post-operatively. One case demonstrated a 45% reduction in total HCC tumour burden whereas another showed stable disease with ICIs. No adverse clinical outcomes such as graft rejection or poor wound healing were noted post-transplant. Indeed, all three patients were successfully transplanted with excellent graft function at the last follow-up. Our observations and data suggest ICIs are a viable option for treatment in the pre-transplant setting. It does not routinely lead to fatal graft rejection and may lengthen eligibility times until a donor organ is available.
| S-EPMC10772681 | biostudies-literature