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Simple Summary: Liver transplantation is one of the most effective treatments for hepatocellular carcinoma, but only when specific transplantation criteria are met. Local therapies may be used to prevent the tumor from exceeding the transplantation criteria (i.e., so-called bridging therapy). However, the impact of bridging therapy on transplantation outcomes and its predictive value are still not known. We performed a systematic review on both radiological and histopathological responses as prognostic indicators of transplantation outcomes. Five studies were included. The overall risk of bias was serious across the studies. If the tumor showed a good radiological response to bridging therapy, there was a greater chance of better transplantation outcomes. Complete tumor necrosis was not associated with better transplantation outcomes. Future predictive models should include radiological, pathological, histological, cellular, and molecular tumor features. Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC) in cirrhotic livers. Neoadjuvant bridging treatment in patients qualifying and listed for LT is advised but is still debatable owing to the low level of evidence. The aim of this study was to perform a systematic review to assess the prognostic value of bridging therapy, in terms of radiological and histopathological examination outcomes, for survival after LT. The systematic review was performed according to the PRISMA 2020 guidelines. The MEDLINE and Web of Science databases were searched. In total, five studies were included. An evaluation with the ROBINS-I resulted in studies classified as the following: moderate risk of bias (n = 1) and serious risk of bias (n = 4). The results of the analysis indicated that favorable LT outcomes were most common with complete response or partial radiological response. Poor radiological response or progressive disease during bridging treatment was generally associated with worse overall LT survival. There were not enough data to support the use of this approach to achieve a complete pathologic response. Radiological, pathological, histological, cellular, and molecular tumor features should be included in future LT qualification models. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a common cancer and a leading cause of cancer-related deaths worldwide. However, HCC can be effectively treated in selected cases, with liver transplantation representing one of the limited options for potential cure. Unfortunately, many patients are ineligible for liver transplantation either due to an advanced tumor at initial diagnosis or due to disease progression while awaiting liver transplantation. Our review discusses the role of systemic therapies as a bridging treatment to liver transplantation, thereby enabling more HCC patients to undergo potentially curative liver transplantation. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curative for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists and/or to downstage patients who are beyond the Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine kinase inhibitors (TKIs) can be used as a systemic bridging therapy to LT in patients with contraindications for locoregional liver-directed therapies. Immune checkpoint inhibitor (ICI) treatment can be utilized either as a monotherapy or as a combination therapy with bevacizumab or TKIs prior to LT. Acute rejection after liver transplantation is a concern in the context of ICI treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The usefulness of transarterial radioembolization (TARE) as a treatment has been endorsed by different authors and recommended by a multidisciplinary working group in terms of its safety, efficacy and feasibility for the surgical resection of patients with borderline-resectable hepatocellular carcinoma (HCC). In contrast, in the field of liver transplant (LT), the role of TARE is under debate and there are still no clear and unified guidelines for its indication. Background: Transarterial radioembolization in HCC for LT as downstaging/bridging has been increasing in recent years but some indication criteria are still unclear. Methods: We conducted a systematic literature search of primary research publications conducted in PubMed, Scopus and ScienceDirect databases until November 2022. Relevant data about patient selection, HCC features and oncological outcomes after TARE for downstaging or bridging in LT were analyzed. Results: A total of 14 studies were included (7 downstaging, 3 bridging and 4 mixed downstaging and bridging). The proportion of whole liver TARE was between 0 and 1.6%. Multiple TARE interventions were necessary for 16.7% up to 28% of the patients. A total of 55 of 204 patients across all included studies undergoing TARE for downstaging were finally transplanted. The only RCT included presents a higher tumor response with the downstaging rate for LT of TARE than TACE (9/32 vs. 4/34, respectively). Grade 3 or 4 adverse effects rate were detected between 15 and 30% of patients. Conclusions: TARE is a safe therapeutic option with potential advantages in its capacity to necrotize and reduce the size of the HCC for downstaging or bridging in LT. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of hepatocellular carcinoma (HCC). In addition to their role in advanced HCC, there is considerable interest in using ICIs in the neoadjuvant setting, either as a downstaging or bridging therapy, prior to potentially curative liver transplantation. In this article, we reviewed all the available literature on ICI use in this context. We postulate that ICIs may be utilized safely prior to liver transplant; however, further research is needed in this area. Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed. [ABSTRACT FROM AUTHOR]