Hepatic arterial infusion chemotherapy versus transarterial chemoembolization for unresectable hepatocellular carcinoma: A systematic review with meta-analysis.

Background: Interest has revived in the use of hepatic arterial infusion chemotherapy (HAIC) for intermediate-advanced hepatocellular carcinoma (HCC) while transarterial chemoembolization (TACE) has been a longstanding loco-regional therapy. Aim: We conducted a systematic review and meta-analysis of patients with unresectable HCC treated with HAIC or TACE to look for differences in survival, adverse events, mortality and downstaging. Methods: All studies published before 29 July 2022 were identified by searching PubMed, Embase, Web of Science and Cochrane Library databases for patients with unresectable HCC and received HAIC or TACE as initial treatment. Data extracted from studies was statistically analysed using RevMan5.3 software. Results: A total of one randomized controlled trial (RCT) and 7 cohort studies (5 retrospective, 2 prospective) including 1,060 (TACE group: 534, HAIC group: 526) patients were screened. Compared with the TACE group, patients who received HAIC as initial therapy had better overall survival (OS) (HR = 0.53, 95%CI [0.40, 0.69]) and progression-free survival (PFS) (HR = 0.54, 95%CI [0.40, 0.72]). Further subgroup analysis revealed that HAIC showed priority over TACE on prognosis outcome regardless of tumour stage, especially in patients with advanced portal vein tumour thrombus (PVTT). Utilization of port system will not boost the efficacy of HAIC whereas using a replaced-microcatheter for each procedure could better reduce the progressive disease (PD) rate (RR = 0.55, 95%CI [0.40, 0.76]). The pooled RR favoured the HAIC group with regard to partial response (PR) (RR = 2.87, 95%CI [2.18, 3.78]) and this was validated by both GRADE summary and trial sequential analysis. The rate of resection after treatment was higher in the HAIC group (RR = 2.37, 95%CI [1.54, 3.66]), whilst no difference was found with procedure-related mortality (RR = 0.56, 95%CI [0.13, 2.38]) between two groups. Compared with the traditional chemotherapy regimen (fluorouracil/leucovorin/oxaliplatin) FOLFOX-HAIC appears to be better in improving the treatment efficacy. Conclusion: Patients with unresectable HCC could potentially benefit more from HAIC rather than standard TACE treatment. A re-evaluation of HAIC as a treatment option in intermediate and advanced HCC is warranted.

Artificial Intelligence in Liver Transplantation.

BACKGROUND: Advancements based on artificial intelligence have emerged in all areas of medicine. Many decisions in organ transplantation can now potentially be addressed in a more precise manner with the aid of artificial intelligence. METHOD/RESULTS: All elements of liver transplantation consist of a set of input variables and a set of output variables. Artificial intelligence identifies relationships between the input variables; that is, how they select the data groups to train patterns and how they can predict the potential outcomes of the output variables. The most widely used classifiers to address the different aspects of liver transplantation are artificial neural networks, decision tree classifiers, random forest, and naïve Bayes classification models. Artificial intelligence applications are being evaluated in liver transplantation, especially in organ allocation, donor-recipient matching, survival prediction analysis, and transplant oncology. CONCLUSION: In the years to come, deep learning-based models will be used by liver transplant experts to support their decisions, especially in areas where securing equitability in the transplant process needs to be optimized.

Expression Levels of Three Key Genes CCNB1, CDC20, and CENPF in HCC Are Associated With Antitumor Immunity.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a low 5-year survival rate. The heterogeneity of HCC makes monotherapy unlikely. The development of diagnostic programs and new treatments targeting common genetic events in the carcinogenic process are providing further insights into the management of HCC. The aim of this study was firstly to validate key genes that are involved in promoting HCC development and as biomarkers for early diagnosis and, secondly, to define their links with antitumor immunity including inhibitory checkpoints. METHODS: Multiple databases including Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, UALCAN, and Oncomine were used for target gene screening and establishment of a co-expression network. Clinical data and RNAseq of 367 HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The diagnostic and prognostic value of screened genes were tested by receiver operating characteristic (ROC) curve and correlation analysis. The links with the key genes in HCC and antitumor immunity were defined using both blood and liver tissue collected prospectively from HCC patients in our center. RESULTS: Upregulation of CCNB1, CDC20, and CENPF was commonly observed in HCC and are involved in the p53 signal pathway. The hepatic mRNA expression levels of these three genes were strongly associated with patients' prognosis and expressed high value of area under the ROC curve (AUC). Further analysis revealed that these three genes were positively correlated with the gene expression levels of IFN-γ, TNF-α, and IL-17 in peripheral blood. In addition, the expression of CENPF showed positive correlation with the percentage of CD8pos T cells and negative correlation with the percentage of CD4pos T cells in the peripheral blood. In the HCC microenvironment, the transcript levels of these three genes and inhibitory checkpoint molecules including PD-1, CTLA-4, and TIM-3 were positively correlated. CONCLUSION: The upregulation of CCNB1, CDC20, and CENPF genes was a common event in hepatocarcinogenesis. Expression levels of CCNB1, CDC20, and CENPF showed potential for early diagnosis and prediction of prognosis in HCC patients. There is a close association between three genes and Th1/Th17 cytokines as well as the count of CD4pos and CD8pos T cells. The positive correlation between the three genes and inhibitory checkpoint genes, PD-1, CTLA-4, and TIM-3, indicates that these genes are linked with weakened antitumor immunity in HCC. Our findings may provide further insights into developing novel therapies for HCC.

Computational Analysis of Cholangiocarcinoma Phosphoproteomes Identifies Patient-Specific Drug Targets.

Cholangiocarcinoma is a form of hepatobiliary cancer with an abysmal prognosis. Despite advances in our understanding of cholangiocarcinoma pathophysiology and its genomic landscape, targeted therapies have not yet made a significant impact on its clinical management. The low response rates of targeted therapies in cholangiocarcinoma suggest that patient heterogeneity contributes to poor clinical outcome. Here we used mass spectrometry-based phosphoproteomics and computational methods to identify patient-specific drug targets in patient tumors and cholangiocarcinoma-derived cell lines. We analyzed 13 primary tumors of patients with cholangiocarcinoma with matched nonmalignant tissue and 7 different cholangiocarcinoma cell lines, leading to the identification and quantification of more than 13,000 phosphorylation sites. The phosphoproteomes of cholangiocarcinoma cell lines and patient tumors were significantly correlated. MEK1, KIT, ERK1/2, and several cyclin-dependent kinases were among the protein kinases most frequently showing increased activity in cholangiocarcinoma relative to nonmalignant tissue. Application of the Drug Ranking Using Machine Learning (DRUML) algorithm selected inhibitors of histone deacetylase (HDAC; belinostat and CAY10603) and PI3K pathway members as high-ranking therapies to use in primary cholangiocarcinoma. The accuracy of the computational drug rankings based on predicted responses was confirmed in cell-line models of cholangiocarcinoma. Together, this study uncovers frequently activated biochemical pathways in cholangiocarcinoma and provides a proof of concept for the application of computational methodology to rank drugs based on efficacy in individual patients. SIGNIFICANCE: Phosphoproteomic and computational analyses identify patient-specific drug targets in cholangiocarcinoma, supporting the potential of a machine learning method to predict personalized therapies.

Low prevalence and disease severity of COVID-19 in post-liver transplant recipients-A single centre experience.

Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is driving a present day global pandemic. Immunosuppressed patients are regarded as a high-risk cohort. The following is a short report on COVID-19 in liver transplant recipients (n = 5) from a high volume UK liver transplant unit with a large follow-up cohort (n = 4500). Based on this limited data, liver transplant recipients appear to have a low incidence of COVID-19, with less severe symptoms than expected, when compared with the general population and other solid organ recipients. This possibly could be related to self-isolation adherence and/or the 'ideal' level of immunosuppression that favourably modulates the immune response to COVID-19.

An in silico argument for mitochondrial microRNA as a determinant of primary non function in liver transplantation.

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.

The Effect of Recipient Body Mass Index and Its Extremes on Survival and Graft Vascular and Biliary Complications After Liver Transplantation: A Single Center Retrospective Study.

BACKGROUND This is the largest UK-based study on the effect of recipient body mass index (BMI) and its extremes (BMI <18.5 and BMI ≥35 kg/m²) on liver transplant (LT) outcomes. Its purpose was to analyze the BMI effect on post-LT mortality, graft loss, primary non-function (PNF), and graft vascular and biliary complications. MATERIAL AND METHODS Data were retrieved from a single-center LT database of 2,115 consecutive patients receiving first LT during period February 2004 to September 2015. Survivals were compared across the BMI groups; the effects of recipient BMI on survival, PNF, and graft vascular and biliary complications were analyzed via regression. RESULTS Autoimmune disease and nonalcoholic steatohepatitis were prevalent among underweight and morbidly obese adults, respectively. Graft survival was similar across BMI classes at 30 days and in 1, 2, 5, and 10 years (p=0.75) and on obese versus non-obese (p=0.33). BMI <35 kg/m² versus BMI ≥35 kg/m² mean graft survival was similar (p=0.84). BMI <18.5 kg/m² recipients tended to have inferior mean graft and patient survivals; however, the difference was non-significant (p=0.09 and p=0.1 respectively). BMI <18.5 kg/m² recipients were at higher risk of hepatic artery thrombosis (HR, 1.73, 95% CI 1.73-3, p<0.05). Adult underweight status was an independent HAT risk factor (HR 3, 95% CI 1-8.6, p=0.046). BMI class did not affect ischemic cholangiopathy risk (p=0.84). However, the overall biliary complication risk increased by 3% for every 1 kg/m² BMI rise. CONCLUSIONS Post-LT survival is independent of recipient BMI. Underweight status is linked to higher HAT risk. Biliary complication risk increases with rising recipient BMI. After appropriate recipient selection, recipient BMI extremes are not a contraindication for LT.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation.

AIM: To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use. METHODS: The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated. RESULTS: DCD graft survival predictors were primary indication for transplant (P = 0.066), retransplantation (P = 0.176), MELD > 25 (P = 0.05), cold ischemia > 10 h (P = 0.292) and donor hepatectomy time > 60 min (P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively. CONCLUSION: The DCD-RI score independently predicted graft loss (P < 0.001) and the DCD-RI class predicted graft survival (P < 0.001).

Is size the only determinant of delayed abdominal closure in pediatric liver transplant?

The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft-to-recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352-360 2017 AASLD.

An institutional experience of pre-emptive liver transplantation for pediatric primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre-emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30-46) mL/min/1.73 m(2) and five underwent sequential combined liver-kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used "early" or "late." Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m(2) ), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.

Does Donation After Cardiac Death Utilization Adversely Affect Hepatocellular Cancer Survival?

BACKGROUND: Hepatocellular cancer (HCC) is an established indication for liver transplantation. This group is often allocated a donor after cardiac death (DCD) liver as a solution for waiting times. There are concerns that this approach may oncologically disadvantage HCC recipients. The aim of this study was to determine whether DCD transplantation was associated with poorer cancer-related survival in HCC. METHODS: Study population was from a single institute (2001-2014) with an HCC listing diagnosis. Variables related to recipient, tumor, and graft were analyzed to determine association with HCC death. RESULTS: There were 347 recipients listed for HCC of which 91 received a DCD. Donor after cardiac death and donor after brain stem death (DBD) had equivalent 1-, 3-, and 5-year overall (P = 0.115) and cancer-specific survival (P = 0.7). On univariate analysis recipient age, sex, model for end stage liver disease, viral etiology had no bearing on the risk of HCC death. Neither did the graft variables of type (DCD vs DBD), donor age, steatosis, cold ischemic time, peak aspartate transaminase, day 5 bilirubin or international normalized ratio after transplant. Only tumor variables of alpha-fetoprotein, number, total diameter, microvascular invasion, and differentiation were predictors of HCC death. On multivariate analysis, predictors of HCC death remained tumor number (P = 0.002), total diameter of tumor(s) (P < 0.001), microvascular invasion (P = 0.025), and poor differentiation (P = 0.021). CONCLUSIONS: Donor liver quality in terms of graft type (DCD) has no influence on cancer related survival in transplant for HCC (hazards ratio, 1.143; 95% confidence interval, 0.528-2.423; P = 0.752).

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence.

The introduction of liver transplant listing criteria for hepatocellular cancer (HCC) has significantly improved oncological outcomes and survival. But despite this HCC recurrence is still problematic. There is emerging evidence that the choice of immunosuppression (IS) after transplant for HCC can influence oncological survival and HCC recurrence. The following is a short summary of what has been published on HCC recurrence with the different classes of immunosuppressive agents in present use, concluding with the possible rationalization of the use of these immunosuppressive agents in the post-transplant patient at high risk of recurrence.

Caval agenesis in the pediatric liver donor.

The following is the first report of a pediatric organ donor with caval agenesis and the subsequent use of this liver for transplantation. Caval embryology and potential implications of utilizing a donor liver with caval agenesis are reviewed.

The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function.

Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.

Presentation, diagnosis, and management of early hepatic venous outflow complications in whole cadaveric liver transplant.

Early hepatic venous outflow obstruction (HVOO) can be a devastating complication leading to graft loss after liver transplantation (LT). A retrospective study on 777 adult LT recipients over a 5-year period (August 2007 to August 2012) was undertaken to determine the incidence of early HVOO presenting within 3 months of transplant, its clinical features and management, and potential technical risk factors related to the implanting technique. Cases of early HVOO were screened for by identifying recipients with problematic ascites within 3 months of transplant. Definitive diagnosis for HVOO was based on a wedge pressure of >12 mm Hg. Considering only whole livers, the incidence of early problematic ascites was 3% (20/695) of which more than one-third (35%, 7/20) were then confirmed to have HVOO. Overall, the incidence of early HVOO was 1% (7/695). Two hepatic veins (HVs) with extension piggybacks (PBs; n = 423) were the dominant implanting technique in the time period of study rather than the 3 HV PB (n = 182) and caval replacement techniques (n = 82). Considering the implantation technique, all cases of HVOO occurred after 2 HVs when extension PBs had been used with an incidence of 1.7% (7/423). Institutionally, early HVOO was mainly managed surgically by either cavoplasty within a month of transplant (n = 4) or retransplant (n = 1), and the remainder (n = 2) were medically managed with diuretics. In conclusion, early HVOO is rare, and there is no evidence from this study that a given implantation technique is at a higher risk of developing HVOO (2 HV with extension versus 3 HV and caval replacement; P = 0.11). However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for when surgical cavoplasty or radiological stenting is technically not possible.

Diaphragmatic hernia after liver transplantation in children: case series and review of the literature.

A diaphragmatic hernia (DH) is a rare complication of pediatric liver transplantation (LT), with multiple factors implicated in the pathophysiology. It is a potentially life-threatening condition in the absence of early recognition and surgical treatment. A DH after LT has been reported in 16 patients in 7 case series. We report 10 cases from our institution and review the published literature to understand the underlying pathophysiology. The study sample included all children (<18 years of age) who underwent LT from October 1989 to August 2013 at our center and subsequently presented with a DH. Among 4433 LT procedures performed in this time period, 1032 were for children. Ten DH cases were recognized, and risk factors were assessed. The mean age at diagnosis was 4.9 years, all patients with a DH received left lateral segment split grafts, and the mean graft weight was 248 ± 41 g with a mean graft-to-recipient body weight ratio (GBWR) of 3% ± 1.22% (range = 1.7%-5.0%). The mean cold ischemia time was 510.7 ± 307.6 minutes (range = 60-900 minutes). Six patients had a primary abdominal muscle closure, 3 had a temporary Silastic mesh closure, and 1 had a skin closure only. Postoperative ascites and pleural effusion did not appear to be significant risk factors. All 10 children presented with a right posterolateral DH, with 1 also having a left DH. The small bowel was herniated in the majority. All patients underwent prompt surgical intervention without complications. An early age, a split graft, and a high GBWR may be risk factors for a DH. A high index of suspicion and prompt surgical intervention minimize complications.

The effect of anterograde persufflation on energy charge and hepatocyte function in donation after cardiac death livers unsuitable for transplant.

Donation after cardiac death (DCD) livers are considered to be marginal organs for solid organ and cell transplantation. Low energy charge (EC) and low purine quantity within the liver parenchyma has been associated with poor outcome after liver transplantation. The aim of this work was to assess the effect of anterograde persufflation (A-PSF) using an electrochemical concentrator on DCD liver energy status and hepatocyte function. Organs utilized for research were DCD livers considered not suitable for transplant. Each liver was formally split, and the control non-persufflated (non-PSF) section was stored in University of Wisconsin (UW) solution at 4°C. The A-PSF liver section was immersed in UW solution on ice, and A-PSF was performed via the portal vein with 40% oxygen. Tissue samples were taken 2 hours after A-PSF from the A-PSF and control non-PSF liver sections for snap freezing. Purine analysis was performed with photodiode array detection. Hepatocytes were isolated from A-PSF and control non-PSF liver sections using a standard organs utilized for research were DCD livers considered not suitable for transplant collagenase perfusion technique. Hepatocyte function was assessed using mitochondrial dehydrogenase activity {3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl tetrazolium bromide (MTT)} and the sulforhodamine B (SRB) assay for cell attachment. In DCD livers with <30% steatosis (n = 6), A-PSF increased EC from 0.197 ± 0.025 to 0.23 ± 0.035 (P = 0.04). In DCD livers with >30% steatosis (n = 4), A-PSF had no beneficial effect. After isolation (n=4, <30% steatosis), A-PSF was found to increase MTT from 0.92 ± 0.045 to 1.19 ± 0.55 (P < 0.001) and SRB from 2.53 ± 0.12 to 3.2 ± 0.95 (P < 0.001). In conclusion, A-PSF can improve the EC and function of isolated hepatocytes from DCD livers with <30% steatosis.

Strategies to reduce hepatitis C virus recurrence after liver transplantation.

Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients.