Recurrence Post Liver Transplantation Research Articles

Sequential Use of Sorafenib and Regorafenib in Hepatocellular Cancer Recurrence After Liver Transplantation: Treatment Strategies and Outcomes.

During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as sorafenib and regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group. We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022 across 11 oncology centers in Turkey. Patients were categorized according to Child-Pugh classification and treated with sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analyzed using the Kaplan-Meier method, and risk factors were evaluated using Cox regression analysis. Of the 73 patients included in the study, 62 were male (84.9%), and 11 were female (15.1%), with a mean age of 61.5 ± 10.9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45.2% (n = 33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with sorafenib was 5.6 months, and the one-year survival rate was 24.3%. The median progression-free survival (PFS2) time with regorafenib, which was administered as second-line treatment, was also calculated as 5.9 months. Overall survival (OS) duration was determined as 35.9 months. The most common side effects associated with both drugs included fatigue, hand and foot syndrome, and hypertension. Significantly better survival outcomes were shown in the Child-Pugh A group compared to other patients. These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group.

Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope?

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.

P.390: Impact of explant pathologic factors on hepatocellular carcinoma recurrence post-liver transplantation: Insights from a retrospective cohort study.

P.390: Impact of explant pathologic factors on hepatocellular carcinoma recurrence post-liver transplantation: Insights from a retrospective cohort study.

Comprehensive assessment of circulatory miRNAs as potential diagnostic markers in HCV recurrence post liver transplantation

HCV recurrence after liver transplantation is one of the causal agents for graft rejection. This study aims to profile non-invasive biomarkers in patients with HCC who had liver transplants. One hundred participants were categorized into three groups (20 control, 32 recurrent HCV (RHCV), and 48 non-RHCV). The expression of six miRNAs (hsa-miR-124-3p, hsa-miR-155-5p, hsa-miR-205-5p, hsa-miR-499a-5p, hsa-miR-574-3p, and hsa-miR-103a-3p) and two mRNAs IL-1β, STAT1 were quantified. RHCV group has higher levels of hsa-miR-574-3p and hsa-miR-155-5p and lesser levels of hsa-miR-499a-5p than control groups (p = 0.024, 0.0001, 0.002; respectively). RHCV and non-RHCV groups revealed a significant reduction in levels of IL-1β and STAT1 mRNA compared to the control (p = 0.011, 0.014; respectively). According to ROC analysis, miR-155-5p can differentiate among the patients’ groups, while miR-574-3p, IL-1β, and STAT1 mRNA can discriminate between RHCV and control groups. In conclusion, RHCV patients have dysregulated expression of five transcripts compared to non-RHCV and control groups.

S3269 A Rare Case of HCC Recurrence as a Bleeding Gastric Ulcer

Introduction: Hepatocellular Carcinoma (HCC) is a potential complication of cirrhosis. Liver transplantation is often viewed as curative of HCC when fulfilling the Milan criteria prior to surgery. However, recurrence rates of HCC post-transplant remain high. Here, we present a case of post-transplant HCC recurrence presenting as a bleeding gastric ulcer. Case Description/Methods: A 72-year-old Caucasian female presented with coffee-ground emesis. Three years prior, she had orthotopic liver transplantation due to hepatitis C virus (HCV) related cirrhosis, previously treated with Vosevi/ribavarin with sustained virologic response and HCC with evidence of moderate differentiation and focus of vascular invasion on explanted liver. Upper endoscopy revealed a cratered gastric ulcer with heaped edges. Biopsies from the ulcer edges showed poorly differentiated adenocarcinoma with signet ring features. Immunohistochemical testing showed tumor cells positive for CK8/18, Glutamine Synthetase, and polyclonal CEA with canalicular pattern; features consistent with high grade HCC. CT scan revealed a necrotic mass replacing most of the pancreatic body and tail, a lung mass and multiple vertebral compression fractures. Fine needle biopsy of pancreatic mass was consistent with metastatic carcinoma compatible with HCC. (Figure) Discussion: Tumor recurrence post-liver transplantation is noted in 15-20% of cases after 5 years. There is no clear consensus for Standard post-transplantation monitoring. A multi-center study has proposed a protocol using the RETREAT (Risk Estimation of Tumor Recurrence Post-Transplantation) scoring system for determining screening of HCC recurrence. This includes: AFP levels prior to transplant (max score of 3 for AFP >1000), vascular invasion (max score of 2 for any evidence of invasion), and sum of the diameters of HCC lesions (max score of 3 for sum >10). In our patient, with microvascular invasion, a score of 2 would standardize her to screening every 6 months for 2 years which was consistent with the monitoring she had. The median time to HCC tumor recurrence is within 12-16 months post-transplantation, with over 75% occurring in first 2 years. Initial presentation of HCC recurrence as a direct gastrointestinal invasion is exceeding rare. There have been few case reports describing similar presentations as in our case, however, none have occurred after liver transplantation. Given its rarity, differential diagnosis of gastric ulcers in patients with history of HCC should include metastatic disease.Figure 1.: A. Gastric Ulcer B. Pancreatic Mass C. Lung Mass.

A218 THE RISK OF RECURRENT HEPATOCELLULAR CARDINOMA IN POST-LIVER TRANSPLANT PATIENTS RECEIVING CAPECITABINE TREATMENT

BackgroundLittle is known on how to reduce the risk of hepatocellular carcinoma (HCC) recurrence post liver transplantation (LT). We examined if adjuvant oral Capecitabine reduces the risk of recurrent HCC in a high-risk group post-LT.AimsTo examine if adjuvant oral Capecitabine reduces the risk of recurrent HCC in a high-risk group post-LT.MethodsA retrospective study was performed from a pre-existing liver transplant database from the Liver Transplant Unit at London Health Sciences Center, London; Canada. This database contains demographic, clinical parameters and follow-up of all patients transplanted for HCC. Data was extracted for patients who underwent LT between January 2000 – April 2018 and included follow up until May 31st, 2020. High-risk of tumor recurrence was defined as a RETREAT score ≥5 or PARFITT score ≥10.5. Log rank test compared the recurrence of HCC or death among patients who were and were not prescribed Capecitabine.ResultsOut of 168 LT for HCC, 25 patients were identified as high-risk group for recurrence. The median age was 63 years (IQR=60–65). 19 (76%) patients had viral hepatitis including Hepatitis B and Hepatitis C as their primary disease while 4 (16%) patients had NASH. The remaining 2 (8%) patients had Autoimmune Hepatitis. 7 (28%) patients received Capecitabine while 18 (72%) did not. All patients were followed for a median of 22 months (IQR=8.9–57.5). No statistical significance difference was found between the two groups with respect to HCC recurrence or death (p=0.56).ConclusionsAmong patients with high risk features for recurrence of HCC, adding Capecitabine therapy added to conventional immunosuppression had no overall effect on reducing overall tumor recurrence or survival.Funding AgenciesNone

Transarterial Chemoembolization (TACE) Plus Sorafenib Compared to TACE Alone in Transplant Recipients with Hepatocellular Carcinoma: An Institution Experience.

Simple SummaryHepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by most clinical practice guidelines. The purpose of this current study was to compare the outcomes of HCC transplant candidates treated at our institution with TACE combined with sorafenib versus TACE monotherapy, which will provide further evidence for clinical practice. This study found that using TACE plus sorafenib is generally well-tolerated and associated with improved overall survival in transplant recipient patients with unresectable HCC. A multi-center and prospective study is needed. Randomized and controlled trials are needed to confirm these preliminary findings.Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by most clinical practice guidelines. The most recent trials of the TACE plus sorafenib combined therapy in patients with unresectable HCC have yielded inconsistent outcomes. The purpose of this study was to compare the outcomes of HCC patients treated with the TACE sorafenib combination as opposed to TACE monotherapy. Methods: This retrospective study included all patients with unresectable HCC who underwent liver transplantation and were treated by either TACE alone or TACE plus sorafenib between July 2008–December 2019. Demographic and clinical data as well as HCC recurrence post-liver transplant (LT) were reported as frequencies and proportions for categorical variables and as the median and interquartile range (IQR) or mean. Chi-square or Fisher’s exact tests were performed for categorical variables and the Kruskal-Wallis test or unpaired test was performed for continuous variables. Kaplan-Meier curves present overall patient survival and HCC-free survival. Results: A total of 128 patients received LT, with a median (IQR) age of 61.4 (57.0, 66.3) years; most were males (77%). Within the TACE-only group, 79 (77%) patients met the Milan criteria and 24 (23%) were beyond the Milan criteria, while the TACE plus sorafenib group had a higher proportion of patients beyond the Milan criteria: 16 (64%) vs. 9 (36%); p = 0.01. The five-year disease-free survival (DFS) between the treatment groups approached significance, with 100% DFS in the TACE plus sorafenib group vs. 67.2% in the TACE-alone group, p = 0.07. Five-year patient survival was 77.8% in the TACE plus sorafenib group compared to 61.5% in the TACE-alone group (p = 0.51). However, in patients who met the beyond Milan criteria, those who received TACE alone had a lower average amount of (percent) tumor necrosis on explant pathology (43.8% ± 32%) compared to patients who received TACE plus sorafenib (69.6% ± 32.8%, p = 0.03). Conclusion: This study identified that using TACE plus sorafenib is generally well-tolerated and demonstrated improved overall survival compared to TACE only in transplant recipients with unresectable HCC. A multi-center and prospective randomized controlled trial is needed to substantiate these findings.

State of the art treatment of hepatitis B virus hepatocellular carcinoma and the role of hepatitis B surface antigen post-liver transplantation and resection.

Chronic hepatitis B virus (HBV) infection is the major aetiology of hepatocellular carcinoma (HCC). The optimal goal of therapy, hepatitis B surface antigen (HBsAg) loss and anti‐HBs production, is achieved rarely and HBsAg‐associated HCC risk is well recognized. Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post‐liver transplantation or resection, and the implications for therapy. HBV‐associated carcinogenesis is a multifactorial process. The observation that HBV‐related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg‐positive patients post‐liver transplantation has been reported in 10%‐15% of patients and is likely to be because of expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post‐liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV‐derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post‐surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post‐liver transplantation. Use of hepatitis B immunoglobulins that target HBsAg directly, alongside immune‐oncology therapies, may be relevant in this setting.

Risk stratification of patients with hepatocellular carcinoma undergoing trans arterial chemoembolization using an alpha-fetoprotein model

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are multiple factors that could affect the malignancy and progression of HCC including tumor number, size, and macrovascular invasion. The alpha-fetoprotein (AFP) model was validated as a predictor for HCC recurrence post-liver transplantation, especially in France. However, the AFP model has not been studied on patients with HCC undergoing locoregional treatment. This study aimed to assess the prognostic value of the AFP model in patients with HCC undergoing trans arterial chemoembolization (TACE). This cohort study was conducted at Ain Shams University Hospitals, Cairo, Egypt. We included all newly diagnosed patients with HCC who were fit for TACE from January 2012 to January 2017. The AFP model was calculated for each patient before TACE. Subsequently, we classified them into low- and high-risk groups for TACE. The patients were followed up by AFP level and triphasic spiral CT performed 1 month after TACE to evaluate the response then at 4 months and 7 months post TACE to evaluate the local and distant recurrence.ResultsOne hundred and thirty-two patients were included in the study. Complete response (CR) was achieved nonsignificantly at a higher percentage in the low-risk group in comparison with the high-risk group. One- and three-year recurrence-free survivals (RFS) were longer in the low-risk group in comparison with the high-risk group (50% and 24.1% vs. 29.1% and 16.2%, respectively). One- and three-year overall survival (OS) rates were 97% and 37.3% in the low-risk group vs. 98.1% and 11.6% in the high-risk group, respectively, without statistical significance. On classifying patients with AFP levels < 100 IU/mL into low- and high-risk patients, CR was achieved in a significantly higher percentage in the low-risk group in comparison with the high-risk group(P < 0.05). Recurrence occurred nonsignificantly in a less percentage in low than high-risk group. The median OS was significantly higher in the low-risk group in comparison with that in the high-risk group (18 vs. 16 months respectively) (P < 0.01).ConclusionThe AFP model may have a prognostic value for patients with HCC undergoing TACE especially in patients with an AFP level < 100 IU/mL.

Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan

Background and aimsLiver 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.MethodsPatients 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.ResultsSeventy-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.ConclusionsSignificantly 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.

Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

BackgroundOrthotropic liver transplantation (OLT) offers a therapeutic choice for hepatocellular carcinoma (HCC) patients. The poor outcome of liver transplantation is HCV recurrence. Several genome-wide associated studies (GWAS) have reported many genetic variants to be associated with HCV recurrence. Seven gene polymorphisms formed a cirrhosis risk score (CRS) signature that could be used to distinguish chronic HCV patients at high risk from those at low risk for cirrhosis in non-transplant patients. This study aims to examine the association of CRS score and other clinical parameters with the probability for HCC emergence and/or the rate of HCV recurrence following liver transplantation. ResultsSeven gene polymorphisms, forming the CRS, were genotyped by real-time PCR using allelic discrimination protocol in 199 end-stage liver disease patients (79 child A, 43 child B, and 77child C), comprising 106 patients who encountered liver transplantation. Recipient CRS scores were correlated with HCV recurrence (HCV-Rec) at the end of the third year after OLT. Around 81% (39) recipients with low steatosis (LS; < 3.5%) donor percentage revealed no HCV recurrence (non-Rec) (p<0.001). CRS score could distinguish between child A, child B, and child C only at the low-risk group. Among the HCV Rec group 27% (8/30), 40% (12/30), and 33% (10/30) fell into the high, moderate, and low CRS risk groups, respectively. Stepwise logistic regression evinced two features more likely to be seen in HCV-Rec patients: abnormal ALT [OR, 1.1; 95% CI, 1.02–1.2] and donor steatosis >3.5% [OR, 46.07; 95% CI, 1.5–1407.8]. ConclusionsAccordingly, the CRS score seems to be less useful to predict HCV recurrence after OLT. ALT and donor steatosis (exceed 3.5%) can significantly promote the HCV recurrence post-OLT. Moreover, the combination of MMF and CNI positively heightens HCV recurrence.

Sex-based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation.

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. 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. 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). 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.

PSC recurrence post liver transplantation: retransplantation justified or not?

Post-liver transplant (LT), primary disease recurrence is a major cause of graft failure and long-term patient mortality (1). For decades, hepatitis C virus (HCV) recurrence was the number one cause of graft loss (2); however, with the development of potent anti-viral therapy, HCV transplant recipients no longer experience graft loss and death. In contrast, recurrence of autoimmune disease - particularly Primary Sclerosing Cholangitis (PSC) - remains a valid concern for the liver transplant community. This is despite an excellent short-term outcome post LT, with a survival rate above 90 % within the first year after transplant (3).

S1083 Assessing Predictors of Microvascular Invasion of HCC at Explant in Liver Transplantation

INTRODUCTION: Liver transplant (LT) is curative in patients with cirrhosis complicated by hepatocellular cancer (HCC) within T2/Milan Criteria. Microvascular invasion (MVI) of HCC portends poor prognosis and is associated with higher risk of recurrence post LT; however, is often undetectable with multiphasic imaging modalities during pre-LT staging. Factors associated with the presence of MVI at LT remain poorly defined. Our aim is to examine pre-LT clinical demographic and tumor related factors and their association with MVI on explant at LT. METHODS: Retrospective evaluation identifying 154 consecutive patients undergoing LT with HCC over a 5-year timeframe (2012-2017). HCC explant pathologic specimen reports reviewed identifying tumor focality, site, size (greatest dimension), histologic type and grade; and presence/absence of microvascular and perineural invasion. Review allowed for stratification into MVI on explant and no MVI on explant groups. Demographic and tumor variables were collected for the MVI and no MVI groups assessing for differences in: age, days on wait-list ( > or < 365) , gender, race, BMI, etiology of cirrhosis, biologic model for end-stage liver disease (MELD) score, number of presenting lesions, tumor volume, type of locoregional therapy (LRT), response to initial and number of bridging therapies; categorical variables analyzed using Fisher’s exact test; continuous variables compared using Levine’s t-test for equal variances and student’s t-test; P < 0.05, significant. RESULTS: 154 LT recipients for HCC reviewed with 16 (10.4%) demonstrating MVI on explant. No significant demographic differences between MVI and non MVI groups apart from age 59 +/- 6 years vs 60+/- 6 years (P < 0.0001) [Table 1]. No significant differences in LRT modality or number of presenting lesions. Although trends associated with presence of MVI were seen (shorter wait times for LT, larger total tumor volume, and increased number of LRT sessions); differences did not reach significance between cohorts. CONCLUSION: Demographic and current staging modalities for HCC do not reliably capture or predict the phenomenon of MVI on explant. Presence of MVI may be associated with larger tumor volumes and shorter wait times. Results support the current approach of 6 month wait times for MELD exception points and call further attention to the unmet need for tissue or serum-based biomarkers in HCC prognosis.Table 1.: Characteristics of liver transplant patients

Single-Center North American Experience of Liver Transplantation in Autoimmune Hepatitis: Infrequent Indication but Good Outcomes for Patients.

Background and AimsA 40% risk of disease recurrence post-liver transplantation (LT) for autoimmune hepatitis (AIH) has been previously reported. Risk factors for recurrence and its impact on long-term patient outcome are poorly defined. We aimed to assess prevalence, time to disease recurrence, as well as patient and graft survival in patients with recurrent AIH (rAIH) versus those without recurrence.MethodsSingle-center retrospective study of adult recipients who underwent LT for AIH between January 2007 and December 2017. Patients with AIH overlap syndromes were excluded.ResultsA total of 1436 LTs were performed during the study period, of whom 46 (3%) for AIH. Eight patients had AIH overlap syndromes and were excluded. Patients were followed up for 4.4 ± 3.4 years and mean age at LT was 46.8 years. Average transplant MELD (Model for End-Stage Liver Disease) score was 24.9. About 21% of patients (8 of 38) were transplanted for acute onset of AIH; 66% of patients (n = 25) received a deceased donor liver graft, and 34% a living donor organ. rAIH occurred in 7.8% (n = 3/38) of recipients. Time to recurrence was 1.6, 12.2 and 60.7 months. Patient and graft survival in patients without recurrence was 88.6% and 82.8% in 5 years, whereas in those with rAIH, it was 66.7%, respectively.ConclusionAlthough AIH recurs post-LT, our data indicate a lower recurrence rate when compared to the literature and excellent patient and graft survival.

AFP ratio predicts HCC recurrence after liver transplantation.

Background/aimsHepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels.MethodsWe performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence.Results19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5.ConclusionA rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.

Recipient interleukin 6 gene polymorphism and expression predict HCV recurrence post liver transplantation.

Liver transplantation (LTX)is a lifesaving- effective protocol for patients suffering end stage liver disease (ESLD) and its complications post HCV infection. Recurrence of disease is a frequent clinical complication that is observed in patients undergoing LTX. Cytokines play a central role in the immunological events occurring after the surgery. Using Allelic Discrimination PCR, the allelic variation G174C of IL-6 gene was investigated. The abundance of IL6- mRNA and plasma IL6 cytokine levels were evaluated by using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and enzyme-linked immunosorbent assay (ELISA) respectively in 76 liver transplant recipients recruited from Al Sahel teaching hospital, Ministry of Health and Population Cairo Egypt within the period between June 2015 and October 2017. The frequencies of IL-6 GG genotype and the G allele were significantly detected more in LTX recipients who experienced HCV recurrence versus those who did not suffer recurrence when compared to healthy controls (P=0.001) and (P=0.006), respectively. On the contrary, levels of IL-6 related transcripts in PBMC's of recurrent patients were indifferent from non-recurrent patients and healthy controls (P≥0.124). Interestingly, the circulating IL-6 protein in plasma was significantly elevated in recurrent as compared to the non-recurrent recipients (P=0.002). HCV recurrence post liver transplantation occur more frequently in patients with -174 G/G IL-6 genotype and elevated plasma IL-6 levels.

Evaluation of Different Regimens of New Direct Acting Antiviral drugs (DAAs) for treatment of Recurrent Hepatitis C Virus Infection after Liver Transplantation

Abstract Aim of the work To compare between different available regimens of DAAs (sofosbuvir/ daclatasvir and sofosbuvir / ledipasvir) regarding the efficacy and safety for treatment of compensated recurrent hepatitis C Virus infection after liver transplantation in Egyptian patients and to study the correlation between sofosbuvir / daclatasvir and sofosbuvir / ledipasvir and post-transplant complications. Background Liver transplantation is the only curative treatment for ESLD and HCC. Liver disease resulting from chronic HCV infection is the leading indication for liver transplantation. For patients with detectable HCV-RNA levels at the time of transplantation, postoperative recurrence of HCV infection was “immediate and universal.” Recurrent HCV infection follows an aggressive course and retransplantation frequently is associated with a poor outcome. Patients and Methods This prospective study was conducted on recipients, who underwent living donor liver transplantation in Ain Shams Center for Organ Transplantation (ASCOT) at Ain Shams University Specialized Hospital (ASUSH), Cairo, Egypt between June, 2016 and May, 2017. Data of the recipients, who underwent living donor liver transplantation during the study period, were reviewed and the patients who fulfilled the inclusion criteria were enrolled into this study. The patients who fulfilled the inclusion criteria and received antiviral treatment were followed up monthly during their treatment and after finishing treatment for at least 3 months. Results Treatment of HCV recurrence in liver transplant recipients with SOF+DCV+RBV or SOF/LDV+RBV seems to confer high rates of SVR. There was no difference between both regimens regarding adverse events. Prolonged treatment of HCV recurrence after LDLT (24 weeks) was significantly associated with a higher SVR (P = 0.035). Conclusion Adding RBV to antiviral regimens in the treatment of HCV recurrence in liver transplant recipients doesn’t seem to add to the efficacy of DAAs. Adherence to prolonged course of antiviral treatment (6 months) when treating HCV recurrence post liver transplantation seems to be associated with higher rates of SVR than shorter course (3 months) with no increase in the incidence of adverse events or rejection episodes.

Milan-out Criteria and Worse Intention-to-Treat Outcome Postliver Transplantation.

Background.Milan criteria are widely used for liver transplantation selection in hepatocellular carcinoma but have been recognized to be too restrictive. Milan-out criteria are increasingly being adopted. Our aim was to analyze if liver transplantation waitlisted Milan-out hepatocellular carcinoma patients have different outcome than Milan patients.Methods.Retrospective study including all consecutive patients with hepatocellular carcinoma admitted in the waiting list for liver transplantation between January 2012 and January 2015. We included 177 patients, 146 of which eventually transplanted. Downstaging was achieved in the Milan-out cases (n = 29) before waitlisting.Results.From diagnosis to last follow-up, 29% patients died. Survival at 1 and 5 years from diagnosis was 93% and 75%, respectively in the within Milan group compared with 91% and 61% in the Milan-out group (P = 0.03). Treatment failure occurred in 20% of cases due to tumor progression in the waiting list (44%), death on the waiting list (20%), and hepatocellular carcinoma recurrence postliver transplantation (9%). Milan-out criteria was the only variable predictive of treatment failure remaining in the multivariate analysis with a hazard ratio (HR) of 1.7 (HR, 1.7; 95% confidence interval, 1.34-4.55; P = 0.010) and HR of 1.43 (1.23-6.5) in the hepatocellular carcinoma recurrence.Conclusions.Milan-out criteria are associated with a higher intention-to-treat liver transplantation failure from time of inclusion in the waiting list. However, survival rates are still >50% at 5 years of follow-up.

Effect of cyclosporine A versus tacrolimus on the response to antiviral therapy after hepatitis C genotype‐4 recurrence post–liver transplantation: A prospective cohort trial

The influence of immunosuppression on the response to antiviral therapy (AVT) for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients remains controversial, especially for the rarely investigated genotype 4. This study aims to compare the effects of the two widely used calcineurin inhibitors (CNIs) (cyclosporine A (CsA) and tacrolimus (Tac)) on the therapeutic response to different AVT regimens. A prospective, dual-centre, cohort study of 126 Egyptian living donor liver transplant (LDLT) recipients with recurrent HCV genotype 4 infection, who were categorized into three groups according to the AVT used. Group I received pegylated interferon (Peg-IFN-α 2a) plus ribavirin (RBV) (n=44), group II received the direct antiviral agent (DAA) sofosbuvir plus RBV (n=52) and group III received daclatasvir and sofosbuvir (also DAAs) plus RBV (n=30). Each group was further subdivided according to the primary immunosuppression (CsA or Tac). The sustained virological response (SVR) and relapse rates were considered the primary therapeutic outcomes of AVT. No significant intergroup differences were observed in the achievement of primary and secondary outcomes. SVR rates in the IFN-based regimen were 75% and 66.7% in CsA and Tac users and 81.2% and 83% in DAAs, respectively. Relapse rates in the IFN-based regimen were 10% and 16.7% in CsA and Tac users and 12.5% and 14.9% in DAAs, respectively. Within the limitations of a relatively small study, CsA did not offer an advantage over Tac regarding the response to AVT after HCV genotype 4 recurrence in LDLT recipients.