Hepatocellular Carcinoma In Non-cirrhotic Liver Research Articles

Comparison of Characteristics and Survival of New-Onset Hepatocellular Carcinomas With or Without Cirrhosis in a Tertiary Center.

Although hepatocellular carcinoma (HCC) usually develops in cirrhotic livers, HCCs could also arise in non-cirrhotic livers. We aimed to compare the characteristics and survival of cirrhotic- and non-cirrhotic HCCs. Data of HCC patients between 2011 and 2021 in a single tertiary center was evaluated retrospectively. Demographic, clinical, laboratory, tumoral and pathological features, and survival outcomes of cirrhotic and non-cirrhotic HCCs were compared. The study included 188 HCC patients. Median age was 64 (26-92) years and similar for study groups (P = .208). Both groups had similar male/female ratio. Forty-two patients (22.3%) had HCC in non-cirrhotic liver. Non-cirrhotic HCCs had similar tumor differentiation type, radiological characteristics, Milan, University of California San Francisco, and the Barcelona Clinic Liver Cancer stages, but more unifocal lesion (78.6% vs. 59.6%) and larger tumor size (89.5 (16-240) mm vs. 59.0 (12-290) mm) at presentation compared to non-cirrhotic HCCs. Despite larger tumor size, non-cirrhotic HCC patients had better overall, disease-free and progression-free survival rates than cirrhotic HCCs. Overall survivals for 1 and 3 years were 71.4% and 49.7% for non-cirrhotic and 54% and 28.3% for cirrhotic HCCs, respectively (P = .035). According to Cox analyses, Eastern Cooperative Oncology Group score (P <.001, hazards ratio (HR): 4.05) and curative treatments (P < .001, HR: 0.21) were predictive for overall survival in cirrhotic HCCs. Curative treatment (P = .027, HR: 0.31) was found to be a significant predictor for overall survival in non-cirrhotic HCCs. Vascular invasion was the only independent predictor for disease-free survival (HR: 2.62, 95% CI 1.01-6.93, P = .049) for non-cirrhotic HCCs. Despite larger tumor size and similar tumor stages, compared to cirrhotic HCCs, non-cirrhotic HCCs were associated with better survival outcomes.

An Uncommon Presentation of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, with an important characteristic being the development on a background of cirrhosis. HCC in non-cirrhotic liver is rare. We report a case of an HCC on a non-cirrhotic liver in a 66-year-old patient who was admitted with a 3 months history of right hypochondriac pain and weight loss. He had a medical history of hypertension, type 2 diabetes, obesity, and no alcohol abuse. Abdominal computed tomography (CT) and hepatic magnetic resonance imaging (MRI) showed a 115x100x110mm mass in the segment V and VIII, hypodense with heterogeneous and early arterial enhancement, and clearing in portal and late phase. He underwent a liver biopsy that confirmed an HCC without underlying cirrhosis. Surgical treatment was not an option since our patient presented multiple risk factors of recurrence. The patient underwent two sessions of transarterial chemoembolization (TACE) but the follow-up showed signs of progression.

The expression of VEGF and cyclin D1/EGFR in common primary liver carcinomas in Egypt: an immunohistochemical study.

The most common types of primary malignant liver tumours are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Treatment options for patients who are inoperable/advanced, or recurring are challenging. Cyclin D1, epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGR) are common carcinogenic proteins that have potential therapeutic targets in various cancers. They have been implicated in the development of HCC and CCA. In this study, we aimed to evaluate the oncogenic function expression of cyclin D1, EGFR and VEGF in HCC and CCA of Egyptian patients. This could help to validate their therapeutic potential. Tumour cases were selected from 82 cases of primary liver carcinomas, with 58 cases being from HCC and 24 cases from CCA compared to 51 non-tumour adjacent liver cases and 18 from normal liver tissue. The immunohistochemical study of cyclin D1, EGFR and VEGR was conducted. Cyclin D1, EGFR and VEGF are overexpressed in HCC and CCA as compared to the control group (p < 0.001). Cyclin D1 was related to well-differentiated grade and early pathologic stage in HCC (p = 0.016 and p = 0.042, respectively). The well-differentiated grade showed significantly higher VEGF levels (p = 0.04). In the CCA group, however, EGFR was strongly related to high tumour size (p = 0.047). EGFR and VEGF were overexpressed in HCC raised in the non-cirrhotic liver compared to those developed in post-hepatitic liver cirrhosis (p = 0.003 and p = 0.014). Cyclin D1, EGFR and VEGF shared significant overexpression in HCC and CCA. EGFR and VEGF may play an oncogenic function in the development of HCC in non-cirrhotic liver. Furthermore, cyclin D1 and VEGF may play a good prognostic function in HCC, but EGFR may play a bad prognostic role in CCA.

Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma.

Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma.

Case Report: Non-Cirrhotic Hepatoma BCLC-C With Vertebrae Metastasis

Background: Hepatocellular carcinoma (HCC) can arise from either cirrhosis or non-cirrhosis of the liver. HCC in non-cirrhotic livers is still uncommon and can present insidiously in patients. HCC may develop in people with non-cirrhotic chronic liver illness, such as chronic hepatitis B virus infection and chronic HCV infection. More than half of non-cirrhotic individuals with HCC may not exhibit any symptoms, and the disease is frequently detected when it is advanced and incurable. Case Report: Here we presented a 47-year-old man went to the emergency room complaining of upper right side abdominal discomfort that suddenly arose and spread to the back and right shoulder. He also experiencing upper right abdominal fullness for the past two months, along with a sense of a lump growing larger and harder. Hepatic stigmata were not discovered, whole blood revealed a thrombocytosis and significant rising AFP from the expected result of 71,000 ng/dL, with hepatitis B testing was positive. Abdominal ultrasound revealed hepatomegaly and several hypo-hyperechoic nodules. CT scan revealed multiple solid lesions and lytic lesions of the vertebrae bodies. The patient recieved palliative treatment.. Conclusion: This case study demonstrates a non-cirrhotic hepatoma that came at an80 tan advanced stage and was more likely to be asymptomatic than a cirrhotic hepatoma that showed signs of liver failure, such as hepatic stigmata and other physiologic abnormalities. This case report demonstrates the This case study demonstrates the importance of strengthening general HHC preventative measures in order to lower non-cirrhotic HHC's incidence and fatality rate.

Giant hepatocellular carcinoma in non-cirrhotic liver: Treatment with ALPPS and MINIALPPS

Background: Oncological resection of liver tumors continues to be the best alternative to increase survival and the disease-free period of patients. Thanks to liver regeneration, liver hypertrophy techniques are a great alternative in the surgical management of patients with high tumor burden. A few years ago, a surgical technique for liver hypertrophy called ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy) was described. In recent years, groups in Chile and Argentina have developed a variant of this which they have called MINIALPPS.

Outcome after Resection for Hepatocellular Carcinoma in Noncirrhotic Liver-A Single Centre Study.

Liver cirrhosis is the most common risk factor for the development of hepatocellular carcinoma (HCC). However, 10 to 15% of all HCC arise in a non-cirrhotic liver. Few reliable data exist on outcome after liver resection in a non-cirrhotic liver. The aim of this single-centre study was to evaluate the outcome of resection for HCC in non-cirrhotic liver (NC-HCC) and to determine prognostic factors for overall (OS) and intrahepatic recurrence-free (RFS) survival. From 2008 to 2020, a total of 249 patients were enrolled in this retrospective study. Primary outcome was OS and RFS. Radiological and pathological findings, such as tumour size, number of nodules, Tumour-, Nodes-, Metastases- (TNM) classification and vascular invasion as well as extent of surgical resection and laboratory liver function were collected. Here, 249 patients underwent liver resection for NC-HCC. In this case, 50% of patients underwent major liver resection, perioperative mortality was 6.4%. Median OS was 35.4 months (range 1–151 months), median RFS was 10.5 months (range 1–128 moths). Tumour diameter greater than three centimetres, multifocal tumour disease, vascular invasion, preoperative low albumin and increased alpha-fetoprotein (AFP) values were associated with significantly worse OS. Our study shows that resection for NC-HCC is an acceptable treatment approach with comparatively good outcome even in extensive tumours.

Imaging Features of Hepatocellular Carcinoma in the Non-Cirrhotic Liver with Sonazoid-Enhanced Contrast-Enhanced Ultrasound.

Purpose: To investigate the Sonazoid-enhanced contrast-enhanced ultrasound (CEUS) features of hepatocellular carcinoma (HCC) in a non-cirrhosis liver background, in comparison to those in liver cirrhosis. Methods: In this retrospective study, 19 patients with surgery and histopathologically proven HCC lesions in non-cirrhosis liver background were included regarding Sonazoid-enhanced CEUS characteristics. Two radiologists evaluated the CEUS features of HCC lesions according to the WFUMB (World Federation of Societies for Ultrasound in Medicine and Biology) guidelines criteria. Thirty-six patients with HCC lesions in liver cirrhosis were included as a control group. Final diagnoses were confirmed by surgery and histopathological results. Results: Liver background of the non-cirrhosis group including normal liver (n = 7), liver fibrosis (n = 11), and alcoholic liver disease (n = 1). The mean size of non-cirrhosis HCC lesions was 60.8 ± 46.8 mm (ranging from 25 to 219 mm). During the arterial phase of Sonazoid-enhanced CEUS, most HCCs in non-cirrhotic liver (94.7%, 18/19) and in cirrhotic liver (83.3%, 30/36) presented non-rim hyperenhancement. During the portal venous phase, HCC lesions in the non-cirrhosis liver group showed relatively early washout (68.4%, 13/19) (p = 0.090). Meanwhile, HCC lesions in liver cirrhosis background showed isoenhancement (55.6%, 20/36). All lesions in the non-cirrhotic liver group showed hypoenhancement in the late phase and the Kupffer phase (100%, 19/19). Five cases of HCC lesions in liver cirrhosis showed isoenhancement during the late phase and hypoenhancement during the Kupffer phase (13.9%, 5/36). The rest of the cirrhotic HCC lesions showed hypoenhancement during the late phase and the Kupffer phase (86.1%, 31/36). Additional hypoenhanced lesions were detected in three patients in the non-cirrhosis liver group and eight patients in the liver cirrhosis group (mean size: 13.0 ± 5.6 mm), which were also suspected to be HCC lesions. Conclusions: Heterogeneous hyperenhancement during the arterial phase as well as relatively early washout are characteristic features of HCC in the non-cirrhotic liver on Sonazoid-enhanced CEUS.

Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers

Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers

Differentiation of hepatocellular adenoma by subtype and hepatocellular carcinoma in non-cirrhotic liver by fractal analysis of perfusion MRI

BackgroundTo investigate whether fractal analysis of perfusion differentiates hepatocellular adenoma (HCA) subtypes and hepatocellular carcinoma (HCC) in non-cirrhotic liver by quantifying perfusion chaos using four-dimensional dynamic contrast-enhanced magnetic resonance imaging (4D-DCE-MRI).ResultsA retrospective population of 63 patients (47 female) with histopathologically characterized HCA and HCC in non-cirrhotic livers was investigated. Our population consisted of 13 hepatocyte nuclear factor (HNF)-1α-inactivated (H-HCAs), 7 β-catenin-exon-3-mutated (bex3-HCAs), 27 inflammatory HCAs (I-HCAs), and 16 HCCs. Four-dimensional fractal analysis was applied to arterial, portal venous, and delayed phases of 4D-DCE-MRI and was performed in lesions as well as remote liver tissue. Diagnostic accuracy of fractal analysis was compared to qualitative MRI features alone and their combination using multi-class diagnostic accuracy testing including kappa-statistics and area under the receiver operating characteristic curve (AUC). Fractal analysis allowed quantification of perfusion chaos, which was significantly different between lesion subtypes (multi-class AUC = 0.90, p < 0.001), except between I-HCA and HCC. Qualitative MRI features alone did not allow reliable differentiation between HCA subtypes and HCC (κ = 0.35). However, combining qualitative MRI features and fractal analysis reliably predicted the histopathological diagnosis (κ = 0.89) and improved differentiation of high-risk lesions (i.e., HCCs, bex3-HCAs) and low-risk lesions (H-HCAs, I-HCAs) from sensitivity and specificity of 43% (95% confidence interval [CI] 23–66%) and 47% (CI 32–64%) for qualitative MRI features to 96% (CI 78–100%) and 68% (CI 51–81%), respectively, when adding fractal analysis.ConclusionsCombining qualitative MRI features with fractal analysis allows identification of HCA subtypes and HCCs in patients with non-cirrhotic livers and improves differentiation of lesions with high and low risk for malignant transformation.

Is there a role for liver transplantation in the treatment of hepatocellular carcinoma in non-cirrhotic liver?

Is there a role for liver transplantation in the treatment of hepatocellular carcinoma in non-cirrhotic liver?

Histopathological growth patterns modify the prognostic impact of microvascular invasion in non-cirrhotic hepatocellular carcinoma.

Microvascular invasion (MVI) is an established prognosticator in hepatocellular carcinoma (HCC). Histopathological growth patterns (HGPs) classify the invasive margin of hepatic tumors, with superior survival observed for the desmoplastic HGP. Our aim was to investigate non-cirrhotic HCC in light of MVI and the HGP. A retrospective cohort study was performed in resected non-cirrhotic HCC. MVI was assessed prospectively. The HGP was determined retrospectively, blinded, and according to guidelines. Overall and disease-free survival (OS, DFS) were evaluated by Kaplan-Meier and multivariable Cox regression. The HGP was determined in 155 eligible patients, 55 (35%) featured a desmoplastic HGP. MVI was observed in 92 (59%) and was uncorrelated with HGP (64% vs 57%, p=0.42). On multivariable analysis, non-desmoplastic and MVI-positive were associated with an adjusted HR [95%CI] of 1.61 [0.98-2.65] and 3.22 [1.89-5.51] for OS, and 1.59 [1.05-2.41] and 2.30 [1.52-3.50] for DFS. Effect modification for OS existed between HGP and MVI (p<0.01). Non-desmoplastic MVI-positive patients had a 5-year OS of 36% (HR: 5.21 [2.68-10.12]), compared to 60% for desmoplastic regardless of MVI (HR: 2.12 [1.08-4.18]), and 86% in non-desmoplastic MVI-negative. HCCs in non-cirrhotic livers display HGPs which may be of prognostic importance, especially when combined with MVI.

Higher Accumulation of Visceral Adipose Tissue Is an Independent Risk Factor for Hepatocellular Carcinoma among Viral Hepatitis Patients with Non-Cirrhotic Livers.

Simple SummaryHepatocellular carcinoma (HCC) occurring in non-cirrhotic livers is often overlooked in clinical practice because the present HCC surveillance strategies usually focus only on patients with cirrhotic livers. This study aimed to determine the risk factors for HCC among viral hepatitis patients with non-cirrhotic livers. The findings of this study could be very useful in detecting HCC at an early stage, especially in patients with viral hepatitis who may not have developed extensive cirrhosis.This study aimed to determine the risk factors for hepatocellular carcinoma in non-cirrhotic livers among viral hepatitis patients. A total of 333 HCC cases, including 69 hepatitis B virus (HBV)-related and 264 hepatitis C virus (HCV)-related, were divided into cirrhotic (Fibrosis-4 [FIB-4] index > 3.25) and non-cirrhotic groups (FIB-4 index ≤ 3.25). The clinical characteristics of the two groups were compared. The independent risk factors for the development of HCC were analyzed using logistic regression analysis. The patients with HBV-related HCC were significantly younger, had better Child-Pugh scores, lower FIB-4 index and Mac-2 binding protein glycosylated isomers (M2BPGi) levels, more progressive cancer stage, and higher alpha-fetoprotein (AFP) levels than those with HCV-related HCC. Diabetes mellitus and hypertension were less common in patients with HBV-related HCC. The non-cirrhotic group with HBV-related HCC had a higher visceral adipose tissue index (VATI), better Child-Pugh score, and higher hemoglobin A1c (HbA1c), whereas the one with HCV-related HCC had a higher proportion of men, higher VATI, better Child-Pugh score, higher HbA1c, and a higher prevalence of hypertension, than the corresponding cirrhotic groups. Logistic regression analyses demonstrated that age, male sex, VATI, HbA1c, the presence of hypertension, and HBV etiology were independent risk factors for HCC in a non-cirrhotic liver. A high accumulation of VAT is a risk factor for HCC in patients with non-cirrhotic livers.

Hepatocellular Carcinoma: Does the Background Liver With or Without Cirrhosis Matter?

The pathologic differences between hepatocellular carcinoma (HCC) arising in noncirrhotic and cirrhotic livers have not been well studied. We performed a retrospective analysis of 378 HCC cases (95 in noncirrhotic, 283 in cirrhotic livers) from pathology archives (2010-2017). Patients without cirrhosis were more likely to have hepatitis B (13.68% vs 2.83%, P < .001) or no known liver disease (30.53% vs 4.24%, P < .001), while hepatitis C was more common in patients with cirrhosis (65.72% vs 30.53%, P < .001). HCCs in noncirrhotic livers were larger in size (P < .001); were more likely to have a macrotrabecular histologic pattern (13.68% vs 4.95%, P < .01); were more likely to have fibrolamellar (3.16% vs 0%, P = .02), macrotrabecular-massive (13.68% vs 6.01%, P = .03), and clear cell (16.84% vs 6.71%, P < .01) subtypes; have a higher histologic grade (P < .01); be anaplastic tumor cells (P < .001); have a higher rate of vascular invasion (P < .01); and have a higher tumor stage (P = .04). The findings indicate that HCCs in noncirrhotic livers demonstrate a larger tumor size; have a more macrotrabecular histologic pattern; have fibrolamellar, macrotrabecular-massive, and clear cell subtypes; have a higher tumor grade and stage; have a higher rate of vascular invasion; and have more anaplastic tumor cells compared with cirrhotic livers. Further studies to explore different pathways that promote oncogenesis in noncirrhotic livers are needed to better understand the pathogenesis of HCC.

Hepatocellular Carcinoma in Non-cirrhotic Liver Arises with a More Advanced Tumoral Appearance: A Single-Center Cohort Study.

A small proportion of all hepatocellular carcinomas (HCCs) arise in a non-cirrhotic liver (NCL). However, our knowledge about the HCCs developing in a NCL is scarce. This study was undertaken to investigate the characteristics and survival course of this patient group. We retrospectively analyzed the database of patients with HCC at a tertiary center during a 10-year period (2009-2019). All demographic, clinical, laboratory, and tumoral features with survival outcomes were compared between the HCC-CL and HCC-NCL groups. Out of 384 HCC cases, 11.2% (n = 43) had no cirrhosis. The dominant etiology in the HCC-NCL group was hepatitis B virus (n = 26, 60.5%), followed by non-alcoholic fatty liver disease (n = 10, 23.2%), and hepatitis C virus (n = 7, 16.3%). The maximum tumor diameter was approximately 2 times larger in the HCC-NCL group (HCC-NCL: 90 mm vs. HCC-CL: 46.5 mm, P < .001). The proportion of patients with vascular (HCC-NCL: 27.9% vs. HCC-CL: 8.6%, P < .001) and extrahepatic invasion (HCC-NCL: 14% vs. HCC-CL: 3%, P = .001) were prominently higher in the HCC-NCL group. Patients with HCC-NCL were less often detected in early-curable stages (BCLC 0-A) than those in the HCC-CL group (HCC-NCL: 16.3% vs. HCC-CL: 34.9%, P = .004). The overall survival was not different between the 2 groups (HCC-NCL: 19.4 ± 9.8 months vs. HCC-CL: 17.5 ± 2.3 months, P = .581). HCC in NCL is diagnosed at more advanced tumoral stages with larger tumor size and more often with vascular and extrahepatic spread. Despite the preserved liver functions, the overall survival is not prolonged in HCCs without cirrhosis, due to the late recognition.

Liver Resections Can Be Safely Performed in Cirrhotic Patients after Careful Patient Selection

Hepatocellular Carcinoma (HCC) is the most frequent malignant primary liver tumour in a cirrhotic liver. Liver transplantation and resection are the only curative treatment options in compensated liver cirrhosis, but liver resections are associated with increased perioperative morbidity and mortality. We identified 108 cirrhotic patients, who underwent liver resections at the University Hospital of Mainz between January 2008 and December 2019. During the same period, 185 liver resections were performed for HCC in non-cirrhotic livers. Furthermore, 167 liver resections served as control group, which were performed for colorectal liver metastases (CRLM) with comparable extent of resection to HCC in cirrhotic livers. Preoperatively, we assessed the Charlson Comorbidity Index (CCI), MELD and Child scores in addition to the general patient characteristics. Perioperative morbidity was graded according to the Clavien-Dindo classification. Resections of HCC in cirrhosis and liver metastases were additionally compared by a matched-pair analysis. The three groups were comparable in age. Preoperative liver function was best in patients with CRLM (p < 0.001). Resections for HCC in non-cirrhotic livers were more extended than in cirrhotic livers (p < 0.001). The overall morbidity (Clavien/Dindo stage III - IV) was higher after resections in cirrhotic livers than in CRLM resections (p = 0.026). Postoperative mortality was comparably low in all three groups (2.2%). Neither MELD nor Child score was predictive for postoperative morbidity or mortality (area under the curve: AUC < 0.6, each). Preoperative CCI was predictive for postoperative mortality (AUC = 0.78). Liver resections in cirrhotic livers are feasible after adequate patient selection and limitation of the extent of surgery. Comorbidities additionally increase the postoperative mortality in addition to impaired liver function and should therefore always be included into the preoperative assessment of patients undergoing liver surgery.

Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma in noncirrhotic liver. A case report and systematic review.

IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer. Spontaneous rupture of HCC is an acute complication with a high mortality rate. The HCC principally arises in the background of chronic liver disease and cirrhosis of the liver. In the last few years, the rising incidence of HCC in noncirrhotic liver suggests the presence of other factors that may play a role in liver carcinogenesis.MethodsWe reviewed all cases treated at the University Surgical Department of Ospedali Riuniti of Foggia from 2009 to 2018. Only a single case of hemoperitoneum caused by spontaneous rupture of HCC in noncirrhotic liver was found. An extensive search of the relevant literature was carried out using MEDLINE, and a total of 58 published studies were screened from the sources listed.ConclusionsThe management of this devastating emergency should be carefully analyzed, with stabilization of vital signs as soon as possible. Patient with ruptured HCC and hemoperitoneum without a prior history of cirrhosis and viral infections benefited from the role of transcatheter arterial embolization (TAE) as the preliminary treatment in order to have a more precise diagnosis and an optimal stabilization of the patient. Delayed or staged hepatectomy after TAE represents the definitive treatment.

New frontiers in liver resection for hepatocellular carcinoma.

SummaryLiver resection is one of the main curative options for early hepatocellular carcinoma (HCC) in patients with cirrhosis and is the treatment of choice in non-cirrhotic patients. However, careful patient selection is required to balance the risk of postoperative liver failure and the potential benefit on long-term outcomes. In the last decades, improved surgical techniques and perioperative management, as well as better patient selection, have enabled the indications for liver resection to be expanded. In this review, we aim to describe the main indications for liver resection in the management of HCC, its role compared to percutaneous ablation and liver transplantation in the therapeutic algorithm, as well as the recent advances in liver surgery that could be used to improve the prognosis of patients with HCC.

Surgical treatment of hepatic tumors-liver resection and transplantation

The most frequent primary hepatic malignancies are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (intrahepatic cholangiocellular adenocarcinoma [iCCA]). For HCC in cirrhosis, liver transplantation offers the advantage of acomplete hepatectomy radically removing all tumorous tissue along with the surrounding cirrhotic parenchyma, which is otherwise associated with a very high risk of recurrence. For HCC in non-cirrhotic livers and iCCA, liver resection is the treatment of choice. Nowadays, even extended resections can be performed with low mortality in experienced centers. Surgical therapy is more and more embedded into multimodal treatment concepts and decision making should be interdisciplinary as for other gastrointestinal tumors.

Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23–1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99–1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21–3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31–2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.