Hepatocellular Carcinoma In Cirrhotic Liver Research Articles

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

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

Contrast-Enhanced Ultrasound Features of Histopathologically Proven Hepatocellular Carcinoma in the Non-cirrhotic Liver: A Multicenter Study.

Current literature on the role of contrast-enhanced ultrasound (CEUS) in the diagnosis of hepatocellular carcinoma (HCC) in non-cirrhotic patients is limited. The aim of this retrospective multicenter study was to analyze CEUS features of histologically proven HCC in patients with non-cirrhotic liver. In this multicenter study, 96 patients from eight medical institutions with histologically proven HCC lesions in non-cirrhotic liver were retrospectively reviewed regarding SonoVue-enhanced CEUS features. Two ultrasound experts assessed the CEUS enhancement pattern and came to a consensus using the World Federation of Societies for Ultrasound in Medicine and Biology guideline criteria. The mean size of HCC lesions included was 60.3 ± 37.8 mm (mean ± standard deviation). Most of the lesions were heterogeneous but predominantly hypo-echoic on B-mode ultrasound (64.5%, 62/96), with ill-defined margins and irregular shapes. During the arterial phase of CEUS, most of the HCC lesions in non-cirrhotic liver exhibited heterogeneous hyperenhancement (78.1%, 75/96) compared with the surrounding liver parenchyma. Almost 30% of HCC lesions (28.1%, 27/96) exhibited early wash-out (<60 s). All lesions exhibited wash-out and hypo-enhancement in the late phase. CEUS features of HCC lesions in non-cirrhotic patients typically include hyperenhancement in the arterial phase and relatively rapid wash-out in the portal venous phase, which is different from HCC in cirrhotic livers and more similar to liver metastasis.

Morphological, dynamic and functional characteristics of liver pseudolesions and benign lesions.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and one of the most common causes of death among patients with cirrhosis, developing in 1-8% of them every year, regardless of their cirrhotic stage. The radiological features of HCC are almost always sufficient for reaching the diagnosis; thus, histological confirmation is rarely needed. However, the study of cirrhotic livers remains a challenge for radiologists due to the developing of fibrous and regenerative tissue that cause the distortion of normal liver parenchyma, changing the typical appearances of benign lesions and pseudolesions, which therefore may be misinterpreted as malignancies. In addition, a correct distinction between pseudolesions and malignancy is crucial to allow appropriate targeted therapy and avoid treatment delays.The present review encompasses technical pitfalls and describes focal benign lesions and pseudolesions that may be misinterpreted as HCC in cirrhotic livers, providing the imaging features of regenerative nodules, large regenerative nodules, siderotic nodules, hepatic hemangiomas (including rapidly filling and sclerosed hemangiomas), segmental hyperplasia, arterioportal shunts, focal confluent fibrosis and focal fatty changes. Lastly, the present review explores the most promising new imaging techniques that are emerging and that could help radiologists differentiate benign lesions and pseudolesions from overt HCC.

Hepatocellular Carcinoma in Cirrhotic versus Non-Cirrhotic Liver - Treatment and Survival Differences in a Nationwide Cohort

Introduction: Many studies report a superior survival for patients with hepatocellular carcinoma (HCC) in a non-cirrhotic liver compared to HCC in cirrhotic liver. This study aimed to describe clinical presentation, treatment, recurrence and survival differences depending on cirrhosis or non-cirrhosis in a population-based cohort. Method: Patients diagnosed with HCC in Sweden between 2008 and 2018 were identified and extracted from the Swedish Liver registry. Descriptive and survival statistics were applied. Results: A total of 4259 patients were identified of which 1431 (34%) had HCC in a non-cirrhotic liver. Non-cirrhotic patients were older with larger tumor burden at diagnosis. Patients with HCC in a cirrhotic liver were more often planned for (45% vs. 37%, p<0.001) and subsequently underwent curative interventions (40% vs. 31%, p<0.001). If curatively treated, cirrhotic patients underwent transplantation and ablation in 29% and 44% respectively, while 85% of non-cirrhotic patients had a hepatic resection. Recurrence was more common in non-cirrhotic HCC (43% vs. 31%) but were less often treated with a re-intervention (13% vs. 30%). Median survival in cirrhotic patients was 19 months and 13 months in non-cirrhotic HCC, p<0.001. In multivariable analysis, cirrhosis was not an independent predictor of survival, neither among curatively treated patients (p=0.427) nor in the entire cohort (p=0.067). Conclusions: Patients with HCC in cirrhotic liver are treated with curative intent to a greater extent and benefit from a superior survival as compared to patients with HCC in a non-cirrhotic liver due to differences in patient and tumor characteristics rather than cirrhotic status.Tabled 1EP01B-031Univariable and multivariable estimates for overall mortality in patients with hepatocellular carcinoma treated with curative intent Univariable HR (95% CI) p Multivariable HR (95% CI) pAge (years)1.03 (1.02-1.04)<0.0011.02 (1.01-1.03)0.002ECOG >21.20 (0.92-1.56)0.1871.58 (1.18-2.12)0.002Cirrhosis0.82 (0.70-0.98)0.0251.14 (0.83-1.56)0.427No of tumors >41.32 (0.93-1.86)0.1151.49 (0.96-2.30)0.075Size of largest tumor >51 (mm)1.30 (1.06-1.60)0.0141.48 (1.01-2.15)0.042T3-T41.56 (1.19-2.05)0.0011.28 (0.86-1.91)0.227Treatment (transplantation ref.)Hepatic resection2.76 (2.16-3.53)<0.0013.31 (2.18-5.03)<0.001Ablation3.71 (2.89-4.76)<0.0014.52 (3.07-6.64)<0.001 Open table in a new tab

Circulating HOTAIR potentially predicts hepatocellular carcinoma in cirrhotic liver and prefigures the tumor stage.

Aim of the studyHomeobox transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA classified as an oncogene and has been implicated in liver cancer initiation and progression. This study investigated the clinical usefulness of serum HOTAIR to predict hepatocellular carcinoma (HCC) and prefigure the tumor stage.Material and methodsThis study included 80 patients with de novo HCC divided into 40 late-stage HCC patients (group IA) and 40 early-stage HCC patients (group IB), 40 patients with non-tumorous liver cirrhosis (group II), and 20 healthy controls (group III). Serum HOTAIR was measured using real-time quantitative polymerase chain reaction. Serum α-fetoprotein (AFP) was measured via enzyme-linked immunosorbent assay.ResultsSerum HOTAIR was significantly higher in groups IA, IB and II compared to healthy subjects. Serum HOTAIR was significantly higher in group IA than group IB, and in groups IA and IB compared to group II. Serum HOTAIR at cut-off value > 15.45 (AUC = 0.71) showed 66% sensitivity and 78% specificity in discriminating HCC patients of group IB from HCC patients of group IA. When combined with AFP, the discriminative sensitivity and specificity increased to 74% and 90% respectively (AUC = 0.85). Serum HOTAIR at cut-off value > 9.42 (AUC = 0.823) showed 67.5% sensitivity and 93.3% specificity in discriminating HCC patients of group IB from patients with non-tumorous cirrhotic liver. When combined with AFP, the discriminative sensitivity and specificity increased to 80% and 98.3% respectively (AUC = 0.954).ConclusionsCirculating HOTAIR is a potential biomarker which may be used solely, or preferably in combination with AFP, to help HCC detection in cirrhotic liver and prefigure the tumor stage.

Challenges in Diagnosis of Hepatocellular Carcinoma in Cirrhotic Liver: A Pathologist's Perspective.

Challenges in Diagnosis of Hepatocellular Carcinoma in Cirrhotic Liver: A Pathologist's Perspective.

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.

Total robotic ALPPS approach for hepatocellular carcinoma in cirrhotic liver.

Hepatocellular carcinoma (HCC) is a common indication for associating liver partition with portal vein ligation for staged hepatectomy (ALPPS). Robotic liver resection has been done for HCC, but robotic ALPPS is a rare procedure. To present three cases of totally robotic ALPPS in cirrhotic patients with HCC. Three cirrhotic male patients with HCC underwent ALPPS; the mean age was 54.3 years. MELD score was ≤9 and tumour size between 90 and 140mm. The mean hypertrophy of the future liver remnant after the first stage was 77.5% and no postoperative liver failure was reported. Mean operative time of stage 1 was 7:30h and of stage 2 was 4:37h, without blood transfusion. The mean hospital stay for the first stage was 10 days and for the second stage was 9.3 days. No postoperative complication was recorded. Robotic ALPPS in cirrhotic patients with HCC is safe and feasible.

Comparison of LI-RADS with other non-invasive liver MRI criteria and radiological opinion for diagnosing hepatocellular carcinoma in cirrhotic livers using gadoxetic acid with histopathological explant correlation

To establish the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) and compare its performance to that of international criteria from European Assofor the Study of the Liver (EASL), Japan Society of Hepatology (JSH), Asian Pacific Association for the Study of the Liver (APASL), and Organ Procurement and Transplantation Network (OPTN), and to the reporting radiologist's overall opinion regarding the probability of a nodule being a HCC by correlating with a histological diagnosis from whole liver explants. The present single-centre, retrospective review selected participants based on the following criteria: adults (≥18 years) listed for liver transplantation in 2014/2015, with liver cirrhosis at the time of magnetic resonance imaging (MRI) with hepatocyte specific contrast agent, and at least one liver lesion ≥10 mm on MRI with histology from subsequent liver explant for comparison. Each lesion was assessed against international criteria and given a "radiologist opinion" score of 1-5 (1=definitely benign, 5=definitely HCC). Total 268 patient records were reviewed, with 105 eligible lesions identified from 47 patients. Median lesion size was 15.5 mm (range 10-68 mm). Sensitivity (%), specificity (%), and positive predictive value (PPV; %) for LI-RADS LR5 was 45, 89, and 89, for LI-RADS LR4+5+TIV was 61, 80, and 86, for EASL was 44, 86 and 86, for JSH/APASL was 64, 81, and 87, for OPTN was 36, 90, and 88, and for "radiologist impression" of probably or definitely HCC was 79, 79, and 88 respectively. MRI has moderate sensitivity and good specificity for the diagnosis of HCC with considerable variation depending on criteria used. OPTN criteria have the best specificity, but low sensitivity. "Radiologist opinion" gives highest overall accuracy with increases in sensitivity and reduction in specificity when compared to the imaging criteria.

Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report

Spontaneous rupture of hepatocellular carcinoma (HCC), defined as T4 in TNM stage by the American Joint Committee on Cancer (eighth edition), is a serious life-threatening complication. Effective treatment remains challenging because of a high 1-month mortality, a short median survival, and the potential of peritoneal metastasis. We reported on a case that received a living related donor liver transplantation (LDLT) after successful consecutive downstaging therapies. A 63-year-old man with alcohol-related liver cirrhosis and multiple HCC developed spontaneous rupture and hemoperitoneum. He received 3 sessions of transcatheter hepatic arterial chemoembolization and target therapy with sorafenib. Computed tomography scans and magnetic resonance imaging after 11 months of treatment showed that the patient's HCCs fulfilled the Milan criteria and the University of California San Francisco criteria prior to LDLT. The perioperative course was rather smooth. After discharge, interval follow-up computed tomography studies of chest and liver and a whole-body bone scan showed no tumor recurrence or metastasis up to 20 months post-operation. Successful downstaging therapies of ruptured HCC to fulfill Milan criteria to receive liver transplantation is advisable in highly selected patients.

Diffusion-weighted MRI as a screening tool for hepatocellular carcinoma in cirrhotic livers: correlation with explant data-a pilot study.

The purpose of this study was to compare the sensitivity and specificity of diffusion-weighted liver MRI alone with complete, multiphasic gadoteridol-enhanced MRI for the detection of hepatocellular carcinoma in cirrhotic patients before liver transplant. This single institution retrospective study was performed after IRB approval and was HIPAA compliant. MRI scans of 37 patients who underwent liver transplant were evaluated and findings correlated with liver explant (36) or biopsy (1). All MRI scans were obtained within six months of explant. MRI from 17 patients with liver lesions by report at imaging subsequently proven to be HCC at pathology and 20 controls without liver lesions by imaging and pathology were reviewed in random order on the radiology PACS by three independent readers blinded to the MRI reports and pathology reports in two separate sittings. First, only the diffusion-weighted images (DWI) were interpreted. Second, the complete multiphasic MRI exam with DWI was reviewed. A consensus read was obtained by two separate radiologists who had access to the patients' explant data in order to map lesions. Reader-specific and pooled classification was assessed using sensitivity, specificity, positive predictive value, and negative predictive values and corresponding 95% confidence intervals (CI) for both DWI and complete MRI examination readings compared to pathology. McNemar's test and Kappa coefficient were used to assess differences (agreement) in DWI and complete examination readings. A total of 37 patients have been studied (25M 12F age range 21-70). Averaged results of the three independent readers demonstrated a sensitivity of 78% (95% CI 65-89%) and specificity of 88% (95% CI 77-95%) for DWI alone for detection of liver lesions, with a positive predictive value of 85% (95% CI 72-94%) and a negative predictive value of 83% (95% CI 71-91%). Review of the complete MRI exam showed a sensitivity of 90% (95% CI 76-97%) and a specificity of 82% (95% CI 66-92%) with a positive predictive value of 83% (95% CI 69-93%) and a negative predictive value of 89% (95% CI 74-97%). McNemar's agreement test revealed no significant difference between the DWI and complete multiphasic interpretations (p=0.3458), with simple Kappa coefficient of 0.6716 (95% CI 0.5332-0.8110). Lesions identified on DWI ranged in size from 1.5 to 5 cm. Detection of lesions was decreased in the presence of artifact from motion, large ascites, and technical issues. Diffusion-weighted MRI has NPV and PPV comparable to complete multiphasic MRI examination for liver lesion detection in cirrhotic patients and may have a role in screening.

Small hepatocellular carcinoma: which criteria for liver transplantation?

Hepatocellular carcinoma (HCC) is the most common hepatic tumor and the best options for treatments are liver resection and liver transplantation. Many new locoregional treatments are available for HCC. Of them, radioembolization is the most discussed innovative one (1-3). Liver transplantation has the advantage to cure both tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver.

Differentiation of Intrahepatic Cholangiocellular Carcinoma from Hepatocellular Carcinoma in the Cirrhotic Liver Using Contrast-enhanced MR Imaging

This study aimed to investigate the potential of contrast-enhanced magnetic resonance imaging features to differentiate between mass-forming intrahepatic cholangiocellular carcinoma (ICC) and hepatocellular carcinoma (HCC) in cirrhotic livers. This study, performed between 2001 and 2013, included 64 baseline magnetic resonance imaging examinations with pathohistologically proven liver cirrhosis, presenting with either ICC (n = 32) or HCC (n = 32) tumors. To distinguish ICC form HCC tumors, 20 qualitative single-lesion descriptors were evaluated by two readers, in consensus, and statistically classified using the chi-square automatic interaction detection (CHAID) methodology. Diagnostic performance was assessed by a receiver operating characteristic analysis. The CHAID algorithm identified three independent categorical lesion descriptors, including (1) liver capsular retraction; (2) progressive or persistent enhancement pattern or wash-out on the T1-weighted delayed phase; and (3) signal intensity appearance on T2-weighted images that could help to reliably differentiate ICC from HCC, which resulted in an AUC of 0.807, and a sensitivity and specificity of 68.8 and 90.6 (95% confidence interval 75.0-98.0), respectively. The proposed CHAID algorithm provides a simple and robust step-by-step classification tool for a reliable and solid differentiation between ICC and HCC tumors in cirrhotic livers.

Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines

Background and aimsLiver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of...

Sudden cardiac death in a patient with advanced hepatocellular carcinoma with good response to sorafenib treatment: A case report with literature analysis.

Hepatocellular carcinoma (HCC) is the principal primary liver tumor, representing the third largest cause of cancer-associated death worldwide. The actual reference standard systemic treatment for advanced HCC is represented by sorafenib, a multi-targeted orally active small-molecule tyrosine kinase inhibitor. Sorafenib has exhibited a good general safety profile in multiple clinical trials. However, adverse drug-associated events are common, occasionally severe, and special attention should be paid to cardiovascular adverse events, particularly in patients with risk factors or known heart disease. In the present study, the case of a patient with no known cardiovascular risk factors affected by highly enhancing advanced HCC in cirrhotic liver, who died during successful sorafenib monotherapy, is reported.

Case report of the fourth laparoscopic liver resection and review of repeat laparoscopic resection for recurrent hepatocellular carcinoma in cirrhotic liver

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Utility of diffusion-weighted magnetic resonance imaging in diagnosing hepatocellular carcinoma in cirrhotic liver

Utility of diffusion-weighted magnetic resonance imaging in diagnosing hepatocellular carcinoma in cirrhotic liver

A case of deeply located small hepatocellular carcinoma in cirrhotic liver treated with laparoscopic small anatomic liver resection

The laparoscopic approach has weaknesses in terms of its inability to provide an adequate overview of the operative field and its lack of tactile sensation, easily leading to disorientation during surgery. This is especially true in liver resection for deeply located small tumors. Anatomic resection, which removes the portal territory of the tumorbearing area, is recommended for treatment of hepatocellular carcinoma (HCC) because it increases the chance of removing all transportal tumor cell dissemination and secures clearance of small tumors inside the area. Preservation of residual liver volume is also required for patients with deteriorated liver function. We performed laparoscopic small (one segment or less) anatomic liver resection for a deeply located small tumor in a cirrhotic liver with preoperative three-dimensional computed tomography (3D-CT) simulation. A 70-year-old man with hepatitis C virus-related liver cirrhosis was admitted for treatment of a lesion in liver segment 6. CT demonstrated a 1.0-cm lesion deep within segment 6 between the portal branches of subsegments 6a and 6c. The patient underwent laparoscopic anatomic liver resection of subsegments 6a and 6c using 3D-CT simulation. The deeply located small HCC was contained in the resected specimen with a negative margin, and pathological examination showed well-differentiated HCC. The patient’s postoperative course was uneventful, and he was well without recurrence 26 months postoperatively. Laparoscopic small anatomic liver resection with preoperative 3D-CT simulation facilitates removal of deeply located small tumors with an increased chance of removing transportal cancer cell dissemination, maximizing liver preservation, and achieving negative-margin resection.

MDCT features of hepatocellular carcinoma (HCC) in non-cirrhotic liver.

To describe the multidetector row computed tomography (MDCT) imaging features of HCC that develops in patients who are free from underlying liver cirrhosis and to determine if the MDCT presentation of this specific tumor differs from that of the more common HCC that develops in patients with liver cirrhosis using a retrospective case-control study. The MDCT examinations of 38 patients with HCC in non-cirrhotic liver (group 1) were quantitatively and qualitatively analyzed and compared to those obtained in 38 patients with HCC in cirrhotic liver (group 2) matched for age and gender. Quantitative and qualitative characteristics of HCC of both groups were compared using univariate analysis. HCCs were significantly larger in group 1 (81.5mm±55.5) than in group 2 (44.5mm±39.1 SD; P=0.0015). In group 1, HCCs were more frequently single tumors (87%) than in group 2 (37%) (P<0.0001), encapsulated (92% vs. 47% respectively; P<0.0001), had more frequently fatty component (24% vs. 8%, respectively; P=0.0279) and internal hemorrhage (29% vs. 3%, respectively; P=0.0033). No significant differences were found between the two groups for location, hyperenhancement of HCC during the arterial phase, washout during the portal phase, endoluminal portal involvement by HCC, endoportal cruoric thrombus, invasion of adjacent organs and underlying liver steatosis. HCC in non-cirrhotic liver are larger than those observed in cirrhotic liver and more frequently present as a single encapsulated tumor. They have the same patterns of enhancement than HCC that develops in cirrhotic liver.

Value of MR susceptibility weighted imaging for characterization of small hepatocellular carcinoma in cirrhotic livers

Objective To investigate the value of susceptibility-weighted imaging (SWI) for characterization of small hepatocellular carcinoma (sHCC) in cirrhotic livers. Methods Two hundred seventy-two patients suspiciousof HCC underwent conventional MR imaging and susceptibility-weighted imaging (SWI). Two hundred and five patients were excluded due to either size larger than 3.0 cm, no cirrhosis or HCC. Finally, a total of 84 hepatocellular nodules in 67 patients were included in this prospective study. There were 22 DNs in 12 cases, 8 DNs with HCC foci in 7 cases, and 54 overt HCCs in 48 cases. Two abdominal radiologists independently evaluated signal intensity and enhancing pattern using conventional MRI set and conventional MRI combining with SWI set. A five-point scale was performed to evaluate diagnostic confidence of HCC. Kappa analysis was performed to assess interobserver agreement of the two sets by two readers.The diagnostic performance and confidence level were compared for each image set,ROC was used to evaluate the diagnostic efficiency. Results Good interobserver agreement was identified with a Kappa value of 0.923 for conventional MRI set and 0.865 for conventional MRI combining with SWI set, respectively. The diagnostic sensitivity, specificity, accuracy, and area under the alternative-free response ROC (Az) were 80.6% and 80.6%, 81.8% and 77.3%, 81.0% and 79.8%, 0.804 and 0.782 using conventional MRI set, and 93.5% and 85.5%, 90.9% and 86.4%, 92.9% and 85.7%, 0.898 and 0.859 using conventional MRI combining with SWI set for reader 1 and reader 2, respectively.The diagnostic confidence level of conventional MRI combining with SWI set for diagnosis of HCC with less than 2 cm in size(n=36) was significantly higher than that of conventional MRI (reader 1, 3.86±0.47 vs 3.40±0.91;reader 2, 3.85±0.57 vs 3.41±0.92;t values were 3.733 and 2.468, P were 0.001 and 0.018). Conclusion SWI can provide additional valuable information and improve diagnostic performance for characterization of sHCC in cirrhotic livers. Key words: Liver tumor; Cirrhosis; Magnetic resonance imaging