Hepatocellular Carcinoma In Cirrhotic Patients Research Articles

Hepatitis B Virus Infection Promotes Hepatocellular Carcinoma Progression Through LPC/ENPP2/LPA Axis

Background: Hepatitis B virus (HBV) infection is considered as an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC) patients, but the molecular mechanisms have not been fully elucidated. Ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA) and participates in virus replication and tumor progress. This study aimed to elucidate whether HBV infection inducing HCC progression via LPC/ENPP2/LPA axis. Methods: The clinical data for HCC patients were collected and prognosis was analyzed. The in vitro and in vivo experiments were used to investigate the influences of HBV, ENPP2 and activated hepatic stellate cell (HSC) on HCC progression. Findings: We found that ENPP2 expression was positively related to HBV infection and poor prognosis. HBV-induced HCC progression via ENPP2 was enhanced by LPC which was secreted by activated HSC. HCC patients with high ENPP2 combined with cirrhosis had worse prognosis than non-cirrhotic patients. In cirrhotic HCC patients, high ENPP2 expression cohort also had worse prognosis than low expression cohort. Interpretation: In HBV positive cirrhotic HCC patients, HBV enhanced host cell secretion of ENPP2, combined with LPC secreted by fibroblast to promote tumor progression via LPC/ENPP2/LPA. These findings may provide insights into novel approaches to HBV associated HCC therapy. Funding Statement: This study was supported by the National Natural Science Foundation of China (81801999, 81772597, 81672412, 81972255), the Guangdong Science and Technology Foundation (2017A030311002), the Science Foundation of Jiangxi (20181BAB214002), the Education Department Science and Technology Foundation of Jiangxi (GJJ170936) and grant from Guangdong Science and Technology Department (2017B030314026). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The clinicopathologic information of HCC patient (n = 774) and tumor tissues (n = 158) were obtained from Sun Yat-sen Memorial Hospital after approval by the hospital Ethical Committee. Animal studies were carried out in the South China University of Technology and approved by the Laboratory Animal Welfare and Ethics Committee of the South China University of Technology. All animal experiments conformed to the approved guidelines of Animal Care and Use Committee of South China University of Technology.

Accuracy of ultrasound in detection of Hepatocellular Carcinoma in cirrhotic patients.

Objectives: Evaluate the accuracy of ultrasonography in the diagnosis of hepatocellular carcinoma among cirrhotic patients by comparing it with contrast enhanced multiphasic MRI. Study Design: Cross sectional study. Setting: Radiology Department through OPD\Admitted\emergency, Allied Hospital, Faisalabad. Period: 01-01-2018 to 30-06-2018. Material & Methods: A total of 91 cases, having symptoms of fatigue, weakness, vomiting, nausea, loss of appetite, abdominal pain, weight loss and bloating when the fluid is accumulated in abdominal cavity, itching, spider-like blood vessels on the skin were included in the study. Informed written consent was taken from all the patients or their next of kin after explaining the procedure, objectives and benefits of study. All the patients were examined with Conventional gray scale ultrasound using curvilinear probe of 5MHz and then with 1.5 tesla MR imager. Results: The diagnostic accuracy was computed as 42.86%(n=39) as true positive, 1.10%(n=1) as false positive, 49.45%(n=45) false negative and 6.59%(n=6) had true negative, while 46.43%(sensitivity), 85.71%(specificity), 97.5%(positive predictive value), 88.24%(negative predictive value), and 49.45%(diagnostic accuracy) were calculated. Conclusion: We concluded that the accuracy of ultrasonography for the diagnosis of hepatocellular carcinoma among cirrhotic patients by comparing it with contrast enhanced multiphasic MRI is in agreement with the previous studies, though its accuracy rate is lower but specificity is significantly higher and recommended in our country in low resource settings and tertiary care setups where diagnostic facilities are limited functional.

Surveillance of hepatocellular carcinoma in cirrhotic patients: Current knowledge and future directions.

Patients with cirrhosis are at the highest risk to develop hepatocellular carcinoma (HCC), with a variable annual risk of 1–8%. Currently, biannual abdominal ultrasound (USG) with or without alpha fetoprotein (AFP) is the recommended HCC surveillance strategy of major professional liver societies for all cirrhotic patients. However, the effectiveness of USG and AFP has been a sprawling subject of debate due to conflicting results and the low quality of the evidence. The role of cross-sectional imaging is controversial due to potential harm and cost-effectiveness concerns. Several novel serum biomarkers have been introduced for HCC screening, but have yet to be validated for various geographic regions. A risk-stratified algorithm is needed to increase the yield of HCC surveillance by distinguishing a high-risk group that requires more intense screening with cross-sectional imaging and serum biomarkers, and a low-risk group, where the standard surveillance strategy is continued. In this review, the strengths and concerns related to standard USG-based surveillance strategy are discussed, as well as efforts to increase the effectiveness of surveillance.

Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria. Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary. Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053). Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.

Managing hepatocellular carcinoma in cirrhotic patients in a national hospital in Argentina

Background: Liver transplantation and surgery are accepted curative treatments for HCC in cirrhosis, being the first the gold standard but not always available due to scarcity of donors. Materials & Methods: Descriptive analysis of cirrhotic patients with HCC during 2013-2018 in a high-volume center. Patients were stratified by exception points, and blood type. Results in percentages, means, t-test and Chi2 were used. Significance: p<0.05. Kaplan Meyer and log rank test for survival. Results: 179 cirrhotic patients diagnosed with HCC. 131 candidates for liver transplantation. 83 were given additional MELD exception points for HCC and 48 were included on the waiting list with intention to treat and downstaging. There were no differences between age, sex, BMI or Child score. 73 patients were transplanted: 81,9% of the exception points group with a drop out of 16,9% and 10,4% of the intention to treat group (p<0,0001), with a drop out of 66,7% (p<0,0001). Mortality was higher in the second group (58,3%) (p<0,0001). In the first group 43 patients were treated while waiting with TACE (41) and RFA (3), and 37 patients on the second group: TACE (30), RFA (1) and 6 patients were submitted to surgery. The ones resected are alive with a median overall survival of 478,6 days, with one recurrence (16,7%). Analyzing blood type, Blood type 0 has longer waiting time since exception points are given (m=219 days, r 5-369) (p<0,0001) thus most received TACE (76%, p<0,0001). Global 1-year Survival was 76,8%, and 5-year 49,6%, but in the first group 1-year and 5-year survival were 83,3% and 62,6% and 65,7% and 27,2% in second group (p<0,0001). Conclusion: Additional MELD exception points are essential in HCC providing better access to liver transplantation. Drop out is still high and bridge therapies acquire a fundamental role, especially surgery if possible, with excellent long-term Results.

Impact of Tumor Size as a Prognostic Factor After One Stage Liver Resection for Solitary Hepatocellular Carcinoma in Cirrhotic Patients

Aim: This study is to assess tumor size as a prognostic factor predicting outcomes after one staged hepatectomy for cirrhotic patients with solitary hepatocellular carcinoma. Patients and methods: The study included 41 patients with single hepatocellular carcinoma (HCC) of different sizes who underwent single-stage hepatectomy. Patients were divided according to their tumor size into 2 groups, group A involved patient with tumors ≤ 5 cm and group B which involved patients with tumors > 5 cm. The effect of the tumor size on overall survival and disease-free survival was studied in both groups. Results: The mean age of the studied groups was 59.60±6.89 years. Hepatitis C infection was found 82.9% of patients. Six patients (17.1%) received treatment of HCV. All patients were of Child-Pugh class A (77.1% were scores 5 and 22.9% were score 6). The median Alpha-fetoprotein (AFP) level was 240 ng/ml. The mean operative time was 186.4±52.4 min. During the follow-up period (12-24 months), 12 patients (34.3%) developed recurrence. The mean time of recurrence was 15.50±4.23 months. Cumulative disease-free survival (DFS) at the end of the study was 65.7%. The cumulative overall survival (OAS) proportion at the end of the study was 74.3%. Conclusion: Our results suggest that surgical resection for large HCC is safe and effective and that the first-line treatment for large HCC to be considered is surgical resection in selected patients. Our study showed that hepatectomy for large HCC could be performed with an acceptable morbidity and mortality rate. With the improvement in patient selection and treatment strategy, solitary large HCC is not a contraindication to surgical therapy.

Comparison of clinical manifestations and outcomes of noncirrhotic and cirrhotic hepatocellular carcinoma patients with chronic hepatitis B.

The differences of the clinical features and survival outcomes between cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection remain to be determined. We evaluated clinical characteristics and survival outcomes of noncirrhotic HBV-associated HCC patients compared with cirrhotic patients. Between January 2005 and December 2015, 1345 patients were diagnosed to have HCC at our hospital. Of these, 860 HBV-associated HCC patients with (cirrhotic group, n = 519, 60.3%) or without cirrhosis (noncirrhotic group, n = 341, 39.7%) were retrospectively analyzed. Propensity score matching (PSM) was used to adjust for differences between the two groups. The noncirrhotic group had lower Child-Turcotte-Pugh (CTP) classes and greater tumor sizes and were less likely to have portal vein thrombosis than the cirrhotic group. Age and sex were not significantly different between the two groups. Cumulative overall survival (OS) rates at 2, 4, 6, and 8 years after treatment were significantly higher in the noncirrhotic group (67.2, 57.1, 43.2, and 38.3 vs. 58.3, 41.3, 33.2, and 27.8%, respectively, P < 0.001). However, no significant intergroup difference in OS rates was observed after PSM (P = 0.680). Significant predictive factors of OS were CTP class, tumor size, tumor number, and curative-intended treatment for the noncirrhotic group, and serum alanine aminotransferase, CTP class, tumor size, tumor number, and curative-intended treatment for the cirrhotic group. After PSM, cumulative OS rates were similar between HBV-related HCC patients with and without cirrhosis, and they were clearly dependent on CTP class, regardless of the presence of cirrhosis itself both in cirrhotic and noncirrhotic patients.

Intra-procedural dual phase cone beam computed tomography has a better diagnostic accuracy over pre-procedural MRI and MDCT in detection and characterization of HCC in cirrhotic patients undergoing TACE procedure

PurposeThis study was directed to compare diagnostic accuracy of dual-phase cone beam computed tomography (DP-CBCT) vs pre-procedural second line imaging modality (SLIM [multidetector computed tomography and magnetic resonance imaging]) to detect and characterize hepatocellular carcinoma (HCC) in cirrhotic patients with indication for trans-arterial chemoembolization (TACE). MethodsThis is a single centre, retrospective, and observational study. Exclusion criteria were not-assisted DP-CBCT TACE, and unavailable follow-up SLIM. We evaluated 280 consecutive patients (January/2015-Febraury/2019). Seventy-two patients were eligible. Three radiologists in consensus reviewed: pre-procedural SLIM, DP-CBCT, and SLIM at follow-up, with 4 months of interval between each reading. Hyper-vascular foci (HVF) were detected and characterized. Diameter was recorded. Radiological behaviour, according to LI‐RADS criteria, of HFV throughout follow-up time was the reference standard. Diagnostic accuracy was calculated for pre-procedural SLIM and DP-CBCT and evaluated through receiver operating characteristic curve. HVF only visible on DP-CBCT (defined as occult) were analysed. Tumour diameters were compared. ResultsMedian time between pre-procedural SLIM and DP-CBCT and between DP-CBCT and definitive radiological diagnosis of HVF were 46.0 days (95%CI 36.5–55.0) and 30.5 days (95%CI 29.0–33.0), respectively.DP-CBCT had a better diagnostic performance than pre-examination SLIM (sensitivity 99%vs78%; specificity 89%vs85%; PPV 99%vs99%; NPV 92%vs30%; and accuracy 94%vs79%). DP-CBCT diagnosed 63 occult HVF. Occult HCC were 54/243 (22.2%). Six were occult angiomas. Three were false positive. Mean diameter was significantly higher in DP-CBCT vs pre-procedural SLIM (+7.5% [95%CI 3.7–11.3], p < 0.05). ConclusionsDP-CBCT has a better diagnostic accuracy and NPV than pre-procedural SLIM in cirrhotic patients with indication for TACE.

The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis.

We evaluated the characteristics of hepatocellular carcinoma (HCC) in patients who had non-alcoholic fatty liver disease (NAFLD) without cirrhosis. We prospectively followed NAFLD patients at our University hospital. NAFLD was diagnosed from detection of steatosis by histology or imaging, no alcohol intake, and exclusion of other liver diseases. Cirrhosis was defined by histological features, imaging data, and symptoms. We compared NAFLD-related HCC with or without cirrhosis and non-cirrhotic NAFLD with or without HCC. There were 48 non-cirrhotic HCC patients and 71 cirrhotic HCC patients. Multiple logistic regression analysis revealed that other than liver function factors, male gender (OR: 5.603, 95%CI: 1.577-19.900), light drinker (OR: 2.797, 95%CI: 1.031-7.589), and tumor size (OR: 1.031, 95%CI 1.009-1.055) differ significantly between these two groups. The recurrence rate was significantly lower in the non-cirrhotic HCC group than the cirrhotic HCC group, with risk factors being des-γ-carboxy prothrombin and the number of HCCs. The non-cirrhotic HCC group showed significantly better survival because of absence of non-cancerous liver failure. Comparison between non-cirrhotic NAFLD patients with or without HCC (n=612) revealed the following risk factors for HCC: male gender (OR: 7.774, 95%CI: 2.176-27.775), light drinker (OR: 4.893, 95%CI: 1.923-12.449), and high FIB4 index (OR 2.634, 95%CI: 1.787-3.884). In patients with non-cirrhotic NAFLD, important risk factors for HCC were male gender, alcohol consumption, and the FIB4 index. HCC recurrence and survival were only influenced by the tumor stage. We should be aware of alcohol consumption as a modifiable risk factor for HCC.

VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma

BackgroundTo investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis.MethodsSerum levels of alpha-fetoprotein, des-γ-carboxy prothrombin, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis.ResultsThe von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 and p < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels.ConclusionsThe von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.

Impact of Toll-like Receptors 2(TLR2) and TLR 4 Gene Variations on HCV Susceptibility, Response to Treatment and Development of Hepatocellular Carcinoma in Cirrhotic HCV Patients

ABSTRACTBackground and Aims: Genetic polymorphisms of Toll-like receptors (TLRs) have been proposed to affect susceptibility to HCV infection and progression to end-stage liver disease. This study was conducted to clarify the association of SNPS of TLR2 and TLR4 with clinical outcome of hepatitis C, response to treatment and development of HCC.Methods: The current study examined 3295 individuals from 725 families that were categorized into groups comprising chronic HCV (CH), spontaneous viral clearance (SC) and control subjects. Treated patients were classified into responders (RT) and non-responders (NRT). In addition, patients with liver cirrhotic (LC), and hepatocellular carcinoma (HCC) were also included. All subjects were genotyped for five single nucleotide polymorphisms (SNPs) of TLR2 and four SNPs of TLR4 and their haplotypes using allelic discrimination real-time PCR.Results: Results demonstrated strong association with allele A of rs13105517 of TLR2 and allele C of rs10116253 of TLR4 with CH in comparison to SC group. However, The peak of risk of HCC was observed with allele C of rs3804099 of TLR2 and C allele of rs10116253 TLR4 (p < 0.001).A strong association was found with allele T of rs1816702 of TLR2 and allele A of rs5030728 of TLR4 in non responder group in comparison to responders (p < 0.001). Haplotypes CAGT of TLR4 and ATAC of TLR2 showed significant association with CH and HCC groups in comparison to other groups.Conclusions: This study shows an association of minor alleles of TLR2 and TLR4 with outcome of HCV infection, response to therapy and development of HCC in cirrhotic patients.

Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: a United States multicentre study.

Limited data exist on the burden and features of non-cirrhotic hepatocellular carcinoma (HCC) in the United States. To evaluate characteristics, aetiologies, trends and outcomes of non-cirrhotic HCC from 2000 to 2014 at five large US centres METHODS: Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non-cirrhotic patients were older (64.1 vs 61.2years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P<.001 for all). Among non-cirrhotic patients, non-alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non-cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P<.0001]) and NAFLD (0.66% [P=.003]). Patients with non-cirrhotic HCC had larger tumours (8.9 vs 5.3cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P<.001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3years, P=.004). Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non-cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non-cirrhotic patients presented with more advanced HCC, their survival was better.

Radiomics machine-learning signature for diagnosis of hepatocellular carcinoma in cirrhotic patients with indeterminate liver nodules.

To enhance clinician's decision-making by diagnosing hepatocellular carcinoma (HCC) in cirrhotic patients with indeterminate liver nodules using quantitative imaging features extracted from triphasic CT scans. We retrospectively analyzed 178 cirrhotic patients from 27 institutions, with biopsy-proven liver nodules classified as indeterminate using the European Association for the Study of the Liver (EASL) guidelines. Patients were randomly assigned to a discovery cohort (142 patients (pts.)) and a validation cohort (36 pts.). Each liver nodule was segmented on each phase of triphasic CT scans, and 13,920 quantitative imaging features (12 sets of 1160 features each reflecting the phenotype at one single phase or its change between two phases) were extracted. Using machine-learning techniques, the signature was trained and calibrated (discovery cohort), and validated (validation cohort) to classify liver nodules as HCC vs. non-HCC. Effects of segmentation and contrast enhancement quality were also evaluated. Patients were predominantly male (88%) and CHILD A (65%). Biopsy was positive for HCC in 77% of patients. LI-RADS scores were not different between HCC and non-HCC patients. The signature included a single radiomics feature quantifying changes between arterial and portal venous phases: DeltaV-A_DWT1_LL_Variance-2D and reached area under the receiver operating characteristic curve (AUC) of 0.70 (95%CI 0.61-0.80) and 0.66 (95%CI 0.64-0.84) in discovery and validation cohorts, respectively. The signature was influenced neither by segmentation nor by contrast enhancement. A signature using a single feature was validated in a multicenter retrospective cohort to diagnose HCC in cirrhotic patients with indeterminate liver nodules. Artificial intelligence could enhance clinicians' decision by identifying a subgroup of patients with high HCC risk. • In cirrhotic patients with visually indeterminate liver nodules, expert visual assessment using current guidelines cannot accurately differentiate HCC from differential diagnoses. Current clinical protocols do not entail biopsy due to procedural risks. Radiomics can be used to non-invasively diagnose HCC in cirrhotic patients with indeterminate liver nodules, which could be leveraged to optimize patient management. • Radiomics features contributing the most to a better characterization of visually indeterminate liver nodules include changes in nodule phenotype between arterial and portal venous phases: the "washout" pattern appraised visually using EASL and EASL guidelines. • A clinical decision algorithm using radiomics could be applied to reduce the rate of cirrhotic patients requiring liver biopsy (EASL guidelines) or wait-and-see strategy (AASLD guidelines) and therefore improve their management and outcome.

TIPS Is Not Associated with a Higher Risk of Developing HCC in Cirrhotic Patients: A Systematic Review and Meta-analysis.

Background and Aims: The association between portal-systemic shunt and hepatocellular carcinoma (HCC) development in patients who have cirrhosis is still controversial. This systematic review with meta-analysis was performed to systematically clarify the potential role of portal-systemic shunt in the development of HCC.Methods: The PubMed, Embase, and Cochrane Library databases were searched for potentially eligible literature. Meta-analysis with random-effects model was performed to combine the incidence rates of HCC after portal-systemic shunt. Finally, seven studies were included. In the present review, we mainly focused on 859 patients (365 in the transjugular intrahepatic portal-systemic shunt (TIPS) group and 494 in the non-TIPS group) from five studies to analyze incidence rates after TIPS.Results: At the end of follow-up, there were 66 (18%, 66/365) patients who developed HCC after TIPS intervention and 63 (13%, 63/494) patients who developed HCC after non-TIPS treatments. Pooled estimates with random-effects model did not demonstrate a significant increase of incidence of HCC after TIPS (risk ratio: 1.37 [confidence interval (CI): 0.96 to 1.97]; p = 0.08) compared with non-TIPS treatments. Subgroup analyses for those patients with transplanted liver also did not detect a significant difference between the TIPS group and non-TIPS group (risk ratio: 1.10 [CI: 0.59 to 2.07]; p = 0.75).Conclusions: Current evidence suggests that portal-systemic shunt is not associated with a higher risk of HCC development in cirrhotic patients.

Effect of Propranolol Treatment on the Incidence of Hepatocellular Carcinoma in Patients Waiting for Liver Transplant With Cirrhosis: A Retrospective, Surveillance Study in a Tertiary Center.

Hepatocellular carcinoma is the most frequent primary malignant tumor of the liver and the third most common cause of all cancer-related mortalities. There is a need to develop new strategies to prevent hepatocellular carcinoma, as the incidence of this cancer continues to increase despite all advancements. In this study, our aim was to determine the effects of propranolol treatment on the incidence of hepatocellular carcinoma in cirrhotic patients waiting for liver transplant. We retrospectively reviewed the data of patients waiting for liver transplant with cirrhosis due to various causes registered at the Hepatocellular Carcinoma Surveillance Program between June 2011 and December 2017 in our center. These data were compared between patients using propranolol and those not using propranolol. Of the 231 patients, 135 (58.4%) were male and 96 (41.6%) were female. The mean age was 58.1 ± 14 years. We noted that 153 of total patients (66.2%) were using propranolol. Three patients (2%) were using 20 mg propranolol, 125 (81.7%) were using 40 mg propranolol, 10 (6.5%) were using 60 mg propranolol, and 15 (9.8%) were using 80 mg propranolol. Of total patients, 36 (15.6%) developed hepatocellular carcinoma, including in 12 patients (7.8%) using propranolol and 24 patients (30.8%) who did not use this agent (P < .001). Thus, the hepatocellular carcinoma frequency was 5.22 times lower in patients receiving propranolol than in those not receiving propranolol. Although causes of cirrhosis and initial stages were similar in both groups using and not using propranolol, incidence of hepatocellular carcinoma was significantly lower in the propranolol group than in the group without propranolol. This result showed that propranolol treatment has a protective effect for hepatocellular carcinoma in patients waiting for liver transplant with cirrhosis.

Mo1457 – The Risk of Hepatocellular Carcinoma in Cirrhotic Patients with Hbv and Hcv Infection: Not an Equal Opportunity

Mo1457 – The Risk of Hepatocellular Carcinoma in Cirrhotic Patients with Hbv and Hcv Infection: Not an Equal Opportunity

Role of Liver Stiffness Measurement in Predicting HCC Occurrence in Direct-Acting Antivirals Setting: A Real-Life Experience.

The aim of this study was to evaluate the relationship between the liver stiffness measurement and the risk of developing hepatocellular carcinoma (HCC) in HCV cirrhotic patients undergoing new direct-acting antivirals. From April 2015 to April 2017, all consecutive HCV cirrhotic patients treated by direct-acting antivirals were enrolled. A liver stiffness measurement was computed at baseline, and an ultrasound evaluation was provided for all patients at baseline and every 6months until 1year after the stopping of the antiviral therapy. The diagnosis of HCC was performed according to international guidelines by imaging technique workup. Two hundred and fifty-eight HCV patients with a diagnosis of cirrhosis were identified. The median liver stiffness was 25.5kPa. Thirty-five patients developed HCC. Patients were divided into three groups, based on their liver stiffness: < 20kPa (n = 72), between 20 and 30kPa (n = 92) and > 30kPa (n = 94). Compared to the < 20kPa and 20-30kPa groups, the > 30kPa group showed a statistically significant increased risk of HCC (p = 0.019; HR 0.329; 95% CI 0.131-0.830). A ROC curve analysis to assess the overall predictive performance of liver stiffness measurement on the HCC risk was performed. The results allow us to identify a cutoff value of liver stiffness measurement equal to 27.8kPa, which guarantees the highest sensitivity and specificity (respectively, 72% and 65%). The data underline that the baseline liver stiffness measurement and ultrasound surveillance is a valuable tool for assessing the risk of HCC in cirrhotic patients undergoing the direct-acting antivirals treatment.

SAT-030-Annual contrast-enhanced MRI is highly effective in the surveillance of hepatocellular carcinoma in cirrhotic patients

SAT-030-Annual contrast-enhanced MRI is highly effective in the surveillance of hepatocellular carcinoma in cirrhotic patients

Liver resection versus transarterial chemoembolization for the treatment of intermediate-stage hepatocellular carcinoma.

BackgroundThe role of transarterial chemoembolization (TACE) as the standard treatment for intermediate‐stage hepatocellular carcinoma (HCC) is being challenged by increasing studies supporting liver resection (LR); but evidence of survival benefits of LR is lacking. We aimed to compare the overall survival (OS) of LR with that of TACE for the treatment of intermediate‐stage HCC in cirrhotic patients.MethodsA Markov model, comparing LR with TACE over 15 years, was developed based on the data from 31 literatures. Additionally, external validation of the model was performed using a data set (n = 1735; LR: 701; TACE: 1034) from a tertiary center with propensity score matching method. We conducted one‐way and two‐way sensitivity analyses, in addition to a Monte Carlo analysis with 10 000 patients allocated into each arm.ResultsThe mean expected survival times and survival rates at 5 years were 77.8 months and 47.1% in LR group, and 48.6 months and 25.7% in TACE group, respectively. Sensitivity analyses found that initial LR was the most favorable treatment. The 95% CI for the difference in OS was 2.42‐2.46 years between the two groups (P < 0.001). In the validation set, the 5‐year survival rates after LR were significantly better than those after TACE before (40.2% vs. 25.9%, P < 0.001) and after matching (43.2% vs 30.9%, P < 0.001), which was comparable to the model results.ConclusionsFor cirrhotic patients with resectable intermediate‐stage HCC, LR may provide survival benefit over TACE, but large‐scale studies are required to further stratify patients at this stage for different optimal treatments.

Risk factors of unfavorable prognosis of chronic hepatitis C.

To investigate risk factors of unfavorable prognosis in patients with chronic hepatitis C (CHC), including liver cirrhosis (LC), decompensated cirrhosis, hepatocellular carcinoma (HCC), cryoglobulinemic vasculitis (CryoVas) and B-cell non-Hodgkin's lymphoma. This was a retrospective study using data of 824 patients with CHC hospitalized between 2010 and 2016 in clinic named after E.M. Tareev. We used multivariate analysis including logistic regression to calculate odds ratios (ORs) for potential risk factors/predictors associated with unfavorable outcomes in patients with CHC. The rate of LC, decompensated LC, HCC, serious CryoVas and B-cell lymphoma in patients with CHC was 39.1% (322/824), 14.0% (115/824), 2.8% (23/824), 5.2% (43/824) and 1.2% (10/824), respectively. After adjustment for sex and age the rate of LC, decompensated LC, HCC was 22.8, 8.0 and 1.5%, respectively. Annual rate of LC in patients with CHC was 1.5%; in cirrhotic patients annual rate of decompensated LC and HCC was 2.9 and 1%, respectively. Risk factors independently associated with development of LC were elevated body mass index (OR 1.43), immunosuppressive therapy (OR 1.67), diabetes type 2 (OR 2.03), absence of antiviral therapy (OR 2.15), alcohol abuse (OR 2.34), duration of infection ≥20 years (ОR 2.74) and an absence of sustained virological responce (SVR) (OR 2.98). Independent risk factors for decompensation in cirrhotic patients included diabetes type 2 (OR 1.47), alcohol abuse (OR 1.53), an absence of antiviral therapy (OR 2.36) and an absence of SVR (OR 1.94). An episode of decompensation was the independent predictor of HCC in cirrhotic patients (OR 3.99). Genotype 1b (OR 1.66) and an absence of antiviral therapy (OR 3.31) were independently associated with serious CryoVas. Two prognostic scales were offered for risk evaluation of LC and its complications. Multivariate analysis showed several factors independently associated with higher risk for LC, decompensation of LC, HCC, serious CryoVas in patients with CHC. The rate of unfavorable outcomes of CHC is found, including rare extrahepatic manifestations.