Screening for hepatocellular carcinoma: patient selection and perspectives

Hepatocellular carcinoma (HCC) develops on the background of liver cirrhosis often from multiple, simultaneous factors. The diagnosis of a single small HCC comes with good prognosis and provides a potential for cure. In contrast, the diagnosis of multifocal, large HCC has high mortality and poor prognosis. Unfortunately, the majority of HCC is diagnosed at such late stages. A surveillance program endorsed by regional liver societies involves six-monthly ultrasound surveillance of at-risk patients. This had been in action for the last two decades. It has led to marked increase in the proportion of patients presenting with small unifocal nodules found on surveillance. The development of tools to enhance our ability in optimizing available surveillance is likely to improve the prognosis of patients with HCC. In this review, we discuss the difficulties in utilizing HCC surveillance and possible means of improvement

Healthcare costs of transarterial chemoembolization in the treatment of hepatocellular carcinoma

Background: A meta-analysis comparing drug-eluting beads transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (cTACE) has recently been published. On balance, no significant differences were found in terms of objective response and overall survival. The impact on healthcare costs had been studied in small series based on a hypothetical model and was in favor of DEB-TACE. We aimed to evaluate and compare healthcare costs and effectiveness of both modalities in a cohort of patients from Nottingham, UK. Methods: Using a dedicated radiology database, we identified all patients who had undergone cTACE or DEB-TACE between 2006 and 2012 at a single tertiary referral center based in Nottingham. We collected clinical data, including treatment response, postprocedure complications and 30-day mortality. Costing models were constructed to present both our local hospital perspective as well as the national health service position. Results: During our study period, 101 procedures were performed on 43 patients (76 cTACE procedures on 26 patients and 25 DEB-TACE procedures on 17 patients). Overall, 11/26 in cTACE and 5/17 in DEB-TACE group had progressive disease (p=0.52). Adverse events were seen in 6/76 cTACE compared with 7/25 DEB-TACE group (p=0.16). Based on the predetermined standard pathway there was an unadjusted average cost difference of £3770.30 (TACE =£9070.44, DEB-TACE =£5300.14) in favor of the DEB-TACE. Results from our costing models indicated a £2715.33 (95% CI £580.88–4849.77) cost difference in favor of the same procedure. Conclusions: Even when the extra costs of DEB-TACE were considered, the overall treatment costs per patient were lower in relation to cTACE

Validation of the aMAP score to predict hepatocellular carcinoma development in a cohort of alcohol‐related cirrhosis patients

Background and AimsThe aMAP score was recently devised to predict hepatocellular carcinoma (HCC) development. However, its performance was not tested in alcohol-related cirrhosis (ALC). We aimed to validate the aMAP score in a cohort of ALC patients.MethodStudy participants with ALC from a prior genome-wide association study were included. All participants had a history of high alcohol consumption. Cirrhosis was defined clinically, using fibroscan and/or histology. Patients were followed until the last liver imaging, HCC, liver transplantation (LT) or death with the latter two adjusted as competing risks.ResultsA total of 269 ALC patients were included: male (72.5%), Caucasian (98.9%), median age 56 years, and median Child-Pugh score 7. The median aMAP score was 60: 12.3% low-risk, 35.3% medium-risk and 52.4% high-risk. After a median follow-up of 41 months, 14 patients developed HCC, 27 received LT and 104 died. The aMAP score predicted HCC development (hazard ratio 1.12 per point increase, P < .001) with good separation of cumulative incidence function between risk groups. The area under the time-dependent receiver operating characteristics curve for predicting HCC development was 0.83 at 1 year and 0.82 at 5 years which was similar to ADRESS-HCC and Veterans Affairs Healthcare System scores respectively.ConclusionsWe validated the excellent performance of the aMAP score in ALC and affirm its applicability across wider aetiologies

The impact of preexisting and post-transplant diabetes mellitus on outcomes following liver transplantation

Background: Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and post-transplant DM on liver transplant (LT) recipients.Method: A single centre retrospective analysis of prospectively collected data of LT recipients (1990–2015) was undertaken.Results: Of the 2,209 patients, 13% (n=298) had Pre-DM, 16% (n=362) developed PTDM, 5% (n=118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n=1,431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM was similar to that of patients with pre-DM. Incidence of PTDM peaked during first-year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), non-alcoholic fatty liver disease and the use of Tacrolimus and Sirolimus use were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycaemic control throughout the follow-up period. Those who developed t-HG seems to have a unique characteristic compared to others. Overall, 9%, 5%, and 8% developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, re-LT, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM.Conclusions: In this largest non-registry study, patients with pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up

Textbook Outcome After Trans-arterial Chemoembolization for Hepatocellular Carcinoma

PurposeTextbook Outcome (TO) is inclusive of quality indicators and it not been provided for trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Materials and methodsData on treatment-naïve HCC patients receiving TACE from 10 centers were reviewed. TO was defined as "no post-TACE grade 3-4 complications, no prolonged hospital stay (defined as a post-procedure stay ≤ 75th percentile of the median values from the total cohort), no 30-day mortality/readmission and the achievement of an objective response (OR) at post-TACE imaging." Grade of adverse event was classified according to the Common Terminology Criteria for Adverse Events and short-term efficacy was assessed by response. Pooled estimates were calculated to account for hospital's effect and risk-adjustment was applied to allow for diversity of patients in each center.ResultsA total of 1124 patients (2014-2018) fulfilling specific inclusion criteria were included. Baseline clinical features showed considerable heterogeneity (I2 > 0.75) across centers. TACE-related mortality was absent in 97.6%, readmission was not required after 94.9% of procedures, 91.5% of patients had no complication graded 3-4, 71.8% of patients did not require prolonged hospitalization, OR of the target lesion was achieved in 68.5%. Risk-adjustment showed that all indicators were achieved in 43.1% of patients, and this figure was similar across centers. The median overall survival for patients who achieved all indicators was 33.1 months, 11.9 months longer than for patients who did not.ConclusionsA useful benchmark for TACE in HCC patients has been developed, which provides an indication of survival and allows for a comparison of treatment quality across different hospitals

Prediction of survival among patients receiving transarterial chemoembolization for hepatocellular carcinoma: A response-based approach

Background and aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. Approach and results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognosticatio

Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers.

BACKGROUND & AIMS Carriage of rs738409:G in patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with PNPLA3 rs738409:G. This study explores the risk-associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including: 1,031 with alcohol-related cirrhosis and HCC; 1,653 with alcohol-related cirrhosis without HCC; 2,588 alcohol misusers with no liver disease; and 899 healthy controls. Genetic associations with the risks for alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for both cirrhosis (OR 0.79 [95% CI 0.72-0.88], p=8.13×10-6) and HCC (OR 0.77 [95% CI 0.68-0.89], p=2.27×10-4), while carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR 1.70 [95% CI 1.54-1.88], p=1.52x10-26) and HCC (OR 1.77 [95% CI 1.58-1.98], p=2.31×10-23). These associations remained significant after adjusting for age, sex, body mass index, type II diabetes mellitus and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women but the protective effect against the subsequent development of HCC was only observed in men (p=1.72×10-4; ORallelic, 0.75; 95% CI, 0.64-0.87). CONCLUSIONS Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach

Background and Aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. Approach and Results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological response (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) was also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A new pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. Median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, etiology, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared to existing models (the HAP score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. Conclusion: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication