Evaluating hepatocellular carcinoma (HCC) surveillance through an early diagnostic centre: An implementation science approach at a tertiary hepatology centre in England

International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma

Changes in Hepatocellular Carcinoma Surveillance and Risk Factors for Noncompletion in the Veterans Health Administration Cohort During the Coronavirus Disease 2019 Pandemic

Is the measurement of tumor marker levels effective for monitoring patients after the treatment of hepatocellular carcinoma? RECOMMENDATIONFor patients in whom tumor marker levels were elevated before treatment, tumor markers measured after treatment may serve as useful indices of the effects of treatment.(grade C1) 30

Introduction Hepatocellular carcinoma (HCC) mortality and incidence is increasing worldwide. Current guidelines recommend biannual surveillance with ultrasound (USS) and/or alpha-fetoprotein (AFP) to ensure early detection and prompt treatment, yet the benefit on patient outcomes is uncertain in the absence of high quality data. We aimed to describe the merits of HCC surveillance in a single-centre cohort with an ethnically diverse population. Methods We retrospectively identified patients diagnosed with HCC from 2010 to 2017. We determined whether HCC occurred on surveillance or not. We collected information including demographic data, aetiology and severity of liver disease, AFP levels, tumour size, initial treatment, survival status and cause of death. Results 101 cases were identified. Median age was 71 years (range 47–94), 75% were male. 63% were white and 25% from South Asian background. The commonest aetiology was Non-Alcoholic Fatty Liver Disease (NAFLD, 22.8%), followed by Alcohol-Related Liver Disease (ARLD, 19.8%), Hepatitis C (HCV, 21.8%) and Hepatitis B (HBV, 5%). 7/22 patients with HCV had achieved SVR. Only 1 received direct-acting antivirals (DAA) prior to HCC diagnosis. 25/101 patients were diagnosed on HCC surveillance; 11/101 presented with acute decompensated cirrhosis (9 were under a surveillance programme, 2 had failed to attend); 43/101 presented with symptoms and 22/101 were incidental findings. HCV was the predominant aetiology in those presenting symptomatically. AFP was normal in half of all cases. Of those on surveillance, 63% had AFP measured prior to diagnosis and 8.5% had a raised AFP when initial imaging was normal. 57% patients were Child’s A, 38% Child’s B and 5% Child’s C at diagnosis. Patients were more likely to have HCC diagnosed at an early stage on surveillance (68.6% vs 30.3%) and receive curative treatment (22.8% vs 12.1%) than the non-surveillance group. 1 and 3 year survival rates were greater on surveillance (67.7% vs 41.1% and 22.2% vs 8.16%, respectively). Median survival after diagnosis in the surveillance group was greater than those presenting for the first time. Conclusions Surveillance was associated with earlier stage cancers and receipt of potentially curative treatment. However, patients known to secondary care made up a minority of HCC diagnoses. Improving identification and diagnosis of cirrhosis in primary care may therefore help identify at-risk patients earlier, although not all patients will engage with follow-up. AFP measurement may identify additional cases of HCC that go undetected by USS, but should be weighed against potential patient harms from false-positive Results. Further studies should continue to inform an optimum HCC surveillance strategy.

Covering the Cover

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Hepatocellular carcinoma surveillance: The road ahead.

α-Fetoprotein for Hepatocellular Carcinoma Diagnosis: The Demise of a Brilliant Star

Hepatology Clinical.

Background and AimsRisk factors for hepatocellular carcinoma (HCC) include cirrhosis and diabetes, but patient- and disease-related factors in prognosis have not been widely explored. Evidence highlights ethnic disparity in HCC...

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in patients with cirrhosis, and HCC survival is directly correlated with stage at diagnosis. Current guidelines recommend HCC surveillance with an abdominal ultrasound every 6 months, but unfortunately many patients do not meet this threshold.1 Our aim was to determine whether distance to a radiology center, measured in travel time, was associated with HCC surveillance rates. Methods: We included data on adult patients with cirrhosis within the OneFlorida Clinical Research Consortium from October 1, 2015- December 31, 2019. The primary outcome was a continuous measure of the percentage of time up to date with HCC surveillance (PTUDS) based on abdominal ultrasound (US), triple phase CT, and/or MRI with contrast. Travel time was calculated using ArcGIS geomodelling software as the estimated minimum travel time between the geographic centroid of patient’s zip code and the nearest American College of Radiology-accredited center for US, CT, and/or MRI. Linear regression models were fit with PTUDS as the outcome; all covariates with a p< 0.05 were included in the final multivariable model. (Figure) Results: Among 25,299 patients with cirrhosis (median follow-up=4.1 years), the median PTUDS was 10.0% (interquartile range 0-29.9%). Variables found to have a statistically significant association with PTUDS are displayed in Table. Travel time, hepatic encephalopathy at baseline, and ascites at baseline were associated with increased PTUDS. Patients with alcohol-related liver disease, nonalcoholic steatohepatitis, and cryptogenic cirrhosis had lower PTUDS compared with patients with HCV. Conclusion: Travel time to the nearest radiology center is not associated with lower HCC surveillance rates while race, etiology of liver disease, and disease severity do appear to variably influence surveillance. By establishing factors associated with currently suboptimal surveillance rates, we can create targeted interventions to improve surveillance and, ultimately, patient outcomes.Figure 1.: Median PTUDS by County Table 1. - Multivariable Linear Regression Model of Factors Associated with HCC Surveillance Variable Beta Coefficient, 95% CI P-Value Travel Time 0.0016 (0.0012-0.0020) <0.001 Liver Disease Etiology Hepatitis C Virus Reference - Hepatitis B Virus 0.0246 (0.0019-0.0473) 0.034 Wilson's Disease 0.0137 (-0.571-0.0845) 0.704 Hemochromatosis 0.0067 (-0.0220-0.0354) 0.647 a1-Antitrypsin Deficiency 0.0673 (0.0200-0.1145) 0.005 Alcohol-Related Liver Disease -0.0720 (-0.0801- -0.0639) <0.001 Primary Biliary Cholangitis -0.0037 (-0.0261- 0.0186) 0.745 Autoimmune Hepatitis -0.0193 (-0.0406- 0.0019) 0.075 Primary Sclerosing Cholangitis 0.0123 (-0.0462- 0.0708) 0.680 Nonalcoholic Steatohepatitis -0.0835 (-0.0917- -0.0752) <0.001 Unknown/Cryptogenic -0.01566 (-0.1664- -0.1467) <0.001 Race White/Caucasian Reference - American Indian/Alaskan -0.0207 (-0.0871- 0.0457) 0.541 Asian 0.0531 (0.0258- 0.0805) <0.001 Black 0.0171 (0.0082- 0.0260) <0.001 Native Hawaiian/Pacific Islander -0.0075 (-0.1109- 0.0959) 0.887 Multiple Race -0.0474 (-0.0781- -0.0168) 0.002 Refuse to answer 0.0904 (0.0212- 0.1596) 0.010 No information 0.0575 (0.0283- 0.0866) <0.001 Other 0.0050 (-0.0048- 0.0148) 0.318 Unknown -0.0591 (-0.0837- -0.0346) <0.001 Disease Severity Hepatic Encephalopathy at Baseline 0.0431 (0.0328- 0.0534) <0.001 Ascites at Baseline 0.0638 (0.0551- 0.0724) <0.001

Liver Field during Immunotherapy of Hepatocellular Carcinoma: Some Like It Hot

Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis

Disparities in receipt of hepatocellular carcinoma (HCC) surveillance contribute to disparities in overall survival outcomes. We aim to evaluate disparities in receipt of routine HCC surveillance among patients with cirrhosis in a large urban safety-net hospital. Consecutive adults (age≥18) with cirrhosis from July 1, 2014, to December 31, 2015, were retrospectively evaluated to determine rates of receiving appropriate HCC surveillance within 6months and 1year after diagnosis of cirrhosis. Rates of HCC surveillance were stratified by sex, race/ethnicity, and liver disease etiology. Multivariate Cox proportional hazards models were utilized to evaluate for predictors of receiving appropriate HCC surveillance. Among 157 cirrhosis patients enrolled [hepatitis C virus (HCV): 29.9%, hepatitis B virus: 13.4%, alcoholic cirrhosis: 44.6%, nonalcoholic steatohepatitis (NASH): 8.9%], mean age of cirrhosis diagnosis was 53.8±9.0years. Among these patients, 49% received (n=77) HCC surveillance within 6months and 78% (n=123) were surveyed within 1year of cirrhosis diagnosis. On multivariate analyses, patients with NASH cirrhosis were significantly less likely to receive HCC surveillance compared with chronic HCV cirrhosis patients (HR 0.44, 95% CI 0.19-0.99, p<0.05). No significant sex-specific or race/ethnicity-specific disparities in receipt of HCC surveillance were observed. Among a diverse safety-net hospital population, sub-optimal HCC surveillance rates were observed: Only 49% of cirrhosis patients received HCC surveillance within 6months, and 78% of cirrhosis patients received HCC surveillance within 1year. Differences in rates of HCC screening by liver disease etiology were observed.

To evaluate rates and predictors of retention into hepatocellular carcinoma (HCC) surveillance beyond initial screening among underserved cirrhosis patients. Although initial HCC screening among cirrhosis patients remains low, few studies have evaluated retention to HCC surveillance beyond initial screening. We retrospectively evaluated all consecutive adults with cirrhosis from 2014 to 2017 at a single underserved safety net hospital system to determine rates of HCC surveillance at 6 months and at 1 year beyond initial screening. Rates of HCC surveillance was stratified by sex, race/ethnicity, and etiology of liver disease. Multivariate Cox proportional hazards models evaluated predictors of retention into HCC surveillance. Among 235 cirrhosis patients [hepatitis C virus: 35.7%, hepatitis B virus (HBV): 15.7%, alcoholic cirrhosis: 36.2%, nonalcoholic steatohepatitis (NASH): 8.1%], mean age of cirrhosis diagnosis was 54.2±8.9 years. Overall, 74.8% received initial screening within 1 year of cirrhosis diagnosis. Among those who completed initial screening, 47.6% [95% confidence interval (CI), 41.4-54.2) received second surveillance within 1 year. On multivariate analyses, patients with NASH and HBV were significantly more likely to receive second HCC surveillance compared with hepatitis C virus, HBV (hazard ratio, 2.32; 95% CI, 1.18-4.56; P=0.014) and NASH (hazard ratio, 2.49; 95% CI, 1.22-5.11; P=0.012). No sex or race-specific/ethnicity-specific differences in HCC surveillance retention were observed. Although overall rates of initial HCC screening among cirrhosis patients is nearly 75%, retention into continued HCC surveillance is poor, with less than half of patients undergoing subsequent HCC surveillance. Cirrhosis patients with HBV and NASH were more likely to be retained into HCC surveillance.