Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

ABSTRACT Background and Aims This study aimed to analyse the impact of the aetiology of underlying cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and two prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results Among 3533 patients (1926 virus - VIR, 1167 alcohol - ALC, 440 combined- MIX), 431 HCC were diagnosed after a median follow-up of 57.1 months. The five-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but BCLC early stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of more impaired ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have a : i) lowest five-year HCC incidence; ii) poorer prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay Summary The futility of HCC early detection in patients with alcoholic cirrhosis has been suggested. By comparing the outcome of more than 3000 patients with compensated cirrhosis included in surveillance programs as a function of the cause of liver disease, this study suggests that HCC surveillance enables early diagnosis in most of patients with alcoholic cirrhosis despite higher rates of competing risks of death. We also report similar access to first-line curative HCC treatment in these patients as compared to patients with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death independantly from the cause of cirrhosis. Registration CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links ( https://clinicaltrials.gov/ct2/show/NCT00190385 ) and https://clinicaltrials.gov/ct2/show/NCT01213927 , respectively). The full CirVir protocol is available via the ANRS Web site ( http://anrs.fr ).