Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: A randomized trial comparing 3- and 6-month periodicities

Abstract

Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC 30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n 5 640; Gr6M, n 5 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, 30 mm in diameter 74%). Focal-lesion incidence was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus 13.2%, P 5 0.067) but incidence of lesions 10 mm was increased (41% in Gr3M versus 28% in Gr6M, P 5 0.002). No difference in either HCC incidence (P 5 0.13) or in prevalence of tumors 30 mm in diameter (79% versus 70%, P 5 0.30) was observed between the randomized groups. Conclusion: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures.

Priority of Alpha-L- Fucosidase Over Alpha fetoprotein in Early Detection of Hepatocellular Carcinoma in Animals and Human

“…The current gold standard and most commonly used biomarker for patients at risk for HCC is AFP. AFP along with ultrasound every 6 to 12 months, despite being the most applicable tool for HCC diagnosis, yet proved to have serious limitations (25)(26)(27).Some reports have indicated that the high serum concentration of AFP correlates with the poor prognosis of HCC patients (28). However, two thirds of HCC patients with the nodule less than 4 cm have serum AFP levels less than 200 ng/mL and up to 20% HCC patients do not produce AFP.…”

Ultrasound screening for hepatocellular carcinoma in patients with advanced liver fibrosis. An overview

“…According to the meta-analysis by Singal et al [22], US sensitivities for detecting early-HCC may be improved by US at 6 month intervals, compared to surveillance intervals between 6-12 month (sensitivities: 70% vs 50%, p=0.001). A recent randomized control trial [23] investigated whether a 3-mo interval of US surveillance was more effective than a 6-mo interval and no differences in detection rates of small HCC, eligible for curative treatment, were observed between the two randomized groups.…”

Role of Surveillance in Prevention of Hepatocellular Carcinoma

“…16 However, recently a randomized trial was conducted comparing 3-and 6-month periodicities in Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis and authors concluded that surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures. 36 A prospective cohort study from Italy which had done surveillance using AFP and USG at 6-month intervals found the cost to be US$112,993 per life-year saved. 37 Two systematic reviews have also looked at cost effective strategies for surveillance in HCC.…”