Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study

Abstract

Background: Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC). Aims: The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound. Methods: We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1 cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively. Results: Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7 cm (interquartile range: 0.5–0.8 cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3–6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2–47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10 ng/mL (HR: 4.01, 95% CI, 1.85–8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95–12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27–5.08). Conclusions: Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3–6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.

AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma

“…[96] Patients with a subcentimeter liver lesion on ultrasound (US-2) can be safely observed with repeat short-interval surveillance using ultrasound and AFP in 3-6 months given a low risk of HCC, suboptimal performance of CT or MRI to accurately diagnose HCC in lesions <1 cm, and expected tumor doubling time if the lesion were HCC. [87,97,98] If the liver lesion remains stable on two or more follow-up ultrasound exams, the risk of HCC is likely sufficiently low for the patient to return to semiannual surveillance. Visualization limitations (LI-RADS visualization scores B or C) may be observed in ∼20% of patients, particularly patients with obesity and those with nonviral etiologies of cirrhosis, and the optimal recall strategy in these patients is unknown.…”

“…APHE and delayed washout are the characteristics most strongly associated with HCC 113 . LI-RADS criteria consider tumor size because accuracy for imaging techniques decreases in lesions < 2 cm 97,98,114 . Therefore, for nodules ≥2 cm, APHE and one additional criteria (washout, enhancing capsule, or threshold growth) suffices for HCC diagnosis.…”

“…[113] LI-RADS criteria consider tumor size because accuracy for imaging techniques decreases in lesions < 2 cm. [97,98,114] Therefore, for nodules ≥ 2 cm, APHE and one additional criteria (washout, enhancing capsule, or threshold growth) suffices for HCC diagnosis. For nodules 10-19 mm in size, APHE and either washout or threshold growth are required, or APHE and two major criteria.…”

“…[133,134] Sensitivity of liver biopsy ranges between 70% and 93% for most tumors but has been reported as low as ∼60% in tumors < 2 cm. [97,[135][136][137] A negative biopsy does not eliminate the possibility of HCC, and a second biopsy is recommended when findings are inconclusive, particularly if tumor growth or change in enhancement pattern are identified during follow-up but the lesion is still not categorized as LR-5. [97] Risk of complications after liver biopsy, such as tumor seeding and bleeding, has been reported to be ∼3%, although this has substantially decreased with coaxial needle technique.…”

“…[97,[135][136][137] A negative biopsy does not eliminate the possibility of HCC, and a second biopsy is recommended when findings are inconclusive, particularly if tumor growth or change in enhancement pattern are identified during follow-up but the lesion is still not categorized as LR-5. [97] Risk of complications after liver biopsy, such as tumor seeding and bleeding, has been reported to be ∼3%, although this has substantially decreased with coaxial needle technique. [138] Diagnostic biomarkers AFP, at a threshold of 400 ng/ml, was previously recommended as a diagnostic criterion for HCC, although over 40% of HCC have normal AFP levels, and elevated AFP levels can be observed in other cancers, including intrahepatic cholangiocarcinoma, gastric cancer, and germ cell tumors.…”