Factors That Affect Efficacy of Ultrasound Surveillance for Early Stage Hepatocellular Carcinoma in Patients With Cirrhosis

doi:10.1016/j.cgh.2014.02.025

Clinical Gastroenterology and Hepatology

Volume 12, Issue 11, November 2014, Pages 1927-1933.e2

https://doi.org/10.1016/j.cgh.2014.02.025 Get rights and content

Background & Aims

Ultrasound surveillance does not detect early stage hepatocellular carcinomas (HCCs) in some patients with cirrhosis, although the reasons for this have not been well studied. We assessed the rate at which ultrasound fails to detect early stage HCCs and factors that affect its performance.

Methods

We collected information on 1170 consecutive patients included in the Italian Liver Cancer (ITA.LI.CA) database who had Child–Pugh A or B cirrhosis and were diagnosed with HCC during semiannual or annual ultrasound surveillance, from January 1987 through December 2008. Etiologies included hepatitis C virus infection (59.3%), alcohol abuse (11.3%), hepatitis B virus infection (9%), a combination of factors (15.6%), and other factors (4.7%). Surveillance was considered to be a failure when patients were diagnosed with HCC at a stage beyond the Milan criteria (1 nodule ≤5 cm or ≤3 nodules each ≤3 cm).

Results

HCC was found beyond Milan criteria in 34.3% of surveilled patients (32.2% during semi-annual surveillance and 41.3% during annual surveillance; P < .01). Nearly half of surveillance failures were associated with at least one indicator of aggressive HCC (levels of AFP >1000 ng/mL, infiltrating tumors, or vascular invasion and metastases). Semiannual surveillance, female sex, Child–Pugh class A, and α-fetoprotein levels of 200 ng/mL or less were associated independently with successful ultrasound screening for HCC.

Conclusions

Based on our analysis of surveillance for HCC in patients with cirrhosis, the efficacy of ultrasound-based screening is acceptable. Ultrasound was least effective in identifying aggressive HCC, and at surveillance intervals of more than 6 months.

Section snippets

Patients

We retrospectively analyzed the data from the ITA.LI.CA database, including 3027 consecutive patients diagnosed with HCC from January 1987 through December 2008 at 11 Italian medical institutions (6 academic tertiary care centers and 5 hepatology/gastroenterology units located in general hospitals). The data were collected prospectively and updated every 2 years. Among the initial 3027 patients, we selected the 1170 Child–Pugh A or B cirrhotic patients diagnosed with HCC during semiannual or

Results

Of the 1430 cirrhotic patients undergoing ultrasound surveillance, 1170 patients eventually were available for the study (Figure 1). Their demographic and clinical characteristics are summarized in Table 1. HCC was diagnosed by noninvasive criteria in 1013 patients and histologically in 157 patients. In the latter cases, all studied variables were obtained at the time of biopsy, which was performed no later than 1 to 2 months after imaging.

Surveillance was performed with ultrasound plus AFP

Discussion

In our study, nearly one third of HCCs diagnosed during semiannual or annual ultrasound surveillance were detected beyond Milan criteria, which define the upper limit to apply curative treatments. As previously reported,¹¹ surveillance failures were reduced significantly by the more stringent surveillance program, recommended by international guidelines. Notably, half of the failures observed in semiannually surveyed patients were associated with tumors presenting with features of biological

Acknowledgments

Other ITA.LI.CA members who participated in the data acquisition are as follows: Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum–Università di Bologna: Mauro Bernardi, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Marta Frigerio, Annagiulia Gramenzi, Francesca Garuti, Barbara Lenzi, Donatella Magalotti, and Matteo Ravaioli; Dipartimento di Medicina Clinica e Sperimentale, Università di Padova: Alfredo Alberti, Angelo Gatta, and Maurizio Gios;

References (27)

L.L. Wong et al.
Improved survival with screening for hepatocellular carcinoma
Liver Transpl
(2000)
D. Pateron et al.
Prospective study of screening of hepatocellular carcinoma in Caucasian patients with cirrhosis
J Hepatol
(1994)
F. Trevisani et al.
Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and survival
Am J Gastroenterol
(2002)
V. Santi et al.
The changing scenario of hepatocellular carcinoma over the last two decades in Italy
J Hepatol
(2012)
V. Santi et al.
Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival
J Hepatol
(2010)
Y.H. Kuo et al.
Hepatocellular carcinoma surveillance and appropriate treatment options improve survival for patients with cirrhosis
Eur J Cancer
(2010)
P. Richardson et al.
Determinants of serum alpha-fetoprotein levels in hepatitis C infected patients
Clin Gastroenterol Hepatol
(2012)
E. Lee et al.
Improving screening for hepatocellular carcinoma by incorporating data on levels of alpha-fetoprotein over time
Clin Gastroenterol Hepatol
(2013)
R. Lencioni et al.
Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma
J Hepatol
(2008)
H. El Serag et al.
Alpha-fetoprotein in hepatocellular carcinoma surveillance: mend it but do not end it
Clin Gastroenterol Hepatol
(2013)

A. Cucchetti et al.

Cost-effectiveness of semi-annual surveillance for hepatocellular carcinoma in cirrhotic patients of the Italian liver cancer population

J Hepatol

(2012)

Clinical practice guidelines: management of hepatocellular carcinoma

J Hepatol

(2012)

H.B. El-Serag et al.

Effectiveness of AFP and ultrasound tests on hepatocellular carcinoma mortality in HCV-infected patients in the USA

Gut

(2011)

Cited by (101)

The relationship between the efficacy of thermal ablation and inflammatory response and immune status in early hepatocellular carcinoma and the progress of postoperative adjuvant therapy
2023, International Immunopharmacology
Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Thermal ablation has the advantages of being equivalent to surgical resection, minimally invasive, low cost and significantly reducing hospital stay. Therefore, it is recommended as one of the first-line radical treatment for early HCC. However, with the deepening of research on early HCC, more and more studies have found that not all patients with early HCC can obtain similar efficacy after radical thermal ablation, which may be related to the heterogeneity of HCC. Previous studies have shown that inflammation and immunity play an extremely important role in the prognostic heterogeneity of patients with HCC. Therefore, the inflammatory response and immune status of patients may be closely related to the efficacy of early HCC after curative thermal ablation. This article elaborates the mechanism of high inflammatory response and poor immune status in the poor prognosis after radical thermal ablation of early HCC, and clarifies the population who may benefit from adjuvant therapy after radical thermal ablation in patients with early HCC, which provides a new idea for the precise adjuvant treatment after radical ablation of early HCC in the future.
Serum Protein Kinase C Delta: New Kid on the Block for Early Detection of Hepatocellular Carcinoma
2023, Gastro Hep Advances
Dynamic Changes in Ultrasound Quality for Hepatocellular Carcinoma Screening in Patients With Cirrhosis
2022, Clinical Gastroenterology and Hepatology
Identifying patients in whom ultrasound may be inadequate to exclude the presence of hepatocellular carcinoma (HCC) can inform interventions to improve screening effectiveness. We aimed to characterize correlates of suboptimal ultrasound quality and changes in ultrasound quality over time in patients with cirrhosis undergoing HCC screening.
We performed a retrospective cohort study of patients with cirrhosis who underwent ultrasound examination at 2 large health systems between July 2016 and July 2019. Exam adequacy was graded by radiologists using the LI-RADS Visualization Score (A, B, C); we evaluated changes in visualization over time among patients with >1 ultrasound exams. We performed multivariable logistic regression to identify characteristics associated with limited ultrasound visualization (scores B or C).
Of 2053 cirrhosis patients, 1685 (82.1%) had ultrasounds with score A, 262 (12.8%) had score B, and 106 (5.2%) had score C. Limited visualization was associated with alcohol-related or nonalcoholic fatty liver disease cirrhosis and presence of class II-III obesity. Among 1546 patients with >1 ultrasounds, 1129 (73.0%) had the same visualization score on follow-up (1046 score A, 60 score B, 23 score C). However, 255 (19.6%) of 1301 with score A at baseline had limited visualization when repeated (230 score B, 25 score C), and 130 (53.1%) of 245 patients with baseline limited visualization had good visualization when repeated.
Nearly 1 in 5 patients with cirrhosis had moderately-severely limited ultrasound visualization for HCC nodules, particularly those with obesity or alcohol-related or nonalcoholic fatty liver disease cirrhosis. Ultrasound quality can change between exams, including improvement in many patients with limited visualization.
Outcomes of liver transplantation for nonalcoholic steatohepatitis-associated hepatocellular carcinoma
2022, HPB
Nonalcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is the second-leading cause of liver transplantation (LT) performed for HCC. Despite this, little is known about the clinical characteristics and outcomes of NASH-HCC.
Patients undergoing LT for HCC from 2001 to 2017 at a single center were reviewed. Outcomes of NASH-HCC (n = 51) were compared to other etiologies of HCC including hepatitis C (HCV) hepatitis B (HBV), and alcoholic liver disease (ALD). Outcomes of NASH-HCC were also compared to HCV in the direct-acting antiviral (DAA) era (2014–2017).
The frequency of NASH-HCC as the primary indication for LT in patients with HCC increased significantly during the study period from 4.4% (2001–2008) to 15.6% in 2017. NASH-HCC patients were significantly older (median age 65 vs. 60; P < 0.001) with significantly lower alpha-fetoprotein levels (7.5 vs. 26.5, P < 0.001) compared to other etiologies. The 1-, 3-, and 5-year overall survival of NASH-HCC was 92%, 86%, and 80%. Overall survival of NASH-HCC was not significantly different compared to HCV, HBV, or ALD. Compared to HCV-HCC in the DAA era (n = 99), NASH-HCC had comparable post-LT survival (3-year survival 87% vs. 86%, P = 0.870).
In this large single-center experience of NASH-HCC, we demonstrate favorable outcomes of NASH-HCC following LT comparable to other common etiologies of HCC.
Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information
2022, Journal of the Formosan Medical Association
Citation Excerpt :
In our study population, 60% of the patients had liver cirrhosis in both the large-scale TCR database and the KCGMH HCC registry. Many factors affect the efficacy of US surveillance for early stage HCC in patients with liver cirrhosis, including operator dependency, and lower-quality imaging in patients with obesity, severe fatty liver, or increased liver nodularity.14,15 As per the current AASLD guidelines, the recommended modality for HCC screening and surveillance is liver US with or without AFP, performed every 6 months.6
Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels.
This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017.
The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC.
This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.
Changes in the ultrasound presentation of hepatocellular carcinoma: a center’s three decades of experience
2024, Journal of Ultrasound

View all citing articles on Scopus

: Conflicts of interest The authors disclose no conflicts.

View full text

Original articlePancreas, biliary tract, and liverFactors That Affect Efficacy of Ultrasound Surveillance for Early Stage Hepatocellular Carcinoma in Patients With Cirrhosis

Background & Aims

Methods

Results

Conclusions

Section snippets

Patients

Results

Discussion

Acknowledgments

Liver Transpl

J Hepatol

Am J Gastroenterol

J Hepatol

J Hepatol

Eur J Cancer

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

J Hepatol

Clin Gastroenterol Hepatol

J Hepatol

Clinical practice guidelines: management of hepatocellular carcinoma

J Hepatol

Effectiveness of AFP and ultrasound tests on hepatocellular carcinoma mortality in HCV-infected patients in the USA

Gut

Original article
Pancreas, biliary tract, and liver
Factors That Affect Efficacy of Ultrasound Surveillance for Early Stage Hepatocellular Carcinoma in Patients With Cirrhosis