Poor Adherence to Hepatocellular Carcinoma Surveillance

A Systematic Review and Meta-analysis of a Complex Issue

Changqing Zhao; Mingjuan Jin; Richard Hieu Le; Michael Huan Le; Vincent Lingzhi Chen; Michelle Jin; Grace Lai-Hung Wong; Vincent Wai-Sun Wong; Young-Suk Lim; Wan-Long Chuang; Ming-Lung Yu; Mindie H. Nguyen


Liver International. 2018;38(3):503-514. 

In This Article

Abstract and Introduction


Background & Aims Hepatocellular carcinoma (HCC) surveillance is associated with improved outcomes and long-term survival. Our goal is to evaluate adherence rates to HCC surveillance.

Methods We performed a systematic search of the PubMed and Scopus databases and abstract search of relevant studies from recent major liver meetings. All searches and data extraction were performed independently by two authors. Analysis was via random-effects models and multivariate meta-regression.

Results A total of 22 studies (n = 19 511) met inclusion criteria (original non-interventional studies with defined cirrhosis or chronic hepatitis B or chronic hepatitis C with advanced fibrosis populations, and surveillance tests and intervals). Overall adherence rate was 52% (95% CI 38%-66%). Adherence was significantly higher in cirrhotic patients compared to chronic hepatitis B and other high-risk patients, in European compared to North American studies, in less than 12-month compared to yearly surveillance intervals, and in prospective compared to retrospective studies (71%, 95% CI 64%-78% vs 39%, 95% CI 26%-51%, P < .001). The between-study heterogeneity of all above analyses was significant (P < .001). Only the study design (retrospective vs prospective cohort) had statistical significance in a multivariate meta-regression model (P < .05) and could account for some of the differences above.

Conclusions Overall adherence rate to HCC surveillance was suboptimal at 52% with no significant differences by liver disease aetiology or study location in multivariate meta-regression analysis. Further research and educational efforts are needed to improve the current rate of HCC surveillance.


Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide, the second leading cause of cancer-related death and the leading cause of death in patients with cirrhosis.[1] HCC surveillance is the serial application of screening tests to detect the presence of HCC among at-risk populations before it becomes clinically suspected or evident. Major HCC practice guidelines recommend that all patients at high risk for developing HCC should be entered into surveillance programmes.[2–4] The rationale for conducting HCC surveillance is that regular screening of at-risk asymptomatic patients may detect tumours at an early stage when potentially curative treatment can be offered.

In fact, a prior meta-analysis by Davila et al has shown that HCC surveillance was associated with improved early stage detection, curative treatment rates and survival.[5] However, HCC surveillance in real-life practice is under-utilized with adherence rate less than 20% reported in two different studies of American patients with cirrhosis and 12% in another American cohort of patients with hepatitis C virus (HCV) infection from the Veterans Administration healthcare system.[6–8]

Another previous systematic review by Singal et al conducted in the USA included patients diagnosed with HCC or cirrhosis to determine the adherence rate to the HCC national guidelines. They reported an adherence rate of only 18.4% though surveillance rates were significantly higher among patients followed in subspecialty gastroenterology clinics compared to those followed in primary care clinics (51.7% vs 16.9%, P < .001). Another recent meta-analysis reported that only one-third of patients with HCC were diagnosed by screening, surveillance and without symptoms.[9]

Since the systematic review performed by Singal et al was conducted prior to the updated AASLD HCC surveillance guidelines where recommended screening was changed from every 6 to 12 months to every 6 months, it was apparent that an updated systematic review and meta-analysis was necessary to determine if the new AASLD guidelines have impacted the rate of surveillance adherence. This type of review was especially necessary given the high rate of mortality of HCC when diagnosed late and as noted in Jin et al's study only 33% of patients diagnosed with HCC were actually diagnosed through surveillance suggesting that patients' HCC was found in the later stages when curative treatment is less an option.[9] Therefore, the purposes of this study were to perform a systematic review and meta-analysis to estimate pooled adherence rates for at-risk patients who were free of HCC at inclusion from diverse geographical regions and different liver disease aetiologies as well as to identify factors that may influence HCC adherence.