HCC SCREENING: POSSIBLE IMPROVEMENTS

These conflicting results should prompt investigators and health care authorities to evaluate the topic of HCC screening limits and explore possible improvements at various levels.

Failure to identify at-risk patients


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It is well known that up to 40% of patients present with HCC without having previously recognized liver disease and/or cirrhosis.58,59 In addition, the failure to recognize cirrhosis is strongly associated with advanced HCC stage at diagnosis and may be related to patient evaluation by non specialist care providers.60

In order to improve the recognition of those subjects at risk, a number of measures could be implemented:

  1. Increasing the use of electronic medical records to facilitate the recognition of patients with positive viral markers and the assessment of non invasive laboratory markers of liver disease and/or fibrosis such as the AST to platelet ratio index (APRI)58,61–63 in order to trigger the cascade of instrumental and/laboratory screening modalities (se below) in a larger population of patients;
  2. Reduce under-recognition of HCV-positive cases: Centers for Disease Control and Prevention and the US Public Health Task Force recommended one-time testing for anti-HCV for people born between the years 1945 and 1965, a period of time when the highest incidence of HCV was found.64,65 Recently, in France and the United States, universal screening for HCV has been proposed based on the assumption that it is cost-effective in terms of increased life expectancy and quality-adjusted life years, provided that early therapy is started with direct-acting Antivirals (DAA) regardless of the stage of fibrosis.66–68
  3. Inclusion of other subsets of patients at risk: in NAFDL/non-alcoholic steatohepatitis (NASH) patients (especially those with obesity and/or diabetes) HCC may occur in the absence of cirrhosis69 in approximately 15% of cases, and is often recognized at an advanced stage when survival times are shorter.70 These poor outcomes do not result from a greater biological aggressiveness of NAFLD-related HCC but from delayed referral to tertiary care (or specialist) centers.71 What kind of NAFLD patients at risk for HCC should undergo regular surveillance is likely to be the huge health care question over the next few years. This will occur due to a decline in HCV infection as a consequence of effective eradicative therapy and the reduction of baby boomers, who are the major reservoir of HCV. On the basis of the most recent epidemiological data,34 it seems logical to assume that at least NAFLD-related cirrhosis warrants surveillance. Alcoholic etiology of cirrhosis should be reconsidered as well in the light of recent epidemiological evidence that annual HCC incidence in this specific population is well above the threshold which makes screening programs cost-effective.32
  4. Education of primary care providers (PCPs): it is maintained that PCPs under-recognize chronic liver disease and cirrhosis and may have misconceptions about how best to perform surveillance (timing and/or type of screening tools) and report several barriers to implementation (eg, not being up-to-date with current guidelines, lack of reminder systems for HCC surveillance).72 It is not by chance that the adherence rate improves dramatically if patients seek hepatogastroenterologic visits.59,72,73 Therefore, efforts should be undertaken to educate PCPs regarding at-risk populations with chronic liver disease of any etiology, the correct use of screening tools and the benefit of HCC surveillance. Since PCPs are one of the main steps toward improving screening, automated reminders could also be a mean to increase their awareness of HCC screening.74 A pilot study in Italy75 showed that implementation of a training program targeting PCPs, aimed at improving the identification of cirrhotic patients living in an area with a high prevalence of disease, led to improved HCC patient survival.

Failure to access care

Although patients’ adherence is not considered a major barrier to HCC screening, patient non compliance accounted for <10% of cases in which surveillance was not completed.73 Difficulty with the scheduling process, costs of surveillance testing and transportation difficulties may prevent access to screening especially in socio economically disadvantaged patients.76 Conversely, high levels of instruction and income, living in urban areas, and insurance coverage are all associated with more regular and effective surveillance.15,16,73

In this context, the type of health care system plays a pivotal role: wherever government health care authorities cover patient expenses and offer more screening tests and shorter screening intervals, a higher compliance to HCC surveillance is expected. This is the case of Japan, one of the few countries which carried out a national screening program.77 In contrast, in the United States different health care insurance systems exist, which explains, at least in part, the HCC screening adherence rate widely ranging between 12% and 80%.44,59,78–82 In addition, participation in screening campaigns of cirrhotic patients may be improved by mailed outreach strategies by providing information about HCC risk and the importance of semi annual surveillance, as well as direct patient telephone interviews aimed at encouraging those who did not adhere to surveillance.83 However, these strategies were not capable of either pushing surveillance rate above 30% in the enrolled population or significantly increasing the detection rate of early-stage HCC compared to standard surveillance modality (ie, HCC surveillance ordered by clinicians during any outpatient visit).

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