Key messages
In people with chronic liver disease,
· computerised tomography (CT: cross-sectional scans inside the body) probably misses liver cancer in 22.5% of people who would not receive timely or appropriate treatment, and also, CT incorrectly finds liver cancer in 8.7% of people who would receive unnecessary treatment.
· CT probably misses liver cancer in 28.6% of people with liver cancer who could have surgery to remove part of their liver, and CT incorrectly finds liver cancer in 7.7% of people who undergo inappropriate surgery.
· The studies were too different from each other to allow us to draw firm conclusions based on the evidence.
Why is it important to diagnose liver cancer accurately?
Liver cancer, or ‘hepatocellular carcinoma’ occurs mostly in people with chronic liver disease, regardless of the cause. It is the sixth most common cancer in the world and the fourth most common cause of death due to cancer. It is difficult to diagnose because early symptoms are similar to those of liver disease. People with blood test or ultrasound results that suggest liver cancer may go on to have further tests, such as scans that produce images of the liver, or biopsy where a small piece of the liver is removed and examined. If liver cancer is detected early, people may be treated with surgery to remove part of the liver (a liver resection) or with a liver transplant. If the liver cancer is more advanced, people may need chemotherapy. If liver cancer is missed, people will not receive appropriate treatment. However, incorrectly diagnosing liver cancer when it is not present means that people may undergo unnecessary testing or treatment.
What is computed tomography and how might it diagnose liver cancer?
Computed tomography (CT) produces images that show a cross-section or ‘slice’ of the bones, blood vessels and tissues inside the body. The images consist of a series of X-rays that are directed and combined by a computer. CT scans can detect the presence of abnormalities in the liver that might be cancer. Current guidelines recommend using either CT or another type of imaging, magnetic resonance imaging (MRI), to confirm the presence of liver cancer in people who might have liver cancer, and to judge the size and spread (stage) of the cancer.
What did we want to find out?
We wanted to find out if CT is accurate enough to diagnose liver cancer in adults with chronic liver disease. We were interested firstly, in liver cancers of any size and stage and secondly, in liver cancers that were suitable for resection.
What did we do?
We searched for studies that assessed the accuracy of CT scans compared to the best available tests to confirm liver cancer in adults with chronic liver disease. The best available tests are examination of the liver, or part of the liver under a microscope.
What did we find?
We found a total of 21 studies with 3101 people.
Based on the studies, around 520 (52%) out of 1000 adults with chronic liver disease have confirmed liver cancer. Of these 1000 people, CT may:
· correctly detect liver cancer in 403 people
· miss liver cancer in 117 people
· incorrectly detect liver cancer in 42 cancer-free people
· correctly detect no liver cancer in 438 people.
Based on the studies, around 350 (35%) out of 1000 adults with chronic liver disease have confirmed resectable liver cancer. Of these 1000 people, CT may:
· correctly detect resectable liver cancer in 250 people
· miss resectable liver cancer in 100 people
· incorrectly detect resectable liver cancer in 50 people; and
· correctly detect no resectable liver cancer in 600 people.
What are the limitations of the evidence?
Our confidence in the evidence is limited because the studies used different methods to select study participants and used different definitions for the presence of liver disease. This means CT scans could be more or less accurate than suggested by the evidence.
How up to date is this evidence?
The evidence is up to date to 4 May 2021.
In the clinical pathway for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, CT has roles as a confirmatory test for hepatocellular carcinoma lesions, and for staging assessment. We found that using CT in detecting hepatocellular carcinoma of any size and stage, 22.5% of people with hepatocellular carcinoma would be missed, and 8.7% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 28.6% of people with resectable hepatocellular carcinoma would improperly not be resected, while 8% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.
Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and fourth in terms of cancer deaths. In clinical practice, computed tomography (CT) is used as a second-line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha-foetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast-enhanced imaging study CT or magnetic resonance imaging (MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is valid to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma is, therefore, missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of CT may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CT in people with chronic liver disease, who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma.
Primary: to assess the diagnostic accuracy of multidetector, multiphasic contrast-enhanced CT for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, either in a surveillance programme or in a clinical setting.
Secondary: to assess the diagnostic accuracy of CT for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease.
We searched the Cochrane Hepato-Biliary Trials Register, Cochrane Hepato-Biliary Diagnostic-Test-Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index – Science until 4 May 2021. We applied no language or document-type restrictions.
Studies assessing the diagnostic accuracy of CT for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six-month follow-up.
At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses.
We included 21 studies, with a total of 3101 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time-interval between the index test and the reference standard was rarely defined. Regarding applicability in the patient selection domain, we judged 14% (3/21) of studies to be at low concern and 86% (18/21) of studies to be at high concern owing to characteristics of the participants who were on waiting lists for orthotopic liver transplantation.
CT for hepatocellular carcinoma of any size and stage: sensitivity 77.5% (95% CI 70.9% to 82.9%) and specificity 91.3% (95% CI 86.5% to 94.5%) (21 studies, 3101 participants; low-certainty evidence).
CT for resectable hepatocellular carcinoma: sensitivity 71.4% (95% CI 60.3% to 80.4%) and specificity 92.0% (95% CI 86.3% to 95.5%) (10 studies, 1854 participants; low-certainty evidence).
In the three studies at low concern for applicability (861 participants), we found sensitivity 76.9% (95% CI 50.8% to 91.5%) and specificity 89.2% (95% CI 57.0% to 98.1%).
The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results.