Image: Very high magnification micrograph of fibrolamellar hepatocellular carcinoma showing the characteristic laminated fibrosis between the tumor cells with a low N/C ratio. H&E stain (Photo courtesy of Wikimedia Commons).
Investigators discovered that patients with cirrhosis who underwent surveillance (using liver ultrasound with or without measurement of serum alpha fetoprotein) for hepatocellular carcinoma (HCC) had cancers detected at an earlier stage, were more likely to receive curative instead of palliative treatment, and had longer survival.
In a systematic review and meta-analysis of 47 studies with 15,158 patients, Dr. Amit Singal, from the University of Texas Southwestern Medical Center (Dallas, USA) and colleagues reported that the pooled thee-year survival rate across all the studies was 50.8% among the 4,735 patients who underwent HCC surveillance, compared to 27.9% among the 6,115 patients without earlier surveillance (p
The finding of longer survival persisted after the authors limited their review to studies that took into account lead time bias. Lead time bias, as it applies to this study, is the time between when a disease would normally be diagnosed without screening and when the disease is diagnosed with screening. Detecting disease earlier through screening can at times seen be to increase survival when instead it only prolongs the time the person has the diagnosis. However, in this case, studies that accounted for lead time bias statistically still found that screening increased survival. Among the six studies that adjusted for lead time bias, those who underwent HCC surveillance had three-year survival rates of 39.7%, vs. 29.1% among those who did not (p
The authors noted that while screening for HCC in patients with Hepatitis B virus
(HBV) infection is supported by a large randomized trial, no such randomized trials exist for patients with cirrhosis. Therefore the authors systematically reviewed published research that evaluated whether screening was associated with improved patient outcomes. While guidelines of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver recommend monitoring with ultrasound every six months in high-risk patients (which includes those with chronic HBV infection and/or cirrhosis), the authors noted that studies have shown that surveillance in the United States is performed in less than 20% of these patients nationally, with lower rates among primary care physicians than gastroenterologists/hepatologists (physicians who specialize in caring for patients with liver disease).
A drawback of the study is that the studies were quite heterogeneous, suggesting benefits of surveillance may not be uniform among all patients, and studies did not include functional status, an important factor in determining appropriate treatment.
The authors concluded that, “the preponderance of data that consistently demonstrate benefits should provide sufficient rationale to recommend HCC surveillance, even in the absence of a randomized controlled trial among patients with cirrhosis.”
University of Texas Southwestern Medical Center