Liver cancer screening in patients with liver cirrhosis can improve the early diagnosis, early treatment and survival rate

 

Editor's note: Due to the lack of randomized control data, the overall value of monitoring hepatocellular carcinoma (HCC) in patients with liver cirrhosis is controversial. Considering that the epidemiology has changed from active viral hepatitis to viral hepatitis with sustained virological response (SVR), and the proportion of patients with nonalcoholic steatohepatitis (NASH) has increased, the benefits of HCC monitoring also need to be reassessed. From September 1 to 4, 2022, at the 16th ILCA 2022 Annual Meeting held in Spain, Professor Amit Singal of the Southwest Medical Center of the University of Texas reported a systematic review and meta-analysis, evaluated the clinical value of HCC monitoring in patients with liver cirrhosis, and won the best wall report of the meeting. Professor Amit Singal was specially invited by the magazine to conduct an exclusive interview, which gave an in-depth interpretation of the main success and clinical significance of the study. Now the content is arranged into a text for the readers.

 Interview with Professor Amit Singal, Southwest Medical Center, University of Texas

First of all, would you please introduce to us a study on liver cancer screening of patients with liver cirrhosis that you conducted at this conference? What did it find? What kind of application value does this have for the diagnosis, treatment and prognosis prediction of liver cancer?

Dr Singal: What we performed was a meta-analysis of the studies looking at the benefits and harms of HCC surveillance in patients with cirrhosis. When we look at this on a broader scale, we have very good data that came out of China showing that HCC surveillance was of benefit in patients with chronic hepatitis B in a large randomized controlled trial. We don’t have similar randomized controlled trial data in patients with cirrhosis, so we are forced to depend on cohort studies. So we conducted a meta-analysis of the cohort studies that have been conducted in the last 5-6 year period. We felt this was important giving changing epidemiology over time, where we have more and more patients presenting with hepatitis C cure, and more and more patients presenting with alcohol-related or NASH-related cirrhosis, in terms of underlying etiologies. We looked at the association between surveillance receipt and three clinical outcomes to define benefits - early detection, curative treatment receipt and reduced mortality - and we found that HCC surveillance was significantly associated with all three clinical benefits. Conversely, we also looked at potential harms of HCC surveillance, and that can include physical harms (diagnostic workup of false positive or indeterminate results), psychological harms and financial harms. We found four studies that quantified the physical harms of HCC surveillance, and no studies that looked at psychological or financial harms of HCC surveillance. The four studies that looked at potential physical harms of HCC surveillance showed this ranged from 8% to 28% across the studies, with most of those harms being mild in nature. So our conclusion was that, right now, the data show or suggest that HCC surveillance is of high value and should be performed in patients with cirrhosis, although we do recommend continued studies to evaluate this in emerging patient populations, most notably those with underlying NASH.

 

Clinically, the earlier the liver cancer is discovered, the better the treatment effect. What are your suggestions on how to detect liver cancer as soon as possible?

Dr Singal: I think the first is to identify those populations that are at high risk. Right now, most guidelines agree those are subsets of patients with chronic hepatitis B and then any patient with cirrhosis from any etiology. We know that HCC surveillance should be on a semi-annual basis (so every six months), and the current recommended tests are ultrasound with or without alpha-fetoprotein (AFP), depending on which Societal guidelines you follow. For example, EASL Guidelines recommend ultrasound alone. The American Association for the Study of Liver Disease (AASLD) Guidelines recommend ultrasound with AFP. My current suggestion is to perform ultrasound with alpha-fetoprotein because the available data suggest that the sensitivity is significantly higher using the two tests in combination. Then I think you need to take a look at how well those tests perform in your underlying population. We do know that ultrasound has poor visualization and is more prone to failure in some patients, particularly those with underlying NASH and those with underlying obesity. If you learn that ultrasound does not give you good visualization, those are patients for whom we would look for alternative modalities, although we are waiting for those newer emerging surveillance tests, whether they are biomarker-based or imaging-based to be validated. Those are studies that still need to be done.

 

From your perspective, how to further improve the accuracy of early diagnosis of liver cancer?

Dr Singal: I think there are two things that really need to be done in terms of improving the effectiveness of HCC surveillance. We, and others, have pointed out that surveillance is often underused in clinical practice, so many patients fail to receive HCC surveillance. So the first thing is that we need to continue to work through interventions that can increase HCC surveillance in our clinical practice. The second is our search for better tests. Right now, as I mentioned, we are doing ultrasound and AFP, but that combination misses HCC in its early stage in around one-third of patients - the sensitivity of that combination is about 63-65%. We clearly need more accurate tests, whether that is blood-based biomarkers (liquid biopsy techniques, etc.), or imaging-based techniques (such as MRI-based surveillance). We still have some work to do to validate those emerging modalities, but I think we need to work in parallel, both in terms of utilization, as well as new tests that can improve sensitivity.