Primary hepatocellular carcinoma (HCC) is currently one of the most lethal malignant tumors worldwide, and the incidence rate has a yearly increasing trend worldwide. Early diagnosis is essential for the prognosis of HCC patients, especially for those at high risk of liver cancer. We specifically invites Prof. singal, who has made an online interview with good suggestions regarding the issues currently present in liver cancer early screening and shares recent advances in molecular markers for early diagnosis of HCC.
Q:How would you rate current liver cancer screening strategies for patients with viral hepatitis, and what are the latest recommendations?
A:Viral hepatitis continues to be the most common risk factor for hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide. Given the stark contrast in treatment options and expected survival based on tumor stage at diagnosis, professional society guidelines recommend HCC surveillance in high-risk groups, including subsets with chronic HBV infection and those with cirrhosis from any etiology. A meta-analysis of recent cohort studies highlights a consistent association between surveillance receipt and improved clinical outcomes, including early detection, curative treatment receipt, and overall survival. Despite these recommendations, most HCC continue to be diagnosed at an advanced stage. There are several failures in our current surveillance strategies that must be addressed to improve HCC surveillance effectiveness and reduce HCC mortality. First, our current “one-size-fits-all” paradigm ignores variation in HCC risk between individuals for whom surveillance is recommended as well as among excluded populations. This concept may be particularly useful to identify high-risk patients with advanced fibrosis but not cirrhosis who warrant surveillance after SVR as well as low-risk patients with cirrhosis who do not require surveillance. While several risk scores (as well as a blood-based biomarker, PLSec-AFP) have been derived and internally validated, few have been externally validated and achieve sufficient accuracy for routine use in clinical practice. Second, most professional societies recommend ultrasound-based surveillance, which is operator dependent and has suboptimal sensitivity for early HCC detection – missing approximately half of early-stage HCC if used alone and approximately one-third if used in combination with AFP. Several imaging- and blood-based surveillance strategies (e.g., abbreviated MRI, GALAD, and methylated DNA marker panels) have promising accuracy for early-stage HCC detection, although large prospective validation in diverse patient cohorts are still needed. Finally, HCC surveillance is underused in clinical practice, with a recent systematic review finding only one-fourth of at-risk patients are undergoing surveillance, with even lower estimates when considering consistent semi-annual surveillance over extended periods of time. Surveillance underuse is related to severalpatient- and provider-barriers, which must be addressed to increased utilization. Notably, some barriers appear to be specific to imaging-based surveillance so validation of blood-based biomarkers may also improve utilization and maximize surveillance effectiveness. Several inreach and outreach interventions have demonstrated efficacy to increase HCC surveillance, and studies are now needed to evaluate how best to implement these interventions in clinical practice.Although HCC continues to have a poor overall prognosis at this time, there have been dramatic advances in all three of these areas, highlighting promise for improved outcomes in the near future.
Q:What are the new findings in recent years in terms of molecular markers for early diagnosis of HCC?
A:This has been an area of immense interest in terms of blood-based biomarkers for early detection of HCC. I think the protein marker that likely has the best data for early detection of HCC is GALAD, a biomarker panel that includes AFP, AFP-L3 and DCP combined with age and gender. This has been shown to be highly sensitive as well as specific for the detection of HCC in a large multinational case control study, as well as now some early cohort studies. There are some data that will be coming out later this year in terms of large cohort validation of GALAD, but I think at this time, this is really the best evaluated protein biomarker. There has also been immense interest in liquid biopsy techniques for early detection of HCC, and I think one of the areas that is probably furthest along are methylated DNA panels. Those have been evaluated in large case control studies. There are two methylated DNA panels that have recently undergone case control validation, and both of those have been published in the past few months. One of those methylated DNA marker panels was shown to be highly sensitive and specific, with a sensitivity >80% for early stage HCC detection, and a specificity exceeding 85%. Those are now undergoing further validation in studies at this time
Q:To the best of your knowledge, is the examination of serum virological level meaningful in the early screening of liver cancer? How clinically valuable are their results?
A:I think that really the reason why serum virology is important is, first, it is important obviously to check serologies for the detection of chronic hepatitis B and chronic hepatitis C so you can identify the at-risk patients. Then, of course, the viral load. We know that chronic hepatitis B correlates with HCC risk, so the higher your viral load, the higher your HCC risk is. So these havebeen incorporated into risk models among patients with chronic hepatitis B. I think those are the main reasons to check serum virology levels - mainly to evaluate risk level, but not necessarily as a screening test among those patients
评论
发表评论