编者按：2021年2月4～6日，第30届亚太肝病研究学会（APASL）年会以线上形式盛大召开。此次大会旨在推进肝病学科进展和基础教育，交流理念并达成共识，鼓励在肝病学领域开展医学实践，并协调各区域在不同肝病相关学科间的科学研究。

 

美国肝病研究学会（AASLD）候任主席、美国马萨诸塞州总医院肝病和肝脏中心主任Raymond Chung教授应邀于2月6日发表题为“Should we stop HCC surveillance after the eradication of viral hepatitis?”的主题报告，《国际肝病》记者有幸邀请到Chung教授作内容前瞻，并就病毒性肝炎相关肝细胞癌（HCC）的危险因素、监测和预防作最新述评。

 

 

抗病毒治疗可降低HCC发生风险，但不同患者有差异

 

对丙型肝炎患者进行病毒根治治疗以及对乙型肝炎患者进行病毒抑制治疗，与患者的最终临床获益密切相关。抗病毒治疗一方面降低了肝硬化和失代偿期肝病的发病率，另一方面减少了HCC的发生。

 

对于乙型肝炎病毒（HBV）感染者，当不合并肝硬化或应用核苷（酸）类似物聚合酶抑制剂抗病毒治疗时，HCC的发生风险降低80%；当肝硬化且有高危肝癌风险因素时，经合理抗病毒治疗后，HCC发生风险也可降低30%。虽然目前仍然无法做到彻底清除HBV达到乙型肝炎功能性治愈，但我们期待新型疗法的出现，进一步降低HCC发病率。

 

在重度肝纤维化或肝硬化的患者中，即使实现乙型肝炎完全治愈，也无法消除进展为肝癌的风险；所以对重度肝纤维化或肝硬化患者，我们需要密切监测随访HCC发生的可能。但总体而言，合理抗病毒治疗可减少近3/4的肝硬化患者进展为肝癌。

 

因此，我们仍应努力使丙型肝炎达到彻底治愈，使乙型肝炎实现功能性治愈，同时对所有肝炎患者进行密切监测。

 

《国际肝病》: Is there any difference in the incidence of hepatocellular carcinoma after virus eradication amongst patients trialed with different therapies?

 

Dr Chung: It is absolutely clear that both curing the virus (for hepatitis C) and suppressing the virus (most often the case for hepatitis B) are associated with real clinical benefits. That is not just improvements in the rate of cirrhosis and the rate of decompensated liver disease, but also the rates of HCC.

 

For instance, with HBV, we know that patients who suppress the virus with nucleoside analogs/polymerase inhibitors and who are non-cirrhotic, that risk reduction is around 80% for HCC. Moreover, patients with cirrhosis who are at greater risk for liver cancer, their risk reduction, if successfully suppressed, is around 30%. Clearly, there are benefits to suppressing the virus. If you can succeed with loss of HBsAg and achieve a functional cure, which doesn’t happen for the vast majority of patients currently but we hope to be able to do with newer therapies, there may be an even greater benefit in terms of the future incidence of hepatocellular carcinoma. So we should still endeavor to achieve functional cure in hepatitis B to reduce that future risk for HCC.

 

For hepatitis C, we can cure these patients. However, for patients with advanced fibrosis or cirrhosis with the highest risk for subsequent HCC, we know that even curing their HCV does not fully eliminate that risk moving forward. They need to continue to be monitored for this subsequent risk for HCC if they have advanced fibrosis. We do know the risk reduction for HCC is still significant. Most studies suggest a risk reduction of around 75% in patients with cirrhosis for their subsequent development of HCC.

 

Put another way, we are reducing that risk by three-quarters. It’s not a 100% reduction, but it is pretty close. We can say to patients that we can reduce their risk dramatically, but they will still require monitoring for HCC moving forward.

 

肝炎病毒清除后，还有这些危险因素促进HCC发生

 

病毒性肝炎彻底清除后，肝硬化是进展为HCC的最重要危险因素，随访中可通过临床表现或超声弹性成像等无创手段，评估肝硬化严重程度。此外，年龄、糖尿病、脂肪肝、饮酒也是发展为肝癌的重要影响因素。虽然这些危险因素导致肝癌进展，与肝炎病毒清除后的特定基因过度表达或缺失有关，但目前尚无生物学标志物可对病毒性肝炎根除后患者的HCC风险进行预测。

 

《国际肝病》: What are the risk factors for HCC development in patients after eradication of viral hepatitis?

 

Dr. Chung: The most important risk factor for the subsequent development of HCC after the elimination of viral hepatitis is the state of cirrhosis. If there is cirrhosis, particularly advanced cirrhosis, which can be assessed using elastography or clinically based on the appearance of the liver or through the existence of decompensation, then this is associated with the highest risk for subsequent HCC, even after cure.

 

There are other factors like age and diabetes that are important risks for the subsequent development of liver cancer. The co-existence of fatty liver or heavy alcohol use are important cofactors for subsequent HCC risk.

 

Ultimately, it is hoped that markers will be developed to help prognosticate that risk in patients who have cleared their virus. We don’t have those yet. These may be related to specific gene expression signatures or defects that persist in these patients after virus elimination.

 

在临床实践中，如何提高HCC监测和预防效果？

 

Raymond Chung教授认为最重要的方式是加强监测。一方面，对人群进行高危和低危的分层，对高危人群采取更严密的监测策略；另一方面，希望通过前瞻性随机对照研究，探索化学预防对降低HCC的疗效。除此之外，还可应用他汀类等常用药物，在以上基础上进一步降低患者发生HCC的风险。

 

《国际肝病》: How do we improve HCC surveillance to optimize outcomes in clinical practice?

 

Dr. Chung: I think the main thing is going to be intensifying surveillance by selecting those patients who we view to be at particularly high risk – separating the high-risk patients from the low-risk patients. We take those high-risk patients and subject them to more intensive surveillance. That is the best way for us to arrive at early detection and therefore treatment in those who subsequently develop HCC.

 

The other possibility, and something we are hoping to test in prospective controlled trials, would be the use of chemopreventive strategies. Even after eliminating the virus and by stratifying those patients at increased risk, we could apply additional treatment to further reduce the risk of that patient developing subsequent hepatocellular carcinoma. There may be some promising approaches in that regard using common agents, such as statins, for example.

 

如何管理AFP等生物标志物异常，但影像学阴性的患者？

 

影像学证据对HCC的诊断至关重要。即使患者提示有循环肿瘤细胞、AFP等生物标志物的异常，但缺乏影像学检查，就无法对肝癌进行诊断。通过影像学评估，我们可以对HCC的侵犯范围和浸润深度进行判断和了解，便于对HCC进行分期以给予最佳治疗选择。因此，一方面需要尽可能为患者做影像学检查，另一方面，选择更为敏感的成像方式进行影像学评估。

 

《国际肝病》: How should we manage patients with abnormal alpha-fetoprotein or other biomarkers in the absence of scans and other imaging modalities?

 

Dr. Chung: We can’t really diagnose HCC without an imaging modality. That is critically important. I think we are eventually going to need to find a way to get any patient who is at risk access to imaging. It is very hard to arrive at a diagnosis of HCC without imaging because you need to know the extent of the tumor. What I would say is that if someone has abnormal biomarkers, it will be very important to get that patient some form of imaging, the more sensitive the better.

 

I do believe all of this rests on an important imaging approach. Even in those patients where we check circulating tumor cells and use other sophisticated biomarkers, at the end of the day, we are still going to need to understand the extent of the tumor in order to manage it optimally. Imaging will be critical at the end of the day.

 

（来源：《国际肝病》编辑部）