Section snippets

Case History

The patient is a 54-year-old man with history of cirrhosis related to metabolic dysfunction-associated steatotic liver disease who is being followed in the hepatology clinic. His cirrhosis has been complicated by ascites and hepatic encephalopathy, which is well-controlled on spironolactone 100 mg/d, furosemide 20 mg twice per day, and lactulose. He has been listed for liver transplantation for the past year, with a Model for End-stage Liver Disease (MELD) 3.0 score of 15. He feels well, with

What Are the Key Radiographic Features to Determine Whether a Liver Lesion Is LR-3 or LR-4?

BT: LI-RADS is a standardized framework developed by the American College of Radiology to classify liver lesions in patients at increased risk for hepatocellular carcinoma (HCC), that is, those with chronic hepatitis B, cirrhosis from any etiology, or a prior history of HCC.¹ Notably, LI-RADS should not be applied to liver masses detected in other patients in whom LI-RADS has not been validated (eg, patients without cirrhosis). The goal of LI-RADS is to ensure consistency in the interpretation

From a Pathology Perspective, What Do LR-3 and LR-4 Lesions Represent Histologically?

PG: Histopathological correlates of LR-3 and LR-4 lesions were reported in a single-center study with 90 patients who underwent liver transplantation, including 58 with LR-3 lesions and 32 with ≥1 LR-4 lesion.⁵ Most patients with LR-3 lesions (58.6%) had no correlate on pathological examination, 31.0% were found to have HCC, and 10.3% had a dysplastic nodule. In contrast, most patients with LR-4 lesions (65.6%) were found to have HCC on explant, with 6.3% having a dysplastic nodule and 28.1%

Once a Diagnosis of LR-3 or LR-4 Is Confirmed, What Is the Anticipated Natural History?

AGS: Several studies have examined the natural history of LR-3 and LR-4 lesions (Table 1), although it is difficult to draw robust conclusions given nonconsecutive enrollment and concerns about selection bias, as well as wide variation in the reported outcomes. Indeed, a meta-analysis identified 12 studies published between 2013 and 2022 that evaluated clinical outcomes in patients with LR-3 lesions and 9 studies that evaluated outcomes in patients with LR-4 lesions; however, these studies

How Can We Differentiate Patients at Higher vs Lower Risk of Developing HCC?

FK: Patients with LR-3 and LR-4 lesions have a high yet variable risk for developing HCC. Hence, oversurveillance of low-risk patients and missed cancers in high-risk patients both present significant clinical challenges. Despite a high risk, most patients with LR-3 and nearly one-half of patients with LR-4 lesions do not progress to HCC within 2 years of follow-up. Unfortunately, the current recommended strategy of intensive frequent surveillance (contrast-enhanced MRI or CT every 3–6 months

How Are Patients With LR-3 and LR-4 Lesions Typically Managed in Clinical Practice?

AGS: There is wide variation in observed practice patterns, underscoring that the optimal management strategy for patients with LR-3 and LR-4 lesions is currently unknown. Studies show that up to one-fourth of patients with LR-3 or LR-4 lesions receive no follow-up imaging, some undergo CT/MRI alternating with US examination, and others undergo quarterly cross-sectional imaging for years without developing HCC.⁷ Management of patients with these lesions should be guided by balancing

What Is the Recommended Management Strategy for Patients With LR-3 Lesions?

NDP: Based on the available data, most patients with LR-3 lesions can be monitored with repeat imaging every 3–6 months, depending on the size of the lesion, growth over time, changes in imaging appearance (eg, new delayed phase washout), and other factors such as AFP levels (Figure 2). For patients with subcentimeter LR-3 lesions, clinicians could repeat CT/MRI every 6 months for 1 year to confirm stability and then transition back to US examination-based surveillance given a low risk of HCC.

What Is the Recommended Management Strategy for Patients With LR-4 Lesions?

NDP: Compared with patients with LR-3 lesions, more intense surveillance of those with LR-4 lesions is warranted given the higher HCC risk. Although some patients with LR-4 lesions can be monitored with repeat imaging, risk varies based on size of the lesion as well as additional factors such as AFP levels, prior history of HCC, transplant eligibility, and patient goals of care (Figure 3). If an LR-4 observation is subcentimeter at detection, CT/MRI every 3 months for observation are reasonable

What Emerging Surveillance Strategies Are Being Evaluated for Patients With LR-3 and LR-4 Lesions?

AGS: Several imaging-based techniques (eg, abbreviated MRI or contrast-enhanced US examination) and blood-based biomarkers (eg, methylated DNA panels) are being evaluated for HCC surveillance. Most abbreviated MRI protocols (eg, non-contrast or use of hepatobiliary agents) are focused on the detection of HCC in patients with cirrhosis, but they require diagnostic dynamic contrast-enhanced MRI for characterization to diagnose HCC. Contrast-enhanced abbreviated MRI could concurrently detect and

Back to Our Patient

Our patient was listed for liver transplantation and found to have one 2.1-cm LR-4 and one 1.4-cm LR-3 lesion in the setting of decompensated cirrhosis. The first important step is review of imaging in a multidisciplinary tumor board with expert radiologists given known interobserver variability in interpretation and the possibility of making a diagnosis of HCC on imaging (ie, LR-5). Review of the imaging in this case confirmed the initial diagnosis. Given LR-4 lesions have a high risk of HCC,

中文翻译：

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LI-RADS 3 和 4 病变的评估

 部分片段

 病历

患者是一名 54 岁男性，有与代谢功能障碍相关的脂肪性肝病相关的肝硬化病史，正在肝病门诊接受随访。他的肝硬化并发腹水和肝性脑病，螺内酯 100 mg/d、呋塞米 20 mg 每天两次和乳果糖控制良好。他在过去一年中被列入肝移植名单，终末期肝病模型 （MELD） 3.0 评分为 15。他感觉很好，带着

确定肝脏病变是 LR-3 还是 LR-4 的关键影像学特征是什么？

BT：LI-RADS 是由美国放射学会开发的标准化框架，用于对肝细胞癌 （HCC） 风险增加的患者的肝脏病变进行分类，即患有慢性乙型肝炎、任何病因引起的肝硬化或既往有 HCC 病史的患者。¹ 值得注意的是，LI-RADS 不应应用于在 LI-RADS 尚未验证的其他患者（例如，无肝硬化的患者）中检测到的肝脏肿块。LI-RADS 的目标是确保解释的一致性

从病理学的角度来看，LR-3 和 LR-4 病变在组织学上代表什么？

PG：一项单中心研究报道了 LR-3 和 LR-4 病灶的组织病理学相关性，该研究纳入了 90 例肝移植患者，其中 58 例为 LR-3 病灶，32 例为 ≥1 LR-4 病灶。⁵ 大多数 LR-3 病变患者 （58.6%） 在病理检查中无相关性，31.0% 发现患有 HCC，10.3% 患有发育不良结节。相比之下，大多数 LR-4 病变患者 （65.6%） 在外植体时被发现患有 HCC，其中 6.3% 有发育不良结节，28.1%

一旦确诊为 LR-3 或 LR-4，预期的自然病程是怎样的？

AGS：几项研究检查了 LR-3 和 LR-4 病变的自然病程（表 1），尽管鉴于非连续入组和对选择偏倚的担忧以及报告结果的广泛差异，很难得出可靠的结论。事实上，一项荟萃分析确定了 2013 年至 2022 年间发表的 12 项研究，这些研究评估了 LR-3 病变患者的临床结果，以及 9 项评估 LR-4 病变患者结果的研究;然而，这些研究

我们如何区分 HCC 风险较高和较低的患者？

FK：LR-3 和 LR-4 病变患者发生 HCC 的风险很高，但存在差异。因此，对低风险患者的过度监测和高危患者的漏诊癌症都带来了重大的临床挑战。尽管风险很高，但大多数 LR-3 患者和近一半的 LR-4 病变患者在 2 年随访后未进展为 HCC。不幸的是，目前推荐的强化频繁监测策略（每 3-6 个月进行一次对比增强 MRI 或 CT

在临床实践中，通常如何管理 LR-3 和 LR-4 病变患者？

AGS：观察到的实践模式存在很大差异，这强调 LR-3 和 LR-4 病变患者的最佳管理策略目前尚不清楚。研究表明，多达四分之一的 LR-3 或 LR-4 病变患者没有接受后续影像学检查，一些患者接受 CT/MRI 与超声检查交替进行，而另一些患者则接受季度横断面成像多年而未发生 HCC。⁷ 这些病变患者的管理应以平衡为指导

对于 LR-3 病变患者，推荐的管理策略是什么？

国庆庆典：根据现有数据，大多数 LR-3 病变患者可以每 3-6 个月重复成像一次，具体取决于病变的大小、随时间的生长、影像学外观的变化（例如，新的延迟期清除）以及 AFP 水平等其他因素（图2）。对于亚 cm级 LR-3 病变的患者，临床医生可以每 6 个月重复一次 CT/MRI，持续 1 年以确认稳定性，然后鉴于 HCC 风险较低，可以过渡回基于检查的美国监测。

对于 LR-4 病变患者，推荐的管理策略是什么？

国庆庆典：与 LR-3 病变患者相比，鉴于 HCC 风险较高，需要对 LR-4 病变患者进行更严格的监测。虽然一些 LR-4 病变患者可以通过重复成像进行监测，但风险因病变大小以及其他因素而异，例如 AFP 水平、HCC 既往病史、移植资格和患者护理目标（图 3）。如果 LR-4 观察在检测到时为亚厘米，则每 3 个月进行一次 CT/MRI 观察是合理的

针对 LR-3 和 LR-4 病变患者正在评估哪些新兴的监测策略？

AGS：几种基于影像学检查的技术（如简化MRI或造影剂增强超声检查）和基于血液的生物标志物（如甲基化DNA面板）正在评估HCC监测。大多数简化的 MRI 方案（例如，平扫或使用肝胆药物）侧重于检测肝硬化患者的 HCC，但它们需要诊断性动态对比增强 MRI 来表征 HCC。对比增强简化 MRI 可以同时检测和

 回到我们的患者

我们的患者被列入肝移植名单，发现在失代偿性肝硬化的情况下有 1 个 2.1 cm LR-4 和 1 个 1.4 cm LR-3 病灶。第一个重要步骤是在多学科肿瘤委员会中由放射科医生进行影像学检查，因为已知的观察者间解释存在差异，并且有可能在影像学上诊断为 HCC（即 LR-5）。该病例的影像学检查证实了初步诊断。鉴于 LR-4 病变具有 HCC 的高风险，