[EASL2012]慢性肝病的评估：非侵入性肝纤维化、肝癌、脂肪性

StephenW

[EASL2012]慢性肝病的评估：非侵入性肝纤维化、肝癌、脂肪性肝病——欧洲胃肠病学联盟学术委员M. Pinzani教授访谈            

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来源： 作者：M.Pinzani 发布时间：2012-4-23 15:53:17   阅读：182

                                    
            　　最新进展是我们认为精确分期并不是准确的，因为用来取代肝活检评估的半定量评分系统，能检测极早期和极晚期纤维化。但是其不能精确定义显著纤维化分期，而显著纤维化分期是介于正常肝脏与肝硬化之间的纤维化。
                                               
                                                      

　　Hepatology Digest: Precise staging of fibrosis in chronic liver disease is important for patient management in clinical practice and significant progress has been made in the field of non-invasive diagnosis of liver fibrosis. Would you please give us a brief introduction on the latest progress?
　　Hepatology Digest: 在临床中，慢性肝病纤维化的精确分期对于患者的治疗来说是非常重要的，目前无创性纤维化诊断方面已经取得了重大进展。请您给我们简要介绍其最新进展？
　　Dr Pinzani: The latest progress is that what we thought was precise staging is not very precise because the semiquantitative scoring system which is able to be used for the evaluation of liver biopsies from patients with chronic liver disease， is able to detect very early stages of disease and very advanced stages but what is missing is that it doesn’t have a precise definition for the stage of significant fibrosis which is halfway between a normal liver and a cirrhotic liver. So right now， basically there are no precise methods as even biopsy which is used erroneously as a gold standard of non-invasive technology， is still unable to detect with 100% accuracy a stage like F2. The real progress then is having reached this awareness. What we are expecting is that everything which comes up as a research or development project this year， will be based on this awareness and things may get more precise. As I have discussed with my colleagues， I would suggest that good integration of the use of liver biopsy with a non-invasive method such as a biomarker or transient elastography or whatever is available， would， like two tango dancers， make for better management compared to what was available before the non-invasive methods were invented or available.
　　Pinzani教授:最新进展是我们认为精确分期并不是准确的，因为用来取代肝活检评估的半定量评分系统，能检测极早期和极晚期纤维化。但是其不能精确定义显著纤维化分期，而显著纤维化分期是介于正常肝脏与肝硬化之间的纤维化。所以，现在基本上没有无创性检测方法如肝活检那样精确检测纤维化分期，因此，目前的检测方法仍然不能达到100%的精确度，如F2。真正的进展是要具有这种意识。我们期待的是今年所有上升为研究或发展规划的检测方法都要基于这种认识，这样可能会更为精确。我和我的同事讨论过，我建议在可用于临床的无创性检测手段发明或应用之前，将肝活检与无创性检测手段如生物标记物或瞬时弹性成像或其他任何可用的手段整合起来，如两位探戈舞者那样，将更有助于治疗。
　　Hepatology Digest: Liver biopsy is considered as the gold standard for assessment of hepatic fibrosis. However， some studies indicate that the accuracy of different non-invasive methods for evaluating liver fibrosis may decrease when they are combined. What’s your view on the future of the combination of different non-invasive methods for assessing liver fibrosis?
　　Hepatology Digest:肝活检被认为是肝脏纤维化评估的金标准。然而，一些研究表明当不同的无创性评估方法联合应用时，其评估的准确性下降。您对未来无创性检测方法联合应用评估肝脏纤维化有何看法？
　　Dr Pinzani: You may find that you have an improvement in the assessment and sometimes， paradoxically， there is a worsening. Because this system is based on liver biopsy as a gold standard and since liver biopsy does not give a precise definition， the combination of two different systems may be even less precise than biopsy alone and may not be helpful. I would stick to the concept of needing a liver biopsy and a non-invasive method in clinical practice and using the non-invasive method to assess which patient might not need a biopsy because they have a predicted very low level of fibrosis and also to exclude those patients who already have advanced liver disease and consequently restrict the number of patients needing a biopsy by 50% which is already a major improvement. Then you need to do the best you can do with the biopsy; you need a good pathologist and a biopsy of good length and standard to make a fair evaluation of the sample.
　　Pinzani教授:你可能发现联合应用有时会使评估改善，相反，有时会使评估变得更糟。因为这个体系是以肝活检为金标准，既然肝活检不能提供一个准确的定义，那么两个不同体系的联合，其准确性可能比单纯肝活检差，而且未必有益。我坚持这样一个概念：肝活检和无创性检测方法的必要性。例如应用无创性检测方法评估那些不需要肝活检的患者（具有较低水平纤维化或者排除终末期肝病），那么，大约50%患者不需要进行肝活检，这是一个重大改善。如果想应用肝活检，那么你需要尽自己最大的努力，如一个好的病理学家，活检组织长度较好以及作出公正评价的标准。
　　Hepatology Digest: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Currently， several markers associated with poor survival are being used to stratify HCC into groups of different prognosis. Would you please talk about the latest progress of prognostic markers in hepatocellular carcinoma?
　　Hepatology Digest: 肝细胞癌（HCC）是肝癌的最主要类型。最近一些与生存期差有关的指标用来将HCC患者分为不同的预后组。您能谈谈这些诊断性标记物在HCC中的最新进展吗？
　　Dr Pinzani: The issue of prognostic markers for HCC is another big area of non-invasive evaluation that is not yet validated. There are a lot of suggestions; for example， there are markers in the biopsy of an HCC， markers of progenitor cells suggesting that the cancer is derived largely from progenitor cells which would give a worse prognostic outlook for the disease. There are other markers that are genetically associated with cancer but not necessarily specific for hepatocellular carcinoma. However， HCC is not just a tumor with a homogeneous characteristic. If you examine ten patients with HCC they will each have a different molecular path and even within the same cancer you have different clonal features. So I would say that the markers for HCC are valid if they are obtained by doing a biopsy of the cancer and doing several stainings because there are good correlations between a good prognosis and progenitor cell markers. This is accurate but you have to do a biopsy of the cancer or look at the cancer after resection. Of the circulating markers， I don’t think there is anything safe and there is nothing new to appear on the market currently. We are still using alpha-fetoprotein. The really good marker that can substitute alpha-fetoprotein is not there. There are some attempts now underway to try the possibility of isolating circulating hepatocellular carcinoma cells coming from the primary tumor. This could be very important in allocating patients for liver transplantation. Regardless of meeting Milan criteria for example， if you have positive circulating cells it may decrease the possibility of allocation to transplant. But there is a lot to be developed in this area. There are many studies coming out of China but they need validation. China is so full of ideas but usually they are small studies and possibly they could be extended into large studies because of the larger population if there was funding available.
　　Pinzani教授：HCC的预后标记物研究是无创性诊断的另一个大领域，但还没有得到应用。目前的研究表明：如HCC肝穿标本和前体细胞中的标记物，如果提示大部分肿瘤起源于前体细胞，这可能是预后不良的表现。有些标记物总的来说与癌症相关，但没有HCC疾病特异性。HCC不仅仅是一种肿瘤，它具有非均一性的特点。假如你检测10个HCC患者，将会得到不同的分子病理；即使是相同的肿瘤，也可能得到不同的克隆特点。所以我想说的是如果你得到的HCC标本及其染色良好，那么HCC的标记物就可以应用，因为预后良好与前体细胞的标记物具有较好的相关性。这是非常准确的，但是你必须进行肿瘤活检或观察肝脏切除后的肿瘤标本。而在血液循环的标记物中，我认为没有任何安全的标记物，但有很多新的标记物。尽管如此，我们仍然应用甲胎蛋白。一些研究试图寻找真正好可以代替甲胎蛋白的标记物，但目前还没有出现。有些研究试图分离出血液循环中来源于原发肿瘤的HCC细胞。这对于肝移植患者的器官分配是非常重要的。例如尽管符合米兰标准，如果你有阳性循环细胞，这可能降低你获得肝移植的可能性。但是这个领域具有很大的发展前途。中国也有很多这方面的研究结果但是还需要验证。中国人充满着很多想法，但其样本量小需要扩大样本量来验证，但大样本量需要更多的资金。
　　Hepatology Digest: A recent study showed that neutrophil to lymphocyte ratio can be used as a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). What’s your opinion on this?
　　Hepatology Digest: 最近的研究表明中性粒细胞与淋巴细胞比值可以预测非酒精性脂肪性肝炎患者的脂肪性肝炎和纤维化。您对此有何看法？
　　Dr Pinzani: I don’t have any experience with this but it makes some sense because you have a predominantly neutrophil infiltrate in NASH. So that could be the case but I don’t know the study or have experience on the topic.
　　Pinzani教授：关于这个我没有任何经验，但这是非常有意义的。在NASH患者的肝脏中，其主要表现为中性粒细胞侵润。我不知道这项研究，且对此也没有经验。