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Chinese Journal of Hepatology logoLink to Chinese Journal of Hepatology
. 2019 Mar 20;27(3):182–191. [Article in Chinese] doi: 10.3760/cma.j.issn.1007-3418.2019.03.004

瞬时弹性成像技术诊断肝纤维化专家共识（2018年更新版）

Consensus on clinical application of transient elastography detecting liver fibrosis: a 2018 update

Chinese Foundation for Hepatitis Prevention and Control; Chinese Society of Infectious Disease and Chinese Society of Hepatology, Chinese Medical Association; Liver Disease Committee of Chinese Research Hospital Association; Ganbing Zhuanye Weiyuanhui
Editor: 彭 智
PMCID: PMC12869178  PMID: 30929334

Abstract

Transient elastography is a noninvasive, rapid ultrasonic elastography, and assess liver fibrosis by detetcting liver stiffness. Current consensus focuses on understanding influence factors on operation and diagnosis, recommendations for clinical application on detetcting liver fibrosis of chronic liver disease and monitoring development of related complication hepatocelullar carcinoma, high risk esophageal varices, and also summarizes the potential aplication on liver disease screening and liver fibrosis regression assessment.

【Key words】: Liver disease, Liver fibrosis, Diagnosis, Transient elastography, Consensus

英语名词缩写：

ALT: alanine aminotransferase，丙氨酸氨基转移酶

AUC: area under receiver operating characteristics curve，受试者工作特征曲线下面积

BMI:body mass index，体质量指数

CHB: chronic hepatitis B，慢性乙型病毒性肝炎

CHC: chronic hepatitis C，慢性丙型病毒性肝炎

HCC: hepatocellular carcinoma，肝细胞癌

HREV: high risk esophageal varies，高风险食管静脉曲张

LSM: liver stiffness measurement，肝脏硬度值

NLR: negative likelihood ratio，阴性似然比

PLR: positive likelihood ratio，阳性似然比

TE: transient elastography，瞬时弹性成像技术

ULN: upper limit of normal，正常值上限

肝纤维化是各种慢性肝脏损害所导致的肝脏纤维结缔组织过度沉积，也是发展为肝硬化的共同途径。正确评估并及时发现进展期肝纤维化、早期肝硬化是优化慢性肝病管理的关键步骤。然而，多数慢性肝病所致肝纤维化乃至早期肝硬化无特异性症状、体征及常规血液生物化学指标异常，如果不进行肝脏组织病理学检查则不易被及时发现[1]。作为一种重要的肝纤维化无创诊断技术，瞬时弹性成像技术（transient elastography, TE）可以通过检测肝脏硬度值（liver stiffness measurement, LSM）来判断肝纤维化状态，已先后在欧洲、亚太地区及美国被批准应用于临床[2,3]。在2013年版《瞬时弹性成像技术诊断肝纤维化专家意见》[4]的基础上，中国肝炎防治基金会于2018年再次组织专家讨论、修订，力求反映本领域里的最新进展，从而为临床应用提供客观、实用的指导意见。

本共识中的证据等级分为A、B、C三个级别，推荐等级分为1、2两个级别（表1）。

表1. 推荐意见的证据级别和推荐等级（根据GRADE分级系统[5,6]修订）.

级别 详细说明
证据级别
A高质量 进一步研究不大可能改变对该检查评估有效性的信心
B中等质量 进一步研究有可能对该检查评估有效性的信心产生重要影响
C低质量 进一步研究很有可能影响该检查评估有效性信心，且该检查评估有效性很可能改变
推荐等级
1强推荐 充分考虑到了证据的质量、患者可能的预后情况及相应检查成本而最终得出的推荐意见
2 弱推荐 证据价值参差不齐，推荐意见存在不确定性，或推荐的检查评估意见可能会有较差的成本效益比等，更倾向于较低等级的推荐
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一、肝纤维化无创诊断应用的方法学原则

在临床实践中，失代偿期肝硬化因其具有腹水、食管胃静脉曲张（出血）及肝性脑病等相关并发症而较易做出临床诊断，故无创诊断主要集中代偿期肝硬化和具有桥接样纤维化的进展期肝纤维化（≥Metavir F3）。临床上常将患者划分为进展期肝纤维化/肝硬化高风险、中间灰色区域及进展期肝纤维化/肝硬化低风险[7,8]，肝纤维化无创评估目的在于确定和排除进展期肝纤维化及肝硬化（Metavir F4）。随着抗病毒药物等病因治疗的发展，有必要对识别出存在明显纤维间隔的显著肝纤维化（≥Metavir F2）肝病患者并进行病因干预，以期逆转肝纤维化。

在诊断中，低风险界值需保证排除诊断的高度敏感性及低阴性似然比（negative likelihood ratio, NLR），以避免漏诊导致严重临床后果；高风险界值则需保证诊断的高度特异度及高阳性似然比（positive likelihood ratio, PLR），以免误诊而造成过度医疗；对于检测值处于高风险界值与低风险界值之间灰色区域的患者，应根据临床情况决定是否采用肝穿刺活组织学检查确定肝纤维化状态[8,9]。在统计学上，PLR＞10.0的诊断界值具有足够的阳性证据强度诊断疾病，而NLR＜0.1的诊断界值则具有足够阴性证据强度排除疾病诊断[10]；高、低界值的确定应当满足上述要求。基于上述原则，本共识选择NLR为0.1左右的界值用于确定低风险而排除诊断，PLR为10.0左右的界值用于确定高风险而考虑诊断；对于某些疾病，由于研究数据的缺失或研究样本量不足，目前尚无法提出明确诊断指导意见。

目前国内已有多种TE技术设备应用于临床，其中以FibroScan及FibroTouch应用较多。弹性成像技术不同模态、系统及设备检测的LSM结果存在差异，因而肝纤维化分期诊断界值可能因模态、系统及设备差异而不同[11]。在FibroTouch与FibroScan头对头比较中，与FibroScan 5.3（4.3～8.6）kPa相比，FibroTouch同一检测点及影像定位检测点检测的LSM分别为5.7（4.5～8.0）kPa（P=0.321）、6.1（4.7～8.9）kPa（P=0.141），相关系数≥0.8[12]；1 621例受检者资料显示两者LSM存在线性回归关系：FibroTouch=4.435+0.477 FibroScan，相关系数0.645[13]。以下分别叙述针对这两种检测设备的共识意见。

二、瞬时弹性成像技术无创诊断肝纤维化的共识意见

（一）瞬时弹性成像技术FibroScan®

1.操作要求及影响因素：TE操作主要受患者肥胖、肋间隙狭窄及明显腹水等因素限制。检测失败主要与操作者操作经验＜500次、受检者体质量指数（body mass index, BMI）＞30kg/m2、年龄＞52岁和2型糖尿病等有关，受检者腰围（女性＞80cm、男性＞94cm）是最重要因素[14]；在中国受检者中，BMI≥28.0kg/m2、中心型肥胖（女性腹围＞80cm、男性腹围＞90cm）、年龄＞50岁、女性是操作失败或不可靠检测的独立影响因素[15,16]。在BMI≥28.0kg/m2受检者中，XL型探头操作成功率及可靠性均优于M型探头，XL型探头检测值较低，与M型探头检测值差异平均为2.3kPa（中位数1.4kPa），显著肝纤维化界值降低1～2kPa，肝硬化界值降低4.0kPa左右[17,18,19,20,21,22]。胸围＜75cm的肋间隙狭窄者及＜14岁未成年人可应用S型探头，5岁以下儿童检测失败率明显升高；较大探头检测中位数较低：S2较S1降低0.76（0.31～1.21）kPa、M较S2降低1.2（0.51～1.88）kPa[23,24]，但我国4～6岁学龄前儿童M型探头有效检测率达到96.5%[25]。LSM检测可靠性尚与检测值四分位间距与中位数比有关：≤0.10非常可靠，＜0.10～0.30或＞0.30且LSM中位数＜7.1kPa可靠[26]。

可能导致LSM升高的因素包括：表现为丙氨酸氨基转移酶（alanine aminotransferase, ALT）或胆红素水平升高的肝脏炎症活动度[27,28,29]、高BMI[30]、肝外胆汁淤积可能[31,32]、肝静脉淤血[33,34]、酒精摄入过量（戒酒后1周45.3%受试者明显下降）[35,36,37]和进食（肝硬化患者更明显，餐后2～3h恢复至基线）[38,39]。鉴于存在上述升高LSM非肝病因素而可能存在假阳性，Baveno Ⅳ共识建议非同日2次TE检测确认有效检测[40]。重度脂肪变性可能提高非进展期肝纤维化M型探头检测值，但不影响XL型探头诊断阳性率[17,41]。TE通过检测肝硬度而测定肝脏纤维化含量，并不能反映因肝纤维化进展而导致的肝组织结构变化；不同病因的肝脏炎症水平及肝纤维化结构存在差别，相应诊断界值可能存在差异。

共识1：操作者应接受规范培训并严格遵守操作规程，操作经验最好在500次以上；操作人员不宜频繁更换（B1）。

共识2：操作时一般选择M型探头检测，超声显示重度脂肪肝及M型探头无法取得可靠检测的超体重、中心型肥胖者选择XL型探头，M型探头无法取得有效检测的14岁以下或胸围＜75cm患者依次采用S2、S1型探头（B1）。

共识3：有效检测需满足以下条件：同一检测点至少成功检测10次、检测值四分位差距与中位数比值小于0.3（A1）。

共识4：患者应在血清胆红素＜51 μmol/L情况下空腹或餐后3h接受检测，过量饮酒者应戒酒1周后接受检测；诊断界值选择需参照病因及血清ALT水平，并排除右心衰竭可能；疑检测结果假性升高者非同日再次检测确认（B1）。

2.诊断界值：（1）慢性乙型病毒性肝炎：TE诊断慢性乙型病毒性肝炎（chronic hepatitis B, CHB）显著肝纤维化、进展期肝纤维化和代偿期肝硬化的受试者工作特征曲线下面积（area under receiver operating characteristics curve, AUC）分别为0.77～0.95、0.85～0.94及0.84～0.98[42,43,44,45,46,47,48,49,50,51,52,53,54]，胆红素异常对TE诊断效能有明显影响[42,43]。诊断肝硬化时，LSM11.6kPa（NLR 0.2）[43]、LSM 12.9kPa（PLR 7.33、NLR 0.52）、14.1kPa（PLR 5.6、NLR 0.19）、11.0kPa（PLR 7.3、NLR 0.28）诊断、排除证据强度不足[45,46,47]，提示诊断界值应高于14.1kPa，而排除界值应低于11.0kPa；LSM 9.4kPa的NLR 0.02[48]，排除界值可考虑高于9.4kPa；两项研究LSM 11.0kPa的NLR分别为0.08、0.2[49,53]、国内较大样本研究LSM 10.6kPa（NLR 0.09）[42]、LSM 10.7kPa（NLR 0.12）[44]均可考虑排除诊断，LSM 16kPa（PLR 16.9）[42]、18.2kPa（PLR 19）[49]可考虑肝硬化诊断；多中心研究纳入肝组织长度10～15mm患者，可能漏诊少数肝硬化、降低PLR而导致建议界值升高，肝硬化诊断界值宜低于21.0kPa[44]；对于ALT正常患者，LSM 10.1kPa的PLR 7.3、NLR 0.15[50]、9.0kPa的NLR o、12.0kPa的PLR 12.9[51]，提示诊断界值应高于10.0kPa，而排除界值应低于10.0kPa。诊断进展期肝纤维化时，LSM 10.2kPa的PLR 9.0、NLR 0.15[46]、8.1kPa的PLR 4.6、NLR 0.15[47]，诊断界值需稍高于10.2kPa，排除界值低于8.1kPa;LSM 10.5kPa（PLR 14.4）[48]、12.0kPa（PLR 25.5）[49]、12.7kPa[PLR 15.3, ALT 2倍正常值上限（upper limit of normal,ULN）]及10.6kPa（PLR 10.5,ALT＜2×ULN）[52]、多中心研究12.4kPa（PLR 12.3）[44]均可作为诊断界值，而LSM 8.1kPa（NLR0.16）、7.5kPa（NLR 0.07）[49]、7.4kPa（NLR 0.11）[50]均可考虑排除进展期肝纤维化；对于ALT正常患者，LSM 6.0kPa（NLR0.15）、9.0kPa（PLR）[51]可分别考虑作为排除、诊断界值。诊断显著肝纤维化时，多中心研究LSM 9.1kPa的PLR 6.4[44]，诊断界值应进一步提高，LSM9.8kPa（PLR 11.0）[52]、9.4kPa（PLR 14）[48]均可作为诊断界值；其他建议界值因PLR低于5.0或NLR高于0.2而无应用价值[43,45,46,47,49,50]。

尽管已有临床研究探讨接受抗病毒治疗的CHB患者LSM动态变化与肝纤维化相关性，但目前尚无明确结论，尚需更多临床研究提供循证医学证据。

共识5：胆红素正常、ALT＜5×ULN的CHB患者LSM 17.0kPa考虑肝硬化，LSM 12.4kPa（1×ULN＜ALT＜2×ULN时10.6kPa）考虑进展期肝纤维化；LSM＜10.6kPa排除肝硬化可能；LSM 9.4kPa考虑显著肝纤维化；LSM＜7.4kPa排除进展期肝纤维化；LSM 7.4～9.4kPa患者如无法确定临床决策，考虑肝穿刺活组织学检查；胆红素异常患者应进行动态评估（A1）。

共识6：胆红素、ALT正常的CHB患者LSM 12.0kPa考虑肝硬化，LSM 9.0kPa考虑进展期肝纤维化，LSM＜9.0kPa排除肝硬化，LSM＜6.0kPa排除进展期肝纤维化，LSM 6.0～9.0kPa者如无法决定临床决策，考虑肝穿刺活组织学检查（B1）。

鉴于现有FibroScan评估肝纤维化分期研究证据均来源于未抗病毒治疗患者，本共识意见临床应用仅限于未抗病毒治疗患者，具体参考图1，结合患者临床病毒学资料确定相应干预措施。

图1. 瞬时弹性扫描技术诊断未抗病毒治疗代偿期乙型肝炎病毒感染者肝纤维化分期.

图1

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注：ALT：丙氨酸氨基转移酶；LSM：肝脏硬度值

（2）慢性丙型病毒性肝炎：TE诊断慢性丙型病毒性肝炎（chronic hepatitis C, CHC）肝硬化的AUC 0.90～0.97[43,45,47,55,56,57,58,59]。诊断肝硬化时，LSM 12.5kPa的PLR分别为14.7、16.6[47,55]，LSM 12.3kPa的PLR 18.9[56]，但更大样本研究LSM 12.8kPa的PLR 5.09（n=560）[57]LSM 12.9kPa的PLR 6.8（n=913）[45]，故诊断界值需考虑高于12.9kPa；LSM 14.5kPa、14.6kPa的PLR分别为7.4[43]、21.5[58]，可考虑肝硬化诊断[43,57]；大样本研究LSM 12.9kPa、12.8kPa排除肝硬化的NLR分别为0.31、0.28[45,57]，排除肝硬化界值需进一步调低；LSM 9.3kPa排除肝硬化的NLR 0.07。诊断进展期肝纤维化时，LSM 9.5kPa、9.3kPa诊断进展期肝纤维化的PLR分别为8.5、21.5[47,56]，但更大样本研究LSM 9.6kPa的PLR仅3.6[57]，诊断界值需调高；界值8.6kPa、7.3kPa排除进展期肝纤维化的NLR分别0.2、0.07[43,56]。多项研究提出的显著肝纤维化界值均无足够证据强度诊断或排除显著肝纤维化，界值7.1kPa诊断显著肝纤维化的PLR 6.0～6.1[47,59], LSM8.8kPa的PLR 6.2[58]，但界值8.4kPa的PLR仅2.3[57]。

因缺乏肝穿刺活组织学检查对照，接受直接抗病毒药治疗的CHC患者LSM变化与肝纤维化相关性仍待确定。

共识7：CHC患者LSM 14.6kPa考虑肝硬化，LSM＜10.0kPa可排除肝硬化；LSM＜7.3kPa排除进展期肝纤维化，目前缺乏进展期肝纤维化、显著肝纤维化可靠诊断界值（A1）。

（3）非酒精性脂肪性肝病：TE诊断非酒精性脂肪肝病显著肝纤维化、进展期肝纤维化、肝硬化的AUC分别为0.76～0.85、0.81～0.94、0.87～0.96[60,61,62,63,64,65];Cassinotto等[60]研究纳入了肝穿刺活组织长度仅10～15mm的受试者，可能存在肝纤维化低估、肝硬化漏诊而导致界值PPV、PLR降低；另一大样本研究中肝活组织学检查与TE非同步进行，时间差长达12个月，界值可靠性难以确定[61]。其他4项研究中，仅两项研究样本量约250例[62,65]，其余两项研究样本量约100例。诊断肝硬化时，LSM 11.5kPa、11.7kPa、15.0kPa、19.4kPa诊断肝硬化的PLR分别为8.4、7.5、10.4、38.1，诊断界值应高于12.0kPa；排除界值10.0kPa、10.3kPa、10.6kPa、10.8kPa的NLR分别为0.2、0.09、0、0.10[17,62,63,64]。诊断进展期肝纤维化时，LSM 9.6kPa、10.0kPa、11.2kPa、11.7kPa、12.0kPa诊断进展期肝纤维化的PLR分别为8.9、6.6、10.9、6.1、3.6，证据强度差异较大[17,62,63,64,65]，LSM 7.8kPa、7.9kPa、8.0kPa排除进展期肝纤维化的NLR分别为0.04、0.12、0.1，可视为进展期肝纤维化排除界值[62,63,64]。诊断显著肝纤维化时，LSM 9.0kPa、8.2kPa、7.4kPa的PLR分别为6.3、5.8、7.5[62,63,64]，诊断界值应高于9.0kPa。此外，与BMI＜30kg/m2相比，BMI≥30kg/m2患者同一界值灵敏度较高[17]，提示诊断界值需略提高。

共识8：非酒精性脂肪肝病患者LSM 15.0kPa考虑肝硬化，LSM 11.0kPa考虑进展期肝纤维化，LSM＜10.0kPa考虑排除肝硬化，LSM＜8.0kPa考虑排除进展期肝纤维化；LSM处于8.0～11.0kPa患者需接受肝活组织学检查明确肝纤维化状态；BMI≥30.0kg/m2患者诊断价值略提高（B1）。

（4）酒精性肝病：涉及TE诊断酒精性肝病肝纤维化的研究均包含肝穿刺活组织长度10～15mm病例，其中Nguyen-Khac等研究肝组织长度≥15mm病例仅21例，可能因标本不足而导致漏诊、诊断界值提高[66,67,68,69]。LSM 19.7kPa诊断肝硬化的灵敏度97%、NLR 0.03、特异度90%、PLR 9.7[69]。包含8项研究564例患者涉及重度肝纤维化评估的M eta分析表明LSM 9.5kPa诊断进展期肝纤维化的灵敏度0.92（0.89～0.96）、NLR 0.11（0.06～0.16）;7项研究336例患者涉及肝硬化评估的M eta分析表明界值12.5kPa诊断肝硬化灵敏度0.95（0.87～0.98）、NLR 0.07（0.03～0.19）[70]。

共识9：酒精性肝病患者LSM≥20.0kPa考虑肝硬化，LSM＜12.5 KPa排除肝硬化，LSM＜9.5kPa排除进展期肝纤维化（C2）。

（5）自身免疫性肝炎与原发性硬化性胆管炎：在一项涉及自身免疫性肝炎肝纤维化非创伤性诊断Meta分析中，7项研究429例患者涉及TE诊断应用，诊断显著肝纤维化、进展期肝纤维化及肝硬化的AUC分别为0.90（0.87～0.92）、0.91（0.89～0.93）、0.89（0.86～0.92）;LSM中位数6.3（5.8～7.0）kPa诊断显著肝纤维化的NLR 0.23（0.13～0.42），排除显著肝纤维化界值应调低进入正常参考值范围，LSM（9.1～10.1）kPa的PLR 14.6（1.4～151.6）；诊断进展期肝纤维化时，LSM中位数8.5（8.2～8.8）kPa的NLR 0.24（0.16～0.35），排除界值可能调低至8.0kPa，中位数10.7（10.4～12.1）kPa诊断进展期肝纤维化的PLR 7.7（2.9～20.5），诊断界值应高于10.7kPa；诊断肝硬化时，LSM中位数12.4（11.0～12.7）kPa的NLR 0.14（0.07～0.27），16.0～19.0kPa的PLR 21.7（5.1～92.3）[71]。上述界值诊断评估指标与CHB类似。来自法国小样本（n=66）研究显示TE诊断原发性胆汁性胆管炎显著肝纤维化、进展期肝纤维化及肝硬化的AUC分别为0.84、0.93及0.95，LSM＜9.6kPa排除进展期肝纤维化的灵敏度93%、NLR 0.08，LSM14.4诊断肝硬化的灵敏度100%、NLR o、特异度88%、PLR 8.3[72]。

共识10：自身免疫性肝炎肝纤维化诊断界值参照ALT＜2 ULN的CHB标准，目前缺乏原发性胆汁性胆管炎可靠诊断界值（C2）。

（6）食管静脉曲张：慢性肝病管理中，初级预防高风险食管静脉曲张（high risk esophageal varies, HREV）破裂出血对于改善肝病预后具有重要临床价值，所有肝硬化患者均应筛查HREV。HREV一般指肝功能代偿的中/重度食管静脉曲张及肝功能失代偿的食管静脉曲张。多数研究包含各种病因慢性肝病，诊断能力（AUC 0.76～0.87）及建议界值存在较大差异，排除诊断价值更高（NLR＜0.3）[73,74,75,76,77]。混合病因肝病患者研究提示界值19.0kPa、19.8kPa排除中重度静脉曲张的灵敏度均为91%、NLR分别为0.14、0.16，界值25.6kPa、21.0kPa的NLR则分别提高至0.22、0.27，提示中重度食管静脉曲张合理排除界值应低于19.0kPa。门脉高压BavenoⅥ共识建议LSM＜20kPa且血小板计数＞150×109/L患者存在HREV的风险非常低[40]，四项研究证实诊断HREV灵敏度分别为97.8%（NLR 0.08）、100%、100%、94%（NLR 0.16）][78,79,80,81]；近期扩展BavenoⅥ共识将排除标准调整为LSM＜25kPa且血小板计数＞110×109/L[82]，一项验证研究显示其诊断HREV灵敏度仅84%（NLR 0.30）[81]，漏诊率高达16%。

共识11：无单一LSM界值预测HREV，LSM＜20kPa且血小板计数＞150×109/L可排除HREV（A1）。

（7）慢性肝病肝细胞癌风险评估：随着LSM升高，肝细胞癌（hepatocellular carcinoma, HCC）风险随之升高。大队列（n=866）CHC前瞻性研究发现LSM（10.0kPa患者HCC年发生率仅0.11%，10.1～15.0kPa患者2.9%,＞25.0kPa患者高达14.4%[83]。小样本（n=157）研究提示LSM12.5kPa为HCC发生的独立预测因子[84]，LSM＜12.0kPa患者5年HCC累积发生率仅0.9%,LSM（12.0～24.0）kPa及LSM＞24.0kPa患者分别升高至9.5%、45.1%，且随访LSM下降预示着HCC风险降低[85]；接受直接抗病毒药物治疗的CHC患者如基线为进展性肝病且LSM较基线下降低于30%者HCC风险更高[86]。CHB患者不管是否存在临床诊断肝硬化，LSM≤13.0kPa患者的HCC年发生率均低于0.9%,LSM＞13.0kPa非肝硬化患者升高至3.26%，而临床诊断肝硬化患者则高达5.84%；动态随访LSM变化同样与HCC发生密切相关：LSM持续≥13.0kPa者年发生率高于持续＜13.0kPa者（4.31%对比0.44%），基线LSM≤13.0kPa、但随访LSM＞13.0kPa者也升高至2.05%，基线LSM＞13.0kPa但随访LSM≤13.0kPa者则降低至1.96%[87]。在超声波诊断肝硬化获得持续病毒学应答患者中，治疗2年时LSM＜11.6kPa者HCC风险显著降低，30个月后HCC发生率无增长趋势，而LSM≥11.6kPa者HCC发生率持续增长[88]。

共识12：在慢性肝病管理中，LSM＞10.0kPa患者HCC风险增加，LSM＞13.0kPa患者应考虑HCC监测（B2）。

（8）其他临床应用：①评估肝纤维化逆转：核苷类药物治疗CHB患者过程的LSM降低表现为快速下降及缓慢下降双相变化，LSM降低＞30%者发生肝纤维化逆转比例更高[89]，抗病毒治疗78周的肝纤维化逆转仅与基线纤维化分期独立相关，而治疗78周后LSM的降低和治疗前肝脏炎症程度重（HAI评分）、ALT高水平密切相关，而不能反映肝脏纤维化程度的变化[90,91]，治疗104周肝纤维化逆转则同时与基线纤维化分期、52周LSM降低比例独立相关[92]，提示抗病毒治疗78周前后的LSM绝对值降低更多反映的是肝脏炎症消退，LSM的动态变化和更长疗程核苷类药物治疗逆转肝脏纤维化间的相关性仍待更长疗程的大样本研究提供循证医学证据。基于消除肝脏炎症后的LSM处于低水平，其降低比例是否足以确定纤维化逆转仍待更长疗程抗病毒治疗研究证实，但乙型肝炎肝硬化抗病毒治疗26周时LSM降低值可预测2年肝脏相关性事件[93]，包括肝功能失代偿、肝癌发生及肝病相关性死亡等。上述LSM变化模式同样体现在CHC抗病毒治疗过程，但无病毒学应答患者降低幅度减少，而且停药后再次出现LSM进行性升高[94]。②社区人群肝病筛查：纳入1 190例年龄＞45岁的大规模社区人群筛查发现89名LSM＞8.0kPa均可发现某一特定慢性肝病，9例LSM＞13.0kPa患者肝活组织学检查证实为肝硬化[95]；静脉药瘾者LSM＞7.1kPa也提示HCV感染可能[96]，表明TE可以作为普通人群中筛选肝硬化及健康人群中发现未诊断慢性肝病的重要手段，LSM＞8.0kPa受试者均应筛查潜在肝病病因。③改善TE诊断性能：TE检测的LSM评估肝纤维化因炎症等多种因素影响而存在少数诊断不一致、诊断结果与其他诊断方法不符等现象，炎症较轻的肝硬化可出现低LSM而漏诊，而重度炎症则可能高估LSM而误诊肝硬化。当对TE诊断存在质疑时，结合B超肝实质、血管形态及血小板、白蛋白、凝血等血液指标可有效降低肝硬化漏诊率[97]。常规血清生物标志对于TE检查处于灰色区域而不能确定诊断患者仍可发挥补充诊断价值：在保证诊断界值具备足够统计学诊断证据（PLR 10.0或NLR 0.1）前提下，序贯联合APRI、FIB-4、γ-谷氨酰转移酶-血小板比值及红细胞体积分布宽度-血小板比值等常规参数组合有望提高肝硬化诊断率及诊断准确性[98,99]。

（二）瞬时弹性成像技术FibroTouch®

通过PubMed检索发现的5项FibroTouch®诊断肝纤维化研究中，一项研究纳入未行肝穿刺活组织检查健康人作为无肝纤维化患者，将肝功能失代偿期CHB患者列入肝硬化组，肝组织学病理学诊断存在不合理性[100]；另一项研究仅纳入16例自身免疫性肝炎患者进行诊断分析[101]。其余三项研究提示诊断肝硬化、进展期肝纤维化及显著肝纤维化的AUC分别为0.834～0.961、0.856～0.938、0.857～0.915[102,103,104]，仅建议单一界值诊断肝纤维化分期，建议诊断界值缺乏一致性。诊断肝硬化时，慢性肝病患者界值16.3kPa诊断、排除肝硬化均有足够强度统计学证据（PLR 11.8、NLR 0.07）[102]，但更大样本CHB患者研究建议界值15.9kPa诊断、排除肝硬化证据强度均较弱（PLR 3.6、NLR 0.41），诊断界值需调高，排除界值需降低[103]，而小样本CHB患者研究建议界值12.3kPa的NLR 0.15[104]，排除界值亦需进一步下调。诊断进展期肝纤维化时，三项研究建议界值均有利于排除诊断：界值12.6kPa排除诊断证据强度较好（NLR 0.13）[102]，但更大样本研究建议界值9.9kPa（NLR 0.22）与小样本研究建议界值较接近（10.8kPa, NLR 0.24）[103,104]；排除进展期肝纤维化界值应低于10.0kPa；诊断显著肝纤维化时，大样本研究建议界值9.9kPa具有足够诊断证据强度（PLR 35.2kPa）[103]，但另一建议界值9.6kPa更有利于排除诊断（NLR 0.19）[102]。

共识13：现有FibroTouch®诊断肝纤维化建议界值可靠性仍待更多临床研究确认（C2）。

三、未来研究方向

（1）大样本肝活检对照评估FibroTouch诊断肝纤维化分期，以建立其诊断肝纤维化分期可靠界值，并评估与FibroScan诊断界值的一致性。

（2）长期随访观察各种慢性肝病LSM动态变化对于预测HCC风险的临床价值。

（3）开展更多研究以验证扩展BavenoⅥ共识标准的有效性，同时结合脾脏大小等参数协助确定高风险食管静脉曲张，以提高不需进行胃镜检查患者的比例。

（4）在接受3～4年以上核苷（酸）类药物治疗CHB患者中，观察LSM联合影像学（如脾脏肿大减轻）、血液学（如血小板减少改善）等其他门静脉高压无创指标对于预测肝纤维化逆转的价值。

（5）阐明接受病因干预后的慢性肝病肝纤维化的在其他影响因素，探索其他校正方法以更准评估断肝纤维化的逆转。

顾问：

杨希忠（中国肝炎防治基金会）

庄辉（北京大学医学部）

王福生（解放军总医院第五医学中心）

贾继东（首都医科大学附属北京友谊医院）

侯金林（南方医科大学南方医院）

专家：（按姓氏拼音排序）

陈成伟（解放军海军军医大学九〇五医院）

陈国凤（解放军总医院第五医学中心）

陈永鹏（南方医科大学南方医院）

窦晓光（中国医科大学附属盛京医院）

段钟平（首都医科大学附属佑安医院）

范建高（上海交通大学医学院附属新华医院）

侯金林（南方医科大学南方医院）

贾继东（首都医科大学附属北京友谊医院）

李杰（北京大学基础医学院）

梁携儿（南方医科大学南方医院）

林锋（海南省人民医院）

陆伦根（上海交通大学医学院附属第一人民医院）

马红（首都医科大学附属北京友谊医院）

宁琴（华中科技大学同济医学院附属同济医院）

牛俊奇（吉林大学白求恩第一医院）

任红（重庆医科大学附属第二医院）

施军平（杭州师范大学附属医院）

舒建昌（暨南大学附属广州市红十字会医院）

孙剑（南方医科大学南方医院）

唐红（四川大学华西医院）

汪艳（南方医科大学南方医院）

王福生（解放军总医院第五医学中心）

王贵强（北京大学第一医院）

魏来（清华大学北京清华长庚医院）

谢青（上海交通大学医学院附属瑞金医院）

徐小元（北京大学第一医院）

杨永平（解放军总医院第五医学中心）

尤红（首都医科大学附属北京友谊医院）

赵鸿（北京大学第一医院）

庄辉（北京大学医学部）

利益冲突

所有作者均声明不存在利益冲突

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