Staging liver fibrosis and cirrhosis using non-invasive tests in people with chronic hepatitis B to inform WHO 2024 guidelines: a systematic review and meta-analysis.

We updated the systematic reviewand meta-analysisthat informed the 2015 guidelines to inform new cutoffs for non-invasive tests for the diagnosis of significant fibrosis and cirrhosis for the 2024 WHO guidelines for chronic hepatitis B.

我们更新了系统评价和荟萃分析，这些分析为2015年指南提供了信息，以确定2024年世界卫生组织慢性乙型肝炎指南中用于诊断显著纤维化和肝硬化的无创检测新临界值。

Methods

We searched PubMed (MEDLINE), Embase, and Science Citation Index Expanded (Web of Science) for studies published in any language between Jan 1, 2014, and Feb 15, 2023.

我们在PubMed (MEDLINE)、Embase和科学引文索引扩展(Science Citation Index Expanded, Web of Science)中检索了2014年1月1日至2023年2月15日间发表的所有语言的研究文献。

We included all studies that reported cross-sectional data on the staging of fibrosis or cirrhosis with APRI, Fibrosis-4 (FIB-4), and FibroScan compared with liver biopsy as the reference standard in people with chronic hepatitis B.

我们纳入了所有报告了使用APRI、Fibrosis-4 (FIB-4)和FibroScan对慢性乙型肝炎患者进行纤维化或肝硬化分期的横断面数据的研究，并以肝活检作为参考标准。

We excluded studies in which the maximum interval between liver biopsy and non-invasive fibrosis test was more than 6 months; that reported on fewer than ten patients with advanced fibrosis or cirrhosis; that were done exclusively in children; and did not report diagnostic accuracy across our prespecified ranges of test cutoffs.

我们排除了肝活检与无创性纤维化测试之间最大间隔超过6个月的研究；报告的晚期纤维化或肝硬化患者少于十人；仅在儿童中进行的研究；以及未报告我们预先设定的测试截断值范围内的诊断准确性。

The results of this updated search were collated with the meta-analysisthat informed the 2015 guidelines.

这次更新的搜索结果与为2015年指南提供信息的荟萃分析进行了汇总。

Outcomes of interest were the sensitivity and specificity of non-invasive tests using defined index test cutoffs for detecting significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) based on the METAVIR staging system.

关注的结果是使用定义的指数测试截断值来检测显著纤维化（≥F2）、高级纤维化（≥F3）和肝硬化（F4）的非侵入性测试的敏感性和特异性，基于METAVIR分期系统。

We performed meta-analyses using a bivariate random-effects model.

我们使用双变量随机效应模型进行了荟萃分析。

Results

Of 19 933 records identified by our search strategy, 195 were eligible for our systematic reviewand combined with the 69 studies from the previous meta-analysisto total 264.

通过我们的搜索策略，共识别出19,933条记录，其中195条符合我们的系统评价标准，并与之前元分析中的69项研究相结合，总计264项研究。

Two studies were at low risk of bias, 31 studies had unclear risk of bias, and 231 studies had a high risk of bias.

两项研究存在低风险偏倚，31项研究偏倚风险不明确，231项研究存在高风险偏倚。

Of these 264, 211 studies with 61 665 patients were used in the meta-analysis.

在这264项研究中，有211项研究涉及61,665名患者被用于元分析。

For the diagnosis of significant fibrosis (≥F2), sensitivity and specificity were 72·9% (95% CI 70·2-75·5) and 64·7% (95% CI 61·0-68·2) for the APRI low cutoff (>0·3 to 0·7), 30·5% (23·7-38·3) and 92·3% (89·3-94·6) for the APRI high cutoff (>1·3 to 1·7), and 75·1% (72·2-77·7) and 79·3% (76·2-82·2) for FibroScan (>6·0 to 8·0 kPa), respectively.

对于显著纤维化的诊断（≥F2），APRI低临界值（>0.3至0.7）的敏感性和特异性分别为72.9%（95%置信区间70.2-75.5）和64.7%（95%置信区间61.0-68.2），APRI高临界值（>1.3至1.7）的敏感性和特异性分别为30.5%（23.7-38.3）和92.3%（89.3-94.6），FibroScan高临界值（>6.0至8.0 kPa）的敏感性和特异性分别为75.1%（72.2-77.7）和79.3%（76.2-82.2）。

For the diagnosis of cirrhosis (F4), sensitivity and specificity were 59·4% (53·2-65·2) and 73·9% (70·1-77·4) for the APRI low cutoff (>0·8 to 1·2), 30·2% (24·2-36·9) and 88·2% (85·4-90·6) for the APRI high cutoff (>1·8 to 2·2), and 82·6% (77·8-86·5) and 89·0% (86·3-91·2) for FibroScan (>11·0 to 14·0 kPa), respectively.

在肝硬化（F4）的诊断中，APRI低临界值（>0.8至1.2）的敏感性和特异性分别为59.4%（53.2-65.2）和73.9%（70.1-77.4），APRI高临界值（>1.8至2.2）的敏感性和特异性分别为30.2%（24.2-36.9）和88.2%（85.4-90.6），而FibroScan（>11.0至14.0 kPa）的敏感性和特异性分别为82.6%（77.8-86.5）和89.0%（86.3-91.2）。

Using a hypothetical population of 1000 unselected patients with chronic hepatitis B with a 25% prevalenceof significant fibrosis (≥F2), the APRI low cutoff for significant fibrosis (≥F2) would result in 262 (26·2%) false positives but only 68 (6·8%) false negatives.

在一个假设有1000名未经筛选的慢性乙型肝炎患者中，其中25%的患者有显著纤维化（≥F2）的患病率，使用APRI低临界值（≥F2）进行显著纤维化的诊断将导致262例（26.2%）假阳性，但仅有68例（6.8%）假阴性。

The FibroScan cutoff would result in 158 (15·8%) false positives and 63 (6·3%) false negatives.

使用 FibroScan 截断值会导致 158 例（15.8%）假阳性病例和 63 例（6.3%）假阴性病例。

In a population with a 5% prevalenceof cirrhosis (F4), the APRI low cutoff for cirrhosis (F4) would result in 247 (24·7%) false positives and 21 (2·1%) false negatives and the FibroScan cutoff would result in 105 (10·5%) false positives and nine (0·9%) false negatives.

在一个肝硬化（F4）患病率为 5% 的人群中，APRI 用于诊断肝硬化（F4）的低截断值会导致 247 例（24.7%）假阳性病例和 21 例（2.1%）假阴性病例，而 FibroScan 截断值会导致 105 例（10.5%）假阳性病例和 9 例（0.9%）假阴性病例。

interpretation

These findings have informed new thresholds of APRI and FibroScan for diagnosis of significant fibrosis and cirrhosis in the 2024 WHO guidelines on chronic hepatitis B, with an APRI score greater than 0·5 or a FibroScan value greater than 7·0 kPa considered to identify most adults with significant fibrosis (≥F2) and an APRI score greater than 1·0 or a FibroScan value greater than 12·5 kPa to identify most adults with cirrhosis (F4).

这些发现为2024年世界卫生组织关于慢性乙型肝炎的指南提供了新的APRI和FibroScan诊断显著纤维化和肝硬化的阈值，APRI评分大于0.5或FibroScan值大于7.0 kPa被认为是识别大多数具有显著纤维化（≥F2）的成人，而APRI评分大于1.0或FibroScan值大于12.5 kPa被认为是识别大多数具有肝硬化（F4）的成人。

These patients are a priority for antiviral treatment.

这些患者是抗病毒治疗的优先对象。

funding

WHO.

世界卫生组织。