Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, 100700, China.
Department of Rheumatology and Immunology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, China.
Metabolomics. 2022 Jun 27;18(7):43. doi: 10.1007/s11306-022-01890-y.
A large number of studies have explored the potential biomarkers for detecting liver cirrhosis in an early stage, yet consistent conclusions are still warranted.
To conduct a review and a meta-analysis of the existing studies that test the serum level of bile acids in cirrhosis as the potential biomarkers to predict cirrhosis.
Six databases had been searched from inception date to April 12, 2021. Screening and selection of the records were based on the inclusion criteria. The risk of bias was assessed with the Newcastle-Ottawa quality assessment scale (NOS). Mean difference (MD) and confidence intervals 95% (95% CI) were calculated by using the random effect model for the concentrations of bile acids in the meta-analysis, and I statistic was used to measure studies heterogeneity. This study was registered on PROSPERO.
A total of 1583 records were identified and 31 studies with 2679 participants (1263 in the cirrhosis group, 1416 in the healthy control group) were included. The quality of included studies was generally high, with 25 studies (80.6%) rated over 7 stars. A total of 45 bile acids or their ratios in included studies were extracted. 36 increased in the cirrhosis group compared with those of the healthy controls by a qualitative summary, 5 decreased and 4 presented with mixing results. The result of meta-analysis among 12 studies showed that 13 bile acids increased, among which four primary conjugated bile acids showed the most significant elevation in the cirrhosis group: GCDCA (MD = 11.38 μmol/L, 95% CI 8.21-14.55, P < 0.0001), GCA (MD = 5.72 μmol/L, 95% CI 3.47-7.97, P < 0.0001), TCDCA (MD = 3.57 μmol/L, 95% CI 2.64-4.49, P < 0.0001) and TCA (MD = 2.14 μmol/L, 95% CI 1.56-2.72, P < 0.0001). No significant differences were found between the two groups in terms of DCA (MD = - 0.1 μmol/L, 95% CI - 0.18 to - 0.01, P < 0.0001) and LCA (MD = - 0.01 μmol/L, 95% CI - 0.01 to - 0.02, P < 0.0001), UDCA (MD = - 0.14 μmol/L, 95% CI - 0.04 to - 0.32, P < 0.0001), and TLCA (MD = 0 μmol/L, 95% CI 0-0.01, P < 0.0001). Subgroup analysis in patients with hepatitis B cirrhosis showed similar results.
Altered serum bile acids profile seems to be associated with cirrhosis. Some specific bile acids (GCA, GCDCA, TCA, and TCDCA) may increase with the development of cirrhosis, which possibly underlay their potential role as predictive biomarkers for cirrhosis. Yet this predictive value still needs further investigation and validation in larger prospective cohort studies.
大量研究探索了用于早期检测肝硬化的潜在生物标志物，但仍需要得出一致的结论。
对检测肝硬化患者血清胆汁酸水平作为潜在生物标志物以预测肝硬化的现有研究进行综述和荟萃分析。
从建库日期到 2021 年 4 月 12 日，在 6 个数据库中进行检索。根据纳入标准筛选和选择记录。使用纽卡斯尔-渥太华质量评估量表（NOS）评估偏倚风险。使用随机效应模型计算荟萃分析中胆汁酸浓度的均数差（MD）和 95%置信区间（95%CI），并使用 I 统计量测量研究异质性。本研究已在 PROSPERO 上注册。
共确定了 1583 条记录，纳入了 31 项研究，共 2679 名参与者（肝硬化组 1263 名，健康对照组 1416 名）。纳入研究的质量总体较高，25 项研究（80.6%）的评分超过 7 星。共提取了 45 种胆汁酸或其比值。定性总结显示，与健康对照组相比，肝硬化组中有 36 种胆汁酸升高，5 种降低，4 种结果混杂。12 项研究的荟萃分析结果表明，有 13 种胆汁酸升高，其中 4 种初级结合胆汁酸在肝硬化组中升高最显著：甘氨胆酸（MD=11.38 μmol/L，95%CI 8.21-14.55，P<0.0001）、甘氨胆酸（MD=5.72 μmol/L，95%CI 3.47-7.97，P<0.0001）、牛磺胆酸（MD=3.57 μmol/L，95%CI 2.64-4.49，P<0.0001）和牛磺胆酸（MD=2.14 μmol/L，95%CI 1.56-2.72，P<0.0001）。两组间 DCA（MD=-0.1 μmol/L，95%CI -0.18 至-0.01，P<0.0001）和 LCA（MD=-0.01 μmol/L，95%CI -0.01 至-0.02，P<0.0001）、熊去氧胆酸（MD=-0.14 μmol/L，95%CI -0.04 至-0.32，P<0.0001）和 TLCA（MD=0 μmol/L，95%CI 0-0.01，P<0.0001）无显著差异。乙型肝炎肝硬化患者的亚组分析结果相似。
血清胆汁酸谱的改变似乎与肝硬化有关。一些特定的胆汁酸（甘氨胆酸、甘氨胆酸、牛磺胆酸和牛磺胆酸）可能随着肝硬化的发展而增加，这可能是它们作为肝硬化预测生物标志物的潜在作用。然而，这种预测价值仍需要在更大的前瞻性队列研究中进一步研究和验证。
