Xu Han1, Juan Wang1, Hao Gu1, Hongtao Guo2, Yili Cai3, Xing Liao4, Miao Jiang5. 1. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, 100700, China. 2. Department of Rheumatology and Immunology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, China. 3. Ningbo First Hospital, Ningbo, China. 4. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, 100700, China. okfrom2008@hotmail.com. 5. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, 100700, China. miao_jm@vip.126.com.
Abstract
INTRODUCTION: A large number of studies have explored the potential biomarkers for detecting liver cirrhosis in an early stage, yet consistent conclusions are still warranted. OBJECTIVES: 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. METHODS: 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 I2 statistic was used to measure studies heterogeneity. This study was registered on PROSPERO. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: A large number of studies have explored the potential biomarkers for detecting liver cirrhosis in an early stage, yet consistent conclusions are still warranted. OBJECTIVES: 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. METHODS: 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 I2 statistic was used to measure studies heterogeneity. This study was registered on PROSPERO. RESULTS: 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. CONCLUSION: 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.
Authors: Jasmohan S Bajaj; Phillip B Hylemon; Jason M Ridlon; Douglas M Heuman; Kalyani Daita; Melanie B White; Pamela Monteith; Nicole A Noble; Masoumeh Sikaroodi; Patrick M Gillevet Journal: Am J Physiol Gastrointest Liver Physiol Date: 2012-07-19 Impact factor: 4.052
Authors: Jasmohan S Bajaj; Andrew Fagan; Masoumeh Sikaroodi; Genta Kakiyama; Hajme Takei; Yordanos Degefu; William M Pandak; Phillip B Hylemon; Michael Fuchs; Binu John; Douglas M Heuman; Edith Gavis; Hiroshi Nittono; Rohan Patil; Patrick M Gillevet Journal: Clin Gastroenterol Hepatol Date: 2019-03-21 Impact factor: 11.382
Authors: K Chisaki; T Nakajima; K Iwasawa; H Iida; A Matsumoto; M Tada; Y Komatsu; K Hirose; K Miyamoto; Y Okuda; Y Shiratori; A Goto; Y Hirata; R Nagai; M Omata Journal: Jpn Heart J Date: 2001-05