Gut microbiota as prognosis markers for patients with HBV-related acute-on-chronic liver failure

Ke Wang, Zhao Zhang, Zhi-Shuo Mo, Xiao-Hua Yang, Bing-Liang Lin, Liang Peng, Yang Xu, Chun-Yan Lei, Xiao-Dong Zhuang, Ling Lu, Rui-Fu Yang, Tao Chen, Zhi-Liang Gao, Ke Wang, Zhao Zhang, Zhi-Shuo Mo, Xiao-Hua Yang, Bing-Liang Lin, Liang Peng, Yang Xu, Chun-Yan Lei, Xiao-Dong Zhuang, Ling Lu, Rui-Fu Yang, Tao Chen, Zhi-Liang Gao

Abstract

The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut microbiota in HBV-ACLF and in other HBV associated pathologies. We analyzed the gut microbiome in patients with HBV-ACLF or other HBV associated pathologies and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. 212 patients with HBV-ACLF, 252 with chronic hepatitis B (CHB), 162 with HBV-associated cirrhosis (HBV-LC) and 877 healthy individuals were recruited for the study. CHB and HBV-LC patients are grouped as HBV-Other. We discovered striking differences in the microbiome diversity between the HBV-ACLF, HBV-Other and healthy groups using 16S rRNA sequencing. The ratio of cocci to bacilli was significantly elevated in the HBV-ACLF group compared with healthy group. Further analysis within the HBV-ACLF group identified 52 genera showing distinct richness within the group where Enterococcus was enriched in the progression group whilst Faecalibacterium was enriched in the regression group. Metagenomic sequencing validated these findings and further uncovered an enrichment of Lactobacillus casei paracasei in progression group, while Alistipes senegalensis, Faecalibacterium prausnitzii and Parabacteroides merdae dominated the regression group. Importantly, our analysis revealed that there was a rapid increase of Enterococcus faecium during the progression of HBV-ACLF. The gut microbiota displayed distinct composition at different phases of HBV-ACLF. High abundance of Enterococcus is associated with progression while that of Faecalibacterium is associated with regression of HBV-ACLF. Therefore, the microbiota features hold promising potential as prognostic markers for HBV-ACLF.

Keywords: 16S rRNA sequencing; Hepatitis B; acute-on-chronic liver failure; gut microbiota; metagenomic sequencing.

Figures

Figure 1.
Figure 1.
Gut microbiota distribution among groups. (a) Alpha diversity analysis (P = 3.57E-06). (b) A t-distributed stochastic neighbor embedding (t-SNE) visualization (P = .001). (c) Lef Se analysis showed predominant gut microbiota. (d) The ratio of cocci to bacilli was compared among the three groups. **P < .01
Figure 1.
Figure 1.
Gut microbiota distribution among groups. (a) Alpha diversity analysis (P = 3.57E-06). (b) A t-distributed stochastic neighbor embedding (t-SNE) visualization (P = .001). (c) Lef Se analysis showed predominant gut microbiota. (d) The ratio of cocci to bacilli was compared among the three groups. **P < .01
Figure 2.
Figure 2.
A classification model for the healthy, HBV-Other and the HBV-ACLF group. (a) 18 most important taxa in the classification model among the 3 groups. (b) The decomposition visualization of the 18 most important taxa among the 3 groups
Figure 2.
Figure 2.
A classification model for the healthy, HBV-Other and the HBV-ACLF group. (a) 18 most important taxa in the classification model among the 3 groups. (b) The decomposition visualization of the 18 most important taxa among the 3 groups
Figure 3.
Figure 3.
The abundance of the genera with the highest richness Enterococcus and Faecalibacterium. The relative abundance of Enterococcus was significantly elevated in the progression group, and that of Faecalibacterium was significantly elevated in the regression group
Figure 3.
Figure 3.
The abundance of the genera with the highest richness Enterococcus and Faecalibacterium. The relative abundance of Enterococcus was significantly elevated in the progression group, and that of Faecalibacterium was significantly elevated in the regression group
Figure 4.
Figure 4.
Correlation between the gut microbiota and clinical indicators. The common genera associated with ALT/AST (relevant to liver inflammation), TBIL/INR/MELD (relevant to liver disease severity) and WBC/NEUT%/PCT (relevant to the degree of infection), respectively. Blue square represents the common genera selected by the trained Regressor that with clinical relevant
Figure 4.
Figure 4.
Correlation between the gut microbiota and clinical indicators. The common genera associated with ALT/AST (relevant to liver inflammation), TBIL/INR/MELD (relevant to liver disease severity) and WBC/NEUT%/PCT (relevant to the degree of infection), respectively. Blue square represents the common genera selected by the trained Regressor that with clinical relevant
Figure 5.
Figure 5.
Difference of gut microbiota between the progression and regression groups. Relative abundance of genus at day-1 (fecal sample collected at day 1 after admission), day 7 and day 14 between the progression and regression group of HBV-ACLF. (a) Enterococcus and Faecalibacterium, and (b) species Lactobacillus casei paracasei, Alistipes senegalensis, Faecalibacterium prausnitzii and Parabacteroides merdae. *P 

Figure 5.

Difference of gut microbiota between…

Figure 5.

Difference of gut microbiota between the progression and regression groups. Relative abundance of…

Figure 5.
Difference of gut microbiota between the progression and regression groups. Relative abundance of genus at day-1 (fecal sample collected at day 1 after admission), day 7 and day 14 between the progression and regression group of HBV-ACLF. (a) Enterococcus and Faecalibacterium, and (b) species Lactobacillus casei paracasei, Alistipes senegalensis, Faecalibacterium prausnitzii and Parabacteroides merdae. *P 

Figure 6.

The key species of different…

Figure 6.

The key species of different gut microbiota were further validated by qPCR. qPCR…

Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 

Figure 6.

The key species of different…

Figure 6.

The key species of different gut microbiota were further validated by qPCR. qPCR…

Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 
All figures (12)
Similar articles
Cited by
References
    1. Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF.. Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol. 2018;12(4):341–15. doi:10.1080/17474124.2018.1426459. - DOI - PubMed
    1. Li H, Chen LY, Zhang NN, Li ST, Zeng B, Pavesi M, Amoros A, Mookerjee RP, Xia Q, Xue F, et al. Characteristics, diagnosis and prognosis of acute-on-chronic liver failure in cirrhosis associated to hepatitis B. Sci Rep. 2016;6:25487. doi:10.1038/srep25487. - DOI - PMC - PubMed
    1. Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology. 2015;62(1):232–242. doi:10.1002/hep.27795. - DOI - PubMed
    1. Zheng MH, Shi KQ, Fan YC, Li H, Ye C, Chen QQ, Chen YP. A model to determine 3-month mortality risk in patients with acute-on-chronic hepatitis B liver failure. Clin Gastroenterol Hepatol. 2011;9(4):351–6 e3. doi:10.1016/j.cgh.2010.12.027. - DOI - PubMed
    1. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–1836. doi:10.1042/BCJ20160510. - DOI - PMC - PubMed
Show all 44 references
Publication types
MeSH terms
Related information
LinkOut - more resources
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Follow NCBI
Figure 5.
Figure 5.
Difference of gut microbiota between the progression and regression groups. Relative abundance of genus at day-1 (fecal sample collected at day 1 after admission), day 7 and day 14 between the progression and regression group of HBV-ACLF. (a) Enterococcus and Faecalibacterium, and (b) species Lactobacillus casei paracasei, Alistipes senegalensis, Faecalibacterium prausnitzii and Parabacteroides merdae. *P 

Figure 6.

The key species of different…

Figure 6.

The key species of different gut microbiota were further validated by qPCR. qPCR…

Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 

Figure 6.

The key species of different…

Figure 6.

The key species of different gut microbiota were further validated by qPCR. qPCR…

Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 
All figures (12)
Similar articles
Cited by
References
    1. Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF.. Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol. 2018;12(4):341–15. doi:10.1080/17474124.2018.1426459. - DOI - PubMed
    1. Li H, Chen LY, Zhang NN, Li ST, Zeng B, Pavesi M, Amoros A, Mookerjee RP, Xia Q, Xue F, et al. Characteristics, diagnosis and prognosis of acute-on-chronic liver failure in cirrhosis associated to hepatitis B. Sci Rep. 2016;6:25487. doi:10.1038/srep25487. - DOI - PMC - PubMed
    1. Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology. 2015;62(1):232–242. doi:10.1002/hep.27795. - DOI - PubMed
    1. Zheng MH, Shi KQ, Fan YC, Li H, Ye C, Chen QQ, Chen YP. A model to determine 3-month mortality risk in patients with acute-on-chronic hepatitis B liver failure. Clin Gastroenterol Hepatol. 2011;9(4):351–6 e3. doi:10.1016/j.cgh.2010.12.027. - DOI - PubMed
    1. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–1836. doi:10.1042/BCJ20160510. - DOI - PMC - PubMed
Show all 44 references
Publication types
MeSH terms
Related information
LinkOut - more resources
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Follow NCBI
Figure 6.
Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 

Figure 6.

The key species of different…

Figure 6.

The key species of different gut microbiota were further validated by qPCR. qPCR…

Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 
All figures (12)
Similar articles
Cited by
References
    1. Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF.. Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol. 2018;12(4):341–15. doi:10.1080/17474124.2018.1426459. - DOI - PubMed
    1. Li H, Chen LY, Zhang NN, Li ST, Zeng B, Pavesi M, Amoros A, Mookerjee RP, Xia Q, Xue F, et al. Characteristics, diagnosis and prognosis of acute-on-chronic liver failure in cirrhosis associated to hepatitis B. Sci Rep. 2016;6:25487. doi:10.1038/srep25487. - DOI - PMC - PubMed
    1. Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology. 2015;62(1):232–242. doi:10.1002/hep.27795. - DOI - PubMed
    1. Zheng MH, Shi KQ, Fan YC, Li H, Ye C, Chen QQ, Chen YP. A model to determine 3-month mortality risk in patients with acute-on-chronic hepatitis B liver failure. Clin Gastroenterol Hepatol. 2011;9(4):351–6 e3. doi:10.1016/j.cgh.2010.12.027. - DOI - PubMed
    1. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–1836. doi:10.1042/BCJ20160510. - DOI - PMC - PubMed
Show all 44 references
Publication types
MeSH terms
Related information
LinkOut - more resources
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 6.
Figure 6.
The key species of different gut microbiota were further validated by qPCR. qPCR validation of the relative abundance of Enterococcus faecium, Faecalibacterium prausnitzii, Lactobacillus casei paracasei, Clostridium citroniae and Dorea longicatena between progression and regression group of HBV-ACLF. **P 
All figures (12)

References

    1. Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF.. Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol. 2018;12(4):341–15. doi:10.1080/17474124.2018.1426459.
    1. Li H, Chen LY, Zhang NN, Li ST, Zeng B, Pavesi M, Amoros A, Mookerjee RP, Xia Q, Xue F, et al. Characteristics, diagnosis and prognosis of acute-on-chronic liver failure in cirrhosis associated to hepatitis B. Sci Rep. 2016;6:25487. doi:10.1038/srep25487.
    1. Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology. 2015;62(1):232–242. doi:10.1002/hep.27795.
    1. Zheng MH, Shi KQ, Fan YC, Li H, Ye C, Chen QQ, Chen YP. A model to determine 3-month mortality risk in patients with acute-on-chronic hepatitis B liver failure. Clin Gastroenterol Hepatol. 2011;9(4):351–6 e3. doi:10.1016/j.cgh.2010.12.027.
    1. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–1836. doi:10.1042/BCJ20160510.
    1. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–1920. doi:10.1126/science.1104816.
    1. Hold GL, Hansen R. Impact of the gastrointestinal microbiome in health and disease: co-evolution with the host immune system. Curr Top Microbiol Immunol. 2019;421:303–318. doi:10.1007/978-3-030-15138-6_12.
    1. Boullier S, Tanguy M, Kadaoui KA, Caubet C, Sansonetti P, Corthesy B, Phalipon A. Secretory IgA-mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down-regulating inflammatory circuits. J Immunol. 2009;183(9):5879–5885. doi:10.4049/jimmunol.0901838.
    1. Guarner F, Malagelada J-R. Gut flora in health and disease. Lancet. 2003;361(9356):512–519. doi:10.1016/S0140-6736(03)12489-0.
    1. Biagi E, Rampelli S, Turroni S, Quercia S, Candela M, Brigidi P. The gut microbiota of centenarians: signatures of longevity in the gut microbiota profile. Mech Ageing Dev. 2017;165(Pt B):180–184. doi:10.1016/j.mad.2016.12.013.
    1. Chen L, Zhang YH, Huang T, Cai YD. Gene expression profiling gut microbiota in different races of humans. Sci Rep. 2016;6:23075. doi:10.1038/srep23075.
    1. Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, Abe F, Osawa R. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 2016;16:90. doi:10.1186/s12866-016-0708-5.
    1. Flint HJ, Duncan SH, Scott KP, Louis P. Interactions and competition within the microbial community of the human colon: links between diet and health. Environ Microbiol. 2007;9(5):1101–1111. doi:10.1111/j.1462-2920.2007.01281.x.
    1. Macfarlane GT, Steed H, Macfarlane S. Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics. J Appl Microbiol. 2008;104(2):305–344. doi:10.1111/j.1365-2672.2007.03520.x.
    1. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258–1270. doi:10.1016/j.cell.2012.01.035.
    1. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904. doi:10.1152/physrev.00045.2009.
    1. Chen Y, Guo J, Qian G, Fang D, Shi D, Guo L, Li L. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality. J Gastroenterol Hepatol. 2015;30(9):1429–1437. doi:10.1111/jgh.12932.
    1. Sandler NG, Koh C, Roque A, Eccleston JL, Siegel RB, Demino M, Kleiner DE, Deeks SG, Liang TJ, Heller T, et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology. 2011;141(4):1220–30, 30.e1-3. doi:10.1053/j.gastro.2011.06.063.
    1. Giannelli V, Di Gregorio V, Iebba V, Giusto M, Schippa S, Merli M, Thalheimer U. Microbiota and the gut-liver axis: bacterial translocation, inflammation and infection in cirrhosis. World J Gastroenterol. 2014;20(45):16795–16810. doi:10.3748/wjg.v20.i45.16795.
    1. Zeuzem S. Gut-liver axis. Int J Colorectal Dis. 2000;15(2):59–82. doi:10.1007/s003840050236.
    1. Han DW. Intestinal endotoxemia as a pathogenetic mechanism in liver failure. World J Gastroenterol. 2002;8(6):961–965. doi:10.3748/wjg.v8.i6.961.
    1. Palma P, Mihaljevic N, Hasenberg T, Keese M, Koeppel TA. Intestinal barrier dysfunction in developing liver cirrhosis: an in vivo analysis of bacterial translocation. Hepatol Res. 2007;37(1):6–12. doi:10.1111/j.1872-034X.2007.00004.x.
    1. Ramachandran A, Balasubramanian KA. Intestinal dysfunction in liver cirrhosis: its role in spontaneous bacterial peritonitis. J Gastroenterol Hepatol. 2001;16(6):607–612. doi:10.1046/j.1440-1746.2001.02444.x.
    1. Liu JE, Zhang Y, Zhang J, Dong PL, Chen M, Duan ZP. Probiotic yogurt effects on intestinal flora of patients with chronic liver disease. Nurs Res. 2010;59(6):426–432. doi:10.1097/NNR.0b013e3181fa4dc6.
    1. Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004;39(5):1441–1449. doi:10.1002/hep.20194.
    1. Shukla S, Shukla A, Mehboob S, Guha S. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther. 2011;33(6):662–671. doi:10.1111/j.1365-2036.2010.04574.x.
    1. Mariat D, Firmesse O, Levenez F, Guimaraes V, Sokol H, Dore J, Corthier G, Furet JP. The firmicutes/bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 2009;9:123. doi:10.1186/1471-2180-9-123.
    1. Liu Q, Li F, Zhuang Y, Xu J, Wang J, Mao X, Zhang Y, Liu X. Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma. Gut Pathog. 2019;11:1. doi:10.1186/s13099-018-0281-6.
    1. Ren YD, Ye ZS, Yang LZ, Jin LX, Wei WJ, Deng YY, Chen XX, Xiao CX, Yu XF, Xu HZ, et al. Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy. Hepatology. 2017;65(5):1765–1768. doi:10.1002/hep.29008.
    1. Yun Y, Chang Y, Kim HN, Ryu S, Kwon MJ, Cho YK, Kim HL, Cheong HS, Joo EJ. Alterations of the gut microbiome in chronic hepatitis B virus infection associated with alanine aminotransferase level. J Clin Med. 2019;8:2. doi:10.3390/jcm8020173.
    1. Low DE, Keller N, Barth A, Jones RN. Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY antimicrobial surveillance program, 1997–1999. Clin Infect Dis. 2001;32(Suppl 2):S133–45. doi:10.1086/320185.
    1. Mou H, Yang F, Zhou J, Bao C. Correlation of liver function with intestinal flora, vitamin deficiency and IL-17A in patients with liver cirrhosis. Exp Ther Med. 2018;16(5):4082–4088. doi:10.3892/etm.2018.6663.
    1. Hold GL, Schwiertz A, Aminov RI, Blaut M, Flint HJ. Oligonucleotide probes that detect quantitatively significant groups of butyrate-producing bacteria in human feces. Appl Environ Microbiol. 2003;69(7):4320–4324. doi:10.1128/AEM.69.7.4320-4324.2003.
    1. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105(43):16731–16736. doi:10.1073/pnas.0804812105.
    1. De Palma G, Nadal I, Medina M, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 2010;10:63. doi:10.1186/1471-2180-10-63.
    1. Balamurugan R, Rajendiran E, George S, Samuel GV, Ramakrishna BS. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol. 2008;23(8 Pt 1):1298–1303. doi:10.1111/j.1440-1746.2008.05490.x.
    1. Lu H, Wu Z, Xu W, Yang J, Chen Y, Li L. Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients. Microb Ecol. 2011;61(3):693–703. doi:10.1007/s00248-010-9801-8.
    1. Zhang Y, Zhao R, Shi D, Sun S, Ren H, Zhao H, Wu W, Jin L, Sheng J, Shi Y. Characterization of the circulating microbiome in acute-on-chronic liver failure associated with hepatitis B. Liver Int. 2019. doi:10.1111/liv.14097.
    1. Hill D, Sugrue I, Tobin C, Hill C, Stanton C, Ross RP. The Lactobacillus casei Group: history and health related applications. Front Microbiol. 2018;9:2107. doi:10.3389/fmicb.2018.02107.
    1. Cassard AM, Gerard P, Perlemuter G. Microbiota, liver diseases, and alcohol. Microbiol Spectr. 2017;5:4. doi:10.1128/microbiolspec.BAD-0007-2016.
    1. Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther. 2020;51(5):505–526. doi:10.1111/apt.15604
    1. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D'Amico G, Dickson ER, Kim WR. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464–470. doi:10.1053/jhep.2001.22172
    1. Zheng Y-B, Xie D-Y, Gu Y-R, Yan Y, Wu Y-B, Lei Z-Y, Peng L, Xie S-B, Gao Z-L, Ke W-M, et al. Development of a sensitive prognostic scoring system for the evaluation of severity of acute-on-chronic hepatitis B liver failure: a retrospective cohort study. Clin Invest Med. 2012;35(2):E75–85. doi:10.25011/cim.v35i2.16291.
    1. Morrissey ER. GRENITS: gene regulatory network inference using time series. Systems Biology Doctoral Training Centre; 2011.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe