HBeAg seroconversion is an important process during antiviral therapy for patients with HBeAg-positive chronic hepatitis B( CHB),while the first-line antiviral drugs,such as entecavir and tenofovir disoproxil fumarate,tend to have low HBeAg clearance rate and/or seroconversion rate,and at present,there is still a lack of effective radical treatment regimens. Latest studies have shown that fecal microbial transplantation( FMT) can induce HBeAg clearance in HBeAg-positive CHB patients receiving long-term antiviral therapy.This article reviews the research advances in the role of FMT in inducing HBeAg clearance in HBeAg-positive CHB patients and points out that FMT may become a new treatment regimen for HBeAg-positive CHB patients.
[1] World Health Organization. Global hepatitis report 2017[R].Geneva:WHO,2017.
|
[2] TERRAULT NA,BZOWEJ NH,CHANG KM,et al. AASLD guidelines for treatment of chronichepatitis B[J]. Hepatology,2016,63(1):261-283.
|
[3] XIAO C,ZHANG B,REN J. Improvements in chronic hepatitis B patients and the alteration in gut microbiota after fecal microbiota transplantation[J]. United Eur Gastroent,2017,5(5):a633.
|
[4] REN YD,YE ZS,YANG LZ,et al. Fecal microbiota transplantation induces hepatitis B virus e-antigen(HBe Ag)clearance in patients with positive HBe Ag after long-term antiviral therapy[J]. Hepatology,2017,65(5):1765-1768.
|
[5] CHOU HH,CHEN WH,WU LL,et al. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota[J]. Proc Natl Acad Sci U S A,2015,112(7):2175-2180.
|
[6] HIGASHI-KUWATA N,HAYASHI S,DAS D,et al. CMCdG,a novel nucleoside analog with favorable safety features,exerts potent activity against wild-type and entecavir-resistant hepatitis B virus[J]. Antimicrob Agents Chemother,2019,63(4):e02143-18.
|
[7] HVAS CL,DAHL JORGENSEN SM2,JORGENSEN SP,et al.Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent clostridium difficile infection[J]. Gastroenterology,2019,156(5):1324-1332.
|
[8] COSTELLO SP,HUGHES PA,WATERS O,et al. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis:A randomized clinical trial[J]. JAMA,2019,321(2):156-164.
|
[9] IANIRO G,MASUCCI L,QUARANTA G,et al. Randomised clinical trial:Faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions[J]. Aliment Pharmacol Ther,2018,48(2):152-159.
|
[10] HALKJAER SI,CHRISTENSEN AH,LO BZS,et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome:Results from a randomised,doubleblind placebo-controlled study[J]. Gut,2018,67(12):2107-2115.
|
[11] PARAMSOTHY S,KAMM MA,KAAKOUSH NO,et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis:A randomised placebo-controlled trial[J].Lancet,2017,389(10075):1218-1228.
|
[12] KELLY CR,KHORUTS A,STALEY C,et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent clostridium difficile infection:A randomized trial[J]. Ann Intern Med,2016,165(9):609-616.
|
[13] HARRISON TJ. Genetic variation in hepatitis B virus[J]. Eur J Gastroenterol Hepatol,1996,8(4):306-311.
|
[14] ISOGAWA M,ROBEK MD,FURUICHI Y,et al. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo[J].J Virol,2005,79(11):7269-7272.
|
[15] BAJAJ JS,FAGAN A,GAVIS EA et al. Long-term outcomes of fecal microbiota transplantation in patients with cirrhosis[J].Gastroenterology,2019,156(6):1921-1923.
|
[16] JOHNSEN PH,HILPÜSCH F,CAVANAGH JP,et al. Faecal microbiota transplantation versus placebo for moderate-tosevere irritable bowel syndrome:A double-blind,randomised,placebo-controlled,parallel-group,single-centre trial[J]. Lancet Gastroenterol Hepatol,2018,3(1):17-24.
|
[17] MOAYYEDI P,SURETTE MG,KIM PT,et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial[J]. Gastroenterology,2015,149(1):102-109.
|
[18] HOLVOET T,JOOSSENS M,WANG J,et al. Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating[J]. Gut,2017,66(5):980-982.
|
[19] European Association for the Study of the Liver. EASL 2017clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol,2017,67(2):370-398.
|
[20] KNOLLE PA,UHRIG A,HEGENBARTH S,et al. IL-10 downregulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules[J]. Clin Exp Immunol,1998,114(3):427-433.
|
[21] VISVANATHAN K,SKINNER NA,THOMPSON AJ,et al. Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein[J]. Hepatology,2007,45(1):102-110.
|
[22] LI M,SUN R,XU L,et al. Kupffer cells support hepatitis B virus-mediated CD8+T cell exhaustion via hepatitis B core antigen-TLR2 interactions in mice[J]. J Immunol,2015,195(7):3100-3109.
|
[23] MIAO J,YANG XQ,GAO Z,et al. Redox-responsive chitosan oligosaccharide-SS-Octadecylamine polymeric carrier for efficient anti-hepatitis B virus gene therapy[J]. Carbohydr Polym,2019,212:215-221.
|
[24] LOK AS,ZOULIM F,DUSHEIKO G,et al. Hepatitis B cure:From discovery to regulatory approval[J]. J Hepatol,2017,67(4):847-861.
|
[25] LIAW YF,LAU GK,KAO JH,et al. Hepatitis B e antigen seroconversion:A critical event in chronic hepatitis B virus infection[J]. Dig Dis Sci,2010,55(10):2727-2734.
|
[26] CHEN MT,BILLAUD JN,SALLBERG M,et al. A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen[J]. Proc Natl Acad Sci U S A,2004,101(41):14913-14918.
|
[27] LIU Q,LI F,ZHUANG Y,et al. Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma[J]. Gut Pathog,2019,11:1.
|
[28] WANG S,CHEN Z,HU C,et al. Hepatitis B virus surface antigen selectively inhibits TLR2 ligand-induced IL-12 production in monocytes/macrophages by interfering with JNK activation[J]. J Immunol,2013,190(10):5142-5151.
|
[29] LU H,WU Z,XU W,et al. Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients[J]. Microb Ecol,2011,61(3):693-703.
|
[30] WEI X,YAN X,ZOU D,et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach[J]. BMC Gastroenterol,2013,13:175.
|
[31] MULLISH BH,McDONALD JAK,THURSZ MR,et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy:A randomized clinical trial[J]. Hepatology,2017,66(4):1354-1355.
|
[32] BRENNER DA,PAIK YH,SCHNABL B. Role of gut microbiota in liver disease[J]. J Clin Gastroenterol,2015,49(Suppl 1):s25-s27.
|
[33] MA HD,WANG YH,CHANG C,et al. The intestinal microbiota and microenvironment in liver[J]. Autoimmun Rev,2015,14(3):183-191.
|
[34] WANG J,WANG Y,ZHANG X,et al. Gut microbial dysbiosis is associated with altered hepatic functions and serum metabolites in chronic hepatitis B patients[J]. Front Microbiol,2017,8:2222.
|
[35] LIMMER A,OHL J,KURTS C,et al. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+T cells results in antigen-specific T-cell tolerance[J]. Nat Med,2000,6(12):1348-1354.
|
[36] ACHARYA C,BAJAJ JS. Altered microbiome in patients with cirrhosis and complications[J]. Clin Gastroenterol Hepatol,2019,17(2):307-321.
|
[37] WANG B,LI L. Who determines the outcomes of HBV exposure?[J]. Trends Microbiol,2015,23(6):328-329.
|