晚期血吸虫病基础和临床研究新进展

doi:10.12140/j.issn.1000-7423.2021.04.002

摘要/Abstract

摘要：

当前我国血吸虫病疫情已经处于历史最低水平,感染率大幅下降,但仍存在大量晚期血吸虫病患者。晚期血吸虫病是血吸虫病进程中最严重的类型,严重危害患者的生命健康和生活质量。血吸虫虫卵引起的肝脏肉芽肿和纤维化病变是导致晚期血吸虫病患者死亡的主要原因。本文就晚期血吸虫病的病理机制、肝纤维化判定、治疗以及预后评估等方面的基础和临床研究进展进行综述,以期为今后血吸虫病防治工作提供参考。

关键词: 血吸虫病, 晚期, 肝纤维化, 基础, 临床

Abstract:

At present, the endemic situation of schistosomiasis is at the lowest level in history in China, and the infection rate has decreased significantly, but there are still a large number of patients with advanced schistosomiasis. Advanced schistosomiasis is the most serious type of schistosomiasis, which seriously endangers the health and quality of life of patients. Liver granuloma and fibrosis caused by Schistosoma eggs are the leading cause for the death of advanced schistosomiasis patients. This article summarizes the pathological mechanism, determine approaches, treatment and prognosis of liver fibrosis in basic and clinical research of advanced schistosomiasis, hoping to provide reference information for future schistosomiasis prevention and treatment.

Key words: Schistosomiasis, Advanced, Hepatic fibrosis, Basic, Clinical

中图分类号:

R532.2

刘蓉, 闻礼永. 晚期血吸虫病基础和临床研究新进展[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 429-436.

LIU Rong, WEN Li-yong. New progress in basic and clinical research of advanced schistosomiasis[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2021, 39(4): 429-436.

参考文献 74

[1]	Xu J, Li SZ, Zhang LJ, et al. Surveillance-based evidence: elimination of schistosomiasis as a public health problem in the People’s Republic of China[J]. Infect Dis Poverty, 2020, 9:63. doi: 10.1186/s40249-020-00676-5
[2]	Zhang LJ, Xu ZM, Dang H, et al. Endemic status of schistosomiasis in People’s Republic of China in 2019[J]. Chin J Schisto Control, 2020, 32(6):551-558. (in Chinese)
	(张利娟, 徐志敏, 党辉, 等. 2019年全国血吸虫病疫情通报[J]. 中国血吸虫病防治杂志, 2020, 32(6):551-558.)
[3]	Wu W, Feng AC, Huang YX. Research and control of advanced schistosomiasis japonica in China[J]. Parasitol Res, 2015, 114(1):17-27. doi: 10.1007/s00436-014-4225-x
[4]	Song L, Wu X, Zhang B, et al. A cross-sectional survey comparing a free treatment program for advanced schistosomiasis japonica to a general assistance program[J]. Parasitol Res, 2017, 116(11):2901-2909. doi: 10.1007/s00436-017-5596-6
[5]	Kamdem SD, Moyou-Somo R, Brombacher F, et al. Host regulators of liver fibrosis during human schistosomiasis[J]. Front Immunol, 2018, 9:2781. doi: 10.3389/fimmu.2018.02781
[6]	Guimarães CM, Marcello DAJ, Mauro PJ. Schistosomiasis: clinical management of liver disease[J]. Clin Liver Dis (Hoboken), 2015, 6(3):59-62.
[7]	Cabantous S, Hou XY, Louis L, et al. Evidence for an important role of host microRNAs in regulating hepatic fibrosis in humans infected with Schistosoma japonicum[J]. Int J Parasitol, 2017, 47(13):823-830. doi: S0020-7519(17)30207-2 pmid: 28739251
[8]	Cai PF, Mu Y, Olveda RM, et al. Serum exosomal miRNAs for grading hepatic fibrosis due to schistosomiasis[J]. Int J Mol Sci, 2020, 21(10):E3560.
[9]	Xiao Q, Yu H, Zhu X. The associations of hub gene polymorphisms in PI3K/AKT/mTOR pathway and schistosomiasis japonica infection and hepatic fibrosis[J]. Infect Genet Evol, 2020, 85:104423. doi: S1567-1348(20)30254-9 pmid: 32554084
[10]	Long X, Chen Q, Zhao JP, et al. An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum[J]. PLoS One, 2015, 10(8):e0135360. doi: 10.1371/journal.pone.0135360
[11]	Zhu X, Zhang J, Fan W, et al. MAPKAP1 rs10118570 polymorphism is associated with anti-infection and anti-hepatic fibrogenesis in schistosomiasis japonica[J]. PLoS One, 2014, 9(8):e105995. doi: 10.1371/journal.pone.0105995
[12]	Guan F, Zhang CY, Jiang CJ, et al. ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica[J]. Parasite Immunol, 2020, 42(12):e12785.
[13]	He X, Pan WQ. Research progress on miRNA-mediated schistosome-host interactions[J]. Chin J Parasitol Parasit Dis, 2020, 38(3):259-262. (in Chinese)
	(何兴, 潘卫庆. miRNA介导血吸虫和宿主相互作用的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(3):259-262.)
[14]	Wang Y, Fan X, Lei N, et al. A microRNA derived from Schistosoma japonicum promotes schistosomiasis hepatic fibrosis by targeting host secreted frizzled-related protein 1[J]. Front Cell Infect Microbiol, 2020, 10:101. doi: 10.3389/fcimb.2020.00101
[15]	He X, Wang YG, Fan XB, et al. A schistosome miRNA promotes host hepatic fibrosis by targeting transforming growth factor beta receptor Ⅲ[J]. J Hepatol, 2020, 72(3):519-527. doi: 10.1016/j.jhep.2019.10.029
[16]	Wang LF, Liao Y, Yang RB, et al. Sja-miR-71a in schistosome egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D[J]. J Extracell Vesicles, 2020, 9(1):1785738. doi: 10.1080/20013078.2020.1785738
[17]	Zhou YH, Yang YY, Fan XL, et al. The role of Th17/Treg imbalance in liver fibrosis in schistosomiasis[J]. Chin J Parasitol Parasit Dis, 2017, 35(1):89-92. (in Chinese)
	(周永华, 杨莹莹, 范小琳, 等. Th17/Treg免疫失衡在血吸虫病肝纤维化中的作用[J]. 中国寄生虫学与寄生虫病杂志, 2017, 35(1):89-92.)
[18]	Wang XL, Hu Y, Cao JP. Associations of natural killer cells and their receptors with liver fibrosis in schistosomiasis[J]. Chin J Parasitol Parasit Dis, 2018, 36(5):504-509. (in Chinese)
	(王晓玲, 胡媛, 曹建平. 自然杀伤细胞及其受体与血吸虫病肝纤维化[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(5):504-509.)
[19]	Liu X, Qi YF, Yu YR. Effects of soluble egg antigens on hepatic stellate cells in the progression of schistosomiasis-associated liver fibrosis[J]. Chin J Parasitol Parasit Dis, 2019, 37(2):218-222. (in Chinese)
	(刘欣, 齐永芬, 鱼艳荣. 血吸虫病肝纤维化中可溶性虫卵抗原对肝星状细胞的作用[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(2):218-222.)
[20]	Chen XJ, Xu ZP, Wei C, et al. Follicular helper T cells recruit eosinophils into host liver by producing CXCL12 during Schistosoma japonicum infection[J]. J Cell Mol Med, 2020, 24(4):2566-2572. doi: 10.1111/jcmm.v24.4
[21]	Gieseck RL 3rd, Ramalingam TR, Hart KM, et al. Interleukin-13 activates distinct cellular pathways leading to ductular reaction, steatosis, and fibrosis[J]. Immunity, 2016, 45(1):145-158. doi: 10.1016/j.immuni.2016.06.009
[22]	Liu X, Zhang YR, Cai C, et al. Taurine alleviates Schistosoma-induced liver injury by inhibiting the TXNIP/NLRP3 inflammasome signal pathway and pyroptosis[J]. Infect Immun, 2019, 87(12):e00732-e00719.
[23]	Zhang LN, Wang XF, Qi QQ, et al. Study on role of TIGIT signal in Th1/Th2 balance in Schistosoma japonicum-infected mice[J]. Chin J Schisto Control, 2018, 30(2):136-139, 144. (in Chinese)
	(张丽娜, 王小番, 齐倩倩, 等. TIGIT信号在日本血吸虫感染小鼠Th1/Th2反应平衡中的作用研究[J]. 中国血吸虫病防治杂志, 2018, 30(2):136-139, 144.)
[24]	Nono JK, Ndlovu H, Aziz NA, et al. Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha[J]. PLoS Negl Trop Dis, 2017, 11(8):e0005861. doi: 10.1371/journal.pntd.0005861
[25]	Zhu J, Zhang W, Zhang L, et al. IL-7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum-infected mice[J]. J Cell Mol Med, 2018, 22(7):3353-3363. doi: 10.1111/jcmm.2018.22.issue-7
[26]	Zhao YM, Dang ZS, Chong SG. Mmu-miR-92a-2-5p targets TLR2 to relieve Schistosoma japonicum-induced liver fibrosis[J]. Int Immunopharmacol, 2019, 69:126-135. doi: 10.1016/j.intimp.2019.01.007
[27]	Liu C, Zhang YS, Chen F, et al. Immunopathology in schistosomiasis is regulated by TLR2, 4- and IFN-γ-activated MSC through modulating Th1/Th2 responses[J]. Stem Cell Res Ther, 2020, 11(1):217. doi: 10.1186/s13287-020-01735-2
[28]	Vicentino ARR, Carneiro VC, Allonso D, et al. Emerging role of HMGB1 in the pathogenesis of schistosomiasis liver fibrosis[J]. Front Immunol, 2018, 9:1979. doi: 10.3389/fimmu.2018.01979 pmid: 30258438
[29]	Deng JH, Tao R, Song QQ, et al. Regulation of hepatic stellate cell membrane receptors by Hsp47-shRNA affects hepatic fibrosis in mice with Schistosoma japonicum infection[J]. Chin J Parasitol Parasit Dis, 2018, 36(4):317-324. (in Chinese)
	(邓菊红, 陶然, 宋启琴, 等. 热休克蛋白47-shRNA调节肝星状细胞膜受体对日本血吸虫鼠肝纤维化的影响[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(4):317-324.)
[30]	Kong HY, He JN, Guo SS, et al. Endothelin receptors promote schistosomiasis-induced hepatic fibrosis via splenic B cells[J]. PLoS Pathog, 2020, 16(10):e1008947. doi: 10.1371/journal.ppat.1008947
[31]	Chuah C, Jones MK, McManus DP, et al. Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica[J]. Int J Parasitol, 2016, 46(4):239-252. doi: 10.1016/j.ijpara.2015.12.004
[32]	Li G, Lian LF, Huang SS, et al. Nomograms to predict 2-year overall survival and advanced schistosomiasis-specific survival after discharge: a competing risk analysis[J]. J Transl Med, 2020, 18(1):187. doi: 10.1186/s12967-020-02353-5
[33]	Ning A, Wu XY, Li HY, et al. Abnormal liver function in different patients with Schistosoma japonicum[J]. Parasitol Res, 2015, 114(1):85-90. doi: 10.1007/s00436-014-4163-7 pmid: 25287714
[34]	Omar HH. Impact of chronic schistosomiasis and HBV/HCV co-infection on the liver: current perspectives[J]. Hepatic Med, 2019, 11:131-136.
[35]	Xu F, Cheng RT, Miao SH, et al. Prior Toxoplasma gondii infection ameliorates liver fibrosis induced by Schistosoma japonicum through inhibiting Th2 response and improving balance of intestinal flora in mice[J]. Int J Mol Sci, 2020, 21(8):E2711.
[36]	Ding YY, Tao ZH, Wang HJ, et al. Predictive value of the red blood cell distribution width-to-platelet ratio for hepatic fibrosis[J]. Scand J Gastroenterol, 2019, 54(1):81-86. doi: 10.1080/00365521.2018.1558786
[37]	Cai PF, Mu Y, Olveda RM, et al. Circulating miRNAs as footprints for liver fibrosis grading in schistosomiasis[J]. EBioMedicine, 2018, 37:334-343. doi: 10.1016/j.ebiom.2018.10.048
[38]	Lambrecht J, Jan Poortmans P, Verhulst S, et al. Circulating ECV-associated miRNAs as potential clinical biomarkers in early stage HBV and HCV induced liver fibrosis[J]. Front Pharmacol, 2017, 8:56. doi: 10.3389/fphar.2017.00056 pmid: 28232800
[39]	Matsuura K, de Giorgi V, Schechterly C, et al. Circulating let-7 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C[J]. Hepatology, 2016, 64(3):732-745. doi: 10.1002/hep.28660 pmid: 27227815
[40]	Wu S, Tseng Y, Xu N, et al. Evaluation of transient elastography in assessing liver fibrosis in patients with advanced schistosomiasis japonica[J]. Parasitol Int, 2018, 67(3):302-308. doi: 10.1016/j.parint.2018.01.004
[41]	Carvalho Santos J, Dória Batista A, Maria Mola Vasconcelos C, et al. Liver ultrasound elastography for the evaluation of periportal fibrosis in schistosomiasis mansoni: a cross-sectional study[J]. PLoS Negl Trop Dis, 2018, 12(11):e0006868. doi: 10.1371/journal.pntd.0006868
[42]	Cheng DY, Wan G, Sun L, et al. A novel diagnostic nomogram for noninvasive evaluating liver fibrosis in patients with chronic hepatitis B virus infection[J]. Biomed Res Int, 2020, 2020:5218930.
[43]	Gatselis NK, Tornai T, Shums Z, et al. Golgi protein-73: a biomarker for assessing cirrhosis and prognosis of liver disease patients[J]. World J Gastroenterol, 2020, 26(34):5130-5145. doi: 10.3748/wjg.v26.i34.5130
[44]	Waghorn PA, Ferreira DS, Erstad DJ, et al. Quantitative, noninvasive MRI characterization of disease progression in a mouse model of non-alcoholic steatohepatitis[J]. Sci Rep, 2021, 11(1):6105. doi: 10.1038/s41598-021-85679-4 pmid: 33731798
[45]	Zhu DD, Song K, Chen JL, et al. Expression of Septin4 in Schistosoma japonicum-infected mouse livers after praziquantel treatment[J]. Parasit Vectors, 2015, 8:19. doi: 10.1186/s13071-015-0640-9
[46]	Liu JF, Kong DL, Qiu JF, et al. Praziquantel ameliorates CCl4-induced liver fibrosis in mice by inhibiting TGF-β/Smad signalling via up-regulating Smad7 in hepatic stellate cells[J]. Br J Pharmacol, 2019, 176(24):4666-4680. doi: 10.1111/bph.v176.24
[47]	Shen J, Wang LF, Peng M, et al. Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model[J]. Parasit Vectors, 2019, 12(1):457. doi: 10.1186/s13071-019-3697-z pmid: 31547847
[48]	Zheng SS, Lu Q, Xu YH, et al. GdCl3 attenuates schistosomiasis japonicum egg-induced granulomatosis accompanied by decreased macrophage infiltration in murine liver[J]. PLoS One, 2015, 10(8):e0132222. doi: 10.1371/journal.pone.0132222
[49]	Hasby Saad MA, El-Anwar N. Bevacizumab as a potential anti-angiogenic therapy in schistosomiasis: a double-edged, but adjustable weapon[J]. Parasite Immunol, 2020, 42(10):e12724.
[50]	Huang P, Zhou MY, Cheng SY, et al. Myricetin possesses anthelmintic activity and attenuates hepatic fibrosis via modulating TGFβ1 and Akt signaling and shifting Th1/Th2 balance in Schistosoma japonicum-infected mice[J]. Front Immunol, 2020, 11:593. doi: 10.3389/fimmu.2020.00593 pmid: 32373112
[51]	Boyer-Diaz Z, Aristu-Zabalza P, Andrés-Rozas M, et al. Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease[J]. J Hepatol, 2021, 74(5):1188-1199. doi: 10.1016/j.jhep.2020.11.045 pmid: 33278455
[52]	Wan CP, Jin F, Du YQ, et al. Genistein improves schistosomiasis liver granuloma and fibrosis via dampening NF-kB signaling in mice[J]. Parasitol Res, 2017, 116(4):1165-1174. doi: 10.1007/s00436-017-5392-3
[53]	Huang YZ, Lu J, Xu YL, et al. Xiaochaihu decorction relieves liver fibrosis caused by Schistosoma japonicum infection via the HSP47/TGF-β pathway[J]. Parasit Vectors, 2020, 13(1):254. doi: 10.1186/s13071-020-04121-2
[54]	Garbuzenko DV. Current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding[J]. Curr Med Res Opin, 2016, 32(3):467-475. doi: 10.1185/03007995.2015.1124846
[55]	Gunarathne LS, Rajapaksha H, Shackel N, et al. Cirrhotic portal hypertension: From pathophysiology to novel therapeutics[J]. World J Gastroenterol, 2020, 26(40):6111-6140. doi: 10.3748/wjg.v26.i40.6111
[56]	An Y, Bai ZH, Xu XB, et al. No benefit of hemostatic drugs on acute upper gastrointestinal bleeding in cirrhosis[J]. Biomed Res Int, 2020, 2020:4097170.
[57]	Toshikuni N, Takuma Y, Tsutsumi M. Management of gastroesophageal varices in cirrhotic patients: current status and future directions[J]. Ann Hepatol, 2016, 15(3):314-325. doi: 10.5604/16652681.1198800 pmid: 27049485
[58]	Wang AJ, Zheng XL, Hong JB, et al. Cap-assisted endoscopic sclerotherapy vs ligation in the long-term management of medium esophageal varices: a randomized trial[J]. Clin Transl Gastroenterol, 2020, 11(12):e00285. doi: 10.14309/ctg.0000000000000285
[59]	Wang J, Zhang XH, Zhao SL. Transparent cap-assisted endoscopic injection sclerotherapy for the treatment of patients with esophageal varices[J]. Medicine (Baltimore), 2020, 99(24):e20721. doi: 10.1097/MD.0000000000020721
[60]	Park JS, Bang BW, Hong SJ, et al. Efficacy of a novel hemostatic adhesive powder in patients with refractory upper gastrointestinal bleeding: a pilot study[J]. Endoscopy, 2019, 51(5):458-462. doi: 10.1055/a-0809-5276
[61]	Park JS, Kim HK, Shin YW, et al. Novel hemostatic adhesive powder for nonvariceal upper gastrointestinal bleeding[J]. Endosc Int Open, 2019, 7(12):E1763-E1767. doi: 10.1055/a-0982-3194
[62]	Ghoz H, Patel P, Stancampiano F, et al. Proton-pump-inhibitor use associated with lower short-term rebleeding and mortality in patients receiving esophageal variceal band ligation: a retrospective cohort study[J]. Eur J Gastroenterol Hepatol, 2020, 32(12):1571-1578. doi: 10.1097/MEG.0000000000001905
[63]	Schmidt SC, Mǒller J, Bürgel N, et al. Minimally invasive accessory splenectomy for recurrent gastric variceal bleeding due to left-sided portal hypertension: report of the first case[J]. J Surg Case Rep, 2021, 2021(2):rjab008. doi: 10.1093/jscr/rjab008
[64]	Tian GJ, Li DY, Yu HB, et al. Splenic bed laparoscopic splenectomy approach for massive splenomegaly secondary to portal hypertension and liver cirrhosis[J]. Am Surg, 2018, 84(6):1033-1038.
[65]	Piano S, Tonon M, Angeli P. Management of ascites and hepatorenal syndrome[J]. Hepatol Int, 2018, 12(Suppl 1):122-134. doi: 10.1007/s12072-017-9815-0
[66]	Xu XY, Duan ZP, Ding HG, et al. Chinese guidelines on the management of ascites and its related complications in cirrhosis[J]. Hepatol Int, 2019, 13(1):1-21.
[67]	Yosry A, Soliman ZA, Eletreby R, et al. Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: results of a pilot study[J]. Eur J Gastroenterol Hepatol, 2019, 31(3):345-351. doi: 10.1097/MEG.0000000000001277
[68]	Rai N, Singh B, Singh A, et al. Midodrine and tolvaptan in patients with cirrhosis and refractory or recurrent ascites: a randomised pilot study[J]. Liver Int, 2017, 37(3):406-414. doi: 10.1111/liv.2017.37.issue-3
[69]	Pose E, Cardenas A. Translating our current understanding of ascites management into new therapies for patients with cirrhosis and fluid retention[J]. Dig Dis Basel Switz, 2017, 35(4):402-410.
[70]	Bureau C, Thabut D, Oberti F, et al. Transjugular intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites[J]. Gastroenterology, 2017, 152(1):157-163.
[71]	Bureau C, Adebayo D, Chalret de Rieu M, et al. Alfapump^® system vs large volume paracentesis for refractory ascites: a multicenter randomized controlled study[J]. J Hepatol, 2017, 67(5):940-949.
[72]	Li G, Zhou XR, Liu JB, et al. Comparison of three data mining models for prediction of advanced schistosomiasis prognosis in the Hubei Province[J]. PLoS Negl Trop Dis, 2018, 12(2):e6262.
[73]	Fernández L, Mediano P, García R, et al. Risk factors predicting infectious lactational mastitis: decision tree approach versus logistic regression analysis[J]. Matern Child Health J, 2016, 20(9):1895-1903.
[74]	Ashour DS, Abou RD, Maher AM, et al. Hybrid feature extraction techniques for microscopic hepatic fibrosis classification[J]. Microsc Res Tech, 2018, 81(3):338-347.