直接抗病毒药物治疗对丙型肝炎患者肝外疾病预后的影响

王晓燕; 张缭云

doi:10.12449/JCH240224

直接抗病毒药物治疗对丙型肝炎患者肝外疾病预后的影响

DOI: 10.12449/JCH240224

王晓燕,
张缭云^, ,

山西医科大学第一医院感染病科，太原 030001

基金项目:

山西省科技厅重点研发计划项目 (201903D421056)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：王晓燕负责文献查找，资料分析，撰写论文；张缭云负责拟定写作思路，指导撰写文章，修改论文并最后定稿。

详细信息

通信作者:
张缭云， zlysgzy@163.com （ORCID： 0000-0002-7666-7368）

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- 被引次数: 0
出版历程
- 收稿日期: 2023-05-12
- 录用日期: 2023-06-12
- 出版日期: 2024-02-19

Effect of treatment with direct-acting antiviral agents on the prognosis of extrahepatic diseases in patients with hepatitis C

Xiaoyan WANG,
Liaoyun ZHANG^{,
,}

Department of Infectious Diseases，The First Hospital of Shanxi Medical University，Taiyuan 030001，China

Research funding:

Key R & D Projects of Department of Science and Technology of Shanxi Province (201903D421056)

More Information

Corresponding author: ZHANG Liaoyun， zlysgzy@163.com （ORCID： 0000-0002-7666-7368）

摘要

摘要: HCV感染者的预后不仅取决于肝脏病变，还取决于肝外后遗症。直接抗病毒药物（DAAs）作为当前治疗丙型肝炎的一线用药，使越来越多的患者获得持续病毒学应答及临床治愈，但其对肝外疾病转归的影响尚不清楚。本文就DAAs治疗对丙型肝炎患者肝外疾病预后的影响作一综述，提示丙型肝炎治愈患者仍需进行长期随访监测。
- 丙型肝炎 /
- 直接抗病毒药物 /
- 肝外表现
Abstract: The prognosis of patients with hepatitis C virus infection depends not only on liver lesions， but also on extrahepatic sequelae. Direct-acting antiviral agents （DAAs）， as the first-line drugs in the treatment of hepatitis C， have helped more and more patients achieve sustained virologic response and clinical cure， but its effect on the prognosis of extrahepatic diseases remains unclear. This article reviews the effect of DAAs treatment on the prognosis of extrahepatic diseases in patients with hepatitis C and points out that long-term follow-up monitoring is still required for patients with hepatitis C after cure.
- Hepatitis C /
- Direct-Acting Antiviral Agents /
- Extrahepatic Manifestations

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参考文献(48)

[1]	MESSINA JP, HUMPHREYS I, FLAXMAN A, et al. Global distribution and prevalence of hepatitis C virus genotypes[J]. Hepatology, 2015, 61( 1): 77- 87. DOI: 10.1002/hep.27259.
[2]	TERGAST TL, BLACH S, TACKE F, et al. Updated epidemiology of hepatitis C virus infections and implications for hepatitis C virus elimination in Germany[J]. J Viral Hepat, 2022, 29( 7): 536- 542. DOI: 10.1111/jvh.13680.
[3]	MADA PK, MALUS ME, PARVATHANENI A, et al. Impact of treatment with direct acting antiviral drugs on glycemic control in patients with hepatitis C and diabetes mellitus[J]. Int J Hepatol, 2020, 2020: 6438753. DOI: 10.1155/2020/6438753.
[4]	MORALES AL, JUNGA Z, SINGLA MB, et al. Hepatitis C eradication with sofosbuvir leads to significant metabolic changes[J]. World J Hepatol, 2016, 8( 35): 1557- 1563. DOI: 10.4254/wjh.v8.i35.1557.
[5]	POPESCU MS, FIRU DM, PĂDUREANU V, et al. Effects of achieving sustained virologic response after direct-acting antiviral agents on long-term liver fibrosis in diabetics vs. in non-diabetic patients with chronic hepatitis C infection[J]. Biomedicines, 2022, 10( 9): 2093. DOI: 10.3390/biomedicines10092093.
[6]	KUMAR R, GARCÍA-COMPEÁN D, MAJI T. Hepatogenous diabetes: Knowledge, evidence, and skepticism[J]. World J Hepatol, 2022, 14( 7): 1291- 1306. DOI: 10.4254/wjh.v14.i7.1291.
[7]	YAO LX, NIU B. Research progress of type 2 diabetes mellitus induced by hepatitis C virus infection[J]. Med Recapitul, 2022, 28( 6): 1186- 1192. DOI: 10.3969/j.issn.1006-2084.2022.06.026. 姚利璇, 牛奔. 丙型肝炎病毒感染诱发2型糖尿病的相关研究进展[J]. 医学综述, 2022, 28( 6): 1186- 1192. DOI: 10.3969/j.issn.1006-2084.2022.06.026.
[8]	XU LZ, ZUO WZ. Relationship between serum HCV-RNA load and FPG, FA, HbA1C in patients with chronic hepatitis C complicated with diabetes mellitus[J]. Shandong Med J, 2015, 55( 12): 80- 81. DOI: 10.3969/j.issn.1002-266X.2015.12.033. 徐兰芝, 左维泽. 慢性丙型病毒性肝炎合并糖尿病患者血清HCV-RNA载量与FPG、FA、HbA1C的关系[J]. 山东医药, 2015, 55( 12): 80- 81. DOI: 10.3969/j.issn.1002-266X.2015.12.033.
[9]	MAHMOUD B, ABDEL MONEIM A, MABROUK D. The impact of HCV eradication on hyperglycemia, insulin resistance, cytokine production, and insulin receptor substrate-1 and 2 expression in patients with HCV infection[J]. Clin Exp Med, 2022, 22( 4): 583- 593. DOI: 10.1007/s10238-021-00773-1.
[10]	ABDEL MONEIM A, SULEIMAN HA, MAHMOUD B, et al. Viral clearance ameliorates hematological and inflammatory markers among diabetic patients infected with hepatitis C genotype 4[J]. Clin Exp Med, 2020, 20( 2): 231- 240. DOI: 10.1007/s10238-019-00605-3.
[11]	LAPUMNUAYPOL K, PISARCIK D, PUTTHAPIBAN P, et al. Direct-acting antiviral agents decrease haemoglobin A1c level in patients with diabetes infected with hepatitis C virus: A systematic review& meta-analysis[J]. Indian J Med Res, 2020, 152( 6): 562- 567. DOI: 10.4103/ijmr.IJMR_1088_18.
[12]	WEIDNER P, BOETTCHE D, ZIMMERER T, et al. Impact of direct acting antiviral(DAA) treatment on glucose metabolism and reduction of pre-diabetes in patients with chronic hepatitis C[J]. J Gastrointestin Liver Dis, 2018, 27( 3): 281- 289. DOI: 10.15403/jgld.2014.1121.273.daa.
[13]	CACCIOLA I, RUSSO G, FILOMIA R, et al. Over time evaluation of glycaemic control in direct-acting antiviral-treated hepatitis C virus/diabetic individuals with chronic hepatitis or with cirrhosis[J]. Liver Int, 2021, 41( 9): 2059- 2067. DOI: 10.1111/liv.14905.
[14]	DOYLE MA, GALANAKIS C, MULVIHILL E, et al. Hepatitis C direct acting antivirals and ribavirin modify lipid but not glucose parameters[J]. Cells, 2019, 8( 3): 252. DOI: 10.3390/cells8030252.
[15]	DAWOOD AA, NOOH MZ, ELGAMAL AA. Factors associated with improved glycemic control by direct-acting antiviral agent treatment in Egyptian type 2 diabetes mellitus patients with chronic hepatitis C genotype 4[J]. Diabetes Metab J, 2017, 41( 4): 316- 321. DOI: 10.4093/dmj.2017.41.4.316.
[16]	GRAF C, WELZEL T, BOGDANOU D, et al. Hepatitis C clearance by direct-acting antivirals impacts glucose and lipid homeostasis[J]. J Clin Med, 2020, 9( 9): 2702. DOI: 10.3390/jcm9092702.
[17]	GILAD A, FRICKER ZP, HSIEH A, et al. Sustained improvement in type 2 diabetes mellitus is common after treatment of hepatitis C virus with direct-acting antiviral therapy[J]. J Clin Gastroenterol, 2019, 53( 8): 616- 620. DOI: 10.1097/MCG.0000000000001168.
[18]	CIANCIO A, BOSIO R, BO S, et al. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents[J]. J Med Virol, 2018, 90( 2): 320- 327. DOI: 10.1002/jmv.24954.
[19]	LI J, GORDON SC, RUPP LB, et al. Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes[J]. Aliment Pharmacol Ther, 2019, 49( 5): 599- 608. DOI: 10.1111/apt.15102.
[20]	KOENIG LR, ROSENBLATT R, PATEL RM, et al. Comorbid hepatitis C does not modulate prevalence or severity of diabetic retinopathy[J]. Clin Ophthalmol, 2019, 13: 1681- 1687. DOI: 10.2147/OPTH.S209274.
[21]	LI J, GORDON SC, RUPP LB, et al. Sustained virological response does not improve long-term glycaemic control in patients with type 2 diabetes and chronic hepatitis C[J]. Liver Int, 2019, 39( 6): 1027- 1032. DOI: 10.1111/liv.14031.
[22]	TRIFAN A, STRATINA E, ROTARU A, et al. Changes in liver steatosis using controlled attenuation parameter among patients with chronic hepatitis C infection treated with direct-acting antivirals therapy who achieved sustained virological response[J]. Diagnostics(Basel), 2022, 12( 3): 702. DOI: 10.3390/diagnostics12030702.
[23]	OGASAWARA N, KOBAYASHI M, AKUTA N, et al. Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b[J]. J Med Virol, 2018, 90( 2): 313- 319. DOI: 10.1002/jmv.24950.
[24]	ROUT G, NAYAK B, PATEL AH, et al. Therapy with oral directly acting agents in hepatitis C infection is associated with reduction in fibrosis and increase in hepatic steatosis on transient elastography[J]. J Clin Exp Hepatol, 2019, 9( 2): 207- 214. DOI: 10.1016/j.jceh.2018.06.009.
[25]	CASAS-DEZA D, MARTÍNEZ-SAPIÑA A, ESPINA S, et al. Evaluation of cardiovascular risk factors after hepatitis C virus eradication with direct-acting antivirals in a cohort of treatment-Naïve patients without history of cardiovascular disease[J]. J Clin Med, 2022, 11( 14): 4049. DOI: 10.3390/jcm11144049.
[26]	HUANG CF, DAI CY, YEH ML, et al. Cure or curd: Modification of lipid profiles and cardio-cerebrovascular events after hepatitis C virus eradication[J]. Kaohsiung J Med Sci, 2020, 36( 11): 920- 928. DOI: 10.1002/kjm2.12275.
[27]	RAMADAN MS, BOCCIA F, MORETTO SM, et al. Cardiovascular risk in patients with chronic hepatitis C treated with direct acting antivirals[J]. J Clin Med, 2022, 11( 19): 5781. DOI: 10.3390/jcm11195781.
[28]	KAWAGISHI N, SUDA G, NAKAMURA A, et al. Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis[J]. PLoS One, 2018, 13( 12): e0209615. DOI: 10.1371/journal.pone.0209615.
[29]	SCHMIDT FP, ZIMMERMANN T, WENZ T, et al. Interferon- and ribavirin-free therapy with new direct acting antivirals(DAA) for chronic hepatitis C improves vascular endothelial function[J]. Int J Cardiol, 2018, 271: 296- 300. DOI: 10.1016/j.ijcard.2018.04.058.
[30]	FREEKH DA, HELMY MW, SAID M, et al. The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection[J]. Saudi Pharm J, 2021, 29( 10): 1120- 1128. DOI: 10.1016/j.jsps.2021.08.006.
[31]	MUÑOZ-HERNÁNDEZ R, AMPUERO J, MILLÁN R, et al. Hepatitis C virus clearance by direct-acting antivirals agents improves endothelial dysfunction and subclinical atherosclerosis: HEPCAR study[J]. Clin Transl Gastroenterol, 2020, 11( 8): e00203. DOI: 10.14309/ctg.0000000000000203.
[32]	DI MINNO MND, AMBROSINO P, BUONOMO AR, et al. Direct-acting antivirals improve endothelial function in patients with chronic hepatitis: A prospective cohort study[J]. Intern Emerg Med, 2020, 15( 2): 263- 271. DOI: 10.1007/s11739-019-02163-8.
[33]	PETTA S, ADINOLFI LE, FRACANZANI AL, et al. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis[J]. J Hepatol, 2018, 69( 1): 18- 24. DOI: 10.1016/j.jhep.2018.02.015.
[34]	REVUELTO ARTIGAS T, BETRIU BARS À, ZARAGOZA VELASCO N, et al. Antiviral treatment does not improve subclinical atheromatosis in patients with chronic hepatitis caused by hepatitis C virus[J]. Gastroenterol Hepatol, 2019, 42( 6): 362- 371. DOI: 10.1016/j.gastrohep.2019.02.002.
[35]	CALVARUSO V, PETTA S, CACCIOLA I, et al. Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort[J]. J Viral Hepat, 2021, 28( 8): 1190- 1199. DOI: 10.1111/jvh.13523.
[36]	YANG YH, CHIANG HJ, YIP HK, et al. Risk of new-onset atrial fibrillation among Asian chronic hepatitis C virus carriers: A nationwide population-based cohort study[J]. J Am Heart Assoc, 2019, 8( 22): e012914. DOI: 10.1161/JAHA.119.012914.
[37]	POL S, PARLATI L, JADOUL M. Hepatitis C virus and the kidney[J]. Nat Rev Nephrol, 2019, 15( 2): 73- 86. DOI: 10.1038/s41581-018-0081-8.
[38]	MA Y, HUANG Z, JIAN Z, et al. The association between hepatitis C virus infection and renal cell cancer, prostate cancer, and bladder cancer: A systematic review and meta-analysis[J]. Sci Rep, 2021, 11: 10833. DOI: 10.1038/s41598-021-90404-2.
[39]	TANG MZ, ZHANG KQ. Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts[J]. Ogran Transplant, 2023, 14( 2): 235- 240. DOI: 10.3969/j.issn.1674-7445.2023.02.009. 唐茂芝, 张克勤. HCV阴性受者接受HCV阳性供肾肾移植临床研究现状[J]. 器官移植, 2023, 14( 2): 235- 240. DOI: 10.3969/j.issn.1674-7445.2023.02.009.
[40]	RIDRUEJO E, GARCIA-AGUDO R, MENDIZABAL M, et al. Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease[J]. Nefrologia(Engl Ed), 2020, 40( 1): 46- 52. DOI: 10.1016/j.nefro.2019.03.013.
[41]	NEVOLA R, RINALDI L, ZENI L, et al. Metabolic and renal changes in patients with chronic hepatitis C infection after hepatitis C virus clearance by direct-acting antivirals[J]. JGH Open, 2020, 4( 4): 713- 721. DOI: 10.1002/jgh3.12324.
[42]	VILLANI R, ROMANO AD, SANGINETO M, et al. Direct-acting antivirals improve kidney function in diabetic patients with HCV infection and chronic kidney disease[J]. Intern Emerg Med, 2021, 16( 5): 1239- 1245. DOI: 10.1007/s11739-020-02628-1.
[43]	de CASTRO GLC, da SILVA GRAÇA AMORAS E, ARAÚJO MS, et al. High prevalence of antinuclear antibodies in patients with chronic hepatitis C virus infection[J]. Eur J Med Res, 2022, 27( 1): 180. DOI: 10.1186/s40001-022-00809-6.
[44]	ROMANO C, TORTORELLA O, DALLA MORA L, et al. Prevalence and outcome of serum autoantibodies in chronic hepatitis C patients undergoing direct-acting antiviral treatment[J]. Front Immunol, 2022, 13: 882064. DOI: 10.3389/fimmu.2022.882064.
[45]	BONACCI M, LENS S, MARIÑO Z, et al. Long-term outcomes of patients with HCV-associated cryoglobulinemic vasculitis after virologic cure[J]. Gastroenterology, 2018, 155( 2): 311- 315. DOI: 10.1053/j.gastro.2018.04.024.
[46]	TERZIROLI BERETTA-PICCOLI B, DI BARTOLOMEO C, DELEONARDI G, et al. Autoimmune liver serology before and after successful treatment of chronic hepatitis C by direct acting antiviral agents[J]. J Autoimmun, 2019, 102: 89- 95. DOI: 10.1016/j.jaut.2019.04.019.
[47]	FACCIOLI J, NARDELLI S, GIOIA S, et al. Neurological and psychiatric effects of hepatitis C virus infection[J]. World J Gastroenterol, 2021, 27( 29): 4846- 4861. DOI: 10.3748/wjg.v27.i29.4846.
[48]	KLEEFELD F, HELLER S, INGILIZ P, et al. Interferon-free therapy in hepatitis C virus(HCV) monoinfected and HCV/HIV coinfected patients: Effect on cognitive function, fatigue, and mental health[J]. J Neurovirol, 2018, 24( 5): 557- 569. DOI: 10.1007/s13365-018-0647-z.