Skip to main content

Advertisement

SpringerLink
Log in

Human genetics of HCV infection phenotypes in the era of direct-acting antivirals

  • Review
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

The recent introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C virus (HCV) therapy by improving virus eradication rates to over 90% in most patient groups. However, the impact of DAAs on global disease burden is currently limited, and a large number of chronically infected individuals remain at risk of developing liver complications, such as liver cirrhosis and hepatocellular carcinoma (HCC). The identification of patients at risk of liver complications and a greater understanding of the biological mechanisms involved in HCV disease progression might improve disease control. Recent genome-wide association and exome sequencing studies have identified several host genetic variants influencing the progression of liver fibrosis and the development of HCC associated with HCV infection and are reviewed here. Interestingly, some of the genetic variants associated with those HCV-associated liver complications were also associated with the clinical course of non-viral chronic hepatitis. Future challenges include the incorporation of this genetic information into clinical risk models for personalized disease management and the study of emerging phenotypes such as liver fibrosis regression and HCC development after HCV eradication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • About F, Oudot-Mellakh T, Niay J, Rabiega P, Pedergnana V, Duffy D, Sultanik P, Cagnot C, Carrat F, Marcellin P, Zoulim F, Larrey D, Hezode C, Fontaine H, Bronowicki JP, Pol S, Albert ML, Theodorou I, Cobat A, Abel L, Group ACCs (2015) Impact of IL28B, APOH and ITPA polymorphisms on efficacy and safety of TVR- or BOC-based triple therapy in treatment-experienced HCV-1 patients with compensated cirrhosis from the ANRS CO20-CUPIC study. PLoS ONE 10:e0145105. https://doi.org/10.1371/journal.pone.0145105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • About F, Abel L, Cobat A (2018) HCV-associated liver fibrosis and HSD17B13. N Engl J Med 379:1875–1876. https://doi.org/10.1056/NEJMc1804638

    Article  PubMed  Google Scholar 

  • About F, Bibert S, Jouanguy E, Nalpas B, Lorenzo L, Rattina V, Zarhrate M, Hanein S, Munteanu M, Mullhaupt B, Semela D, Semmo N, Casanova JL, Theodorou I, Sultanik P, Poynard T, Pol S, Bochud PY, Cobat A, Abel L, Swiss Hepatitis CCSG, French AHCEPGSG (2019) Identification of an endoglin variant associated with HCV-related liver fibrosis progression by next-generation sequencing. Front Genet 10:1024. https://doi.org/10.3389/fgene.2019.01024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, Stevis P, Liu Y, Kozlitina J, Stender S, Wood GC, Stepanchick AN, Still MD, McCarthy S, O'Dushlaine C, Packer JS, Balasubramanian S, Gosalia N, Esopi D, Kim SY, Mukherjee S, Lopez AE, Fuller ED, Penn J, Chu X, Luo JZ, Mirshahi UL, Carey DJ, Still CD, Feldman MD, Small A, Damrauer SM, Rader DJ, Zambrowicz B, Olson W, Murphy AJ, Borecki IB, Shuldiner AR, Reid JG, Overton JD, Yancopoulos GD, Hobbs HH, Cohen JC, Gottesman O, Teslovich TM, Baras A, Mirshahi T, Gromada J, Dewey FE (2018) A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med 378:1096–1106. https://doi.org/10.1056/NEJMoa1712191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akuta N, Suzuki F, Fukushima T, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Hara T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H (2013) Prediction of treatment efficacy and telaprevir-resistant variants after triple therapy in patients infected with hepatitis C virus genotype 1. J Clin Microbiol 51:2862–2868. https://doi.org/10.1128/JCM.01129-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ali M, Yopp A, Gopal P, Beg MS, Zhu H, Lee W, Singal AG (2016) A variant in PNPLA3 associated with fibrosis progression but not hepatocellular carcinoma in patients with hepatitis C virus infection. Clin Gastroenterol Hepatol 14:295–300. https://doi.org/10.1016/j.cgh.2015.08.018

    Article  CAS  PubMed  Google Scholar 

  • Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729

    Article  CAS  PubMed  Google Scholar 

  • Bibert S, Roger T, Calandra T, Bochud M, Cerny A, Semmo N, Duong FH, Gerlach T, Malinverni R, Moradpour D, Negro F, Mullhaupt B, Bochud PY, Swiss Hepatitis CCS (2013) IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med 210:1109–1116. https://doi.org/10.1084/jem.20130012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bochud PY, Bibert S, Kutalik Z, Patin E, Guergnon J, Nalpas B, Goossens N, Kuske L, Mullhaupt B, Gerlach T, Heim MH, Moradpour D, Cerny A, Malinverni R, Regenass S, Dollenmaier G, Hirsch H, Martinetti G, Gorgiewski M, Bourliere M, Poynard T, Theodorou I, Abel L, Pol S, Dufour JF, Negro F, Swiss Hepatitis CCSG, Group AHEGS (2012) IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatology 55:384–394. https://doi.org/10.1002/hep.24678

    Article  CAS  PubMed  Google Scholar 

  • Bourliere M, Pietri O (2019) Hepatitis C virus therapy: No one will be left behind. Int J Antimicrob Agents 53:755–760. https://doi.org/10.1016/j.ijantimicag.2018.12.010

    Article  CAS  PubMed  Google Scholar 

  • Burza MA, Motta BM, Mancina RM, Pingitore P, Pirazzi C, Lepore SM, Spagnuolo R, Doldo P, Russo C, Lazzaro V, Fischer J, Berg T, Aghemo A, Cheroni C, De Francesco R, Fargion S, Colombo M, Datz C, Stickel F, Valenti L, Romeo S (2016) DEPDC5 variants increase fibrosis progression in Europeans with chronic hepatitis C virus infection. Hepatology 63:418–427. https://doi.org/10.1002/hep.28322

    Article  CAS  PubMed  Google Scholar 

  • Chayama K, Hayes CN, Abe H, Miki D, Ochi H, Karino Y, Toyota J, Nakamura Y, Kamatani N, Sezaki H, Kobayashi M, Akuta N, Suzuki F, Kumada H (2011) IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C. J Infect Dis 204:84–93. https://doi.org/10.1093/infdis/jir210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chhatwal J, Wang X, Ayer T, Kabiri M, Chung RT, Hur C, Donohue JM, Roberts MS, Kanwal F (2016) Hepatitis C disease burden in the United States in the era of oral direct-acting antivirals. Hepatology 64:1442–1450. https://doi.org/10.1002/hep.28571

    Article  CAS  PubMed  Google Scholar 

  • Duggal P, Thio CL, Wojcik GL, Goedert JJ, Mangia A, Latanich R, Kim AY, Lauer GM, Chung RT, Peters MG, Kirk GD, Mehta SH, Cox AL, Khakoo SI, Alric L, Cramp ME, Donfield SM, Edlin BR, Tobler LH, Busch MP, Alexander G, Rosen HR, Gao X, Abdel-Hamid M, Apps R, Carrington M, Thomas DL (2013) Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts. Ann Intern Med 158:235–245. https://doi.org/10.7326/0003-4819-158-4-201302190-00003

    Article  PubMed  PubMed Central  Google Scholar 

  • Eslam M, Hashem AM, Leung R, Romero-Gomez M, Berg T, Dore GJ, Chan HL, Irving WL, Sheridan D, Abate ML, Adams LA, Mangia A, Weltman M, Bugianesi E, Spengler U, Shaker O, Fischer J, Mollison L, Cheng W, Powell E, Nattermann J, Riordan S, McLeod D, Armstrong NJ, Douglas MW, Liddle C, Booth DR, George J, Ahlenstiel G, International Hepatitis CGC (2015) Interferon-lambda rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease. Nat Commun 6:6422. https://doi.org/10.1038/ncomms7422

    Article  CAS  PubMed  Google Scholar 

  • Eslam M, McLeod D, Kelaeng KS, Mangia A, Berg T, Thabet K, Irving WL, Dore GJ, Sheridan D, Gronbaek H, Abate ML, Hartmann R, Bugianesi E, Spengler U, Rojas A, Booth DR, Weltman M, Mollison L, Cheng W, Riordan S, Mahajan H, Fischer J, Nattermann J, Douglas MW, Liddle C, Powell E, Romero-Gomez M, George J, International Liver Disease Genetics C (2017) IFN-lambda3, not IFN-lambda4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis. Nat Genet 49:795–800. https://doi.org/10.1038/ng.3836

    Article  CAS  PubMed  Google Scholar 

  • Farhang Zangneh H, Wong WWL, Sander B, Bell CM, Mumtaz K, Kowgier M, van der Meer AJ, Cleary SP, Janssen HLA, Chan KKW, Feld JJ (2019) cost effectiveness of hepatocellular carcinoma surveillance after a sustained virologic response to therapy in patients with hepatitis C virus infection and advanced fibrosis. Clin Gastroenterol Hepatol 17(1840–1849):e16. https://doi.org/10.1016/j.cgh.2018.12.018

    Article  Google Scholar 

  • Franco S, Aparicio E, Parera M, Clotet B, Tural C, Martinez MA (2014) IFNL4 ss469415590 variant is a better predictor than rs12979860 of pegylated interferon-alpha/ribavirin therapy failure in hepatitis C virus/HIV-1 coinfected patients. AIDS 28:133–136. https://doi.org/10.1097/QAD.0000000000000052

    Article  CAS  PubMed  Google Scholar 

  • Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401. https://doi.org/10.1038/nature08309

    Article  CAS  PubMed  Google Scholar 

  • WHO (2017) Global Hepatitis Report 2017. World Health Organization, Geneva. Licence: CC BY-NC-SA 3.0 IGO

  • Goossens N, Singal AG, King LY, Andersson KL, Fuchs BC, Besa C, Taouli B, Chung RT, Hoshida Y (2017) Cost-effectiveness of risk score-stratified hepatocellular carcinoma screening in patients with cirrhosis. Clin Transl Gastroenterol 8:e101. https://doi.org/10.1038/ctg.2017.26

    Article  PubMed  PubMed Central  Google Scholar 

  • Hajarizadeh B, Grebely J, Dore GJ (2013) Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 10:553–562. https://doi.org/10.1038/nrgastro.2013.107

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K (2011) Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet 43:455–458

    Article  CAS  PubMed  Google Scholar 

  • Lee MH, Huang YH, Chen HY, Khor SS, Chang YH, Lin YJ, Jen CL, Lu SN, Yang HI, Nishida N, Sugiyama M, Mizokami M, Yuan Y, L'Italien G, Tokunaga K, Chen CJ, Group R-HCS (2018) Human leukocyte antigen variants and risk of hepatocellular carcinoma modified by hepatitis C virus genotypes: a genome-wide association study. Hepatology 67:651–661. https://doi.org/10.1002/hep.29531

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, Gores G (2016) Hepatocellular carcinoma. Nat Rev Dis Primers 2:16018. https://doi.org/10.1038/nrdp.2016.18

    Article  PubMed  Google Scholar 

  • Marshall AD, Pawlotsky JM, Lazarus JV, Aghemo A, Dore GJ, Grebely J (2018) The removal of DAA restrictions in Europe—one step closer to eliminating HCV as a major public health threat. J Hepatol 69:1188–1196. https://doi.org/10.1016/j.jhep.2018.06.016

    Article  PubMed  Google Scholar 

  • Matsuura K, Sawai H, Ikeo K, Ogawa S, Iio E, Isogawa M, Shimada N, Komori A, Toyoda H, Kumada T, Namisaki T, Yoshiji H, Sakamoto N, Nakagawa M, Asahina Y, Kurosaki M, Izumi N, Enomoto N, Kusakabe A, Kajiwara E, Itoh Y, Ide T, Tamori A, Matsubara M, Kawada N, Shirabe K, Tomita E, Honda M, Kaneko S, Nishina S, Suetsugu A, Hiasa Y, Watanabe H, Genda T, Sakaida I, Nishiguchi S, Takaguchi K, Tanaka E, Sugihara J, Shimada M, Kondo Y, Kawai Y, Kojima K, Nagasaki M, Tokunaga K, Tanaka Y, Japanese Genome-Wide Association Study Group for Viral H (2017) Genome-wide association study identifies TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus infection. Gastroenterology 152:1383–1394. https://doi.org/10.1053/j.gastro.2017.01.041

    Article  CAS  PubMed  Google Scholar 

  • Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, Ikeda K, Kumada H, Toyota J, Morizono T, Tsunoda T, Kubo M, Nakamura Y, Kamatani N, Chayama K (2011) Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet 43:797–800

    Article  CAS  PubMed  Google Scholar 

  • Musso G, Cassader M, De Michieli F, Paschetta E, Pinach S, Saba F, Bongiovanni D, Framarin L, Berrutti M, Leone N, Corvisieri S, Parente R, Molinaro F, Sircana A, Bo S, Gambino R (2017) MERTK rs4374383 variant predicts incident nonalcoholic fatty liver disease and diabetes: role of mononuclear cell activation and adipokine response to dietary fat. Hum Mol Genet 26:1785. https://doi.org/10.1093/hmg/ddx126

    Article  CAS  PubMed  Google Scholar 

  • Nahon P, Bourcier V, Layese R, Audureau E, Cagnot C, Marcellin P, Guyader D, Fontaine H, Larrey D, De Ledinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Leroy V, Riachi G, Cales P, Peron JM, Alric L, Bourliere M, Mathurin P, Dharancy S, Blanc JF, Abergel A, Serfaty L, Mallat A, Grange JD, Attali P, Bacq Y, Wartelle C, Dao T, Benhamou Y, Pilette C, Silvain C, Christidis C, Capron D, Bernard-Chabert B, Zucman D, Di Martino V, Thibaut V, Salmon D, Ziol M, Sutton A, Pol S, Roudot-Thoraval F, Group ACC (2017) Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 152(142–156):e2. https://doi.org/10.1053/j.gastro.2016.09.009

    Article  Google Scholar 

  • Nahon P, Layese R, Bourcier V, Cagnot C, Marcellin P, Guyader D, Pol S, Larrey D, De Ledinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Riachi G, Cales P, Peron JM, Alric L, Bourliere M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grange JD, Attali P, Bacq Y, Wartelle C, Dao T, Thabut D, Pilette C, Silvain C, Christidis C, Nguyen-Khac E, Bernard-Chabert B, Zucman D, Di Martino V, Sutton A, Roudot-Thoraval F, Audureau E, Group ACC (2018) Incidence of hepatocellular carcinoma after direct antiviral therapy for HCV in patients with cirrhosis included in surveillance programs. Gastroenterology 155(1436–1450):e6. https://doi.org/10.1053/j.gastro.2018.07.015

    Article  Google Scholar 

  • Nahon P, Zucman-Rossi J (2012) Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J Hepatol 57:663–674

    Article  CAS  PubMed  Google Scholar 

  • O'Brien TR, Lang Kuhs KA, Pfeiffer RM (2014) Subgroup differences in response to 8 weeks of ledipasvir/sofosbuvir for chronic hepatitis C. Open Forum Infect Dis. https://doi.org/10.1093/ofid/ofu110

    Article  PubMed  PubMed Central  Google Scholar 

  • O'Brien TR, Kottilil S, Feld JJ, Morgan TR, Pfeiffer RM (2017a) Race or genetic makeup for hepatitis C virus treatment decisions? Hepatology 65:2124–2125. https://doi.org/10.1002/hep.29057

    Article  PubMed  Google Scholar 

  • O'Brien TR, Kottilil S, Pfeiffer RM (2017b) IFNL4 genotype is associated with virologic relapse after 8-week treatment with Sofosbuvir, Velpatasvir, and Voxilaprevir. Gastroenterology 153:1694–1695. https://doi.org/10.1053/j.gastro.2017.06.069

    Article  PubMed  Google Scholar 

  • Patin E, Kutalik Z, Guergnon J, Bibert S, Nalpas B, Jouanguy E, Munteanu M, Bousquet L, Argiro L, Halfon P, Boland A, Mullhaupt B, Semela D, Dufour JF, Heim MH, Moradpour D, Cerny A, Malinverni R, Hirsch H, Martinetti G, Suppiah V, Stewart G, Booth DR, George J, Casanova JL, Brechot C, Rice CM, Talal AH, Jacobson IM, Bourliere M, Theodorou I, Poynard T, Negro F, Pol S, Bochud PY, Abel L, Swiss Hepatitis C Cohort Study Group IHCGC, French AHCEPGSG (2012) Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection. Gastroenterology 143(1244–1252):e12. https://doi.org/10.1053/j.gastro.2012.07.097

    Article  CAS  Google Scholar 

  • Peng Q, Lao X, Chen Z, Lai H, Deng Y, Wang J, Mo C, Sui J, Wu J, Zhai L, Yang S, Qin X, Li S (2013) TP53 and MDM2 gene polymorphisms, gene–gene interaction, and hepatocellular carcinoma risk: evidence from an updated meta-analysis. PLoS ONE 8:e82773. https://doi.org/10.1371/journal.pone.0082773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petta S, Valenti L, Marra F, Grimaudo S, Tripodo C, Bugianesi E, Camma C, Cappon A, Di Marco V, Di Maira G, Dongiovanni P, Rametta R, Gulino A, Mozzi E, Orlando E, Maggioni M, Pipitone RM, Fargion S, Craxi A (2016) MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease. J Hepatol 64:682–690. https://doi.org/10.1016/j.jhep.2015.10.016

    Article  CAS  PubMed  Google Scholar 

  • Petta S, Valenti L, Tuttolomondo A, Dongiovanni P, Pipitone RM, Camma C, Cabibi D, Di Marco V, Fracanzani AL, Badiali S, Nobili V, Fargion S, Grimaudo S, Craxi A (2017) Interferon lambda 4 rs368234815 TT%3edeltaG variant is associated with liver damage in patients with nonalcoholic fatty liver disease. Hepatology 66:1885–1893. https://doi.org/10.1002/hep.29395

    Article  CAS  PubMed  Google Scholar 

  • Pol S, Lagaye S (2019) The remarkable history of the hepatitis C virus. Microbes Infect. https://doi.org/10.1016/j.micinf.2019.06.008

    Article  PubMed  Google Scholar 

  • Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, Dickensheets H, Hergott D, Porter-Gill P, Mumy A, Kohaar I, Chen S, Brand N, Tarway M, Liu L, Sheikh F, Astemborski J, Bonkovsky HL, Edlin BR, Howell CD, Morgan TR, Thomas DL, Rehermann B, Donnelly RP, O'Brien TR (2013) A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 45:164–171. https://doi.org/10.1038/ng.2521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramamurthy N, Marchi E, Ansari MA, Pedergnana V, McLean A, Hudson E, Consortium SH, Bowden R, Spencer CCA, Barnes E, Klenerman P (2018) Impact of IFNL4 genotype on Interferon-stimulated gene expression during DAA therapy for hepatitis C. Hepatology. https://doi.org/10.1002/hep.29877

    Article  PubMed  Google Scholar 

  • Rauch A, Kutalik Z, Descombes P, Cai T, Di Iulio J, Mueller T, Bochud M, Battegay M, Bernasconi E, Borovicka J, Colombo S, Cerny A, Dufour JF, Furrer H, Gunthard HF, Heim M, Hirschel B, Malinverni R, Moradpour D, Mullhaupt B, Witteck A, Beckmann JS, Berg T, Bergmann S, Negro F, Telenti A, Bochud PY (2010) Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 138:1338–1345. https://doi.org/10.1053/j.gastro.2009.12.056(1345 e1–7)

    Article  CAS  PubMed  Google Scholar 

  • Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH (2008) Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40:1461–1465. https://doi.org/10.1038/ng.257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rothlin CV, Carrera-Silva EA, Bosurgi L, Ghosh S (2015) TAM receptor signaling in immune homeostasis. Annu Rev Immunol 33:355–391. https://doi.org/10.1146/annurev-immunol-032414-112103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rueger S, Bochud PY, Dufour JF, Mullhaupt B, Semela D, Heim MH, Moradpour D, Cerny A, Malinverni R, Booth DR, Suppiah V, George J, Argiro L, Halfon P, Bourliere M, Talal AH, Jacobson IM, Patin E, Nalpas B, Poynard T, Pol S, Abel L, Kutalik Z, Negro F (2015) Impact of common risk factors of fibrosis progression in chronic hepatitis C. Gut 64:1605–1615. https://doi.org/10.1136/gutjnl-2014-306997

    Article  CAS  PubMed  Google Scholar 

  • Salmon D, Mondelli MU, Maticic M, Arends JE, Hepatitis ESGfV (2018) The benefits of hepatitis C virus cure: every rose has thorns. J Viral Hepat 25:320–328. https://doi.org/10.1111/jvh.12823

    Article  CAS  PubMed  Google Scholar 

  • Sato M, Kondo M, Tateishi R, Fujiwara N, Kato N, Yoshida H, Taguri M, Koike K (2014) Impact of IL28B genetic variation on HCV-induced liver fibrosis, inflammation, and steatosis: a meta-analysis. PLoS ONE 9:e91822. https://doi.org/10.1371/journal.pone.0091822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherman M (2017) HCC risk scores: useful or not? Semin Liver Dis 37:287–295. https://doi.org/10.1055/s-0037-1607452

    Article  PubMed  Google Scholar 

  • Sterling RK, Kuo A, Rustgi VK, Sulkowski MS, Stewart TG, Fenkel JM, El-Genaidi H, Mah'moud MA, Abraham GM, Stewart PW, Akushevich L, Nelson DR, Fried MW, Di Bisceglie AM (2015) Virological outcomes and treatment algorithms utilisation in observational study of patients with chronic hepatitis C treated with boceprevir or telaprevir. Aliment Pharmacol Ther 41:671–685. https://doi.org/10.1111/apt.13095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Muller T, Bahlo M, Stewart GJ, Booth DR, George J (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41:1100–1104. https://doi.org/10.1038/ng.447

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41:1105–1109. https://doi.org/10.1038/ng.449

    Article  CAS  PubMed  Google Scholar 

  • Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798–801. https://doi.org/10.1038/nature08463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG (2010) Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 139(120–9):e18. https://doi.org/10.1053/j.gastro.2010.04.013

    Article  CAS  Google Scholar 

  • Trepo E, Franchimont D, Moreno C (2011) Association of PNPLA3 (rs738409 C%3eG) with liver damage in liver diseases: one step closer to personalized medicine? Per Med 8:595–597. https://doi.org/10.2217/pme.11.66

    Article  CAS  PubMed  Google Scholar 

  • Tsubota A, Shimada N, Atsukawa M, Abe H, Kato K, Ika M, Matsudaira H, Nagatsuma K, Matsuura T, Aizawa Y (2014) Impact of IL28B polymorphisms on 24-week telaprevir-based combination therapy for Asian chronic hepatitis C patients with hepatitis C virus genotype 1b. J Gastroenterol Hepatol 29:144–150. https://doi.org/10.1111/jgh.12402

    Article  CAS  PubMed  Google Scholar 

  • Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG (2018) Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 154(1706–1718):e1. https://doi.org/10.1053/j.gastro.2018.01.064

    Article  CAS  Google Scholar 

  • Ulveling D, Le Clerc S, Cobat A, Labib T, Noirel J, Laville V, Coulonges C, Carpentier W, Nalpas B, Heim MH, Poynard T, Cerny A, Pol S, Bochud PY, Dabis F, Theodorou I, Levy Y, Salmon D, Abel L, Dominguez S, Zagury JF, Group HACCS, Swiss Hepatitis CCSG, French AHCEPGSG (2016) A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus-coinfected patients. Hepatology 64:1462–1472. https://doi.org/10.1002/hep.28695

    Article  CAS  PubMed  Google Scholar 

  • Urabe Y, Ochi H, Kato N, Kumar V, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Lo PH, Tanikawa C, Omata M, Koike K, Miki D, Abe H, Kamatani N, Toyota J, Kumada H, Kubo M, Chayama K, Nakamura Y, Matsuda K (2013) A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. J Hepatol 58:875–882. https://doi.org/10.1016/j.jhep.2012.12.024

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Cao H, Xu Z, Wang D, Zeng Y (2019) SNP rs2596542G%3eA in MICA is associated with risk of hepatocellular carcinoma: a meta-analysis. Biosci Rep. https://doi.org/10.1042/BSR20181400

    Article  PubMed  PubMed Central  Google Scholar 

  • Wiktor S (2019) How feasible is the global elimination of HCV infection? Lancet 393:1265–1267. https://doi.org/10.1016/S0140-6736(18)32750-8

    Article  PubMed  Google Scholar 

  • Wray NR, Yang J, Hayes BJ, Price AL, Goddard ME, Visscher PM (2013) Pitfalls of predicting complex traits from SNPs. Nat Rev Genet 14:507–515. https://doi.org/10.1038/nrg3457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasui K, Kawaguchi T, Shima T, Mitsuyoshi H, Seki K, Sendo R, Mizuno M, Itoh Y, Matsuda F, Okanoue T (2015) Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C. J Gastroenterol 50:887–893. https://doi.org/10.1007/s00535-014-1018-z

    Article  CAS  PubMed  Google Scholar 

  • Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149(1226–1239):e4. https://doi.org/10.1053/j.gastro.2015.05.061

    Article  CAS  Google Scholar 

Download references

Acknowledgement

We thank Laurent Abel, Jean-Laurent Casanova and both branches of the Laboratory of Human Genetics of Infectious Diseases for helpful discussion and support. The Necker branch of the Laboratory of Human Genetics of Infectious Diseases is supported by The National Agency for Research on AIDS and Viral Hepatitis (ANRS), National Institute of Health and Medical Research (INSERM), Paris Descartes University, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID) and the French National Research Agency under the “Investments for the future” program (Grant number ANR-10-IAHU-01).

Author information

Authors and Affiliations

  1. AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France

    Pierre Nahon

  2. University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre Le Cancer”, Bobigny, France

    Pierre Nahon

  3. Inserm UMR-1162, Functional Genetics of Solid Tumors, Paris, France

    Pierre Nahon

  4. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France

    Aurélie Cobat

  5. Université de Paris, Imagine Institute, Paris, France

    Aurélie Cobat

Authors
  1. Pierre Nahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aurélie Cobat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aurélie Cobat.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nahon, P., Cobat, A. Human genetics of HCV infection phenotypes in the era of direct-acting antivirals. Hum Genet 139, 855–863 (2020). https://doi.org/10.1007/s00439-020-02136-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-020-02136-4

Search

Navigation