Advertisement

Liver Diseases pp 181-195 | Cite as

Viral Hepatitis C

  • Luigi Elio AdinolfiEmail author
  • Emanuele Durante Mangoni
  • Aldo Marrone
  • Rosa Zampino
  • Luca Rinaldi
Chapter

Abstract

Hepatitis C virus (HCV) is a blood-borne virus endemic throughout the world and a major cause of liver disease. HCV is transmitted parenterally and less than 25% of cases of acute infection become clinically evident. Most patients who acquire HCV cannot eliminate it spontaneously and develop a chronic infection with a high propensity to evolve into liver cirrhosis and hepatocellular carcinoma. Furthermore, HCV plays a role in a wide range of extrahepatic manifestations, including lipid and glucose metabolic imbalances. Therefore, the clinical and prognostic impact of HCV infection depends not only on liver-related complications and death, but also on extrahepatic manifestations. Although viral replication occurs primarily in the liver, HCV is able to infect and replicate into most human cells and tissues causing local and systemic inflammation. Consequently, HCV infection is considered a systemic disease. In recent years, direct-acting antiviral agents have been approved and these drugs are able to achieve HCV clearance in up to 98% of cases with a positive clinical impact on hepatic and extrahepatic manifestations. This favorable therapeutic scenario has allowed the World Health Organization to hope for the global eradication of viral hepatitis C by 2030.

Keywords

HCV Acute hepatitis Chronic hepatitis Cirrhosis HCC Extrahepatic manifestations DAA treatments 

Notes

Glossary

AHC

Acute hepatitis C

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

CHC

Chronic hepatitis C

DAAs

Direct-acting antivirals

DBS

Dry blood spot

EGDS

Esophagogastroduodenoscopy

EIA

Enzyme immunoassays

ER

Endoplasmic reticulum

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

IR

Insulin resistance

LVP

Lipoviroparticles

MC

Mixed cryoglobulinemia

MTP

Microsomal triglyceride transfer protein

NS

Non-structural proteins

NSBB

Non-selective beta blockers

POC

Point of care

SBP

Spontaneous bacterial peritonitis

SVR

Sustained virological response

T2DM

Type 2 diabetes mellitus

TIPS

Transjugular intrahepatic portosystemic shunt

VLDL

Very low-density lipoprotein

WHO

World Health Organization

References

  1. 1.
    Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59:318–27.CrossRefGoogle Scholar
  2. 2.
    Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C. Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol. 2016;22:7824–40.CrossRefGoogle Scholar
  3. 3.
    Catanese MT, Uryu K, Kopp M, Edwards TJ, Andrus L, Rice WJ, Silvestry M, Kuhn RJ, Rice CM. Ultrastructural analysis of hepatitis C virus particles. Proc Natl Acad Sci U S A. 2013;110:9505–10.CrossRefGoogle Scholar
  4. 4.
    Li Y, Yamane D, Masaki T, Lemon SM. The Yin and Yang of hepatitis C: synthesis and decay of HCV RNA. Nat Rev Microbiol. 2015;13:544–58.CrossRefGoogle Scholar
  5. 5.
    Lindenbach BD, Rice CM. The ins and outs of hepatitis C virus entry and assembly. Nat Rev Microbiol. 2013;11:688–700.CrossRefGoogle Scholar
  6. 6.
    Paul D, Madan V, Bartenschlager R. Hepatitis C virus RNA replication and assembly: living on the fat of the land. Cell Host Microbe. 2014;16:569–79.CrossRefGoogle Scholar
  7. 7.
    Scheel TKH, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19:837–49.CrossRefGoogle Scholar
  8. 8.
    Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017;2:161–76.CrossRefGoogle Scholar
  9. 9.
    WHO. Global Hepatitis report 2017. Hepatitis C, 18 July 2018. World Health Organization. http://www.who.int/iris/handle/10665/255016.
  10. 10.
    Kamili S, Drobeniuc J, Araujo AC, Hayden TM. Laboratory diagnostics for hepatitis C virus infection. Clin Infect Dis. 2012;55:S43–8.CrossRefGoogle Scholar
  11. 11.
    Rockstroh JK, Feld JJ, Chevaliez S, Cheng K, Wedemeyer H, Sarrazin C, Maasoumy B, Herman C, Hackett J Jr, Cohen DE, Dawson GJ, Cloherty G, Pawlotsky JM. HCV core antigen as an alternate test to HCV RNA for assessment of virologic responses to all-oral, interferon-free treatment in HCV genotype 1 infected patients. J Virol Methods. 2017;245:14–8.CrossRefGoogle Scholar
  12. 12.
    Ciotti M, D’Agostini C, Marrone A. Advances in the diagnosis and monitoring of hepatitis C virus infection. Gastroenterology Res. 2013;6:161–70.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Applegate TL, Fajardo E, Sacks JA. Hepatitis C virus diagnosis and the holy grail. Infect Dis Clin North Am. 2018;32:425–45.CrossRefGoogle Scholar
  14. 14.
    Llibre A, Shimakawa Y, Mottez E, Ainsworth S, Buivan TP, Firth R, Harrison E, Rosenberg AR, Meritet JF, Fontanet A, Castan P, Madejón A, Laverick M, Glass A, Viana R, Pol S, McClure CP, Irving WL, Miele G, Albert ML, Duffy D. Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut. 2018. Apr 3. pii: gutjnl-2017-315783.Google Scholar
  15. 15.
    Grebely J, Page K, Sacks-Davis R, van der Loeff MS, Rice TM, Bruneau J, Morris MD, Hajarizadeh B, Amin J, Cox AL, Kim AY, McGovern BH, Schinkel J, George J, Shoukry NH, Lauer GM, Maher L, Lloyd AR, Hellard M, Dore GJ, Prins M, C3 Study Group. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59:109–20.CrossRefGoogle Scholar
  16. 16.
    Spada E, Mele A, Mariano A, Zuccaro O, Tosti ME, SEIEVA collaborating group. Risk factors for and incidence of acute hepatitis C after the achievement of blood supply safety in Italy: results from the national surveillance system. J Med Virol. 2013;85:433–40.CrossRefGoogle Scholar
  17. 17.
    Sagnelli E, Santantonio T, Coppola N, Fasano M, Pisaturo M, Sagnelli C. Acute hepatitis C: clinical and laboratory diagnosis, course of the disease, treatment. Infection. 2014;42:601–10.CrossRefGoogle Scholar
  18. 18.
    Mendes LC, Stucchi RSB, Vigani AG. Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies. Hepat Med. 2018;10:13–22.CrossRefGoogle Scholar
  19. 19.
    Adinolfi LE, Rinaldi L, Guerrera B, Restivo L, Marrone A, Giordano M, Zampino R. NAFLD and NASH in HCV infection: prevalence and significance in hepatic and extrahepatic manifestations. Int J Mol Sci. 2016;17:803–15.CrossRefGoogle Scholar
  20. 20.
    de Franchis R, on behalf of the Baveno VI Faculty. Expanding consensus in portal hypertension report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63:743–52.CrossRefGoogle Scholar
  21. 21.
    Zampino R, Lebano R, Coppola N, Macera M, Grandone A, Rinaldi L, De Sio I, Tufano A, Stornaiuolo G, Adinolfi LE, Durante-Mangoni E, Gaeta GB, Niglio A. The use of nonselective beta blockers is a risk factor for portal vein thrombosis in cirrhotic patients. Saudi J Gastroenterol. 2018;24:25–9.CrossRefGoogle Scholar
  22. 22.
    Nevola R, Rinaldi L, Giordano M, Marrone A, Adinolfi LE. Mechanisms and clinical behavior of hepatocellular carcinoma in HBV and HCV infection and alcoholic and non-alcoholic fatty liver disease. Hepatoma Res. 2018;4:55.CrossRefGoogle Scholar
  23. 23.
    Nault JC, Colombo M. Hepatocellular carcinoma and direct acting antiviral treatments: controversy after the revolution. J Hepatol. 2016;65:663–5.CrossRefGoogle Scholar
  24. 24.
    Cacoub P, Comarmond C, Domont F, Savey L, Desbois AC, Saadoun D. Extrahepatic manifestations of chronic hepatitis C virus infection. Ther Adv Infect Dis. 2016;3:3–14.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P, ISG-EHCV. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev. 2017;16:523–41.CrossRefGoogle Scholar
  26. 26.
    Adinolfi LE, Rinaldi L, Marrone A, Giordano M. The effect of sustained virological response by direct-acting antivirals on insulin resistance and diabetes mellitus in patients with chronic hepatitis C. Expert Rev Anti Infect Ther. 2018;16:595–7.CrossRefGoogle Scholar
  27. 27.
    Petta S, Adinolfi LE, Fracanzani AL, Rini F, Caldarella R, Calvaruso V, Cammà C, Ciaccio M, Di Marco V, Grimaudo S, Licata A, Marrone A, Nevola R, Pipitone RM, Pinto A, Rinaldi L, Torres D, Tuttolomondo A, Valenti L, Fargion S, Craxì A. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis. J Hepatol. 2018;69:18–24.CrossRefGoogle Scholar
  28. 28.
    Cacoub P, Si Ahmed SN, Ferfar Y, Pol S, Thabut D, Hezode C, Alric L, Comarmond C, Ragab G, Quartuccio L, Hegazy M, Poynard T, Resche Rigon M, Saadoun D. Long-term efficacy of interferon-free antiviral treatment regimens in patients with hepatitis C virus-associated cryoglobulinemia vasculitis. Clin Gastroenterol Hepatol. 2019;17(3):518–26.CrossRefGoogle Scholar
  29. 29.
    Mihăilă RG. Hepatitis C virus – associated B cell non-Hodgkin’s lymphoma. World J Gastroenterol. 2016;22:6214–23.CrossRefGoogle Scholar
  30. 30.
    Adinolfi LE, Zampino R, Restivo L, Lonardo A, Guerrera B, Marrone A, Nascimbeni F, Florio A, Loria P. Chronic hepatitis C virus infection and atherosclerosis: clinical impact and mechanisms. World J Gastroenterol. 2014;20:3410–7.CrossRefGoogle Scholar
  31. 31.
    Adinolfi LE, Nevola R, Lus G, Restivo L, Guerrera B, Romano C, Zampino R, Rinaldi L, Sellitto A, Giordano M. Chronic hepatitis C virus infection and neurological and psychiatric disorders: an overview. World J Gastroentrol. 2015;21:2269–80.CrossRefGoogle Scholar
  32. 32.
    Kralj D, Virović Jukić L, Stojsavljević S, Duvnjak M, Smolić M, Bilić Čurčić I. Hepatitis C virus, insulin resistance, and steatosis. J Clin Transl Hepatol. 2016;4:66–75.CrossRefGoogle Scholar
  33. 33.
    Hammerstad SS, Grock SF, Lee HJ, Hasham A, Sundaram N, Tomer Y. Diabetes and hepatitis C: a two-way association. Front Endocrinol (Lausanne). 2015;6:134–53.CrossRefGoogle Scholar
  34. 34.
    Adinolfi LE, Nevola R, Guerrera B, D’alterio G, Marrone A, Giordano M, Rinaldi L. Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J Gastroenterol Hepatol. 2018;33:1379–82.CrossRefGoogle Scholar
  35. 35.
    Adinolfi LE, Guerrera B. All-oral interferon-free treatments: the end of hepatitis C virus story, the dream and the reality. World J Hepatol. 2015;7:2363–8.CrossRefGoogle Scholar
  36. 36.
    European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;  https://doi.org/10.1016/j.jhep.2018.03.026.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Luigi Elio Adinolfi
    • 1
    Email author
  • Emanuele Durante Mangoni
    • 2
  • Aldo Marrone
    • 1
  • Rosa Zampino
    • 1
  • Luca Rinaldi
    • 1
  1. 1.Department of Advanced Medical and Surgical SciencesUniversity of Campania “L. Vanvitelli”NaplesItaly
  2. 2.Department of Precision MedicineUniversity of Campania “L. Vanvitelli”NaplesItaly

Personalised recommendations