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Semin Liver Dis 2020; 40(03): 233-239
DOI: 10.1055/s-0040-1702944
Review Article

Postsustained Virological Response Management in Hepatitis C Patients

Chiara Masetti 
1   Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
,
Ana Lleo 
1   Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
2   Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
,
Matteo Colombo
1   Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
2   Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
,
Massimo Colombo
1   Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
,
Alessio Aghemo 
1   Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
2   Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
› Author Affiliations Funding No financial support was received for the present study.
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Abstract

The introduction of direct-acting antiviral agents (DAA) has revolutionized management and care of patients with chronic hepatitis C virus (HCV) infection, leading to cure rates higher than 90% in patients with advanced liver disease as well. Viral eradication has been associated with longer survival, reduced mortality from both hepatic and extrahepatic causes, improvement in liver function, and reduced incidence of HCV-related extrahepatic diseases. While patients with mild fibrosis can safely be discharged after achievement of a sustained virological response, patients with advanced fibrosis and cirrhosis remain at risk of developing complications of liver disease, thus requiring regular and life-long surveillance. Major complications of cirrhosis that need to be monitored are hepatocellular carcinoma onset and development or progression of clinically significant portal hypertension.

Keywords

HCV - SVR - complications

Author Contributions

All authors equally contributed to this paper with the conception and design of the study, literature review, and analysis, drafting, critical revision and editing, and approval of the final version.




Publication History

Article published online:
27 February 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 WHO. Global Hepatitis Report, 2017. Available at: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/ . Accessed February 19, 2020
    PubMed
  • 2 Lee MH, Yang HI, Lu SN. , et al; R.E.V.E.A.L.-HCV Study Group. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. J Infect Dis 2012; 206 (04) 469-477
    CrossrefPubMedSearch in Google Scholar
  • 3 European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol 2018; 69 (02) 461-511
    CrossrefPubMedSearch in Google Scholar
  • 4 AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology 2015; 62 (03) 932-954
    CrossrefPubMedSearch in Google Scholar
  • 5 Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS. Oral direct-acting agent therapy for hepatitis C virus infection. Ann Intern Med 2017; 166 (09) 637-648
    CrossrefPubMedSearch in Google Scholar
  • 6 Swain MG, Lai MY, Shiffman ML. , et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010; 139 (05) 1593-1601
    CrossrefPubMedSearch in Google Scholar
  • 7 Hayashi K, Ishigami M, Ishizu Y. , et al. Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy. J Viral Hepat 2018; 25 (12) 1446-1451
    CrossrefPubMedSearch in Google Scholar
  • 8 Schwabe C, Lawitz EJ, Pol S, Shafran SD, Hyland R, Chen F. , et al. Sustained viral response following treatment with direct acting antiviral regimens is durable in more than 6,600 patients: results of the Gilead Sustained Virologic Response Registry Study. Hepatol 2018; 68 (s1): A595
    PubMedSearch in Google Scholar
  • 9 Wei L, Huang HY. Long-term outcomes in patients with chronic hepatitis C in the current era of direct-acting antiviral agents. Expert Rev Ant-Infect Ther 2019; 17 (Suppl. 05) 311-325
    CrossrefPubMedSearch in Google Scholar
  • 10 Midgard H, Weir A, Palmateer N. , et al. HCV epidemiology in high-risk groups and the risk of reinfection. J Hepatol 2016; 65 (1, suppl): S33-S45
    CrossrefPubMedSearch in Google Scholar
  • 11 Berenguer J, Gil-Martin Á, Jarrin I. , et al; Madrid-CoRe Study Group. Reinfection by hepatitis C virus following effective all-oral direct-acting antiviral drug therapy in HIV/hepatitis C virus coinfected individuals. AIDS 2019; 33 (04) 685-689
    CrossrefPubMedSearch in Google Scholar
  • 12 Bhandari R, Morey S, Hamoodi A. , et al. High rates of hepatitis C reinfection following antiviral treatment in the North East England prisons. J Viral Hepat 2019; (e-pub ahead of print)
    CrossrefPubMedSearch in Google Scholar
  • 13 Terrault NA. Care of patients following cure of hepatitis C virus infection. Gastroenterol Hepatol (N Y) 2018; 14 (11) 629-634
    PubMedSearch in Google Scholar
  • 14 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 Med Virol 2018; 90 (02) 320-327
    CrossrefPubMedSearch in Google Scholar
  • 15 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 Hepatol 2018; 69 (01) 18-24
    CrossrefPubMedSearch in Google Scholar
  • 16 Cacoub P, Si Ahmed SN, Ferfar Y. , et al. Long-term efficacy of interferon-free antiviral treatment regimens in patients with hepatitis C virus-associated cryoglobulinemia vasculitis. Clin Gastroenterol Hepatol 2019; 17 (03) 518-526
    CrossrefPubMedSearch in Google Scholar
  • 17 Carrat F, Fontaine H, Dorival C. , et al; French ANRS CO22 Hepather Cohort. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet 2019; 393 (10179): 1453-1464
    CrossrefPubMedSearch in Google Scholar
  • 18 Nahon P, Bourcier V, Layese R. , et al; ANRS CO12 CirVir Group. Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 2017; 152 (01) 142-156.e2
    CrossrefPubMedSearch in Google Scholar
  • 19 Cacoub P, Nahon P, Layese R. , et al; ANRS CO12 CirVir group. Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients. Am Heart J 2018; 198: 4-17
    CrossrefPubMedSearch in Google Scholar
  • 20 El-Serag HB, Christie IC, Puenpatom A, Castillo D, Kanwal F, Kramer JR. The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection. Aliment Pharmacol Ther 2019; 49 (11) 1442-1447
    CrossrefPubMedSearch in Google Scholar
  • 21 Peveling-Oberhag J, Arcaini L, Bankov K, Zeuzem S, Herrmann E. The anti-lymphoma activity of antiviral therapy in HCV-associated B-cell non-Hodgkin lymphomas: a meta-analysis. J Viral Hepat 2016; 23 (07) 536-544
    CrossrefPubMedSearch in Google Scholar
  • 22 Arcaini L, Besson C, Frigeni M. , et al. Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection. Blood 2016; 128 (21) 2527-2532
    CrossrefPubMedSearch in Google Scholar
  • 23 Bonacci M, Lens S, Mariño Z. , et al. Long term outcomes of patients with HCV-associated cryoglobulinemic vasculitis after virologic cure. Gastroenterology 2018; 155 (02) 311-315.e6
    CrossrefPubMedSearch in Google Scholar
  • 24 Mahale P, Torres HA, Kramer JR. , et al. Hepatitis C virus infection and the risk of cancer among elderly US adults: a registry-based case-control study. Cancer 2017; 123 (07) 1202-1211
    CrossrefPubMedSearch in Google Scholar
  • 25 Pol S, Vallet-Pichard A, Hermine O. Extrahepatic cancers and chronic HCV infection. Nat Rev Gastroenterol Hepatol 2018; 15 (05) 283-290
    CrossrefPubMedSearch in Google Scholar
  • 26 Nahon P, Bourcier V, Layese R. , et al; ANRS CO12 CirVir Group. Eradication of hepatitis C virus in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 2017; 152 (01) 142-156.e2
    CrossrefPubMedSearch in Google Scholar
  • 27 Allaire M, Nahon P, Layese R. , et al; ANRS CO12 CirVir Group. Extrahepatic cancers are the leading cause of death in patients achieving hepatitis B virus control or hepatitis C virus eradication. Hepatology 2018; 68 (04) 1245-1259
    CrossrefPubMedSearch in Google Scholar
  • 28 Backus LI, Belperio PS, Shahoumian TA, Mole LA. Direct-acting antiviral sustained virologic response: impact on mortality in patients without advanced liver disease. Hepatology 2018; 68 (03) 827-838
    CrossrefPubMedSearch in Google Scholar
  • 29 Bruno S, Di Marco V, Iavarone M. , et al. Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population. J Hepatol 2016; 64 (06) 1217-1223
    CrossrefPubMedSearch in Google Scholar
  • 30 Lleo A, Aglitti A, Aghemo A, Maisonneuve P, Bruno S, Persico M. ; collaborators. Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals. Dig Liver Dis 2019; 51 (02) 310-317
    CrossrefPubMedSearch in Google Scholar
  • 31 Calvaruso V, Cabibbo G, Cacciola I. , et al; Rete Sicilia Selezione Terapia–HCV (RESIST-HCV). Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology 2018; 155 (02) 411-421.e4
    CrossrefPubMedSearch in Google Scholar
  • 32 Degasperi E, D'Ambrosio R, Iavarone M. , et al. Factors associated with increased risk of de-novo or recurrent hepatocellular carcinoma in patients with cirrhosis treated with direct-acting antivirals for HCV infection. Clin Gastroenterol Hepatol 2019; 17 (06) 1183-1191.e7
    CrossrefPubMedSearch in Google Scholar
  • 33 Walker AJ, Peacock CJ, Pedergnana V, Irving WL. STOP-HCV Consortium. Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: a systematic review. J Viral Hepat 2018; 25 (05) 442-456
    CrossrefPubMedSearch in Google Scholar
  • 34 Nguyen K, Jimenez M, Moghadam N. , et al. Decrease of alpha-fetoprotein in patients with cirrhosis treated with direct-acting antivirals. J Clin Transl Hepatol 2017; 5 (01) 43-49
    PubMedSearch in Google Scholar
  • 35 Masetti C, Lionetti R, Lupo M. , et al. Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis. J Viral Hepat 2018; 25 (12) 1493-1500
    CrossrefPubMedSearch in Google Scholar
  • 36 Conti F, Buonfiglioli F, Scuteri A. , et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016; 65 (04) 727-733
    CrossrefPubMedSearch in Google Scholar
  • 37 Reig M, Mariño Z, Perelló C. , et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016; 65 (04) 719-726
    CrossrefPubMedSearch in Google Scholar
  • 38 Lens S, Alvarado-Tapias E, Mariño Z. , et al. Effects of all-oral antiviral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis. Gastroenterology 2017; 153 (05) 1273-1283.e1
    CrossrefPubMedSearch in Google Scholar
  • 39 Afdhal N, Everson GT, Calleja JL. , et al. Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension. J Viral Hepat 2017; 24 (10) 823-831
    CrossrefPubMedSearch in Google Scholar
  • 40 Di Marco V, Calvaruso V, Ferraro D. , et al. Effects of eradicating hepatitis C virus infection in patients with cirrhosis differ with stages of portal hypertension. Gastroenterology 2016; 151 (01) 130-139.e2
    CrossrefPubMedSearch in Google Scholar
  • 41 de Franchis R. 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 (03) 743-752
    CrossrefPubMedSearch in Google Scholar
  • 42 Thabut D, Bureau C, Layese R. , et al; ANRS CO12 CirVir group. Validation of Baveno VI criteria for screening and surveillance of esophageal varices in patients with compensated cirrhosis and a sustained response to antiviral therapy. Gastroenterology 2019; 156 (04) 997-1009.e5
    CrossrefPubMedSearch in Google Scholar
  • 43 de Franchis R. The changing scenario of screening and surveillance of esophageal varices. Gastroenterology 2019; 156 (04) 864-866
    CrossrefPubMedSearch in Google Scholar
  • 44 Velosa J. Why is viral eradication so important in patients with HCV-related cirrhosis?. Antivir Ther 2017; 22 (01) 1-12
    CrossrefPubMedSearch in Google Scholar
  • 45 Romano J, Sims OT, Richman J. , et al. Resolution of ascites and hepatic encephalopathy and absence of variceal bleeding in decompensated hepatitis C virus cirrhosis patients. JGH Open 2018; 2 (06) 317-321
    CrossrefPubMedSearch in Google Scholar
  • 46 Gentile I, Scotto R, Coppola C. , et al. Treatment with direct-acting antivirals improves the clinical outcome in patients with HCV-related decompensated cirrhosis: results from an Italian real-life cohort (Liver Network Activity-LINA cohort). Hepatol Int 2019; 13 (01) 66-74
    CrossrefPubMedSearch in Google Scholar
  • 47 Belli LS, Berenguer M, Cortesi PA. , et al; European Liver and Intestine Association (ELITA). Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol 2016; 65 (03) 524-531
    CrossrefPubMedSearch in Google Scholar
  • 48 D'Ambrosio R, Aghemo A, Fraquelli M. , et al. The diagnostic accuracy of Fibroscan for cirrhosis is influenced by liver morphometry in HCV patients with a sustained virological response. J Hepatol 2013; 59 (02) 251-256
    CrossrefPubMedSearch in Google Scholar
  • 49 D'Ambrosio R, Degasperi E, Aghemo A. , et al. Serological tests do not predict residual fibrosis in hepatitis C cirrhotics with a sustained virological response to interferon. PLoS One 2016; 11 (06) e0155967
    CrossrefPubMedSearch in Google Scholar
  • 50 Terrault NA, Hassanein TI. Management of the patient with SVR. J Hepatol 2016; 65 (1, suppl): S120-S129
    CrossrefPubMedSearch in Google Scholar
  • 51 Noureddin M, Wong MM, Todo T, Lu SC, Sanyal AJ, Mena EA. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals. World J Gastroenterol 2018; 24 (11) 1269-1277
    CrossrefPubMedSearch in Google Scholar
  • 52 Mauss S, Buendgens L, Christensen S. , et al. Risk factors for remaining liver injury in patients with virological elimination of chronic hepatitis C. Z Gastroenterol 2019; 57 (02) 139-147
    Thieme ConnectPubMedSearch in Google Scholar
  • 53 Spadaccini M, Lleo A, Ceriani R. , et al. Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era. Hepatobiliary Pancreat Dis Int 2018; 17 (06) 570-574
    CrossrefPubMedSearch in Google Scholar