After treatment for chronic hepatitis C virus (HCV) infection, follow-up care is based on individual patient factors, including response to recent treatment, previous treatment history, degree of hepatic fibrosis, comorbidities, and cofactors for other sources of liver injury, such as alcohol use or fatty liver disease.
Evaluating the Response to HCV Treatment
All treated individuals should have HCV RNA testing performed 12 weeks after treatment. If there is no detectable HCV RNA at 12 weeks, HCV infection has been cured. In the absence of recurrent risk factors, subsequent HCV testing is not required. However, with late relapse reported in rare (<0.5%) cases, some clinicians may choose to retest at 24 and/or 48 weeks after end of treatment .
Successful treatment of chronic HCV infection results in no detectable HCV RNA, but antibodies to HCV are typically retained for life. It is important for treated individuals to understand that they will continue to have antibodies but not active HCV infection. It is also important for patients to understand that, although antibodies to HCV will continue to be present after treatment, HCV antibodies do not offer protection from HCV reinfection. All individuals with no detectable HCV RNA are considered susceptible to reinfection if re-exposed to HCV. While the overall rate of reinfection is low, it is elevated among populations at higher risk . A meta-analysis of 59 studies reporting on recurrence after a sustained viral response (SVR) in 9,049 patients found that the summary 5-year risk of HCV reinfection among high-risk populations was 10.67% . High risk was defined as having one or more risk factors for reinfection (current or former persons who inject drugs [PWID], imprisonment, and men who have sex with men [MSM]). Among low-risk populations, defined as those with no known risk factors, the summary 5-year recurrence risk of was 0.95% . For discussion of risk factors, see the Screening and Diagnosis sections of this guideline.
It is important to monitor for the resolution of patients’ HCV treatment-related adverse events. RBV-containing regimens are teratogenic; patients receiving RBV-containing regimens and their partners should be counseled to avoid pregnancy during treatment and up to 6 months post-treatment. Two forms of effective birth control should be used .
See Monitoring During DAA Treatment > Table 29: Adverse Events Associated with DAAs, for a list of adverse events associated with DAA regimens. During treatment with RBV, patients may experience hemolytic anemia, nausea, cough, shortness of breath, rash, dry skin, pruritus, lactic acidosis, or pancreatitis . Patients should be monitored through the follow-up period for resolution of any symptoms.
Hepatitis B virus (HBV) reactivation: HBV-related hepatic flares have been reported during and after DAA therapy in patients who were not receiving concurrent HBV treatment [5-11]. The U.S. Food and Drug Administration (FDA) has issued a drug safety warning regarding these risks. Although data are insufficient to make a definitive recommendation regarding monitoring in the setting of isolated anti-HBc , it is important to consider HBV reactivation as part of the differential diagnosis for patients with HBV infection who experience unexplained increases in liver enzymes either during or after completion of DAA treatment.
Patients with Persistent Liver Disease
While cessation of the progression of fibrosis and histological improvement are among the benefits of treating chronic HCV infection [13,14], patients should still be monitored for potential risk of post-treatment decompensation .
Individuals in whom HCV infection is cured remain at risk of liver disease progression if their baseline fibrosis is sufficiently advanced or if they have comorbidities, such as metabolic syndrome, alcohol use, or uncontrolled coinfection with HIV or HBV, or are at risk of liver injury from drugs or dietary supplements .
Although there is wide individual variation in the time needed for fibrosis progression to occur in chronic HCV infection, it is important to maintain an elevated level of suspicion for progression of fibrosis and the complications associated with hepatic decompensation, particularly in individuals with long-term chronic HCV infection or comorbidities that would predispose them to faster progression. Transient elastography is not available in all clinical settings, but once it is more widely available, it will aid in monitoring fibrosis progression after HCV treatment.
For patients with bridging fibrosis or cirrhosis, an ultrasound should be performed every 6 months, regardless of SVR, to screen for HCC . The risk of HCC for patients with stage 3 or higher fibrosis is 1.5% to 5% per year, but it is not known whether the histologic improvement after successful treatment mitigates this risk .
- Jacobson IM LJ, Fried MW. American Gastroenterological Association Institute Clinical Practice Update—Expert Review: Care of Patients Who Have Achieved a Sustained Virologic Response After Antiviral Therapy for Chronic Hepatitis C Infection. Gastroenterology 2017;152(6):1578-1587. [PMID: 28344022]
- Martinello M, Grebely J, Petoumenos K, et al. HCV reinfection incidence among individuals treated for recent infection. J Viral Hepat 2017;24(5):359-70. [PMID: 28027424]
- Simmons B, Saleem J, Hill A, et al. Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis. Clin Infect Dis 2016;62(6):683-94. [PMID: 26787172]
- FDA. Copegus (ribavirin) tablets. 2015 [accessed March 7, 2017]. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm218877.htm
- Hayashi K IM, Ishizu Y1, Kuzuya T, Honda T, Nishimura D, Goto H1, Hirooka Y. A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis? Clin J Gastroenterol 2016;Aug;9(4):252-6. [PMID: 27329484]
- Takayama H ST, Ikeda F, Fujiki S. Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection. Hepatol Res 2016 Mar 46(5):489-91. [PMID: 26297529]
- Ende AR KN, Yeh MM, Harper J, Landis CS. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep 2015 Jul 28:164. [PMID: 26215390]
- Collins JM RK, Terry C, Cartwright EJ, Pillai A, Anania FA, Farley MM. Hepatitis B Virus Reactivation During Successful Treatment of Hepatitis C Virus With Sofosbuvir and Simeprevir. Clin Infect Dis 2015 Oct 15;61(8):1304-6. [PMID: 26082511]
- De Monte A CJ, Anty R, Cua E, Naqvi A, Mondain V, Cottalorda J, Ollier L, Giordanengo V. Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge. J Clin Virol 2016;May;78:27-30. [PMID: 26967675]
- Sulkowski MS CW, Kao JH3, Yang JC, Gao 4, Brainard DM, Han KH5, Gane E. No Evidence of Reactivation of Hepatitis B Virus Among Patients Treated With Ledipasvir-Sofosbuvir for Hepatitis C Virus Infection. Clin Infect Dis 2016 Nov 1;63(9):1202-04. [PMID: 27486112]
- Wang C JD, Chen J, Shao Q, Li B, Liu J, Wu V, Wong A, Wang Y, Zhang X, Lu L, Wong C, Tsang S, Zhang Z, Sun J, Hou J, Chen G, Lau G. Hepatitis due to Reactivation of Hepatitis B Virus in Endemic Areas Among Patients With Hepatitis C Treated With Direct-acting Antiviral Agents. Clin Gastroenterol Hepatol 2017 Jan;15(1):132-36. [PMID: 27392759]
- American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. August 24, 2016 [accessed 2017 Apr 26]. http://www.hcvguidelines.org
- George SL, Bacon BR, Brunt EM, et al. Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients. Hepatology 2009;49(3):729-38. [PMID: 19072828]
- Toccaceli F, Laghi V, Capurso L, et al. Long-term liver histology improvement in patients with chronic hepatitis C and sustained response to interferon. J Viral Hepat 2003;10(2):126-33. [PMID: 12614469]
- Vandenbulcke H, Moreno C, Colle I, et al. Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study. J Hepatol 2016;65(3):543–51. [PMID: 27180899]
- Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53(3):1020-2. [PMID: 21374666]