Hepatitis C

Monitoring during treatment

• Full blood count: after 4 weeks of treatment and as clinically indicated, particularly in patients on ribavirin.

• Renal function: after 4 weeks of treatment and as clinically indicated.

• Hepatic function: patients on elbasvir/grazoprevir should be monitored at 8 weeks and again at 12 weeks if receiving 16 weeks of treatment. A ≥10-fold increase in alanine aminotransferase (ALT) activity from baseline at any time during treatment, or an increase of less than 10-fold from baseline accompanied by weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or international normalised ratio (INR) should prompt cessation of therapy. Asymptomatic increases in ALT of less than 10-fold from baseline should prompt close monitoring and the test repeated at 2-week intervals. If levels are persistently elevated, cessation of therapy should be considered.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• Hepatitis C virus (HCV) RNA (HCV viral load): recommended 12 or more weeks following completion of therapy to document sustained virological response (SVR).[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• Haemoglobin: anaemia is a common adverse effect with ribavirin and serum haemoglobin should be monitored during treatment. Baseline haemoglobin and haemoglobin percentage drop (along with estimated glomerular filtration rate) have been used to predict the risk of anaemia in one study.[131]Molina-Cuadrado E, Mateo-Carrasco H, Collado A, et al. Anaemia predictors in patients with chronic hepatitis C treated with ribavirin and direct-acting antiviral agents. Eur J Hosp Pharm. 2018 May;25(3):132-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452397 http://www.ncbi.nlm.nih.gov/pubmed/31157007?tool=bestpractice.com

• Pregnancy test: recommended at appropriate intervals during and for 6 months after therapy with ribavirin-containing regimens.

• Blood glucose level: monitor for hypoglycaemia.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org Monitor closely in patients with diabetes, especially during the first 3 months of treatment. A rapid reduction in hepatitis C viral load may lead to improvements in glucose metabolism resulting in symptomatic hypoglycaemia in patients with diabetes. The dose of antidiabetic medication may need to be modified, or the patient switched to an alternative antidiabetic medication.[132]Medicines and Healthcare products Regulatory Agency. Direct-acting antivirals for chronic hepatitis C: risk of hypoglycaemia in patients with diabetes. Dec 2018 [internet publication]. https://www.gov.uk/drug-safety-update/direct-acting-antivirals-for-chronic-hepatitis-c-risk-of-hypoglycaemia-in-patients-with-diabetes

• INR: monitoring for sub-therapeutic anticoagulation is recommended for patients who are on warfarin.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• Other: patients should be monitored during treatment for adherence, adverse effects, and drug interactions.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

Hepatitis B reactivation

• Cases of hepatitis B reactivation have been reported during, or after, therapy with direct-acting antiviral agents.[91]US Food and Drug Administration. FDA drug safety communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C. Oct 2016 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-risk-hepatitis-b-reactivating-some-patients-treated [113]European Medicines Agency. PRAC warns of risk of hepatitis B re-activation with direct-acting antivirals for hepatitis C. Dec 2016 [internet publication]. https://www.ema.europa.eu/en/news/prac-warns-risk-hepatitis-b-re-activation-direct-acting-antivirals-hepatitis-c

• All patients should be assessed for active hepatitis B infection, by testing for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc), before starting therapy with direct-acting antiviral agents. Hepatitis B vaccination is recommended for all susceptible individuals.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• In patients who are HBsAg positive, a hepatitis B virus DNA test should be obtained prior to starting therapy. Patients who meet criteria for the treatment of active hepatitis B infection should be started on hepatitis B therapy at the same time as, or before, starting direct-acting antivirals. Patients who do not meet criteria for treatment should be either: (1) started on prophylactic antiviral therapy for hepatitis B infection and continued until 12 weeks after completion of direct-acting antiviral therapy; or (2) monitored during and immediately after direct-acting antiviral therapy ( hepatitis B virus DNA levels), and antiviral therapy for hepatitis B infection given in the event of a rise of hepatitis B virus DNA >10-fold above baseline or to >1000 IU/mL in those with a previously undetectable or unquantifiable hepatitis B virus DNA level.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• In patients who test positive for anti-HBs or anti-HBc, hepatitis B reactivation should be considered in the event of unexplained increases in liver enzymes during (or after) treatment with direct-acting antivirals.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

Monitoring in patients who achieve an SVR

• SVR is defined as undetectable HCV RNA virus in the serum 12 or more weeks after treatment completion, which correlates well with long-term absence of virus.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• The American Association For The Study of Liver Diseases (AASLD) recommends the following:[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

  • Ultrasound exam with or without alpha fetoprotein: to screen for hepatocellular carcinoma in patients with cirrhosis (performed in accordance with relevant guidance).

  • Endoscopy: to screen for oesophageal varices in patients with cirrhosis (performed in accordance with relevant guidance).

  • HCV RNA (HCV viral load): to test for recurrence or re-infection in patients with ongoing risk factors for infection (e.g., people who inject drugs) or if unexplained hepatic dysfunction develops.

  • Patients who develop persistently abnormal liver tests after SVR should be assessed for other causes of hepatic disease.

• The American Gastroenterological Association recommends the following in patients who have achieved an SVR after treatment with oral direct-acting antiviral regimens:[103]Jacobson IM, Lim JK, 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 May;152(6):1578-87. https://www.gastrojournal.org/article/S0016-5085(17)30327-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/28344022?tool=bestpractice.com

  • Virological response: confirm at 48 weeks after treatment.

  • Endoscopy: continue screening for varices in all patients with cirrhosis. If no varices are identified within 2 to 3 years, further surveillance is not necessary in patients who are not at risk of progressive liver disease.

  • Ultrasound exam: continue surveillance for hepatocellular carcinoma in patients with stage 3 fibrosis or liver cirrhosis indefinitely. No surveillance is recommended for patients with earlier stages of fibrosis.

Monitoring in patients who do not achieve an SVR

• Patients who do not achieve an SVR (i.e., due to failure of treatment to clear infection or maintain clearance of infection with relapse after treatment completion), have the possibility of continued liver injury and transmission with ongoing infection.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• FBC, INR, and hepatic panel: every 6 to 12 months to assess for disease progression if patients are not retreated or fail a second or third treatment course.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• Ultrasound exam with or without alpha fetoprotein: every 6 months in patients with cirrhosis to screen for hepatocellular carcinoma.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• Endoscopy: to screen for oesophageal varices in patients with cirrhosis (performed in accordance with relevant guidance).[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• Evaluation for re-treatment is recommended as alternative treatments become available.

Monitoring in patients with incomplete adherence

• Missing doses of direct-acting antivirals (DAAs) is common. There are few data on which to base recommendations regarding how to manage patients who have discontinued DAAs for several days or weeks. However, opinion-based recommendations are available if needed.[66]American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Dec 2023 [internet publication]. https://www.hcvguidelines.org

• All patients should be asked about factors contributing to adherence or non-adherence, and counselled regarding the importance of adherence.