On-treatment monitoring

In contrast to IFN-based treatment regimens, intense monitoring of people undergoing DAA therapy is usually unnecessary. This simplification recognises the high efficacy of these regimens, the lack of a role for response-guided therapy and the considerably improved side effect profile. During treatment, follow-up intervals need to be established on a case-by-case basis to optimise adherence, assess adverse events and potential drug–drug interactions and monitor blood test results necessary for patient safety (Table 4). All patients should be provided with contact details for a clinician to contact if problems arise in between appointments. For many people, no assessment will be required during treatment, and review at 12 weeks after completion of therapy can be organised to document SVR.

More intensive monitoring may be required in certain populations. On-treatment and end-of-treatment virological assessments may be considered if there are concerns about adherence to therapy, particularly if there are risk factors for reinfection. Low levels of plasma HCV RNA can be detected in up to 20% of people using sensitive PCR assays at Week 4 of treatment, but this does not predict treatment failure, nor does it require treatment extension. The product information for the regimen of elbasvir plus grazoprevir recommends that liver function tests be performed at Week 8 for people treated for 12 weeks’ duration, and at Week 8 and Week 12 for those receiving 16 weeks of treatment.49

Patients treated with ribavirin require monitoring of haemoglobin levels. People with advanced liver disease (portal hypertension or hepatic decompensation) require more intensive monitoring. In this setting, more frequent liver function tests are advisable to monitor for medication adherence and early evidence of hepatic decompensation related to drug reaction. Calculation of MELD and Child–Pugh scores, as well as measurement of body weight, is useful for detecting deteriorating liver function or ascites in people with cirrhosis.

Screening for HCC is recommended at baseline for all people living with cirrhosis. We recommend ongoing surveillance with liver ultrasound every 6 months. The impact of DAA treatment on HCC risk is not yet clear (see Direct-acting antiviral therapy and risk of hepatocellular carcinoma in people with cirrhosis). HCV treatment should not suspend HCC screening programs. We recommend a liver ultrasound be performed before starting DAA treatment (within 1 month before starting treatment) for all patients with cirrhosis to ensure that HCC screening remains up to date during the treatment and follow-up period.

People with HCV–HBV coinfection are at risk of HBV reactivation during DAA therapy for HCV (see Treatment of HCV in the setting of HBV coinfection). Specific monitoring for HBV reactivation is required. It is recommended that these people be treated by a specialist with experience in treating HCV and HBV infection.

Table 4. Monitoring of patients receiving antiviral therapy for hepatitis C virus (HCV) infection: (A) on-treatment and post-treatment monitoring for virological response; and (B) monitoring after SVR

A. On-treatment and post-treatment monitoring for virological response

Routine monitoring for an 8–12-week treatment regimen:

Week 0

  • Pre-treatment blood tests, including LFTs, HCV PCR (Table 1)

Week 8–12 post-treatment (SVR)

  • LFTs, HCV PCR (qualitative)
  • More intensive monitoring may be required in certain populations (see text).
  • People treated with elbasvir plus grazoprevir should have LFTs at Week 8 to screen for hepatotoxicity.

B. Monitoring after SVR

SVR, no cirrhosis and normal LFT results (males, ALT ≤ 30 U/L; females, ALT ≤ 19 U/L):

  • Patients who are cured do not require clinical follow-up for HCV

SVR and abnormal LFT results (males, ALT > 30 U/L; females, ALT > 19 U/L):

  • Patients with persistently abnormal LFT results require evaluation for other liver diseases and should be referred for gastroenterology review. Investigations to consider include: fasting glucose level, fasting lipid levels, iron studies, ANA, ASMA, anti-LKM antibodies, total IgG and IgM, AMA, coeliac serology, copper level, caeruloplasmin level and a-1-antitrypsin level

SVR and cirrhosis:

Patients with cirrhosis require long-term monitoring and should be enrolled in screening programs for:

  • HCC — liver ultrasound ± serum a-fetoprotein level
  • oesophageal varices — gastroscopy
  • osteoporosis — dual emission x-ray absorptiometry

SVR and risk of reinfection:

  • Patients with ongoing risk of HCV infection should have at least annual HCV RNA testing
  • Anti-HCV antibodies will remain positive in all people with prior exposure and this does not require repeated testing

ALT = alanine aminotransferase; AMA = anti-mitochondrial antibody; ANA = anti-nuclear antibodies; ASMA = anti-smooth muscle antibodies; HCC = hepatocellular carcinoma; LFT = liver function test; LKM = liver–kidney microsome; PCR = polymerase chain reaction; SVR = sustained virological response at least 12 weeks after treatment (cure).