Hepatitis C (HCV) : Antiviral therapy – Guidance on treatment with pegylated interferon and ribavirin

Antiviral Therapy

This section gives guidance on treatment with pegylated interferon and ribavirin and the evidence supporting their use.

Quick links on this page

Antiviral therapy
Sustained viral response
Genotype and duration of treatment

Antiviral therapy

Several meta-analyses and systematic reviews confirm that a combination of pegylated IFN with ribavirin is effective in treating patients with CHC, leading to high levels of SVR.^{7, 118-120} Two commercial brands of pegylated IFN and ribavirin are available but they have not been directly compared in an RCT. All patients should be considered as candidates for treatment. A summary of results is illustrated in Table 1. 1++

Table 1: Results from randomised controlled trials of therapy with combination peginterferon and ribavirin in naïve patients* ¹²¹
Study	Results	Genotype 1		Genotype 2/3
* Reproduced from Clinical Gastroenterology & Hepatology, 3, Wong W, Update on Chronic Hepatitis C, 507–20, Copyright (2005), with permission from American Gastroenterological Association.
		No. treated	SVR	No. treated	SVR
Manns et al, 2001	IFN alfa-2b, 3 mU 3 times/wk + ribavirin (1000 mg < 75 kg, 1200 mg ≥ 75 kg) X 48 wk	343	33%	146	79%
	Peg-IFN alfa-2b 1.5 (4 wk) →.5 ug/kg/wk (44 wk) + ribavirin (1000 mg < 75 kg, 1200 mg ≥ 75 kg) X 48 wk	349	34%	153	80%
	Peg-IFN alfa-2b 1.5 ug/kg/wk + ribavirin 800 mg/dly) X 48 wk	348	42%	147	82%
Fried et al, 2002	IFN alfa-2b 3 mU TIW + ribavirin (1000 mg <75 kg, 1200 mg ≥75kg) X 48 wk	285	36%	145	61%
	Peg-IFN alfa-2a 180 ug/wk + ribavirin (1000 mg <75 kg, 1200 mg ≥75 kg) X 48 wk	298	46%	140	76%
	Peg-IFN alfa-2a 180 ug/wk X 48 wk	145	21%	69	45%
Hadziyannis et al, 2004	Peg-IFN alfa-2a 180 ug/wk + ribavirin (800 mg/dly) X 24 wk	101	29%	106	78%
	Peg-IFN alfa-2a 180 ug/wk + ribavirin (1000 mg <75 kg, 1200 mg =75 kg) X 24 wk	118	41%	162	78%
	Peg-IFN alfa-2a 180 ug/wk + ribavirin (800 mg/dly) X 48 wk	250	40%	111	73%
	Peg-IFN alfa-2a 180 ug/wk + ribavirin (1000 mg <75 kg, 1200 mg ≥75kg) X 48 wk	271	51%	165	77%

A combination of pegylated IFN and ribavirin is the treatment of choice for patients with hepatitis C.

Sustained viral response

Sustained viral response has become the accepted objective of treatment programmes for CHC and is currently achieved in 41-51% of patients with genotype 1 disease and 73-82% of patients with genotype 2 and 3 disease who have received a course of combination therapy with pegylated IFN and ribavirin.^{122, 123} Data are available on long term outcomes after SVR but are limited in number, quality and length of follow up:

viral relapse is uncommon after SVR (1-13% of patients)^124-126 1+
mortality is reduced after SVR¹²⁷ 2+
patients with an SVR have a reduced risk of developing cirrhosis and primary hepatocellular carcinoma^{124, 128} 2++
occult hepatitis C may persist in macrophages, lymphocytes or hepatocytes in some patients who have achieved an SVR. There may be a small risk of future relapse in this event.^{129, 130} 3

Sustained viral response should be used as a marker for viral clearance.

An SVR of 80% is achieved in patients who take 80% of the dose of both pegylated IFN and ribavirin for more than 80% of the duration. This compares with 33% in less compliant patients.¹³¹ 2+

Genotype and duration of treatment

The optimal duration of treatment for patients with genotype 1 or 4 is 48 weeks. For patients with genotype 2 or 3, 24 weeks has been the standard.^{7, 118, 119} 1++

Patients with genotype 1 infection who fail to achieve an early viral response at 12 weeks have a less than five per cent chance of achieving a sustained viral response.⁸ Of those genotype 1 patients who failed to achieve an EVR but continued on therapy and were still HCV RNA positive at 24 weeks, none had an SVR.¹³² 1+

Patients with genotype 2 and 3 infection who achieve a rapid viral response (HCV RNA negative) at four weeks can receive 12 or 16 weeks of pegylated IFN and ribavirin therapy with similar results to 24 weeks of treatment.^{9, 10} 1+

The duration of treatment with a combination of pegylated IFN with ribavirin, should be 12-24 weeks for patients with genotype 2 or 3 and 48 weeks for patients with genotype 1 or 4.

Patients with genotype 1 infection should be tested for an early viral response at 12 weeks.
Patients with genotype 1 infection who fail to achieve an EVR at 12 weeks should be considered for cessation of treatment.
Patients with genotype 1 infection with an EVR at 12 weeks should continue treatment for 48 weeks. Those who are still HCV RNA positive at 24 weeks should be considered for cessation of treatment.

Patients with genotype 2 or 3 infection should have an HCV RNA test performed four weeks after starting antiviral therapy, and if this is negative, may be considered for a reduced duration of therapy of 12 or 16 weeks.