The first Hepatitis C treatment guidelines of the French Association for the Study of Liver Diseases (AFEF) were published in 2015.  These guidelines are updated annually, and one of the main objectives for the 2017 update was to simplify the management before, during, and after treatment. This is a review of the main points.

 AFEF Hep C

 

 

The goal of the guidelines for pre-treatment is to screen out other etiologies of liver disease, to tailor treatment to the patient co-morbidities, and to screen for fibrosis or cirrhosis.  This last part is addressed with noninvasive tests of fibrosis, used for the screening of complications from severe fibrosis (including hepatocellular carcinoma and the portal hypertension according to the specific guidelines of Baveno VI).

 

If the decision is to not treat the patient, a yearly follow-up with a consultation and a noninvasive test of fibrosis is necessary.

 

Several different combinations of Direct Acting Antivirals (DAAs) exist, and they are prescribed partially based on the viral genotype (See table 1).   The screening of baseline resistance associated substitutions is recommended only in case of:

  • Failure of a first DAA treatment,
  • Just before the retreatment (in the event of failure), according also to the identification of the genotype (allowing distinguishing a relapse or a re-infection),
  • To the history of the treatment (compliance, combination used, ribavirin or not, drug-drug interaction, safety and any previous early discontinuation).

 

Some specificities are necessary in particular populations.

  • In patients with a current or past decompensated cirrhosis, the protease inhibitors are not recommended because of the risk of aggravation of the liver function.
  • In patients on the liver transplant waiting list, treatment is evaluated on a case by case basis, according the MELD and the indication (hepatocellular carcinoma or not). After the liver transplantation, the treatment is started quickly to avoid the risk of severe and early liver injuries associated with the recurrence of the HCV infection, including drug-drug interactions with the immunosuppressive treatments, anemia risk associated with ribavirin and the frequent renal insufficiency in this population.
  • The treatment is also recommended in all patients awaiting for organ transplantation, or after the operation, taking into account the same considerations.
  • In patients with a renal insufficiency, there are no recommendations to modify therapy in patients with a creatinine clearance above 30 ml/mn. In patients with creatinine clearance below 30 ml/mm, the choice has to be discussed in multidisciplinary concertation meeting and avoid ribavirin and sofosbuvir use.
  • In patients with current drug use, the treatment has to be associated with an overall management approach before, during and after the DAA treatment. The risk of a potential reinfection after a first sustained virological response has to be explained to the patient and the reinfections treated.

 

Similarly, in men having sex with men, the risk of reinfection has to be explained, screened and the reinfections treated.

The pregnancy and a breast-feeding are two contra-indication to DAA treatment.

The on-treatment follow-up for patients is relatively simple. Most of adverse events are mild, but the screening of the arterial pulmonary hypertension is necessary in cirrhotic patients; likewise, the screening of hepatocellular carcinoma could be improved with a MRI every 3 months during the year after the initiation of DAA therapy. The sustained virological response is confirmed by an undetectable RNA from 12 to 24 weeks after the end of treatment.

 The drug-drug interactions have to be screened before and during the treatment. Lastly, the combined use of amiodarone and sofosbuvir is contra-indicated because of significant drug interactions.

After the end of DAA therapy, only patients with no or moderate liver fibrosis and an undetectable fibrosis 48 weeks after the end of therapy (without comorbidities nor risk of reinfection) could discontinue follow-up by the specialist.

Patients with portal hypertension and other complications of cirrhosis, patients with cirrhosis (or severe fibrosis), need to maintain the follow-up and the management of comorbidities (particularly the metabolic syndrom and/or an exccessive alcohol consumption) and should be screened for hepatocellular carcinoma on a regular basis.

 

Conditions

Treatments

Duration

(weeks)

Genotype 1

-all patients

-without cirrhosis

-genotype 1b

-genotype 1a and RNA < 800000 IU/mL

-genotype 1b, without fibrosis, naive patients

-genotype 1b

-without cirrhosis

-cirrhosis

Sofosbuvir-Velpatasvir

Sofosbuvir-Ledipasvir

Grazoprevir-Elbasvir

Grazoprevir-Elbasvir

Paritaprevir-Ombitasvir-Dasabuvir

Paritaprevir-Ombitasvir-Dasabuvir

Glecaprevir-Pibrentasvir

Glecaprevir-Pibrentasvir

12

8

12

12

8

12

8

12

Genotype 2

-all patients

-without cirrhosis

Sofosbuvir-Velpatasvir

Glecaprevir-Pibrentasvir

12

8

Genotype 3

Sofosbuvir-Velpatasvir

Sofosbuvir-Velpatasvir-Voxilaprevir

Glecaprevir-Pibrentasvir

12

8

12

Genotype 4

-all patients

-naive patients

-without cirrhosis

Sofosbuvir-velpatasvir

Grazoprevir-Elbasvir

Glecaprevir-Pibrentasvir

12

12

8

Genotype 5 ou 6

-all patients

-without cirrhosis

Sofosbuvir-Velpatasvir

Glecaprevir-Pibrentasvir

12

8

 

The lines written in italic concern the combinations not available at the time of the publication of these guidelines, except in temporary authorization of use.