Therapeutic targets
- To inhibit viral replication as completely as possible (counteracting the emergence of resistance).
- Prevention of the emergence of a clinically relevant immunodeficiency.
- Prevention of complications
- Healing
- Partner management, i.e., infected partners, if any, must be located and treated (contacts must be traced back to estimated time of infection)
Therapy recommendations
- There is no postexposure prophylaxis after infection with hepatitis C. However, if hepatitis C is detected and treated in the first six months after infection, 24 weeks of interferon therapy (see below) can lead to cure in more than 90% of cases before the disease takes a chronic course.
- Chronic hepatitis C is basically an indication for antiviral therapy (see below)!
- Interferon-based therapy can no longer be recommended as standard therapy in chronic hepatitis C virus infection, because directly antivirally active drugs against various proteins of the hepatitis C virus (HCV) are available.
- Direct-acting antivirals (DAAV), which do not require the addition of interferon, are indicated for:
- All patients with higher grade fibrosis/cirrhosis.
- Extrahepatic manifestations (outside the liver) of HCV infection:
- Insulin resistance (decreased or abolished action of the hormone insulin).
- Fatigue syndrome (exhaustion syndrome).
- Cryoglobulinemia – chronic recurrent immune complex vasculitis (immune disease of the vessels) characterized by the detection of abnormal cold precipitating serum proteins (cold antibodies).
- Lymphoma – collective term for lymph node enlargement or swelling and tumors of the lymphatic tissue.
- Membranoproliferative glomerulonephritis (MPGN).
- The surrogate marker of cure is considered to be sustained virologic response (SVR). This is defined as the absence of detection of HCV RNA in the blood six months after the end of therapy.
- See also under “Further therapy”.
Note: The FDA recommends HBV serology be performed in all patients with hepatitis C prior to the use of direct-acting antiviral (DAA) medications.Overview of recommended daily regimens and effectiveness for different HCV genotypes (GT) (February 2015 S3 guideline).
| Therapy | GT1 | GT2 | GT3 | GT4 | GT5 | GT6 |
| Ledipasvir + sofosbuvir +/ – ribavirin for 8, 12, or 24 weeks [Level of evidence: Ib]. | x | |||||
| Paritaprevir/r + ombitasvir plus dasabuvir +/ – ribavirin for 12 or 24 weeks [Level of evidence: Ib]. | x | |||||
| Simeprevir + sofosbuvir +/ – ribavirin for 12 weeks [Level of Evidence: IIb] | x | |||||
| Daclatasvir plus sofosbuvir +/ – ribavirin for 12 and 24 weeks, respectively [level of evidence: IIb and V, respectively]. | x | |||||
| Sofosbuvir + ribavirin for 12 weeks (level of evidence Ib). | x | |||||
| Sofosbuvir + ribavirin for 24 weeks (level of evidence Ib). | x | |||||
| Daclatasvir + sofosbuvir for 12 weeks in patients without cirrhosis (level of evidence Ib) | x | |||||
| Daclatasvir + sofosbuvir + ribavirin for 24 weeks in patients with liver cirrhosis (level of evidence V) | x | |||||
| Ledipasvir + sofosbuvir + ribavirin for 24 weeks in patients with liver cirrhosis (level of evidence V ) | x | |||||
| Ledipasvir + sofosbuvir +/ – ribavirin for 12 weeks (level of evidence IIb). | x | |||||
| Paritaprevir + ombitasvir and ribavirin for 1 2 weeks in patients without cirrhosis (level of evidence I Ib) | x | |||||
| Simeprevir + sofosbuvir +/ – ribavirin for 12 weeks (Level of Evidence V). | x | |||||
| Daclatasvir + sofosbuvir +/ – ribavirin for 12 weeks (Level of Evidence V). | x | |||||
| Ledipasvir + sofosbuvir + ribavirin for 12 weeks (level of evidence IIb). | x | x |
Attention. The European Medicines Agency (EMA) is urging physicians to avoid prescribing the antiarrhythmic drug amiodarone together with sofosbuvir + ledipasvir, as well as the free combination of sofosbuvir and daclatasvir. Taking these preparations could cause severe heart problems in patients who are also taking amiodarone. Note
- In the context of certain direct-acting antivirals (DAAVs; Engl. direct-acting antivirals, DAA) such as Daklinza (daclatasvir), Exviera (dasabuvir), Harvoni (sofosbuvir/ledipasvir), Olysio (simeprivir), Sovaldi (sofosbuvir), and Viekirax (ombitasvir/paritaprevir/ritonavir) without interferon: hepatitis B reactivation of current or previous HBV infection possible within four to eight weeks of starting treatment.
- Direct-acting antiviral drugs (DAAV) for the treatment of hepatitis C: risk of hypoglycemia in patients with diabetes mellitus; the following drug/drug combinations are affected: Daclatasvir, Dasabuvir, Elbasvir/ Grazoprevir, Glecaprevir/Pibrentasvir, Ledipasvir/Sofosbuvir, Ombitasvir/Pariteprevir/Ritonavir, Sofosbuvir, Sofosbuvir/Velpatasvir, Sofosbuvir/Velpatasvir/Voxilaprevir.
New approvals as of 2016
- 2016: fixed combination elbasvir 50 mg/grazoprevir 100 mg for the treatment of adults with chronic hepatitis C virus (HCV) infection of genotypes 1 or 4 in combination with or without ribavirin; mode of action: NS5A inhibitor elbasvir and the NS3/4A protease inhibitor grazoprevir; dosage: 1 x 1 tbl/d.
- 2017: sofosbuvir/velpatasvir/voxilaprevir, SOF/VEL/VOX approved in chronic hepatitis C for all genotypes or regardless of genotype with chronic hepatitis C without cirrhosis and with compensated cirrhosis, inclu. Patients who have not responded to prior DAA-containing regimens.Duration of therapy: 8 weeks for DAA-naive patients without cirrhosis (liver tissue is irreparably remodeled into scar and connective tissue); 12 weeks for DAA-naive patients with compensated cirrhosis, although it may be shortened to eight weeks in genotype 3 infection.
EASL (European Association for the Study of the Liver) recommendations for the treatment of hepatitis C 2016.
| Therapy | GT1 | GT2 | GT3 | GT4 | GT5 | GT6 |
| Sofosbuvir/ledipasvir | x | x | x | x | ||
| Sofosbuvir/velpatasvir | x | x | x | x | x | x |
| Ombitasvir/ritonavir-boosted paritaprevir + dasabuvir | x | |||||
| Grazoprevir/elbasvir | x | x | ||||
| Sofosbuvir + daclatasvir | x | x | x | x | x | x |
| Ombitasvir/paritaprevir/ritonavir | x | x | ||||
| Sofosbuvir + simeprevir | x |
Notes on the duration of therapy:
- Genotype 1:
- Therapy-naïve, non-cirrhotic patients: eight weeks of therapy without ribavirin.
- Pretreated: minimum at twelve weeks
- Therapy-experienced patients with genotype 1a: twelve weeks of therapy + ribavirin;
- Genotype 2: sofosbuvir plus velpatasvir (without ribavirin).
- Genotype 3: sofosbuvir/velpatasvir.
- Therapy-naive patients: twelve-week therapy duration without ribavirin.
- Therapy-experienced patients, the nucleoside analogue is added at twelve-week duration, and may be omitted at 24-week therapy.
- Genotype 4:
- Distinction between therapy-naive and -experienced patients: Combinations: Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and the so-called 2D combination (ombitasvir/paritaprevir plus ritonavir). Duration of therapy: 12 weeks; only in individual cases (pre-treatment, 2D-combi) the additional administration of ribavirin is required.
Interferon alpha
Interferon are substances that trigger various effects within the cell, which have an antiviral effect. They are used for hepatitis B and hepatitis C. Flu-like symptoms are more frequently observed as side effects. Liver parameters may also be elevated. For acute hepatitis C, interferon alpha is given for 24 weeks.
Antiretroviral drugs
Antiretroviral drugs act against retroviruses, which is a specific subgroup of viruses that includes the viruses responsible for hepatitis C. The following groups of antiretroviral drugs are distinguished:
- Protease inhibitors
- NS5A inhibitors
- Non-nucleoside polymerase (NS5B) inhibitors.
- Nucleos(t)idic polymerase (NS5B) inhibitors
In chronic hepatitis C, ribavirin – in combination with the above antiviral drugs – is used. It is a nucleoside analog and is relatively well tolerated. For treatment recommendations for chronic kidney disease grade 4-5 (CKD4-5), see AASLD/IDSA HCV Guidance Panel (2015).
