Treatment Of Hepatitis C

Treatment of chronic hepatitis C has undergone a remarkable evolution in recent years.

Hepatitis C is a viral disease that causes inflammation of the liver. Treatment is changing rapidly but access to it remains limited.

The hepatitis C virus (HCV) was identified in 1989, it is RNA type and belongs to the genus Hepacivirus of the Flaviviridae family . Although more than 6 genotypes and more than 80 subtypes are distinguished, the most frequent is genotype 1.

Hepatitis C virus infection is estimated to affect 170-180 million people worldwide (2%). Its annual incidence is 4 million new cases and causes around 500,000 deaths.

Causes of hepatitis

The main feature of this pathology is hepatitis. This word refers to inflammation of the liver, which can be due to numerous causes, among which are:

• Presence of a hepatotrophic virus (affinity for the liver) or other infections.
• Toxic substances (alcohol, drugs or pharmaceuticals). This point justifies the importance of detoxifying our body from time to time, avoiding the accumulation of these substances.

• Autoimmune diseases.

Viral hepatitis is a group of infectious diseases with great clinical and public relevance. The main cause of liver inflammation is hepatotropic viruses. The most important are those of hepatitis A, B, C, D and E.

Evaluation of the patient with hepatitis C

Transmission is almost always parenterally, accounting for 90% of post-transfusion hepatitis. Acute HCV infection is generally asymptomatic, although it is rarely associated with fatal disease.

If left untreated, 15% of patients with chronic hepatitis C will eventually develop cirrhosis and 20% will develop hepatocellular carcinoma. For this reason, it  is the leading cause of liver transplantation in Spain.

In 80% of cases, HCV infection becomes chronic and 20-30% of those infected will develop cirrhosis. Treatment must be individualized, paying attention to some variables such as:

• Severity of liver disease.
• Potential risk of side effects.
• Probability of response.
• Comorbidity

All patients who are candidates for treatment will be confirmed by means of a liver biopsy to assess the severity of the disease. Today the biopsy is being replaced by an elastography, a less invasive technique. This technique is complemented with biochemical tests:

• Determination of anti-HCV antibodies by ELISA.
• PCR (polymerase chain reaction) for confirmation with the presence of serum RNA.

First treatments for hepatitis C

Initially, the treatment of hepatitis C was based on the administration of subcutaneous interferon alfa (or pegylated interferon to increase its biological life) and oral ribavirin. However, this treatment could last between 24 and 72 weeks.

In 2011, the use of two new drugs was approved : boceprevir and telaprevir.  Both constituted the first generation of selective and reversible inhibitors of the NS3 protease (involved in the processing of viral proteins).

Thus, triple therapy was born since both had to be combined with ribavirin and interferon.

This strategy was useful for the treatment of type 1 hepatitis C in both treated and untreated patients. A response rate of around 70% was achieved. In addition, this treatment made it possible to shorten its duration from 48 to 24 weeks.

However, boceprevir and telaprevir had two drawbacks :

•  An important toxicological profile.  For this reason, treatment was suspended in a higher percentage of patients than those treated only with interferon and ribavirin.
•  Large number of drug interactions.

The evolution of hepatitis C treatment

After this first generation of HCV protease inhibitors, new therapeutic agents appeared in 2014. Its efficacy and safety properties were more satisfactory. They stand out among them:

•  Simeprevir.
• Daclatasvir 
• Sofosbuvir (viral polymerase inhibitors). Sustained viral response rates of over 80% have been achieved.

In view of the results, the treatment of hepatitis C began to consist of a fixed-dose combination of these drugs.  Some of them are the association of:

• Ledipasvir and sofosbuvir,
• Ombitasvir and paritaprevir (plus a protease inhibitor such as ritonavir)
• Elbasvir and grazoprevir.

With these new drugs, results have been optimized. The duration of the treatments has also been reduced to twelve weeks. In turn, the appearance of resistance has decreased and tolerance is also much better.