Hepatitis C

What is Hepatitis C?

Hepatitis C is an acute inflammatory disease of the liver; if it is not resolved, it becomes a chronic infection that can lead to liver cirrhosis in (5-10% of cases) and liver cancer. The World Health Organization estimates that 3% of the world population, approximately 170 million people, suffer from hepatitis C.

Since a patient begins to suffer from chronic hepatitis C there are several stages of evolution from less to more serious. The degree of severity is determined by the presence of fibrosis in the liver, there being five phases: F0 (there is no liver fibrosis), F1 (there is portal fibrosis without bridges), F2 (portal fibrosis with some bridges), F3 (portal fibrosis with many bridges, without cirrhosis) and F4 (liver cirrhosis). The majority of hepatitis C patients are in stages F0-F2 (77%), with F3 being 11% and F4 being 9.6%. The evolution of the disease from F0 to F4 is very slow: they can go from 20 to 47 years or more until the development of liver cirrhosis.

Causes of Hepatitis C

Hepatitis C is caused by infection with hepatitis C virus (HCV), which is an RNA virus of the Hepacivirus family within the genus Flaviviridae.

The VCH has a lipid envelope formed by the E1 and E2 proteins, and a core or Core where the RNA that produces all the structural proteins (Core, E1, E2 / NS1) and non-structural (NS2, NS3, NS4 and NS5) is found ). The NS3 and NS5 proteins are essential for the replication of HCV and therefore are therapeutic targets. There are 6 main types of VCH (called genotypes from 1 to 6, each with several subtypes) that have a different global distribution. Thus, genotypes 1 (subtypes 1b and 1a) and 3 (subtype 3a) predominate in Spain (and Europe), although there are also cases by genotypes 2 and 4 of VCH.

Genotype 5 is found in sub-Saharan Africa and genotype 6 in Asia. Hepatitis C is sometimes associated with infection with hepatitis B virus, which worsens the prognosis. Likewise, it can be associated with infection with human immunodeficiency virus (HIV), which aggravates liver damage.

Most patients do not have symptoms due to Hepatitis C.
Dr. Vicente Carreño

Pathways of infection of Hepatitis C

Hepatitis C is transmitted by transfusions, tattoos, acupuncture, intravenous drug abuse, sexually transmitted, vertical route from mother to child. Each year 3 to 4 million people worldwide are infected and around 350,000 die. The probability of transmission of hepatitis C by injection with a contaminated syringe is 1.5-4%. There is no preventive vaccine so in case of exposure to HCV should be taken precautionary measures.

It is important to note that a patient with hepatitis C can perform a normal family, social and work activity, without taking any precautions to avoid the transmission of the disease. Only if at some point you have bleeding you should avoid contact of your blood with other people.

Diagnosis

The majority of patients do not have symptoms, so the diagnosis is made by analyzing liver enzymes (transaminases) and detecting antibodies to virus C (anti-HCV) and RNA virus in the blood.

Treatment of Hepatitis C

Among patients with hepatitis C, it is a priority to treat patients with prerhythmic (F3) and cirrhotic (F4). The classic treatment of hepatitis C involves the administration of pegylated interferon alfa (PegIFN) and ribavirin, but due to its limited efficacy (50% response) and its toxicity (flu syndrome, joint pain, etc.) it is no longer used .

Currently there are several new drugs available that have a direct antiviral effect against hepatitis C. Sofosbuvir (Sovaldi @), Simeprevir (Olysio @), Daclatasvir (Daklinza @), Sofosbuvir + Ledipasvir (Harvoni @), Ombitasvir + Paritaprevir + Dasabuvir + Ritonavir (Viekira pak @), etc. These new drugs have great advantages compared to the old ones:

tolerance is excellent and only 20% of patients notice mild symptoms (headache, tiredness)
Its effectiveness is much higher than that of previous drugs: they prevent inflammation and destruction and eliminate the virus in about 90% of cases.

The duration of treatment varies between 12 and 24 weeks depending on the characteristics of hepatitis C at the beginning of treatment: patients with cirrhosis, high viral load (concentration of HCV RNA) or who have not responded to previous treatments need to receive the drugs during a longer period.

Currently, new studies are underway to try to reduce the duration of treatment to 6-8 weeks in patients with certain characteristics: low viral load, absence of cirrhosis, etc. There are several combinations of these drugs that can be used: Sofosbuvir + Simeprevir, Sofosbuvir + Daclatasvir, Sofosbuvir + Ledipasvir, etc. Patients with HCV genotypes 1, 2, 4, 5 and 6 respond well to these treatments but those with genotype 3 respond worse. In some cases, ribavirin is added to improve efficacy.

It is important to point out that from the published studies it can be concluded that both the efficacy and the tolerance of the different drugs are similar and no studies have been done comparing the different combinations. Although it is possible to normalize the liver tests and eliminate the virus C from the blood, later it is necessary to follow up the patients until confirming the complete regeneration of the liver. PegIFN can also be used with ribavirin and one of the drugs mentioned above (Sofosbuvir, Simeprevir, Ledipasvir, Daclatasvir, Viekira pak, etc.) although the toxicity is higher.

In patients who do not have access to new drugs or who can wait before being treated, there are measures that can prevent the progression of the disease and that must be applied (phases F0-F2):

slimming diet if there is overweight;
do not drink alcohol or smoke;
metabolic corrections (normalize cholesterol, triglyceride or glucose levels if elevated);
practicing at least 3 hours of weekly exercise decreases the progression of the disease;
if the patient has high levels of ferritin (protein that transports iron) the treatment with phlebotomies (blood extractions) and iron-poor diet stops the progression of the disease in 69% of patients;
there are other drugs that can be useful (ursodeoxycholic acid, vitamin E);
Intake of 2-5 cups of coffee daily can prevent the progression of the disease. Neither artichokes nor any other type of food are useful.

In patients who do not respond to treatment, hepatitis C disease may require a liver transplant.

In 2004, the Viral Hepatitis Study Foundation discovered a new form of Hepatitis, the hidden C virus, as a result of its research work.

How aggression and evolution can be predicted

To predict the evolution of Hepatitis C patients, the degree of inflammation and the liver fibrosis stage can be determined by performing a liver biopsy. Liver ultrasound and fibroscan are also used.

The determination of PNPLA3 gene polymorphism is very useful to know the future evolution of the disease. For this analysis, a small puncture is made on the patient’s finger (identical to the one done to determine glucose) and blood is deposited on a card that adsorbs human DNA. The analysis can give the following results:

Homozygous CC: no risk of progression of liver damage.
Heterozygous CG: low risk of progression of liver damage.
Homozygous GG: with risk of progression to more severe forms of liver damage (increased liver fibrosis)

Knowing the PNPLA3 gene polymorphism result, the hepatologist can program the frequency of consultations and treatment intensity.

References

Carreño V, Castillo I (eds.). Hepatitis víricas: Biología, clínica y tratamiento. 1ª ed. Barcelona: Spriger Verlag Ibérica. Parte IV: Virus C de la hepatitis. 2001; p 241.
Thein HH, et al. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology 2008;48:418-31.
Gower E, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014;61(Suppl.1):S45-57.
Kabiri M, et al. The changing burden of hepatitis C virus infection in the United States: model-based predictions. Ann Intern Med 2014;161:170-80.
Liang TJ, Ghany MG. Therapy of hepatitis C-back to the future. N Engl J Med 2014;370:2043-7.
Carreño V. Review article: management of chronic hepatitis C in patients with contraindications to anti-viral therapy. Aliment Pharmacol Ther 2014;39:148-62.
Gane E, et al. Strategies to manage hepatitis C virus (HCV) infection disease burden – volume 2. J Viral Hepat 2015;22(Suppl.1):46-73.