Viral Hepatitis C

Epidemiology of HCV

The prevalence of HCV infection in the population varies across different countries from tenths of a percent to ten percent. Overall, it is estimated that around 150 million people worldwide are infected with the hepatitis C virus. The number of HCV-infected persons in the Czech Republic is estimated at 20,000-40,000.

The main routes of transmission (risk factors for HCV infection) are:

• Transmission through blood derivatives and products
• Intravenous drug use
• Regular dialysis treatment
• Occupational risk of HCV exposure
• Sexual contact with an HCV-positive person
• Vertical transmission from an HCV-positive mother to the newborn (perinatal transmission)
• Iatrogenic route

Natural course of untreated HCV infection

Our knowledge of the natural course of UNTREATED HCV infection is currently not entirely satisfactory; there are many reasons for the lack of information. Most of them stem from the fact that the moment of infection onset is often very poorly defined in HCV infection, it can run completely asymptomatically for many years, or conversely it is detected in earlier stages and, based on current knowledge, antiviral therapy is initiated at that point.

Figure 1 shows factors associated with a lower risk of developing liver cirrhosis (below 20%) and, conversely, with a higher risk of its development after 20 years of HCV infection. Evaluating the mosaic of listed factors and their influence on the development of liver disease in each individual case is very complex, sometimes impossible. Part of the basic examination of every person with HCV infection must therefore include an effort to determine the stage of liver fibrosis -- the degree of liver scarring. Currently, a whole range of non-invasive methods suitable for this purpose are available -- transient elastography, ARFI, shear wave elastography, etc. All these methods measure so-called liver stiffness, which depends on the amount of fibrous tissue in the liver. These examinations are crucial because the amount of fibrous tissue in the liver is a measure of the severity (and progression) of the disease.

From the above, it follows that factors such as "liver test" values, duration of infection, or mode of transmission are entirely secondary in determining the severity of liver disease and cannot be used for this purpose. Only the elastography result is decisive in this regard. In cases where elastography reveals liver cirrhosis, several additional examinations are needed to distinguish several further stages, because "not all cirrhosis is the same."

ANTIVIRAL THERAPY

Therapeutic goal

The goal of antiviral treatment is unequivocally to achieve a sustained virological response, defined as negative serum HCV RNA at 12 weeks after the completion of any antiviral treatment. If this condition is met, the patient is cured of HCV infection. The probability of infection recurrence over a ten-year horizon is < 1%, but new infection, i.e. HCV reinfection upon new exposure to the virus, is possible.

There is currently clear evidence that patients who achieve cure of the infection experience histological improvement -- the amount of fibrous tissue in their liver recedes. This regression depends on the degree of damage at the time treatment was initiated. Generally speaking, in patients who do not have liver cirrhosis at the time treatment begins, there is almost complete disappearance of tissue fibrosis. In cases where these individuals have another reason for liver disease (obesity, increased alcohol intake, etc.), the regression of fibrosis may not be complete, but it is still significant. Regression of fibrosis is also apparent in cirrhotic patients, although in their case it is more a matter of improved liver function, improved long-term prognosis, and some degree of fibrosis likely persists for life. A significant effect of successful treatment is that in all patients, including those with liver cirrhosis, there is a significant reduction in the risk of developing primary liver cancer.

Therapeutic options

In 2011, the treatment of viral hepatitis C entered an entirely new era characterised by the rapid introduction of so-called directly acting antivirals into treatment combinations for this serious infection. The beginning was marked by the approval of the first two representatives of this heterogeneous group of drugs, boceprevir and telaprevir, for use in chronic HCV infection. Boceprevir and telaprevir are representatives of the first generation of antivirals that are no longer used today.

Directly Acting Antivirals (DAAs) derive their name from their mechanism of action. Substances in this group directly block one of the enzymes involved in the HCV life cycle. Individual antivirals need to be combined with each other; in the case of therapy with a single antiviral, resistance develops almost always very quickly, i.e. the antiviral ceases to be effective and all positive effects of treatment are lost. Currently, interferon-free combinations are used, so oral treatment regimens or interferon-free regimens are commonly discussed. All currently available regimens have high efficacy, approximately 97%, and in some subgroups even 100%. A significant advantage is the short duration of treatment, usually 12 weeks, and the absence of significant side effects. The choice of treatment combination depends primarily on the HCV genotype in the individual case and on the degree of liver damage.

Current situation and treatment rules in the Czech Republic

In the Czech Republic, all antivirals are marked with the symbol S, which means their reimbursement under the centralised treatment regime. Treatment is therefore not available from every hepatogastroenterologist or infectologist, but at 15 specialised centres throughout the country that have long been dedicated to HCV infection and have all the necessary laboratory, diagnostic, and clinical facilities. The actual treatment of HCV infection is governed by Czech standards developed by the Czech Hepatological Society of the Czech Medical Association and the Society of Infectious Medicine of the Czech Medical Association, and is available e.g. at www.ces-hep.cz. The basic criterion for deciding on initiating antiviral treatment is the presence of liver fibrosis F2.

Practical procedure for a haemophilia patient with HCV infection

The above-mentioned centres capable of treating chronic HCV infection with oral regimens are in the vast majority of cases departments at university or regional hospitals. University departments cooperate well with the main haemophilia treatment centres in the Czech Republic. There is therefore no administrative barrier that would prevent examining a haemophilia patient at a specialised hepatological or infectious disease department regarding the indication for antiviral treatment with an interferon-free regimen. However, not every patient is indicated for immediate initiation of treatment. Given the conditions for antiviral reimbursement, certain rules must be followed, the most important of which has already been mentioned: there must be demonstrable liver fibrosis of at least stage F2. The final decision on initiating or postponing treatment is in the hands of the treating hepatologist or infectologist, because there are certain criteria under which antiviral treatment can be initiated even with a less significant degree of liver fibrosis.